Realistic facial expression of virtual human based on color, sweat, and tears effects.

PubMed

Alkawaz, Mohammed Hazim; Basori, Ahmad Hoirul; Mohamad, Dzulkifli; Mohamed, Farhan

2014-01-01

Generating extreme appearances such as scared awaiting sweating while happy fit for tears (cry) and blushing (anger and happiness) is the key issue in achieving the high quality facial animation. The effects of sweat, tears, and colors are integrated into a single animation model to create realistic facial expressions of 3D avatar. The physical properties of muscles, emotions, or the fluid properties with sweating and tears initiators are incorporated. The action units (AUs) of facial action coding system are merged with autonomous AUs to create expressions including sadness, anger with blushing, happiness with blushing, and fear. Fluid effects such as sweat and tears are simulated using the particle system and smoothed-particle hydrodynamics (SPH) methods which are combined with facial animation technique to produce complex facial expressions. The effects of oxygenation of the facial skin color appearance are measured using the pulse oximeter system and the 3D skin analyzer. The result shows that virtual human facial expression is enhanced by mimicking actual sweating and tears simulations for all extreme expressions. The proposed method has contribution towards the development of facial animation industry and game as well as computer graphics.

Realistic Facial Expression of Virtual Human Based on Color, Sweat, and Tears Effects

PubMed Central

Alkawaz, Mohammed Hazim; Basori, Ahmad Hoirul; Mohamad, Dzulkifli; Mohamed, Farhan

2014-01-01

Generating extreme appearances such as scared awaiting sweating while happy fit for tears (cry) and blushing (anger and happiness) is the key issue in achieving the high quality facial animation. The effects of sweat, tears, and colors are integrated into a single animation model to create realistic facial expressions of 3D avatar. The physical properties of muscles, emotions, or the fluid properties with sweating and tears initiators are incorporated. The action units (AUs) of facial action coding system are merged with autonomous AUs to create expressions including sadness, anger with blushing, happiness with blushing, and fear. Fluid effects such as sweat and tears are simulated using the particle system and smoothed-particle hydrodynamics (SPH) methods which are combined with facial animation technique to produce complex facial expressions. The effects of oxygenation of the facial skin color appearance are measured using the pulse oximeter system and the 3D skin analyzer. The result shows that virtual human facial expression is enhanced by mimicking actual sweating and tears simulations for all extreme expressions. The proposed method has contribution towards the development of facial animation industry and game as well as computer graphics. PMID:25136663

EMMPRIN co-expressed with matrix metalloproteinases predicts poor prognosis in patients with osteosarcoma.

PubMed

Futamura, Naohisa; Nishida, Yoshihiro; Urakawa, Hiroshi; Kozawa, Eiji; Ikuta, Kunihiro; Hamada, Shunsuke; Ishiguro, Naoki

2014-06-01

Several studies have focused on the relationships between the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and the prognosis of patients with malignant tumors. However, few of these have investigated the expression of EMMPRIN in osteosarcoma. We examined expression levels of EMMPRIN immunohistochemically in 53 cases of high-grade osteosarcoma of the extremities and analyzed the correlation of its expression with patient prognosis. The correlation between matrix metalloproteinases (MMPs) and EMMPRIN expression and the prognostic value of co-expression were also analyzed. Staining positivity for EMMPRIN was negative in 7 cases, low in 17, moderate in 19, and strong in 10. The overall and disease-free survivals (OS and DFS) in patients with higher EMMPRIN expression (strong-moderate) were significantly lower than those in the lower (weak-negative) group (0.037 and 0.024, respectively). In multivariate analysis, age (P=0.004), location (P=0.046), and EMMPRIN expression (P=0.038) were significant prognostic factors for overall survival. EMMPRIN expression (P=0.024) was also a significant prognostic factor for disease-free survival. Co-expression analyses of EMMPRIN and MMPs revealed that strong co-expression of EMMPRIN and membrane-type 1 (MT1)-MMP had a poor prognostic value (P=0.056 for DFS, P=0.006 for OS). EMMPRIN expression and co-expression with MMPs well predict the prognosis of patients with extremity osteosarcoma, making EMMPRIN a possible therapeutic target in these patients.

Printing Proteins as Microarrays for High-Throughput Function Determination

NASA Astrophysics Data System (ADS)

MacBeath, Gavin; Schreiber, Stuart L.

2000-09-01

Systematic efforts are currently under way to construct defined sets of cloned genes for high-throughput expression and purification of recombinant proteins. To facilitate subsequent studies of protein function, we have developed miniaturized assays that accommodate extremely low sample volumes and enable the rapid, simultaneous processing of thousands of proteins. A high-precision robot designed to manufacture complementary DNA microarrays was used to spot proteins onto chemically derivatized glass slides at extremely high spatial densities. The proteins attached covalently to the slide surface yet retained their ability to interact specifically with other proteins, or with small molecules, in solution. Three applications for protein microarrays were demonstrated: screening for protein-protein interactions, identifying the substrates of protein kinases, and identifying the protein targets of small molecules.

Synonymous codon choices in the extremely GC-poor genome of Plasmodium falciparum: compositional constraints and translational selection.

PubMed

Musto, H; Romero, H; Zavala, A; Jabbari, K; Bernardi, G

1999-07-01

We have analyzed the patterns of synonymous codon preferences of the nuclear genes of Plasmodium falciparum, a unicellular parasite characterized by an extremely GC-poor genome. When all genes are considered, codon usage is strongly biased toward A and T in third codon positions, as expected, but multivariate statistical analysis detects a major trend among genes. At one end genes display codon choices determined mainly by the extreme genome composition of this parasite, and very probably their expression level is low. At the other end a few genes exhibit an increased relative usage of a particular subset of codons, many of which are C-ending. Since the majority of these few genes is putatively highly expressed, we postulate that the increased C-ending codons are translationally optimal. In conclusion, while codon usage of the majority of P. falciparum genes is determined mainly by compositional constraints, a small number of genes exhibit translational selection.

64Cu-DOTA-anti-CTLA-4 mAb enabled PET visualization of CTLA-4 on the T-cell infiltrating tumor tissues.

PubMed

Higashikawa, Kei; Yagi, Katsuharu; Watanabe, Keiko; Kamino, Shinichiro; Ueda, Masashi; Hiromura, Makoto; Enomoto, Shuichi

2014-01-01

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) targeted therapy by anti-CTLA-4 monoclonal antibody (mAb) is highly effective in cancer patients. However, it is extremely expensive and potentially produces autoimmune-related adverse effects. Therefore, the development of a method to evaluate CTLA-4 expression prior to CTLA-4-targeted therapy is expected to open doors to evidence-based and cost-efficient medical care and to avoid adverse effects brought about by ineffective therapy. In this study, we aimed to develop a molecular imaging probe for CTLA-4 visualization in tumor. First, we examined CTLA-4 expression in normal colon tissues, cultured CT26 cells, and CT26 tumor tissues from tumor-bearing BALB/c mice and BALB/c nude mice by reverse transcription polymerase chain reaction (RT-PCR) analysis and confirmed whether CTLA-4 is strongly expressed in CT26 tumor tissues. Second, we newly synthesized 64Cu-1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid-anti-mouse CTLA-4 mAb (64Cu-DOTA-anti-CTLA-4 mAb) and evaluated its usefulness in positron emission tomography (PET) and ex-vivo biodistribution analysis in CT26-bearing BALB/c mice. High CTLA-4 expression was confirmed in the CT26 tumor tissues of tumor-bearing BALB/c mice. However, CTLA-4 expression was extremely low in the cultured CT26 cells and the CT26 tumor tissues of tumor-bearing BALB/c nude mice. The results suggested that T cells were responsible for the high CTLA-4 expression. Furthermore, 64Cu-DOTA-anti-CTLA-4 mAb displayed significantly high accumulation in the CT26 tumor, thereby realizing non-invasive CTLA-4 visualization in the tumor. Together, the results indicate that 64Cu-DOTA-anti-CTLA-4 mAb would be useful for the evaluation of CTLA-4 expression in tumor.

64Cu-DOTA-Anti-CTLA-4 mAb Enabled PET Visualization of CTLA-4 on the T-Cell Infiltrating Tumor Tissues

PubMed Central

Higashikawa, Kei; Yagi, Katsuharu; Watanabe, Keiko; Kamino, Shinichiro; Ueda, Masashi; Hiromura, Makoto; Enomoto, Shuichi

2014-01-01

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) targeted therapy by anti-CTLA-4 monoclonal antibody (mAb) is highly effective in cancer patients. However, it is extremely expensive and potentially produces autoimmune-related adverse effects. Therefore, the development of a method to evaluate CTLA-4 expression prior to CTLA-4-targeted therapy is expected to open doors to evidence-based and cost-efficient medical care and to avoid adverse effects brought about by ineffective therapy. In this study, we aimed to develop a molecular imaging probe for CTLA-4 visualization in tumor. First, we examined CTLA-4 expression in normal colon tissues, cultured CT26 cells, and CT26 tumor tissues from tumor-bearing BALB/c mice and BALB/c nude mice by reverse transcription polymerase chain reaction (RT-PCR) analysis and confirmed whether CTLA-4 is strongly expressed in CT26 tumor tissues. Second, we newly synthesized 64Cu-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-anti-mouse CTLA-4 mAb (64Cu-DOTA-anti-CTLA-4 mAb) and evaluated its usefulness in positron emission tomography (PET) and ex-vivo biodistribution analysis in CT26-bearing BALB/c mice. High CTLA-4 expression was confirmed in the CT26 tumor tissues of tumor-bearing BALB/c mice. However, CTLA-4 expression was extremely low in the cultured CT26 cells and the CT26 tumor tissues of tumor-bearing BALB/c nude mice. The results suggested that T cells were responsible for the high CTLA-4 expression. Furthermore, 64Cu-DOTA-anti-CTLA-4 mAb displayed significantly high accumulation in the CT26 tumor, thereby realizing non-invasive CTLA-4 visualization in the tumor. Together, the results indicate that 64Cu-DOTA-anti-CTLA-4 mAb would be useful for the evaluation of CTLA-4 expression in tumor. PMID:25365349

RNA-Seq reveals 10 novel promising candidate genes affecting milk protein concentration in the Chinese Holstein population

PubMed Central

Li, Cong; Cai, Wentao; Zhou, Chenghao; Yin, Hongwei; Zhang, Ziqi; Loor, Juan J.; Sun, Dongxiao; Zhang, Qin; Liu, Jianfeng; Zhang, Shengli

2016-01-01

Paired-end RNA sequencing (RNA-Seq) was used to explore the bovine transcriptome from the mammary tissue of 12 Chinese Holstein cows with 6 extremely high and 6 low phenotypic values for milk protein percentage. We defined the differentially expressed transcripts between the two comparison groups, extremely high and low milk protein percentage during the peak lactation (HP vs LP) and during the non-lactating period (HD vs LD), respectively. Within the differentially expressed genes (DEGs), we detected 157 at peak lactation and 497 in the non-lactating period with a highly significant correlation with milk protein concentration. Integrated interpretation of differential gene expression indicated that SERPINA1, CLU, CNTFR, ERBB2, NEDD4L, ANG, GALE, HSPA8, LPAR6 and CD14 are the most promising candidate genes affecting milk protein concentration. Similarly, LTF, FCGR3A, MEGF10, RRM2 and UBE2C are the most promising candidates that in the non-lactating period could help the mammary tissue prevent issues with inflammation and udder disorders. Putative genes will be valuable resources for designing better breeding strategies to optimize the content of milk protein and also to provide new insights into regulation of lactogenesis. PMID:27254118

Spatiotemporal variability of extreme temperature frequency and amplitude in China

NASA Astrophysics Data System (ADS)

Zhang, Yuanjie; Gao, Zhiqiu; Pan, Zaitao; Li, Dan; Huang, Xinhui

2017-03-01

Temperature extremes in China are examined based on daily maximum and minimum temperatures from station observations and multiple global climate models. The magnitude and frequency of extremes are expressed in terms of return values and periods, respectively, estimated by the fitted Generalized Extreme Value (GEV) distribution of annual extreme temperatures. The observations suggest that changes in temperature extremes considerably exceed changes in the respective climatological means during the past five decades, with greater amplitude of increases in cold extremes than in warm extremes. The frequency of warm (cold) extremes increases (decreases) over most areas, with an increasingly faster rate as the extremity level rises. Changes in warm extremes are more dependent on the varying shape of GEV distribution than the location shift, whereas changes in cold extremes are more closely associated with the location shift. The models simulate the overall pattern of temperature extremes during 1961-1981 reasonably well in China, but they show a smaller asymmetry between changes in warm and cold extremes primarily due to their underestimation of increases in cold extremes especially over southern China. Projections from a high emission scenario show the multi-model median change in warm and cold extremes by 2040 relative to 1971 will be 2.6 °C and 2.8 °C, respectively, with the strongest changes in cold extremes shifting southward. By 2040, warm extremes at the 1971 20-year return values would occur about every three years, while the 1971 cold extremes would occur once in > 500 years.

Beyond pleasure and pain: Facial expression ambiguity in adults and children during intense situations.

PubMed

Wenzler, Sofia; Levine, Sarah; van Dick, Rolf; Oertel-Knöchel, Viola; Aviezer, Hillel

2016-09-01

According to psychological models as well as common intuition, intense positive and negative situations evoke highly distinct emotional expressions. Nevertheless, recent work has shown that when judging isolated faces, the affective valence of winning and losing professional tennis players is hard to differentiate. However, expressions produced by professional athletes during publicly broadcasted sports events may be strategically controlled. To shed light on this matter we examined if ordinary people's spontaneous facial expressions evoked during highly intense situations are diagnostic for the situational valence. In Experiment 1 we compared reactions with highly intense positive situations (surprise soldier reunions) versus highly intense negative situations (terror attacks). In Experiment 2, we turned to children and compared facial reactions with highly positive situations (e.g., a child receiving a surprise trip to Disneyland) versus highly negative situations (e.g., a child discovering her parents ate up all her Halloween candy). The results demonstrate that facial expressions of both adults and children are often not diagnostic for the valence of the situation. These findings demonstrate the ambiguity of extreme facial expressions and highlight the importance of context in everyday emotion perception. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Modeling the Pineapple Express phenomenon via Multivariate Extreme Value Theory

NASA Astrophysics Data System (ADS)

Weller, G.; Cooley, D. S.

2011-12-01

The pineapple express (PE) phenomenon is responsible for producing extreme winter precipitation events in the coastal and mountainous regions of the western United States. Because the PE phenomenon is also associated with warm temperatures, the heavy precipitation and associated snowmelt can cause destructive flooding. In order to study impacts, it is important that regional climate models from NARCCAP are able to reproduce extreme precipitation events produced by PE. We define a daily precipitation quantity which captures the spatial extent and intensity of precipitation events produced by the PE phenomenon. We then use statistical extreme value theory to model the tail dependence of this quantity as seen in an observational data set and each of the six NARCCAP regional models driven by NCEP reanalysis. We find that most NCEP-driven NARCCAP models do exhibit tail dependence between daily model output and observations. Furthermore, we find that not all extreme precipitation events are pineapple express events, as identified by Dettinger et al. (2011). The synoptic-scale atmospheric processes that drive extreme precipitation events produced by PE have only recently begun to be examined. Much of the current work has focused on pattern recognition, rather than quantitative analysis. We use daily mean sea-level pressure (MSLP) fields from NCEP to develop a "pineapple express index" for extreme precipitation, which exhibits tail dependence with our observed precipitation quantity for pineapple express events. We build a statistical model that connects daily precipitation output from the WRFG model, daily MSLP fields from NCEP, and daily observed precipitation in the western US. Finally, we use this model to simulate future observed precipitation based on WRFG output driven by the CCSM model, and our pineapple express index derived from future CCSM output. Our aim is to use this model to develop a better understanding of the frequency and intensity of extreme precipitation events produced by PE under climate change.

Gene expression changes leading extreme alkaline tolerance in Amur ide (Leuciscus waleckii) inhabiting soda lake

PubMed Central

2013-01-01

Background Amur ide (Leuciscus waleckii) is an economically and ecologically important cyprinid species in Northern Asia. The Dali Nor population living in the soda lake Dali Nor can adapt the extremely high alkalinity, providing us a valuable material to understand the adaptation mechanism against extreme environmental stress in teleost. Results In this study, we generated high-throughput RNA-Seq data from three tissues gill, liver and kidney of L. waleckii living in the soda lake Dali Nor and the fresh water lake Ganggeng Nor, then performed parallel comparisons of three tissues. Our results showed that out of assembled 64,603 transcript contigs, 28,391 contigs had been assigned with a known function, corresponding to 20,371 unique protein accessions. We found 477, 2,761 and 3,376 differentially expressed genes (DEGs) in the gill, kidney, and liver, respectively, of Dali Nor population compared to Ganggeng Nor population with FDR ≤ 0.01and fold-change ≥ 2. Further analysis revealed that well-known functional categories of genes and signaling pathway, which are associated with stress response and extreme environment adaptation, have been significantly enriched, including the functional categories of “response to stimulus”, “transferase activity”, “transporter activity” and “oxidoreductase activity”, and signaling pathways of “mTOR signaling”, “EIF2 signaling”, “superpathway of cholesterol biosynthesis”. We also identified significantly DEGs encoding important modulators on stress adaptation and tolerance, including carbonic anhydrases, heat shock proteins, superoxide dismutase, glutathione S-transferases, aminopeptidase N, and aminotransferases. Conclusions Overall, this study demonstrated that transcriptome changes in L. waleckii played a role in adaptation to complicated environmental stress in the highly alkalized Dali Nor lake. The results set a foundation for further analyses on alkaline-responsive candidate genes, which help us understand teleost adaptation under extreme environmental stress and ultimately benefit future breeding for alkaline-tolerant fish strains. PMID:24094069

Analysis of Pax6 contiguous gene deletions in the mouse, Mus musculus, identifies regions distinct from Pax6 responsible for extreme small-eye and belly-spotting phenotypes.

PubMed

Favor, Jack; Bradley, Alan; Conte, Nathalie; Janik, Dirk; Pretsch, Walter; Reitmeir, Peter; Rosemann, Michael; Schmahl, Wolfgang; Wienberg, Johannes; Zaus, Irmgard

2009-08-01

In the mouse Pax6 function is critical in a dose-dependent manner for proper eye development. Pax6 contiguous gene deletions were shown to be homozygous lethal at an early embryonic stage. Heterozygotes express belly spotting and extreme microphthalmia. The eye phenotype is more severe than in heterozygous Pax6 intragenic null mutants, raising the possibility that deletions are functionally different from intragenic null mutations or that a region distinct from Pax6 included in the deletions affects eye phenotype. We recovered and identified the exact regions deleted in three new Pax6 deletions. All are homozygous lethal at an early embryonic stage. None express belly spotting. One expresses extreme microphthalmia and two express the milder eye phenotype similar to Pax6 intragenic null mutants. Analysis of Pax6 expression levels and the major isoforms excluded the hypothesis that the deletions expressing extreme microphthalmia are directly due to the action of Pax6 and functionally different from intragenic null mutations. A region distinct from Pax6 containing eight genes was identified for belly spotting. A second region containing one gene (Rcn1) was identified for the extreme microphthalmia phenotype. Rcn1 is a Ca(+2)-binding protein, resident in the endoplasmic reticulum, participates in the secretory pathway and expressed in the eye. Our results suggest that deletion of Rcn1 directly or indirectly contributes to the eye phenotype in Pax6 contiguous gene deletions.

Genome editing of BmFib-H gene provides an empty Bombyx mori silk gland for a highly efficient bioreactor

PubMed Central

Ma, Sanyuan; Shi, Run; Wang, Xiaogang; Liu, Yuanyuan; Chang, Jiasong; Gao, Jie; Lu, Wei; Zhang, Jianduo; Zhao, Ping; Xia, Qingyou

2014-01-01

Evolution has produced some remarkable creatures, of which silk gland is a fascinating organ that exists in a variety of insects and almost half of the 34,000 spider species. The impressive ability to secrete huge amount of pure silk protein, and to store proteins at an extremely high concentration (up to 25%) make the silk gland of Bombyx mori hold great promise to be a cost-effective platform for production of recombinant proteins. However, the extremely low production yields of the numerous reported expression systems greatly hindered the exploration and application of silk gland bioreactors. Using customized zinc finger nucleases (ZFN), we successfully performed genome editing of Bmfib-H gene, which encodes the largest and most abundant silk protein, in B. mori with efficiency higher than any previously reported. The resulted Bmfib-H knocked-out B. mori showed a smaller and empty silk gland, abnormally developed posterior silk gland cells, an extremely thin cocoon that contain only sericin proteins, and a slightly heavier pupae. We also showed that removal of endogenous Bmfib-H protein could significantly increase the expression level of exogenous protein. Furthermore, we demonstrated that the bioreactor is suitable for large scale production of protein-based materials. PMID:25359576

Thermal reactionomes reveal divergent responses to thermal extremes in warm and cool-climate ant species.

PubMed

Stanton-Geddes, John; Nguyen, Andrew; Chick, Lacy; Vincent, James; Vangala, Mahesh; Dunn, Robert R; Ellison, Aaron M; Sanders, Nathan J; Gotelli, Nicholas J; Cahan, Sara Helms

2016-03-02

The distributions of species and their responses to climate change are in part determined by their thermal tolerances. However, little is known about how thermal tolerance evolves. To test whether evolutionary extension of thermal limits is accomplished through enhanced cellular stress response (enhanced response), constitutively elevated expression of protective genes (genetic assimilation) or a shift from damage resistance to passive mechanisms of thermal stability (tolerance), we conducted an analysis of the reactionome: the reaction norm for all genes in an organism's transcriptome measured across an experimental gradient. We characterized thermal reactionomes of two common ant species in the eastern U.S, the northern cool-climate Aphaenogaster picea and the southern warm-climate Aphaenogaster carolinensis, across 12 temperatures that spanned their entire thermal breadth. We found that at least 2 % of all genes changed expression with temperature. The majority of upregulation was specific to exposure to low temperatures. The cool-adapted A. picea induced expression of more genes in response to extreme temperatures than did A. carolinensis, consistent with the enhanced response hypothesis. In contrast, under high temperatures the warm-adapted A. carolinensis downregulated many of the genes upregulated in A. picea, and required more extreme temperatures to induce down-regulation in gene expression, consistent with the tolerance hypothesis. We found no evidence for a trade-off between constitutive and inducible gene expression as predicted by the genetic assimilation hypothesis. These results suggest that increases in upper thermal limits may require an evolutionary shift in response mechanism away from damage repair toward tolerance and prevention.

Whole blood transcriptional profiling comparison between different milk yield of Chinese Holstein cows using RNA-seq data.

PubMed

Bai, Xue; Zheng, Zhuqing; Liu, Bin; Ji, Xiaoyang; Bai, Yongsheng; Zhang, Wenguang

2016-08-22

The objective of this research was to investigate the variation of gene expression in the blood transcriptome profile of Chinese Holstein cows associated to the milk yield traits. We used RNA-seq to generate the bovine transcriptome from the blood of 23 lactating Chinese Holstein cows with extremely high and low milk yield. A total of 100 differentially expressed genes (DEGs) (p < 0.05, FDR < 0.05) were revealed between the high and low groups. Gene ontology (GO) analysis demonstrated that the 100 DEGs were enriched in specific biological processes with regard to defense response, immune response, inflammatory response, icosanoid metabolic process, and fatty acid metabolic process (p < 0.05). The KEGG pathway analysis with 100 DEGs revealed that the most statistically-significant metabolic pathway was related with Toll-like receptor signaling pathway (p < 0.05). The expression level of four selected DEGs was analyzed by qRT-PCR, and the results indicated that the expression patterns were consistent with the deep sequencing results by RNA-Seq. Furthermore, alternative splicing analysis of 100 DEGs demonstrated that there were different splicing pattern between high and low yielders. The alternative 3' splicing site was the major splicing pattern detected in high yielders. However, in low yielders the major type was exon skipping. This study provides a non-invasive method to identify the DEGs in cattle blood using RNA-seq for milk yield. The revealed 100 DEGs between Holstein cows with extremely high and low milk yield, and immunological pathway are likely involved in milk yield trait. Finally, this study allowed us to explore associations between immune traits and production traits related to milk production.

Random Dynamics

NASA Astrophysics Data System (ADS)

Bennett, D. L.; Brene, N.; Nielsen, H. B.

1987-01-01

The goal of random dynamics is the derivation of the laws of Nature as we know them (standard model) from inessential assumptions. The inessential assumptions made here are expressed as sets of general models at extremely high energies: gauge glass and spacetime foam. Both sets of models lead tentatively to the standard model.

The Survival of Native American Languages.

ERIC Educational Resources Information Center

Forbes, Jack D.

1981-01-01

Before the white invasion, Native American peoples possessed an extremely rich and varied heritage with highly developed oral literatures, and constant development of new phrases, expressions, and patterns of pronunciation. Examples of Indian people's adeptness with language include: many learned to speak more than two languages fluently;…

Morphology, sex steroid level and gene expression analysis in gonadal sex reversal of triploid female (XXX) rainbow trout (Oncorhynchus mykiss).

PubMed

Xu, Gefeng; Huang, Tianqing; Jin, Xian; Cui, Cunhe; Li, Depeng; Sun, Cong; Han, Ying; Mu, Zhenbo

2016-02-01

In non-mammalian vertebrates, estrogens and expressions of cyp19a1 and foxl2 play critical roles in maintaining ovary differentiation and development, while dmrt1 and sox9 are male-specific genes in testicular differentiation and are highly conserved. In order to deeply understand the morphological change, sex steroids level and molecular mechanism of triploid female gonadal reversal in rainbow trout, we studied the ovary morphology, tendency of estradiol-17β (E2) and testosterone (T) levels and the relative expressions of dmrt1, cyp19a1, sox9 and foxl2 in juvenile and adult fish. Our results demonstrated that the development of triploid female gonads in rainbow trout went through arrested development, oocytes dedifferentiation, ovary reconstruction and sex reversal finally. During early gonadal development (154-334 days post-fertilization), the expressions of foxl2 and cyp19a1 increased linearly, while expressions of dmrt1 and sox9 were extremely suppressed, and E2 level was higher, while T level was lower. During the mid-to-late period of triploid female gonadal development (574-964 days post-fertilization), the expressions of dmrt1 and sox9 remained high and were very close to the quantity of diploid male genes, and T levels were even reaching diploid male plasma concentrations, while expressions of cyp19a1 and foxl2 were decreased, leading to decrease in E2 level. We realized that the development model of rainbow trout triploid female gonads was extremely rare, and the regulatory mechanism was very special. Genes involved in gonadal development and endogenous estrogens are pivotal factors in fish natural sex reversal.

Comparative genome sequencing reveals genomic signature of extreme desiccation tolerance in the anhydrobiotic midge

PubMed Central

Gusev, Oleg; Suetsugu, Yoshitaka; Cornette, Richard; Kawashima, Takeshi; Logacheva, Maria D.; Kondrashov, Alexey S.; Penin, Aleksey A.; Hatanaka, Rie; Kikuta, Shingo; Shimura, Sachiko; Kanamori, Hiroyuki; Katayose, Yuichi; Matsumoto, Takashi; Shagimardanova, Elena; Alexeev, Dmitry; Govorun, Vadim; Wisecaver, Jennifer; Mikheyev, Alexander; Koyanagi, Ryo; Fujie, Manabu; Nishiyama, Tomoaki; Shigenobu, Shuji; Shibata, Tomoko F.; Golygina, Veronika; Hasebe, Mitsuyasu; Okuda, Takashi; Satoh, Nori; Kikawada, Takahiro

2014-01-01

Anhydrobiosis represents an extreme example of tolerance adaptation to water loss, where an organism can survive in an ametabolic state until water returns. Here we report the first comparative analysis examining the genomic background of extreme desiccation tolerance, which is exclusively found in larvae of the only anhydrobiotic insect, Polypedilum vanderplanki. We compare the genomes of P. vanderplanki and a congeneric desiccation-sensitive midge P. nubifer. We determine that the genome of the anhydrobiotic species specifically contains clusters of multi-copy genes with products that act as molecular shields. In addition, the genome possesses several groups of genes with high similarity to known protective proteins. However, these genes are located in distinct paralogous clusters in the genome apart from the classical orthologues of the corresponding genes shared by both chironomids and other insects. The transcripts of these clustered paralogues contribute to a large majority of the mRNA pool in the desiccating larvae and most likely define successful anhydrobiosis. Comparison of expression patterns of orthologues between two chironomid species provides evidence for the existence of desiccation-specific gene expression systems in P. vanderplanki. PMID:25216354

The Characteristic Long-Term Upregulation of Hippocampal NF-κB Complex in PTSD-Like Behavioral Stress Response Is Normalized by High-Dose Corticosterone and Pyrrolidine Dithiocarbamate Administered Immediately after Exposure

PubMed Central

Cohen, Hagit; Kozlovsky, Nitsan; Matar, Michael A; Zohar, Joseph; Kaplan, Zeev

2011-01-01

Nuclear factor-κB (NF-κB) is a ubiquitously expressed transcription factor for genes involved in cell survival, differentiation, inflammation, and growth. This study examined the role of NF-κB pathway in stress-induced PTSD-like behavioral response patterns in rats. Immunohistochemical technique was used to detect the expression of the NF-κB p50 and p65 subunits, I-κBα, p38, and phospho-p38 in the hippocampal subregions at 7 days after exposure to predator scent stress. Expression of p65 nuclear translocation was quantified by western blot as the level of NF-κB activation. The effects of intraperitoneally administered corticosterone or a selective NF-κB inhibitor (pyrrolidine dithiocarbamate (PDTC)) at 1 h post exposure on behavioral tests (elevated plus-maze and acoustic startle response) were evaluated 7 days later. Hippocampal expressions of those genes were subsequently evaluated. All data were analyzed in relation to individual behavior patterns. Extreme behavioral responder animals displayed significant upregulation of p50 and p65 with concomitant downregulation of I-κBα, p38, and phospho-p38 levels in hippocampal structures compared with minimal behavioral responders and controls. Immediate post-exposure treatment with high-dose corticosterone and PDTC significantly reduced prevalence rates of extreme responders and normalized the expression of those genes. Stress-induced upregulation of NF-κB complex in the hippocampus may contribute to the imbalance between what are normally precisely orchestrated and highly coordinated physiological and behavioral processes, thus associating it with stress-related disorders. PMID:21734649

Boron stress response and accumulation potential of the extremely tolerant species Puccinellia frigida.

PubMed

Rámila, Consuelo D P; Contreras, Samuel A; Di Domenico, Camila; Molina-Montenegro, Marco A; Vega, Andrea; Handford, Michael; Bonilla, Carlos A; Pizarro, Gonzalo E

2016-11-05

Phytoremediation is a promising technology to tackle boron toxicity, which restricts agricultural activities in many arid and semi-arid areas. Puccinellia frigida is a perennial grass that was reported to hyperaccumulate boron in extremely boron-contaminated sites. To further investigate its potential for phytoremediation, we determined its response to boron stress under controlled conditions (hydroponic culture). Also, as a first step towards understanding the mechanisms underlying its extreme tolerance, we evaluated the presence and expression of genes related with boron tolerance. We found that P. frigida grew normally even at highly toxic boron concentrations in the medium (500mg/L), and within its tissues (>5000mg/kg DW). We postulate that the strategies conferring this extreme tolerance involve both restricting boron accumulation and an internal tolerance mechanism; this is consistent with the identification of putative genes involved in both mechanisms, including the expression of a possible boron efflux transporter. We also found that P. frigida hyperaccumulated boron over a wide range of boron concentrations. We propose that P. frigida could be used for boron phytoremediation strategies in places with different soil characteristics and boron concentrations. Further studies should pave the way for the development of clean and low-cost solutions to boron toxicity problems. Copyright © 2016 Elsevier B.V. All rights reserved.

Survival and Energy Producing Strategies of Alkane Degraders Under Extreme Conditions and Their Biotechnological Potential.

PubMed

Park, Chulwoo; Park, Woojun

2018-01-01

Many petroleum-polluted areas are considered as extreme environments because of co-occurrence of low and high temperatures, high salt, and acidic and anaerobic conditions. Alkanes, which are major constituents of crude oils, can be degraded under extreme conditions, both aerobically and anaerobically by bacteria and archaea of different phyla. Alkane degraders possess exclusive metabolic pathways and survival strategies, which involve the use of protein and RNA chaperones, compatible solutes, biosurfactants, and exopolysaccharide production for self-protection during harsh environmental conditions such as oxidative and osmotic stress, and ionic nutrient-shortage. Recent findings suggest that the thermophilic sulfate-reducing archaeon Archaeoglobus fulgidus uses a novel alkylsuccinate synthase for long-chain alkane degradation, and the thermophilic Candidatus Syntrophoarchaeum butanivorans anaerobically oxidizes butane via alkyl-coenzyme M formation. In addition, gene expression data suggest that extremophiles produce energy via the glyoxylate shunt and the Pta-AckA pathway when grown on a diverse range of alkanes under stress conditions. Alkane degraders possess biotechnological potential for bioremediation because of their unusual characteristics. This review will provide genomic and molecular insights on alkane degraders under extreme conditions.

Development of Perceptual Expertise in Emotion Recognition

ERIC Educational Resources Information Center

Pollak, Seth D.; Messner, Michael; Kistler, Doris J.; Cohn, Jeffrey F.

2009-01-01

How do children's early social experiences influence their perception of emotion-specific information communicated by the face? To examine this question, we tested a group of abused children who had been exposed to extremely high levels of parental anger expression and physical threat. Children were presented with arrays of stimuli that depicted…

Extremely High Expression of Antisense RNA for Wilms' Tumor 1 in Active Osteoclasts: Suppression of Wilms' Tumor 1 Protein Expression during Osteoclastogenesis.

PubMed

Li, Yin-Ji; Kukita, Akiko; Kyumoto-Nakamura, Yukari; Kukita, Toshio

2016-09-01

Wilms' tumor 1 (WT1), a zinc-finger transcription regulator of the early growth response family, identified as the product of a tumor suppressor gene of Wilms' tumors, bears potential ability to induce macrophage differentiation in blood cell differentiation. Herein, we examined the involvement of WT1 in the regulation of osteoclastogenesis. We detected a high level of WT1 protein expression in osteoclast precursors; however, WT1 expression was markedly suppressed during osteoclastogenesis. We examined expression of WT1 transcripts in bone tissue by RNA in situ hybridization. We found a high level of antisense transcripts in osteoclasts actively resorbing bone in mandible of newborn rats. Expression of antisense WT1 RNA in mandible was also confirmed by Northern blot analysis and strand-specific RT-PCR. Overexpression of antisense WT1 RNA in RAW-D cells, an osteoclast precursor cell line, resulted in a marked enhancement of osteoclastogenesis, suggesting that antisense WT1 RNA functions to suppress expression of WT1 protein in osteoclastogenesis. High level expression of antisense WT1 RNA may contribute to commitment to osteoclastogenesis, and may allow osteoclasts to maintain or stabilize their differentiation state. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

IrrE, a Global Regulator of Extreme Radiation Resistance in Deinococcus radiodurans, Enhances Salt Tolerance in Escherichia coli and Brassica napus

PubMed Central

Zhou, Zhengfu; Yan, Yongliang; Zhang, Wei; Lu, Wei; Ping, Shuzhen; Dai, Qilin; Yuan, Menglong; Feng, Bin; Hou, Xiaoguang; Zhang, Ying; Ruiqiang; Liu, Tingting; Feng, Lu; Wang, Lei; Chen, Ming; Lin, Min

2009-01-01

Background Globally, about 20% of cultivated land is now affected by salinity. Salt tolerance is a trait of importance to all crops in saline soils. Previous efforts to improve salt tolerance in crop plants have met with only limited success. Bacteria of the genus Deinococcus are known for their ability to survive highly stressful conditions, and therefore possess a unique pool of genes conferring extreme resistance. In Deinococcus radiodurans, the irrE gene encodes a global regulator responsible for extreme radioresistance. Methodology/Principal Findings Using plate assays, we showed that IrrE protected E. coli cells against salt shock and other abiotic stresses such as oxidative, osmotic and thermal shocks. Comparative proteomic analysis revealed that IrrE functions as a switch to regulate different sets of proteins such as stress responsive proteins, protein kinases, glycerol-degrading enzymes, detoxification proteins, and growth-related proteins in E. coli. We also used quantitative RT-PCR to investigate expression of nine selected stress-responsive genes in transgenic and wild-type Brassica napus plants. Transgenic B. napus plants expressing the IrrE protein can tolerate 350 mM NaCl, a concentration that inhibits the growth of almost all crop plants. Conclusions Expression of IrrE, a global regulator for extreme radiation resistance in D. radiodurans, confers significantly enhanced salt tolerance in both E. coli and B. napus. We thus propose that the irrE gene might be used as a potentially promising transgene to improve abiotic stress tolerances in crop plants. PMID:19204796

Increases of heat shock proteins and their mRNAs at high hydrostatic pressure in a deep-sea piezophilic bacterium, Shewanella violacea.

PubMed

Sato, Hiroshi; Nakasone, Kaoru; Yoshida, Takao; Kato, Chiaki; Maruyama, Tadashi

2015-07-01

When non-extremophiles encounter extreme environmental conditions, which are natural for the extremophiles, stress reactions, e.g., expression of heat shock proteins (HSPs), are thought to be induced for survival. To understand how the extremophiles live in such extreme environments, we studied the effects of high hydrostatic pressure on cellular contents of HSPs and their mRNAs during growth in a piezophilic bacterium, Shewanella violacea. HSPs increased at high hydrostatic pressures even when optimal for growth. The mRNAs and proteins of these HSPs significantly increased at higher hydrostatic pressure in S. violacea. In the non-piezophilic Escherichia coli, however, their mRNAs decreased, while their proteins did not change. Several transcriptional start sites (TSSs) for HSP genes were determined by the primer extension method and some of them showed hydrostatic pressure-dependent increase of the mRNAs. A major refolding target of one of the HSPs, chaperonin, at high hydrostatic pressure was shown to be RplB, a subunit of the 50S ribosome. These results suggested that in S. violacea, HSPs play essential roles, e.g., maintaining protein complex machinery including ribosomes, in the growth and viability at high hydrostatic pressure, and that, in their expression, the transcription is under the control of σ(32).

House spider genome uncovers evolutionary shifts in the diversity and expression of black widow venom proteins associated with extreme toxicity.

PubMed

Gendreau, Kerry L; Haney, Robert A; Schwager, Evelyn E; Wierschin, Torsten; Stanke, Mario; Richards, Stephen; Garb, Jessica E

2017-02-16

Black widow spiders are infamous for their neurotoxic venom, which can cause extreme and long-lasting pain. This unusual venom is dominated by latrotoxins and latrodectins, two protein families virtually unknown outside of the black widow genus Latrodectus, that are difficult to study given the paucity of spider genomes. Using tissue-, sex- and stage-specific expression data, we analyzed the recently sequenced genome of the house spider (Parasteatoda tepidariorum), a close relative of black widows, to investigate latrotoxin and latrodectin diversity, expression and evolution. We discovered at least 47 latrotoxin genes in the house spider genome, many of which are tandem-arrayed. Latrotoxins vary extensively in predicted structural domains and expression, implying their significant functional diversification. Phylogenetic analyses show latrotoxins have substantially duplicated after the Latrodectus/Parasteatoda split and that they are also related to proteins found in endosymbiotic bacteria. Latrodectin genes are less numerous than latrotoxins, but analyses show their recruitment for venom function from neuropeptide hormone genes following duplication, inversion and domain truncation. While latrodectins and other peptides are highly expressed in house spider and black widow venom glands, latrotoxins account for a far smaller percentage of house spider venom gland expression. The house spider genome sequence provides novel insights into the evolution of venom toxins once considered unique to black widows. Our results greatly expand the size of the latrotoxin gene family, reinforce its narrow phylogenetic distribution, and provide additional evidence for the lateral transfer of latrotoxins between spiders and bacterial endosymbionts. Moreover, we strengthen the evidence for the evolution of latrodectin venom genes from the ecdysozoan Ion Transport Peptide (ITP)/Crustacean Hyperglycemic Hormone (CHH) neuropeptide superfamily. The lower expression of latrotoxins in house spiders relative to black widows, along with the absence of a vertebrate-targeting α-latrotoxin gene in the house spider genome, may account for the extreme potency of black widow venom.

Transcriptome analysis of the cyanobacterium Synechocystis sp. PCC 6803 and mechanisms of photoinhibition tolerance under extreme high light conditions.

PubMed

Ogawa, Kenichi; Yoshikawa, Katsunori; Matsuda, Fumio; Toya, Yoshihiro; Shimizu, Hiroshi

2018-06-12

Photoinhibition, or cell damage caused by excessively intense light is a major issue for the industrial use of cyanobacteria. To investigate the mechanism of responses to extreme high light intensity, gene expression analysis was performed using the model cyanobacterium Synechocystis sp. PCC 6803 (PCC 6803) cultured under various light intensities. The culture profile data demonstrated that, in contrast to the slow cell growth observed under low light intensities (30 and 50 μmol m -2  s -1 ), maximal cell growth was observed under mid light conditions (300 and 1000 μmol m -2  s -1 ). PCC 6803 cells exhibited photoinhibition when cultured under excessive high light intensities of 1100 and 1300 μmol m -2  s -1 . From the low to the mid light conditions, the expression of genes related to light harvesting systems was repressed, whereas that of CO 2 fixation and of D1 protein turnover-related genes was induced. Gene expression data also revealed that the down-regulation of genes related to flagellum synthesis (pilA2), pyridine nucleotide transhydrogenase (pntA and pntB), and sigma factor (sigA and sigF) represents the key responses of PCC 6803 under excessive high light conditions. The results obtained in this study provide further understanding of high light tolerance mechanisms and should help to improve the productivity of bioprocess using cyanobacteria. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Characterization of heat shock protein 70 transcript from Nilaparvata lugens (Stål): Its response to temperature and insecticide stresses.

PubMed

Lu, Kai; Chen, Xia; Liu, Wenting; Zhang, Zhichao; Wang, Ying; You, Keke; Li, Yue; Zhang, Rongbin; Zhou, Qiang

2017-10-01

The brown planthopper, Nilaparvata lugens, possesses a strong adaptability to extreme temperature and insecticide stresses. Heat shock proteins (Hsps) are highly conserved molecular chaperones and play a pivotal role in response to various environmental stresses in insects. However, little is known about the response of Hsps to stresses in N. lugens. In the present study, an inducible Hsp70 (NlHsp70) was isolated from this insect and transcriptional expression patterns of NlHsp70 under temperature and insecticide stresses were analyzed. The full-length of NlHsp70 was 2805bp with an open reading frame (ORF) of 1896bp, showing high homology to its counterparts in other species. Expression of NlHsp70 was not altered by heat shock for 1h, nor following recovery from thermal stress. Conversely, decreased expression of NlHsp70 was observed in response to cold shock. In addition, the expression of NlHsp70 increased after imidacloprid exposure. RNA interference experiment combined with insecticide injury assay also demonstrated that NlHsp70 was essential for resistance against insecticide exposure. These observations indicated that NlHsp70 was an important gene involved in the resistance or tolerance to environmental stresses in N. lugens. Interestingly, weak changes in mRNA expression levels of two thermal-inducible Hsp genes, NlHsp90 and NlHsc70 were observed in imidacloprid-exposed N. lugens adults, suggesting that different Hsps may respond differential to the extreme temperature and insecticide stresses. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis of the precipitation and streamflow extremes in Northern Italy using high resolution reanalysis dataset Express-Hydro

NASA Astrophysics Data System (ADS)

Silvestro, Francesco; Parodi, Antonio; Campo, Lorenzo

2017-04-01

The characterization of the hydrometeorological extremes, both in terms of rainfall and streamflow, in a given region plays a key role in the environmental monitoring provided by the flood alert services. In last years meteorological simulations (both near real-time and historical reanalysis) were available at increasing spatial and temporal resolutions, making possible long-period hydrological reanalysis in which the meteo dataset is used as input in distributed hydrological models. In this work, a very high resolution meteorological reanalysis dataset, namely Express-Hydro (CIMA, ISAC-CNR, GAUSS Special Project PR45DE), was employed as input in the hydrological model Continuum in order to produce long time series of streamflows in the Liguria territory, located in the Northern part of Italy. The original dataset covers the whole Europe territory in the 1979-2008 period, at 4 km of spatial resolution and 3 hours of time resolution. Analyses in terms of comparison between the rainfall estimated by the dataset and the observations (available from the local raingauges network) were carried out, and a bias correction was also performed in order to better match the observed climatology. An extreme analysis was eventually carried on the streamflows time series obtained by the simulations, by comparing them with the results of the same hydrological model fed with the observed time series of rainfall. The results of the analysis are shown and discussed.

Spatial patterns of frequent floods in Switzerland

NASA Astrophysics Data System (ADS)

Schneeberger, Klaus; Rössler, Ole; Weingartner, Rolf

2017-04-01

Information about the spatial characteristics of high and extreme streamflow is often needed for an accurate analysis of flood risk and effective co-ordination of flood related activities, such as flood defence planning. In this study we analyse the spatial dependence of frequent floods in Switzerland across different scales. Firstly, we determine the average length of high and extreme flow events for 56 runoff time series of Swiss rivers. Secondly, a dependence measure expressing the probability that streamflow peaks are as high as peaks at a conditional site is used to describe and map the spatial extend of joint occurrence of frequent floods across Switzerland. Thirdly, we apply a cluster analysis to identify groups of sites that are likely to react similarly in terms of joint occurrence of high flow events. The results indicate that a time interval with a length of 3 days seems to be most appropriate to characterise the average length of high streamflow events across spatial scales. In the main Swiss basins, high and extreme streamflows were found to be asymptotically independent. In contrast, at the meso-scale distinct flood regions, which react similarly in terms of occurrence of frequent flood, were found. The knowledge about these regions can help to optimise flood defence planning or to estimate regional flood risk properly.

Upper extremity sensory feedback therapy in chronic cerebrovascular accident patients with impaired expressive aphasia and auditory comprehension.

PubMed

Balliet, R; Levy, B; Blood, K M

1986-05-01

Electromyographic (EMG) sensory feedback therapy (SFT) was used in the neuromuscular retraining of the nonfunctional upper extremity in five chronic left cerebrovascular accident (CVA) patients with impaired expressive and auditory comprehension. Speech diagnoses included global, moderate-to-severe Broca, and Wernicke aphasias. These patients had experienced increased despondency associated with previous therapy failures and often had indicated that they wished to have their involved extremity amputated, so that it would no longer be in the way. In this study, specific behavioral training strategies to increase patient involvement were used, including: general relaxation, modified SFT instruction, and home exercises, which were supported by family and/or friends. After an average of 50 therapy sessions, all patients were successfully retrained to use their right upper extremity at the gross-assist level. This resulted in feelings of increased self-esteem to the extent that amputation was no longer requested. It is concluded that EMG SFT can be beneficial in the neuromuscular reeducation of paretic upper extremity muscles of CVA patients with expressive aphasia and (impaired) auditory comprehension.

Cloning of heat shock protein genes (hsp70, hsc70 and hsp90) and their expression in response to larval diapause and thermal stress in the wheat blossom midge, Sitodiplosis mosellana.

PubMed

Cheng, Weining; Li, Dan; Wang, Yue; Liu, Yang; Zhu-Salzman, Keyan

2016-12-01

Sitodiplosis mosellana Géhin, one of the most important pests of wheat, undergoes obligatory diapause as a larva to survive unfavorable temperature extremes during hot summers and cold winters. To explore the potential roles of heat shock proteins (hsp) in this process, we cloned full-length cDNAs of hsp70, hsc70 and hsp90 from S. mosellana larvae, and examined their expression in response to diapause and short-term temperature stresses. Three hsps included all signature sequences of corresponding protein family and EEVD motifs. They showed high homology to their counterparts in other species, and the phylogenetic analysis of hsp90 was consistent with the known classification of insects. Expression of hsp70 and hsp90 were highly induced by diapause, particularly pronounced during summer and winter. Interestingly, hsp70 was more strongly expressed in summer than in winter whereas hsp90 displayed the opposite pattern. Abundance of hsc70 mRNA was comparable prior to and during diapauses and was highly up-regulated when insects began to enter the stage of post-diapause quiescence. Heat-stressed over-summering larvae (⩾30°C) or cold-stressed over-wintering larvae (⩽0°C) could further elevate expression of these three genes, but temperature extremes i.e. as high as 45°C or as low as -15°C failed to trigger such expression patterns. Notably, hsp70 was most sensitive to heat stress and hsp90 was most sensitive to cold stress. These results suggested that hsp70 and hsp90 play key roles in diapause maintenance and thermal stress; the former may be more prominent contributor to heat tolerance and the latter for cold tolerance. In contrast, hsc70 most likely is involved in developmental transition from diapause to post-diapause quiescence, and thus may serve as a molecular marker to predict diapause termination. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using Extreme Tropical Precipitation Statistics to Constrain Future Climate States

NASA Astrophysics Data System (ADS)

Igel, M.; Biello, J. A.

2017-12-01

Tropical precipitation is characterized by a rapid growth in mean intensity as the column humidity increases. This behavior is examined in both a cloud resolving model and with high-resolution observations of precipitation and column humidity from CloudSat and AIRS, respectively. The model and the observations exhibit remarkable consistency and suggest a new paradigm for extreme precipitation. We show that the total precipitation can be decomposed into a product of contributions from a mean intensity, a probability of precipitation, and a global PDF of column humidity values. We use the modeling and observational results to suggest simple, analytic forms for each of these functions. The analytic representations are then used to construct a simple expression for the global accumulated precipitation as a function of the parameters of each of the component functions. As the climate warms, extreme precipitation intensity and global precipitation are expected to increase, though at different rates. When these predictions are incorporated into the new analytic expression for total precipitation, predictions for changes due to global warming to the probability of precipitation and the PDF of column humidity can be made. We show that strong constraints can be imposed on the future shape of the PDF of column humidity but that only weak constraints can be set on the probability of precipitation. These are largely imposed by the intensification of extreme precipitation. This result suggests that understanding precisely how extreme precipitation responds to climate warming is critical to predicting other impactful properties of global hydrology. The new framework can also be used to confirm and discount existing theories for shifting precipitation.

Finding differentially expressed genes in high dimensional data: Rank based test statistic via a distance measure.

PubMed

Mathur, Sunil; Sadana, Ajit

2015-12-01

We present a rank-based test statistic for the identification of differentially expressed genes using a distance measure. The proposed test statistic is highly robust against extreme values and does not assume the distribution of parent population. Simulation studies show that the proposed test is more powerful than some of the commonly used methods, such as paired t-test, Wilcoxon signed rank test, and significance analysis of microarray (SAM) under certain non-normal distributions. The asymptotic distribution of the test statistic, and the p-value function are discussed. The application of proposed method is shown using a real-life data set. © The Author(s) 2011.

High Laccase Expression by Trametes versicolor in a Simulated Textile Effluent with Different Carbon Sources and PHs.

PubMed

Ottoni, Cristiane; Simões, Marta F; Fernandes, Sara; Santos, Cledir R; Lima, Nelson

2016-08-02

Textile effluents are highly polluting and have variable and complex compositions. They can be extremely complex, with high salt concentrations and alkaline pHs. A fixed-bed bioreactor was used in the present study to simulate a textile effluent treatment, where the white-rot fungus, Trametes versicolor, efficiently decolourised the azo dye Reactive Black 5 over 28 days. This occurred under high alkaline conditions, which is unusual, but advantageous, for successful decolourisation processes. Active dye decolourisation was maintained by operation in continuous culture. Colour was eliminated during the course of operation and maximum laccase (Lcc) activity (80.2 U∙L(-1)) was detected after glycerol addition to the bioreactor. Lcc2 gene expression was evaluated with different carbon sources and pH values based on reverse transcriptase-PCR (polymerase chain reaction). Glycerol was shown to promote the highest lcc2 expression at pH 5.5, followed by sucrose and then glucose. The highest levels of expression occurred between three and four days, which corroborate the maximum Lcc activity observed for sucrose and glycerol on the bioreactor. These results give new insights into the use of T. versicolor in textile dye wastewater treatment with high pHs.

An Ultra-High Fluorescence Enhancement and High Throughput Assay for Revealing Expression and Internalization of Chemokine Receptor CXCR4.

PubMed

He, Hua; Wang, Xiaojuan; Cheng, Tiantian; Xia, Yongqing; Lao, Jun; Ge, Baosheng; Ren, Hao; Khan, Naseer Ullah; Huang, Fang

2016-04-18

Revealing chemokine receptor CXCR4 expression, distribution, and internalization levels in different cancers helps to evaluate cancer progression or prognosis and to set personalized treatment strategy. We here describe a sensitive and high-throughput immunoassay for determining CXCR4 expression and distribution in cancer cells. The assay is accessible to a wide range of users in an ordinary lab only by dip-coating poly(styrene-co-N-isopropylacrylamide) spheres on the glass substrate. The self- assembled spheres form three-dimensional photonic colloidal crystals which enhance the fluorescence of CF647 and Alexa Fluor 647 by a factor of up to 1000. CXCR4 in cells is detected by using the sandwich immunoassay, where the primary antibody recognizes CXCR4 and the secondary antibody is labeled with CF647. With the newly established assay, we quantified the total expression of CXCR4, its distribution on the cell membrane and cytoplasm, and revealed their internalization level upon SDF-1α activation in various cancer cells, even for those with extremely low expression level. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ethylene Mediates Alkaline-Induced Rice Growth Inhibition by Negatively Regulating Plasma Membrane H+-ATPase Activity in Roots

PubMed Central

Chen, Haifei; Zhang, Quan; Cai, Hongmei; Xu, Fangsen

2017-01-01

pH is an important factor regulating plant growth. Here, we found that rice was better adapted to low pH than alkaline conditions, as its growth was severely inhibited at high pH, with shorter root length and an extreme biomass reduction. Under alkaline stress, the expression of genes for ethylene biosynthesis enzymes in rice roots was strongly induced by high pH and exogenous ethylene precursor ACC and ethylene overproduction in etol1-1 mutant aggravated the alkaline stress-mediated inhibition of rice growth, especially for the root elongation with decreased cell length in root apical regions. Conversely, the ethylene perception antagonist silver (Ag+) and ein2-1 mutants could partly alleviate the alkaline-induced root elongation inhibition. The H+-ATPase activity was extremely inhibited by alkaline stress and exogenous ACC. However, the H+-ATPase-mediated rhizosphere acidification was enhanced by exogenous Ag+, while H+ efflux on the root surface was extremely inhibited by exogenous ACC, suggesting that ethylene negatively regulated H+-ATPase activity under high-pH stress. Our results demonstrate that H+-ATPase is involved in ethylene-mediated inhibition of rice growth under alkaline stress. PMID:29114258

Small RNA-mediated responses to low- and high-temperature stresses in cotton

PubMed Central

Wang, Qiongshan; Liu, Nian; Yang, Xiyan; Tu, Lili; Zhang, Xianlong

2016-01-01

MicroRNAs (miRNAs) are one class of endogenous non-coding RNAs modulating the expression of target genes involved in plant development and stress tolerance, by degrading mRNA or repressing translation. In this study, small RNA and mRNA degradome sequencing were used to identify low- and high-temperature stress-responsive miRNAs and their targets in cotton (Gossypium hirsutum). Cotton seedlings were treated under different temperature conditions (4, 12, 25, 35, and 42 °C) and then the effects were investigated. In total, 319 known miRNAs and 800 novel miRNAs were identified, and 168 miRNAs were differentially expressed between different treatments. The targets of these miRNAs were further analysed by degradome sequencing. Based on studies from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, the majority of the miRNAs are from genes that are likely involved in response to hormone stimulus, oxidation-reduction reaction, photosynthesis, plant–pathogen interaction and plant hormone signal transduction pathways. This study provides new insight into the molecular mechanisms of plant response to extreme temperature stresses, and especially the roles of miRNAs under extreme temperatures. PMID:27752116

Non-thermal recombination - a neglected source of flare hard X-rays and fast electron diagnostics (Corrigendum)

NASA Astrophysics Data System (ADS)

Brown, J. C.; Mallik, P. C. V.; Badnell, N. R.

2010-06-01

Brown and Mallik (BM) recently claimed that non-thermal recombination (NTR) can be a dominant source of flare hard X-rays (HXRs) from hot coronal and chromospheric sources. However, major discrepancies between the thermal continua predicted by BM and by the Chianti database as well as RHESSI flare data, led us to discover substantial errors in the heuristic expression used by BM to extend the Kramers expressions beyond the hydrogenic case. Here we present the relevant corrected expressions and show the key modified results. We conclude that, in most cases, NTR emission was overestimated by a factor of 1-8 by BM but is typically still large enough (as much as 20-30% of the total emission) to be very important for electron spectral inference and detection of electron spectral features such as low energy cut-offs since the recombination spectra contain sharp edges. For extreme temperature regimes and/or if the Fe abundance were as high as some values claimed, NTR could even be the dominant source of flare HXRs, reducing the electron number and energy budget, problems such as in the extreme coronal HXR source cases reported by e.g. Krucker et al.

Adaptation and evolution of deep-sea scale worms (Annelida: Polynoidae): insights from transcriptome comparison with a shallow-water species

NASA Astrophysics Data System (ADS)

Zhang, Yanjie; Sun, Jin; Chen, Chong; Watanabe, Hiromi K.; Feng, Dong; Zhang, Yu; Chiu, Jill M. Y.; Qian, Pei-Yuan; Qiu, Jian-Wen

2017-04-01

Polynoid scale worms (Polynoidae, Annelida) invaded deep-sea chemosynthesis-based ecosystems approximately 60 million years ago, but little is known about their genetic adaptation to the extreme deep-sea environment. In this study, we reported the first two transcriptomes of deep-sea polynoids (Branchipolynoe pettiboneae, Lepidonotopodium sp.) and compared them with the transcriptome of a shallow-water polynoid (Harmothoe imbricata). We determined codon and amino acid usage, positive selected genes, highly expressed genes and putative duplicated genes. Transcriptome assembly produced 98,806 to 225,709 contigs in the three species. There were more positively charged amino acids (i.e., histidine and arginine) and less negatively charged amino acids (i.e., aspartic acid and glutamic acid) in the deep-sea species. There were 120 genes showing clear evidence of positive selection. Among the 10% most highly expressed genes, there were more hemoglobin genes with high expression levels in both deep-sea species. The duplicated genes related to DNA recombination and metabolism, and gene expression were only enriched in deep-sea species. Deep-sea scale worms adopted two strategies of adaptation to hypoxia in the chemosynthesis-based habitats (i.e., rapid evolution of tetra-domain hemoglobin in Branchipolynoe or high expression of single-domain hemoglobin in Lepidonotopodium sp.).

Adaptation and evolution of deep-sea scale worms (Annelida: Polynoidae): insights from transcriptome comparison with a shallow-water species

PubMed Central

Zhang, Yanjie; Sun, Jin; Chen, Chong; Watanabe, Hiromi K.; Feng, Dong; Zhang, Yu; Chiu, Jill M.Y.; Qian, Pei-Yuan; Qiu, Jian-Wen

2017-01-01

Polynoid scale worms (Polynoidae, Annelida) invaded deep-sea chemosynthesis-based ecosystems approximately 60 million years ago, but little is known about their genetic adaptation to the extreme deep-sea environment. In this study, we reported the first two transcriptomes of deep-sea polynoids (Branchipolynoe pettiboneae, Lepidonotopodium sp.) and compared them with the transcriptome of a shallow-water polynoid (Harmothoe imbricata). We determined codon and amino acid usage, positive selected genes, highly expressed genes and putative duplicated genes. Transcriptome assembly produced 98,806 to 225,709 contigs in the three species. There were more positively charged amino acids (i.e., histidine and arginine) and less negatively charged amino acids (i.e., aspartic acid and glutamic acid) in the deep-sea species. There were 120 genes showing clear evidence of positive selection. Among the 10% most highly expressed genes, there were more hemoglobin genes with high expression levels in both deep-sea species. The duplicated genes related to DNA recombination and metabolism, and gene expression were only enriched in deep-sea species. Deep-sea scale worms adopted two strategies of adaptation to hypoxia in the chemosynthesis-based habitats (i.e., rapid evolution of tetra-domain hemoglobin in Branchipolynoe or high expression of single-domain hemoglobin in Lepidonotopodium sp.). PMID:28397791

Superior Cross-Species Reference Genes: A Blueberry Case Study

PubMed Central

Die, Jose V.; Rowland, Lisa J.

2013-01-01

The advent of affordable Next Generation Sequencing technologies has had major impact on studies of many crop species, where access to genomic technologies and genome-scale data sets has been extremely limited until now. The recent development of genomic resources in blueberry will enable the application of high throughput gene expression approaches that should relatively quickly increase our understanding of blueberry physiology. These studies, however, require a highly accurate and robust workflow and make necessary the identification of reference genes with high expression stability for correct target gene normalization. To create a set of superior reference genes for blueberry expression analyses, we mined a publicly available transcriptome data set from blueberry for orthologs to a set of Arabidopsis genes that showed the most stable expression in a developmental series. In total, the expression stability of 13 putative reference genes was evaluated by qPCR and a set of new references with high stability values across a developmental series in fruits and floral buds of blueberry were identified. We also demonstrated the need to use at least two, preferably three, reference genes to avoid inconsistencies in results, even when superior reference genes are used. The new references identified here provide a valuable resource for accurate normalization of gene expression in Vaccinium spp. and may be useful for other members of the Ericaceae family as well. PMID:24058469

The high-level expression of human tissue plasminogen activator in the milk of transgenic mice with hybrid gene locus strategy.

PubMed

Zhou, Yanrong; Lin, Yanli; Wu, Xiaojie; Xiong, Fuyin; Lv, Yuemeng; Zheng, Tao; Huang, Peitang; Chen, Hongxing

2012-02-01

Transgene expression for the mammary gland bioreactor aimed at producing recombinant proteins requires optimized expression vector construction. Previously we presented a hybrid gene locus strategy, which was originally tested with human lactoferrin (hLF) as target transgene, and an extremely high-level expression of rhLF ever been achieved as to 29.8 g/l in mice milk. Here to demonstrate the broad application of this strategy, another 38.4 kb mWAP-htPA hybrid gene locus was constructed, in which the 3-kb genomic coding sequence in the 24-kb mouse whey acidic protein (mWAP) gene locus was substituted by the 17.4-kb genomic coding sequence of human tissue plasminogen activator (htPA), exactly from the start codon to the end codon. Corresponding five transgenic mice lines were generated and the highest expression level of rhtPA in the milk attained as to 3.3 g/l. Our strategy will provide a universal way for the large-scale production of pharmaceutical proteins in the mammary gland of transgenic animals.

Selective probing of mRNA expression levels within a living cell.

PubMed

Nawarathna, D; Turan, T; Wickramasinghe, H Kumar

2009-08-24

We report on a selective and nondestructive measurement of mRNA (messenger ribonucleic acid) expression levels within a living cell. We first modify an atomic force microscope tip to create a tapered nanoscale coaxial cable. Application of an ac (alternating potential) between the inner and outer electrodes of this cable creates a dielectrophoretic force attracting mRNA molecules toward the tip-end which is pretreated with gene specific primers. We selectively extracted and analyzed both high ( approximately 2500) and extremely low (11 0) copy number mRNA from a living cell mRNA in less than 10 s.

Cell wall metabolism and hexose allocation contribute to biomass accumulation in high yielding extreme segregants of a Saccharum interspecific F2 population.

PubMed

Wai, Ching Man; Zhang, Jisen; Jones, Tyler C; Nagai, Chifumi; Ming, Ray

2017-10-11

Sugarcane is an emerging dual-purpose biofuel crop for energy and sugar production, owing to its rapid growth rate, high sucrose storage in the stems, and high lignocellulosic yield. It has the highest biomass production reaching 1.9 billion tonnes in 2014 worldwide. To improve sugarcane biomass accumulation, we developed an interspecific cross between Saccharum officinarum 'LA Purple' and Saccharum robustum 'MOL5829'. Selected F1 individuals were self-pollinated to generate a transgressive F2 population with a wide range of biomass yield. Leaf and stem internodes of fourteen high biomass and eight low biomass F2 extreme segregants were used for RNA-seq to decipher the molecular mechanism of rapid plant growth and dry weight accumulation. Gene Ontology terms involved in cell wall metabolism and carbohydrate catabolism were enriched among 3274 differentially expressed genes between high and low biomass groups. Up-regulation of cellulose metabolism, pectin degradation and lignin biosynthesis genes were observed in the high biomass group, in conjunction with higher transcript levels of callose metabolic genes and the cell wall loosening enzyme expansin. Furthermore, UDP-glucose biosynthesis and sucrose conversion genes were differentially expressed between the two groups. A positive correlation between stem glucose, but not sucrose, levels and dry weight was detected. We thus postulated that the high biomass sugarcane plants rapidly convert sucrose to UDP-glucose, which is the building block of cell wall polymers and callose, in order to maintain the rapid plant growth. The gene interaction of cell wall metabolism, hexose allocation and cell division contributes to biomass yield.

Endometrial gene expression profile of pregnant sows with extreme phenotypes for reproductive efficiency.

PubMed

Córdoba, S; Balcells, I; Castelló, A; Ovilo, C; Noguera, J L; Timoneda, O; Sánchez, A

2015-10-05

Prolificacy can directly impact porcine profitability, but large genetic variation and low heritability have been found regarding litter size among porcine breeds. To identify key differences in gene expression associated to swine reproductive efficiency, we performed a transcriptome analysis of sows' endometrium from an Iberian x Meishan F2 population at day 30-32 of gestation, classified according to their estimated breeding value (EBV) as high (H, EBV > 0) and low (L, EBV < 0) prolificacy phenotypes. For each sample, mRNA and small RNA libraries were RNA-sequenced, identifying 141 genes and 10 miRNAs differentially expressed between H and L groups. We selected four miRNAs based on their role in reproduction, and five genes displaying the highest differences and a positive mapping into known reproductive QTLs for RT-qPCR validation on the whole extreme population. Significant differences were validated for genes: PTGS2 (p = 0.03; H/L ratio = 3.50), PTHLH (p = 0.03; H/L ratio = 3.69), MMP8 (p = 0.01; H/L ratio =4.41) and SCNN1G (p = 0.04; H/L ratio = 3.42). Although selected miRNAs showed similar expression levels between H and L groups, significant correlation was found between the expression level of ssc-miR-133a (p < 0.01) and ssc-miR-92a (p < 0.01) and validated genes. These results provide a better understanding of the genetic architecture of prolificacy-related traits and embryo implantation failure in pigs.

Non-conventional expression systems for the production of vaccine proteins and immunotherapeutic molecules

PubMed Central

Legastelois, Isabelle; Buffin, Sophie; Peubez, Isabelle; Mignon, Charlotte; Sodoyer, Régis; Werle, Bettina

2017-01-01

ABSTRACT The increasing demand for recombinant vaccine antigens or immunotherapeutic molecules calls into question the universality of current protein expression systems. Vaccine production can require relatively low amounts of expressed materials, but represents an extremely diverse category consisting of different target antigens with marked structural differences. In contrast, monoclonal antibodies, by definition share key molecular characteristics and require a production system capable of very large outputs, which drives the quest for highly efficient and cost-effective systems. In discussing expression systems, the primary assumption is that a universal production platform for vaccines and immunotherapeutics will unlikely exist. This review provides an overview of the evolution of traditional expression systems, including mammalian cells, yeast and E.coli, but also alternative systems such as other bacteria than E. coli, transgenic animals, insect cells, plants and microalgae, Tetrahymena thermophila, Leishmania tarentolae, filamentous fungi, cell free systems, and the incorporation of non-natural amino acids. PMID:27905833

Rapid changes in gene expression direct rapid shifts in intestinal form and function in the Burmese python after feeding.

PubMed

Andrew, Audra L; Card, Daren C; Ruggiero, Robert P; Schield, Drew R; Adams, Richard H; Pollock, David D; Secor, Stephen M; Castoe, Todd A

2015-05-01

Snakes provide a unique and valuable model system for studying the extremes of physiological remodeling because of the ability of some species to rapidly upregulate organ form and function upon feeding. The predominant model species used to study such extreme responses has been the Burmese python because of the extreme nature of postfeeding response in this species. We analyzed the Burmese python intestine across a time series, before, during, and after feeding to understand the patterns and timing of changes in gene expression and their relationship to changes in intestinal form and function upon feeding. Our results indicate that >2,000 genes show significant changes in expression in the small intestine following feeding, including genes involved in intestinal morphology and function (e.g., hydrolases, microvillus proteins, trafficking and transport proteins), as well as genes involved in cell division and apoptosis. Extensive changes in gene expression occur surprisingly rapidly, within the first 6 h of feeding, coincide with changes in intestinal morphology, and effectively return to prefeeding levels within 10 days. Collectively, our results provide an unprecedented portrait of parallel changes in gene expression and intestinal morphology and physiology on a scale that is extreme both in the magnitude of changes, as well as in the incredibly short time frame of these changes, with up- and downregulation of expression and function occurring in the span of 10 days. Our results also identify conserved vertebrate signaling pathways that modulate these responses, which may suggest pathways for therapeutic modulation of intestinal function in humans. Copyright © 2015 the American Physiological Society.

Presence of the P2RY8-CRLF2 rearrangement is associated with a poor prognosis in non-high-risk precursor B-cell acute lymphoblastic leukemia in children treated according to the ALL-BFM 2000 protocol.

PubMed

Cario, Gunnar; Zimmermann, Martin; Romey, Renja; Gesk, Stefan; Vater, Inga; Harbott, Jochen; Schrauder, André; Moericke, Anja; Izraeli, Shai; Akasaka, Takashi; Dyer, Martin J S; Siebert, Reiner; Schrappe, Martin; Stanulla, Martin

2010-07-01

High-level expression of the cytokine receptor-like factor 2 gene, CRLF2, in precursor B-cell acute lymphoblastic leukemia (pB-ALL) was shown to be caused by a translocation involving the IGH@ locus or a deletion juxtaposing CRLF2 with the P2RY8 promoter. To assess its possible prognostic value, CRLF2 expression was analyzed in 555 childhood pB-ALL patients treated according to the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster 2000 (ALL-BFM 2000) protocol. Besides CRLF2 rearrangements, high-level CRLF2 expression was seen in cases with supernumerary copies of the CRLF2 locus. On the basis of the detection of CRLF2 rearrangements, a CRLF2 high-expression group (n = 49) was defined. This group had a 6-year relapse incidence of 31% plus or minus 8% compared with 11% plus or minus 1% in the CRLF2 low-expression group (P = .006). This difference was mainly attributable to an extremely high incidence of relapse (71% +/- 19%) in non-high-risk patients with P2RY8-CRLF2 rearrangement. The assessment of CRLF2 aberrations may therefore serve as new stratification tool in Berlin-Frankfurt-Münster-based protocols by identifying additional high-risk patients who may benefit from an intensified and/or targeted treatment.

First characterization of extremely halophilic 2-deoxy-D-ribose-5-phosphate aldolase.

PubMed

Ohshida, Tatsuya; Hayashi, Junji; Satomura, Takenori; Kawakami, Ryushi; Ohshima, Toshihisa; Sakuraba, Haruhiko

2016-10-01

2-Deoxy-d-ribose-5-phosphate aldolase (DERA) catalyzes the aldol reaction between two aldehydes and is thought to be a potential biocatalyst for the production of a variety of stereo-specific materials. A gene encoding DERA from the extreme halophilic archaeon, Haloarcula japonica, was overexpressed in Escherichia coli. The gene product was successfully purified, using procedures based on the protein's halophilicity, and characterized. The expressed enzyme was stable in a buffer containing 2 M NaCl and exhibited high thermostability, retaining more than 90% of its activity after heating at 70 °C for 10 min. The enzyme was also tolerant to high concentrations of organic solvents, such as acetonitrile and dimethylsulfoxide. Moreover, H. japonica DERA was highly resistant to a high concentration of acetaldehyde and retained about 35% of its initial activity after 5-h' exposure to 300 mM acetaldehyde at 25 °C, the conditions under which E. coli DERA is completely inactivated. The enzyme exhibited much higher activity at 25 °C than the previously characterized hyperthermophilic DERAs (Sakuraba et al., 2007). Our results suggest that the extremely halophilic DERA has high potential to serve as a biocatalyst in organic syntheses. This is the first description of the biochemical characterization of a halophilic DERA. Copyright © 2016 Elsevier Inc. All rights reserved.

High Laccase Expression by Trametes versicolor in a Simulated Textile Effluent with Different Carbon Sources and PHs

PubMed Central

Ottoni, Cristiane; Simões, Marta F.; Fernandes, Sara; Santos, Cledir R.; Lima, Nelson

2016-01-01

Textile effluents are highly polluting and have variable and complex compositions. They can be extremely complex, with high salt concentrations and alkaline pHs. A fixed-bed bioreactor was used in the present study to simulate a textile effluent treatment, where the white-rot fungus, Trametes versicolor, efficiently decolourised the azo dye Reactive Black 5 over 28 days. This occurred under high alkaline conditions, which is unusual, but advantageous, for successful decolourisation processes. Active dye decolourisation was maintained by operation in continuous culture. Colour was eliminated during the course of operation and maximum laccase (Lcc) activity (80.2 U∙L−1) was detected after glycerol addition to the bioreactor. Lcc2 gene expression was evaluated with different carbon sources and pH values based on reverse transcriptase-PCR (polymerase chain reaction). Glycerol was shown to promote the highest lcc2 expression at pH 5.5, followed by sucrose and then glucose. The highest levels of expression occurred between three and four days, which corroborate the maximum Lcc activity observed for sucrose and glycerol on the bioreactor. These results give new insights into the use of T. versicolor in textile dye wastewater treatment with high pHs. PMID:27490563

A nested observation and model approach to non linear groundwater surface water interactions.

NASA Astrophysics Data System (ADS)

van der Velde, Y.; Rozemeijer, J. C.; de Rooij, G. H.

2009-04-01

Surface water quality measurements in The Netherlands are scattered in time and space. Therefore, water quality status and its variations and trends are difficult to determine. In order to reach the water quality goals according to the European Water Framework Directive, we need to improve our understanding of the dynamics of surface water quality and the processes that affect it. In heavily drained lowland catchment groundwater influences the discharge towards the surface water network in many complex ways. Especially a strong seasonal contracting and expanding system of discharging ditches and streams affects discharge and solute transport. At a tube drained field site the tube drain flux and the combined flux of all other flow routes toward a stretch of 45 m of surface water have been measured for a year. Also the groundwater levels at various locations in the field and the discharge at two nested catchment scales have been monitored. The unique reaction of individual flow routes on rainfall events at the field site allowed us to separate the discharge at a 4 ha catchment and at a 6 km2 into flow route contributions. The results of this nested experimental setup combined with the results of a distributed hydrological model has lead to the formulation of a process model approach that focuses on the spatial variability of discharge generation driven by temporal and spatial variations in groundwater levels. The main idea of this approach is that discharge is not generated by catchment average storages or groundwater heads, but is mainly generated by points scale extremes i.e. extreme low permeability, extreme high groundwater heads or extreme low surface elevations, all leading to catchment discharge. We focused on describing the spatial extremes in point scale storages and this led to a simple and measurable expression that governs the non-linear groundwater surface water interaction. We will present the analysis of the field site data to demonstrate the potential of nested-scale, high frequency observations. The distributed hydrological model results will be used to show transient catchment scale relations between groundwater levels and discharges. These analyses lead to a simple expression that can describe catchment scale groundwater surface water interactions.

Prognostic value of proliferation in pleomorphic soft tissue sarcomas: a new look at an old measure.

PubMed

Seinen, Jojanneke M; Jönsson, Mats; Bendahl, Pär-Ola O; Baldetorp, Bo; Rambech, Eva; Åkerman, Måns; Rydholm, Anders; Nilbert, Mef; Carneiro, Ana

2012-12-01

Though proliferation has repeatedly shown a prognostic role in sarcomas, it has not reached clinical application. We performed a comprehensive evaluation of the prognostic role of 5 proliferation measures in a large series of soft tissue sarcomas of the extremities and the trunk wall. One hundred ninety-six primary soft tissue sarcomas of the extremities and the trunk wall were subjected to DNA flow cytometry for quantification of S-phase fraction and to immunohistochemical evaluation of Ki-67, Top2a, p21, and p27Kip1. In univariate analysis, positive expression of Ki-67 (hazard ratio = 4.5, CI = 1.6-12.1), Top2a (hazard ratio = 2.2, CI = 1.2-3.5) and high S-phase fraction (hazard ratio = 1.8, CI = 1.2-3.7) significantly correlated with risk for metastasis. When combined with currently used prognostic factors, Ki-67, S-phase fraction and Top2a fraction contributed to refined identification of prognostic risk groups. Proliferation, as assessed by expression of Ki-67 and Top2a and evaluation of S-phase fraction and applied to statistical decision-tree models, provides prognostic information in soft tissue sarcomas of the extremity and trunk wall. Though proliferation contributes independently to currently applied prognosticators, its role is particularly strong when few other factors are available, which suggests a role in preoperative decision-making related to identification of high-risk individuals who would benefit from neoadjuvant therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Exposure to an extremely low-frequency electromagnetic field only slightly modifies the proteome of Chromobacterium violaceumATCC 12472.

PubMed

Baraúna, Rafael A; Santos, Agenor V; Graças, Diego A; Santos, Daniel M; Ghilardi, Rubens; Pimenta, Adriano M C; Carepo, Marta S P; Schneider, Maria P C; Silva, Artur

2015-05-01

Several studies of the physiological responses of different organisms exposed to extremely low-frequency electromagnetic fields (ELF-EMF) have been described. In this work, we report the minimal effects of in situ exposure to ELF-EMF on the global protein expression of Chromobacterium violaceum using a gel-based proteomic approach. The protein expression profile was only slightly altered, with five differentially expressed proteins detected in the exposed cultures; two of these proteins (DNA-binding stress protein, Dps, and alcohol dehydrogenase) were identified by MS/MS. The enhanced expression of Dps possibly helped to prevent physical damage to DNA. Although small, the changes in protein expression observed here were probably beneficial in helping the bacteria to adapt to the stress generated by the electromagnetic field.

Characterization of reference genes for RT-qPCR in the desert moss Syntrichia caninervis in response to abiotic stress and desiccation/rehydration

PubMed Central

Li, Xiaoshuang; Zhang, Daoyuan; Li, Haiyan; Gao, Bei; Yang, Honglan; Zhang, Yuanming; Wood, Andrew J.

2015-01-01

Syntrichia caninervis is the dominant bryophyte of the biological soil crusts found in the Gurbantunggut desert. The extreme desert environment is characterized by prolonged drought, temperature extremes, high radiation and frequent cycles of hydration and dehydration. S. caninervis is an ideal organism for the identification and characterization of genes related to abiotic stress tolerance. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) expression analysis is a powerful analytical technique that requires the use of stable reference genes. Using available S. caninervis transcriptome data, we selected 15 candidate reference genes and analyzed their relative expression stabilities in S. caninervis gametophores exposed to a range of abiotic stresses or a hydration-desiccation-rehydration cycle. The programs geNorm, NormFinder, and RefFinder were used to assess and rank the expression stability of the 15 candidate genes. The stability ranking results of reference genes under each specific experimental condition showed high consistency using different algorithms. For abiotic stress treatments, the combination of two genes (α-TUB2 and CDPK) were sufficient for accurate normalization. For the hydration-desiccation-rehydration process, the combination of two genes (α-TUB1 and CDPK) were sufficient for accurate normalization. 18S was among the least stable genes in all of the experimental sets and was unsuitable as reference gene in S. caninervis. This is the first systematic investigation and comparison of reference gene selection for RT-qPCR work in S. caninervis. This research will facilitate gene expression studies in S. caninervis, related moss species from the Syntrichia complex and other mosses. PMID:25699066

Interaction between platelet-derived microRNAs and CYP2C19*2 genotype on clopidogrel antiplatelet responsiveness in patients with ACS.

PubMed

Peng, Li; Liu, Jun; Qin, Liuan; Liu, Jia; Xi, Shaozhi; Lu, Caiyi; Yin, Tong

2017-09-01

Both platelet-derived microRNAs and the genotype of CYP2C19*2 were implicated for the variability of clopidogrel antiplatelet responsiveness. However, their interaction on the antiplatelet responsiveness of clopidogrel in patients with acute coronary syndrome (ACS) remains unknown. Consecutive clopidogrel-treated patients with ACS were recruited, with their antiplatelet responsiveness evaluated by the relative platelet inhibition (RI), as measured by light transmittance aggregometry (LTA) at baseline and 5days' after the maintenance treatment of clopidogrel. Extreme cases were selected according to the octiles of RI value. Expression of the microRNAs targeting the mRNAs of P2RY12 was analyzed in the platelet of the extreme cases. Genotyping of CYP2C19*2 was performed for each extreme case. Among the included 272 ACS patients, 21 cases were screened as the extremely high-responders with RI>84%, and 18 as the extremely low-responders with RI<10%. Bioinformatics tools predicted the candidate microRNAs of miR-223, miR-221, and miR-21 could bind directly to the mRNA of P2RY12. Compared with the extremely low-responders, the expression of miR-223, miR-221, and miR-21 was significantly higher in the extremely high-responders (miR-223: 7.18±2.95 vs. 0.99±0.64, p=0.022; miR-221: 3.60±2.54 vs. 1.14±0.81, p=0.004; miR-21: 4.36±3.33 vs. 2.31±1.69, p=0.01). ROC curve showed ideal discriminatory power of the platelet-derived miRNAs for the prediction of clopidogrel antiplatelet responsiveness (c-index=0.70 for miR-223; c-index=0.76 for miR-221; c-index=0.79 for miR-21). After stratified by the carrier status of CYP2C19*2, the association between platelet-derived miRNAs and clopidogrel antiplatelet responsiveness could be found only in CYP2C19*2 carriers, but not in non-carriers. Platelet-derived miRNAs (miR-223, miR-221 and miR-21) are independently associated with clopidogrel antiplatelet responsiveness in ACS patients. However, the association could be influenced by the interaction with CYP2C19*2 genotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quantitative analysis of lentiviral transgene expression in mice over seven generations.

PubMed

Wang, Yong; Song, Yong-tao; Liu, Qin; Liu, Cang'e; Wang, Lu-lu; Liu, Yu; Zhou, Xiao-yang; Wu, Jun; Wei, Hong

2010-10-01

Lentiviral transgenesis is now recognized as an extremely efficient and cost-effective method to produce transgenic animals. Transgenes delivered by lentiviral vectors exhibited inheritable expression in many species including those which are refractory to genetic modification such as non-human primates. However, epigenetic modification was frequently observed in lentiviral integrants, and transgene expression found to be inversely correlated with methylation density. Recent data showed that about one-third lentiviral integrants exhibited hypermethylation and low expression, but did not demonstrate whether those integrants with high expression could remain constant expression and hypomethylated during long term germline transmission. In this study, using lentiviral eGFP transgenic mice as the experimental animals, lentiviral eGFP expression levels and its integrant numbers in genome were quantitatively analyzed by fluorescent quantitative polymerase-chain reaction (FQ-PCR), using the house-keeping gene ribosomal protein S18 (Rps18) and the single copy gene fatty acid binding protein of the intestine (Fabpi) as the internal controls respectively. The methylation densities of the integrants were quantitatively analyzed by bisulfite sequencing. We found that the lentiviral integrants with high expression exhibited a relative constant expression level per integrant over at least seven generations. Besides, the individuals containing these integrants exhibited eGFP expression levels which were positively and almost linearly correlated with the integrant numbers in their genomes, suggesting that no remarkable position effect on transgene expression of the integrants analyzed was observed. In addition, over seven generations the methylation density of these integrants did not increase, but rather decreased remarkably, indicating that these high expressing integrants were not subjected to de novo methylation during at least seven generations of germline transmission. Taken together, these data suggested that transgenic lines with long term stable expression and no position effect can be established by lentiviral transgenesis.

The Maternal Maverick/GDF15-like TGF-β Ligand Panda Directs Dorsal-Ventral Axis Formation by Restricting Nodal Expression in the Sea Urchin Embryo.

PubMed

Haillot, Emmanuel; Molina, Maria Dolores; Lapraz, François; Lepage, Thierry

2015-01-01

Specification of the dorsal-ventral axis in the highly regulative sea urchin embryo critically relies on the zygotic expression of nodal, but whether maternal factors provide the initial spatial cue to orient this axis is not known. Although redox gradients have been proposed to entrain the dorsal-ventral axis by acting upstream of nodal, manipulating the activity of redox gradients only has modest consequences, suggesting that other factors are responsible for orienting nodal expression and defining the dorsal-ventral axis. Here we uncover the function of Panda, a maternally provided transforming growth factor beta (TGF-β) ligand that requires the activin receptor-like kinases (Alk) Alk3/6 and Alk1/2 receptors to break the radial symmetry of the embryo and orient the dorsal-ventral axis by restricting nodal expression. We found that the double inhibition of the bone morphogenetic protein (BMP) type I receptors Alk3/6 and Alk1/2 causes a phenotype dramatically more severe than the BMP2/4 loss-of-function phenotype, leading to extreme ventralization of the embryo through massive ectopic expression of nodal, suggesting that an unidentified signal acting through BMP type I receptors cooperates with BMP2/4 to restrict nodal expression. We identified this ligand as the product of maternal Panda mRNA. Double inactivation of panda and bmp2/4 led to extreme ventralization, mimicking the phenotype caused by inactivation of the two BMP receptors. Inhibition of maternal panda mRNA translation disrupted the early spatial restriction of nodal, leading to persistent massive ectopic expression of nodal on the dorsal side despite the presence of Lefty. Phylogenetic analysis indicates that Panda is not a prototypical BMP ligand but a member of a subfamily of TGF-β distantly related to Inhibins, Lefty, and TGF-β that includes Maverick from Drosophila and GDF15 from vertebrates. Indeed, overexpression of Panda does not appear to directly or strongly activate phosphoSmad1/5/8 signaling, suggesting that although this TGF-β may require Alk1/2 and/or Alk3/6 to antagonize nodal expression, it may do so by sequestering a factor essential for Nodal signaling, by activating a non-Smad pathway downstream of the type I receptors, or by activating extremely low levels of pSmad1/5/8. We provide evidence that, although panda mRNA is broadly distributed in the early embryo, local expression of panda mRNA efficiently orients the dorsal-ventral axis and that Panda activity is required locally in the early embryo to specify this axis. Taken together, these findings demonstrate that maternal panda mRNA is both necessary and sufficient to orient the dorsal-ventral axis. These results therefore provide evidence that in the highly regulative sea urchin embryo, the activity of spatially restricted maternal factors regulates patterning along the dorsal-ventral axis.

The Maternal Maverick/GDF15-like TGF-β Ligand Panda Directs Dorsal-Ventral Axis Formation by Restricting Nodal Expression in the Sea Urchin Embryo

PubMed Central

Haillot, Emmanuel; Molina, Maria Dolores; Lapraz, François; Lepage, Thierry

2015-01-01

Specification of the dorsal-ventral axis in the highly regulative sea urchin embryo critically relies on the zygotic expression of nodal, but whether maternal factors provide the initial spatial cue to orient this axis is not known. Although redox gradients have been proposed to entrain the dorsal-ventral axis by acting upstream of nodal, manipulating the activity of redox gradients only has modest consequences, suggesting that other factors are responsible for orienting nodal expression and defining the dorsal-ventral axis. Here we uncover the function of Panda, a maternally provided transforming growth factor beta (TGF-β) ligand that requires the activin receptor-like kinases (Alk) Alk3/6 and Alk1/2 receptors to break the radial symmetry of the embryo and orient the dorsal-ventral axis by restricting nodal expression. We found that the double inhibition of the bone morphogenetic protein (BMP) type I receptors Alk3/6 and Alk1/2 causes a phenotype dramatically more severe than the BMP2/4 loss-of-function phenotype, leading to extreme ventralization of the embryo through massive ectopic expression of nodal, suggesting that an unidentified signal acting through BMP type I receptors cooperates with BMP2/4 to restrict nodal expression. We identified this ligand as the product of maternal Panda mRNA. Double inactivation of panda and bmp2/4 led to extreme ventralization, mimicking the phenotype caused by inactivation of the two BMP receptors. Inhibition of maternal panda mRNA translation disrupted the early spatial restriction of nodal, leading to persistent massive ectopic expression of nodal on the dorsal side despite the presence of Lefty. Phylogenetic analysis indicates that Panda is not a prototypical BMP ligand but a member of a subfamily of TGF-β distantly related to Inhibins, Lefty, and TGF-β that includes Maverick from Drosophila and GDF15 from vertebrates. Indeed, overexpression of Panda does not appear to directly or strongly activate phosphoSmad1/5/8 signaling, suggesting that although this TGF-β may require Alk1/2 and/or Alk3/6 to antagonize nodal expression, it may do so by sequestering a factor essential for Nodal signaling, by activating a non-Smad pathway downstream of the type I receptors, or by activating extremely low levels of pSmad1/5/8. We provide evidence that, although panda mRNA is broadly distributed in the early embryo, local expression of panda mRNA efficiently orients the dorsal-ventral axis and that Panda activity is required locally in the early embryo to specify this axis. Taken together, these findings demonstrate that maternal panda mRNA is both necessary and sufficient to orient the dorsal-ventral axis. These results therefore provide evidence that in the highly regulative sea urchin embryo, the activity of spatially restricted maternal factors regulates patterning along the dorsal-ventral axis. PMID:26352141

Neutron scattering reveals the dynamic basis of protein adaptation to extreme temperature.

PubMed

Tehei, Moeava; Madern, Dominique; Franzetti, Bruno; Zaccai, Giuseppe

2005-12-09

To explore protein adaptation to extremely high temperatures, two parameters related to macromolecular dynamics, the mean square atomic fluctuation and structural resilience, expressed as a mean force constant, were measured by neutron scattering for hyperthermophilic malate dehydrogenase from Methanococcus jannaschii and a mesophilic homologue, lactate dehydrogenase from Oryctolagus cunniculus (rabbit) muscle. The root mean square fluctuations, defining flexibility, were found to be similar for both enzymes (1.5 A) at their optimal activity temperature. Resilience values, defining structural rigidity, are higher by an order of magnitude for the high temperature-adapted protein (0.15 Newtons/meter for O. cunniculus lactate dehydrogenase and 1.5 Newtons/meter for M. jannaschii malate dehydrogenase). Thermoadaptation appears to have been achieved by evolution through selection of appropriate structural rigidity in order to preserve specific protein structure while allowing the conformational flexibility required for activity.

Rational engineering of a mesohalophilic carbonic anhydrase to an extreme halotolerant biocatalyst

PubMed Central

Warden, Andrew C.; Williams, Michelle; Peat, Thomas S.; Seabrook, Shane A.; Newman, Janet; Dojchinov, Greg; Haritos, Victoria S.

2015-01-01

Enzymes expressed by highly salt-tolerant organisms show many modifications compared with salt-affected counterparts including biased amino acid and lower α-helix content, lower solvent accessibility and negative surface charge. Here, we show that halotolerance can be generated in an enzyme solely by modifying surface residues. Rational design of carbonic anhydrase II is undertaken in three stages replacing 18 residues in total, crystal structures confirm changes are confined to surface residues. Catalytic activities and thermal unfolding temperatures of the designed enzymes increase at high salt concentrations demonstrating their shift to halotolerance, whereas the opposite response is found in the wild-type enzyme. Molecular dynamics calculations reveal a key role for sodium ions in increasing halotolerant enzyme stability largely through interactions with the highly ordered first Na+ hydration shell. For the first time, an approach to generate extreme halotolerance, a trait with broad application in industrial biocatalysis, in a wild-type enzyme is demonstrated. PMID:26687908

Transcriptomic Profiling and Physiological Responses of Halophyte Kochia sieversiana Provide Insights into Salt Tolerance

PubMed Central

Zhao, Long; Yang, Zongze; Guo, Qiaobing; Mao, Shun; Li, Shaoqiang; Sun, Fasheng; Wang, Huan; Yang, Chunwu

2017-01-01

Halophytes are remarkable plants that can tolerate extremely high-salinity conditions, and have different salinity tolerance mechanisms from those of glycophytic plants. In this work, we investigated the mechanisms of salinity tolerance of an extreme halophyte, Kochia sieversiana (Pall.) C. A. M, using RNA sequencing and physiological tests. The results showed that moderate salinity stimulated the growth and water uptake of K. sieversiana and, even under 480-mM salinity condition, K. sieversiana maintained an extremely high water content. This high water content may be a specific adaptive strategy of K. sieversiana to high salinity. The physiological analysis indicated that increasing succulence and great accumulations of sodium, alanine, sucrose, and maltose may be favorable to the water uptake and osmotic regulation of K. sieversiana under high-salinity stress. Transcriptome data indicated that some aquaporin genes and potassium (K+) transporter genes may be important for water uptake and ion balance, respectively, while different members of those gene families were employed under low- and high-salinity stresses. In addition, several aquaporin genes were up-regulated in low- but not high-salinity stressed roots. The highly expressed aquaporin genes may allow low-salinity stressed K. sieversiana plants to uptake more water than control plants. The leaf K+/root K+ ratio was enhanced under low- but not high-salinity stress, which suggested that low salinity might promote K+ transport from the roots to the shoots. Hence, we speculated that low salinity might allow K. sieversiana to uptake more water and transport more K+ from roots to shoots, increasing the growth rate of K. sieversiana. PMID:29225608

Revealing complex function, process and pathway interactions with high-throughput expression and biological annotation data.

PubMed

Singh, Nitesh Kumar; Ernst, Mathias; Liebscher, Volkmar; Fuellen, Georg; Taher, Leila

2016-10-20

The biological relationships both between and within the functions, processes and pathways that operate within complex biological systems are only poorly characterized, making the interpretation of large scale gene expression datasets extremely challenging. Here, we present an approach that integrates gene expression and biological annotation data to identify and describe the interactions between biological functions, processes and pathways that govern a phenotype of interest. The product is a global, interconnected network, not of genes but of functions, processes and pathways, that represents the biological relationships within the system. We validated our approach on two high-throughput expression datasets describing organismal and organ development. Our findings are well supported by the available literature, confirming that developmental processes and apoptosis play key roles in cell differentiation. Furthermore, our results suggest that processes related to pluripotency and lineage commitment, which are known to be critical for development, interact mainly indirectly, through genes implicated in more general biological processes. Moreover, we provide evidence that supports the relevance of cell spatial organization in the developing liver for proper liver function. Our strategy can be viewed as an abstraction that is useful to interpret high-throughput data and devise further experiments.

Exploring societal solidarity in the context of extreme prematurity.

PubMed

Hendriks, Manya J; Bucher, Hans Ulrich; Klein, Sabine D; Streuli, Jürg C; Baumann-Hölzle, Ruth; Fauchère, Jean-Claude

2017-03-21

Extreme prematurity can result in long-term disabilities. Its impact on society is often not taken into account and deemed controversial. Our study examined attitudes of the Swiss population regarding extreme prematurity and people's perspectives regarding the question of solidarity with disabled people. We conducted a nationwide representative anonymous telephone survey with 1210 Swiss residents aged 18 years or older. We asked how people estimate their own personal solidarity, the solidarity of their social environment and the solidarity across the country with disabled persons. Spearman's correlation calculations were used to assess if a correlation exists between solidarity and setting financial limits to intensive care and between solidarity and withholding neonatal intensive care. According to 36.0% of the respondents intensive medical care should not be withheld from extremely preterm infants, even if their chances for an acceptable quality of life were poor. For 28.8%, intensive care should be withheld from these infants, and 26.9% held an intermediate position depending on the situation. A total of 31.5% were against setting a financial limit to treatment of extremely preterm newborns with an uncertain future quality of life, 34.2% were in favour and 26.9% were deliberating. A majority (88.8%) considered their solidarity toward disabled people as substantial; the solidarity of their personal environment and of the society at large was estimated as high by 79.1% and 48.6%, respectively. The Swiss population expressed a high level of solidarity which may alleviate some pressure on parents and health care providers in the decision-making process in neonatal intensive care units. In addition, there was no relationship between solidarity and people's willingness to pay for the care or withholding treatment of extremely preterm babies.

Modelling the occurrence of heat waves in maximum and minimum temperatures over Spain and projections for the period 2031-60

NASA Astrophysics Data System (ADS)

Abaurrea, J.; Asín, J.; Cebrián, A. C.

2018-02-01

The occurrence of extreme heat events in maximum and minimum daily temperatures is modelled using a non-homogeneous common Poisson shock process. It is applied to five Spanish locations, representative of the most common climates over the Iberian Peninsula. The model is based on an excess over threshold approach and distinguishes three types of extreme events: only in maximum temperature, only in minimum temperature and in both of them (simultaneous events). It takes into account the dependence between the occurrence of extreme events in both temperatures and its parameters are expressed as functions of time and temperature related covariates. The fitted models allow us to characterize the occurrence of extreme heat events and to compare their evolution in the different climates during the observed period. This model is also a useful tool for obtaining local projections of the occurrence rate of extreme heat events under climate change conditions, using the future downscaled temperature trajectories generated by Earth System Models. The projections for 2031-60 under scenarios RCP4.5, RCP6.0 and RCP8.5 are obtained and analysed using the trajectories from four earth system models which have successfully passed a preliminary control analysis. Different graphical tools and summary measures of the projected daily intensities are used to quantify the climate change on a local scale. A high increase in the occurrence of extreme heat events, mainly in July and August, is projected in all the locations, all types of event and in the three scenarios, although in 2051-60 the increase is higher under RCP8.5. However, relevant differences are found between the evolution in the different climates and the types of event, with a specially high increase in the simultaneous ones.

Microbial Diversity-Based Novel Crop Protection Products

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pioneer Hi-Bred International Inc.; DuPont Experimental Station; Yalpani, Ronald Flannagan, Rafael Herrmann, James Presnail, Tamas Torok, and Nasser

Extremophilic microorganisms are adapted to survive in ecological niches with high temperatures, extremes of pH, high salt concentrations, high pressure, radiation, etc. Extremophiles produce unique biocatalysts and natural products that function under extreme conditions comparab le to those prevailing in various industrial processes. Therefore, there is burgeoning interest in bioprospecting for extremophiles with potential immediate use in agriculture, the food, chemical, and pharm aceutical industries, and environmental biotechnology. Over the years, several thousand extremophilic bacteria, archaea, and filamentous fungi were collected at extreme environmental sites in the USA, the Chernobyl Exclusion Zone surrounding the faeild nuclear power plant in Ukraine,more » in and around Lake Baikal in Siberia, and at geothermal sites on the Kamchatka peninsula in Russia. These organisms were cultured under proprietary conditions, and the cell- free supernatants were screened for biological activities against plant pathogenic fungi and major crop damaging insects. Promising peptide lead molecules were isolated, characterized, and sequenced. Relatively high hit rates characterized the tested fermentation broths. Of the 26,000 samples screened, over thousand contained biological activity of interest. A fair number of microorganisms expressed broad- spectrum antifungal or insecticidal activity. Two- dozen broadly antifungal peptides (AFPs) are alr eady patent protected, and many more tens are under further investigation. Tapping the gene pool of extremophilic microorganisms to provide novel ways of crop protection proved a successful strategy.« less

Selective probing of mRNA expression levels within a living cell

PubMed Central

Nawarathna, D.; Turan, T.; Wickramasinghe, H. Kumar

2009-01-01

We report on a selective and nondestructive measurement of mRNA (messenger ribonucleic acid) expression levels within a living cell. We first modify an atomic force microscope tip to create a tapered nanoscale coaxial cable. Application of an ac (alternating potential) between the inner and outer electrodes of this cable creates a dielectrophoretic force attracting mRNA molecules toward the tip-end which is pretreated with gene specific primers. We selectively extracted and analyzed both high (∼2500) and extremely low (11¯0) copy number mRNA from a living cell mRNA in less than 10 s. PMID:19777090

Re-engineering adenovirus vector systems to enable high-throughput analyses of gene function.

PubMed

Stanton, Richard J; McSharry, Brian P; Armstrong, Melanie; Tomasec, Peter; Wilkinson, Gavin W G

2008-12-01

With the enhanced capacity of bioinformatics to interrogate extensive banks of sequence data, more efficient technologies are needed to test gene function predictions. Replication-deficient recombinant adenovirus (Ad) vectors are widely used in expression analysis since they provide for extremely efficient expression of transgenes in a wide range of cell types. To facilitate rapid, high-throughput generation of recombinant viruses, we have re-engineered an adenovirus vector (designated AdZ) to allow single-step, directional gene insertion using recombineering technology. Recombineering allows for direct insertion into the Ad vector of PCR products, synthesized sequences, or oligonucleotides encoding shRNAs without requirement for a transfer vector Vectors were optimized for high-throughput applications by making them "self-excising" through incorporating the I-SceI homing endonuclease into the vector removing the need to linearize vectors prior to transfection into packaging cells. AdZ vectors allow genes to be expressed in their native form or with strep, V5, or GFP tags. Insertion of tetracycline operators downstream of the human cytomegalovirus major immediate early (HCMV MIE) promoter permits silencing of transgenes in helper cells expressing the tet repressor thus making the vector compatible with the cloning of toxic gene products. The AdZ vector system is robust, straightforward, and suited to both sporadic and high-throughput applications.

Exposure to an extremely low-frequency electromagnetic field only slightly modifies the proteome of Chromobacterium violaceumATCC 12472

PubMed Central

Baraúna, Rafael A.; Santos, Agenor V.; Graças, Diego A.; Santos, Daniel M.; Ghilardi, Rubens; Pimenta, Adriano M. C.; Carepo, Marta S. P.; Schneider, Maria P.C.; Silva, Artur

2015-01-01

Several studies of the physiological responses of different organisms exposed to extremely low-frequency electromagnetic fields (ELF-EMF) have been described. In this work, we report the minimal effects of in situ exposure to ELF-EMF on the global protein expression of Chromobacterium violaceum using a gel-based proteomic approach. The protein expression profile was only slightly altered, with five differentially expressed proteins detected in the exposed cultures; two of these proteins (DNA-binding stress protein, Dps, and alcohol dehydrogenase) were identified by MS/MS. The enhanced expression of Dps possibly helped to prevent physical damage to DNA. Although small, the changes in protein expression observed here were probably beneficial in helping the bacteria to adapt to the stress generated by the electromagnetic field. PMID:26273227

Protection conferred by recombinant Yersinia pestis antigens produced by a rapid and highly scalable plant expression system

PubMed Central

Santi, Luca; Giritch, Anatoli; Roy, Chad J.; Marillonnet, Sylvestre; Klimyuk, Victor; Gleba, Yuri; Webb, Robert; Arntzen, Charles J.; Mason, Hugh S.

2006-01-01

Plague is still an endemic disease in different regions of the world. Increasing reports of incidence, the discovery of antibiotic resistance strains, and concern about a potential use of the causative bacteria Yersinia pestis as an agent of biological warfare have highlighted the need for a safe, efficacious, and rapidly producible vaccine. The use of F1 and V antigens and the derived protein fusion F1-V has shown great potential as a protective vaccine in animal studies. Plants have been extensively studied for the production of pharmaceutical proteins as an inexpensive and scalable alternative to common expression systems. In the current study the recombinant plague antigens F1, V, and fusion protein F1-V were produced by transient expression in Nicotiana benthamiana by using a deconstructed tobacco mosaic virus-based system that allowed very rapid and extremely high levels of expression. All of the plant-derived purified antigens, administered s.c. to guinea pigs, generated systemic immune responses and provided protection against an aerosol challenge of virulent Y. pestis. PMID:16410352

Cytokine stimulation of MUC4 expression in human female reproductive tissue carcinoma cell lines and endometrial cancer.

PubMed

Chapela, Patricia J; Broaddus, Russell R; Hawkins, Shannon M; Lessey, Bruce A; Carson, Daniel D

2015-11-01

MUC4, a transmembrane glycoprotein, interferes with cell adhesion, and promotes EGFR signaling in cancer. Studies in rat models have demonstrated steroid hormonal regulation of endometrial MUC4 expression. In this study, qRT-PCR screening of mouse tissues determined that Muc4 mRNA also was robustly expressed in mouse uteri. Previous studies from our labs have demonstrated MUC4 mRNA was expressed at levels <1% of MUC1 mRNA in human endometrium and endometriotic tissue. Multiple human endometrial adenocarcinoma cell lines were assayed for MUC4 mRNA expression revealing extremely low basal expression in the Ishikawa, RL-95-2, AN3CA, and KLE lines. Moderate to high expression was observed in HEC50 and HEC-1A cells. MUC4 mRNA expression was not affected by progesterone and/or estrogen treatment, but was greatly stimulated at both mRNA and protein levels by proinflammatory cytokines (IFN-γ and TNF-α), particularly when used in combination. In endometrial tissue, MUC4 mRNA levels did not change significantly between normal or cancerous samples; although, a subset of patients with grade 1 and 2 tumors displayed substantially higher expression. Likewise, immunostaining of human endometrial adenocarcinoma tissues revealed little to no staining in many patients (low MUC4), but strong staining in some patients (high MUC4) independent of cancer grade. In cases where staining was observed, it was heterogeneous with some cells displaying robust MUC4 expression and others displaying little or no staining. Collectively, these observations demonstrate that while MUC4 is highly expressed in the mouse uterus, it is not a major mucin in normal human endometrium. Rather, MUC4 is a potential marker of endometrial adenocarcinoma in a subset of patients. © 2015 Wiley Periodicals, Inc.

Diversity in transcripts and translational pattern of stress proteins in marine extremophiles.

PubMed

Ambily Nath, I V; Loka Bharathi, P A

2011-03-01

Extremophiles occur in a diverse range of habitats, from the frigid waters of Antarctic to the superheated plumes of hydrothermal vents. Their in-depth study could provide important insights into the biochemical, ecological and evolutionary aspects of marine microbes. The cellular machinery of such extreme-lovers could be highly flexible to cope with such harsh environments. Extreme conditions of temperature, pressure, salinity, pH, oxidative stress, radiation, etc., above the physiological tolerance level can disrupt the natural conformation of proteins in the cell. The induction of stress proteins (heat/cold shock proteins/salt stress proteins/pressure-induced proteins) plays a vital role in the acclimatization of extremophiles. The present review focuses on the in vitro studies conducted on the transcripts and translational pattern of stress proteins in extremophiles. Though some proteins are unique, a commonality in stress resistance mechanism has been observed, for example, the universal occurrence of HSP60, 70 and the expression of metabolic and DNA repair proteins. The review highlights that among all the stressful conditions, salt/osmotic stress evokes the expression of highest number of transcripts/proteins while psychrophilic condition the least.

Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein

PubMed Central

Hashimoto, Takuma; Horikawa, Daiki D.; Saito, Yuki; Kuwahara, Hirokazu; Kozuka-Hata, Hiroko; Shin-I, Tadasu; Minakuchi, Yohei; Ohishi, Kazuko; Motoyama, Ayuko; Aizu, Tomoyuki; Enomoto, Atsushi; Kondo, Koyuki; Tanaka, Sae; Hara, Yuichiro; Koshikawa, Shigeyuki; Sagara, Hiroshi; Miura, Toru; Yokobori, Shin-ichi; Miyagawa, Kiyoshi; Suzuki, Yutaka; Kubo, Takeo; Oyama, Masaaki; Kohara, Yuji; Fujiyama, Asao; Arakawa, Kazuharu; Katayama, Toshiaki; Toyoda, Atsushi; Kunieda, Takekazu

2016-01-01

Tardigrades, also known as water bears, are small aquatic animals. Some tardigrade species tolerate almost complete dehydration and exhibit extraordinary tolerance to various physical extremes in the dehydrated state. Here we determine a high-quality genome sequence of Ramazzottius varieornatus, one of the most stress-tolerant tardigrade species. Precise gene repertoire analyses reveal the presence of a small proportion (1.2% or less) of putative foreign genes, loss of gene pathways that promote stress damage, expansion of gene families related to ameliorating damage, and evolution and high expression of novel tardigrade-unique proteins. Minor changes in the gene expression profiles during dehydration and rehydration suggest constitutive expression of tolerance-related genes. Using human cultured cells, we demonstrate that a tardigrade-unique DNA-associating protein suppresses X-ray-induced DNA damage by ∼40% and improves radiotolerance. These findings indicate the relevance of tardigrade-unique proteins to tolerability and tardigrades could be a bountiful source of new protection genes and mechanisms. PMID:27649274

Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein.

PubMed

Hashimoto, Takuma; Horikawa, Daiki D; Saito, Yuki; Kuwahara, Hirokazu; Kozuka-Hata, Hiroko; Shin-I, Tadasu; Minakuchi, Yohei; Ohishi, Kazuko; Motoyama, Ayuko; Aizu, Tomoyuki; Enomoto, Atsushi; Kondo, Koyuki; Tanaka, Sae; Hara, Yuichiro; Koshikawa, Shigeyuki; Sagara, Hiroshi; Miura, Toru; Yokobori, Shin-Ichi; Miyagawa, Kiyoshi; Suzuki, Yutaka; Kubo, Takeo; Oyama, Masaaki; Kohara, Yuji; Fujiyama, Asao; Arakawa, Kazuharu; Katayama, Toshiaki; Toyoda, Atsushi; Kunieda, Takekazu

2016-09-20

Tardigrades, also known as water bears, are small aquatic animals. Some tardigrade species tolerate almost complete dehydration and exhibit extraordinary tolerance to various physical extremes in the dehydrated state. Here we determine a high-quality genome sequence of Ramazzottius varieornatus, one of the most stress-tolerant tardigrade species. Precise gene repertoire analyses reveal the presence of a small proportion (1.2% or less) of putative foreign genes, loss of gene pathways that promote stress damage, expansion of gene families related to ameliorating damage, and evolution and high expression of novel tardigrade-unique proteins. Minor changes in the gene expression profiles during dehydration and rehydration suggest constitutive expression of tolerance-related genes. Using human cultured cells, we demonstrate that a tardigrade-unique DNA-associating protein suppresses X-ray-induced DNA damage by ∼40% and improves radiotolerance. These findings indicate the relevance of tardigrade-unique proteins to tolerability and tardigrades could be a bountiful source of new protection genes and mechanisms.

Synthetic dual-input mammalian genetic circuits enable tunable and stringent transcription control by chemical and light.

PubMed

Chen, Xianjun; Li, Ting; Wang, Xue; Du, Zengmin; Liu, Renmei; Yang, Yi

2016-04-07

Programmable transcription factors can enable precise control of gene expression triggered by a chemical inducer or light. To obtain versatile transgene system with combined benefits of a chemical inducer and light inducer, we created various chimeric promoters through the assembly of different copies of the tet operator and Gal4 operator module, which simultaneously responded to a tetracycline-responsive transcription factor and a light-switchable transactivator. The activities of these chimeric promoters can be regulated by tetracycline and blue light synergistically or antagonistically. Further studies of the antagonistic genetic circuit exhibited high spatiotemporal resolution and extremely low leaky expression, which therefore could be used to spatially and stringently control the expression of highly toxic protein Diphtheria toxin A for light regulated gene therapy. When transferring plasmids engineered for the gene switch-driven expression of a firefly luciferase (Fluc) into mice, the Fluc expression levels of the treated animals directly correlated with the tetracycline and light input program. We suggest that dual-input genetic circuits using TET and light that serve as triggers to achieve expression profiles may enable the design of robust therapeutic gene circuits for gene- and cell-based therapies. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Current status and clinical association of beta-catenin with juvenile nasopharyngeal angiofibroma.

PubMed

Mishra, A; Singh, V; Verma, V; Pandey, S; Trivedi, R; Singh, H P; Kumar, S; Dwivedi, R C; Mishra, S C

2016-10-01

A possible role of the APC/beta-catenin pathway in the pathogenesis of sporadic juvenile nasopharyngeal angiofibroma has been suggested. This paper presents its current status and clinical association in our patients. A prospective observational study was conducted at King George Medical University and Central Drug Research Institute, in Lucknow, India. Western blot analysis was undertaken in 16 cases to examine beta-catenin expression. The clinical details were recorded along with follow up observations, to determine associations. Up-regulation of beta-catenin expression was seen in 69 per cent of cases. The clinical variables did not reveal significant differences between patients with extremes of expression (extreme under- vs over-expression). However, absent expression was shown exclusively in young adults aged over 18 years, while enhanced expression was associated with an altered facial profile. Although a beta-catenin association was seen in a subset of our sporadic juvenile nasopharyngeal angiofibroma cases, its expression was not homogeneous. This is in contrast to the Western literature that suggests a universal (homogenous) enhanced expression in the majority. Hence, further research is required to better define its molecular cascade.

A characterization of workflow management systems for extreme-scale applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferreira da Silva, Rafael; Filgueira, Rosa; Pietri, Ilia

We present that the automation of the execution of computational tasks is at the heart of improving scientific productivity. Over the last years, scientific workflows have been established as an important abstraction that captures data processing and computation of large and complex scientific applications. By allowing scientists to model and express entire data processing steps and their dependencies, workflow management systems relieve scientists from the details of an application and manage its execution on a computational infrastructure. As the resource requirements of today’s computational and data science applications that process vast amounts of data keep increasing, there is a compellingmore » case for a new generation of advances in high-performance computing, commonly termed as extreme-scale computing, which will bring forth multiple challenges for the design of workflow applications and management systems. This paper presents a novel characterization of workflow management systems using features commonly associated with extreme-scale computing applications. We classify 15 popular workflow management systems in terms of workflow execution models, heterogeneous computing environments, and data access methods. Finally, the paper also surveys workflow applications and identifies gaps for future research on the road to extreme-scale workflows and management systems.« less

A characterization of workflow management systems for extreme-scale applications

DOE PAGES

Ferreira da Silva, Rafael; Filgueira, Rosa; Pietri, Ilia; ...

2017-02-16

We present that the automation of the execution of computational tasks is at the heart of improving scientific productivity. Over the last years, scientific workflows have been established as an important abstraction that captures data processing and computation of large and complex scientific applications. By allowing scientists to model and express entire data processing steps and their dependencies, workflow management systems relieve scientists from the details of an application and manage its execution on a computational infrastructure. As the resource requirements of today’s computational and data science applications that process vast amounts of data keep increasing, there is a compellingmore » case for a new generation of advances in high-performance computing, commonly termed as extreme-scale computing, which will bring forth multiple challenges for the design of workflow applications and management systems. This paper presents a novel characterization of workflow management systems using features commonly associated with extreme-scale computing applications. We classify 15 popular workflow management systems in terms of workflow execution models, heterogeneous computing environments, and data access methods. Finally, the paper also surveys workflow applications and identifies gaps for future research on the road to extreme-scale workflows and management systems.« less

Evaluating the use of verbal probability expressions to communicate likelihood information in IPCC reports

NASA Astrophysics Data System (ADS)

Harris, Adam

2014-05-01

The Intergovernmental Panel on Climate Change (IPCC) prescribes that the communication of risk and uncertainty information pertaining to scientific reports, model predictions etc. be communicated with a set of 7 likelihood expressions. These range from "Extremely likely" (intended to communicate a likelihood of greater than 99%) through "As likely as not" (33-66%) to "Extremely unlikely" (less than 1%). Psychological research has investigated the degree to which these expressions are interpreted as intended by the IPCC, both within and across cultures. I will present a selection of this research and demonstrate some problems associated with communicating likelihoods in this way, as well as suggesting some potential improvements.

PD-L1 expression in pancreatic ductal adenocarcinoma is a poor prognostic factor in patients with high CD8+ tumor-infiltrating lymphocytes: highly sensitive detection using phosphor-integrated dot staining.

PubMed

Yamaki, So; Yanagimoto, Hiroaki; Tsuta, Koji; Ryota, Hironori; Kon, Masanori

2017-08-01

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. For the development of more effective immunotherapies, it is first necessary to elucidate the immunological escape mechanisms. In this study, we applied our recently developed highly sensitive immunostaining method employing fluorescent phosphor-integrated dot (PID) nanoparticles to evaluate the prevalence of programmed death ligand 1 (PD-L1) in patients with PDAC. This study included 42 patients with PDAC who underwent pancreatectomy. We evaluated PD-L1 expression in these patients using PID staining and correlated PD-L1 expression level with each patient's clinico-pathological features. PD-L1 expression was detected in 61.9% (26/42) of the patients with PDAC by PID staining. There was a significant difference in overall survival between PD-L1-positive and PD-L1-negative patients [hazard ratio (HR) 2.07, 95% confidence interval (CI) 1.00-4.54; P = 0.049]. Among CD8 + -tumor-infiltrating lymphocyte-positive cases, the overall survival of PD-L1-positive patients was significantly poorer than that of PD-L1-negative patients (HR 3.84, 95% CI 1.59-10.35; P = 0.003). Univariate and multivariate analyses indicated that PD-L1 expression was an independent predictive poor prognostic factor in patients with PDAC. PD-L1 expression appears to be an important prognostic factor in patients with PDAC who underwent surgical resection.

Role of GPER1, EGFR and CXCR1 in differentiating between malignant follicular thyroid carcinoma and benign follicular thyroid adenoma

PubMed Central

Zhao, Le; Zhu, Xiao-Yun; Jiang, Rong; Xu, Man; Wang, Ni; Chen, George G; Liu, Zhi-Min

2015-01-01

It is extremely difficult to discriminate between follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) before surgery, because the morphologies of carcinoma cells and adenoma cells obtained by fine needle aspiration biopsy (FNAB) are similar. Molecular markers may be helpful on this issue. The purpose of this study was to assess the role of GPER1, EGFR and CXCR1 in differential diagnosis between FTC and FTA. GPER1, EGFR and CXCR1 mRNA expression levels were examined in 15 FTCs and 10 FTAs using real-time RT-PCR. FTC showed to have significantly increased mRNA levels of the three molecules compared to FTA (P < 0.001 for all the three molecules). GPER1, EGFR and CXCR1 protein expression in 106 FTCs and 128 FTAs were analyzed using immunohistochemistry. The rates of GPER1, EGFR and CXCR1 high expression were 73.6%, 72.6% and 70.8% in FTC and 30.5%, 28.1% and 27.3% in FTA, respectively. Statistical analysis showed that GPER1, EGFR and CXCR1 protein expression were correlated with one another in FTC and concomitant high expression of the three molecules had stronger correlation with the occurrence of FTC than did each alone. The positive predictive values (PPV) for concomitant high expression of the three molecules for discriminating between FTC and FTA were 91.0% for GPER1/EGFR, 93.8% for GPER1/CXCR1, 92.3% for EGFR/CXCR1 and 98.2% for GPER1/EGFR/CXCR1, respectively. These results indicated that the evaluation of GPER1, EGFR and CXCR1 concomitant high expression may be helpful in differential diagnosis between FTC and FTA. PMID:26617848

Role of GPER1, EGFR and CXCR1 in differentiating between malignant follicular thyroid carcinoma and benign follicular thyroid adenoma.

PubMed

Zhao, Le; Zhu, Xiao-Yun; Jiang, Rong; Xu, Man; Wang, Ni; Chen, George G; Liu, Zhi-Min

2015-01-01

It is extremely difficult to discriminate between follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) before surgery, because the morphologies of carcinoma cells and adenoma cells obtained by fine needle aspiration biopsy (FNAB) are similar. Molecular markers may be helpful on this issue. The purpose of this study was to assess the role of GPER1, EGFR and CXCR1 in differential diagnosis between FTC and FTA. GPER1, EGFR and CXCR1 mRNA expression levels were examined in 15 FTCs and 10 FTAs using real-time RT-PCR. FTC showed to have significantly increased mRNA levels of the three molecules compared to FTA (P < 0.001 for all the three molecules). GPER1, EGFR and CXCR1 protein expression in 106 FTCs and 128 FTAs were analyzed using immunohistochemistry. The rates of GPER1, EGFR and CXCR1 high expression were 73.6%, 72.6% and 70.8% in FTC and 30.5%, 28.1% and 27.3% in FTA, respectively. Statistical analysis showed that GPER1, EGFR and CXCR1 protein expression were correlated with one another in FTC and concomitant high expression of the three molecules had stronger correlation with the occurrence of FTC than did each alone. The positive predictive values (PPV) for concomitant high expression of the three molecules for discriminating between FTC and FTA were 91.0% for GPER1/EGFR, 93.8% for GPER1/CXCR1, 92.3% for EGFR/CXCR1 and 98.2% for GPER1/EGFR/CXCR1, respectively. These results indicated that the evaluation of GPER1, EGFR and CXCR1 concomitant high expression may be helpful in differential diagnosis between FTC and FTA.

Multifocal Epithelial Hyperplasia of Oral Cavity Expressing HPV 16 Gene: A Rare Entity

PubMed Central

Prabhat, M. P. V.; Raja Lakshmi, Chintamaneni; Sai Madhavi, N.; Bhavana, Sujana Mulk; Sarat, Gummadapu; Ramamohan, Kodali

2013-01-01

Focal epithelial hyperplasia is a rare contagious disease caused by human papilloma virus. Usually HPV involves either cutaneous or mucosal surfaces, whereas concomitant mucocutaneous involvement is extremely rare. We report such a unique case of multifocal epithelial hyperplasia involving multiple sites of oral cavity along with skin lesions in a 65-year-old female. We also discuss the probable multifactorial etiology and variable clinical presentations of the lesions, including evidence of HPV 16 expression, as detected by polymerase chain reaction. The present report illustrates the need for careful examination and prompt diagnosis of the disease, as it might be associated with high risk genotypes such as HPV 16 and 18. PMID:24455323

The Expression and Characterization of Functionally Active Soluble CD83 by Pichia pastoris Using High-Density Fermentation

PubMed Central

Song, Xiaoping; Zhong, Yongjun; Wang, Chenguang; Jia, Hao; Wu, Lidan; Wang, Dong; Fang, Fang; Ma, Jiajia; Kang, Wenyao; Sun, Jie; Tian, Zhigang; Xiao, Weihua

2014-01-01

CD83 is a highly glycosylated type I transmembrane glycoprotein that belongs to the immunoglobulin superfamily. CD83 is upregulated during dendritic cell (DC) maturation, which is critical for the initiation of adaptive immune responses. The soluble isoform of CD83 (sCD83) is encoded by alternative splicing from full-length CD83 mRNA and inhibits DC maturation, which suggests that sCD83 acts as a potential immune suppressor. In this study, we developed a sound strategy to express functional sCD83 from Pichia pastoris in extremely high-density fermentation. Purified sCD83 was expressed as a monomer at a yield of more than 200 mg/L and contained N-linked glycosylation sites that were characterized by PNGase F digestion. In vitro tests indicated that recombinant sCD83 bound to its putative counterpart on monocytes and specifically blocked the binding of anti-CD83 antibodies to cell surface CD83 on DCs. Moreover, sCD83 from yeast significantly suppressed ConA-stimulated PBMC proliferation. Therefore, sCD83 that was expressed from the P. pastoris was functionally active and may be used for in vivo and in vitro studies as well as future clinical applications. PMID:24586642

Ribosomal Binding Site Switching: An Effective Strategy for High-Throughput Cloning Constructions

PubMed Central

Li, Yunlong; Zhang, Yong; Lu, Pei; Rayner, Simon; Chen, Shiyun

2012-01-01

Direct cloning of PCR fragments by TA cloning or blunt end ligation are two simple methods which would greatly benefit high-throughput (HTP) cloning constructions if the efficiency can be improved. In this study, we have developed a ribosomal binding site (RBS) switching strategy for direct cloning of PCR fragments. RBS is an A/G rich region upstream of the translational start codon and is essential for gene expression. Change from A/G to T/C in the RBS blocks its activity and thereby abolishes gene expression. Based on this property, we introduced an inactive RBS upstream of a selectable marker gene, and designed a fragment insertion site within this inactive RBS. Forward and reverse insertions of specifically tailed fragments will respectively form an active and inactive RBS, thus all background from vector self-ligation and fragment reverse insertions will be eliminated due to the non-expression of the marker gene. The effectiveness of our strategy for TA cloning and blunt end ligation are confirmed. Application of this strategy to gene over-expression, a bacterial two-hybrid system, a bacterial one-hybrid system, and promoter bank construction are also verified. The advantages of this simple procedure, together with its low cost and high efficiency, makes our strategy extremely useful in HTP cloning constructions. PMID:23185557

Towards a General Theory of Extremes for Observables of Chaotic Dynamical Systems.

PubMed

Lucarini, Valerio; Faranda, Davide; Wouters, Jeroen; Kuna, Tobias

2014-01-01

In this paper we provide a connection between the geometrical properties of the attractor of a chaotic dynamical system and the distribution of extreme values. We show that the extremes of so-called physical observables are distributed according to the classical generalised Pareto distribution and derive explicit expressions for the scaling and the shape parameter. In particular, we derive that the shape parameter does not depend on the chosen observables, but only on the partial dimensions of the invariant measure on the stable, unstable, and neutral manifolds. The shape parameter is negative and is close to zero when high-dimensional systems are considered. This result agrees with what was derived recently using the generalized extreme value approach. Combining the results obtained using such physical observables and the properties of the extremes of distance observables, it is possible to derive estimates of the partial dimensions of the attractor along the stable and the unstable directions of the flow. Moreover, by writing the shape parameter in terms of moments of the extremes of the considered observable and by using linear response theory, we relate the sensitivity to perturbations of the shape parameter to the sensitivity of the moments, of the partial dimensions, and of the Kaplan-Yorke dimension of the attractor. Preliminary numerical investigations provide encouraging results on the applicability of the theory presented here. The results presented here do not apply for all combinations of Axiom A systems and observables, but the breakdown seems to be related to very special geometrical configurations.

Towards a General Theory of Extremes for Observables of Chaotic Dynamical Systems

NASA Astrophysics Data System (ADS)

Lucarini, Valerio; Faranda, Davide; Wouters, Jeroen; Kuna, Tobias

2014-02-01

In this paper we provide a connection between the geometrical properties of the attractor of a chaotic dynamical system and the distribution of extreme values. We show that the extremes of so-called physical observables are distributed according to the classical generalised Pareto distribution and derive explicit expressions for the scaling and the shape parameter. In particular, we derive that the shape parameter does not depend on the chosen observables, but only on the partial dimensions of the invariant measure on the stable, unstable, and neutral manifolds. The shape parameter is negative and is close to zero when high-dimensional systems are considered. This result agrees with what was derived recently using the generalized extreme value approach. Combining the results obtained using such physical observables and the properties of the extremes of distance observables, it is possible to derive estimates of the partial dimensions of the attractor along the stable and the unstable directions of the flow. Moreover, by writing the shape parameter in terms of moments of the extremes of the considered observable and by using linear response theory, we relate the sensitivity to perturbations of the shape parameter to the sensitivity of the moments, of the partial dimensions, and of the Kaplan-Yorke dimension of the attractor. Preliminary numerical investigations provide encouraging results on the applicability of the theory presented here. The results presented here do not apply for all combinations of Axiom A systems and observables, but the breakdown seems to be related to very special geometrical configurations.

[Epstein-Barr virus associated gastric carcinoma: the genetic alteration and the expression of CD44 variant].

PubMed

Chong, J M; Fukayama, M

1997-02-01

Epstein-Barr virus (EBV), a ubiquitous human herpes virus, was recently identified in 2-16% of gastric carcinomas. EBV-encoded small RNA was found in nearly all of the carcinoma cells even at the intramucosal stage. EBV in EBV associated gastric carcinoma (EBVaGC) is monoclonal based on Southern blot hybridization using probes adjacent to the unique terminal repeat of EBV-DNA. Furthermore, the genetic pathway of this carcinogenesis is different of EBVaGC: deletion of 5q and/or 17p and microsatellite instability are extremely rare in EBVaGC, in contrast to their high frequency in EBV-negative carcinomas. We also examined the relationship between the expression of CD44 variants and EBVaGC, and found the expression of CD44 variants was significantly correlated with EBV-etiology.

CRISPR/Cas9 mediates efficient conditional mutagenesis in Drosophila.

PubMed

Xue, Zhaoyu; Wu, Menghua; Wen, Kejia; Ren, Menda; Long, Li; Zhang, Xuedi; Gao, Guanjun

2014-09-05

Existing transgenic RNA interference (RNAi) methods greatly facilitate functional genome studies via controlled silencing of targeted mRNA in Drosophila. Although the RNAi approach is extremely powerful, concerns still linger about its low efficiency. Here, we developed a CRISPR/Cas9-mediated conditional mutagenesis system by combining tissue-specific expression of Cas9 driven by the Gal4/upstream activating site system with various ubiquitously expressed guide RNA transgenes to effectively inactivate gene expression in a temporally and spatially controlled manner. Furthermore, by including multiple guide RNAs in a transgenic vector to target a single gene, we achieved a high degree of gene mutagenesis in specific tissues. The CRISPR/Cas9-mediated conditional mutagenesis system provides a simple and effective tool for gene function analysis, and complements the existing RNAi approach. Copyright © 2014 Xue et al.

Towards decrypting cryptobiosis--analyzing anhydrobiosis in the tardigrade Milnesium tardigradum using transcriptome sequencing.

PubMed

Wang, Chong; Grohme, Markus A; Mali, Brahim; Schill, Ralph O; Frohme, Marcus

2014-01-01

Many tardigrade species are capable of anhydrobiosis; however, mechanisms underlying their extreme desiccation resistance remain elusive. This study attempts to quantify the anhydrobiotic transcriptome of the limno-terrestrial tardigrade Milnesium tardigradum. A prerequisite for differential gene expression analysis was the generation of a reference hybrid transcriptome atlas by assembly of Sanger, 454 and Illumina sequence data. The final assembly yielded 79,064 contigs (>100 bp) after removal of ribosomal RNAs. Around 50% of them could be annotated by SwissProt and NCBI non-redundant protein sequences. Analysis using CEGMA predicted 232 (93.5%) out of the 248 highly conserved eukaryotic genes in the assembly. We used this reference transcriptome for mapping and quantifying the expression of transcripts regulated under anhdydrobiosis in a time-series during dehydration and rehydration. 834 of the transcripts were found to be differentially expressed in a single stage (dehydration/inactive tun/rehydration) and 184 were overlapping in two stages while 74 were differentially expressed in all three stages. We have found interesting patterns of differentially expressed transcripts that are in concordance with a common hypothesis of metabolic shutdown during anhydrobiosis. This included down-regulation of several proteins of the DNA replication and translational machinery and protein degradation. Among others, heat shock proteins Hsp27 and Hsp30c were up-regulated in response to dehydration and rehydration. In addition, we observed up-regulation of ployubiquitin-B upon rehydration together with a higher expression level of several DNA repair proteins during rehydration than in the dehydration stage. Most of the transcripts identified to be differentially expressed had distinct cellular function. Our data suggest a concerted molecular adaptation in M. tardigradum that permits extreme forms of ametabolic states such as anhydrobiosis. It is temping to surmise that the desiccation tolerance of tradigrades can be achieved by a constitutive cellular protection system, probably in conjunction with other mechanisms such as rehydration-induced cellular repair.

Towards Decrypting Cryptobiosis—Analyzing Anhydrobiosis in the Tardigrade Milnesium tardigradum Using Transcriptome Sequencing

PubMed Central

Wang, Chong; Grohme, Markus A.; Mali, Brahim; Schill, Ralph O.; Frohme, Marcus

2014-01-01

Background Many tardigrade species are capable of anhydrobiosis; however, mechanisms underlying their extreme desiccation resistance remain elusive. This study attempts to quantify the anhydrobiotic transcriptome of the limno-terrestrial tardigrade Milnesium tardigradum. Results A prerequisite for differential gene expression analysis was the generation of a reference hybrid transcriptome atlas by assembly of Sanger, 454 and Illumina sequence data. The final assembly yielded 79,064 contigs (>100 bp) after removal of ribosomal RNAs. Around 50% of them could be annotated by SwissProt and NCBI non-redundant protein sequences. Analysis using CEGMA predicted 232 (93.5%) out of the 248 highly conserved eukaryotic genes in the assembly. We used this reference transcriptome for mapping and quantifying the expression of transcripts regulated under anhdydrobiosis in a time-series during dehydration and rehydration. 834 of the transcripts were found to be differentially expressed in a single stage (dehydration/inactive tun/rehydration) and 184 were overlapping in two stages while 74 were differentially expressed in all three stages. We have found interesting patterns of differentially expressed transcripts that are in concordance with a common hypothesis of metabolic shutdown during anhydrobiosis. This included down-regulation of several proteins of the DNA replication and translational machinery and protein degradation. Among others, heat shock proteins Hsp27 and Hsp30c were up-regulated in response to dehydration and rehydration. In addition, we observed up-regulation of ployubiquitin-B upon rehydration together with a higher expression level of several DNA repair proteins during rehydration than in the dehydration stage. Conclusions Most of the transcripts identified to be differentially expressed had distinct cellular function. Our data suggest a concerted molecular adaptation in M. tardigradum that permits extreme forms of ametabolic states such as anhydrobiosis. It is temping to surmise that the desiccation tolerance of tradigrades can be achieved by a constitutive cellular protection system, probably in conjunction with other mechanisms such as rehydration-induced cellular repair. PMID:24651535

The smallest natural high-active luciferase: cloning and characterization of novel 16.5-kDa luciferase from copepod Metridia longa.

PubMed

Markova, Svetlana V; Larionova, Marina D; Burakova, Ludmila P; Vysotski, Eugene S

2015-01-30

Coelenterazine-dependent copepod luciferases containing natural signal peptide for secretion are a very convenient analytical tool as they enable monitoring of intracellular events with high sensitivity, without destroying cells or tissues. This property is well suited for application in biomedical research and development of cell-based assays for high throughput screening. We report the cloning of cDNA gene encoding a novel secreted non-allelic 16.5-kDa isoform (MLuc7) of Metridia longa luciferase, which, in fact, is the smallest natural luciferase of known for today. Despite the small size, isoform contains 10 conservative Cys residues suggesting the presence of up to 5 SS bonds. This hampers the efficient production of functionally active recombinant luciferase in bacterial expression systems. With the use of the baculovirus expression system, we produced substantial amounts of the proper folded MLuc7 luciferase with a yield of ∼3 mg/L of a high purity protein. We demonstrate that MLuc7 produced in insect cells is highly active and extremely thermostable, and is well suited as a secreted reporter when expressed in mammalian cells ensuring higher sensitivity of detection as compared to another Metridia luciferase isoform (MLuc164) which is widely employed in real-time imaging. Copyright © 2014 Elsevier Inc. All rights reserved.

Expression of Active Human Tissue-Type Plasminogen Activator in Escherichia coli

PubMed Central

Qiu, Ji; Swartz, James R.; Georgiou, George

1998-01-01

The formation of native disulfide bonds in complex eukaryotic proteins expressed in Escherichia coli is extremely inefficient. Tissue plasminogen activator (tPA) is a very important thrombolytic agent with 17 disulfides, and despite numerous attempts, its expression in an active form in bacteria has not been reported. To achieve the production of active tPA in E. coli, we have investigated the effect of cooverexpressing native (DsbA and DsbC) or heterologous (rat and yeast protein disulfide isomerases) cysteine oxidoreductases in the bacterial periplasm. Coexpression of DsbC, an enzyme which catalyzes disulfide bond isomerization in the periplasm, was found to dramatically increase the formation of active tPA both in shake flasks and in fermentors. The active protein was purified with an overall yield of 25% by using three affinity steps with, in sequence, lysine-Sepharose, immobilized Erythrina caffra inhibitor, and Zn-Sepharose resins. After purification, approximately 180 μg of tPA with a specific activity nearly identical to that of the authentic protein can be obtained per liter of culture in a high-cell-density fermentation. Thus, heterologous proteins as complex as tPA may be produced in an active form in bacteria in amounts suitable for structure-function studies. In addition, these results suggest the feasibility of commercial production of extremely complex proteins in E. coli without the need for in vitro refolding. PMID:9835579

Association of the expression levels in the skeletal muscle and a SNP in the CDC10 gene with growth-related traits in Japanese Black beef cattle.

PubMed

Tong, B; Li, G P; Sasaki, S; Muramatsu, Y; Ohta, T; Kose, H; Yamada, T

2015-04-01

Growth performance, as well as marbling, is the main breeding objective in Japanese Black (JB) cattle, the major beef breed in Japan. The septin 7 (CDC10) gene, involved in cellular proliferation, is located within a genomic region of a quantitative trait locus for growth-related traits. In this study, we first showed that the expression levels of the CDC10 gene in the skeletal muscle were higher in JB steers with extremely high growth performance than in JB steers with extremely low growth, using real-time PCR. Further, a single nucleotide polymorphism (SNP), NC_007302.5:g.63264949G>C, was detected in the promoter region of the CDC10 gene and genotyped in three Japanese cattle breeds (known as 'Wagyu' in Japan) and the Brown Swiss dairy cattle breed. All four cattle populations showed a moderate genetic diversity at the SNP of the CDC10 gene. An association analysis indicated that the SNP was associated with growth-related traits in JB cattle. These findings suggest possible effects of the expression levels in the skeletal muscle and the SNP of the CDC10 gene on growth-related traits in JB cattle. The CDC10 SNP may be useful for effective marker-assisted selection to increase beef productivity in JB beef cattle. © 2015 Stichting International Foundation for Animal Genetics.

Perceiving Facial and Vocal Expressions of Emotion in Individuals with Williams Syndrome

ERIC Educational Resources Information Center

Plesa-Skwerer, Daniela; Faja, Susan; Schofield, Casey; Verbalis, Alyssa; Tager-Flusberg, Helen

2006-01-01

People with Williams syndrome are extremely sociable, empathic, and expressive in communication. Some researchers suggest they may be especially sensitive to perceiving emotional expressions. We administered the Faces and Paralanguage subtests of the Diagnostic Analysis of Nonverbal Accuracy Scale (DANVA2), a standardized measure of emotion…

GATA3 staining in primary cutaneous apocrine cribriform carcinoma: Usefulness to differentiate it from breast cancer metastasis.

PubMed

Llamas-Velasco, Mar; Pérez-Gónzalez, Yosmar C; Daudén, Esteban; Rütten, Arno

2018-05-01

Primary cutaneous apocrine cribriform carcinoma (PCACC) is a rare tumor, clinically appearing as a solitary nodule, mostly involving extremities of females and this lesion usually raises a differential diagnosis with metastatic cribriform carcinomas, especially breast cancer. To study GATA3 expression in a series of 14 primary cutaneous cribriform carcinomas and to test its usefulness to differentiate this tumor from metastatic breast cancer. We retrieved 14 cases with PCACC (each from a different patient) from the files of the authors. Cases were dated from 1994 to 2014. We also evaluated 6 cases of cutaneous breast cancer metastasis RESULTS: No PCACCs expressed GATA3. Breast cancer metastases expressed GATA3 in 100% of our studied cases. Even though GATA3 expression has been reported in many benign and malignant adnexal tumors (mostly of sebaceous, follicular, and apocrine differentiation), as well as in many other neoplasms, GATA3 staining to differentiate PCACC from skin breast cancer metastasis has a high negative predictive value. A positive GATA3 staining in this context should permit one to rule out PCACC with a high level of confidence. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bivariate extreme value distributions

NASA Technical Reports Server (NTRS)

Elshamy, M.

1992-01-01

In certain engineering applications, such as those occurring in the analyses of ascent structural loads for the Space Transportation System (STS), some of the load variables have a lower bound of zero. Thus, the need for practical models of bivariate extreme value probability distribution functions with lower limits was identified. We discuss the Gumbel models and present practical forms of bivariate extreme probability distributions of Weibull and Frechet types with two parameters. Bivariate extreme value probability distribution functions can be expressed in terms of the marginal extremel distributions and a 'dependence' function subject to certain analytical conditions. Properties of such bivariate extreme distributions, sums and differences of paired extremals, as well as the corresponding forms of conditional distributions, are discussed. Practical estimation techniques are also given.

Integrating Genomic Analysis with the Genetic Basis of Gene Expression: Preliminary Evidence of the Identification of Causal Genes for Cardiovascular and Metabolic Traits Related to Nutrition in Mexicans123

PubMed Central

Bastarrachea, Raúl A.; Gallegos-Cabriales, Esther C.; Nava-González, Edna J.; Haack, Karin; Voruganti, V. Saroja; Charlesworth, Jac; Laviada-Molina, Hugo A.; Veloz-Garza, Rosa A.; Cardenas-Villarreal, Velia Margarita; Valdovinos-Chavez, Salvador B.; Gomez-Aguilar, Patricia; Meléndez, Guillermo; López-Alvarenga, Juan Carlos; Göring, Harald H. H.; Cole, Shelley A.; Blangero, John; Comuzzie, Anthony G.; Kent, Jack W.

2012-01-01

Whole-transcriptome expression profiling provides novel phenotypes for analysis of complex traits. Gene expression measurements reflect quantitative variation in transcript-specific messenger RNA levels and represent phenotypes lying close to the action of genes. Understanding the genetic basis of gene expression will provide insight into the processes that connect genotype to clinically significant traits representing a central tenet of system biology. Synchronous in vivo expression profiles of lymphocytes, muscle, and subcutaneous fat were obtained from healthy Mexican men. Most genes were expressed at detectable levels in multiple tissues, and RNA levels were correlated between tissue types. A subset of transcripts with high reliability of expression across tissues (estimated by intraclass correlation coefficients) was enriched for cis-regulated genes, suggesting that proximal sequence variants may influence expression similarly in different cellular environments. This integrative global gene expression profiling approach is proving extremely useful for identifying genes and pathways that contribute to complex clinical traits. Clearly, the coincidence of clinical trait quantitative trait loci and expression quantitative trait loci can help in the prioritization of positional candidate genes. Such data will be crucial for the formal integration of positional and transcriptomic information characterized as genetical genomics. PMID:22797999

Human granulocyte colony-stimulating factor (hG-CSF) expression in plastids of Lactuca sativa.

PubMed

Sharifi Tabar, Mehdi; Habashi, Ali Akbar; Rajabi Memari, Hamid

2013-01-01

Human granulocyte colony-stimulating factor (hG-CSF) can serve as valuable biopharmaceutical for research and treatment of the human blood cancer. Transplastomic plants have been emerged as a new and high potential candidate for production of recombinant biopharmaceutical proteins in comparison with transgenic plants due to extremely high level expression, biosafety and many other advantages. hG-CSF gene was cloned into pCL vector between prrn16S promoter and TpsbA terminator. The recombinant vector was coated on nanogold particles and transformed to lettuce chloroplasts through biolistic method. Callogenesis and regeneration of cotyledonary explants were obtained by Murashige and Skoog media containing 6-benzylaminopurine and 1-naphthaleneacetic acid hormones. The presence of hG-CSF gene in plastome was studied with four specific PCR primers and expression by Western immunoblotting. hG-CSF gene cloning was confirmed by digestion and sequencing. Transplastomic lettuce lines were regenerated and subjected to molecular analysis. The presence of hG-CSF in plastome was confirmed by PCR using specific primers designed from the plastid genome. Western immunoblotting of extracted protein from transplastomic plants showed a 20-kDa band, which verified the expression of recombinant protein in lettuce chloroplasts. This study is the first report that successfully express hG-CSF gene in lettuce chloroplast. The lettuce plastome can provide a cheap and safe expression platform for producing valuable biopharmaceuticals for research and treatment.

Evolutionary Strategies of Viruses, Bacteria and Archaea in Hydrothermal Vent Ecosystems Revealed through Metagenomics

PubMed Central

Anderson, Rika E.; Sogin, Mitchell L.; Baross, John A.

2014-01-01

The deep-sea hydrothermal vent habitat hosts a diverse community of archaea and bacteria that withstand extreme fluctuations in environmental conditions. Abundant viruses in these systems, a high proportion of which are lysogenic, must also withstand these environmental extremes. Here, we explore the evolutionary strategies of both microorganisms and viruses in hydrothermal systems through comparative analysis of a cellular and viral metagenome, collected by size fractionation of high temperature fluids from a diffuse flow hydrothermal vent. We detected a high enrichment of mobile elements and proviruses in the cellular fraction relative to microorganisms in other environments. We observed a relatively high abundance of genes related to energy metabolism as well as cofactors and vitamins in the viral fraction compared to the cellular fraction, which suggest encoding of auxiliary metabolic genes on viral genomes. Moreover, the observation of stronger purifying selection in the viral versus cellular gene pool suggests viral strategies that promote prolonged host integration. Our results demonstrate that there is great potential for hydrothermal vent viruses to integrate into hosts, facilitate horizontal gene transfer, and express or transfer genes that manipulate the hosts’ functional capabilities. PMID:25279954

Expression map of a complete set of gustatory receptor genes in chemosensory organs of Bombyx mori.

PubMed

Guo, Huizhen; Cheng, Tingcai; Chen, Zhiwei; Jiang, Liang; Guo, Youbing; Liu, Jianqiu; Li, Shenglong; Taniai, Kiyoko; Asaoka, Kiyoshi; Kadono-Okuda, Keiko; Arunkumar, Kallare P; Wu, Jiaqi; Kishino, Hirohisa; Zhang, Huijie; Seth, Rakesh K; Gopinathan, Karumathil P; Montagné, Nicolas; Jacquin-Joly, Emmanuelle; Goldsmith, Marian R; Xia, Qingyou; Mita, Kazuei

2017-03-01

Most lepidopteran species are herbivores, and interaction with host plants affects their gene expression and behavior as well as their genome evolution. Gustatory receptors (Grs) are expected to mediate host plant selection, feeding, oviposition and courtship behavior. However, due to their high diversity, sequence divergence and extremely low level of expression it has been difficult to identify precisely a complete set of Grs in Lepidoptera. By manual annotation and BAC sequencing, we improved annotation of 43 gene sequences compared with previously reported Grs in the most studied lepidopteran model, the silkworm, Bombyx mori, and identified 7 new tandem copies of BmGr30 on chromosome 7, bringing the total number of BmGrs to 76. Among these, we mapped 68 genes to chromosomes in a newly constructed chromosome distribution map and 8 genes to scaffolds; we also found new evidence for large clusters of BmGrs, especially from the bitter receptor family. RNA-seq analysis of diverse BmGr expression patterns in chemosensory organs of larvae and adults enabled us to draw a precise organ specific map of BmGr expression. Interestingly, most of the clustered genes were expressed in the same tissues and more than half of the genes were expressed in larval maxillae, larval thoracic legs and adult legs. For example, BmGr63 showed high expression levels in all organs in both larval and adult stages. By contrast, some genes showed expression limited to specific developmental stages or organs and tissues. BmGr19 was highly expressed in larval chemosensory organs (especially antennae and thoracic legs), the single exon genes BmGr53 and BmGr67 were expressed exclusively in larval tissues, the BmGr27-BmGr31 gene cluster on chr7 displayed a high expression level limited to adult legs and the candidate CO 2 receptor BmGr2 was highly expressed in adult antennae, where few other Grs were expressed. Transcriptional analysis of the Grs in B. mori provides a valuable new reference for finding genes involved in plant-insect interactions in Lepidoptera and establishing correlations between these genes and vital insect behaviors like host plant selection and courtship for mating. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Cloning and Stress-Induced Expression Analysis of Calmodulin in the Antarctic Alga Chlamydomonas sp. ICE-L.

PubMed

He, Ying-Ying; Wang, Yi-Bin; Zheng, Zhou; Liu, Fang-Ming; An, Mei-Ling; He, Xiao-Dong; Qu, Chang-Feng; Li, Lu-Lu; Miao, Jin-Lai

2017-08-01

Calmodulin (CaM) is a Ca 2+ -binding protein that plays a role in several Ca 2+ signaling pathways, which dynamically regulates the activities of hundreds of proteins. The ice alga Chlamydomonas sp. ICE-L, which has the ability to adapt to extreme polar conditions, is a crucial primary producer in Antarctic ecosystem. This study hypothesized that Cam helps the ICE-L to adapt to the fluctuating conditions in the polar environment. It first verified the overall length of Cam, through RT-PCR and RACE-PCR, based on partial Cam transcriptome library of ICE-L. Then, the nucleotide and predicted amino acid sequences were, respectively, analyzed by various bioinformatics approaches to gain more insights into the computed physicochemical properties of the CaM. Potential involvements of Cam in responding to certain stimuli (i.e., UVB radiation, high salinity, and temperature) were investigated by differential expression, measuring its transcription levels by means of quantitative RT-PCR. Results showed that CaM was indeed inducible and regulated by high UVB radiation, high salinity, and nonoptimal temperature conditions. Different conditions had different expression tendencies, which provided an important basis for investigating the adaptation mechanism of Cam in ICE-L.

The effect of high concentrations of glufosinate ammonium on the yield components of transgenic spring wheat (Triticum aestivum L.) constitutively expressing the bar gene.

PubMed

Áy, Zoltán; Mihály, Róbert; Cserháti, Mátyás; Kótai, Éva; Pauk, János

2012-01-01

We present an experiment done on a bar(+) wheat line treated with 14 different concentrations of glufosinate ammonium-an effective component of nonselective herbicides-during seed germination in a closed experimental system. Yield components as number of spikes per plant, number of grains per spike, thousand kernel weight, and yield per plant were thoroughly analysed and statistically evaluated after harvesting. We found that a concentration of glufosinate ammonium 5000 times the lethal dose was not enough to inhibit the germination of transgenic plants expressing the bar gene. Extremely high concentrations of glufosinate ammonium caused a bushy phenotype, significantly lower numbers of grains per spike, and thousand kernel weights. Concerning the productivity, we observed that concentrations of glufosinate ammonium 64 times the lethal dose did not lead to yield depression. Our results draw attention to the possibilities implied in the transgenic approaches.

Alpha-amylase from the Hyperthermophilic Archaeon Thermococcus thioreducens

NASA Technical Reports Server (NTRS)

Bernhardsdotter, E. C. M. J.; Pusey, M. L.; Ng, M. L.; Garriott, O. K.

2003-01-01

Extremophiles are microorganisms that thrive in, from an anthropocentric view, extreme environments such as hot springs. The ability of survival at extreme conditions has rendered enzymes from extremophiles to be of interest in industrial applications. One approach to producing these extremozymes entails the expression of the enzyme-encoding gene in a mesophilic host such as E.coli. This method has been employed in the effort to produce an alpha-amylase from a hyperthermophile (an organism that displays optimal growth above 80 C) isolated from a hydrothermal vent at the Rainbow vent site in the Atlantic Ocean. alpha-amylases catalyze the hydrolysis of starch to produce smaller sugars and constitute a class of industrial enzymes having approximately 25% of the enzyme market. One application for thermostable alpha-amylases is the starch liquefaction process in which starch is converted into fructose and glucose syrups. The a-amylase encoding gene from the hyperthermophile Thermococcus thioreducens was cloned and sequenced, revealing high similarity with other archaeal hyperthermophilic a-amylases. The gene encoding the mature protein was expressed in E.coli. Initial characterization of this enzyme has revealed an optimal amylolytic activity between 85-90 C and around pH 5.3-6.0.

Genomic analysis identified a potential novel molecular mechanism for high-altitude adaptation in sheep at the Himalayas.

PubMed

Gorkhali, Neena Amatya; Dong, Kunzhe; Yang, Min; Song, Shen; Kader, Adiljian; Shrestha, Bhola Shankar; He, Xiaohong; Zhao, Qianjun; Pu, Yabin; Li, Xiangchen; Kijas, James; Guan, Weijun; Han, Jianlin; Jiang, Lin; Ma, Yuehui

2016-07-22

Sheep has successfully adapted to the extreme high-altitude Himalayan region. To identify genes underlying such adaptation, we genotyped genome-wide single nucleotide polymorphisms (SNPs) of four major sheep breeds living at different altitudes in Nepal and downloaded SNP array data from additional Asian and Middle East breeds. Using a di value-based genomic comparison between four high-altitude and eight lowland Asian breeds, we discovered the most differentiated variants at the locus of FGF-7 (Keratinocyte growth factor-7), which was previously reported as a good protective candidate for pulmonary injuries. We further found a SNP upstream of FGF-7 that appears to contribute to the divergence signature. First, the SNP occurred at an extremely conserved site. Second, the SNP showed an increasing allele frequency with the elevated altitude in Nepalese sheep. Third, the electrophoretic mobility shift assays (EMSA) analysis using human lung cancer cells revealed the allele-specific DNA-protein interactions. We thus hypothesized that FGF-7 gene potentially enhances lung function by regulating its expression level in high-altitude sheep through altering its binding of specific transcription factors. Especially, FGF-7 gene was not implicated in previous studies of other high-altitude species, suggesting a potential novel adaptive mechanism to high altitude in sheep at the Himalayas.

Dissipation of ‘dark energy’ by cortex in knowledge retrieval

NASA Astrophysics Data System (ADS)

Capolupo, Antonio; Freeman, Walter J.; Vitiello, Giuseppe

2013-03-01

We have devised a thermodynamic model of cortical neurodynamics expressed at the classical level by neural networks and at the quantum level by dissipative quantum field theory. Our model is based on features in the spatial images of cortical activity newly revealed by high-density electrode arrays. We have incorporated the mechanism and necessity for so-called dark energy in knowledge retrieval. We have extended the model first using the Carnot cycle to define our measures for energy, entropy and temperature, and then using the Rankine cycle to incorporate criticality and phase transitions. We describe the dynamics of two interactive fields of neural activity that express knowledge, one at high and the other at low energy density, and the two operators that create and annihilate the fields. We postulate that the extremely high density of energy sequestered briefly in cortical activity patterns can account for the vividness, richness of associations, and emotional intensity of memories recalled by stimuli.

Dissipation of 'dark energy' by cortex in knowledge retrieval.

PubMed

Capolupo, Antonio; Freeman, Walter J; Vitiello, Giuseppe

2013-03-01

We have devised a thermodynamic model of cortical neurodynamics expressed at the classical level by neural networks and at the quantum level by dissipative quantum field theory. Our model is based on features in the spatial images of cortical activity newly revealed by high-density electrode arrays. We have incorporated the mechanism and necessity for so-called dark energy in knowledge retrieval. We have extended the model first using the Carnot cycle to define our measures for energy, entropy and temperature, and then using the Rankine cycle to incorporate criticality and phase transitions. We describe the dynamics of two interactive fields of neural activity that express knowledge, one at high and the other at low energy density, and the two operators that create and annihilate the fields. We postulate that the extremely high density of energy sequestered briefly in cortical activity patterns can account for the vividness, richness of associations, and emotional intensity of memories recalled by stimuli. Copyright © 2013 Elsevier B.V. All rights reserved.

Simulation of Extreme Arctic Cyclones in IPCC AR5 Experiments

NASA Astrophysics Data System (ADS)

Vavrus, S. J.

2012-12-01

Although impending Arctic climate change is widely recognized, a wild card in its expression is how extreme weather events in this region will respond to greenhouse warming. Intense polar cyclones represent one type of high-latitude phenomena falling into this category, including very deep synoptic-scale cyclones and mesoscale polar lows. These systems inflict damage through high winds, heavy precipitation, and wave action along coastlines, and their impact is expected to expand in the future, when reduced sea ice cover allows enhanced wave energy. The loss of a buffering ice pack could greatly increase the rate of coastal erosion, which has already been increasing in the Arctic. These and related threats may amplify if extreme Arctic cyclones become more frequent and/or intense in a warming climate with much more open water to fuel them. This possibility has merit on the basis of GCM experiments, which project that greenhouse forcing causes lower mean sea level pressure (SLP) in the Arctic and a strengthening of the deepest storms over boreal high latitudes. In this study, the latest Coupled Model Intercomparison Project (CMIP5) climate model output is used to investigate the following questions: (1) What are the spatial and seasonal characteristics of extreme Arctic cyclones? (2) How well do GCMs simulate these phenomena? (3) Are Arctic cyclones already showing the expected response to greenhouse warming in climate models? To address these questions, a retrospective analysis is conducted of the transient 20th century simulations among the CMIP5 GCMs (spanning years 1850-2005). The results demonstrate that GCMs are able to reasonably represent extreme Arctic cyclones and that the simulated characteristics do not depend significantly on model resolution. Consistent with observational evidence, climate models generate these storms primarily during winter and within the climatological Aleutian and Icelandic Low regions. Occasionally the cyclones remain very intense over the Arctic Ocean. The historical tendency in Arctic SLP varies considerably among the GCMs, but the intermodel average trend exhibits a lowering of mean-annual pressure over the Arctic during the past 150 years and an increase in extreme cyclones in the vicinity of the Aleutian and Icelandic Lows. However, only weak trends in extreme cyclones are simulated through 2005 over the Arctic Ocean, where simulations of future climate change produce the largest SLP falls.

Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans

PubMed Central

Hulver, Matthew W.; Berggren, Jason R.; Carper, Michael J.; Miyazaki, Makoto; Ntambi, James M.; Hoffman, Eric P.; Thyfault, John P.; Stevens, Robert; Dohm, G. Lynis; Houmard, Joseph A.; Muoio, Deborah M.

2014-01-01

Summary Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity. PMID:16213227

Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans.

PubMed

Hulver, Matthew W; Berggren, Jason R; Carper, Michael J; Miyazaki, Makoto; Ntambi, James M; Hoffman, Eric P; Thyfault, John P; Stevens, Robert; Dohm, G Lynis; Houmard, Joseph A; Muoio, Deborah M

2005-10-01

Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity.

Influence of medium components on the expression of recombinant lipoproteins in Escherichia coli.

PubMed

Tseng, Chi-Ling; Leng, Chih-Hsiang

2012-02-01

Bacterial lipoproteins are crucial antigens for protective immunity against bacterial pathogens. Expression of exogenous lipoproteins in Escherichia coli at high levels is thought to be an extremely difficult endeavor because it frequently results in incomplete or absent lipid modification. Previously, we identified a fusion sequence (D1) from a Neisseria meningitidis lipoprotein that induced a non-lipidated protein, E3 (the domain III of the dengue virus envelope protein), to become lipidated. However, without optimizing the growth conditions, some of the D1-fusion proteins were not lipidated. Here, we report the influence of medium components on the expression of recombinant lipoproteins in E. coli. For high-level expression of mature lipoproteins in the C43 (DE3) strain, M9 medium was better than M63 and the rich medium. Furthermore, we analyzed the influence of other media factors (including nitrogen and carbon sources, phosphate, ferrous ions, calcium, magnesium, and pH) on the levels of lipoprotein expression. The results showed that excess nitrogen sources and phosphate in M9 medium could increase the amount of immature lipoproteins, and glucose was a better carbon source than glycerol for expressing mature lipoproteins. We also found that lipoproteins tended to be completely processed in the alkaline environment, even in the nutrient-rich medium. Additional constructs expressing different immunogens or lipid signal peptides as targets were also utilized, demonstrating that these targets could be expressed as completely mature lipoproteins in the M9 medium but not in the rich medium. Our results provide the useful information for expressing mature exogenous lipoproteins in E. coli.

Both positive and negative regulatory elements mediate expression of a photoregulated CAB gene from Nicotiana plumbaginifolia.

PubMed Central

Castresana, C; Garcia-Luque, I; Alonso, E; Malik, V S; Cashmore, A R

1988-01-01

We have analyzed promoter regulatory elements from a photoregulated CAB gene (Cab-E) isolated from Nicotiana plumbaginifolia. These studies have been performed by introducing chimeric gene constructs into tobacco cells via Agrobacterium tumefaciens-mediated transformation. Expression studies on the regenerated transgenic plants have allowed us to characterize three positive and one negative cis-acting elements that influence photoregulated expression of the Cab-E gene. Within the upstream sequences we have identified two positive regulatory elements (PRE1 and PRE2) which confer maximum levels of photoregulated expression. These sequences contain multiple repeated elements related to the sequence-ACCGGCCCACTT-. We have also identified within the upstream region a negative regulatory element (NRE) extremely rich in AT sequences, which reduces the level of gene expression in the light. We have defined a light regulatory element (LRE) within the promoter region extending from -396 to -186 bp which confers photoregulated expression when fused to a constitutive nopaline synthase ('nos') promoter. Within this region there is a 132-bp element, extending from -368 to -234 bp, which on deletion from the Cab-E promoter reduces gene expression from high levels to undetectable levels. Finally, we have demonstrated for a full length Cab-E promoter conferring high levels of photoregulated expression, that sequences proximal to the Cab-E TATA box are not replaceable by corresponding sequences from a 'nos' promoter. This contrasts with the apparent equivalence of these Cab-E and 'nos' TATA box-proximal sequences in truncated promoters conferring low levels of photoregulated expression. Images PMID:2901343

Mitochondrial function at extreme high altitude.

PubMed

Murray, Andrew J; Horscroft, James A

2016-03-01

At high altitude, barometric pressure falls and with it inspired P(O2), potentially compromising O2 delivery to the tissues. With sufficient acclimatisation, the erythropoietic response increases red cell mass such that arterial O2 content (C(aO2)) is restored; however arterial P(O2)(P(aO2)) remains low, and the diffusion of O2 from capillary to mitochondrion is impaired. Mitochondrial respiration and aerobic capacity are thus limited, whilst reactive oxygen species (ROS) production increases. Restoration of P(aO2) with supplementary O2 does not fully restore aerobic capacity in acclimatised individuals, possibly indicating a peripheral impairment. With prolonged exposure to extreme high altitude (>5500 m), muscle mitochondrial volume density falls, with a particular loss of the subsarcolemmal population. It is not clear whether this represents acclimatisation or deterioration, but it does appear to be regulated, with levels of the mitochondrial biogenesis factor PGC-1α falling, and shows similarities to adapted Tibetan highlanders. Qualitative changes in mitochondrial function also occur, and do so at more moderate high altitudes with shorter periods of exposure. Electron transport chain complexes are downregulated, possibly mitigating the increase in ROS production. Fatty acid oxidation capacity is decreased and there may be improvements in biochemical coupling at the mitochondrial inner membrane that enhance O2 efficiency. Creatine kinase expression falls, possibly impairing high-energy phosphate transfer from the mitochondria to myofibrils. In climbers returning from the summit of Everest, cardiac energetic reserve (phosphocreatine/ATP) falls, but skeletal muscle energetics are well preserved, possibly supporting the notion that mitochondrial remodelling is a core feature of acclimatisation to extreme high altitude. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Analysis of the extreme diversity of salivary alpha-amylase isoforms generated by physiological proteolysis using liquid chromatography-tandem mass spectrometry.

PubMed

Bailey, Ulla-Maja; Punyadeera, Chamindie; Cooper-White, Justin J; Schulz, Benjamin L

2012-12-12

Saliva is a crucial biofluid for oral health and is also of increasing importance as a non-invasive source of disease biomarkers. Salivary alpha-amylase is an abundant protein in saliva, and changes in amylase expression have been previously associated with a variety of diseases and conditions. Salivary alpha-amylase is subject to a high diversity of post-translational modifications, including physiological proteolysis in the oral cavity. Here we developed methodology for rapid sample preparation and non-targeted LC-ESI-MS/MS analysis of saliva from healthy subjects and observed an extreme diversity of alpha-amylase proteolytic isoforms. Our results emphasize the importance of consideration of post-translational events such as proteolysis in proteomic studies, biomarker discovery and validation, particularly in saliva. Copyright © 2012 Elsevier B.V. All rights reserved.

Inferring Spatio-temporal Variations in the Risk of Extreme Precipitation in the Western United States from Tree-ring Chronologies

NASA Astrophysics Data System (ADS)

Steinschneider, S.; Ho, M.; Cook, E. R.; Lall, U.

2017-12-01

This work explores how extreme cold-season precipitation dynamics along the west coast of the United States have varied in the past under natural climate variability through an analysis of the moisture anomalies recorded by tree-ring chronologies across the coast and interior of the western U.S. Winters with high total precipitation amounts in the coastal regions are marked by a small number of extreme storms that exhibit distinct spatial patterns of precipitation across the coast and further inland. Building from this observation, this work develops a novel application of dendroclimatic evidence to explore the following questions: a) how is extreme precipitation variability expressed in a network of tree-ring chronologies; b) can this information provide insight on the space-time variability of storm tracks that cause these extreme events; and c) how can the joint variability of extreme precipitation and storm tracks be modeled to develop consistent, multi-centennial reconstructions of both? We use gridded, tree-ring based reconstructions of the summer Palmer Drought Severity Index (PDSI) extending back 500 years within the western U.S. to build and test a novel statistical framework for reconstructing the space-time variability of coastal extreme precipitation and the associated wintertime storm tracks. Within this framework, we (1) identify joint modes of variability of extreme precipitation fields and tree-ring based PDSI reconstructions; (2) relate these modes to previously identified, unique storm track patterns associated with atmospheric rivers (ARs), which are the dominant type of storm that is responsible for extreme precipitation in the region; and (3) determine latitudinal variations of landfalling ARs across the west coast and their relationship to the these joint modes. To our knowledge, this work is the first attempt to leverage information on storm track patterns stored in a network of paleoclimate proxies to improve reconstruction fidelity.

Inferring Spatio-temporal Variations in the Risk of Extreme Precipitation in the Western United States from Tree-ring Chronologies

NASA Astrophysics Data System (ADS)

Steinschneider, S.; Ho, M.; Cook, E. R.; Lall, U.

2016-12-01

This work explores how extreme cold-season precipitation dynamics along the west coast of the United States have varied in the past under natural climate variability through an analysis of the moisture anomalies recorded by tree-ring chronologies across the coast and interior of the western U.S. Winters with high total precipitation amounts in the coastal regions are marked by a small number of extreme storms that exhibit distinct spatial patterns of precipitation across the coast and further inland. Building from this observation, this work develops a novel application of dendroclimatic evidence to explore the following questions: a) how is extreme precipitation variability expressed in a network of tree-ring chronologies; b) can this information provide insight on the space-time variability of storm tracks that cause these extreme events; and c) how can the joint variability of extreme precipitation and storm tracks be modeled to develop consistent, multi-centennial reconstructions of both? We use gridded, tree-ring based reconstructions of the summer Palmer Drought Severity Index (PDSI) extending back 500 years within the western U.S. to build and test a novel statistical framework for reconstructing the space-time variability of coastal extreme precipitation and the associated wintertime storm tracks. Within this framework, we (1) identify joint modes of variability of extreme precipitation fields and tree-ring based PDSI reconstructions; (2) relate these modes to previously identified, unique storm track patterns associated with atmospheric rivers (ARs), which are the dominant type of storm that is responsible for extreme precipitation in the region; and (3) determine latitudinal variations of landfalling ARs across the west coast and their relationship to the these joint modes. To our knowledge, this work is the first attempt to leverage information on storm track patterns stored in a network of paleoclimate proxies to improve reconstruction fidelity.

In situ expression of eukaryotic ice-binding proteins in microbial communities of Arctic and Antarctic sea ice.

PubMed

Uhlig, Christiane; Kilpert, Fabian; Frickenhaus, Stephan; Kegel, Jessica U; Krell, Andreas; Mock, Thomas; Valentin, Klaus; Beszteri, Bánk

2015-11-01

Ice-binding proteins (IBPs) have been isolated from various sea-ice organisms. Their characterisation points to a crucial role in protecting the organisms in sub-zero environments. However, their in situ abundance and diversity in natural sea-ice microbial communities is largely unknown. In this study, we analysed the expression and phylogenetic diversity of eukaryotic IBP transcripts from microbial communities of Arctic and Antarctic sea ice. IBP transcripts were found in abundances similar to those of proteins involved in core cellular processes such as photosynthesis. Eighty-nine percent of the IBP transcripts grouped with known IBP sequences from diatoms, haptophytes and crustaceans, but the majority represented novel sequences not previously characterized in cultured organisms. The observed high eukaryotic IBP expression in natural eukaryotic sea ice communities underlines the essential role of IBPs for survival of many microorganisms in communities living under the extreme conditions of polar sea ice.

Endothelial cells of extremely premature infants display impaired immune response after proinflammatory stimulation.

PubMed

Wisgrill, Lukas; Muck, Martina; Wessely, Isabelle; Berger, Angelika; Spittler, Andreas; Förster-Waldl, Elisabeth; Sadeghi, Kambis

2018-01-01

BackgroundEndothelial cells (ECs) exert immunological functions such as production of proinflammatory cytokines/chemokines as well as facilitation of extravasation of immune cells into infected tissue. Limited data are available on the functionality of ECs from extremely preterm neonates during infection. Accordingly, the aim of our study was to investigate the immune response of premature ECs after proinflammatory stimulation.MethodsCell adhesion receptors' expression and function, nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFκB) signaling, and chemokine production were analyzed in umbilical cord ECs from extremely preterm and term neonates after proinflammatory stimulation.ResultsP-selectin and E-selectin surface expression as well as NFκB signaling were lower after lipopolysaccharide (LPS) stimulation in premature ECs. Preterm ECs exhibited lower, but significant, cell-adhesive functions after LPS stimulation compared with term ECs. CCL2/CXCL8 chemokine secretion was significantly upregulated after proinflammatory stimulation in both groups. CXCL10 production was significantly increased in term but not in preterm ECs upon stimulation with tumor necrosis factor compared with unstimulated ECs.ConclusionExtremely premature ECs showed partly reduced expression levels and function of cell adhesion molecules. Both NFκB signaling and chemokine/cytokine production were reduced in premature ECs. The diminished endothelial proinflammatory immune response might result in impaired infection control of preterm newborns rendering them prone to severe infection.

A content analysis of tweets about high-potency marijuana.

PubMed

Cavazos-Rehg, Patricia A; Sowles, Shaina J; Krauss, Melissa J; Agbonavbare, Vivian; Grucza, Richard; Bierut, Laura

2016-09-01

"Dabbing" involves heating extremely concentrated forms of marijuana to high temperatures and inhaling the resulting vapor. We studied themes describing the consequences of using highly concentrated marijuana by examining the dabbing-related content on Twitter. Tweets containing dabbing-related keywords were collected from 1/1-1/31/2015 (n=206,854). A random sample of 5000 tweets was coded for content according to pre-determined categories about dabbing-related behaviors and effects experienced using a crowdsourcing service. An examination of tweets from the full sample about respiratory effects and passing out was then conducted by selecting tweets with relevant keywords. Among the 5000 randomly sampled tweets, 3540 (71%) were related to dabbing marijuana concentrates. The most common themes included mentioning current use of concentrates (n=849; 24%), the intense high and/or extreme effects from dabbing (n=763; 22%) and excessive/heavy dabbing (n=517; 15%). Extreme effects included both physiological (n=124/333; 37%) and psychological effects (n=55/333; 17%). The most common physiologic effects, passing out (n=46/333; 14%) and respiratory effects (n=30/333; 9%), were then further studied in the full sample of tweets. Coughing was the most common respiratory effect mentioned (n=807/1179; 68%), and tweeters commonly expressed dabbing with intentions to pass out (416/915; 45%). This study adds to the limited understanding of marijuana concentrates and highlights self-reported physical and psychological effects from this type of marijuana use. Future research should further examine these effects and the potential severity of health consequences associated with concentrates. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Aspen phenylpropanoid genes' expression levels correlate with genets' tannin richness and vary both in responses to soil nitrogen and associations with phenolic profiles.

PubMed

Decker, Vicki H G; Bandau, Franziska; Gundale, Michael J; Cole, Christopher T; Albrectsen, Benedicte R

2017-02-01

Condensed tannin (CT) contents of European aspen (Populus tremula L.) vary among genotypes, and increases in nitrogen (N) availability generally reduce plants' tannin production in favor of growth, through poorly understood mechanisms. We hypothesized that intrinsic tannin production rates may co-vary with gene expression responses to soil N and resource allocation within the phenylpropanoid pathway (PPP). Thus, we examined correlations between soil N levels and both expression patterns of eight PPP genes (measured by quantitative-reverse transcription PCR) and foliar phenolic compounds (measured by liquid chromatography-mass spectrometry) in young aspen genets with intrinsically extreme CT levels. Monitored phenolics included salicinoids, lignins, flavones, flavonols, CT precursors and CTs. The PPP genes were consistently expressed more strongly in high-CT trees. Low N supplements reduced expression of genes throughout the PPP in all genets, while high N doses restored expression of genes at the beginning and end of the pathway. These PPP changes were not reflected in pools of tannin precursors, but varying correlations between gene expression and foliar phenolic pools were detected in young and mature leaves, suggesting that processes linking gene expression and the resulting phenolics vary spatially and temporally. Precursor fluxes suggested that CT-related metabolic rate or sink controls are linked to intrinsic carbon allocation strategies associated with N responses. Overall, we found more negative correlations (indicative of allocation trade-offs) between PPP gene expression and phenolic products following N additions in low-CT plants than in high-CT plants. The tannin-related expression dynamics suggest that, in addition to defense, relative tannin levels may also be indicative of intraspecific variations in the way aspen genets respond to soil fertility. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Multi-temporal scale analysis of impacts of extreme high temperature on net carbon uptake in subtropical coniferous plantation.

PubMed

Zhang, Mi; Wen, Xue Fa; Zhang, Lei Ming; Wang, Hui Min; Guo, Yi Wen; Yu, Gui Rui

2018-02-01

Extreme high temperature is one of important extreme weathers that impact forest ecosystem carbon cycle. In this study, applying CO 2 flux and routine meteorological data measured during 2003-2012, we examined the impacts of extreme high temperature and extreme high temperature event on net carbon uptake of subtropical coniferous plantation in Qianyanzhou. Combining with wavelet analysis, we analyzed environmental controls on net carbon uptake at different temporal scales, when the extreme high temperature and extreme high temperature event happened. The results showed that mean daily cumulative NEE decreased by 51% in the days with daily maximum air temperature range between 35 ℃ and 40 ℃, compared with that in the days with the range between 30 ℃ and 34 ℃. The effects of the extreme high temperature and extreme high temperature event on monthly NEE and annual NEE related to the strength and duration of extreme high tempe-rature event. In 2003, when strong extreme high temperature event happened, the sum of monthly cumulative NEE in July and August was only -11.64 g C·m -2 ·(2 month) -1 . The value decreased by 90%, compared with multi-year average value. At the same time, the relative variation of annual NEE reached -6.7%. In July and August, when the extreme high temperature and extreme high temperature event occurred, air temperature (T a ) and vapor press deficit (VPD) were the dominant controller for the daily variation of NEE. The coherency between NEE T a and NEE VPD was 0.97 and 0.95, respectively. At 8-, 16-, and 32-day periods, T a , VPD, soil water content at 5 cm depth (SWC), and precipitation (P) controlled NEE. The coherency between NEE SWC and NEE P was higher than 0.8 at monthly scale. The results indicated that atmospheric water deficit impacted NEE at short temporal scale, when the extreme high temperature and extreme high temperature event occurred, both of atmospheric water deficit and soil drought stress impacted NEE at long temporal scales in this ecosystem.

Chlorophyll metabolism in pollinated vs. parthenocarpic fig fruits throughout development and ripening.

PubMed

Rosianskey, Yogev; Dahan, Yardena; Yadav, Sharawan; Freiman, Zohar E; Milo-Cochavi, Shira; Kerem, Zohar; Eyal, Yoram; Flaishman, Moshe A

2016-08-01

Expression of 13 genes encoding chlorophyll biosynthesis and degradation was evaluated. Chlorophyll degradation was differentially regulated in pollinated and parthenocarpic fig fruits, leading to earlier chlorophyll degradation in parthenocarpic fruits. Varieties of the common fig typically yield a commercial summer crop that requires no pollination, although it can be pollinated. Fig fruit pollination results in larger fruit size, greener skin and darker interior inflorescence color, and slows the ripening process compared to non-pollinated fruits. We evaluated the effect of pollination on chlorophyll content and levels of transcripts encoding enzymes of the chlorophyll metabolism in fruits of the common fig 'Brown Turkey'. We cloned and evaluated the expression of 13 different genes. All 13 genes showed high expression in the fruit skin, inflorescences and leaves, but extremely low expression in roots. Pollination delayed chlorophyll breakdown in the ripening fruit skin and inflorescences. This was correlated with the expression of genes encoding enzymes in the chlorophyll biosynthesis and degradation pathways. Expression of pheophorbide a oxygenase (PAO) was strongly negatively correlated with chlorophyll levels during ripening in pollinated fruits; along with its high expression levels in yellow leaves, this supports a pivotal role for PAO in chlorophyll degradation in figs. Normalizing expression levels of all chlorophyll metabolism genes in the pollinated and parthenocarpic fruit skin and inflorescences showed three synthesis (FcGluTR1, FcGluTR2 and FcCLS1) and three degradation (FcCLH1, FcCLH2 and FcRCCR1) genes with different temporal expression in the pollinated vs. parthenocarpic fruit skin and inflorescences. FcCAO also showed different expressions in the parthenocarpic fruit skin. Thus, chlorophyll degradation is differentially regulated in the pollinated and parthenocarpic fruit skin and inflorescences, leading to earlier and more sustained chlorophyll degradation in the parthenocarpic fruit.

An intronless form of the tobacco extensin gene terminator strongly enhances transient gene expression in plant leaves.

PubMed

Rosenthal, Sun Hee; Diamos, Andrew G; Mason, Hugh S

2018-03-01

We have found interesting features of a plant gene (extensin) 3' flanking region, including extremely efficient polyadenylation which greatly improves transient expression of transgenes when an intron is removed. Its use will greatly benefit studies of gene expression in plants, research in molecular biology, and applications for recombinant proteins. Plants are a promising platform for the production of recombinant proteins. To express high-value proteins in plants efficiently, the optimization of expression cassettes using appropriate regulatory sequences is critical. Here, we characterize the activity of the tobacco extensin (Ext) gene terminator by transient expression in Nicotiana benthamiana, tobacco, and lettuce. Ext is a member of the hydroxyproline-rich glycoprotein (HRGP) superfamily and constitutes the major protein component of cell walls. The present study demonstrates that the Ext terminator with its native intron removed increased transient gene expression up to 13.5-fold compared to previously established terminators. The enhanced transgene expression was correlated with increased mRNA accumulation and reduced levels of read-through transcripts, which could impair gene expression. Analysis of transcript 3'-ends found that the majority of polyadenylated transcripts were cleaved at a YA dinucleotide downstream from a canonical AAUAAA motif and a UG-rich region, both of which were found to be highly conserved among related extensin terminators. Deletion of either of these regions eliminated most of the activity of the terminator. Additionally, a 45 nt polypurine sequence ~ 175 nt upstream from the polyadenylation sites was found to also be necessary for the enhanced expression. We conclude that the use of Ext terminator has great potential to benefit the production of recombinant proteins in plants.

Heritability of growth traits and correlation with hepatic gene expression among hybrid striped bass exhibiting extremes in performance

USDA-ARS?s Scientific Manuscript database

We set out to better understand the genetic basis behind growth variation in hybrid striped bass (HSB) by determining whether gene expression changes could be detected between the largest and smallest HSB in a population using a global gene expression approach by RNA sequencing of liver. Fingerling...

Heat-shock protein 70 (Hsp70) expression in four limpets of the genus Lottia: interspecific variation in constitutive and inducible synthesis correlates with in situ exposure to heat stress.

PubMed

Dong, Yunwei; Miller, Luke P; Sanders, Jon G; Somero, George N

2008-10-01

Limpets of the genus Lottia occupy a broad vertical distribution on wave-exposed rocky shores, a range that encompasses gradients in the frequency and severity of thermal and desiccation stress brought on by aerial emersion. Using western blot analysis of levels of heat-shock protein 70 (Hsp70), we examined the heat-shock responses of four Lottia congeners: Lottia scabra and L. austrodigitalis, which occur in the high-intertidal zone, and L. pelta and L. scutum, which are restricted to the low- and mid-intertidal zones. Our results suggest distinct strategies of Hsp70 expression in limpets occupying different heights and orientations in the rocky intertidal zone. In freshly field-collected animals and in specimens acclimated at ambient temperature ( approximately 14 degrees C) for 14 days, the two high-intertidal species had higher constitutive levels of Hsp70 than the low- and mid-intertidal species. During aerial exposure to high temperatures, the two low-shore species and L. austrodigitalis exhibited an onset of Hsp70 expression at 28 degrees C; no induction of Hsp70 occurred in L. scabra. Our findings suggest that high-intertidal congeners of Lottia employ a "preparative defense" strategy involving maintenance of high constitutive levels of Hsp70 in their cells as a mechanism for protection against periods of extreme and unpredictable heat stress.

Tilapia and human CLIC2 structures are highly conserved.

PubMed

Zeng, Jiao; Li, Zhengjun; Lui, Eei Yin; Lam, Siew Hong; Swaminathan, Kunchithapadam

2018-01-08

Chloride intracellular channels (CLICs) exist in soluble and membrane bound forms. We have determined the crystal structure of soluble Clic2 from the euryhaline teleost fish Oreochromis mossambicus. Structural comparison of tilapia and human CLIC2 with other CLICs shows that these proteins are highly conserved. We have also compared the expression levels of clic2 in selected osmoregulatory organs of tilapia, acclimated to freshwater, seawater and hypersaline water. Structural conservation of vertebrate CLICs implies that they might play conserved roles. Also, tissue-specific responsiveness of clic2 suggests that it might be involved in iono-osmoregulation under extreme conditions in tilapia. Copyright © 2017 Elsevier Inc. All rights reserved.

The great 2006 heat wave over California and Nevada: Signal of an increasing trend

USGS Publications Warehouse

Gershunov, A.; Cayan, D.R.; Iacobellis, S.F.

2009-01-01

Most of the great California-Nevada heat waves can be classified into primarily daytime or nighttime events depending on whether atmospheric conditions are dry or humid. A rash of nighttime-accentuated events in the last decade was punctuated by an unusually intense case in July 2006, which was the largest heat wave on record (1948-2006). Generally, there is a positive trend in heat wave activity over the entire region that is expressed most strongly and clearly in nighttime rather than daytime temperature extremes. This trend in nighttime heat wave activity has intensified markedly since the 1980s and especially since 2000. The two most recent nighttime heat waves were also strongly expressed in extreme daytime temperatures. Circulations associated with great regional heat waves advect hot air into the region. This air can be dry or moist, depending on whether a moisture source is available, causing heat waves to be expressed preferentially during day or night. A remote moisture source centered within a marine region west of Baja California has been increasing in prominence because of gradual sea surface warming and a related increase in atmospheric humidity. Adding to the very strong synoptic dynamics during the 2006 heat wave were a prolonged stream of moisture from this southwestern source and, despite the heightened humidity, an environment in which afternoon convection was suppressed, keeping cloudiness low and daytime temperatures high. The relative contributions of these factors and possible relations to global warming are discussed. ?? 2009 American Meteorological Society.

Characteristics and safety assessment of intractable proteins in genetically modified crops.

PubMed

Bushey, Dean F; Bannon, Gary A; Delaney, Bryan F; Graser, Gerson; Hefford, Mary; Jiang, Xiaoxu; Lee, Thomas C; Madduri, Krishna M; Pariza, Michael; Privalle, Laura S; Ranjan, Rakesh; Saab-Rincon, Gloria; Schafer, Barry W; Thelen, Jay J; Zhang, John X Q; Harper, Marc S

2014-07-01

Genetically modified (GM) crops may contain newly expressed proteins that are described as "intractable". Safety assessment of these proteins may require some adaptations to the current assessment procedures. Intractable proteins are defined here as those proteins with properties that make it extremely difficult or impossible with current methods to express in heterologous systems; isolate, purify, or concentrate; quantify (due to low levels); demonstrate biological activity; or prove equivalency with plant proteins. Five classes of intractable proteins are discussed here: (1) membrane proteins, (2) signaling proteins, (3) transcription factors, (4) N-glycosylated proteins, and (5) resistance proteins (R-proteins, plant pathogen recognition proteins that activate innate immune responses). While the basic tiered weight-of-evidence approach for assessing the safety of GM crops proposed by the International Life Sciences Institute (ILSI) in 2008 is applicable to intractable proteins, new or modified methods may be required. For example, the first two steps in Tier I (hazard identification) analysis, gathering of applicable history of safe use (HOSU) information and bioinformatics analysis, do not require protein isolation. The extremely low level of expression of most intractable proteins should be taken into account while assessing safety of the intractable protein in GM crops. If Tier II (hazard characterization) analyses requiring animal feeding are judged to be necessary, alternatives to feeding high doses of pure protein may be needed. These alternatives are discussed here. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Two Strategies for Microbial Production of an Industrial Enzyme-Alpha-Amylase

NASA Technical Reports Server (NTRS)

Bernhardsdotter, Eva C. M. J.; Garriott, Owen; Pusey, Marc L.; Ng, Joseph D.

2003-01-01

Extremophiles are microorganisms that thrive in, from an anthropocentric view, extreme environments including hot springs, soda lakes and arctic water. This ability of survival at extreme conditions has rendered extremophiles to be of interest in astrobiology, evolutionary biology as well as in industrial applications. Of particular interest to the biotechnology industry are the biological catalysts of the extremophiles, the extremozymes, whose unique stabilities at extreme conditions make them potential sources of novel enzymes in industrial applications. There are two major approaches to microbial enzyme production. This entails enzyme isolation directly from the natural host or creating a recombinant expression system whereby the targeted enzyme can be overexpressed in a mesophilic host. We are employing both methods in the effort to produce alpha-amylases from a hyperthermophilic archaeon (Thermococcus) isolated from a hydrothermal vent in the Atlantic Ocean, as well as from alkaliphilic bacteria (Bacillus) isolated from a soda lake in Tanzania. Alpha-amylases catalyze the hydrolysis of internal alpha-1,4-glycosidic linkages in starch to produce smaller sugars. Thermostable alpha-amylases are used in the liquefaction of starch for production of fructose and glucose syrups, whereas alpha-amylases stable at high pH have potential as detergent additives. The alpha-amylase encoding gene from Thermococcus was PCR amplified using carefully designed primers and analyzed using bioinformatics tools such as BLAST and Multiple Sequence Alignment for cloning and expression in E.coli. Four strains of Bacillus were grown in alkaline starch-enriched medium of which the culture supernatant was used as enzyme source. Amylolytic activity was detected using the starch-iodine method.

Usefulness of questionnaires on advance directives in haemodialysis units.

PubMed

Jornet, Angel Rodríguez; Castellanos, Loreley Ana Betancourt; Contador, Maria Isabel Bolós; Morera, Juan Carlos Oliva; López, José Antonio Ibeas

2017-10-01

As renal replacement therapy has become universal practice in medicine, there is a need to consider whether this treatment is suitable for elderly people. These patients have high comorbidity and may require dialysis withdrawal in certain clinical circumstances. Advance directives (ADs) drawn up by patients facilitate treatment-related decisions if they lose cognitive capacity. Questionnaires dealing with possible extreme clinical circumstances can thus help clinicians and relatives reach pertinent decisions in such cases. We studied the usefulness of questionnaires on ADs in patients who started periodic haemodialysis over a period of 10 years. Telephone interviews were conducted to assess satisfaction level among relatives/representatives of deceased patients who had been advised to limit therapeutic efforts in certain clinical situations. The questionnaire was assessed using a six-factor degree of satisfaction. Four hundred and forty-three questionnaires were distributed over a period of 10 years. A total of 41.3% of patients stated that they wished to limit therapeutic efforts in the serious clinical situations presented; 37.9% refused to complete the questionnaire; 14.7% expressed their wishes without any written confirmation; and 6.1% expressed their wish to continue on dialysis in all situations. Two hundred and twenty-four patients had died by the study end date. The cause of death in 20.2% was scheduled dialysis withdrawal. Representatives reported an extremely high degree of satisfaction with the questionnaire (94.7%). Younger people, however, were more reluctant to consider and answer questionnaires on ADs. Questionnaires on ADs are a useful tool in daily nephrology practice and should be distributed to those patients willing to consider the limitation of therapeutic efforts in extreme clinical circumstances. In general terms, these questionnaires should be given to all elderly patients. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Autoselection of cytoplasmic yeast virus like elements encoding toxin/antitoxin systems involves a nuclear barrier for immunity gene expression.

PubMed

Kast, Alene; Voges, Raphael; Schroth, Michael; Schaffrath, Raffael; Klassen, Roland; Meinhardt, Friedhelm

2015-05-01

Cytoplasmic virus like elements (VLEs) from Kluyveromyces lactis (Kl), Pichia acaciae (Pa) and Debaryomyces robertsiae (Dr) are extremely A/T-rich (>75%) and encode toxic anticodon nucleases (ACNases) along with specific immunity proteins. Here we show that nuclear, not cytoplasmic expression of either immunity gene (PaORF4, KlORF3 or DrORF5) results in transcript fragmentation and is insufficient to establish immunity to the cognate ACNase. Since rapid amplification of 3' ends (RACE) as well as linker ligation of immunity transcripts expressed in the nucleus revealed polyadenylation to occur along with fragmentation, ORF-internal poly(A) site cleavage due to the high A/T content is likely to prevent functional expression of the immunity genes. Consistently, lowering the A/T content of PaORF4 to 55% and KlORF3 to 46% by gene synthesis entirely prevented transcript cleavage and permitted functional nuclear expression leading to full immunity against the respective ACNase toxin. Consistent with a specific adaptation of the immunity proteins to the cognate ACNases, cross-immunity to non-cognate ACNases is neither conferred by PaOrf4 nor KlOrf3. Thus, the high A/T content of cytoplasmic VLEs minimizes the potential of functional nuclear recruitment of VLE encoded genes, in particular those involved in autoselection of the VLEs via a toxin/antitoxin principle.

Effects of repeated 9 and 30-day exposure to extremely low-frequency electromagnetic fields on social recognition behavior and estrogen receptors expression in olfactory bulb of Wistar female rats.

PubMed

Bernal-Mondragón, C; Arriaga-Avila, V; Martínez-Abundis, E; Barrera-Mera, B; Mercado-Gómez, O; Guevara-Guzmán, R

2017-02-01

We investigated the short- and long-term effects of extremely low-frequency electromagnetic fields (EMF) on social recognition behavior and expression of α- and β-estrogen receptors (ER). Rats were exposed to 60-Hz electromagnetic fields for 9 or 30 days and tested for social recognition behavior. Immunohistochemistry and western blot assays were performed to evaluate α- and β-ER expression in the olfactory bulb of intact, ovariectomized (OVX), and ovariectomized+estradiol (E2) replacement (OVX+E2). Ovariectomization showed impairment of social recognition after 9 days of EMF exposure and a complete recovery after E2 replacement and so did those after 30 days. Short EMF exposure increased expression of β-ER in intact, but not in the others. Longer exposure produced a decrease in intact but an increase in OVX and OVX+E2. Our findings suggest a significant role for β-estrogen receptors and a lack of effect for α-estrogen receptors on a social recognition task. EMF: extremely low frequency electromagnetic fields; ERs: estrogen receptors; OB: olfactory bulb; OVX: ovariectomized; OVX + E 2 : ovariectomized + estradiol replacement; IEI: interexposure interval; β-ER: beta estrogen receptor; E 2 : replacement of estradiol; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; WB: Western blot; PBS: phosphate-buffer saline; PB: phosphate-buffer.

Drug resistance is conferred on the model yeast Saccharomyces cerevisiae by expression of full-length melanoma-associated human ATP-binding cassette transporter ABCB5.

PubMed

Keniya, Mikhail V; Holmes, Ann R; Niimi, Masakazu; Lamping, Erwin; Gillet, Jean-Pierre; Gottesman, Michael M; Cannon, Richard D

2014-10-06

ABCB5, an ATP-binding cassette (ABC) transporter, is highly expressed in melanoma cells, and may contribute to the extreme resistance of melanomas to chemotherapy by efflux of anti-cancer drugs. Our goal was to determine whether we could functionally express human ABCB5 in the model yeast Saccharomyces cerevisiae, in order to demonstrate an efflux function for ABCB5 in the absence of background pump activity from other human transporters. Heterologous expression would also facilitate drug discovery for this important target. DNAs encoding ABCB5 sequences were cloned into the chromosomal PDR5 locus of a S. cerevisiae strain in which seven endogenous ABC transporters have been deleted. Protein expression in the yeast cells was monitored by immunodetection using both a specific anti-ABCB5 antibody and a cross-reactive anti-ABCB1 antibody. ABCB5 function in recombinant yeast cells was measured by determining whether the cells possessed increased resistance to known pump substrates, compared to the host yeast strain, in assays of yeast growth. Three ABCB5 constructs were made in yeast. One was derived from the ABCB5-β mRNA, which is highly expressed in human tissues but is a truncation of a canonical full-size ABC transporter. Two constructs contained full-length ABCB5 sequences: either a native sequence from cDNA or a synthetic sequence codon-harmonized for S. cerevisiae. Expression of all three constructs in yeast was confirmed by immunodetection. Expression of the codon-harmonized full-length ABCB5 DNA conferred increased resistance, relative to the host yeast strain, to the putative substrates rhodamine 123, daunorubicin, tetramethylrhodamine, FK506, or clorgyline. We conclude that full-length ABCB5 can be functionally expressed in S. cerevisiae and confers drug resistance.

Heterogeneous, restricted patterns of Epstein-Barr virus (EBV) latent gene expression in patients with chronic active EBV infection.

PubMed

Yoshioka, M; Ishiguro, N; Ishiko, H; Ma, X; Kikuta, H; Kobayashi, K

2001-10-01

Epstein-Barr virus (EBV) has been shown to infect T lymphocytes and to be associated with a chronic active infection (CAEBV), which has been recognized as a mainly non-neoplastic T-cell lymphoproliferative disorder (T-cell LPD). The systemic distribution of EBV genomes was studied, by real-time PCR, in multiple tissues from six patients with CAEBV, including three patients with T-cell LPD, one patient with B-cell LPD and two patients with undetermined cell-type LPD. There were extremely high loads of EBV genomes in all tissues from the patients. This reflects an abundance of circulating and infiltrating EBV-infected cells and a wide variety of clinical symptoms in the affected tissues. We chose one sample from each patient that was shown by real-time PCR to contain a high load of EBV genomes and examined the expression of EBV latent genes by RT-PCR. EBER1 and EBNA1 transcripts were detected in all samples. Only one sample also expressed EBNA2, LMP1 and LMP2A transcripts in addition to EBER1 and EBNA1 transcripts. Two of the remaining five samples expressed LMP1 and LMP2A transcripts. One sample expressed LMP2A but not LMP1 and EBNA2 transcripts. Another sample expressed EBNA2 but not LMP1 and LMP2A transcripts. The other sample did not express transcripts of any of the other EBNAs or LMPs. None of the samples expressed the viral immediate-early gene BZLF1. These results showed that EBV latent gene expression in CAEBV is heterogeneous and that restricted forms of EBV latency might play a pathogenic role in the development of CAEBV.

Differentially expressed drought-responsive genes in Malus sieversii roots may contribute to this species' adaptation to arid environments

USDA-ARS?s Scientific Manuscript database

Understanding naturally evolved adaptation to arid climates may be a key factor in developing crops that can thrive during extreme climate fluctuations. Malus sieversii (Ledeb.) M. Roem. is a wild apple species that has adapted to harsh environments in Kazakhstan, including extreme cold and dry reg...

Application of RT-PCR in formalin-fixed and paraffin-embedded lung cancer tissues.

PubMed

Zhang, Fan; Wang, Zhuo-min; Liu, Hong-yu; Bai, Yun; Wei, Sen; Li, Ying; Wang, Min; Chen, Jun; Zhou, Qing-hua

2010-01-01

To analyze gene expression in formalin-fixed, paraffin-embedded lung cancer tissues using modified method. Total RNA from frozen tissues was extracted using TRIZOL reagent. RNA was extracted from formalin-fixed, paraffin-embedded tissues by digestion with proteinase K before the acid-phenol:chloroform extraction and carrier precipitation. We modified this method by using a higher concentration of proteinase K and a longer digestion time, optimized to 16 hours. RT-PCR and real-time RT-PCR were used to check reproducibility and the concordance between frozen and paraffin-embedded samples. The results showed that the RNA extracted from the paraffin-embedded lung tissues had high quality with the most fragment length between 28S and 18S bands (about 1000 to 2000 bases). The housekeeping gene GUSB exhibited low variation of expression in frozen and paraffin-embedded lung tissues, whereas PGK1 had the lowest variation in lymphoma tissues. Furthermore, real-time PCR analysis of the expression of known prognostic genes in non-small cell lung carcinoma (NSCLC) demonstrated an extremely high correlation (r>0.880) between the paired frozen and formalin-fixed, paraffin-embedded specimens. This improved method of RNA extraction is suitable for real-time quantitative RT-PCR, and may be used for global gene expression profiling of paraffin-embedded tissues.

Transcriptomic analysis of Crassostrea sikamea × Crassostrea angulata hybrids in response to low salinity stress.

PubMed

Yan, Lulu; Su, Jiaqi; Wang, Zhaoping; Yan, Xiwu; Yu, Ruihai; Ma, Peizhen; Li, Yangchun; Du, Junpeng

2017-01-01

Hybrid oysters often show heterosis in growth rate, weight, survival and adaptability to extremes of salinity. Oysters have also been used as model organisms to study the evolution of host-defense system. To gain comprehensive knowledge about various physiological processes in hybrid oysters under low salinity stress, we performed transcriptomic analysis of gill tissue of Crassostrea sikamea ♀ × Crassostrea angulata♂ hybrid using the deep-sequencing platform Illumina HiSeq. We exploited the high-throughput technique to delineate differentially expressed genes (DEGs) in oysters maintained in hypotonic conditions. A total of 199,391 high quality unigenes, with average length of 644 bp, were generated. Of these 35 and 31 genes showed up- and down-regulation, respectively. Functional categorization and pathway analysis of these DEGs revealed enrichment for immune mechanism, apoptosis, energy metabolism and osmoregulation under low salinity stress. The expression patterns of 41 DEGs in hybrids and their parental species were further analyzed by quantitative real-time PCR (qRT-PCR). This study will serve as a platform for subsequent gene expression analysis regarding environmental stress. Our findings will also provide valuable information about gene expression to better understand the immune mechanism, apoptosis, energy metabolism and osmoregulation in hybrid oysters under low salinity stress.

Transcriptomic analysis of Crassostrea sikamea × Crassostrea angulata hybrids in response to low salinity stress

PubMed Central

Yan, Lulu; Su, Jiaqi; Wang, Zhaoping; Yan, Xiwu; Yu, Ruihai; Ma, Peizhen; Li, Yangchun; Du, Junpeng

2017-01-01

Hybrid oysters often show heterosis in growth rate, weight, survival and adaptability to extremes of salinity. Oysters have also been used as model organisms to study the evolution of host-defense system. To gain comprehensive knowledge about various physiological processes in hybrid oysters under low salinity stress, we performed transcriptomic analysis of gill tissue of Crassostrea sikamea ♀ × Crassostrea angulata♂ hybrid using the deep-sequencing platform Illumina HiSeq. We exploited the high-throughput technique to delineate differentially expressed genes (DEGs) in oysters maintained in hypotonic conditions. A total of 199,391 high quality unigenes, with average length of 644 bp, were generated. Of these 35 and 31 genes showed up- and down-regulation, respectively. Functional categorization and pathway analysis of these DEGs revealed enrichment for immune mechanism, apoptosis, energy metabolism and osmoregulation under low salinity stress. The expression patterns of 41 DEGs in hybrids and their parental species were further analyzed by quantitative real-time PCR (qRT-PCR). This study will serve as a platform for subsequent gene expression analysis regarding environmental stress. Our findings will also provide valuable information about gene expression to better understand the immune mechanism, apoptosis, energy metabolism and osmoregulation in hybrid oysters under low salinity stress. PMID:28182701

Shooting the messenger to spite the message? Exploring reactions to claims of racial bias.

PubMed

Schultz, Jennifer R; Maddox, Keith B

2013-03-01

Two experiments examined aspects of the communicator, message, and audience in producing evaluative backlash toward minorities who make claims of ongoing racial bias. In Experiment 1, participants evaluated a White or Black confederate who gave a speech expressing no claim, a mild claim, or an extreme claim of racial bias. Results indicated a race-specific evaluative backlash: Participants more negatively rated Black compared with White communicators, but only when the claim was extreme. Experiment 2 found that participants more negatively rated Black (vs. White) communicators when they used low-quality arguments, but this backlash was eliminated when Black communicators used high-quality arguments. Furthermore, participants who held stronger meritocracy beliefs and who heard low-quality arguments were more likely to evaluate Black communicators harshly. These findings clarify the conditions under which people from advantaged groups are more likely to recognize claims of racial bias as legitimate and respond favorably to the communicator.

Poverty and fatalism: Impacts on the community dynamics and on hope in Brazilian residents.

PubMed

Cidade, Elívia Camurça; Moura, James Ferreira; Nepomuceno, Bárbara Barbosa; Ximenes, Verônica Morais; Sarriera, Jorge Castellá

2016-01-01

The aim of this study was to analyze the consequences of poverty on expressions of fatalism, hope, and sense of community of two Brazilian States: Ceará and Rio Grande do Sul. Seven-hundred and thirty-one people, divided in four groups (extreme poverty, poverty, median income, and adequate income) answered a questionnaire. The variables sense of community and hope were found to be predictors of fatalism. Individuals in situations of poverty and extreme poverty showed high indices of fatalism, pessimism, divinity control, and luck, and low indices of hope and sense of community. Individuals with adequate income have low levels of fatalism, pessimism, and divinity control. It is concluded that poverty has consequences on the life of those who experience it, and that attitudes of pessimism, hopelessness, and belief in luck as well as the weakening of community networks, articulate and support the maintenance of the status quo.

Associations among measures of sequential processing in motor and linguistics tasks in adults with and without a family history of childhood apraxia of speech: a replication study.

PubMed

Button, Le; Peter, Beate; Stoel-Gammon, Carol; Raskind, Wendy H

2013-03-01

The purpose of this study was to address the hypothesis that childhood apraxia of speech (CAS) is influenced by an underlying deficit in sequential processing that is also expressed in other modalities. In a sample of 21 adults from five multigenerational families, 11 with histories of various familial speech sound disorders, 3 biologically related adults from a family with familial CAS showed motor sequencing deficits in an alternating motor speech task. Compared with the other adults, these three participants showed deficits in tasks requiring high loads of sequential processing, including nonword imitation, nonword reading and spelling. Qualitative error analyses in real word and nonword imitations revealed group differences in phoneme sequencing errors. Motor sequencing ability was correlated with phoneme sequencing errors during real word and nonword imitation, reading and spelling. Correlations were characterized by extremely high scores in one family and extremely low scores in another. Results are consistent with a central deficit in sequential processing in CAS of familial origin.

Associations among measures of sequential processing in motor and linguistics tasks in adults with and without a family history of childhood apraxia of speech: A replication study

PubMed Central

BUTTON, LE; PETER, BEATE; STOEL-GAMMON, CAROL; RASKIND, WENDY H.

2013-01-01

The purpose of this study was to address the hypothesis that childhood apraxia of speech (CAS) is influenced by an underlying deficit in sequential processing that is also expressed in other modalities. In a sample of 21 adults from five multigenerational families, 11 with histories of various familial speech sound disorders, 3 biologically related adults from a family with familial CAS showed motor sequencing deficits in an alternating motor speech task. Compared with the other adults, these three participants showed deficits in tasks requiring high loads of sequential processing, including nonword imitation, nonword reading and spelling. Qualitative error analyses in real word and nonword imitations revealed group differences in phoneme sequencing errors. Motor sequencing ability was correlated with phoneme sequencing errors during real word and nonword imitation, reading and spelling. Correlations were characterized by extremely high scores in one family and extremely low scores in another. Results are consistent with a central deficit in sequential processing in CAS of familial origin. PMID:23339292

Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression

PubMed Central

Dunipace, Leslie; Ozdemir, Anil; Stathopoulos, Angelike

2011-01-01

It has been shown in several organisms that multiple cis-regulatory modules (CRMs) of a gene locus can be active concurrently to support similar spatiotemporal expression. To understand the functional importance of such seemingly redundant CRMs, we examined two CRMs from the Drosophila snail gene locus, which are both active in the ventral region of pre-gastrulation embryos. By performing a deletion series in a ∼25 kb DNA rescue construct using BAC recombineering and site-directed transgenesis, we demonstrate that the two CRMs are not redundant. The distal CRM is absolutely required for viability, whereas the proximal CRM is required only under extreme conditions such as high temperature. Consistent with their distinct requirements, the CRMs support distinct expression patterns: the proximal CRM exhibits an expanded expression domain relative to endogenous snail, whereas the distal CRM exhibits almost complete overlap with snail except at the anterior-most pole. We further show that the distal CRM normally limits the increased expression domain of the proximal CRM and that the proximal CRM serves as a `damper' for the expression levels driven by the distal CRM. Thus, the two CRMs interact in cis in a non-additive fashion and these interactions may be important for fine-tuning the domains and levels of gene expression. PMID:21813571

Transgenic miR156 switchgrass in the field: growth, recalcitrance and rust susceptibility

DOE PAGES

Baxter, Holly L.; Mazarei, Mitra; Dumitrache, Alexandru; ...

2017-04-24

Sustainable utilization of lignocellulosic perennial grass feedstocks will be enabled by high biomass production and optimized cell wall chemistry for efficient conversion into biofuels. MicroRNAs are regulatory elements that modulate the expression of genes involved in various biological functions in plants, including growth and development. In greenhouse studies, overexpressing a microRNA (miR156) gene in switchgrass had dramatic effects on plant architecture and flowering, which appeared to be driven by transgene expression levels. High expressing lines were extremely dwarfed, whereas low and moderate-expressing lines had higher biomass yields, improved sugar release and delayed flowering. Four lines with moderate or low miR156more » overexpression from the prior greenhouse study were selected for a field experiment to assess the relationship between miR156 expression and biomass production over three years. We also analysed important bioenergy feedstock traits such as flowering, disease resistance, cell wall chemistry and biofuel production. Phenotypes of the transgenic lines were inconsistent between the greenhouse and the field as well as among different field growing seasons. One low expressing transgenic line consistently produced more biomass (25%–56%) than the control across all three seasons, which translated to the production of 30% more biofuel per plant during the final season. The other three transgenic lines produced less biomass than the control by the final season, and the two lines with moderate expression levels also exhibited altered disease susceptibilities. Results of this study emphasize the importance of performing multiyear field studies for plants with altered regulatory transgenes that target plant growth and development.« less

Transgenic miR156 switchgrass in the field: growth, recalcitrance and rust susceptibility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baxter, Holly L.; Mazarei, Mitra; Dumitrache, Alexandru

Sustainable utilization of lignocellulosic perennial grass feedstocks will be enabled by high biomass production and optimized cell wall chemistry for efficient conversion into biofuels. MicroRNAs are regulatory elements that modulate the expression of genes involved in various biological functions in plants, including growth and development. In greenhouse studies, overexpressing a microRNA (miR156) gene in switchgrass had dramatic effects on plant architecture and flowering, which appeared to be driven by transgene expression levels. High expressing lines were extremely dwarfed, whereas low and moderate-expressing lines had higher biomass yields, improved sugar release and delayed flowering. Four lines with moderate or low miR156more » overexpression from the prior greenhouse study were selected for a field experiment to assess the relationship between miR156 expression and biomass production over three years. We also analysed important bioenergy feedstock traits such as flowering, disease resistance, cell wall chemistry and biofuel production. Phenotypes of the transgenic lines were inconsistent between the greenhouse and the field as well as among different field growing seasons. One low expressing transgenic line consistently produced more biomass (25%–56%) than the control across all three seasons, which translated to the production of 30% more biofuel per plant during the final season. The other three transgenic lines produced less biomass than the control by the final season, and the two lines with moderate expression levels also exhibited altered disease susceptibilities. Results of this study emphasize the importance of performing multiyear field studies for plants with altered regulatory transgenes that target plant growth and development.« less

Applying Cost-Sensitive Extreme Learning Machine and Dissimilarity Integration to Gene Expression Data Classification.

PubMed

Liu, Yanqiu; Lu, Huijuan; Yan, Ke; Xia, Haixia; An, Chunlin

2016-01-01

Embedding cost-sensitive factors into the classifiers increases the classification stability and reduces the classification costs for classifying high-scale, redundant, and imbalanced datasets, such as the gene expression data. In this study, we extend our previous work, that is, Dissimilar ELM (D-ELM), by introducing misclassification costs into the classifier. We name the proposed algorithm as the cost-sensitive D-ELM (CS-D-ELM). Furthermore, we embed rejection cost into the CS-D-ELM to increase the classification stability of the proposed algorithm. Experimental results show that the rejection cost embedded CS-D-ELM algorithm effectively reduces the average and overall cost of the classification process, while the classification accuracy still remains competitive. The proposed method can be extended to classification problems of other redundant and imbalanced data.

Exposure to extremely low frequency electromagnetic fields alters the behaviour, physiology and stress protein levels of desert locusts

PubMed Central

Wyszkowska, Joanna; Shepherd, Sebastian; Sharkh, Suleiman; Jackson, Christopher W.; Newland, Philip L.

2016-01-01

Electromagnetic fields (EMFs) are present throughout the modern world and are derived from many man-made sources including overhead transmission lines. The risks of extremely-low frequency (ELF) electromagnetic fields are particularly poorly understood especially at high field strengths as they are rarely encountered at ground level. Flying insects, however, can approach close to high field strength transmission lines prompting the question as to how these high levels of exposure affect behaviour and physiology. Here we utilise the accessible nervous system of the locust to ask how exposure to high levels of ELF EMF impact at multiple levels. We show that exposure to ELF EMFs above 4 mT leads to reduced walking. Moreover, intracellular recordings from an identified motor neuron, the fast extensor tibiae motor neuron, show increased spike latency and a broadening of its spike in exposed animals. In addition, hind leg kick force, produced by stimulating the extensor tibiae muscle, was reduced following exposure, while stress-protein levels (Hsp70) increased. Together these results suggest that ELF EMF exposure has the capacity to cause dramatic effects from behaviour to physiology and protein expression, and this study lays the foundation to explore the ecological significance of these effects in other flying insects. PMID:27808167

Adaptation of Bacillus subtilis to Life at Extreme Potassium Limitation.

PubMed

Gundlach, Jan; Herzberg, Christina; Hertel, Dietrich; Thürmer, Andrea; Daniel, Rolf; Link, Hannes; Stülke, Jörg

2017-07-05

Potassium is the most abundant metal ion in every living cell. This ion is essential due to its requirement for the activity of the ribosome and many enzymes but also because of its role in buffering the negative charge of nucleic acids. As the external concentrations of potassium are usually low, efficient uptake and intracellular enrichment of the ion is necessary. The Gram-positive bacterium Bacillus subtilis possesses three transporters for potassium, KtrAB, KtrCD, and the recently discovered KimA. In the absence of the high-affinity transporters KtrAB and KimA, the bacteria were unable to grow at low potassium concentrations. However, we observed the appearance of suppressor mutants that were able to overcome the potassium limitation. All these suppressor mutations affected amino acid metabolism, particularly arginine biosynthesis. In the mutants, the intracellular levels of ornithine, citrulline, and arginine were strongly increased, suggesting that these amino acids can partially substitute for potassium. This was confirmed by the observation that the supplementation with positively charged amino acids allows growth of B. subtilis even at the extreme potassium limitation that the bacteria experience if no potassium is added to the medium. In addition, a second class of suppressor mutations allowed growth at extreme potassium limitation. These mutations result in increased expression of KtrAB, the potassium transporter with the highest affinity and therefore allow the acquisition and accumulation of the smallest amounts of potassium ions from the environment. IMPORTANCE Potassium is essential for every living cell as it is required for the activity for many enzymes and for maintaining the intracellular pH by buffering the negative charge of the nucleic acids. We have studied the adaptation of the soil bacterium Bacillus subtilis to life at low potassium concentrations. If the major high-affinity transporters are missing, the bacteria are unable to grow unless they acquire mutations that result in the accumulation of positively charged amino acids such as ornithine, citrulline, and arginine. Supplementation of the medium with these amino acids rescued growth even in the absence of externally added potassium. Moreover, these growth conditions, which the bacteria experience as an extreme potassium limitation, can be overcome by the acquisition of mutations that result in increased expression of the high-affinity potassium transporter KtrAB. Our results indicate that positively charged amino acids can partially take over the function of potassium. Copyright © 2017 Gundlach et al.

The imprinted brain: how genes set the balance between autism and psychosis.

PubMed

Badcock, Christopher

2011-06-01

The imprinted brain theory proposes that autism spectrum disorder (ASD) represents a paternal bias in the expression of imprinted genes. This is reflected in a preference for mechanistic cognition and in the corresponding mentalistic deficits symptomatic of ASD. Psychotic spectrum disorder (PSD) would correspondingly result from an imbalance in favor of maternal and/or X-chromosome gene expression. If differences in gene expression were reflected locally in the human brain as mouse models and other evidence suggests they are, ASD would represent not so much an 'extreme male brain' as an extreme paternal one, with PSD correspondingly representing an extreme maternal brain. To the extent that copy number variation resembles imprinting and aneuploidy in nullifying or multiplying the expression of particular genes, it has been found to conform to the diametric model of mental illness peculiar to the imprinted brain theory. The fact that nongenetic factors such as nutrition in pregnancy can mimic and/or interact with imprinted gene expression suggests that the theory might even be able to explain the notable effect of maternal starvation on the risk of PSD - not to mention the 'autism epidemic' of modern affluent societies. Finally, the theory suggests that normality represents balanced cognition, and that genius is an extraordinary extension of cognitive configuration in both mentalistic and mechanistic directions. Were it to be proven correct, the imprinted brain theory would represent one of the biggest single advances in our understanding of the mind and of mental illness that has ever taken place, and would revolutionize psychiatric diagnosis, prevention and treatment - not to mention our understanding of epigenomics.

A chloride tolerant laccase from the plant pathogen ascomycete Botrytis aclada expressed at high levels in Pichia pastoris.

PubMed

Kittl, Roman; Mueangtoom, Kitti; Gonaus, Christoph; Khazaneh, Shima Tahvilda; Sygmund, Christoph; Haltrich, Dietmar; Ludwig, Roland

2012-01-20

Fungal laccases from basidiomycetous fungi are thoroughly investigated in respect of catalytic mechanism and industrial applications, but the number of reported and well characterized ascomycetous laccases is much smaller although they exhibit interesting catalytic properties. We report on a highly chloride tolerant laccase produced by the plant pathogen ascomycete Botrytis aclada, which was recombinantly expressed in Pichia pastoris with an extremely high yield and purified to homogeneity. In a fed-batch fermentation, 495 mg L(-1) of laccase was measured in the medium, which is the highest concentration obtained for a laccase by a yeast expression system. The recombinant B. aclada laccase has a typical molecular mass of 61,565 Da for the amino acid chain. The pI is approximately 2.4, a very low value for a laccase. Glycosyl residues attached to the recombinant protein make up for approximately 27% of the total protein mass. B. aclada laccase exhibits very low K(M) values and high substrate turnover numbers for phenolic and non-phenolic substrates at acidic and near neutral pH. The enzyme's stability increases in the presence of chloride ions and, even more important, its substrate turnover is only weakly inhibited by chloride ions (I(50)=1.4M), which is in sharp contrast to most other described laccases. This high chloride tolerance is mandatory for some applications such as implantable biofuel cells and laccase catalyzed reactions, which suffer from the presence of chloride ions. The high expression yield permits fast and easy production for further basic and applied research. Copyright © 2011 Elsevier B.V. All rights reserved.

GENOMIC IMPRINTING, DISRUPTED PLACENTAL EXPRESSION, AND SPECIATION

PubMed Central

Brekke, Thomas D.; Henry, Lindy A.; Good, Jeffrey M.

2016-01-01

The importance of regulatory incompatibilities to the early stages of speciation remains unclear. Hybrid mammals often show extreme parent-of-origin growth effects that are thought to be a consequence of disrupted genetic imprinting (parent-specific epigenetic gene silencing) during early development. Here we test the long-standing hypothesis that abnormal hybrid growth reflects disrupted gene expression due to loss of imprinting (LOI) in hybrid placentas, resulting in dosage imbalances between paternal growth factors and maternal growth repressors. We analyzed placental gene expression in reciprocal dwarf hamster hybrids that show extreme parent-of-origin growth effects relative to their parental species. In massively enlarged hybrid placentas, we observed both extensive transgressive expression of growth-related genes and bi-allelic expression of many genes that were paternally silenced in normal sized hybrids. However, the apparent widespread disruption of paternal silencing was coupled with reduced gene expression levels overall. These patterns are contrary to the predictions of the LOI model and indicate that hybrid misexpression of dosage sensitive genes is caused by other regulatory mechanisms in this system. Collectively, our results support a central role for disrupted gene expression and imprinting in the evolution of mammalian hybrid inviability, but call into question the generality of the widely invoked LOI model. PMID:27714796

Functional Organization of hsp70 Cluster in Camel (Camelus dromedarius) and Other Mammals

PubMed Central

Garbuz, David G.; Astakhova, Lubov N.; Zatsepina, Olga G.; Arkhipova, Irina R.; Nudler, Eugene; Evgen'ev, Michael B.

2011-01-01

Heat shock protein 70 (Hsp70) is a molecular chaperone providing tolerance to heat and other challenges at the cellular and organismal levels. We sequenced a genomic cluster containing three hsp70 family genes linked with major histocompatibility complex (MHC) class III region from an extremely heat tolerant animal, camel (Camelus dromedarius). Two hsp70 family genes comprising the cluster contain heat shock elements (HSEs), while the third gene lacks HSEs and should not be induced by heat shock. Comparison of the camel hsp70 cluster with the corresponding regions from several mammalian species revealed similar organization of genes forming the cluster. Specifically, the two heat inducible hsp70 genes are arranged in tandem, while the third constitutively expressed hsp70 family member is present in inverted orientation. Comparison of regulatory regions of hsp70 genes from camel and other mammals demonstrates that transcription factor matches with highest significance are located in the highly conserved 250-bp upstream region and correspond to HSEs followed by NF-Y and Sp1 binding sites. The high degree of sequence conservation leaves little room for putative camel-specific regulatory elements. Surprisingly, RT-PCR and 5′/3′-RACE analysis demonstrated that all three hsp70 genes are expressed in camel's muscle and blood cells not only after heat shock, but under normal physiological conditions as well, and may account for tolerance of camel cells to extreme environmental conditions. A high degree of evolutionary conservation observed for the hsp70 cluster always linked with MHC locus in mammals suggests an important role of such organization for coordinated functioning of these vital genes. PMID:22096537

Measurement of TFF3 mRNA in aspirates from thyroid nodules using mesh filtration: the first clinical trial in 130 cases.

PubMed

Yamada, Hiroya; Takano, Toru; Kihara, Minoru; Hirokawa, Mitsuyoshi; Yoshida, Hiroshi; Watanabe, Mikio; Iwatani, Yoshinori; Hidaka, Yoh; Miyauchi, Akira

2012-01-01

Measurement of gene expression levels in thyroid tumor cells in aspirates was difficult because it is interfered with peripheral blood cells or infiltrating lymphocytes. In this study, we established a novel method to separate thyroid tumor cells from blood cells efficiently with mesh filtration. The expression level of trefoil factor 3 (TFF3) mRNA was estimated using LGALS3 mRNA as an internal control (T/G ratio) in 148 preoperative thyroid aspirates. Intra-assay coefficients of variation (CV) of T/G ratio for high, moderate, and low samples were 6.5%, 2.5%, and 9.7%, respectively, and inter-assay CV for high, moderate, and low samples were 27.7%, 21.9%, and 38.2%, respectively. Nondiagnostic samples in terms of T/G ratio and cytology were 12.2% and 16.9%, respectively. We observed no interference with the data by contaminating blood cells. Among these patients, 12 patients received more than two repeated aspirations. We did not observe a marked day-to-day variation except in two cases. All 13 preoperative aspirates diagnosed as malignant by cytology showed an extremely low T/G ratio, whereas 93 aspirates diagnosed as benign by cytology showed extremely varied T/G ratios and 21.5% of them showed a T/G ratio below the cut-off value. Eleven cases underwent surgery. All nodules showing a low T/G ratio were diagnosed as papillary carcinoma by pathological diagnosis. However, one nodule diagnosed as follicular adenoma after surgery showed a high T/G ratio. Our present method may be a promising preoperative test for measuring mRNAs in thyroid aspirates.

A pilot genetic study of the continuum between compulsivity and impulsivity in females: the serotonin transporter promoter polymorphism.

PubMed

Baca-García, Enrique; Salgado, Beatríz Rodríguez; Segal, Helen Dolengevich; Lorenzo, Concepción Vaquero; Acosta, Mercedes Navio; Romero, Manuel Arrojo; Hernández, Montserrat Díaz; Saiz-Ruiz, Jeronimo; Fernandez Piqueras, Jose; de Leon, Jose

2005-06-01

According to some authors the obsessive-compulsive (OC) spectrum includes on one extreme, the Obsessive-Compulsive Disorder (OCD) and on the other extreme the most impulsive behaviors. This is a controversial idea and other authors define the OC spectrum in different ways. The serotonin transporter (5-HTT) gene is one of the main genes that control serotonergic function. A polymorphism in the promoter area of this gene classifies subjects with low expression as S individuals (s/s or s/l) and subjects with high expression as L individuals (l/l). This polymorphism was studied in female OCD patients (n = 24), non-impulsive controls (n = 112) and impulsive suicidal patients (n = 118) to support the OC spectrum hypothesis from a genetic perspective. A linear association exists among the serotonin transporter promoter functional genotypes (S versus L individuals) (chi2 linear by linear association = 8.9; df = 1; p = 0.003). The frequency of S individuals (s/l or s/s) was lowest in OCD (54%, 13/24); intermediate in non-impulsive controls (71%, 80/112) and highest in impulsive suicide attempters (82%, 96/117). More importantly, future studies need to consider that genetics may be related to behavioral dimensions (compulsivity to impulsivity) instead of to specific psychiatric disorders defined in clinical terms.

Xylanase from the extremely thermophilic bacterium Caldocellum saccharolyticum: Overexpression of the gene in Escherichia coli and characterization of the gene product

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luethi, E.; Jasmat, N.B.; Bergquist, P.L.

A xylanase encoded by the xynA gene of the extreme thermophile Caldocellum saccharolyticum was overexpressed in Escherichia coli by cloning the gene downstream from the temperature-inducible {lambda} P{sub R} and P{sub L} promoters of the expression vector pJLA602. Induction of up to 55 times was obtained by growing the cells at 42{degrees}C, and the xylanase made up of 20% of the whole-cell protein content. The enzyme was located in the cytoplasmic fraction in E.coli. The temperature and pH optima were determined to be 70{degrees}C and pH 5.5 to 6, respectively. The xylanase was stable for at least 72 h ifmore » incubated at 60{degrees}C, with half-lives of 8 to 9 h at 70{degrees}C and 2 to 3 min at 80{degrees}C. The enzyme had high activity on xylan and ortho-nitrophenyl {beta}-D-xylopyranoside and some activity on carboxymethyl cellulose and para-nitrophenyl {beta}-D-cellobioside. The gene was probably expressed from its own promoter in E. coli. Translation of the xylanase overproduced in E. coli seemed to initiate at a GTG codon and not at an ATG codon as previously determined.« less

Electron-ion relaxation in a dense plasma. [supernovae core physics

NASA Technical Reports Server (NTRS)

Littleton, J. E.; Buchler, J.-R.

1974-01-01

The microscopic physics of the thermonuclear runaway in highly degenerate carbon-oxygen cores is investigated to determine if and how a detonation wave is generated. An expression for the electron-ion relaxation time is derived under the assumption of large degeneracy and extreme relativity of the electrons in a two-temperature plasma. Since the nuclear burning time proves to be several orders of magnitude shorter than the relaxation time, it is concluded that in studying the structure of the detonation wave the electrons and ions must be treated as separate fluids.

A role for the Fas/FasL system in modulating genetic susceptibility to T-cell lymphoblastic lymphomas.

PubMed

Villa-Morales, María; Santos, Javier; Pérez-Gómez, Eduardo; Quintanilla, Miguel; Fernández-Piqueras, José

2007-06-01

The Fas/FasL system mediates induced apoptosis of immature thymocytes and peripheral T lymphocytes, but little is known about its implication in genetic susceptibility to T-cell malignancies. In this article, we report that the expression of FasL increases early in all mice after gamma-radiation treatments, maintaining such high levels for a long time in mice that resisted tumor induction. However, its expression is practically absent in T-cell lymphoblastic lymphomas. Interestingly, there exist significant differences in the level of expression between two mice strains exhibiting extremely distinct susceptibilities that can be attributed to promoter functional polymorphisms. In addition, several functional nucleotide changes in the coding sequences of both Fas and FasL genes significantly affect their biological activity. These results lead us to propose that germ-line functional polymorphisms affecting either the levels of expression or the biological activity of both Fas and FasL genes could be contributing to the genetic risk to develop T-cell lymphoblastic lymphomas and support the use of radiotherapy as an adequate procedure to choose in the treatment of T-cell malignancies.

Investigation of apoptosis-related gene expression levels in preimplantation biopsies as predictors of delayed kidney graft function.

PubMed

Goncalves-Primo, Amador; Mourão, Tuíla B; Andrade-Oliveira, Vinícius; Campos, Erika F; Medina-Pestana, José O; Tedesco-Silva, Hélio; Gerbase-DeLima, Maria

2014-06-27

The purpose of this study was to investigate the expression of the gene coding for the antiapoptotic molecule Bcl-2, the proapoptotic molecule Bax, and the apoptosis executor enzyme caspase-3 in preimplantation renal biopsies (PIB) as markers for delayed graft function. In this prospective single-center study, gene expression levels were evaluated using real-time TaqMan polymerase chain reaction in PIB of kidneys from 72 deceased donors (DDs) and 18 living donors (LDs). CASP3 and BAX expression levels were higher, whereas those of BCL2 were lower, in DD than in LD PIB. In biopsies from DD, BCL2 levels were lower in cases with DGF, whereas no differences were observed concerning CASP3 and BAX. The BAX/BCL2 gene expression ratio greater than 2.29 associated with DGF with an odds ratio of 2.00. A multiple regression analysis including data of TLR4 expression in the first day posttransplant PB from a previous study of our group conducted in the same patients revealed a very strong association of the combination of BAX/BCL2 greater than 2.3 in PIB and TLR4 of 0.95 uRE or lesser in PB with the occurrence of DGF, with OR of 120 and positive and negative predictive values of 91% and 92%, respectively. The power to predict DGF of the combination of high BAX/BCL2 expression in PIB and low TLR4 expression in the first day posttransplant peripheral blood observed in the present study is extremely high, in comparison to any other marker or combinations of markers so far published in the literature.

MDM2 is an important prognostic and predictive factor for platin-pemetrexed therapy in malignant pleural mesotheliomas and deregulation of P14/ARF (encoded by CDKN2A) seems to contribute to an MDM2-driven inactivation of P53.

PubMed

Walter, R F H; Mairinger, F D; Ting, S; Vollbrecht, C; Mairinger, T; Theegarten, D; Christoph, D C; Schmid, K W; Wohlschlaeger, J

2015-03-03

Malignant pleural mesothelioma (MPM) is a highly aggressive tumour that is first-line treated with a combination of cisplatin and pemetrexed. Until now, predictive and prognostic biomarkers are lacking, making it a non-tailored therapy regimen with unknown outcome. P53 is frequently inactivated in MPM, but mutations are extremely rare. MDM2 and P14/ARF are upstream regulators of P53 that may contribute to P53 inactivation. A total of 72 MPM patients were investigated. MDM2 immunoexpression was assessed in 65 patients. MDM2 and P14/ARF mRNA expression was analysed in 48 patients of the overall collective. The expression results were correlated to overall survival (OS) and progression-free survival (PFS). OS and PFS correlated highly significantly with MDM2 mRNA and protein expression, showing a dismal prognosis for patients with elevated MDM2 expression (for OS: Score (logrank) test: P⩽0.002, and for PFS: Score (logrank) test; P<0.007). MDM2 was identified as robust prognostic and predictive biomarker for MPM on the mRNA and protein level. P14/ARF mRNA expression reached no statistical significance, but Kaplan-Meier curves distinguished patients with low P14/ARF expression and hence shorter survival from patients with higher expression and prolonged survival. MDM2 is a prognostic and predictive marker for a platin-pemetrexed therapy of patients with MPMs. Downregulation of P14/ARF expression seems to contribute to MDM2-overexpression-mediated P53 inactivation in MPM patients.

Using Poisson mixed-effects model to quantify transcript-level gene expression in RNA-Seq.

PubMed

Hu, Ming; Zhu, Yu; Taylor, Jeremy M G; Liu, Jun S; Qin, Zhaohui S

2012-01-01

RNA sequencing (RNA-Seq) is a powerful new technology for mapping and quantifying transcriptomes using ultra high-throughput next-generation sequencing technologies. Using deep sequencing, gene expression levels of all transcripts including novel ones can be quantified digitally. Although extremely promising, the massive amounts of data generated by RNA-Seq, substantial biases and uncertainty in short read alignment pose challenges for data analysis. In particular, large base-specific variation and between-base dependence make simple approaches, such as those that use averaging to normalize RNA-Seq data and quantify gene expressions, ineffective. In this study, we propose a Poisson mixed-effects (POME) model to characterize base-level read coverage within each transcript. The underlying expression level is included as a key parameter in this model. Since the proposed model is capable of incorporating base-specific variation as well as between-base dependence that affect read coverage profile throughout the transcript, it can lead to improved quantification of the true underlying expression level. POME can be freely downloaded at http://www.stat.purdue.edu/~yuzhu/pome.html. yuzhu@purdue.edu; zhaohui.qin@emory.edu Supplementary data are available at Bioinformatics online.

Is climate change modifying precipitation extremes?

NASA Astrophysics Data System (ADS)

Montanari, Alberto; Papalexiou, Simon Michael

2016-04-01

The title of the present contribution is a relevant question that is frequently posed to scientists, technicians and managers of local authorities. Although several research efforts were recently dedicated to rainfall observation, analysis and modelling, the above question remains essentially unanswered. The question comes from the awareness that the frequency of floods and the related socio-economic impacts are increasing in many countries, and climate change is deemed to be the main trigger. Indeed, identifying the real reasons for the observed increase of flood risk is necessary in order to plan effective mitigation and adaptation strategies. While mitigation of climate change is an extremely important issue at the global level, at small spatial scales several other triggers may interact with it, therefore requiring different mitigation strategies. Similarly, the responsibilities of administrators are radically different at local and global scales. This talk aims to provide insights and information to address the question expressed by its title. High resolution and long term rainfall data will be presented, as well as an analysis of the frequency of their extremes and its progress in time. The results will provide pragmatic indications for the sake of better planning flood risk mitigation policies.

A timeline for predicting durable medical equipment needs and interventions for amyotrophic lateral sclerosis patients.

PubMed

Bromberg, Mark B; Brownell, Alexander A; Forshew, Dallas A; Swenson, Michael

2010-01-01

ALS is progressive with increasing patient needs for durable medical equipment (DME) and interventions (gastric feeding tube - PEG, and non-invasive ventilation - NIV). We performed a chart review of deceased patients to determine the time-course of needs and their estimated costs. A timeline of needs was based on when clinic personnel felt an item was necessary. The point in time when an item or intervention was needed was expressed as a percentage of a patient's total disease duration. A wide range of DME and interventions was needed irrespective of site of ALS symptom onset (bulbar, upper, lower extremity), beginning at 10% of disease duration of lower extremity onset and increasing thereafter for all sites. The cumulative probability of costs of items and interventions began at 25%-50% of disease duration and increased to between $18,000 and $32,000 (USD), highest for lower extremity onset due to the cost of wheelchairs. We conclude that a high percentage of ALS patients will need a full spectrum of major DME items and interventions during the second half of disease duration. This results in a linear rise in costs over the second half of the disease duration.

Dedifferentiated adenoid cystic carcinoma of the trachea: a case report with respect to the immunohistochemical analyses of mammalian target of rapamycin pathway proteins.

PubMed

Ishida, Mitsuaki; Okabe, Hidetoshi

2013-08-01

Dedifferentiated adenoid cystic carcinoma is an extremely rare and highly aggressive tumor. We describe the first reported case of dedifferentiated adenoid cystic carcinoma of the trachea and analyze the expression profiles of mammalian target of rapamycin pathway proteins. A 66-year-old Japanese man was incidentally found to have stenosis of the trachea, and a bronchial biopsy revealed low-grade adenoid cystic carcinoma. The resected specimen revealed dedifferentiated adenoid cystic carcinoma, which was composed of conventional low-grade adenoid cystic carcinoma with tubular and cribriform patterns, and a dedifferentiated carcinoma component (poorly differentiated adenocarcinoma). Immunohistochemical study showed that mammalian target of rapamycin and 4E-BP1 were expressed in both components; however, phosphorylated 4E-BP1 was expressed only in the dedifferentiated carcinoma component. This report clearly demonstrates that mammalian target of rapamycin pathway proteins were activated in dedifferentiated carcinoma. Mammalian target of rapamycin is a central protein involved in carcinogenesis, and administration of its inhibitors prolonged survival in some types of carcinoma. Therefore, mammalian target of rapamycin inhibitors may be a potential candidate for treatment of this highly aggressive carcinoma. Copyright © 2013 Elsevier Inc. All rights reserved.

Energy balance and hypothalamic effects of a high-protein/low-carbohydrate diet.

PubMed

Kinzig, Kimberly P; Hargrave, Sara L; Hyun, Jayson; Moran, Timothy H

2007-10-22

Diets high in fat or protein and extremely low in carbohydrate are frequently reported to result in weight loss in humans. We previously reported that rats maintained on a low-carbohydrate-high fat diet (LC-HF) consumed similar kcals/day as chow (CH)-fed rats and did not differ in body weight after 7 weeks. LC-HF rats had a 45% decrease in POMC expression in the ARC, decreased plasma insulin, and increased plasma leptin and ghrelin. In the present study we assessed the effects of a low-carbohydrate-high-protein diet (HP: 30% fat, 65% protein, and 5% CHO) on body weight, caloric intake, plasma hormone levels and hypothalamic gene expression. Male rats (n=16) were maintained on CH or HP for 4 weeks. HP rats gained significantly less weight than CH rats (73.4+/-9.4 and 125.0+/-8.2 g) and consumed significantly less kcals/day (94.8+/-1.5 and 123.6+/-1.1). Insulin was significantly reduced in HP rats (HP: 1.8+/-0.6 vs. CH: 4.12+/-0.8 ng/ml), there were no differences between groups in plasma leptin and plasma ghrelin was significantly elevated in HP rats (HP: 127.5+/-45 vs. CH: 76.9+/-8 pg/ml). Maintenance on HP resulted in significantly increased ARC POMC (HP: 121+/-10.0 vs. 100+/-5.9) and DMH NPY (HP: 297+/-82.1 vs. CH: 100+/-37.7) expression compared to CH controls. These data suggest that the macronutrient content of diets differentially influences hypothalamic gene expression in ways that can affect overall intake.

High-dimensional gene expression profiling studies in high and low responders to primary smallpox vaccination.

PubMed

Haralambieva, Iana H; Oberg, Ann L; Dhiman, Neelam; Ovsyannikova, Inna G; Kennedy, Richard B; Grill, Diane E; Jacobson, Robert M; Poland, Gregory A

2012-11-15

The mechanisms underlying smallpox vaccine-induced variations in immune responses are not well understood, but are of considerable interest to a deeper understanding of poxvirus immunity and correlates of protection. We assessed transcriptional messenger RNA expression changes in 197 recipients of primary smallpox vaccination representing the extremes of humoral and cellular immune responses. The 20 most significant differentially expressed genes include a tumor necrosis factor-receptor superfamily member, an interferon (IFN) gene, a chemokine gene, zinc finger protein genes, nuclear factors, and histones (P ≤ 1.06E(-20), q ≤ 2.64E(-17)). A pathway analysis identified 4 enriched pathways with cytokine production by the T-helper 17 subset of CD4+ T cells being the most significant pathway (P = 3.42E(-05)). Two pathways (antiviral actions of IFNs, P = 8.95E(-05); and IFN-α/β signaling pathway, P = 2.92E(-04)), integral to innate immunity, were enriched when comparing high with low antibody responders (false discovery rate, < 0.05). Genes related to immune function and transcription (TLR8, P = .0002; DAPP1, P = .0003; LAMP3, P = 9.96E(-05); NR4A2, P ≤ .0002; EGR3, P = 4.52E(-05)), and other genes with a possible impact on immunity (LNPEP, P = 3.72E(-05); CAPRIN1, P = .0001; XRN1, P = .0001), were found to be expressed differentially in high versus low antibody responders. We identified novel and known immunity-related genes and pathways that may account for differences in immune response to smallpox vaccination.

Tidally Heated Terrestrial Exoplanets

NASA Astrophysics Data System (ADS)

Henning, Wade Garrett

This work models the surface and internal temperatures for hypothetical terrestrial planets in situations involving extreme tidal heating. The feasibility of such planets is evaluated in terms of the orbital perturbations that may give rise to them, their required proximity to a hoststar, and the potential for the input tidal heating to cause significant partial melting of the mantle. Trapping terrestrial planets into 2:1 resonances with migrating Hot Jupiters is considered as a reasonable way for Earth-like worlds to both maintain high eccentricities and to move to short enough orbital periods (1-20 days) for extreme tidal heating to occur. Secular resonance and secular orbital perturbations may support moderate tidal heating at a low equilibrium eccentricity. At orbital periods below 10-30 days, with eccentricities from 0.01 to 0.1, tidal heat may greatly exceed radiogenic heat production. It is unlikely to exceed insolation, except when orbiting very low luminosity hosts, and thus will have limited surface temperature expression. Observations of such bodies many not be able to detect tidal surface enhancements given a few percent uncertainty in albedo, except on the nightside of spin synchronous airless objects. Otherwise detection may occur via spectral detection of hotspots or high volcanic gas concentrations including sulfur dioxide and hydrogen sulfide. The most extreme cases may be able to produce magma oceans, or magma slush mantles with up to 40-60% melt fractions. Tides may alter the habitable zones for smaller red dwarf stars, but are generally detrimental. Multiple viscoelastic models, including the Maxwell, Voigt-Kelvin, Standard Anelastic Solid, and Burgers rheologies are explored and applied to objects such as Io and the super-Earth planet GJ 876d. The complex valued Love number for the Burgers rheology is derived and found to be a useful improvement when modeling the low temperature behavior of tidal bodies, particularly during low eccentricity excursions. Viscoelastic solutions for GJ 876d are typical of extreme short period high eccentricity objects with tidal-convectiveequilibrium heat rates between ˜10,000 to 500,000 terawatts.

MicroRNA Detection by Whole-Mount In Situ Hybridization in C. elegans.

PubMed

Andachi, Yoshiki; Kohara, Yuji

2018-01-01

MicroRNAs (miRNAs) loaded on argonaute proteins guide RNA-induced silencing complexes to target mRNAs. An excellent method to decipher the spatiotemporal expression patterns of miRNAs is whole-mount in situ hybridization (WISH), which has been successfully used in vertebrate embryos but still remains unavailable for many animal species. Here, we describe a WISH method for miRNA detection in Caenorhabditis elegans at both embryonic and post-embryonic stages. Strategies devised for detection include fixation of animals with carbodiimide at a high temperature and subsequent partial digestion of the fixed animals with an extremely high concentration of proteinase. WISH signals are visualized by staining with a chromogenic substrate or a fluorescent dye.

Genes from scratch--the evolutionary fate of de novo genes.

PubMed

Schlötterer, Christian

2015-04-01

Although considered an extremely unlikely event, many genes emerge from previously noncoding genomic regions. This review covers the entire life cycle of such de novo genes. Two competing hypotheses about the process of de novo gene birth are discussed as well as the high death rate of de novo genes. Despite the high death rate, some de novo genes are retained and remain functional, even in distantly related species, through their integration into gene networks. Further studies combining gene expression with ribosome profiling in multiple populations across different species will be instrumental for an improved understanding of the evolutionary processes operating on de novo genes. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Changes in the frequency of extreme air pollution events over the Eastern United States and Europe

NASA Astrophysics Data System (ADS)

Rieder, H. E.; Fiore, A. M.; Fang, Y.; Staehelin, J.

2011-12-01

Over the past few decades, thresholds for national air quality standards, intended to protect public health and welfare, have been lowered repeatedly. At the same time observations, over Europe and the Eastern U.S., demonstrate that extreme air pollution events (high O3 and PM2.5) are typically associated with stagnation events. Recent work showed that in a changing climate high air pollution events are likely to increase in frequency and duration. Within this work we examine meteorological and surface ozone observations from CASTNet over the U.S. and EMEP over Europe and "idealized" simulations with the GFDL AM3 chemistry-climate model, which isolate the role of climate change on air quality. Specifically, we examine an "idealized 1990s" simulation, forced with 20-year mean monthly climatologies for sea surface temperatures and sea ice from observations for 1981-2000, and an "idealized 2090s" simulation forced by the observed climatologies plus the multi-model mean changes in sea surface temperature and sea ice simulated by 19 IPCC AR-4 models under the A1B scenario for 2081-2100. With innovative statistical tools (empirical orthogonal functions (EOFs) and statistics of extremes (EVT)), we analyze the frequency distribution of past, present and future extreme air pollution events over the Eastern United States and Europe. The upper tail of observed values at individual stations (e.g., within the CASTNet), i.e., the extremes (maximum daily 8-hour average (MDA8) O3>60ppb) are poorly described by a Gaussian distribution. However, further analysis showed that applying Peak-Over-Threshold-models, better capture the extremes and allows us to estimate return levels of pollution events above certain threshold values of interest. We next apply EOF analysis to identify regions that vary coherently within the ground-based monitoring networks. Over the United States, the first EOF obtained from the model in both the 1990s and 2090s idealized simulations identifies the Northeast as a region that varies coherently. Correlation analysis reveals that this EOF pattern is most strongly expressed in association with high surface temperature and high surface pressure conditions, consistent with previous work showing that observed O3 episodes over this area reflect the combined impacts of stagnation and increased chemical production. Next steps include the extension of this analysis applying EVT tools to the principal component time series associated with this EOF. The combination of EOF and EVT tools applied to the GFDL AM3 1990s vs. 2090s idealized simulations will enable us to quantify changes in the return levels of air pollution extremes. Therefore the combination of observational data and numerical and statistical models should allow us to identify key driving forces between high air pollution events and to estimate changes in the frequency of such events under different climate change scenarios.

Sex differences in facial emotion recognition across varying expression intensity levels from videos.

PubMed

Wingenbach, Tanja S H; Ashwin, Chris; Brosnan, Mark

2018-01-01

There has been much research on sex differences in the ability to recognise facial expressions of emotions, with results generally showing a female advantage in reading emotional expressions from the face. However, most of the research to date has used static images and/or 'extreme' examples of facial expressions. Therefore, little is known about how expression intensity and dynamic stimuli might affect the commonly reported female advantage in facial emotion recognition. The current study investigated sex differences in accuracy of response (Hu; unbiased hit rates) and response latencies for emotion recognition using short video stimuli (1sec) of 10 different facial emotion expressions (anger, disgust, fear, sadness, surprise, happiness, contempt, pride, embarrassment, neutral) across three variations in the intensity of the emotional expression (low, intermediate, high) in an adolescent and adult sample (N = 111; 51 male, 60 female) aged between 16 and 45 (M = 22.2, SD = 5.7). Overall, females showed more accurate facial emotion recognition compared to males and were faster in correctly recognising facial emotions. The female advantage in reading expressions from the faces of others was unaffected by expression intensity levels and emotion categories used in the study. The effects were specific to recognition of emotions, as males and females did not differ in the recognition of neutral faces. Together, the results showed a robust sex difference favouring females in facial emotion recognition using video stimuli of a wide range of emotions and expression intensity variations.

Highly active promoters and native secretion signals for protein production during extremely low growth rates in Aspergillus niger.

PubMed

Wanka, Franziska; Arentshorst, Mark; Cairns, Timothy C; Jørgensen, Thomas; Ram, Arthur F J; Meyer, Vera

2016-08-20

The filamentous ascomycete Aspergillus niger is used in many industrial processes for the production of enzymes and organic acids by batch and fed-batch cultivation. An alternative technique is continuous cultivation, which promises improved yield and optimized pipeline efficiency. In this work, we have used perfusion (retentostat) cultivation to validate two promoters that are suitable for A. niger continuous cultivation of industrially relevant products. Firstly, promoters of genes encoding either an antifungal protein (Panafp) or putative hydrophobin (PhfbD) were confirmed as active throughout retentostat culture by assessing mRNA and protein levels using a luciferase (mluc) reporter system. This demonstrated the anafp promoter mediates a high but temporally variable expression profile, whereas the hfbD promoter mediates a semi-constant, moderate-to-high protein expression during retentostat culture. In order to assess whether these promoters were suitable to produce heterologous proteins during retentostat cultivation, the secreted antifungal protein (AFP) from Aspergillus giganteus, which has many potential biotechnological applications, was expressed in A. niger during retentostat cultivation. Additionally, this assay was used to concomitantly validate that native secretion signals encoded in anafp and hfbD genes can be harnessed for secretion of heterologous proteins. Afp mRNA and protein abundance were comparable to luciferase measurements throughout retentostat cultivation, validating the use of Panafp and PhfbD for perfusion cultivation. Finally, a gene encoding the highly commercially relevant thermal hysteresis protein (THP) was expressed in this system, which did not yield detectable protein. Both hfbD and anafp promoters are suitable for production of useful products in A. niger during perfusion cultivation. These findings provide a platform for further optimisations for high production of heterologous proteins with industrial relevance.

Cloning, expression and crystallisation of SGT1 co-chaperone protein from Glaciozyma antarctica

NASA Astrophysics Data System (ADS)

Yusof, Nur Athirah; Bakar, Farah Diba Abu; Beddoe, Travis; Murad, Abdul Munir Abdul

2013-11-01

Studies on psycrophiles are now in the limelight of today's post genomic era as they fascinate the research and development industries. The discovery from Glaciozyma antarctica, an extreme cold adapted yeast from Antarctica shows promising future to provide cost effective natural sustainable energy and create wider understanding of the property that permits this organisms to adapt to extreme temperature downshift. In plants and yeast, studies show the interaction between SGT1 and HSP90 are essential for disease resistance and heat stress by activating a number of resistance proteins. Here we report for the first time cloning, expression and crystallization of the recombinant SGT1 protein of G. antarctica (rGa_SGT1), a highly conserved eukaryotic protein that interacts with the molecular chaperones HSP90 (heat shock protein 90) apparently associated in a role of co-chaperone that may play important role in cold adaptation. The sequence analysis of rGa_SGT1 revealed the presence of all the characteristic features of SGT1 protein. In this study, we present the outlines and results of protein structural study of G. antarctica SGT1 protein. We validate this approach by starting with cloning the target insert into Ligation Independent Cloning system proceeded with expression using E. coli system, and crystallisation of the target rGA_SGT1 protein. The work is still on going with the target subunit of the complex proteins yielded crystals. These results, still ongoing, open a platform for better understanding of the uniqueness of this crucial molecular machine function in cold adaptation.

Improved soluble expression and characterization of the Hc domain of Clostridium botulinum neurotoxin serotype A in Escherichia coli by using a PCR-synthesized gene and a Trx co-expression strain.

PubMed

Chen, Rongchang; Shi, Jing; Cai, Kun; Tu, Wei; Hou, Xiaojun; Liu, Hao; Xiao, Le; Wang, Qin; Tang, Yunming; Wang, Hui

2010-05-01

Botulinum neurotoxin serotype A (BoNT/A) is an extremely potent bacterial protein toxin. The Hc fragment of BoNT/A (AHc) was shown to be non-toxic, antigenic, and capable of eliciting a protective immunity in animals challenged with homologous BoNT. In this study, we synthesized AHc gene by using T4 DNA ligase and PCR. The AHc was expressed at a high level in Escherichia coli successfully. Because of using the Trx co-expression strain, the expressed AHc is in a soluble and active form. The yield of the purified AHc was about 70mg/L, and its purity was up to 90% through one-step affinity chromatography. The AHc was positively identified by the antibodies raised against BoNT/A using immunological-dot-blot and Western blot assays. AHc was shown to bind with gangliosides and elicit immunity against BoNT/A, indicating that the expressed and purified AHc protein retains a functionally active conformation. Furthermore, the purified AHc has a strong immunogenicity and can be used as a potential subunit candidate vaccine for botulinum toxin serotype A. Copyright (c) 2009 Elsevier Inc. All rights reserved.

The Persimmon 9-lipoxygenase Gene DkLOX3 Plays Positive Roles in Both Promoting Senescence and Enhancing Tolerance to Abiotic Stress

PubMed Central

Hou, Yali; Meng, Kun; Han, Ye; Ban, Qiuyan; Wang, Biao; Suo, Jiangtao; Lv, Jingyi; Rao, Jingping

2015-01-01

The lipoxygenase (LOX) pathway is a key regulator for lipid peroxidation, which is crucial for plant senescence and defense pathways. In this study, the transcriptional expression patterns of three persimmon (Diospyros kaki L. ‘Fupingjianshi’) 9-lipoxygenase genes (DkLOX1, DkLOX3, and DkLOX4) were investigated. DkLOX1 was specifically expressed in fruit, particularly in young fruit, and showed little response to the postharvest environments. DkLOX4 was expressed in all tissues and slightly stimulated by mechanical damage and low temperature. DkLOX3 was expressed mainly in mature fruit, and the expression was extremely high throughout the storage period, apparently up-regulated by mechanical damage and high carbon dioxide treatments. Further functional analysis showed that overexpression of DkLOX3 in tomato (Solanum lycopersicum cv. Micro-Tom) accelerated fruit ripening and softening. This was accompanied by higher malondialdehyde (MDA) content and lycopene accumulation, advanced ethylene release peak and elevated expression of ethylene synthesis genes, including ACS2, ACO1, and ACO3. In addition, DkLOX3 overexpression promoted dark induced transgenic Arabidopsis leaf senescence with more chlorophyll loss, increased electrolyte leakage and MDA content. Furthermore, the functions of DkLOX3 in response to abiotic stresses, including osmotic stress, high salinity and drought were investigated. Arabidopsis DkLOX3 overexpression (DkLOX3-OX) transgenic lines were found to be more tolerant to osmotic stress with higher germination rate and root growth than wild-type. Moreover, DkLOX3-OX Arabidopsis plants also exhibited enhanced resistance to high salinity and drought, with similar decreased O2- and H2O2 accumulation and upregulation of stress-responsive genes expression, including RD22, RD29A, RD29B, and NCED3, except for FRY1, which plays a negative role in stress response. Overall, these results suggested that DkLOX3 plays positive roles both in promoting ripening and senescence through lipid peroxidation and accelerated ethylene production and in stress response via regulating reactive oxygen species accumulation and stress responsive genes expression. PMID:26697033

Extreme sensitivity of gene expression in human SH-SY5Y neurocytes to ultra-low doses of Gelsemium sempervirens

PubMed Central

2014-01-01

Background Gelsemium sempervirens L. (Gelsemium s.) is a traditional medicinal plant, employed as an anxiolytic at ultra-low doses and animal models recently confirmed this activity. However the mechanisms by which it might operate on the nervous system are largely unknown. This work investigates the gene expression of a human neurocyte cell line treated with increasing dilutions of Gelsemium s. extract. Methods Starting from the crude extract, six 100 × (centesimal, c) dilutions of Gelsemium s. (2c, 3c, 4c, 5c, 9c and 30c) were prepared according to the French homeopathic pharmacopoeia. Human SH-SY5Y neuroblastoma cells were exposed for 24 h to test dilutions, and their transcriptome compared by microarray to that of cells treated with control vehicle solutions. Results Exposure to the Gelsemium s. 2c dilution (the highest dose employed, corresponding to a gelsemine concentration of 6.5 × 10-9 M) significantly changed the expression of 56 genes, of which 49 were down-regulated and 7 were overexpressed. Several of the down-regulated genes belonged to G-protein coupled receptor signaling pathways, calcium homeostasis, inflammatory response and neuropeptide receptors. Fisher exact test, applied to the group of 49 genes down-regulated by Gelsemium s. 2c, showed that the direction of effects was significantly maintained across the treatment with high homeopathic dilutions, even though the size of the differences was distributed in a small range. Conclusions The study shows that Gelsemium s., a medicinal plant used in traditional remedies and homeopathy, modulates a series of genes involved in neuronal function. A small, but statistically significant, response was detected even to very low doses/high dilutions (up to 30c), indicating that the human neurocyte genome is extremely sensitive to this regulation. PMID:24642002

Work-related stress: A survey of Indian anesthesiologists.

PubMed

Bakshi, Sumitra Ganesh; Divatia, Jigeeshu Vasishtha; Kannan, Sadhana; Myatra, Sheila Nainan

2017-01-01

Work-related stress is common among medical caregivers and concerns all perioperative care providers. Although anesthesiologists are known to experience stress, there are limited Indian data addressing this issue. This survey was conducted among Indian anesthesiologists to determine their awareness about work stress and views regarding prevention programs. A survey questionnaire was distributed to delegates visiting the exhibits at the national anesthesiology conference in 2011. The questionnaire had ten questions on the work pattern, five on work-related stress, nine on opinion regarding the need and willingness to participate in stress-related programs. There were 1178 responders. Forty-three percent were faculty in medical institutions, 26% were residents and 25% were in free-lance practice. Ninety-one percent of participants rated their stress as moderate-extreme. There was a significant correlation between the amount of stress and working for more than 8 h ( P < 0.001), handling high risk patients ( P = 0.002), working on weekends ( P = 0.002), and carrying work back home ( P < 0.001). Forty-one percent of respondents were very satisfied professionally. Seventy-six percent of doctors agreed that the questionnaire had made them think about work stress. Eighty-four percent of participants felt the need for stress management programs and 69% expressed their willingness to participate in the same. The majority of participants rated their stress as moderate-extreme and was higher in anesthesiologists working long hours, over the weekend and those handling high-risk patients. A majority of participants felt the survey made them think about work-related stress and expressed their willingness to participate in stress management programs.

Proteomic approach of adaptive response to arsenic stress in Exiguobacterium sp. S17, an extremophile strain isolated from a high-altitude Andean Lake stromatolite.

PubMed

Belfiore, Carolina; Ordoñez, Omar F; Farías, María Eugenia

2013-05-01

The North-Western part of Argentina is particularly rich in wetlands located in the Puna in an altitude between 3,600 and 4,600 m above sea level. Most of these high-altitude Andean lakes are inhospitable areas due to extreme habitat conditions such as high contents of toxic elements, particularly arsenic. Exiguobacterium sp. S17, isolated from stromatolites in Laguna Socompa, exhibited remarkable tolerance to high arsenic concentration, i.e., it tolerated arsenic concentration such as 10 mM of As(III) and 150 mM of As(V). A proteomics approach was conducted to reveal the mechanisms that provide the observed outstanding resistance of Exiguobacterium sp. S17 against arsenic. A comparative analysis of S17, exposed and unexposed to arsenic revealed 25 differentially expressed proteins. Identification of these proteins was performed by MALDI-TOF/MS revealing upregulation of proteins involved in energy metabolism, stress, transport, and in protein synthesis being expressed under arsenic stress. To our knowledge, this work represents the first proteomic study of arsenic tolerance in an Exiguobacterium strain.

A copper-induced metallothionein gene from Exopalaemon carinicauda and its response to heavy metal ions.

PubMed

Zhang, Jiquan; Wang, Jing; Gui, Tianshu; Sun, Zheng; Xiang, Jianhai

2014-09-01

A full-length copper-induced metallothionein (EcMT-Cu) cDNA was obtained from Exopalaemon carinicauda (Holthuis) and it contained a 198 bp open reading frame that encoded a peptide with 65 amino acid residues. Twenty-one cysteines were found in deduced amino acid sequence and the cysteine (Cys)-rich characteristic was also reported in different types of metallothioneins from other species. EcMT-Cu mRNA expression profile showed that it is the hepatopancreas specific gene. The expression of EcMT-Cu was extremely different when shrimp were exposed to seawater containing 50 μM CuSO4 or 2.5 μM CdCl2. The expression of EcMT-Cu in shrimp was significantly up-regulated at 12 and 24 h after exposure to CuSO4, however, its expression was not induced compared to that of pretreatment (p>0.05) when shrimp were exposed to CdCl2. The transcript of EcMT-Cu was found to be extremely low at gastrula and nauplius stage and expression of EcMT-Cu could be detected from egg protozoa stage. Copyright © 2014 Elsevier B.V. All rights reserved.

[Construction of a general AAV vector regulated by minimal and artificial hypoxic-responsive element].

PubMed

Nie, Xiao-wei; Sun, Li-jun; Hao, Yue-wen; Yang, Guang-xiao; Wang, Quan-ying

2011-03-01

To synthesize the minimal and artificial HRE, and to insert it into the anterior extremity of CMV promoter of a AAV plasmid, and then to construct the AAV regulated by hypoxic-responsive element which was introduced into 293 cell by method of Ca3(PO4)2 using three plasmids. Thus obtaining the adenoassociated virus vector regulated by hypoxic-responsive element was possibly used for gene therapy in ischemia angiocardiopathy and cerebrovascular disease. Artificially synthesize the 36 bp nucleotide sequences of four connection in series HIF-binding sites A/GCGTG(4×HBS)and a 35 bp nucleotide sequences spacing inserted into anterior extremity of CMV promoter TATA Box, then amplified by PCR. The cDNA fragment was confirmed to be right by DNA sequencing. Molecular biology routine method was used to construct a AAV vector regulated by minimal hypoxic-responsive element after the normal CMV promoter in AAV vector was replaced by the CMV promoter included minimal hypoxic-responsive element. Then, NT4-6His-PR39 fusogenic peptide was inserted into MCS of the plasmid, the recombinant AAV vector was obtained by three plasmid co-transfection in 293 cells, in which we can also investigate the expression of 6×His using immunochemistry in hypoxia environment. Artificial HRE was inserted into anterior extremity of CMV promoter and there was a correct spacing between the HRE and the TATA-box. The DNA sequencing and restriction enzyme digestion results indicated that the AAV regulated by hypoxic-responsive element was successfully constructed. Compared to the control group, the expressions of 6×His was significantly increased in the experimental groups in hypoxia environment, which confirmed that the AAV effectually regulated by the minimal HRE was inserted into anterior extremity of CMV promoter. The HRE is inserted into anterior extremity of CMV promoter to lack incision enzyme recognition site by PCR. And eukaryotic expression vector regulated by hypoxic-responsive is constructed. The AAV effectually regulated by the minimal HRE inserted into anterior extremity of CMV promoter. The vector is successfully constructed and it has important theoretical and practical value in the synteresis and therapy of ischemia angiocardiopathy and cerebrovascular disease.

Diversity in global gene expression and morphology across a watercress (Nasturtium officinale R. Br.) germplasm collection: first steps to breeding

PubMed Central

Payne, Adrienne C.; Clarkson, Graham J.J.; Rothwell, Steve; Taylor, Gail

2015-01-01

Watercress (Nasturtium officinale R. Br.) is a nutrient intense, leafy crop that is consumed raw or in soups across the globe, but for which, currently no genomic resources or breeding programme exists. Promising morphological, biochemical and functional genomic variation was identified for the first time in a newly established watercress germplasm collection, consisting of 48 watercress accessions sourced from contrasting global locations. Stem length, stem diameter and anti-oxidant (AO) potential varied across the accessions. This variation was used to identify three extreme contrasting accessions for further analysis. Variation in global gene expression was investigated using an Affymetrix Arabidopsis ATH1 microarray gene chip, using the commercial control (C), an accession selected for dwarf phenotype with a high AO potential (dwarfAO, called ‘Boldrewood’) and one with high AO potential alone. A set of transcripts significantly differentially expressed between these three accessions, were identified, including transcripts involved in the regulation of growth and development and those involved in secondary metabolism. In particular, when differential gene expression was compared between C and dwarfAO, the dwarfAO was characterised by increased expression of genes encoding glucosinolates, which are known precursors of phenethyl isothiocyanate, linked to the anti-carcinogenic effects well-documented in watercress. This study provides the first analysis of natural variation across the watercress genome and has identified important underpinning information for future breeding for enhanced anti-carcinogenic properties and morphology traits in this nutrient-intense crop. PMID:26504575

High cyclin A expression, but not Ki67, is associated with early recurrence in desmoid tumors.

PubMed

Santti, Kirsi; Ihalainen, Hanna; Rönty, Mikko; Böhling, Tom; Karlsson, Christina; Haglund, Caj; Tarkkanen, Maija; Blomqvist, Carl

2018-06-07

Desmoid tumors are soft-tissue tumors originating from myofibroblasts with a tendency to recur after surgery. High expression of proliferation markers is associated with shortened progression-free and/or overall survival in many neoplasms, including soft-tissue sarcomas. We investigated the prognostic role of cyclin A and Ki67 in desmoid tumors by immunohistochemistry. The study included 76 patients with desmoid tumor operated at Helsinki University Hospital between 1987 and 2011. A tissue micro array (TMA) was constructed and the TMA sections were immunostained with cyclin A and Ki67 antibodies. A computer-assisted image analysis was performed. Cyclin A expression was evaluable in 74 and Ki67 in 70 patients. Cyclin A immunopositivity varied from 0% to 9.9%, with a mean of 1.9%. Cyclin A expression correlated significantly with Ki67. Cyclin A expression was associated with recurrence-free survival (HR 1.9, 95% CI = 1.1-3.2, P = .02), as were positive margin (HR 6.0, 95% CI = 1.6-22.5, P = .008) and extremity location (HR 5.3, 95% CI = 1.7-16.8, P = 0.005). Ki67 immunopositivity varied from 0.33% to 13.8%, with a mean of 4.6%, but had no significant prognostic impact (HR 1.1, P = .2). Our study indicates that cyclin A may be a new prognostic biomarker in surgically treated desmoid tumors. © 2018 Wiley Periodicals, Inc.

Sequence and expression variations suggest an adaptive role for the DA1-like gene family in the evolution of soybeans.

PubMed

Zhao, Man; Gu, Yongzhe; He, Lingli; Chen, Qingshan; He, Chaoying

2015-05-15

The DA1 gene family is plant-specific and Arabidopsis DA1 regulates seed and organ size, but the functions in soybeans are unknown. The cultivated soybean (Glycine max) is believed to be domesticated from the annual wild soybeans (Glycine soja). To evaluate whether DA1-like genes were involved in the evolution of soybeans, we compared variation at both sequence and expression levels of DA1-like genes from G. max (GmaDA1) and G. soja (GsoDA1). Sequence identities were extremely high between the orthologous pairs between soybeans, while the paralogous copies in a soybean species showed a relatively high divergence. Moreover, the expression variation of DA1-like paralogous genes in soybean was much greater than the orthologous gene pairs between the wild and cultivated soybeans during development and challenging abiotic stresses such as salinity. We further found that overexpressing GsoDA1 genes did not affect seed size. Nevertheless, overexpressing them reduced transgenic Arabidopsis seed germination sensitivity to salt stress. Moreover, most of these genes could improve salt tolerance of the transgenic Arabidopsis plants, corroborated by a detection of expression variation of several key genes in the salt-tolerance pathways. Our work suggested that expression diversification of DA1-like genes is functionally associated with adaptive radiation of soybeans, reinforcing that the plant-specific DA1 gene family might have contributed to the successful adaption to complex environments and radiation of the plants.

Expression, purification and characterization of two truncated peste des petits ruminants virus matrix proteins in Escherichia coli, and production of polyclonal antibodies against this protein.

PubMed

Liu, Fuxiao; Wu, Xiaodong; Li, Lin; Liu, Zengshan; Wang, Zhiliang

2013-09-01

Peste des petits ruminants virus (PPRV), the etiological agent of peste des petits ruminants, is classified into the genus Morbillivirus in the family Paramyxoviridae. The PPRV matrix (M) gene is composed of 1483 base pairs, encoding a 335 amino acids M protein with a molecular weight of approximately 38kD. We have demonstrated previously that the full-length M protein was expressed at an extremely low level or not even expressed in Escherichia coli BL21 (DE3). In this study, the M protein was split into two truncated forms to be successfully expressed in E. coli at a high level using the pET30a (+) vector, respectively, by analysis of SDS-PAGE, western blot and MALDI-TOF-MS. The optimization of culture conditions led us to perform the recombinant protein induction with 0.2mM IPTG at 28°C for 12h, whereby both proteins nevertheless were expressed in the insoluble form. Therefore, both His-tagged proteins were purified under the denaturing condition using a commercially available kit. Balb/c mice were immunized with the complex of purified proteins and then effectively produced polyclonal antibodies, which reached to a relatively high titer by the analysis of ELISA. The specificity of the prepared polyclonal antibodies was checked by western blot and immunofluorescence, revealing them with the desirable specificity against both non-denatured and denatured M proteins. Copyright © 2013 Elsevier Inc. All rights reserved.

Differences in the skeletal muscle transcriptome profile associated with extreme values of fatty acids content.

PubMed

Cesar, Aline S M; Regitano, Luciana C A; Poleti, Mirele D; Andrade, Sónia C S; Tizioto, Polyana C; Oliveira, Priscila S N; Felício, Andrezza M; do Nascimento, Michele L; Chaves, Amália S; Lanna, Dante P D; Tullio, Rymer R; Nassu, Renata T; Koltes, James E; Fritz-Waters, Eric; Mourão, Gerson B; Zerlotini-Neto, Adhemar; Reecy, James M; Coutinho, Luiz L

2016-11-22

Lipids are a class of molecules that play an important role in cellular structure and metabolism in all cell types. In the last few decades, it has been reported that long-chain fatty acids (FAs) are involved in several biological functions from transcriptional regulation to physiological processes. Several fatty acids have been both positively and negatively implicated in different biological processes in skeletal muscle and other tissues. To gain insight into biological processes associated with fatty acid content in skeletal muscle, the aim of the present study was to identify differentially expressed genes (DEGs) and functional pathways related to gene expression regulation associated with FA content in cattle. Skeletal muscle transcriptome analysis of 164 Nellore steers revealed no differentially expressed genes (DEGs, FDR 10%) for samples with extreme values for linoleic acid (LA) or stearic acid (SA), and only a few DEGs for eicosapentaenoic acid (EPA, 5 DEGs), docosahexaenoic acid (DHA, 4 DEGs) and palmitic acid (PA, 123 DEGs), while large numbers of DEGs were associated with oleic acid (OA, 1134 DEGs) and conjugated linoleic acid cis9 trans11 (CLA-c9t11, 872 DEGs). Functional annotation and functional enrichment from OA DEGs identified important genes, canonical pathways and upstream regulators such as SCD, PLIN5, UCP3, CPT1, CPT1B, oxidative phosphorylation mitochondrial dysfunction, PPARGC1A, and FOXO1. Two important genes associated with lipid metabolism, gene expression and cancer were identified as DEGs between animals with high and low CLA-c9t11, specifically, epidermal growth factor receptor (EGFR) and RNPS. Only two out of seven classes of molecules of FA studied were associated with large changes in the expression profile of skeletal muscle. OA and CLA-c9t11 content had significant effects on the expression level of genes related to important biological processes associated with oxidative phosphorylation, and cell growth, survival, and migration. These results contribute to our understanding of how some FAs modulate metabolism and may have protective health function.

Overwintering Is Associated with Reduced Expression of Immune Genes and Higher Susceptibility to Virus Infection in Honey Bees

PubMed Central

Steinmann, Nadja; Corona, Miguel; Neumann, Peter; Dainat, Benjamin

2015-01-01

The eusocial honey bee, Apis mellifera, has evolved remarkable abilities to survive extreme seasonal differences in temperature and availability of resources by dividing the worker caste into two groups that differ in physiology and lifespan: summer and winter bees. Most of the recent major losses of managed honey bee colonies occur during the winter, suggesting that winter bees may have compromised immune function and higher susceptibility to diseases. We tested this hypothesis by comparing the expression of eight immune genes and naturally occurring infection levels of deformed wing virus (DWV), one of the most widespread viruses in A. mellifera populations, between summer and winter bees. Possible interactions between immune response and physiological activity were tested by measuring the expression of vitellogenin and methyl farnesoate epoxidase, a gene coding for the last enzyme involved in juvenile hormone biosynthesis. Our data show that high DWV loads in winter bees correlate with reduced expression of genes involved in the cellular immune response and physiological activity and high expression of humoral immune genes involved in antibacterial defense compared with summer bees. This expression pattern could reflect evolutionary adaptations to resist bacterial pathogens and economize energy during the winter under a pathogen landscape with reduced risk of pathogenic viral infections. The outbreak of Varroa destructor infestation could have overcome these adaptations by promoting the transmission of viruses. Our results suggest that reduced cellular immune function during the winter may have increased honey bee’s susceptibility to DWV. These results contribute to our understanding of honey bee colony losses in temperate regions. PMID:26121358

Generation of mammalian cells stably expressing multiple genes at predetermined levels.

PubMed

Liu, X; Constantinescu, S N; Sun, Y; Bogan, J S; Hirsch, D; Weinberg, R A; Lodish, H F

2000-04-10

Expression of cloned genes at desired levels in cultured mammalian cells is essential for studying protein function. Controlled levels of expression have been difficult to achieve, especially for cell lines with low transfection efficiency or when expression of multiple genes is required. An internal ribosomal entry site (IRES) has been incorporated into many types of expression vectors to allow simultaneous expression of two genes. However, there has been no systematic quantitative analysis of expression levels in individual cells of genes linked by an IRES, and thus the broad use of these vectors in functional analysis has been limited. We constructed a set of retroviral expression vectors containing an IRES followed by a quantitative selectable marker such as green fluorescent protein (GFP) or truncated cell surface proteins CD2 or CD4. The gene of interest is placed in a multiple cloning site 5' of the IRES sequence under the control of the retroviral long terminal repeat (LTR) promoter. These vectors exploit the approximately 100-fold differences in levels of expression of a retrovirus vector depending on its site of insertion in the host chromosome. We show that the level of expression of the gene downstream of the IRES and the expression level and functional activity of the gene cloned upstream of the IRES are highly correlated in stably infected target cells. This feature makes our vectors extremely useful for the rapid generation of stably transfected cell populations or clonal cell lines expressing specific amounts of a desired protein simply by fluorescent activated cell sorting (FACS) based on the level of expression of the gene downstream of the IRES. We show how these vectors can be used to generate cells expressing high levels of the erythropoietin receptor (EpoR) or a dominant negative Smad3 protein and to generate cells expressing two different cloned proteins, Ski and Smad4. Correlation of a biologic effect with the level of expression of the protein downstream of the IRES provides strong evidence for the function of the protein placed upstream of the IRES.

The impact of rare variation on gene expression across tissues.

PubMed

Li, Xin; Kim, Yungil; Tsang, Emily K; Davis, Joe R; Damani, Farhan N; Chiang, Colby; Hess, Gaelen T; Zappala, Zachary; Strober, Benjamin J; Scott, Alexandra J; Li, Amy; Ganna, Andrea; Bassik, Michael C; Merker, Jason D; Hall, Ira M; Battle, Alexis; Montgomery, Stephen B

2017-10-11

Rare genetic variants are abundant in humans and are expected to contribute to individual disease risk. While genetic association studies have successfully identified common genetic variants associated with susceptibility, these studies are not practical for identifying rare variants. Efforts to distinguish pathogenic variants from benign rare variants have leveraged the genetic code to identify deleterious protein-coding alleles, but no analogous code exists for non-coding variants. Therefore, ascertaining which rare variants have phenotypic effects remains a major challenge. Rare non-coding variants have been associated with extreme gene expression in studies using single tissues, but their effects across tissues are unknown. Here we identify gene expression outliers, or individuals showing extreme expression levels for a particular gene, across 44 human tissues by using combined analyses of whole genomes and multi-tissue RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project v6p release. We find that 58% of underexpression and 28% of overexpression outliers have nearby conserved rare variants compared to 8% of non-outliers. Additionally, we developed RIVER (RNA-informed variant effect on regulation), a Bayesian statistical model that incorporates expression data to predict a regulatory effect for rare variants with higher accuracy than models using genomic annotations alone. Overall, we demonstrate that rare variants contribute to large gene expression changes across tissues and provide an integrative method for interpretation of rare variants in individual genomes.

Detection and attribution of climate extremes in the observed record

DOE PAGES

Easterling, David R.; Kunkel, Kenneth E.; Wehner, Michael F.; ...

2016-01-18

We present an overview of practices and challenges related to the detection and attribution of observed changes in climate extremes. Detection is the identification of a statistically significant change in the extreme values of a climate variable over some period of time. Issues in detection discussed include data quality, coverage, and completeness. Attribution takes that detection of a change and uses climate model simulations to evaluate whether a cause can be assigned to that change. Additionally, we discuss a newer field of attribution, event attribution, where individual extreme events are analyzed for the express purpose of assigning some measure ofmore » whether that event was directly influenced by anthropogenic forcing of the climate system.« less

Arsenic trioxide phosphorylates c-Fos to transactivate p21{sup WAF1/CIP1} expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu Zimiao; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; Huang, H.-S.

2008-12-01

An infamous poison, arsenic also has been used as a drug for nearly 2400 years; in recently years, arsenic has been effective in the treatment of acute promyelocytic leukemia. Increasing evidence suggests that opposite effects of arsenic trioxide (ATO) on tumors depend on its concentrations. For this reason, the mechanisms of action of the drug should be elucidated, and it should be used therapeutically only with extreme caution. Previously, we demonstrated the opposing effects of ERK1/2 and JNK on p21{sup WAF1/CIP1} (p21) expression in response to ATO in A431 cells. In addition, JNK phosphorylates c-Jun (Ser{sup 63/73}) to recruit TGIF/HDAC1more » to suppress p21 gene expression. Presently, we demonstrated that a high concentration of ATO sustains ERK1/2 phosphorylation, and increases c-Fos biosynthesis and stability, which enhances p21 gene expression. Using site-directed mutagenesis, a DNA affinity precipitation assay, and functional assays, we demonstrated that phosphorylation of the C-terminus of c-Fos (Thr{sup 232}, Thr{sup 325}, Thr{sup 331}, and Ser{sup 374}) plays an important role in its binding to the p21 promoter, and in conjunction with N-terminus phosphorylation of c-Fos (Ser{sup 70}) to transactivate p21 promoter expression. In conclusion, a high concentration of ATO can sustain ERK1/2 activation to enhance c-Fos expression, then dimerize with dephosphorylated c-Jun (Ser{sup 63/73}) and recruit p300/CBP to the Sp1 sites (- 84/- 64) to activate p21 gene expression in A431 cells.« less

Sulforaphane counteracts aggressiveness of pancreatic cancer driven by dysregulated Cx43-mediated gap junctional intercellular communication

PubMed Central

Zhang, Yiyao; Isayev, Orkhan; Heilmann, Katharina; Schoensiegel, Frank; Liu, Li; Nessling, Michelle; Richter, Karsten; Labsch, Sabrina; Nwaeburu, Clifford C.; Mattern, Juergen; Gladkich, Jury; Giese, Nathalia; Werner, Jens; Schemmer, Peter; Gross, Wolfgang; Gebhard, Martha M.; Gerhauser, Clarissa; Schaefer, Michael; Herr, Ingrid

2014-01-01

The extreme aggressiveness of pancreatic ductal adenocarcinoma (PDA) has been associated with blocked gap junctional intercellular communication (GJIC) and the presence of cancer stem cells (CSCs). We examined whether disturbed GJIC is responsible for a CSC phenotype in established and primary cancer cells and patient tissue of PDA using interdisciplinary methods based in physiology, cell and molecular biology, histology and epigenetics. Flux of fluorescent dyes and gemcitabine through gap junctions (GJs) was intact in less aggressive cells but not in highly malignant cells with morphological dysfunctional GJs. Among several connexins, only Cx43 was expressed on the cell surface of less aggressive and GJIC-competent cells, whereas Cx43 surface expression was absent in highly malignant, E-cadherin-negative and GJIC-incompetent cells. The levels of total Cx43 protein and Cx43 phosphorylated at Ser368 and Ser279/282 were high in normal tissue but low to absent in malignant tissue. si-RNA-mediated inhibition of Cx43 expression in GJIC-competent cells prevented GJIC and induced colony formation and the expression of stem cell-related factors. The bioactive substance sulforaphane enhanced Cx43 and E-cadherin levels, inhibited the CSC markers c-Met and CD133, improved the functional morphology of GJs and enhanced GJIC. Sulforaphane altered the phosphorylation of several kinases and their substrates and inhibition of GSK3, JNK and PKC prevented sulforaphane-induced CX43 expression. The sulforaphane-mediated expression of Cx43 was not correlated with enhanced Cx43 RNA expression, acetylated histone binding and Cx43 promoter de-methylation, suggesting that posttranslational phosphorylation is the dominant regulatory mechanism. Together, the absence of Cx43 prevents GJIC and enhances aggressiveness, whereas sulforaphane counteracts this process, and our findings highlight dietary co-treatment as a viable treatment option for PDA. PMID:24742583

Sulforaphane counteracts aggressiveness of pancreatic cancer driven by dysregulated Cx43-mediated gap junctional intercellular communication.

PubMed

Forster, Tobias; Rausch, Vanessa; Zhang, Yiyao; Isayev, Orkhan; Heilmann, Katharina; Schoensiegel, Frank; Liu, Li; Nessling, Michelle; Richter, Karsten; Labsch, Sabrina; Nwaeburu, Clifford C; Mattern, Juergen; Gladkich, Jury; Giese, Nathalia; Werner, Jens; Schemmer, Peter; Gross, Wolfgang; Gebhard, Martha M; Gerhauser, Clarissa; Schaefer, Michael; Herr, Ingrid

2014-03-30

The extreme aggressiveness of pancreatic ductal adenocarcinoma (PDA) has been associated with blocked gap junctional intercellular communication (GJIC) and the presence of cancer stem cells (CSCs). We examined whether disturbed GJIC is responsible for a CSC phenotype in established and primary cancer cells and patient tissue of PDA using interdisciplinary methods based in physiology, cell and molecular biology, histology and epigenetics. Flux of fluorescent dyes and gemcitabine through gap junctions (GJs) was intact in less aggressive cells but not in highly malignant cells with morphological dysfunctional GJs. Among several connexins, only Cx43 was expressed on the cell surface of less aggressive and GJIC-competent cells, whereas Cx43 surface expression was absent in highly malignant, E-cadherin-negative and GJIC-incompetent cells. The levels of total Cx43 protein and Cx43 phosphorylated at Ser368 and Ser279/282 were high in normal tissue but low to absent in malignant tissue. si-RNA-mediated inhibition of Cx43 expression in GJIC-competent cells prevented GJIC and induced colony formation and the expression of stem cell-related factors. The bioactive substance sulforaphane enhanced Cx43 and E-cadherin levels, inhibited the CSC markers c-Met and CD133, improved the functional morphology of GJs and enhanced GJIC. Sulforaphane altered the phosphorylation of several kinases and their substrates and inhibition of GSK3, JNK and PKC prevented sulforaphane-induced CX43 expression. The sulforaphane-mediated expression of Cx43 was not correlated with enhanced Cx43 RNA expression, acetylated histone binding and Cx43 promoter de-methylation, suggesting that posttranslational phosphorylation is the dominant regulatory mechanism. Together, the absence of Cx43 prevents GJIC and enhances aggressiveness, whereas sulforaphane counteracts this process, and our findings highlight dietary co-treatment as a viable treatment option for PDA.

Opinion Integration and Summarization

ERIC Educational Resources Information Center

Lu, Yue

2011-01-01

As Web 2.0 applications become increasingly popular, more and more people express their opinions on the Web in various ways in real time. Such wide coverage of topics and abundance of users make the Web an extremely valuable source for mining people's opinions about all kinds of topics. However, since the opinions are usually expressed as…

Adaptations to High Salt in a Halophilic Protist: Differential Expression and Gene Acquisitions through Duplications and Gene Transfers

PubMed Central

Harding, Tommy; Roger, Andrew J.; Simpson, Alastair G. B.

2017-01-01

The capacity of halophiles to thrive in extreme hypersaline habitats derives partly from the tight regulation of ion homeostasis, the salt-dependent adjustment of plasma membrane fluidity, and the increased capability to manage oxidative stress. Halophilic bacteria, and archaea have been intensively studied, and substantial research has been conducted on halophilic fungi, and the green alga Dunaliella. By contrast, there have been very few investigations of halophiles that are phagotrophic protists, i.e., protozoa. To gather fundamental knowledge about salt adaptation in these organisms, we studied the transcriptome-level response of Halocafeteria seosinensis (Stramenopiles) grown under contrasting salinities. We provided further evolutionary context to our analysis by identifying genes that underwent recent duplications. Genes that were highly responsive to salinity variations were involved in stress response (e.g., chaperones), ion homeostasis (e.g., Na+/H+ transporter), metabolism and transport of lipids (e.g., sterol biosynthetic genes), carbohydrate metabolism (e.g., glycosidases), and signal transduction pathways (e.g., transcription factors). A significantly high proportion (43%) of duplicated genes were also differentially expressed, accentuating the importance of gene expansion in adaptation by H. seosinensis to high salt environments. Furthermore, we found two genes that were lateral acquisitions from bacteria, and were also highly up-regulated and highly expressed at high salt, suggesting that this evolutionary mechanism could also have facilitated adaptation to high salt. We propose that a transition toward high-salt adaptation in the ancestors of H. seosinensis required the acquisition of new genes via duplication, and some lateral gene transfers (LGTs), as well as the alteration of transcriptional programs, leading to increased stress resistance, proper establishment of ion gradients, and modification of cell structure properties like membrane fluidity. PMID:28611746

Cloning, Expression Analysis and Enzyme Activity Assays of the α-Carbonic Anhydrase Gene from Chlamydomonas sp. ICE-L.

PubMed

Qu, Changfeng; He, Yingying; Zheng, Zhou; An, Meiling; Li, Lulu; Wang, Xixi; He, Xiaodong; Wang, Yibin; Liu, Fangming; Miao, Jinlai

2018-01-01

The α-carbonic anhydrase (α-CA) is a zinc ion-containing enzyme that catalyzes the hydration of carbon dioxide. In this paper, a full-length α-CA gene was cloned from Chlamydomonas sp. ICE-L using RT-PCR and RACE-PCR for bioinformatic analysis. The α-CA open reading frame obtained by PCR was cloned into a vector and transformed into Escherichia coli to generate α-CA-producing bacteria. The α-CA was highly expressed upon induction with isopropyl-β-d-thiogalactoside (IPTG) at a final concentration of 0.8 mM. A single band with a molecular weight of approximate 40 kDa expressed in the recombinant E. coli strain harboring the α-CA vector was observed in SDS-PAGE analysis. The carbon dioxide hydration activity and esterase activity of α-CA expressed by the recombinant strain were 0.404 U/mg and 0.319 U, respectively. In addition, three conditions, temperature, salinity and UVB radiation exposure, were selected to analyze α-CA transcription levels by qRT-PCR. The results suggested UVB exposure increased the expression of relative mRNA; meanwhile, the α-CA mRNA expression was rapidly induced by temperature and salinity stress, indicating that Chlamydomonas sp. ICE-L might modulate the α-CA mRNA expression to adapt to the extreme environments.

Identification and Correction of Sample Mix-Ups in Expression Genetic Data: A Case Study

PubMed Central

Broman, Karl W.; Keller, Mark P.; Broman, Aimee Teo; Kendziorski, Christina; Yandell, Brian S.; Sen, Śaunak; Attie, Alan D.

2015-01-01

In a mouse intercross with more than 500 animals and genome-wide gene expression data on six tissues, we identified a high proportion (18%) of sample mix-ups in the genotype data. Local expression quantitative trait loci (eQTL; genetic loci influencing gene expression) with extremely large effect were used to form a classifier to predict an individual’s eQTL genotype based on expression data alone. By considering multiple eQTL and their related transcripts, we identified numerous individuals whose predicted eQTL genotypes (based on their expression data) did not match their observed genotypes, and then went on to identify other individuals whose genotypes did match the predicted eQTL genotypes. The concordance of predictions across six tissues indicated that the problem was due to mix-ups in the genotypes (although we further identified a small number of sample mix-ups in each of the six panels of gene expression microarrays). Consideration of the plate positions of the DNA samples indicated a number of off-by-one and off-by-two errors, likely the result of pipetting errors. Such sample mix-ups can be a problem in any genetic study, but eQTL data allow us to identify, and even correct, such problems. Our methods have been implemented in an R package, R/lineup. PMID:26290572

Identification and Correction of Sample Mix-Ups in Expression Genetic Data: A Case Study.

PubMed

Broman, Karl W; Keller, Mark P; Broman, Aimee Teo; Kendziorski, Christina; Yandell, Brian S; Sen, Śaunak; Attie, Alan D

2015-08-19

In a mouse intercross with more than 500 animals and genome-wide gene expression data on six tissues, we identified a high proportion (18%) of sample mix-ups in the genotype data. Local expression quantitative trait loci (eQTL; genetic loci influencing gene expression) with extremely large effect were used to form a classifier to predict an individual's eQTL genotype based on expression data alone. By considering multiple eQTL and their related transcripts, we identified numerous individuals whose predicted eQTL genotypes (based on their expression data) did not match their observed genotypes, and then went on to identify other individuals whose genotypes did match the predicted eQTL genotypes. The concordance of predictions across six tissues indicated that the problem was due to mix-ups in the genotypes (although we further identified a small number of sample mix-ups in each of the six panels of gene expression microarrays). Consideration of the plate positions of the DNA samples indicated a number of off-by-one and off-by-two errors, likely the result of pipetting errors. Such sample mix-ups can be a problem in any genetic study, but eQTL data allow us to identify, and even correct, such problems. Our methods have been implemented in an R package, R/lineup. Copyright © 2015 Broman et al.

Multifunctional biocompatible graphene oxide quantum dots decorated magnetic nanoplatform for efficient capture and two-photon imaging of rare tumor cells.

PubMed

Shi, Yongliang; Pramanik, Avijit; Tchounwou, Christine; Pedraza, Francisco; Crouch, Rebecca A; Chavva, Suhash Reddy; Vangara, Aruna; Sinha, Sudarson Sekhar; Jones, Stacy; Sardar, Dhiraj; Hawker, Craig; Ray, Paresh Chandra

2015-05-27

Circulating tumor cells (CTCs) are extremely rare cells in blood containing billions of other cells. The selective capture and identification of rare cells with sufficient sensitivity is a real challenge. Driven by this need, this manuscript reports the development of a multifunctional biocompatible graphene oxide quantum dots (GOQDs) coated, high-luminescence magnetic nanoplatform for the selective separation and diagnosis of Glypican-3 (GPC3)-expressed Hep G2 liver cancer tumor CTCs from infected blood. Experimental data show that an anti-GPC3-antibody-attached multifunctional nanoplatform can be used for selective Hep G2 hepatocellular carcinoma tumor cell separation from infected blood containing 10 tumor cells/mL of blood in a 15 mL sample. Reported data indicate that, because of an extremely high two-photon absorption cross section (40530 GM), an anti-GPC3-antibody-attached GOQDs-coated magnetic nanoplatform can be used as a two-photon luminescence platform for selective and very bright imaging of a Hep G2 tumor cell in a biological transparency window using 960 nm light. Experimental results with nontargeted GPC3(-) and SK-BR-3 breast cancer cells show that multifunctional-nanoplatform-based cell separation, followed by two-photon imaging, is highly selective for Hep G2 hepatocellular carcinoma tumor cells.

Modelling hydrological extremes under non-stationary conditions using climate covariates

NASA Astrophysics Data System (ADS)

Vasiliades, Lampros; Galiatsatou, Panagiota; Loukas, Athanasios

2013-04-01

Extreme value theory is a probabilistic theory that can interpret the future probabilities of occurrence of extreme events (e.g. extreme precipitation and streamflow) using past observed records. Traditionally, extreme value theory requires the assumption of temporal stationarity. This assumption implies that the historical patterns of recurrence of extreme events are static over time. However, the hydroclimatic system is nonstationary on time scales that are relevant to extreme value analysis, due to human-mediated and natural environmental change. In this study the generalized extreme value (GEV) distribution is used to assess nonstationarity in annual maximum daily rainfall and streamflow timeseries at selected meteorological and hydrometric stations in Greece and Cyprus. The GEV distribution parameters (location, scale, and shape) are specified as functions of time-varying covariates and estimated using the conditional density network (CDN) as proposed by Cannon (2010). The CDN is a probabilistic extension of the multilayer perceptron neural network. Model parameters are estimated via the generalized maximum likelihood (GML) approach using the quasi-Newton BFGS optimization algorithm, and the appropriate GEV-CDN model architecture for the selected meteorological and hydrometric stations is selected by fitting increasingly complicated models and choosing the one that minimizes the Akaike information criterion with small sample size correction. For all case studies in Greece and Cyprus different formulations are tested with combinational cases of stationary and nonstationary parameters of the GEV distribution, linear and non-linear architecture of the CDN and combinations of the input climatic covariates. Climatic indices such as the Southern Oscillation Index (SOI), which describes atmospheric circulation in the eastern tropical pacific related to El Niño Southern Oscillation (ENSO), the Pacific Decadal Oscillation (PDO) index that varies on an interdecadal rather than interannual time scale and the atmospheric circulation patterns as expressed by the North Atlantic Oscillation (NAO) index are used to express the GEV parameters as functions of the covariates. Results show that the nonstationary GEV model can be an efficient tool to take into account the dependencies between extreme value random variables and the temporal evolution of the climate.

Expression of Anthocyanins and Proanthocyanidins after Transformation of Alfalfa with Maize Lc12

PubMed Central

Ray, Heather; Yu, Min; Auser, Patricia; Blahut-Beatty, Laureen; McKersie, Brian; Bowley, Steve; Westcott, Neil; Coulman, Bruce; Lloyd, Alan; Gruber, Margaret Y.

2003-01-01

Three anthocyanin regulatory genes of maize (Zea mays; Lc, B-Peru, and C1) were introduced into alfalfa (Medicago sativa) in a strategy designed to stimulate the flavonoid pathway and alter the composition of flavonoids produced in forage. Lc constructs included a full-length gene and a gene with a shortened 5′-untranslated region. Lc RNA was strongly expressed in Lc transgenic alfalfa foliage, but accumulation of red-purple anthocyanin was observed only under conditions of high light intensity or low temperature. These stress conditions induced chalcone synthase and flavanone 3-hydroxylase expression in Lc transgenic alfalfa foliage compared with non-transformed plants. Genotypes containing the Lc transgene construct with a full-length 5′-untranslated region responded more quickly to stress conditions and with a more extreme phenotype. High-performance liquid chromatography analysis of field-grown tissue indicated that flavone content was reduced in forage of the Lc transgenic plants. Leucocyanidin reductase, the enzyme that controls entry of metabolites into the proanthocyanidin pathway, was activated both in foliage and in developing seeds of the Lc transgenic alfalfa genotypes. Proanthocyanidin polymer was accumulated in the forage, but (+)-catechin monomers were not detected. B-Peru transgenic and C1 transgenic populations displayed no visible phenotypic changes, although these transgenes were expressed at detectable levels. These results support the emerging picture of Lc transgene-specific patterns of expression in different recipient species. These results demonstrate that proanthocyanidin biosynthesis can be stimulated in alfalfa forage using an myc-like transgene, and they pave the way for the development of high quality, bloat-safe cultivars with ruminal protein bypass. PMID:12857826

Angular distribution of ions and extreme ultraviolet emission in laser-produced tin droplet plasma

NASA Astrophysics Data System (ADS)

Chen, Hong; Wang, Xinbing; Duan, Lian; Lan, Hui; Chen, Ziqi; Zuo, Duluo; Lu, Peixiang

2015-05-01

Angular-resolved ion time-of-flight spectra as well as extreme ultraviolet radiation in laser-produced tin droplet plasma are investigated experimentally and theoretically. Tin droplets with a diameter of 150 μm are irradiated by a pulsed Nd:YAG laser. The ion time-of-flight spectra measured from the plasma formed by laser irradiation of the tin droplets are interpreted in terms of a theoretical elliptical Druyvesteyn distribution to deduce ion density distributions including kinetic temperatures of the plasma. The opacity of the plasma for extreme ultraviolet radiation is calculated based on the deduced ion densities and temperatures, and the angular distribution of extreme ultraviolet radiation is expressed as a function of the opacity using the Beer-Lambert law. Our results show that the calculated angular distribution of extreme ultraviolet radiation is in satisfactory agreement with the experimental data.

Analytical study of a Kerr-Sen black hole and a charged massive scalar field

NASA Astrophysics Data System (ADS)

Bernard, Canisius

2017-11-01

It is reported that Kerr-Newman and Kerr-Sen black holes are unstable to perturbations of charged massive scalar field. In this paper, we study analytically the complex frequencies which characterize charged massive scalar fields in a near-extremal Kerr-Sen black hole. For near-extremal Kerr-Sen black holes and for charged massive scalar fields in the eikonal large-mass M ≫μ regime, where M is the mass of the black hole, and μ is the mass of the charged scalar field, we have obtained a simple expression for the dimensionless ratio ωI/(ωR-ωc) , where ωI and ωR are, respectively, the imaginary and real parts of the frequency of the modes, and ωc is the critical frequency for the onset of super-radiance. We have also found our expression is consistent with the result of Hod [Phys. Rev. D 94, 044036 (2016), 10.1103/PhysRevD.94.044036] for the case of a near-extremal Kerr-Newman black hole and the result of Zouros and Eardly [Ann. Phys. (N.Y.) 118, 139 (1979), 10.1016/0003-4916(79)90237-9] for the case of neutral scalar fields in the background of a near-extremal Kerr black hole.

Investigating NARCCAP Precipitation Extremes via Bivariate Extreme Value Theory (Invited)

NASA Astrophysics Data System (ADS)

Weller, G. B.; Cooley, D. S.; Sain, S. R.; Bukovsky, M. S.; Mearns, L. O.

2013-12-01

We introduce methodology from statistical extreme value theory to examine the ability of reanalysis-drive regional climate models to simulate past daily precipitation extremes. Going beyond a comparison of summary statistics such as 20-year return values, we study whether the most extreme precipitation events produced by climate model simulations exhibit correspondence to the most extreme events seen in observational records. The extent of this correspondence is formulated via the statistical concept of tail dependence. We examine several case studies of extreme precipitation events simulated by the six models of the North American Regional Climate Change Assessment Program (NARCCAP) driven by NCEP reanalysis. It is found that the NARCCAP models generally reproduce daily winter precipitation extremes along the Pacific coast quite well; in contrast, simulation of past daily summer precipitation extremes in a central US region is poor. Some differences in the strength of extremal correspondence are seen in the central region between models which employ spectral nudging and those which do not. We demonstrate how these techniques may be used to draw a link between extreme precipitation events and large-scale atmospheric drivers, as well as to downscale extreme precipitation simulated by a future run of a regional climate model. Specifically, we examine potential future changes in the nature of extreme precipitation along the Pacific coast produced by the pineapple express (PE) phenomenon. A link between extreme precipitation events and a "PE Index" derived from North Pacific sea-surface pressure fields is found. This link is used to study PE-influenced extreme precipitation produced by a future-scenario climate model run.

Tyrosine decarboxylase activity of enterococci grown in media with different nutritional potential: tyramine and 2-phenylethylamine accumulation and tyrDC gene expression.

PubMed

Bargossi, Eleonora; Tabanelli, Giulia; Montanari, Chiara; Lanciotti, Rosalba; Gatto, Veronica; Gardini, Fausto; Torriani, Sandra

2015-01-01

The ability to accumulate tyramine and 2-phenylethylamine by two strains of Enterococcus faecalis and two strains Enterococcus faecium was evaluated in two cultural media added or not with tyrosine. All the enterococcal strains possessed a tyrosine decarboxylase (tyrDC) which determined tyramine accumulation in all the conditions tested, independently on the addition of high concentration of free tyrosine. Enterococci differed in rate and level of biogenic amines accumulation. E. faecalis EF37 and E. faecium FC12 produced tyramine in high amount since the exponential growth phase, while 2-phenylethylamine was accumulated when tyrosine was depleted. E. faecium FC12 and E. faecalis ATCC 29212 showed a slower tyraminogenic activity which took place mainly in the stationary phase up to 72 h of incubation. Moreover, E. faecalis ATCC 29212 produced 2-phenylethylamine only in the media without tyrosine added. In BHI added or not with tyrosine the tyrDC gene expression level differed considerably depending on the strains and the growth phase. In particular, the tyrDC gene expression was high during the exponential phase in rich medium for all the strains and subsequently decreased except for E. faecium FC12. Even if tyrDC presence is common among enterococci, this study underlines the extremely variable decarboxylating potential of strains belonging to the same species, suggesting strain-dependent implications in food safety.

Molecular characterization, tissue distribution, localization and mRNA expression of the bucky ball gene in the Dabry's sturgeon (Acipenser dabryanus) during oogenesis.

PubMed

Ye, Huan; Yue, Huamei; Yang, Xiaoge; Li, Chuangju; Wei, Qiwei

2018-06-01

In many organisms, germ cells are specified during embryogenesis by the inheritance of maternally deposited RNAs and proteins termed germ plasm. In vertebrates, the bucky ball (buc) gene plays an essential role in the germ plasm aggregation. In this study, the full-length cDNA of buc homologue in Dabry's sturgeon, Adbuc, was isolated and characterized. Multiple sequence alignments showed that the BUVE domain of Buc was highly conserved in vertebrates, despite exhibiting low identities with each other across the whole protein. By quantitative real-time PCR analysis, we found that Adbuc RNAs were only detected in the gonad with a high level in the ovary and a very low level in the testis. During embryogenesis, these RNAs were highly expressed from the unfertilized eggs to blastula, declined dramatically from the gastrula stage, and hardly found after the neurula stage. Moreover, with the development of ovary, the expression level of Adbuc was increasing. By in situ hybridization, the signal of Adbuc was not found in the oogonia, increased slightly in the stage I oocytes, and extremely strong in the stage II oocytes, suggesting that the signal became much stronger with increasing size of oocytes. Additionally, Adbuc co-localized with the mitochondrial cloud. Thus, we conclude that Dabry's sturgeon buc gene might also function in germplasm formation. Copyright © 2018 Elsevier B.V. All rights reserved.

Climate Change: A New Metric to Measure Changes in the Frequency of Extreme Temperatures using Record Data

NASA Technical Reports Server (NTRS)

Munasinghe, L.; Jun, T.; Rind, D. H.

2012-01-01

Consensus on global warming is the result of multiple and varying lines of evidence, and one key ramification is the increase in frequency of extreme climate events including record high temperatures. Here we develop a metric- called "record equivalent draws" (RED)-based on record high (low) temperature observations, and show that changes in RED approximate changes in the likelihood of extreme high (low) temperatures. Since we also show that this metric is independent of the specifics of the underlying temperature distributions, RED estimates can be aggregated across different climates to provide a genuinely global assessment of climate change. Using data on monthly average temperatures across the global landmass we find that the frequency of extreme high temperatures increased 10-fold between the first three decades of the last century (1900-1929) and the most recent decade (1999-2008). A more disaggregated analysis shows that the increase in frequency of extreme high temperatures is greater in the tropics than in higher latitudes, a pattern that is not indicated by changes in mean temperature. Our RED estimates also suggest concurrent increases in the frequency of both extreme high and extreme low temperatures during 2002-2008, a period when we observe a plateauing of global mean temperature. Using daily extreme temperature observations, we find that the frequency of extreme high temperatures is greater in the daily minimum temperature time-series compared to the daily maximum temperature time-series. There is no such observable difference in the frequency of extreme low temperatures between the daily minimum and daily maximum.

Evaluating reproducibility of differential expression discoveries in microarray studies by considering correlated molecular changes.

PubMed

Zhang, Min; Zhang, Lin; Zou, Jinfeng; Yao, Chen; Xiao, Hui; Liu, Qing; Wang, Jing; Wang, Dong; Wang, Chenguang; Guo, Zheng

2009-07-01

According to current consistency metrics such as percentage of overlapping genes (POG), lists of differentially expressed genes (DEGs) detected from different microarray studies for a complex disease are often highly inconsistent. This irreproducibility problem also exists in other high-throughput post-genomic areas such as proteomics and metabolism. A complex disease is often characterized with many coordinated molecular changes, which should be considered when evaluating the reproducibility of discovery lists from different studies. We proposed metrics percentage of overlapping genes-related (POGR) and normalized POGR (nPOGR) to evaluate the consistency between two DEG lists for a complex disease, considering correlated molecular changes rather than only counting gene overlaps between the lists. Based on microarray datasets of three diseases, we showed that though the POG scores for DEG lists from different studies for each disease are extremely low, the POGR and nPOGR scores can be rather high, suggesting that the apparently inconsistent DEG lists may be highly reproducible in the sense that they are actually significantly correlated. Observing different discovery results for a disease by the POGR and nPOGR scores will obviously reduce the uncertainty of the microarray studies. The proposed metrics could also be applicable in many other high-throughput post-genomic areas.

Observations and Impact Assessments of Extreme Space Weather Events

NASA Astrophysics Data System (ADS)

Baker, D. N.

2007-05-01

"Space weather" refers to conditions on the Sun, in the solar wind, and in Earth`s magnetosphere, ionosphere, and thermosphere. Activity on the Sun such as solar flares and coronal mass ejections can lead to high levels of radiation in space and can cause major magnetic storms at the Earth. Space radiation can come as energetic particles or as electromagnetic emissions. Adverse conditions in the near-Earth space environment can cause disruption of satellite operations, communications, navigation, and electric power distribution grids. This can lead to a variety of socioeconomic losses. Astronauts and airline passengers exposed to high levels of radiation are also at risk. Society`s vulnerability to space weather effects is an issue of increasing concern. We are dependent on technological systems that are becoming more susceptible to space weather disturbances. We also have a permanent human presence in space with the International Space Station and the President and NASA have expressed a desire to expand our human space activities with missions to the moon and Mars. This will make space weather of even greater concern in the future. In this talk I will describe many space weather effects and will describe some of the societal and economic impacts that extreme events have had.

Complex Socio-Ecological Dynamics driven by extreme events in the Amazon

NASA Astrophysics Data System (ADS)

Pinho, P. F.

2015-12-01

Several years with extreme floods or droughts in the past decade have caused human suffering in remote communities of the Brazilian Amazon. Despite documented local knowledge and practices for coping with the high seasonal variability characteristic of the region's hydrology (e.g. 10m change in river levels between dry and flood seasons), and despite 'civil Defense' interventions by various levels of government, the more extreme years seem to have exceeded the coping capacity of the community. In this paper, we explore whether there is a real increase in variability, whether the community perceives that recent extreme events are outside the experience which shapes their responses to 'normal' levels of variability, and what science-based policy could contribute to greater local resilience. Hydrological analyses suggest that variability is indeed increasing, in line with expectations from future climate change. However, current measures of hydrological regimes do not predict years with social hardship very well. Interviewees in two regions are able to express their strategies for dealing with 'normal' variability very well, but also identify ways in which abnormal years exceed their ability to cope. Current Civil Defense arrangements struggle to deliver emergency assistance in a sufficiently timely and locally appropriate fashion. Combining these insights in the context of social-ecological change, we suggest how better integration of science, policy and local knowledge could improve resilience to future trends, and identify some contributions science could make into such an arrangement.

Comparative Transcriptomic Analyses of Vegetable and Grain Pea (Pisum sativum L.) Seed Development

PubMed Central

Liu, Na; Zhang, Guwen; Xu, Shengchun; Mao, Weihua; Hu, Qizan; Gong, Yaming

2015-01-01

Understanding the molecular mechanisms regulating pea seed developmental process is extremely important for pea breeding. In this study, we used high-throughput RNA-Seq and bioinformatics analyses to examine the changes in gene expression during seed development in vegetable pea and grain pea, and compare the gene expression profiles of these two pea types. RNA-Seq generated 18.7 G of raw data, which were then de novo assembled into 77,273 unigenes with a mean length of 930 bp. Our results illustrate that transcriptional control during pea seed development is a highly coordinated process. There were 459 and 801 genes differentially expressed at early and late seed maturation stages between vegetable pea and grain pea, respectively. Soluble sugar and starch metabolism related genes were significantly activated during the development of pea seeds coinciding with the onset of accumulation of sugar and starch in the seeds. A comparative analysis of genes involved in sugar and starch biosynthesis in vegetable pea (high seed soluble sugar and low starch) and grain pea (high seed starch and low soluble sugar) revealed that differential expression of related genes at late development stages results in a negative correlation between soluble sugar and starch biosynthetic flux in vegetable and grain pea seeds. RNA-Seq data was validated by using real-time quantitative RT-PCR analysis for 30 randomly selected genes. To our knowledge, this work represents the first report of seed development transcriptomics in pea. The obtained results provide a foundation to support future efforts to unravel the underlying mechanisms that control the developmental biology of pea seeds, and serve as a valuable resource for improving pea breeding. PMID:26635856

High-level expression and characterization of the Bacillus subtilis subsp. subtilis str. BSP1 YwaD aminopeptidase in Pichia pastoris.

PubMed

Tang, Wei; Li, Zhezhe; Li, Chunhua; Yu, Xianhong; Wang, Fei; Wan, Xin; Wang, Yaping; Ma, Lixin

2016-06-01

Aminopeptidases are widely used for creating protein hydrolysates and peptide sequencing. The ywaD gene from a new Bacillus isolate, named Bacillus subtilis subsp. subtilis str. BSP1, was cloned into the yeast expression vector pHBM905A and expressed and secreted by Pichia pastoris strain GS115. The deduced amino acid sequence of the aminopeptidase encoded by the ywaD gene shared up to 98% identity with aminopeptidases from B. subtilis strains 168 and zj016. The yield (3.81 g/l) and specific activity (788 U/mg) of recombinant YwaD in high-density fermentation were extremely high. And 829.83 mg of the purified enzyme (4089.72 U/mg) were harvested. YwaD was glycosylated, and its activity decreased after deglycosylation, which was similar to that of the aminopeptidase from B. subtilis strain zj016. YwaD was most active toward l-arginine-4-nitroanilide. Moreover, it exhibited high resistance to carbamide, which was not true for aminopeptidases from B. subtilis strains 168 and zj016, which could simplify the purification of YwaD. Moreover, the expression and parts of characterization of the aminopeptidase from B. subtilis strain 168 in Pichia pastoris were added as supplementary material. The sequence and other characteristics of YwaD were compared with those of aminopeptidases from B. subtilis strains 168 and zj016, and they will provide a solid foundation for further research on the influence of amino acid mutations on the function of aminopeptidases. Copyright © 2016 Elsevier Inc. All rights reserved.

High-Dimensional Gene Expression Profiling Studies in High and Low Responders to Primary Smallpox Vaccination

PubMed Central

Haralambieva, Iana H.; Oberg, Ann L.; Dhiman, Neelam; Ovsyannikova, Inna G.; Kennedy, Richard B.; Grill, Diane E.; Jacobson, Robert M.; Poland, Gregory A.

2012-01-01

Background. The mechanisms underlying smallpox vaccine-induced variations in immune responses are not well understood, but are of considerable interest to a deeper understanding of poxvirus immunity and correlates of protection. Methods. We assessed transcriptional messenger RNA expression changes in 197 recipients of primary smallpox vaccination representing the extremes of humoral and cellular immune responses. Results. The 20 most significant differentially expressed genes include a tumor necrosis factor–receptor superfamily member, an interferon (IFN) gene, a chemokine gene, zinc finger protein genes, nuclear factors, and histones (P ≤ 1.06E−20, q ≤ 2.64E−17). A pathway analysis identified 4 enriched pathways with cytokine production by the T-helper 17 subset of CD4+ T cells being the most significant pathway (P = 3.42E−05). Two pathways (antiviral actions of IFNs, P = 8.95E−05; and IFN-α/β signaling pathway, P = 2.92E−04), integral to innate immunity, were enriched when comparing high with low antibody responders (false discovery rate, < 0.05). Genes related to immune function and transcription (TLR8, P = .0002; DAPP1, P = .0003; LAMP3, P = 9.96E−05; NR4A2, P ≤ .0002; EGR3, P = 4.52E−05), and other genes with a possible impact on immunity (LNPEP, P = 3.72E−05; CAPRIN1, P = .0001; XRN1, P = .0001), were found to be expressed differentially in high versus low antibody responders. Conclusion. We identified novel and known immunity-related genes and pathways that may account for differences in immune response to smallpox vaccination. PMID:22949304

A Fast SVD-Hidden-nodes based Extreme Learning Machine for Large-Scale Data Analytics.

PubMed

Deng, Wan-Yu; Bai, Zuo; Huang, Guang-Bin; Zheng, Qing-Hua

2016-05-01

Big dimensional data is a growing trend that is emerging in many real world contexts, extending from web mining, gene expression analysis, protein-protein interaction to high-frequency financial data. Nowadays, there is a growing consensus that the increasing dimensionality poses impeding effects on the performances of classifiers, which is termed as the "peaking phenomenon" in the field of machine intelligence. To address the issue, dimensionality reduction is commonly employed as a preprocessing step on the Big dimensional data before building the classifiers. In this paper, we propose an Extreme Learning Machine (ELM) approach for large-scale data analytic. In contrast to existing approaches, we embed hidden nodes that are designed using singular value decomposition (SVD) into the classical ELM. These SVD nodes in the hidden layer are shown to capture the underlying characteristics of the Big dimensional data well, exhibiting excellent generalization performances. The drawback of using SVD on the entire dataset, however, is the high computational complexity involved. To address this, a fast divide and conquer approximation scheme is introduced to maintain computational tractability on high volume data. The resultant algorithm proposed is labeled here as Fast Singular Value Decomposition-Hidden-nodes based Extreme Learning Machine or FSVD-H-ELM in short. In FSVD-H-ELM, instead of identifying the SVD hidden nodes directly from the entire dataset, SVD hidden nodes are derived from multiple random subsets of data sampled from the original dataset. Comprehensive experiments and comparisons are conducted to assess the FSVD-H-ELM against other state-of-the-art algorithms. The results obtained demonstrated the superior generalization performance and efficiency of the FSVD-H-ELM. Copyright © 2016 Elsevier Ltd. All rights reserved.

EPS-LASSO: Test for High-Dimensional Regression Under Extreme Phenotype Sampling of Continuous Traits.

PubMed

Xu, Chao; Fang, Jian; Shen, Hui; Wang, Yu-Ping; Deng, Hong-Wen

2018-01-25

Extreme phenotype sampling (EPS) is a broadly-used design to identify candidate genetic factors contributing to the variation of quantitative traits. By enriching the signals in extreme phenotypic samples, EPS can boost the association power compared to random sampling. Most existing statistical methods for EPS examine the genetic factors individually, despite many quantitative traits have multiple genetic factors underlying their variation. It is desirable to model the joint effects of genetic factors, which may increase the power and identify novel quantitative trait loci under EPS. The joint analysis of genetic data in high-dimensional situations requires specialized techniques, e.g., the least absolute shrinkage and selection operator (LASSO). Although there are extensive research and application related to LASSO, the statistical inference and testing for the sparse model under EPS remain unknown. We propose a novel sparse model (EPS-LASSO) with hypothesis test for high-dimensional regression under EPS based on a decorrelated score function. The comprehensive simulation shows EPS-LASSO outperforms existing methods with stable type I error and FDR control. EPS-LASSO can provide a consistent power for both low- and high-dimensional situations compared with the other methods dealing with high-dimensional situations. The power of EPS-LASSO is close to other low-dimensional methods when the causal effect sizes are small and is superior when the effects are large. Applying EPS-LASSO to a transcriptome-wide gene expression study for obesity reveals 10 significant body mass index associated genes. Our results indicate that EPS-LASSO is an effective method for EPS data analysis, which can account for correlated predictors. The source code is available at https://github.com/xu1912/EPSLASSO. hdeng2@tulane.edu. Supplementary data are available at Bioinformatics online. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Gene expression changes controlling distinct adaptations in the heart and skeletal muscle of a hibernating mammal

PubMed Central

Vermillion, Katie L.; Anderson, Kyle J.; Hampton, Marshall

2015-01-01

Throughout the hibernation season, the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) experiences extreme fluctuations in heart rate, metabolism, oxygen consumption, and body temperature, along with prolonged fasting and immobility. These conditions necessitate different functional requirements for the heart, which maintains contractile function throughout hibernation, and the skeletal muscle, which remains largely inactive. The adaptations used to maintain these contractile organs under such variable conditions serves as a natural model to study a variety of medically relevant conditions including heart failure and disuse atrophy. To better understand how two different muscle tissues maintain function throughout the extreme fluctuations of hibernation we performed Illumina HiSeq 2000 sequencing of cDNAs to compare the transcriptome of heart and skeletal muscle across the circannual cycle. This analysis resulted in the identification of 1,076 and 1,466 differentially expressed genes in heart and skeletal muscle, respectively. In both heart and skeletal muscle we identified a distinct cold-tolerant mechanism utilizing peroxisomal metabolism to make use of elevated levels of unsaturated depot fats. The skeletal muscle transcriptome also shows an early increase in oxidative capacity necessary for the altered fuel utilization and increased oxygen demand of shivering. Expression of the fetal gene expression profile is used to maintain cardiac tissue, either through increasing myocyte size or proliferation of resident cardiomyocytes, while skeletal muscle function and mass are protected through transcriptional regulation of pathways involved in protein turnover. This study provides insight into how two functionally distinct muscles maintain function under the extreme conditions of mammalian hibernation. PMID:25572546

Aflatoxicosis chemoprevention by probiotic Lactobacillius and lack of effect on the major histocompatibility complex.

PubMed

Rawal, Sumit; Bauer, Miranda M; Mendoza, Kristelle M; El-Nezami, Hani; Hall, Jeffery R; Kim, Ji Eun; Stevens, John R; Reed, Kent M; Coulombe, Roger A

2014-10-01

Turkeys are extremely sensitive to aflatoxin B1 (AFB1) which causes decreased growth, immunosuppression and liver necrosis. The purpose of this study was to determine whether probiotic Lactobacillus, shown to be protective in animal and clinical studies, would likewise confer protection in turkeys, which were treated for 11 days with either AFB1 (AFB; 1 ppm in diet), probiotic (PB; 1 × 10(11) CFU/ml; oral, daily), probiotic + AFB1 (PBAFB), or PBS control (CNTL). The AFB1 induced drop in body and liver weights were restored to normal in CNTL and PBAFB groups. Hepatotoxicity markers were not significantly reduced by probiotic treatment. Major histocompatibility complex (MHC) genes BG1 and BG4, which are differentially expressed in liver and spleens, were not significantly affected by treatments. These data indicate modest protection, but the relatively high dietary AFB1 treatment, and the extreme sensitivity of this species may reveal limits of probiotic-based protection strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Linking Automated Data Analysis and Visualization with Applications in Developmental Biology and High-Energy Physics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruebel, Oliver

2009-11-20

Knowledge discovery from large and complex collections of today's scientific datasets is a challenging task. With the ability to measure and simulate more processes at increasingly finer spatial and temporal scales, the increasing number of data dimensions and data objects is presenting tremendous challenges for data analysis and effective data exploration methods and tools. Researchers are overwhelmed with data and standard tools are often insufficient to enable effective data analysis and knowledge discovery. The main objective of this thesis is to provide important new capabilities to accelerate scientific knowledge discovery form large, complex, and multivariate scientific data. The research coveredmore » in this thesis addresses these scientific challenges using a combination of scientific visualization, information visualization, automated data analysis, and other enabling technologies, such as efficient data management. The effectiveness of the proposed analysis methods is demonstrated via applications in two distinct scientific research fields, namely developmental biology and high-energy physics.Advances in microscopy, image analysis, and embryo registration enable for the first time measurement of gene expression at cellular resolution for entire organisms. Analysis of high-dimensional spatial gene expression datasets is a challenging task. By integrating data clustering and visualization, analysis of complex, time-varying, spatial gene expression patterns and their formation becomes possible. The analysis framework MATLAB and the visualization have been integrated, making advanced analysis tools accessible to biologist and enabling bioinformatic researchers to directly integrate their analysis with the visualization. Laser wakefield particle accelerators (LWFAs) promise to be a new compact source of high-energy particles and radiation, with wide applications ranging from medicine to physics. To gain insight into the complex physical processes of particle acceleration, physicists model LWFAs computationally. The datasets produced by LWFA simulations are (i) extremely large, (ii) of varying spatial and temporal resolution, (iii) heterogeneous, and (iv) high-dimensional, making analysis and knowledge discovery from complex LWFA simulation data a challenging task. To address these challenges this thesis describes the integration of the visualization system VisIt and the state-of-the-art index/query system FastBit, enabling interactive visual exploration of extremely large three-dimensional particle datasets. Researchers are especially interested in beams of high-energy particles formed during the course of a simulation. This thesis describes novel methods for automatic detection and analysis of particle beams enabling a more accurate and efficient data analysis process. By integrating these automated analysis methods with visualization, this research enables more accurate, efficient, and effective analysis of LWFA simulation data than previously possible.« less

How Facial Expressions in a Rett Syndrome Population Are Recognised and Interpreted by Those around Them as Conveying Emotions

ERIC Educational Resources Information Center

Bergstrom-Isacsson, Marith; Lagerkvist, Bengt; Holck, Ulla; Gold, Christian

2013-01-01

Rett syndrome (RTT) is a neurodevelopmental disorder, including autonomic nervous system dysfunctions and severe communication impairment with an extremely limited ability to use verbal language. These individuals are therefore dependent on the capacity of caregivers to observe and interpret communicative signals, including emotional expressions.…

[Influence of extremely low-frequency magnetic field on circadian rhythm of cryptochrome in mouse embryonic fibroblasts].

PubMed

Sun, Z Y; Geng, D Y; Chen, C F; Wang, P P; Song, T

2017-06-20

Objective: To investigate the influence of extremely low-frequency magnetic field on periodical expression of cryptochrome ( Cry ) gene in mouse embryonic fibroblast NIH3T3 cells. Methods: The NIH3T3 cells were divided into magnetic field group and sham-exposure group. The NIH3T3 cells in the magnetic field group were stimulated by horse serum and then exposed to an extremely low-frequency magnetic field (50 Hz and 0.3 mT) for 48 hours, and those in the sham-exposure group were also stimulated by horse serum and then exposed to a coil for 48 hours. The NIH3T3 cells were collected, total RNA was extracted, and cDNA was obtained via reverse transcription. Real-time fluorescent quantitative RT-PCR was used to measure the changes in transcription cycles of Cry and Period genes in both groups. Results: There was no significant difference in the proliferation rate at 0, 12, 24, and 48 hours of exposure between the two groups ( P >0.05) . Both sham-exposure group and magnetic field group showed a rhythmic change in the expression of Cry gene, and compared with the sham-exposure group, the magnetic field group had a significantly shortened circadian rhythm of Cry gene in NIH3T3 cells ( t =2.57, P <0.05) . Both groups had rhythmic and periodical expression of Period gene and there was no significant difference between the two groups ( t =0.70, P >0.05) . Conclusion: Extremely low-frequency magnetic field can significantly shorten the circadian rhythm of Cry gene in mouse embryonic fibroblasts, while there is no significant change in the circadian rhythm of Period gene.

Mining the LIPG Allelic Spectrum Reveals the Contribution of Rare and Common Regulatory Variants to HDL Cholesterol

PubMed Central

Raghavan, Avanthi; Neeli, Hemanth; Jin, Weijun; Badellino, Karen O.; Demissie, Serkalem; Manning, Alisa K.; DerOhannessian, Stephanie L.; Wolfe, Megan L.; Cupples, L. Adrienne; Li, Mingyao; Kathiresan, Sekar; Rader, Daniel J.

2011-01-01

Genome-wide association studies (GWAS) have successfully identified loci associated with quantitative traits, such as blood lipids. Deep resequencing studies are being utilized to catalogue the allelic spectrum at GWAS loci. The goal of these studies is to identify causative variants and missing heritability, including heritability due to low frequency and rare alleles with large phenotypic impact. Whereas rare variant efforts have primarily focused on nonsynonymous coding variants, we hypothesized that noncoding variants in these loci are also functionally important. Using the HDL-C gene LIPG as an example, we explored the effect of regulatory variants identified through resequencing of subjects at HDL-C extremes on gene expression, protein levels, and phenotype. Resequencing a portion of the LIPG promoter and 5′ UTR in human subjects with extreme HDL-C, we identified several rare variants in individuals from both extremes. Luciferase reporter assays were used to measure the effect of these rare variants on LIPG expression. Variants conferring opposing effects on gene expression were enriched in opposite extremes of the phenotypic distribution. Minor alleles of a common regulatory haplotype and noncoding GWAS SNPs were associated with reduced plasma levels of the LIPG gene product endothelial lipase (EL), consistent with its role in HDL-C catabolism. Additionally, we found that a common nonfunctional coding variant associated with HDL-C (rs2000813) is in linkage disequilibrium with a 5′ UTR variant (rs34474737) that decreases LIPG promoter activity. We attribute the gene regulatory role of rs34474737 to the observed association of the coding variant with plasma EL levels and HDL-C. Taken together, the findings show that both rare and common noncoding regulatory variants are important contributors to the allelic spectrum in complex trait loci. PMID:22174694

Expression of CD64 on Circulating Neutrophils Favoring Systemic Inflammatory Status in Erythema Nodosum Leprosum

PubMed Central

Prata, Rhana Berto da Silva; Barbosa, Mayara Garcia de Mattos; Mendes, Mayara Abud; Brandão, Sheila Santos; Amadeu, Thaís Porto; Rodrigues, Luciana Silva; Ferreira, Helen; Costa, Fabrício da Mota Ramalho; dos Santos, Jessica Brandão; Pacheco, Fabiana dos Santos; Machado, Alice de Miranda; Nery, José Augusto da Costa; Hacker, Mariana de Andrea; Sales, Anna Maria; Pinheiro, Roberta Olmo; Sarno, Euzenir Nunes

2016-01-01

Erythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates—a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably contributing to the immunopathogenesis of the disease. PMID:27556927

Expression of CD64 on Circulating Neutrophils Favoring Systemic Inflammatory Status in Erythema Nodosum Leprosum.

PubMed

Schmitz, Veronica; Prata, Rhana Berto da Silva; Barbosa, Mayara Garcia de Mattos; Mendes, Mayara Abud; Brandão, Sheila Santos; Amadeu, Thaís Porto; Rodrigues, Luciana Silva; Ferreira, Helen; Costa, Fabrício da Mota Ramalho; Dos Santos, Jessica Brandão; Pacheco, Fabiana Dos Santos; Machado, Alice de Miranda; Nery, José Augusto da Costa; Hacker, Mariana de Andrea; Sales, Anna Maria; Pinheiro, Roberta Olmo; Sarno, Euzenir Nunes

2016-08-01

Erythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates-a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably contributing to the immunopathogenesis of the disease.

An efficient tag derived from the common epitope of tospoviral NSs proteins for monitoring recombinant proteins expressed in both bacterial and plant systems.

PubMed

Cheng, Hao-Wen; Chen, Kuan-Chun; Raja, Joseph A J; Li, Jian-Xian; Yeh, Shyi-Dong

2013-04-15

NSscon (23 aa), a common epitope in the gene silencing suppressor NSs proteins of the members of the Watermelon silver mottle virus (WSMoV) serogroup, was previously identified. In this investigation, we expressed different green fluorescent protein (GFP)-fused deletions of NSscon in bacteria and reacted with NSscon monoclonal antibody (MAb). Our results indicated that the core 9 amino acids, "(109)KFTMHNQIF(117)", denoted as "nss", retain the reactivity of NSscon. In bacterial pET system, four different recombinant proteins labeled with nss, either at N- or C-extremes, were readily detectable without position effects, with sensitivity superior to that for the polyhistidine-tag. When the nss-tagged Zucchini yellow mosaic virus (ZYMV) helper component-protease (HC-Pro) and WSMoV nucleocapsid protein were transiently expressed by agroinfiltration in tobacco, they were readily detectable and the tag's possible efficacy for gene silencing suppression was not noticed. Co-immunoprecipitation of nss-tagged and non-tagged proteins expressed from bacteria confirmed the interaction of potyviral HC-Pro and coat protein. Thus, we conclude that this novel nss sequence is highly valuable for tagging recombinant proteins in both bacterial and plant expression systems. Copyright © 2013 Elsevier B.V. All rights reserved.

Role of the glucocorticoid-induced TNFR-related protein (GITR)-GITR ligand pathway in innate and adaptive immunity.

PubMed

Azuma, Miyuki

2010-01-01

Glucocorticoid-induced TNF receptor-related protein (GITR) is expressed in regulatory T cells at high levels, but is also inducible in conventional effector T cells after activation. Initial studies using an agonistic anti- GITR mAb mislead this line of research with respect to the contribution of GITR stimulation on the function of regulatory T cells. In fact, GITR acts as a costimulatory receptor for both effector and regulatory T cells by enhancing effector and regulatory functions, respectively. Unlike other costimulatory ligands, GITR ligand (GITRL) expression on mature myeloid dendritic cells (DCs) is extremely limited and the GITR-GITRL pathway does not contribute markedly to direct interactions with T cells and antigen-presenting cells in the secondary lymphoid tissues. Rather, GITRL is constitutively expressed on parenchymal tissue cells and interacts with GITR expressed on tissue-infiltrating macrophages and DCs, or effector and regulatory T cells. Interactions with GITR and GITRL at local inflammatory sites induce site-specific production of cytokines and chemokines, resulting in control activation of tissue-infiltrating effector or regulatory cells and their migration. This review summarizes recent reports on the GITR-GITRL pathway, which controls both innate and adaptive immune responses.

Relevance Vector Machine Learning for Neonate Pain Intensity Assessment Using Digital Imaging

PubMed Central

Gholami, Behnood; Tannenbaum, Allen R.

2011-01-01

Pain assessment in patients who are unable to verbally communicate is a challenging problem. The fundamental limitations in pain assessment in neonates stem from subjective assessment criteria, rather than quantifiable and measurable data. This often results in poor quality and inconsistent treatment of patient pain management. Recent advancements in pattern recognition techniques using relevance vector machine (RVM) learning techniques can assist medical staff in assessing pain by constantly monitoring the patient and providing the clinician with quantifiable data for pain management. The RVM classification technique is a Bayesian extension of the support vector machine (SVM) algorithm, which achieves comparable performance to SVM while providing posterior probabilities for class memberships and a sparser model. If classes represent “pure” facial expressions (i.e., extreme expressions that an observer can identify with a high degree of confidence), then the posterior probability of the membership of some intermediate facial expression to a class can provide an estimate of the intensity of such an expression. In this paper, we use the RVM classification technique to distinguish pain from nonpain in neonates as well as assess their pain intensity levels. We also correlate our results with the pain intensity assessed by expert and nonexpert human examiners. PMID:20172803

Carcinoma ex basal cell adenoma of the parotid gland: A report of an extremely rare case.

PubMed

Kusafuka, Kimihide; Kawasaki, Takuya; Nakajima, Takashi; Sugino, Takashi

2017-07-01

Malignant non-basaloid tumors that arise from basal cell adenoma (BCA) are extremely rare. The patient was a 72-year-old Japanese male, who had noticed swelling of the left parotid region 21 years ago. A superficial lobectomy was performed. About 60% of the tumor was made up of cribriform and trabecular tissue composed of basaloid cells, which exhibited mild atypia and nuclear expression of β-catenin. This portion of the tumor was considered to be a BCA. In the other part of the tumor, the proliferation of large eosinophilic atypical cells, most of which formed intraductal structures, was observed. These tumor cells displayed cellular atypia, and some of them formed Roman bridge structures or contributed to intracapsular invasion. Immunohistochemically, these cells were positive for cytokeratin 7, gross cystic disease fluid proten-15 (GCDFP-15), androgen receptor (AR), and mammaglobin (MMG) and exhibited a high Ki-67 labeling index. So, this portion of the tumor was considered to be a salivary duct carcinoma (SDC). The tumor's final diagnosis was SDC ex BCA (intracapsular type), which is extremely rare. GCDFP-15, AR, MMG, and Ki-67 are useful immunohistochemical markers for diagnosing SDC ex BCA. © 2017 The Authors. Pathology International Published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Terbium(III) Modified Fluorescent Carbon Dots for Highly Selective and Sensitive Ratiometry of Stringent.

PubMed

Chen, Bin Bin; Liu, Meng Li; Zhan, Lei; Li, Chun Mei; Huang, Cheng Zhi

2018-03-20

Highly selective and sensitive detection of guanosine 3'-diphosphate-5'-diphosphate (ppGpp), namely, the stringent in plants or microorganisms responding to strict or extreme environmental conditions such as stress and starvation, which plays an important role in gene expression, rRNA and antibiotics production, regulations of virulence of bacteria, and growth of plants, faces a great challenge owing to its extreme similarity to normal nucleotides. By modifying the surface groups of a facile two-step hydrothermal route prepared carbon dots (CDs) with terbium ions (Tb 3+ ) in this contribution, a novel fluorescent probe with excellent properties such as highly physical and chemical stability, narrow emission and excitation wavelength-independent emission was prepared. The Tb 3+ ions on the surface of CDs cannot only preserve the intrinsic fluorescence (FL) of CDs but also keep its own coordination capacity with rare earth complex, and thus the clamp structure (four phosphate groups) of ppGpp can specific binding with Tb 3+ ions on the surface of CDs to produce antenna effect. Therefore, a highly selective and sensitive fluorescent ratiometry of ppGpp was developed by terbium-modified carbon dots (CDs-Tb) with the limit of detection as low as 50 nM based on the synergistic effect of antenna effect of Tb 3+ ions and specific recognition capacity of CDs. The applicability of this assay was demonstrated by CDs-Tb-based paper sensor for high distinguishing ppGpp from other nucleotides with similar structure.

Sex differences in autism: a resting-state fMRI investigation of functional brain connectivity in males and females

PubMed Central

Swinnen, Stephan P.; Wenderoth, Nicole

2016-01-01

Autism spectrum disorders (ASD) are far more prevalent in males than in females. Little is known however about the differential neural expression of ASD in males and females. We used a resting-state fMRI-dataset comprising 42 males/42 females with ASD and 75 male/75 female typical-controls to examine whether autism-related alterations in intrinsic functional connectivity are similar or different in males and females, and particularly whether alterations reflect ‘neural masculinization’, as predicted by the Extreme Male Brain theory. Males and females showed a differential neural expression of ASD, characterized by highly consistent patterns of hypo-connectivity in males with ASD (compared to typical males), and hyper-connectivity in females with ASD (compared to typical females). Interestingly, patterns of hyper-connectivity in females with ASD reflected a shift towards the (high) connectivity levels seen in typical males (neural masculinization), whereas patterns of hypo-connectivity observed in males with ASD reflected a shift towards the (low) typical feminine connectivity patterns (neural feminization). Our data support the notion that ASD is a disorder of sexual differentiation rather than a disorder characterized by masculinization in both genders. Future work is needed to identify underlying factors such as sex hormonal alterations that drive these sex-specific neural expressions of ASD. PMID:26989195

Association of extremely high levels of high-density lipoprotein cholesterol with cardiovascular mortality in a pooled analysis of 9 cohort studies including 43,407 individuals: The EPOCH-JAPAN study.

PubMed

Hirata, Aya; Sugiyama, Daisuke; Watanabe, Makoto; Tamakoshi, Akiko; Iso, Hiroyasu; Kotani, Kazuhiko; Kiyama, Masahiko; Yamada, Michiko; Ishikawa, Shizukiyo; Murakami, Yoshitaka; Miura, Katsuyuki; Ueshima, Hirotsugu; Okamura, Tomonori

2018-02-08

The effect of very high or extremely high levels of high-density lipoprotein cholesterol (HDL-C) on cardiovascular disease (CVD) is not well described. Although a few recent studies have reported the adverse effects of extremely high levels of HDL-C on CVD events, these did not show a statistically significant association between extremely high levels of HDL-C and cause-specific CVD mortality. In addition, Asian populations have not been studied. We examine the impact of extremely high levels of HDL-C on cause-specific CVD mortality using pooled data of Japanese cohort studies. We performed a large-scale pooled analysis of 9 Japanese cohorts including 43,407 participants aged 40-89 years, dividing the participants into 5 groups by HDL-C levels, including extremely high levels of HDL-C ≥2.33 mmol/L (≥90 mg/dL). We estimated the adjusted hazard ratio of each HDL-C category for all-cause death and cause-specific deaths compared with HDL-C 1.04-1.55 mmol/L (40-59 mg/dL) using a cohort-stratified Cox proportional hazards model. During a 12.1-year follow-up, 4995 all-cause deaths and 1280 deaths due to overall CVD were identified. Extremely high levels of HDL-C were significantly associated with increased risk of atherosclerotic CVD mortality (hazard ratio = 2.37, 95% confidence interval: 1.37-4.09 for total) and increased risk for coronary heart disease and ischemic stroke. In addition, the risk for extremely high HDL-C was more evident among current drinkers. We showed extremely high levels of HDL-C had an adverse effect on atherosclerotic CVD mortality in a pooled analysis of Japanese cohorts. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Microbial Fuel Cells under Extreme Salinity

NASA Astrophysics Data System (ADS)

Monzon del Olmo, Oihane

I developed a Microbial Fuel Cell (MFC) that unprecedentedly works (i.e., produces electricity) under extreme salinity (≈ 100 g/L NaCl). Many industries, such as oil and gas extraction, generate hypersaline wastewaters with high organic strength, accounting for about 5% of worldwide generated effluents, which represent a major challenge for pollution control and resource recovery. This study assesses the potential for microbial fuel cells (MFCs) to treat such wastewaters and generate electricity under extreme saline conditions. Specifically, the focus is on the feasibility to treat hypersaline wastewater generated by the emerging unconventional oil and gas industry (hydraulic fracturing) and so, with mean salinity of 100 g/L NaCl (3-fold higher than sea water). The success of this novel technology strongly depends on finding a competent and resilient microbial community that can degrade the waste under extreme saline conditions and be able to use the anode as their terminal electron acceptor (exoelectrogenic capability). I demonstrated that MFCs can produce electricity at extremely high salinity (up to 250 g/l NaCl) with a power production of 71mW/m2. Pyrosequencing analysis of the anode population showed the predominance of Halanaerobium spp. (85%), which has been found in shale formations and oil reservoirs. Promoting Quorum sensing (QS, cell to cell communication between bacteria to control gene expression) was used as strategy to increase the attachment of bacteria to the anode and thus improve the MFC performance. Results show that the power output can be bolstered by adding 100nM of quinolone signal with an increase in power density of 30%, for the first time showing QS in Halanaerobium extremophiles. To make this technology closer to market applications, experiments with real wastewaters were also carried out. A sample of produced wastewater from Barnet Shale, Texas (86 g/L NaCl) produced electricity when fed in an MFC, leading to my discovery of another predominant electroactive and halophile specie in the anode, Marinobacter hydrocarbonoclasticus, which is known for its extraordinary biodegradation capabilities. These findings suggest the potential of the MFC technology to treat hypersaline high-strength wastewaters while producing electricity, a result which would alleviate a major economic and environmental challenge for the oil and gas industry. In addition, this research represents a promising start overall in advancing biological treatment of saline wastewaters in other contexts, which is a largely unexploited field.

Establishment of two basal-like breast cancer cell lines with extremely low tumorigenicity from Taiwanese premenopausal women.

PubMed

Kuo, Wen-Ling; Ueng, Shir-Hwa; Wu, Chun-Hsing; Lee, Li-Yu; Lee, Yun-Shien; Yu, Ming-Chin; Chen, Shin-Cheh; Yu, Chi-Chang; Tsai, Chi-Neu

2018-04-01

The research of carcinogenetic mechanisms of breast cancer in different ethnic backgrounds is an interesting field, as clinical features of breast cancers vary among races. High premenopausal incidence is distinctive in East-Asian breast cancer. However, human cell lines derived from Asian primary breast tumor are rare. To provide alternative cell line models with a relevant genetic background, we aimed to establish breast cancer cell lines from Taiwanese patients of Han-Chinese ethnicity. Fresh tissue from mammary tumors were digested into organoids, plated and grown in basal serum-free medium of human mammary epithelial cells (HuMEC) with supplements. Cells were further enriched by positive selection with CD326 (epithelial cell adhesion molecule; EpCAM)-coated micro-magnetic beads. Two breast cancer cell lines derived from premenopausal women were successfully established by this method, and named Chang-Gung Breast Cancer 01 (CGBC 01) and 02 (CGBC 02). These two cell lines had a similar phenotype with weak expression of estrogen receptor (ER), progesterone receptor (PR), and without amplification of receptor tyrosine protein kinase erbB-2 (HER2/neu). Genome-wide Single Nucleotide Polymorphism (SNP) array showed multiple copy number alterations in both cell lines. Based on gene expression profiles, CGBC 01 and 02 were clustered into basal-like subtype with reference to the breast cancer cell line gene expression database. The tumorigenicity of both cell lines was extremely low in both anchorage-independence assay and transplantation into the mammary fat pads of nude mice. CGBC 01 and CGBC 02 are low tumorigenic breast cancer cell lines, established from Han-Chinese premenopausal breast cancer patients, which serve as in vitro models in studying the biological features of Asian breast cancer.

Developmental temperature affects the expression of ejaculatory traits and the outcome of sperm competition in Callosobruchus maculatus.

PubMed

Vasudeva, R; Deeming, D C; Eady, P E

2014-09-01

The outcome of post-copulatory sexual selection is determined by a complex set of interactions between the primary reproductive traits of two or more males and their interactions with the reproductive traits of the female. Recently, a number of studies have shown the primary reproductive traits of both males and females express phenotypic plasticity in response to the thermal environment experienced during ontogeny. However, how plasticity in these traits affects the dynamics of sperm competition remains largely unknown. Here, we demonstrate plasticity in testes size, sperm size and sperm number in response to developmental temperature in the bruchid beetle Callosobruchus maculatus. Males reared at the highest temperature eclosed at the smallest body size and had the smallest absolute and relative testes size. Males reared at both the high- and low-temperature extremes produced both fewer and smaller sperm than males reared at intermediate temperatures. In the absence of sperm competition, developmental temperature had no effect on male fertility. However, under conditions of sperm competition, males reared at either temperature extreme were less competitive in terms of sperm offence (P(2)), whereas those reared at the lowest temperature were less competitive in terms of sperm defence (P(1)). This suggests the developmental pathways that regulate the phenotypic expression of these ejaculatory traits are subject to both natural and sexual selection: natural selection in the pre-ejaculatory environment and sexual selection in the post-ejaculatory environment. In nature, thermal heterogeneity during development is commonplace. Therefore, we suggest the interplay between ecology and development represents an important, yet hitherto underestimated component of male fitness via post-copulatory sexual selection. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Experimental neuropharmacology of Gelsemium sempervirens: Recent advances and debated issues.

PubMed

Bellavite, Paolo; Bonafini, Clara; Marzotto, Marta

Gelsemium sempervirens L. (Gelsemium) is traditionally used for its anxiolytic-like properties and its action mechanism in laboratory models are under scrutiny. Evidence from rodent models was reported suggesting the existence of a high sensitivity of central nervous system to anxiolytic power of Gelsemium extracts and Homeopathic dilutions. In vitro investigation of extremely low doses of this plant extract showed a modulation of gene expression of human neurocytes. These studies were criticized in a few commentaries, generated a debate in literature and were followed by further experimental studies from various laboratories. Toxic doses of Gelsemium cause neurological signs characterized by marked weakness and convulsions, while ultra-low doses or high Homeopathic dilutions counteract seizures induced by lithium and pilocarpine, decrease anxiety after stress and increases the anti-stress allopregnanolone hormone, through glycine receptors. Low (non-Homeopathic) doses of this plant or its alkaloids decrease neuropathic pain and c-Fos expression in mice brain and oxidative stress. Due to the complexity of the matter, several aspects deserve interpretation and the main controversial topics, with a focus on the issues of high dilution pharmacology, are discussed and clarified. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

Anti-inflammatory activity of horseradish (Armoracia rusticana) root extracts in LPS-stimulated macrophages.

PubMed

Marzocco, Stefania; Calabrone, Luana; Adesso, Simona; Larocca, Marilena; Franceschelli, Silvia; Autore, Giuseppina; Martelli, Giuseppe; Rossano, Rocco

2015-12-01

Horseradish (Armoracia rusticana) is a perennial crop belonging to the Brassicaceae family. Horseradish root is used as a condiment due to its extremely pungent flavour, deriving from the high content of glucosinolates and their breakdown products such as isothiocyanates and other sulfur compounds. Horseradish also has a long history in ethnomedicine. In this study the anti-inflammatory potential of three accessions of Armoracia rusticana on lipopolysaccharide from E. coli treated J774A.1 murine macrophages was evaluated. Our results demonstrate that Armoracia rusticana reduced nitric oxide, tumor necrosis factor-α and interleukin-6 release and nitric oxide synthase and cyclooxygenase-2 expression in macrophages, acting on nuclear transcription factor NF-κB p65 activation. Moreover Armoracia rusticana reduced reactive oxygen species release and increased heme-oxygenase-1 expression, thus contributing to the cytoprotective cellular effect during inflammation.

Simulating the Pineapple Express in the half degree Community Climate System Model, CCSM4

NASA Astrophysics Data System (ADS)

Shields, Christine A.; Kiehl, Jeffrey T.

2016-07-01

Atmospheric rivers are recognized as major contributors to the poleward transport of water vapor. Upon reaching land, these phenomena also play a critical role in extreme precipitation and flooding events. The Pineapple Express (PE) is defined as an atmospheric river extending out of the deep tropics and reaching the west coast of North America. Community Climate System Model (CCSM4) high-resolution ensemble simulations for the twentieth and 21st centuries are diagnosed to identify the PE. Analysis of the twentieth century simulations indicated that the CCSM4 accurately captures the spatial and temporal climatology of the PE. Analysis of the end 21st century simulations indicates a significant increase in storm duration and intensity of precipitation associated with landfall of the PE. Only a modest increase in the number of atmospheric rivers of a few percent is projected for the end of 21st century.

[Neurological adaptations to hypoxia in Tibetan antelope (Pantholops hodgsonii) with a view of molecular biology of respiratory globin-neuroglobin].

PubMed

Bai, Zhen-Zhong; Yang, Ying-Zhong; Jin, Guo-En; Ma, Lan; Ge, Ri-Li

2012-11-01

Neuroglobin (Ngb) is a respiratory protein that is preferentially expressed in brain of mouse and man. In this article, Tibetan antelope, living at altitude of 3 000-5 000 m for millions of years, was selected as the model of hypoxia-tolerant adaptation species. Using reverse transcription polymerase chain reaction (RT-PCR) and Western blot techniques, expression of Ngb gene was amplified and analyzed in antelope brain tissue. Our results showed that Ngb homology protein in Tibetan antelope was identified with more sequence similarity with cattle (96%), sheep (95%), and human (95%). We detected that there were some mutations occurred in the Open Reading Frame of Ngb in Tibetan antelope compared with sheep. Phylogenetic analysis of Ngb chain showed that it was closer to cattle than the others. This study suggests possible roles of central nervous system enriched Ngb in adaptation of Tibetan antelope to extremely high altitude.

Overexpression of Three Heat Shock Proteins Protects Monochamus alternatus (Coleoptera: Cerambycidae) From Thermal Stress

PubMed Central

Cai, Ziling; Chen, Jingxiang; Cheng, Jie

2017-01-01

Abstract Ambient temperature is an important factor limiting the abundance and distribution of insects, and heat shock protein (Hsp) gene expression is sensitive to extremes of cold and heat. In order to explore the role of Hsps during thermal stress and development in Monochamus alternatus Hope (Coleoptera: Cerambycidae), we cloned and characterized full-length Hsp genes, including MaHsp60, MaHsp70, and MaHsp90. M. alternatus were exposed to different temperatures (−15, −5, 5, 15, 25, 35, and 40℃) for 1 h and was allowed to recover at 25℃ for 1 h. Following the treatments, we investigated the expression of the Hsps by quantitative real-time polymerase chain reaction. In third instar larvae, MaHsp60, MaHsp70, and MaHsp90 expression was upregulated in response to cold and heat, but the three Hsps were especially sensitive to heat, specifically at 35℃ and 40℃. After heating M. alternatus to 35℃, the expression of MaHsp60, MaHsp70, and MaHsp90 was higher than at 5℃ and 25℃ in nearly all developmental stages. MaHsp60, MaHsp70, and MaHsp90 expression was highest in later pupal, early adult, and early adult stages, respectively. These results suggest that compared with normal ambient temperatures, thermal stress could induce high expression of the three Hsps.

Separating out the influence of climatic trend, fluctuations, and extreme events on crop yield: a case study in Hunan Province, China

NASA Astrophysics Data System (ADS)

Wang, Zhu; Shi, Peijun; Zhang, Zhao; Meng, Yongchang; Luan, Yibo; Wang, Jiwei

2017-09-01

Separating out the influence of climatic trend, fluctuations and extreme events on crop yield is of paramount importance to climate change adaptation, resilience, and mitigation. Previous studies lack systematic and explicit assessment of these three fundamental aspects of climate change on crop yield. This research attempts to separate out the impacts on rice yields of climatic trend (linear trend change related to mean value), fluctuations (variability surpassing the "fluctuation threshold" which defined as one standard deviation (1 SD) of the residual between the original data series and the linear trend value for each climatic variable), and extreme events (identified by absolute criterion for each kind of extreme events related to crop yield). The main idea of the research method was to construct climate scenarios combined with crop system simulation model. Comparable climate scenarios were designed to express the impact of each climate change component and, were input to the crop system model (CERES-Rice), which calculated the related simulated yield gap to quantify the percentage impacts of climatic trend, fluctuations, and extreme events. Six Agro-Meteorological Stations (AMS) in Hunan province were selected to study the quantitatively impact of climatic trend, fluctuations and extreme events involving climatic variables (air temperature, precipitation, and sunshine duration) on early rice yield during 1981-2012. The results showed that extreme events were found to have the greatest impact on early rice yield (-2.59 to -15.89%). Followed by climatic fluctuations with a range of -2.60 to -4.46%, and then the climatic trend (4.91-2.12%). Furthermore, the influence of climatic trend on early rice yield presented "trade-offs" among various climate variables and AMS. Climatic trend and extreme events associated with air temperature showed larger effects on early rice yield than other climatic variables, particularly for high-temperature events (-2.11 to -12.99%). Finally, the methodology use to separate out the influences of the climatic trend, fluctuations, and extreme events on crop yield was proved to be feasible and robust. Designing different climate scenarios and feeding them into a crop system model is a potential way to evaluate the quantitative impact of each climate variable.

Salinity-related variation in gene expression in wild populations of the black-chinned tilapia from various West African coastal marine, estuarine and freshwater habitats

NASA Astrophysics Data System (ADS)

Tine, Mbaye; McKenzie, David J.; Bonhomme, François; Durand, Jean-Dominique

2011-01-01

This study measured the relative expression of the genes coding for Na +, K +-ATPase 1α(NAKA), voltage-dependent anion channel (VDAC), cytochrome c oxidase-1 (COX), and NADH dehydrogenase (NDH), in gills of six wild populations of a West African tilapia species, acclimatised to a range of seasonal (rainy or dry) salinities in coastal, estuarine and freshwater sites. Previous laboratory experiments have demonstrated that these genes, involved in active ion transport, oxidative phosphorylation, and intra-cellular ATP transport, are relatively over-expressed in gill tissues of this species acclimated to high salinity. Positive correlations between relative expression and ambient salinity were found for all genes in the wild populations (Spearman rank correlation, p < 0.05), although for some genes these were only significant in either the rainy season or dry season. Most significantly, however, relative expression was positively correlated amongst the four genes, indicating that they are functionally interrelated in adaptation of Sarotherodon melanotheron to salinity variations in its natural environment. In the rainy season, when salinity was unstable and ranged between zero and 37 psu across the sites, overall mean expression of the genes was higher than in the dry season, which may have reflected more variable particularly sudden fluctuations in salinity and poorer overall water quality. In the dry season, when the salinity is more stable but ranged between zero and 100 psu across the sites, NAKA, NDH and VDAC expression revealed U-shaped relationships with lowest relative expression at salinities approaching seawater, between 25 and 45 psu. Although it is not simple to establish direct relationship between gene expression levels and energy requirement for osmoregulation, these results may indicate that costs of adaptation to salinity are lowest in seawater, the natural environment of this species. While S. melanotheron can colonise environments with extremely high salinities, up to 100 psu, this was related to high relative expression for all genes studied, indicating that this imposes increased energy demand for osmotic homeostasis in gill tissues. This study is the first to demonstrate, in fish and in wild populations, that expression of NAKA, VDAC, NDH and COX are interrelated in gill tissues, and are involved in long-term acclimatisation to a salinity range between 0 and 100 psu.

Transcriptome Sequencing Identified Genes and Gene Ontologies Associated with Early Freezing Tolerance in Maize

PubMed Central

Li, Zhao; Hu, Guanghui; Liu, Xiangfeng; Zhou, Yao; Li, Yu; Zhang, Xu; Yuan, Xiaohui; Zhang, Qian; Yang, Deguang; Wang, Tianyu; Zhang, Zhiwu

2016-01-01

Originating in a tropical climate, maize has faced great challenges as cultivation has expanded to the majority of the world's temperate zones. In these zones, frost and cold temperatures are major factors that prevent maize from reaching its full yield potential. Among 30 elite maize inbred lines adapted to northern China, we identified two lines of extreme, but opposite, freezing tolerance levels—highly tolerant and highly sensitive. During the seedling stage of these two lines, we used RNA-seq to measure changes in maize whole genome transcriptome before and after freezing treatment. In total, 19,794 genes were expressed, of which 4550 exhibited differential expression due to either treatment (before or after freezing) or line type (tolerant or sensitive). Of the 4550 differently expressed genes, 948 exhibited differential expression due to treatment within line or lines under freezing condition. Analysis of gene ontology found that these 948 genes were significantly enriched for binding functions (DNA binding, ATP binding, and metal ion binding), protein kinase activity, and peptidase activity. Based on their enrichment, literature support, and significant levels of differential expression, 30 of these 948 genes were selected for quantitative real-time PCR (qRT-PCR) validation. The validation confirmed our RNA-Seq-based findings, with squared correlation coefficients of 80% and 50% in the tolerance and sensitive lines, respectively. This study provided valuable resources for further studies to enhance understanding of the molecular mechanisms underlying maize early freezing response and enable targeted breeding strategies for developing varieties with superior frost resistance to achieve yield potential. PMID:27774095

Production of halophilic proteins using Haloferax volcanii H1895 in a stirred-tank bioreactor.

PubMed

Strillinger, Eva; Grötzinger, Stefan Wolfgang; Allers, Thorsten; Eppinger, Jörg; Weuster-Botz, Dirk

2016-02-01

The success of biotechnological processes is based on the availability of efficient and highly specific biocatalysts, which can satisfy industrial demands. Extreme and remote environments like the deep brine pools of the Red Sea represent highly interesting habitats for the discovery of novel halophilic and thermophilic enzymes. Haloferax volcanii constitutes a suitable expression system for halophilic enzymes obtained from such brine pools. We developed a batch process for the cultivation of H. volcanii H1895 in controlled stirred-tank bioreactors utilising knockouts of components of the flagella assembly system. The standard medium Hv-YPC was supplemented to reach a higher cell density. Without protein expression, cell dry weight reaches 10 g L(-1). Two halophilic alcohol dehydrogenases were expressed under the control of the tryptophanase promoter p.tna with 16.8 and 3.2 mg gCDW (-1), respectively, at a maximum cell dry weight of 6.5 g L(-1). Protein expression was induced by the addition of L-tryptophan. Investigation of various expression strategies leads to an optimised two-step induction protocol introducing 6 mM L-tryptophan at an OD650 of 0.4 followed by incubation for 16 h and a second induction step with 3 mM L-tryptophan followed by a final incubation time of 4 h. Compared with the uncontrolled shaker-flask cultivations used until date, dry cell mass concentrations were improved by a factor of more than 5 and cell-specific enzyme activities showed an up to 28-fold increased yield of the heterologous proteins.

Glucose metabolism and gene expression in juvenile zebrafish (Danio rerio) challenged with a high carbohydrate diet: effects of an acute glucose stimulus during late embryonic life.

PubMed

Rocha, Filipa; Dias, Jorge; Engrola, Sofia; Gavaia, Paulo; Geurden, Inge; Dinis, Maria Teresa; Panserat, Stephane

2015-02-14

Knowledge on the role of early nutritional stimuli as triggers of metabolic pathways in fish is extremely scarce. The objective of the present study was to assess the long-term effects of glucose injection in the yolk (early stimulus) on carbohydrate metabolism and gene regulation in zebrafish juveniles challenged with a high-carbohydrate low-protein (HC) diet. Eggs were microinjected at 1 d post-fertilisation (dpf) with either glucose (2 M) or saline solutions. Up to 25 dpf, fish were fed a low-carbohydrate high-protein (LC) control diet, which was followed by a challenge with the HC diet. Survival and growth of 35 dpf juveniles were not affected by injection or the HC diet. Glucose stimulus induced some long-term metabolic changes in the juveniles, as shown by the altered expression of genes involved in glucose metabolism. On glycolysis, the expression levels of hexokinase 1 (HK1) and phosphofructokinase-6 (6PFK) were up-regulated in the visceral and muscle tissues, respectively, of juveniles exposed to the glucose stimulus, indicating a possible improvement in glucose oxidation. On gluconeogenesis, the inhibition of the expression levels of PEPCK in fish injected with glucose suggested lower production of hepatic glucose. Unexpectedly, fructose-1,6-bisphosphatase (FBP) expression was induced and 6PFK expression reduced by glucose stimulus, leaving the possibility of a specific regulation of the FBP-6PFK metabolic cycle. Glucose metabolism in juveniles was estimated using a [¹⁴C]glucose tracer; fish previously exposed to the stimulus showed lower retention of [¹⁴C]glucose in visceral tissue (but not in muscle tissue) and, accordingly, higher glucose catabolism, in comparison with the saline group. Globally, our data suggest that glucose stimulus at embryo stage has the potential to alter particular steps of glucose metabolism in zebrafish juveniles.

SpoVT: From Fine-Tuning Regulator in Bacillus subtilis to Essential Sporulation Protein in Bacillus cereus

PubMed Central

Eijlander, Robyn T.; Holsappel, Siger; de Jong, Anne; Ghosh, Abhinaba; Christie, Graham; Kuipers, Oscar P.

2016-01-01

Sporulation is a highly sophisticated developmental process adopted by most Bacilli as a survival strategy to withstand extreme conditions that normally do not support microbial growth. A complicated regulatory cascade, divided into various stages and taking place in two different compartments of the cell, involves a number of primary and secondary regulator proteins that drive gene expression directed toward the formation and maturation of an endospore. Such regulator proteins are highly conserved among various spore formers. Despite this conservation, both regulatory and phenotypic differences are observed between different species of spore forming bacteria. In this study, we demonstrate that deletion of the regulatory sporulation protein SpoVT results in a severe sporulation defect in Bacillus cereus, whereas this is not observed in Bacillus subtilis. Although spores are initially formed, the process is stalled at a later stage in development, followed by lysis of the forespore and the mother cell. A transcriptomic investigation of B. cereus ΔspoVT shows upregulation of genes involved in germination, potentially leading to premature lysis of prespores formed. Additionally, extreme variation in the expression of species-specific genes of unknown function was observed. Introduction of the B. subtilis SpoVT protein could partly restore the sporulation defect in the B. cereus spoVT mutant strain. The difference in phenotype is thus more than likely explained by differences in promoter targets rather than differences in mode of action of the conserved SpoVT regulator protein. This study stresses that evolutionary variances in regulon members of sporulation regulators can have profound effects on the spore developmental process and that mere protein homology is not a foolproof predictor of similar phenotypes. PMID:27790204

SpoVT: From Fine-Tuning Regulator in Bacillus subtilis to Essential Sporulation Protein in Bacillus cereus.

PubMed

Eijlander, Robyn T; Holsappel, Siger; de Jong, Anne; Ghosh, Abhinaba; Christie, Graham; Kuipers, Oscar P

2016-01-01

Sporulation is a highly sophisticated developmental process adopted by most Bacilli as a survival strategy to withstand extreme conditions that normally do not support microbial growth. A complicated regulatory cascade, divided into various stages and taking place in two different compartments of the cell, involves a number of primary and secondary regulator proteins that drive gene expression directed toward the formation and maturation of an endospore. Such regulator proteins are highly conserved among various spore formers. Despite this conservation, both regulatory and phenotypic differences are observed between different species of spore forming bacteria. In this study, we demonstrate that deletion of the regulatory sporulation protein SpoVT results in a severe sporulation defect in Bacillus cereus , whereas this is not observed in Bacillus subtilis . Although spores are initially formed, the process is stalled at a later stage in development, followed by lysis of the forespore and the mother cell. A transcriptomic investigation of B. cereus Δ spoVT shows upregulation of genes involved in germination, potentially leading to premature lysis of prespores formed. Additionally, extreme variation in the expression of species-specific genes of unknown function was observed. Introduction of the B. subtilis SpoVT protein could partly restore the sporulation defect in the B. cereus spoVT mutant strain. The difference in phenotype is thus more than likely explained by differences in promoter targets rather than differences in mode of action of the conserved SpoVT regulator protein. This study stresses that evolutionary variances in regulon members of sporulation regulators can have profound effects on the spore developmental process and that mere protein homology is not a foolproof predictor of similar phenotypes.

Identification of biochemical adaptations in hyper- or hypocontractile hearts from phospholamban mutant mice by expression proteomics.

PubMed

Pan, Yan; Kislinger, Thomas; Gramolini, Anthony O; Zvaritch, Elena; Kranias, Evangelia G; MacLennan, David H; Emili, Andrew

2004-02-24

Phospholamban (PLN) is a critical regulator of cardiac contractility through its binding to and regulation of the activity of the sarco(endo)plasmic reticulum Ca2+ ATPase. To uncover biochemical adaptations associated with extremes of cardiac muscle contractility, we used high-throughput gel-free tandem MS to monitor differences in the relative abundance of membrane proteins in standard microsomal fractions isolated from the hearts of PLN-null mice (PLN-KO) with high contractility and from transgenic mice overexpressing a superinhibitory PLN mutant in a PLN-null background (I40A-KO) with diminished contractility. Significant differential expression was detected for a subset of the 782 proteins identified, including known membrane-associated biomarkers, components of signaling pathways, and previously uninvestigated proteins. Proteins involved in fat and carbohydrate metabolism and proteins linked to G protein-signaling pathways activating protein kinase C were enriched in I40A-KO cardiac muscle, whereas proteins linked to enhanced contractile function were enriched in PLN-KO mutant hearts. These data demonstrate that Ca2+ dysregulation, leading to elevated or depressed cardiac contractility, induces compensatory biochemical responses.

Overexpression of MTA1 and loss of KAI-1 and KiSS-1 expressions are associated with invasion, metastasis, and poor-prognosis of gallbladder adenocarcinoma.

PubMed

Wang, Wenjun; Yang, Zhu-lin; Liu, Jie-qiong; Yang, Le-ping; Yang, Xiao-jing; Fu, Xi

2014-01-01

Over 90% of patients with gallbladder cancer have invasion and/or metastasis when they are diagnosed at the clinic. Such patients usually have an extremely poor prognosis. The molecular mechanism responsible for the high prevalence of invasion and metastasis remains unknown. We investigated the expression of two metastasis-suppression genes--KAI-1 and KiSS-1--and a metastasis-associated gene--MTA1--in 108 adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using in situ hybridization or immunohistochemistry. We demonstrated that positive MTA1 expression was significantly higher whereas positive expressions of KAI-1 and KiSS-1 genes were significantly lower in gallbladder adenocarcinoma than in peritumoral tissues, polyps, and chronic cholecystitis. Positive MTA1 expression was significantly lower, but positive KAI-1 and KiSS-1 expressions were significantly higher in cases with well-differentiated adenocarcinoma, smaller tumor mass, no metastasis of lymph node, and no invasion of regional tissues than in cases having poorly differentiated adenocarcinoma, larger tumor mass, metastasis and invasion. Univariate Kaplan-Meier analysis showed that increased expression of MTA1 and lowered expression of KAI-1 and KiSS-1 were significantly associated with decreased overall survival. Cox regression analysis showed that tumor mass, lymph node metastasis, invasion, and MTA1 expression levels negatively correlated with survival. Our study suggested that KAI-1, KiSS-1, and MTA1 might be important biological markers involved in the carcinogenesis, metastasis, and invasion of gallbladder adenocarcinoma, but MTA1 is an independent factor of prognosis.

Which Social Elements Are Visible in Virtual Groups? Addressing the Categorization of Social Expressions

ERIC Educational Resources Information Center

Perez-Mateo, M.; Guitert, M.

2012-01-01

Learning is a social process. That is why it is extremely important to understand how students interact socially in online courses and how it affects the learning process. However, social aspects, understood as those expressions or comments that go beyond strictly academic interaction, i.e. the need to carry out group work, are not clearly…

Exacerbation of liver steatosis following exposure to famine and overnutrition.

PubMed

Ning, Zhiyuan; Zhang, Kun; Zhao, Li; Lu, You; Sun, Honglin; Chen, Chi; Nie, Xiaomin; Lu, Meng; Wang, Ningjian; Lu, Yingli

2017-10-01

People suffering from famine in early life and overnutrition in adulthood may have an increased risk for liver steatosis. We aimed to investigate the effects and mechanisms of early nutrition restriction and overnutrition on de novo lipogenesis in the liver. Three-wk-old male rats were food restricted for 4 wk and refed a high-fat or normal fat diet individually in metabolic cages for 9 wk. Weight-matched groups were also set up. Fatty acid synthetase expression was measured to estimate de novo lipogenesis in the liver. Parameters of glucose and lipid metabolism were measured with isotope assays. All four groups had comparable body weights. However, the famine high-fat diet group had the highest degree of liver steatosis, the greatest body fat ratio, and insulin resistance. Lipid accumulation, fatty acid synthetase expression, and gluconeogenesis in the liver were significantly higher in the famine and high-fat diet groups (p < 0.05). Moreover, these groups also had markedly lower muscle glucose uptake. Under famine and high-fat refeeding stress, rats were extremely susceptible to developing hepatic steatosis. This is presumably a consequence of upregulation of de novo lipogenesis and enhanced glucose flux from muscle to de novo lipogenesis in the liver. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cationic antimicrobial peptides in penaeid shrimp.

PubMed

Tassanakajon, Anchalee; Amparyup, Piti; Somboonwiwat, Kunlaya; Supungul, Premruethai

2011-08-01

Penaeid shrimp aquaculture has been consistently affected worldwide by devastating diseases that cause a severe loss in production. To fight a variety of harmful microbes in the surrounding environment, particularly at high densities (of which intensive farming represents an extreme example), shrimps have evolved and use a diverse array of antimicrobial peptides (AMPs) as part of an important first-line response of the host defense system. Cationic AMPs in penaeid shrimps composed of penaeidins, crustins, and anti-lipopolysaccharide factors are comprised of multiple classes or isoforms and possess antibacterial and antifungal activities against different strains of bacteria and fungi. Shrimp AMPs are primarily expressed in circulating hemocytes, which is the main site of the immune response, and hemocytes expressing AMPs probably migrate to infection sites to fight against pathogen invasion. Indeed, most AMPs are produced as early as the nauplii developmental stage to protect shrimp larvae from infections. In this review, we discuss the sequence diversity, expression, gene structure, and antimicrobial activities of cationic AMPs in penaeid shrimps. The information available on antimicrobial activities indicates that these shrimp AMPs have potential therapeutic applications in the control of disease problems in aquaculture.

Hepatitis C Virus-Related Lymphomagenesis in a Mouse Model

PubMed Central

Tsukiyama-Kohara, Kyoko; Sekiguchi, Satoshi; Kasama, Yuri; Salem, Nagla Elwy; Machida, Keigo; Kohara, Michinori

2011-01-01

B cell non-Hodgkin lymphoma is a typical extrahepatic manifestation frequently associated with hepatitis C virus (HCV) infection. The mechanism by which HCV infection leads to lymphoproliferative disorder remains unclear. Our group established HCV transgenic mice that expressed the full HCV genome in B cells (RzCD19Cre mice). We observed a 25.0% incidence of diffuse large B cell non-Hodgkin lymphomas (22.2% in male and 29.6% in female mice) within 600 days of birth. Interestingly, RzCD19Cre mice with substantially elevated serum-soluble interleukin-2 receptor α-subunit (sIL-2Rα) levels (>1000 pg/mL) developed B cell lymphomas. Another mouse model of lymphoproliferative disorder was established by persistent expression of HCV structural proteins through disruption of interferon regulatory factor-1 (irf-1_/_/CN2 mice). Irf-1_/_/CN2 mice showed extremely high incidences of lymphomas and lymphoproliferative disorders. Moreover, these mice showed increased levels of interleukin (IL)-2, IL-10, and Bcl-2 as well as increased Bcl-2 expression, which promoted oncogenic transformation of lymphocytes. PMID:22084693

Expression kinetics of key genes in the early innate immune response to Great Lakes viral hemorrhagic septicemia virus IVb infection in yellow perch (Perca flavescens)

USGS Publications Warehouse

Olson, Wendy; Emmenegger, Eveline; Glenn, Jolene; Simchick, Crystal; Winton, Jim; Goetz, Frederick

2013-01-01

The recently discovered strain of viral hemorrhagic septicemia virus, VHSV-IVb, represents an example of the introduction of an extremely pathogenic rhabdovirus capable of infecting a wide variety of new fish species in a new host-environment. The goal of the present study was to delineate the expression kinetics of key genes in the innate immune response relative to the very early stages of VHSV-IVb infection using the yellow perch (Perca flavescens) as a model. Administration of VHSV-IVb by IP-injection into juvenile yellow perch resulted in 84% cumulative mortality, indicating their high susceptibility to this disease. In fish sampled in the very early stages of infection, a significant up-regulation of Mx gene expression in the liver, as well as IL-1β and SAA activation in the head kidney, spleen, and liver was directly correlated to viral load. The potential down-regulation of Mx in the hematopoietic tissues, head kidney and spleen, may represent a strategy utilized by the virus to increase replication.

Gene Expression Dynamics Accompanying the Sponge Thermal Stress Response.

PubMed

Guzman, Christine; Conaco, Cecilia

2016-01-01

Marine sponges are important members of coral reef ecosystems. Thus, their responses to changes in ocean chemistry and environmental conditions, particularly to higher seawater temperatures, will have potential impacts on the future of these reefs. To better understand the sponge thermal stress response, we investigated gene expression dynamics in the shallow water sponge, Haliclona tubifera (order Haplosclerida, class Demospongiae), subjected to elevated temperature. Using high-throughput transcriptome sequencing, we show that these conditions result in the activation of various processes that interact to maintain cellular homeostasis. Short-term thermal stress resulted in the induction of heat shock proteins, antioxidants, and genes involved in signal transduction and innate immunity pathways. Prolonged exposure to thermal stress affected the expression of genes involved in cellular damage repair, apoptosis, signaling and transcription. Interestingly, exposure to sublethal temperatures may improve the ability of the sponge to mitigate cellular damage under more extreme stress conditions. These insights into the potential mechanisms of adaptation and resilience of sponges contribute to a better understanding of sponge conservation status and the prediction of ecosystem trajectories under future climate conditions.

Identification of the transcriptional regulators by expression profiling infected with hepatitis B virus.

PubMed

Chai, Xiaoqiang; Han, Yanan; Yang, Jian; Zhao, Xianxian; Liu, Yewang; Hou, Xugang; Tang, Yiheng; Zhao, Shirong; Li, Xiao

2016-02-01

The molecular pathogenesis of infection by hepatitis B virus with human is extremely complex and heterogeneous. To date the molecular information is not clearly defined despite intensive research efforts. Thus, studies aimed at transcription and regulation during virus infection or combined researches of those already known to be beneficial are needed. With the purpose of identifying the transcriptional regulators related to infection of hepatitis B virus in gene level, the gene expression profiles from some normal individuals and hepatitis B patients were analyzed in our study. In this work, the differential expressed genes were selected primarily. The several genes among those were validated in an independent set by qRT-PCR. Then the differentially co-expression analysis was conducted to identify differentially co-expressed links and differential co-expressed genes. Next, the analysis of the regulatory impact factors was performed through mapping the links and regulatory data. In order to give a further insight to these regulators, the co-expression gene modules were identified using a threshold-based hierarchical clustering method. Incidentally, the construction of the regulatory network was generated using the computer software. A total of 137,284 differentially co-expressed links and 780 differential co-expressed genes were identified. These co-expressed genes were significantly enriched inflammatory response. The results of regulatory impact factors revealed several crucial regulators related to hepatocellular carcinoma and other high-rank regulators. Meanwhile, more than one hundred co-expression gene modules were identified using clustering method. In our study, some important transcriptional regulators were identified using a computational method, which may enhance the understanding of disease mechanisms and lead to an improved treatment of hepatitis B. However, further experimental studies are required to confirm these findings. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Selection of Reference Genes for Expression Studies of Xenobiotic Adaptation in Tetranychus urticae.

PubMed

Morales, Mariany Ashanty; Mendoza, Bianca Marie; Lavine, Laura Corley; Lavine, Mark Daniel; Walsh, Douglas Bruce; Zhu, Fang

2016-01-01

Quantitative real-time PCR (qRT-PCR) is an extensively used, high-throughput method to analyze transcriptional expression of genes of interest. An appropriate normalization strategy with reliable reference genes is required for calculating gene expression across diverse experimental conditions. In this study, we aim to identify the most stable reference genes for expression studies of xenobiotic adaptation in Tetranychus urticae, an extremely polyphagous herbivore causing significant yield reduction of agriculture. We chose eight commonly used housekeeping genes as candidates. The qRT-PCR expression data for these genes were evaluated from seven populations: a susceptible and three acaricide resistant populations feeding on lima beans, and three other susceptible populations which had been shifted host from lima beans to three other plant species. The stability of the candidate reference genes was then assessed using four different algorithms (comparative ΔCt method, geNorm, NormFinder, and BestKeeper). Additionally, we used an online web-based tool (RefFinder) to assign an overall final rank for each candidate gene. Our study found that CycA and Rp49 are best for investigating gene expression in acaricide susceptible and resistant populations. GAPDH, Rp49, and Rpl18 are best for host plant shift studies. And GAPDH and Rp49 were the most stable reference genes when investigating gene expression under changes in both experimental conditions. These results will facilitate research in revealing molecular mechanisms underlying the xenobiotic adaptation of this notorious agricultural pest.

Selection of Reference Genes for Expression Studies of Xenobiotic Adaptation in Tetranychus urticae

PubMed Central

Morales, Mariany Ashanty; Mendoza, Bianca Marie; Lavine, Laura Corley; Lavine, Mark Daniel; Walsh, Douglas Bruce; Zhu, Fang

2016-01-01

Quantitative real-time PCR (qRT-PCR) is an extensively used, high-throughput method to analyze transcriptional expression of genes of interest. An appropriate normalization strategy with reliable reference genes is required for calculating gene expression across diverse experimental conditions. In this study, we aim to identify the most stable reference genes for expression studies of xenobiotic adaptation in Tetranychus urticae, an extremely polyphagous herbivore causing significant yield reduction of agriculture. We chose eight commonly used housekeeping genes as candidates. The qRT-PCR expression data for these genes were evaluated from seven populations: a susceptible and three acaricide resistant populations feeding on lima beans, and three other susceptible populations which had been shifted host from lima beans to three other plant species. The stability of the candidate reference genes was then assessed using four different algorithms (comparative ΔCt method, geNorm, NormFinder, and BestKeeper). Additionally, we used an online web-based tool (RefFinder) to assign an overall final rank for each candidate gene. Our study found that CycA and Rp49 are best for investigating gene expression in acaricide susceptible and resistant populations. GAPDH, Rp49, and Rpl18 are best for host plant shift studies. And GAPDH and Rp49 were the most stable reference genes when investigating gene expression under changes in both experimental conditions. These results will facilitate research in revealing molecular mechanisms underlying the xenobiotic adaptation of this notorious agricultural pest. PMID:27570487

Extreme Metal Music and Anger Processing

PubMed Central

Sharman, Leah; Dingle, Genevieve A.

2015-01-01

The claim that listening to extreme music causes anger, and expressions of anger such as aggression and delinquency have yet to be substantiated using controlled experimental methods. In this study, 39 extreme music listeners aged 18–34 years were subjected to an anger induction, followed by random assignment to 10 min of listening to extreme music from their own playlist, or 10 min silence (control). Measures of emotion included heart rate and subjective ratings on the Positive and Negative Affect Scale (PANAS). Results showed that ratings of PANAS hostility, irritability, and stress increased during the anger induction, and decreased after the music or silence. Heart rate increased during the anger induction and was sustained (not increased) in the music condition, and decreased in the silence condition. PANAS active and inspired ratings increased during music listening, an effect that was not seen in controls. The findings indicate that extreme music did not make angry participants angrier; rather, it appeared to match their physiological arousal and result in an increase in positive emotions. Listening to extreme music may represent a healthy way of processing anger for these listeners. PMID:26052277

Characterization of the Martian magnetic topology response to extreme solar transient events with MGS data

NASA Astrophysics Data System (ADS)

Xu, S.; Curry, S.; Mitchell, D. L.; Luhmann, J. G.; Lillis, R. J.; Dong, C.

2017-12-01

Characterizing how the solar cycle affects the physics of the Mars-solar wind interaction can improve our understanding of Mars' atmospheric evolution and the plasma environment at Mars. In particular, solar transient events such as Interplanetary Coronal Mass Ejections (ICMEs) and Stream Interaction Regions (SIRs) significantly change the solar-wind interaction, including the magnetic topology and ion acceleration. However, both the Mars Express and Mars Atmosphere Volatile EvolutioN (MAVEN) missions have encountered relatively few extreme solar transient events due to the recent low solar activity (2004-2017). In contrast, Mars Global Surveyor (MGS) was operating during a relatively active solar maximum (1999-2003). Based on new results from MAVEN, this study reanalyzes MGS data to better understand how the Martian plasma environment responds to extreme solar events. In particular, we aim to investigate how the magnetic topology during these extreme events differs from the topology during quiet times. We conduct orbit comparisons of the magnetic topology inferred from MGS electron pitch angle distributions during quiet periods and extreme events to determine how the open and closed field patterns respond to extreme events.

Variability of Extreme Precipitation Events in Tijuana, Mexico During ENSO Years

NASA Astrophysics Data System (ADS)

Cavazos, T.; Rivas, D.

2007-05-01

We present the variability of daily precipitation extremes (top 10 percecnt) in Tijuana, Mexico during 1950-2000. Interannual rainfall variability is significantly modulated by El Nino/Southern Oscillation. The interannual precipitation variability exhibits a large change with a relatively wet period and more variability during 1976- 2000. The wettest years and the largest frequency of daily extremes occurred after 1976-1977, with 6 out of 8 wet years characterized by El Nino episodes and 2 by neutral conditions. However, more than half of the daily extremes during 1950-2000 occurred in non-ENSO years, evidencing that neutral conditions also contribute significantly to extreme climatic variability in the region. Extreme events that occur in neutral (strong El Nino) conditions are associated with a pineapple express and a neutral PNA (negative TNH) teleconnection pattern that links an anomalous tropical convective forcing west (east) of the date line with a strong subtropical jet over the study area. At regional scale, both types of extremes are characterized by a trough in the subtropical jet over California/Baja California, which is further intensified by thermal interaction with an anomalous warm California Current off Baja California, low-level moisture advection from the subtropical warm sea-surface region, intense convective activity over the study area and extreme rainfall from southern California to Baja California.

A linearization of quantum channels

NASA Astrophysics Data System (ADS)

Crowder, Tanner

2015-06-01

Because the quantum channels form a compact, convex set, we can express any quantum channel as a convex combination of extremal channels. We give a Euclidean representation for the channels whose inverses are also valid channels; these are a subset of the extreme points. They form a compact, connected Lie group, and we calculate its Lie algebra. Lastly, we calculate a maximal torus for the group and provide a constructive approach to decomposing any invertible channel into a product of elementary channels.

Future changes in hydro-climatic extremes in the Upper Indus, Ganges, and Brahmaputra River basins

PubMed Central

Lutz, Arthur F.; Nepal, Santosh; Khanal, Sonu; Pradhananga, Saurav; Shrestha, Arun B.; Immerzeel, Walter W.

2017-01-01

Future hydrological extremes, such as floods and droughts, may pose serious threats for the livelihoods in the upstream domains of the Indus, Ganges, Brahmaputra. For this reason, the impacts of climate change on future hydrological extremes is investigated in these river basins. We use a fully-distributed cryospheric-hydrological model to simulate current and future hydrological fluxes and force the model with an ensemble of 8 downscaled General Circulation Models (GCMs) that are selected from the RCP4.5 and RCP8.5 scenarios. The model is calibrated on observed daily discharge and geodetic mass balances. The climate forcing and the outputs of the hydrological model are used to evaluate future changes in climatic extremes, and hydrological extremes by focusing on high and low flows. The outcomes show an increase in the magnitude of climatic means and extremes towards the end of the 21st century where climatic extremes tend to increase stronger than climatic means. Future mean discharge and high flow conditions will very likely increase. These increases might mainly be the result of increasing precipitation extremes. To some extent temperature extremes might also contribute to increasing discharge extremes, although this is highly dependent on magnitude of change in temperature extremes. Low flow conditions may occur less frequently, although the uncertainties in low flow projections can be high. The results of this study may contribute to improved understanding on the implications of climate change for the occurrence of future hydrological extremes in the Hindu Kush–Himalayan region. PMID:29287098

Probabilistic forecasting of extreme weather events based on extreme value theory

NASA Astrophysics Data System (ADS)

Van De Vyver, Hans; Van Schaeybroeck, Bert

2016-04-01

Extreme events in weather and climate such as high wind gusts, heavy precipitation or extreme temperatures are commonly associated with high impacts on both environment and society. Forecasting extreme weather events is difficult, and very high-resolution models are needed to describe explicitly extreme weather phenomena. A prediction system for such events should therefore preferably be probabilistic in nature. Probabilistic forecasts and state estimations are nowadays common in the numerical weather prediction community. In this work, we develop a new probabilistic framework based on extreme value theory that aims to provide early warnings up to several days in advance. We consider the combined events when an observation variable Y (for instance wind speed) exceeds a high threshold y and its corresponding deterministic forecasts X also exceeds a high forecast threshold y. More specifically two problems are addressed:} We consider pairs (X,Y) of extreme events where X represents a deterministic forecast, and Y the observation variable (for instance wind speed). More specifically two problems are addressed: Given a high forecast X=x_0, what is the probability that Y>y? In other words: provide inference on the conditional probability: [ Pr{Y>y|X=x_0}. ] Given a probabilistic model for Problem 1, what is the impact on the verification analysis of extreme events. These problems can be solved with bivariate extremes (Coles, 2001), and the verification analysis in (Ferro, 2007). We apply the Ramos and Ledford (2009) parametric model for bivariate tail estimation of the pair (X,Y). The model accommodates different types of extremal dependence and asymmetry within a parsimonious representation. Results are presented using the ensemble reforecast system of the European Centre of Weather Forecasts (Hagedorn, 2008). Coles, S. (2001) An Introduction to Statistical modelling of Extreme Values. Springer-Verlag.Ferro, C.A.T. (2007) A probability model for verifying deterministic forecasts of extreme events. Wea. Forecasting {22}, 1089-1100.Hagedorn, R. (2008) Using the ECMWF reforecast dataset to calibrate EPS forecasts. ECMWF Newsletter, {117}, 8-13.Ramos, A., Ledford, A. (2009) A new class of models for bivariate joint tails. J.R. Statist. Soc. B {71}, 219-241.

Variation in embryonic mortality and maternal transcript expression among Atlantic cod (Gadus morhua) broodstock: a functional genomics study.

PubMed

Rise, Matthew L; Nash, Gordon W; Hall, Jennifer R; Booman, Marije; Hori, Tiago S; Trippel, Edward A; Gamperl, A Kurt

2014-12-01

Early life stage mortality is an important issue for Atlantic cod aquaculture, yet the impact of the cod maternal (egg) transcriptome on egg quality and mortality during embryonic development is poorly understood. In the present work, we studied embryonic mortality and maternal transcript expression using eggs from 15 females. Total mortality at 7days post-fertilization (7 dpf, segmentation stage) was used as an indice of egg quality. A 20,000 probe (20K) microarray experiment compared the 7hours post-fertilization (7 hpf, ~2-cell stage) egg transcriptome of the two lowest quality females (>90% mortality at 7 dpf) to that of the highest quality female (~16% mortality at 7 dpf). Forty-three microarray probes were consistently differentially expressed in both low versus high quality egg comparisons (25 higher expressed in low quality eggs, and 18 higher expressed in high quality eggs). The microarray experiment also identified many immune-relevant genes [e.g. interferon (IFN) pathway genes ifngr1 and ifrd1)] that were highly expressed in eggs of all 3 females regardless of quality. Twelve of the 43 candidate egg quality-associated genes, and ifngr1, ifrd1 and irf7, were included in a qPCR study with 7 hpf eggs from all 15 females. Then, the genes that were confirmed by qPCR to be greater than 2-fold differentially expressed between 7 hpf eggs from the lowest and highest quality females (dcbld1, ddc, and acy3 more highly expressed in the 2 lowest quality females; kpna7 and hacd1 more highly expressed in the highest quality female), and the 3 IFN pathway genes, were included in a second qPCR study with unfertilized eggs. While some maternal transcripts included in these qPCR studies were associated with extremes in egg quality, there was little correlation between egg quality and gene expression when all females were considered. Both dcbld1 and ddc showed greater than 100-fold differences in transcript expression between females and were potentially influenced by family. The Atlantic cod ddc (dopa decarboxylase) complete cDNA was characterized, and has a 1461bp open reading frame encoding a 486 amino acid protein that contains all eight residues of the conserved pyridoxal 5'-phosphate binding site including the catalytic lysine. This study provides valuable new information and resources related to the Atlantic cod egg transcriptome. Some of these microarray-identified, qPCR-confirmed, Atlantic cod egg transcripts (e.g. ddc, kpna7) play important roles during embryonic development of other vertebrate species, and may have similar functions in Atlantic cod. Copyright © 2014. Published by Elsevier B.V.

In situ Expression of Functional Genes Reveals Nitrogen Cycling at High Temperatures in Terrestrial Hydrothermal Systems

NASA Astrophysics Data System (ADS)

Loiacono, S. T.; Meyer-Dombard, D. R.

2011-12-01

An essential element for life, nitrogen occurs in all living organisms and is critical for the synthesis of amino acids, proteins, nucleic acids, and other forms of biomass. Thus, nitrogen cycling likely plays a vital role in microbial metabolic processes as well as nutrient availability. For microorganisms in "extreme" environments, this means developing adaptations that allow them to survive in harsh conditions and still perform the metabolisms essential to sustain life. Recent studies have screened biofilms and thermal sediments of Yellowstone National Park (YNP) thermal features for the presence of nifH genes, which code for a key enzyme in the nitrogen fixation process [1-4]. Furthermore, analysis of nitrogen isotopes in biofilms across a temperature and chemical gradient revealed that nitrogen fixation likely varies across the chemosynthetic/photosynthetic ecotone [5]. Although research has evaluated and confirmed the presence of nifH genes in various thermophilic microbial communities, the existence of a gene in the DNA of an organism does not verify its use. Instead, other methods, such as culturing, isotope tracer assays, and gene expression studies are required to provide direct evidence of biological nitrogen fixation. Culturing and isotope tracer approaches have successfully revealed high-temperature biological nitrogen fixation in both marine hydrothermal vent microbial communities [6] and in acidic, terrestrial hydrothermal sediment [3]. Transcriptomics-based techniques (using mRNA extracted from samples to confirm in situ expression of targeted genes) have been much more limited in number, and only a few studies have, to date, investigated in situ expression of the nifH gene in thermophilic microbial communities [2, 7]. This study explores the presence and expression of nifH genes in several features of the Lower Geyser Basin (LGB) of YNP. Nucleic acids from chemosynthetic and photosynthetic microbial communities were extracted and then amplified using (reverse-transcription) polymerase chain reaction to identify the presence and expression of nifH genes, and resultant (RT-)PCR product was cloned and sequenced. Results reveal high-temperature in situ expression of nifH in select LGB features [7] which is, to the authors' knowledge, the first direct evidence of nifH transcription in the chemosynthetic zones of terrestrial hydrothermal systems. Results also indicate the presence of novel nifH sequences and allow phylogenetic comparison of nifH genes along geochemical gradients within individual hot spring features and between various thermal features in the LGB. Collectively, these results provide evidence for microbial adaptations that have led to the ability to support basic metabolic processes under "extreme" conditions. [1] Hall et al., 2008. AEM 74: 4910-4922. [2] Steunou et al., 2008. The ISME Journal 2: 364-378. [3] Hamilton et al., 2011. Microb Ecol DOI 10.1007/s00248-011-9824-9. [4] Raymond et al., 2008. EOS Trans AGU. Abstract B14A-03. [5] Havig et al., 2010. J Geophys Res-Biogeo 116: G01005. [6] Mehta & Baross, 2006. Science 314: 1783-1786. [7] Loiacono et al., 2011. Submitted FEMS Microbiol Ecol.

Regularised extreme learning machine with misclassification cost and rejection cost for gene expression data classification.

PubMed

Lu, Huijuan; Wei, Shasha; Zhou, Zili; Miao, Yanzi; Lu, Yi

2015-01-01

The main purpose of traditional classification algorithms on bioinformatics application is to acquire better classification accuracy. However, these algorithms cannot meet the requirement that minimises the average misclassification cost. In this paper, a new algorithm of cost-sensitive regularised extreme learning machine (CS-RELM) was proposed by using probability estimation and misclassification cost to reconstruct the classification results. By improving the classification accuracy of a group of small sample which higher misclassification cost, the new CS-RELM can minimise the classification cost. The 'rejection cost' was integrated into CS-RELM algorithm to further reduce the average misclassification cost. By using Colon Tumour dataset and SRBCT (Small Round Blue Cells Tumour) dataset, CS-RELM was compared with other cost-sensitive algorithms such as extreme learning machine (ELM), cost-sensitive extreme learning machine, regularised extreme learning machine, cost-sensitive support vector machine (SVM). The results of experiments show that CS-RELM with embedded rejection cost could reduce the average cost of misclassification and made more credible classification decision than others.

Exact simulation of max-stable processes.

PubMed

Dombry, Clément; Engelke, Sebastian; Oesting, Marco

2016-06-01

Max-stable processes play an important role as models for spatial extreme events. Their complex structure as the pointwise maximum over an infinite number of random functions makes their simulation difficult. Algorithms based on finite approximations are often inexact and computationally inefficient. We present a new algorithm for exact simulation of a max-stable process at a finite number of locations. It relies on the idea of simulating only the extremal functions, that is, those functions in the construction of a max-stable process that effectively contribute to the pointwise maximum. We further generalize the algorithm by Dieker & Mikosch (2015) for Brown-Resnick processes and use it for exact simulation via the spectral measure. We study the complexity of both algorithms, prove that our new approach via extremal functions is always more efficient, and provide closed-form expressions for their implementation that cover most popular models for max-stable processes and multivariate extreme value distributions. For simulation on dense grids, an adaptive design of the extremal function algorithm is proposed.

An Efficient Means of Determining the Newtonian Potential for Highly Flattened Mass Distributions

NASA Astrophysics Data System (ADS)

Cohl, H.

1999-05-01

In this dissertation talk we present a mathematical result that, to the best of our knowledge, has been previously undiscovered. That is, the Green's function in a variety of orthogonal coordinate systems may be expressed in terms of a single sum over the azimuthal quantum number, m, of terms involving Toroidal Harmonics. We show how this new addition theorem can be effectively applied to a variety of potential problems in gravitation, electrostatics and magnetostatics and, in particular, demonstrate how it may be used to analyze the properties of general nonaxisymmetric disk systems with and without vertical extent. Finally, we describe our numerical implementation of the addition theorem in order to determine the Newtonian potential extremely close to highly flattened mass distributions. This yields an extremely efficient technique for computing the boundary values in a general algorithm that is designed to solve the 3D Poisson equation on a cylindrical coordinate lattice. We acknowledge support from the U.S. National Science Foundation through grant AST-9528424 and DGE-9355007, the latter of which has been issued through the NSF's Graduate Traineeships Program. This work also has been supported, in part, by grants of high-performance-computing time on NPACI facilities at SDSC and UT, Austin, and through the PET program of NAVOCEANO DoD Major Shared Resource Center in Stennis, MS.

Multifunctional Biocompatible Graphene Oxide Quantum Dots Decorated Magnetic Nanoplatform for Efficient Capture and Two-Photon Imaging of Rare Tumor Cells

PubMed Central

2016-01-01

Circulating tumor cells (CTCs) are extremely rare cells in blood containing billions of other cells. The selective capture and identification of rare cells with sufficient sensitivity is a real challenge. Driven by this need, this manuscript reports the development of a multifunctional biocompatible graphene oxide quantum dots (GOQDs) coated, high-luminescence magnetic nanoplatform for the selective separation and diagnosis of Glypican-3 (GPC3)-expressed Hep G2 liver cancer tumor CTCs from infected blood. Experimental data show that an anti-GPC3-antibody-attached multifunctional nanoplatform can be used for selective Hep G2 hepatocellular carcinoma tumor cell separation from infected blood containing 10 tumor cells/mL of blood in a 15 mL sample. Reported data indicate that, because of an extremely high two-photon absorption cross section (40530 GM), an anti-GPC3-antibody-attached GOQDs-coated magnetic nanoplatform can be used as a two-photon luminescence platform for selective and very bright imaging of a Hep G2 tumor cell in a biological transparency window using 960 nm light. Experimental results with nontargeted GPC3(−) and SK-BR-3 breast cancer cells show that multifunctional-nanoplatform-based cell separation, followed by two-photon imaging, is highly selective for Hep G2 hepatocellular carcinoma tumor cells. PMID:25939643

Extreme Fire Severity Patterns in Topographic, Convective and Wind-Driven Historical Wildfires of Mediterranean Pine Forests

PubMed Central

Lecina-Diaz, Judit; Alvarez, Albert; Retana, Javier

2014-01-01

Crown fires associated with extreme fire severity are extremely difficult to control. We have assessed fire severity using differenced Normalized Burn Ratio (dNBR) from Landsat imagery in 15 historical wildfires of Pinus halepensis Mill. We have considered a wide range of innovative topographic, fuel and fire behavior variables with the purposes of (1) determining the variables that influence fire severity patterns among fires (considering the 15 wildfires together) and (2) ascertaining whether different variables affect extreme fire severity within the three fire types (topographic, convective and wind-driven fires). The among-fires analysis showed that fires in less arid climates and with steeper slopes had more extreme severity. In less arid conditions there was more crown fuel accumulation and closer forest structures, promoting high vertical and horizontal fuel continuity and extreme fire severity. The analyses carried out for each fire separately (within fires) showed more extreme fire severity in areas in northern aspects, with steeper slopes, with high crown biomass and in climates with more water availability. In northern aspects solar radiation was lower and fuels had less water limitation to growth which, combined with steeper slopes, produced more extreme severity. In topographic fires there was more extreme severity in northern aspects with steeper slopes and in areas with more water availability and high crown biomass; in convection-dominated fires there was also more extreme fire severity in northern aspects with high biomass; while in wind-driven fires there was only a slight interaction between biomass and water availability. This latter pattern could be related to the fact that wind-driven fires spread with high wind speed, which could have minimized the effect of other variables. In the future, and as a consequence of climate change, new zones with high crown biomass accumulated in non-common drought areas will be available to burn as extreme severity wildfires. PMID:24465492

Extreme fire severity patterns in topographic, convective and wind-driven historical wildfires of Mediterranean pine forests.

PubMed

Lecina-Diaz, Judit; Alvarez, Albert; Retana, Javier

2014-01-01

Crown fires associated with extreme fire severity are extremely difficult to control. We have assessed fire severity using differenced Normalized Burn Ratio (dNBR) from Landsat imagery in 15 historical wildfires of Pinus halepensis Mill. We have considered a wide range of innovative topographic, fuel and fire behavior variables with the purposes of (1) determining the variables that influence fire severity patterns among fires (considering the 15 wildfires together) and (2) ascertaining whether different variables affect extreme fire severity within the three fire types (topographic, convective and wind-driven fires). The among-fires analysis showed that fires in less arid climates and with steeper slopes had more extreme severity. In less arid conditions there was more crown fuel accumulation and closer forest structures, promoting high vertical and horizontal fuel continuity and extreme fire severity. The analyses carried out for each fire separately (within fires) showed more extreme fire severity in areas in northern aspects, with steeper slopes, with high crown biomass and in climates with more water availability. In northern aspects solar radiation was lower and fuels had less water limitation to growth which, combined with steeper slopes, produced more extreme severity. In topographic fires there was more extreme severity in northern aspects with steeper slopes and in areas with more water availability and high crown biomass; in convection-dominated fires there was also more extreme fire severity in northern aspects with high biomass; while in wind-driven fires there was only a slight interaction between biomass and water availability. This latter pattern could be related to the fact that wind-driven fires spread with high wind speed, which could have minimized the effect of other variables. In the future, and as a consequence of climate change, new zones with high crown biomass accumulated in non-common drought areas will be available to burn as extreme severity wildfires.

Effects of the crustal magnetic fields on the Martian atmospheric ion escape rate

NASA Astrophysics Data System (ADS)

Ramstad, R.; Barbash, S.; Futaana, Y.; Nilsson, H.; Holmstrom, M.

2015-12-01

Eight years (2007-2015) of ion flux measurements from Mars Express are used to empirically investigate the influence of the Martian crustal magnetic fields on the atmospheric ion escape rate. We combine ASPERA-3/IMA (Analyzer of Space Plasmas and Energetic Atoms/Ion Mass Analyzer) measurements taken during nominal upstream solar wind and solar Extreme Ultraviolet (EUV) conditions to compute global average ion distribution functions for varying solar zenith angles (SZA) of the strongest crustal field. Escape rates are subsequently calculated from each of the average distribution functions. A statistically significant increase in escape rate is found for high dayside SZA, compared to low SZA.

Optimization of optical systems.

PubMed

Champagne, E B

1966-11-01

The power signal-to-noise ratios for coherent and noncoherent optical detection are presented, with the expression for noncoherent detection being examined in detail. It is found that for the long range optical system to compete with its microwave counterpart it is necessary to optimize the optical system. The optical system may be optimized by using coherent detection, or noncoherent detection if the signal is the dominate noise factor. A design procedure is presented which, in principle, always allows one to obtain signal shot-noise limited operation with noncoherent detection if pulsed operation is used. The technique should make reasonable extremely long range, high data rate systems of relatively simple design.

Quantitative assessment based on kinematic measures of functional impairments during upper extremity movements: A review.

PubMed

de los Reyes-Guzmán, Ana; Dimbwadyo-Terrer, Iris; Trincado-Alonso, Fernando; Monasterio-Huelin, Félix; Torricelli, Diego; Gil-Agudo, Angel

2014-08-01

Quantitative measures of human movement quality are important for discriminating healthy and pathological conditions and for expressing the outcomes and clinically important changes in subjects' functional state. However the most frequently used instruments for the upper extremity functional assessment are clinical scales, that previously have been standardized and validated, but have a high subjective component depending on the observer who scores the test. But they are not enough to assess motor strategies used during movements, and their use in combination with other more objective measures is necessary. The objective of the present review is to provide an overview on objective metrics found in literature with the aim of quantifying the upper extremity performance during functional tasks, regardless of the equipment or system used for registering kinematic data. A search in Medline, Google Scholar and IEEE Xplore databases was performed following a combination of a series of keywords. The full scientific papers that fulfilled the inclusion criteria were included in the review. A set of kinematic metrics was found in literature in relation to joint displacements, analysis of hand trajectories and velocity profiles. These metrics were classified into different categories according to the movement characteristic that was being measured. These kinematic metrics provide the starting point for a proposed objective metrics for the functional assessment of the upper extremity in people with movement disorders as a consequence of neurological injuries. Potential areas of future and further research are presented in the Discussion section. Copyright © 2014 Elsevier Ltd. All rights reserved.

Quantifying the relationship between extreme air pollution events and extreme weather events

NASA Astrophysics Data System (ADS)

Zhang, Henian; Wang, Yuhang; Park, Tae-Won; Deng, Yi

2017-05-01

Extreme weather events can strongly affect surface air quality, which has become a major environmental factor to affect human health. Here, we examined the relationship between extreme ozone and PM2.5 (particular matter with an aerodynamic diameter less than 2.5 μm) events and the representative meteorological parameters such as daily maximum temperature (Tmax), minimum relative humidity (RHmin), and minimum wind speed (Vmin), using the location-specific 95th or 5th percentile threshold derived from historical reanalysis data (30 years for ozone and 10 years for PM2.5). We found that ozone and PM2.5 extremes were decreasing over the years, reflecting EPA's tightened standards and effort on reducing the corresponding precursor's emissions. Annual ozone and PM2.5 extreme days were highly correlated with Tmax and RHmin, especially in the eastern U.S. They were positively (negatively) correlated with Vmin in urban (rural and suburban) stations. The overlapping ratios of ozone extreme days with Tmax were fairly constant, about 32%, and tended to be high in fall and low in winter. Ozone extreme days were most sensitive to Tmax, then RHmin, and least sensitive to Vmin. The majority of ozone extremes occurred when Tmax was between 300 K and 320 K, RHmin was less than 40%, and Vmin was less than 3 m/s. The number of annual extreme PM2.5 days was highly positively correlated with the extreme RHmin/Tmax days, with correlation coefficient between PM2.5/RHmin highest in urban and suburban regions and the correlation coefficient between PM2.5/Tmax highest in rural area. Tmax has more impact on PM2.5 extreme over the eastern U.S. Extreme PM2.5 days were more likely to occur at low RH conditions in the central and southeastern U.S., especially during spring time, and at high RH conditions in the northern U.S. and the Great Plains. Most extreme PM2.5 events occurred when Tmax was between 300 K and 320 K and RHmin was between 10% and 50%. Extreme PM2.5 days usually occurred when Vmin was under 2 m/s. However, during spring season in the Southeast and fall season in Northwest, high winds were found to accompany extreme PM2.5 days, likely reflecting the impact of fire emissions.

Quantifying whole transcriptome size, a prerequisite for understanding transcriptome evolution across species: an example from a plant allopolyploid.

PubMed

Coate, Jeremy E; Doyle, Jeff J

2010-01-01

Evolutionary biologists are increasingly comparing gene expression patterns across species. Due to the way in which expression assays are normalized, such studies provide no direct information about expression per gene copy (dosage responses) or per cell and can give a misleading picture of genes that are differentially expressed. We describe an assay for estimating relative expression per cell. When used in conjunction with transcript profiling data, it is possible to compare the sizes of whole transcriptomes, which in turn makes it possible to compare expression per cell for each gene in the transcript profiling data set. We applied this approach, using quantitative reverse transcriptase-polymerase chain reaction and high throughput RNA sequencing, to a recently formed allopolyploid and showed that its leaf transcriptome was approximately 1.4-fold larger than either progenitor transcriptome (70% of the sum of the progenitor transcriptomes). In contrast, the allopolyploid genome is 94.3% as large as the sum of its progenitor genomes and retains > or =93.5% of the sum of its progenitor gene complements. Thus, "transcriptome downsizing" is greater than genome downsizing. Using this transcriptome size estimate, we inferred dosage responses for several thousand genes and showed that the majority exhibit partial dosage compensation. Homoeologue silencing is nonrandomly distributed across dosage responses, with genes showing extreme responses in either direction significantly more likely to have a silent homoeologue. This experimental approach will add value to transcript profiling experiments involving interspecies and interploidy comparisons by converting expression per transcriptome to expression per genome, eliminating the need for assumptions about transcriptome size.

Differential gene expression of two extreme honey bee (Apis mellifera) colonies showing varroa tolerance and susceptibility.

PubMed

Jiang, S; Robertson, T; Mostajeran, M; Robertson, A J; Qiu, X

2016-06-01

Varroa destructor, an ectoparasitic mite of honey bees (Apis mellifera), is the most serious pest threatening the apiculture industry. In our honey bee breeding programme, two honey bee colonies showing extreme phenotypes for varroa tolerance/resistance (S88) and susceptibility (G4) were identified by natural selection from a large gene pool over a 6-year period. To investigate potential defence mechanisms for honey bee tolerance to varroa infestation, we employed DNA microarray and real time quantitative (PCR) analyses to identify differentially expressed genes in the tolerant and susceptible colonies at pupa and adult stages. Our results showed that more differentially expressed genes were identified in the tolerant bees than in bees from the susceptible colony, indicating that the tolerant colony showed an increased genetic capacity to respond to varroa mite infestation. In both colonies, there were more differentially expressed genes identified at the pupa stage than at the adult stage, indicating that pupa bees are more responsive to varroa infestation than adult bees. Genes showing differential expression in the colony phenotypes were categorized into several groups based on their molecular functions, such as olfactory signalling, detoxification processes, exoskeleton formation, protein degradation and long-chain fatty acid metabolism, suggesting that these biological processes play roles in conferring varroa tolerance to naturally selected colonies. Identification of differentially expressed genes between the two colony phenotypes provides potential molecular markers for selecting and breeding varroa-tolerant honey bees. © 2016 The Royal Entomological Society.

Transcriptome architecture across tissues in the pig

PubMed Central

Ferraz, André LJ; Ojeda, Ana; López-Béjar, Manel; Fernandes, Lana T; Castelló, Anna; Folch, Josep M; Pérez-Enciso, Miguel

2008-01-01

Background Artificial selection has resulted in animal breeds with extreme phenotypes. As an organism is made up of many different tissues and organs, each with its own genetic programme, it is pertinent to ask: How relevant is tissue in terms of total transcriptome variability? Which are the genes most distinctly expressed between tissues? Does breed or sex equally affect the transcriptome across tissues? Results In order to gain insight on these issues, we conducted microarray expression profiling of 16 different tissues from four animals of two extreme pig breeds, Large White and Iberian, two males and two females. Mixed model analysis and neighbor – joining trees showed that tissues with similar developmental origin clustered closer than those with different embryonic origins. Often a sound biological interpretation was possible for overrepresented gene ontology categories within differentially expressed genes between groups of tissues. For instance, an excess of nervous system or muscle development genes were found among tissues of ectoderm or mesoderm origins, respectively. Tissue accounted for ~11 times more variability than sex or breed. Nevertheless, we were able to confidently identify genes with differential expression across tissues between breeds (33 genes) and between sexes (19 genes). The genes primarily affected by sex were overall different than those affected by breed or tissue. Interaction with tissue can be important for differentially expressed genes between breeds but not so much for genes whose expression differ between sexes. Conclusion Embryonic development leaves an enduring footprint on the transcriptome. The interaction in gene × tissue for differentially expressed genes between breeds suggests that animal breeding has targeted differentially each tissue's transcriptome. PMID:18416811

Mechanisms Underlying Adaptation to Life in Hydrogen Sulfide–Rich Environments

PubMed Central

Kelley, Joanna L.; Arias-Rodriguez, Lenin; Patacsil Martin, Dorrelyn; Yee, Muh-Ching; Bustamante, Carlos D.; Tobler, Michael

2016-01-01

Hydrogen sulfide (H2S) is a potent toxicant interfering with oxidative phosphorylation in mitochondria and creating extreme environmental conditions in aquatic ecosystems. The mechanistic basis of adaptation to perpetual exposure to H2S remains poorly understood. We investigated evolutionarily independent lineages of livebearing fishes that have colonized and adapted to springs rich in H2S and compared their genome-wide gene expression patterns with closely related lineages from adjacent, nonsulfidic streams. Significant differences in gene expression were uncovered between all sulfidic and nonsulfidic population pairs. Variation in the number of differentially expressed genes among population pairs corresponded to differences in divergence times and rates of gene flow, which is consistent with neutral drift driving a substantial portion of gene expression variation among populations. Accordingly, there was little evidence for convergent evolution shaping large-scale gene expression patterns among independent sulfide spring populations. Nonetheless, we identified a small number of genes that was consistently differentially expressed in the same direction in all sulfidic and nonsulfidic population pairs. Functional annotation of shared differentially expressed genes indicated upregulation of genes associated with enzymatic H2S detoxification and transport of oxidized sulfur species, oxidative phosphorylation, energy metabolism, and pathways involved in responses to oxidative stress. Overall, our results suggest that modification of processes associated with H2S detoxification and toxicity likely complement each other to mediate elevated H2S tolerance in sulfide spring fishes. Our analyses allow for the development of novel hypotheses about biochemical and physiological mechanisms of adaptation to extreme environments. PMID:26861137

CYP6 P450 enzymes and ACE-1 duplication produce extreme and multiple insecticide resistance in the malaria mosquito Anopheles gambiae.

PubMed

Edi, Constant V; Djogbénou, Luc; Jenkins, Adam M; Regna, Kimberly; Muskavitch, Marc A T; Poupardin, Rodolphe; Jones, Christopher M; Essandoh, John; Kétoh, Guillaume K; Paine, Mark J I; Koudou, Benjamin G; Donnelly, Martin J; Ranson, Hilary; Weetman, David

2014-03-01

Malaria control relies heavily on pyrethroid insecticides, to which susceptibility is declining in Anopheles mosquitoes. To combat pyrethroid resistance, application of alternative insecticides is advocated for indoor residual spraying (IRS), and carbamates are increasingly important. Emergence of a very strong carbamate resistance phenotype in Anopheles gambiae from Tiassalé, Côte d'Ivoire, West Africa, is therefore a potentially major operational challenge, particularly because these malaria vectors now exhibit resistance to multiple insecticide classes. We investigated the genetic basis of resistance to the most commonly-applied carbamate, bendiocarb, in An. gambiae from Tiassalé. Geographically-replicated whole genome microarray experiments identified elevated P450 enzyme expression as associated with bendiocarb resistance, most notably genes from the CYP6 subfamily. P450s were further implicated in resistance phenotypes by induction of significantly elevated mortality to bendiocarb by the synergist piperonyl butoxide (PBO), which also enhanced the action of pyrethroids and an organophosphate. CYP6P3 and especially CYP6M2 produced bendiocarb resistance via transgenic expression in Drosophila in addition to pyrethroid resistance for both genes, and DDT resistance for CYP6M2 expression. CYP6M2 can thus cause resistance to three distinct classes of insecticide although the biochemical mechanism for carbamates is unclear because, in contrast to CYP6P3, recombinant CYP6M2 did not metabolise bendiocarb in vitro. Strongly bendiocarb resistant mosquitoes also displayed elevated expression of the acetylcholinesterase ACE-1 gene, arising at least in part from gene duplication, which confers a survival advantage to carriers of additional copies of resistant ACE-1 G119S alleles. Our results are alarming for vector-based malaria control. Extreme carbamate resistance in Tiassalé An. gambiae results from coupling of over-expressed target site allelic variants with heightened CYP6 P450 expression, which also provides resistance across contrasting insecticides. Mosquito populations displaying such a diverse basis of extreme and cross-resistance are likely to be unresponsive to standard insecticide resistance management practices.

The opposite end of the attention deficit hyperactivity disorder continuum: genetic and environmental aetiologies of extremely low ADHD traits.

PubMed

Greven, Corina U; Merwood, Andrew; van der Meer, Jolanda M J; Haworth, Claire M A; Rommelse, Nanda; Buitelaar, Jan K

2016-04-01

Although attention deficit hyperactivity disorder (ADHD) is thought to reflect a continuously distributed quantitative trait, it is assessed through binary diagnosis or skewed measures biased towards its high, symptomatic extreme. A growing trend is to study the positive tail of normally distributed traits, a promising avenue, for example, to study high intelligence to increase power for gene-hunting for intelligence. However, the emergence of such a 'positive genetics' model has been tempered for ADHD due to poor phenotypic resolution at the low extreme. Overcoming this methodological limitation, we conduct the first study to assess the aetiologies of low extreme ADHD traits. In a population-representative sample of 2,143 twins, the Strength and Weaknesses of ADHD Symptoms and Normal behaviour (SWAN) questionnaire was used to assess ADHD traits on a continuum from low to high. Aetiological influences on extreme ADHD traits were estimated using DeFries-Fulker extremes analysis. ADHD traits were related to behavioural, cognitive and home environmental outcomes using regression. Low extreme ADHD traits were significantly influenced by shared environmental factors (23-35%) but were not significantly heritable. In contrast, high-extreme ADHD traits showed significant heritability (39-51%) but no shared environmental influences. Compared to individuals with high extreme or with average levels of ADHD traits, individuals with low extreme ADHD traits showed fewer internalizing and externalizing behaviour problems, better cognitive performance and more positive behaviours and positive home environmental outcomes. Shared environmental influences on low extreme ADHD traits may reflect passive gene-environment correlation, which arises because parents provide environments as well as passing on genes. Studying the low extreme opens new avenues to study mechanisms underlying previously neglected positive behaviours. This is different from the current deficit-based model of intervention, but congruent with a population-level approach to improving youth wellbeing. © 2015 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

Species-Specific Responses of Juvenile Rockfish to Elevated pCO2: From Behavior to Genomics

PubMed Central

Hamilton, Scott L.; Logan, Cheryl A.; Fennie, Hamilton W.; Sogard, Susan M.; Barry, James P.; Makukhov, April D.; Tobosa, Lauren R.; Boyer, Kirsten; Lovera, Christopher F.; Bernardi, Giacomo

2017-01-01

In the California Current ecosystem, global climate change is predicted to trigger large-scale changes in ocean chemistry within this century. Ocean acidification—which occurs when increased levels of atmospheric CO2 dissolve into the ocean—is one of the biggest potential threats to marine life. In a coastal upwelling system, we compared the effects of chronic exposure to low pH (elevated pCO2) at four treatment levels (i.e., pCO2 = ambient [500], moderate [750], high [1900], and extreme [2800 μatm]) on behavior, physiology, and patterns of gene expression in white muscle tissue of juvenile rockfish (genus Sebastes), integrating responses from the transcriptome to the whole organism level. Experiments were conducted simultaneously on two closely related species that both inhabit kelp forests, yet differ in early life history traits, to compare high-CO2 tolerance among species. Our findings indicate that these congeners express different sensitivities to elevated CO2 levels. Copper rockfish (S. caurinus) exhibited changes in behavioral lateralization, reduced critical swimming speed, depressed aerobic scope, changes in metabolic enzyme activity, and increases in the expression of transcription factors and regulatory genes at high pCO2 exposure. Blue rockfish (S. mystinus), in contrast, showed no significant changes in behavior, swimming physiology, or aerobic capacity, but did exhibit significant changes in the expression of muscle structural genes as a function of pCO2, indicating acclimatization potential. The capacity of long-lived, late to mature, commercially important fish to acclimatize and adapt to changing ocean chemistry over the next 50–100 years is likely dependent on species-specific physiological tolerances. PMID:28056071

Uses for lunar crawler transporters

NASA Astrophysics Data System (ADS)

Kaden, Richard A.

This article discusses state-of-the-art crawler transporters and expresses the need for additional research and development for lunar crawlers. The thrust of the paper illustrates how the basic crawler technology has progressed to a point where extremely large modules can be shop fabricated and move to some distant location at a considerable savings. Also, extremely heavy loads may be lifted by large crawler cranes and placed in designed locations. The Transi-Lift Crawler crane with its traveling counterweight is an attractive concept for lunar construction.

Salt-losing nephropathy in hypothyroidism.

PubMed

Bautista, Aileen Azul; Duya, Jose Eduardo De Leon; Sandoval, Mark Anthony Santiago

2014-05-21

A 35-year-old man presented with recurrent lower extremity weakness associated with polyuria later progressing to generalised weakness with difficulty in breathing. The patient was hypotensive and dry, with normal thyroid and chest examination, weak lower extremity and carpopedal spasm. Workup revealed hypokalaemia, hyponatraemia, hypocalcaemia, hypomagnesaemia, hypochloraemia and hypophosphataemia. Arterial blood gas showed respiratory alkalosis with good oxygenation. Twenty-four-hour urine collection showed normal volume with electrolyte wasting. Thyroid function test revealed overt hypothyroidism with negative antithyroid peroxidase. The patient was well after treatment with levothyroxine, volume and electrolyte replacement and was discharged. Thyroid hormones are related to the expression of the Na-K-ATPase, Na-Pi cotransporter, Mg-ATPase and Na-Ca exchanger pumps in the renal tubules. Sodium, potassium, phosphate, calcium, magnesium and water losses result from decreased expression of these pumps. 2014 BMJ Publishing Group Ltd.

Fifty hertz extremely low-frequency magnetic field exposure elicits redox and trophic response in rat-cortical neurons.

PubMed

Di Loreto, Silvia; Falone, Stefano; Caracciolo, Valentina; Sebastiani, Pierluigi; D'Alessandro, Antonella; Mirabilio, Alessandro; Zimmitti, Vincenzo; Amicarelli, Fernanda

2009-05-01

Large research activity has raised around the mechanisms of interaction between extremely low-frequency magnetic fields (ELF-MFs) and biological systems. ELF-MFs may interfere with chemical reactions involving reactive oxygen species (ROS), thus facilitating oxidative damages in living cells. Cortical neurons are particularly susceptible to oxidative stressors and are also highly dependent on the specific factors and proteins governing neuronal development, activity and survival. The aim of the present work was to investigate the effects of exposures to two different 50 Hz sinusoidal ELF-MFs intensities (0.1 and 1 mT) in maturing rat cortical neurons' major anti-oxidative enzymatic and non-enzymatic cellular protection systems, membrane peroxidative damage, as well as growth factor, and cytokine expression pattern. Briefly, our results showed that ELF-MFs affected positively the cell viability and concomitantly reduced the levels of apoptotic death in rat neuronal primary cultures, with no significant effects on the main anti-oxidative defences. Interestingly, linear regression analysis suggested a positive correlation between reduced glutathione (GSH) and ROS levels in 1 mT MF-exposed cells. On this basis, our hypothesis is that GSH could play an important role in the antioxidant defence towards the ELF-MF-induced redox challenge. Moreover, the GSH-based cellular response was achieved together with a brain-derived neurotrophic factor over-expression as well as with the interleukin 1beta-dependent regulation of pro-survival signaling pathways after ELF-MF exposure.

Dimorphous expressions of positive emotion: displays of both care and aggression in response to cute stimuli.

PubMed

Aragón, Oriana R; Clark, Margaret S; Dyer, Rebecca L; Bargh, John A

2015-03-01

Extremely positive experiences, and positive appraisals thereof, produce intense positive emotions that often generate both positive expressions (e.g., smiles) and expressions normatively reserved for negative emotions (e.g., tears). We developed a definition of these dimorphous expressions and tested the proposal that their function is to regulate emotions. We showed that individuals who express emotions in this dimorphous manner do so as a general response across a variety of emotionally provoking situations, which suggests that these expressions are responses to intense positive emotion rather than unique to one particular situation. We used cute stimuli (an elicitor of positive emotion) to demonstrate both the existence of these dimorphous expressions and to provide preliminary evidence of their function as regulators of emotion. © The Author(s) 2015.

Comparative metagenomic and metatranscriptomic analyses of microbial communities in acid mine drainage.

PubMed

Chen, Lin-xing; Hu, Min; Huang, Li-nan; Hua, Zheng-shuang; Kuang, Jia-liang; Li, Sheng-jin; Shu, Wen-sheng

2015-07-01

The microbial communities in acid mine drainage have been extensively studied to reveal their roles in acid generation and adaption to this environment. Lacking, however, are integrated community- and organism-wide comparative gene transcriptional analyses that could reveal the response and adaptation mechanisms of these extraordinary microorganisms to different environmental conditions. In this study, comparative metagenomics and metatranscriptomics were performed on microbial assemblages collected from four geochemically distinct acid mine drainage (AMD) sites. Taxonomic analysis uncovered unexpectedly high microbial biodiversity of these extremely acidophilic communities, and the abundant taxa of Acidithiobacillus, Leptospirillum and Acidiphilium exhibited high transcriptional activities. Community-wide comparative analyses clearly showed that the AMD microorganisms adapted to the different environmental conditions via regulating the expression of genes involved in multiple in situ functional activities, including low-pH adaptation, carbon, nitrogen and phosphate assimilation, energy generation, environmental stress resistance, and other functions. Organism-wide comparative analyses of the active taxa revealed environment-dependent gene transcriptional profiles, especially the distinct strategies used by Acidithiobacillus ferrivorans and Leptospirillum ferrodiazotrophum in nutrients assimilation and energy generation for survival under different conditions. Overall, these findings demonstrate that the gene transcriptional profiles of AMD microorganisms are closely related to the site physiochemical characteristics, providing clues into the microbial response and adaptation mechanisms in the oligotrophic, extremely acidic environments.

White spot syndrome virus (WSSV) infection in shrimp (Litopenaeus vannamei) exposed to low and high salinity.

PubMed

Ramos-Carreño, Santiago; Valencia-Yáñez, Ricardo; Correa-Sandoval, Francisco; Ruíz-García, Noé; Díaz-Herrera, Fernando; Giffard-Mena, Ivone

2014-09-01

White spot syndrome virus (WSSV) has a worldwide distribution and is considered one of the most pathogenic and devastating viruses to the shrimp industry. A few studies have explored the effect of WSSV on shrimp acclimated to low (5 practical salinity units [psu]) or high ([40 psu) salinity conditions. In this work, we analysed the physiological response of WSSV-infected Litopenaeus vannamei juveniles that were acclimated to different salinities (5, 15, 28, 34 and 54 psu). We evaluated the osmotic response and survival of the shrimp at different times after infection (0 to 48 hours), and we followed the expression levels of a viral gene (vp664) in shrimp haemolymph using real-time PCR. Our results indicate that the susceptibility of the shrimp to the virus increased at extreme salinities (5 and 54 psu), with higher survival rates at 15 and 28 psu, which were closer to the iso-osmotic point (24.7 psu, 727.5 mOsmol/kg). Acute exposure to the virus made the haemolymph less hyperosmotic at 5 and 15 psu and less hypo-osmotic at higher salinities ([28 psu). The capacity of white shrimp to osmoregulate, and thus survive, significantly decreased following WSSV infection. According to our results, extreme salinities (5 or 54 psu) are more harmful than seawater.

RNA-Seq reveals seven promising candidate genes affecting the proportion of thick egg albumen in layer-type chickens.

PubMed

Wan, Yi; Jin, Sihua; Ma, Chendong; Wang, Zhicheng; Fang, Qi; Jiang, Runshen

2017-12-22

Eggs with a much higher proportion of thick albumen are preferred in the layer industry, as they are favoured by consumers. However, the genetic factors affecting the thick egg albumen trait have not been elucidated. Using RNA sequencing, we explored the magnum transcriptome in 9 Rhode Island white layers: four layers with phenotypes of extremely high ratios of thick to thin albumen (high thick albumen, HTA) and five with extremely low ratios (low thick albumen, LTA). A total of 220 genes were differentially expressed, among which 150 genes were up-regulated and 70 were down-regulated in the HTA group compared with the LTA group. Gene Ontology (GO) analysis revealed that the up-regulated genes in HTA were mainly involved in a wide range of regulatory functions. In addition, a large number of these genes were related to glycosphingolipid biosynthesis, focal adhesion, ECM-receptor interactions and cytokine-cytokine receptor interactions. Based on functional analysis, ST3GAL4, FUT4, ITGA2, SDC3, PRLR, CDH4 and GALNT9 were identified as promising candidate genes for thick albumen synthesis and metabolism during egg formation. These results provide new insights into the molecular mechanisms of egg albumen traits and may contribute to future breeding strategies that optimise the proportion of thick egg albumen.

A simple scaling approach to produce climate scenarios of local precipitation extremes for the Netherlands

NASA Astrophysics Data System (ADS)

Lenderink, Geert; Attema, Jisk

2015-08-01

Scenarios of future changes in small scale precipitation extremes for the Netherlands are presented. These scenarios are based on a new approach whereby changes in precipitation extremes are set proportional to the change in water vapor amount near the surface as measured by the 2m dew point temperature. This simple scaling framework allows the integration of information derived from: (i) observations, (ii) a new unprecedentedly large 16 member ensemble of simulations with the regional climate model RACMO2 driven by EC-Earth, and (iii) short term integrations with a non-hydrostatic model Harmonie. Scaling constants are based on subjective weighting (expert judgement) of the three different information sources taking also into account previously published work. In all scenarios local precipitation extremes increase with warming, yet with broad uncertainty ranges expressing incomplete knowledge of how convective clouds and the atmospheric mesoscale circulation will react to climate change.

Extreme throat initial data set and horizon area-angular momentum inequality for axisymmetric black holes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dain, Sergio; Max Planck Institute for Gravitational Physics

2010-11-15

We present a formula that relates the variations of the area of extreme throat initial data with the variation of an appropriate defined mass functional. From this expression we deduce that the first variation, with fixed angular momentum, of the area is zero and the second variation is positive definite evaluated at the extreme Kerr throat initial data. This indicates that the area of the extreme Kerr throat initial data is a minimum among this class of data. And hence the area of generic throat initial data is bounded from below by the angular momentum. Also, this result strongly suggestsmore » that the inequality between area and angular momentum holds for generic asymptotically flat axially symmetric black holes. As an application, we prove this inequality in the nontrivial family of spinning Bowen-York initial data.« less

Site-specific variation in gene expression from Symbiodinium spp. associated with offshore and inshore Porites astreoides in the lower Florida Keys is lost with bleaching and disease stress.

PubMed

Salas, Briana Hauff; Haslun, Joshua A; Strychar, Kevin B; Ostrom, Peggy H; Cervino, James M

2017-01-01

Scleractinian coral are experiencing unprecedented rates of mortality due to increases in sea surface temperatures in response to global climate change. Some coral species however, survive high temperature events due to a reduced susceptibility to bleaching. We investigated the relationship between bleaching susceptibility and expression of five metabolically related genes of Symbiodinium spp. from the coral Porites astreoides originating from an inshore and offshore reef in the Florida Keys. The acclimatization potential of Symbiodinium spp. to changing temperature regimes was also measured via a two-year reciprocal transplant between the sites. Offshore coral fragments displayed significantly higher expression in Symbiodinium spp. genes PCNA, SCP2, G3PDH, PCP and psaE than their inshore counterparts (p<0.05), a pattern consistent with increased bleaching susceptibility in offshore corals. Additionally, gene expression patterns in Symbiodinium spp. from site of origin were conserved throughout the two-year reciprocal transplant, indicating acclimatization did not occur within this multi-season time frame. Further, laboratory experiments were used to investigate the influence of acute high temperature (32°C for eight hours) and disease (lipopolysaccharide of Serratia marcescens) on the five metabolically related symbiont genes from the same offshore and inshore P. astreoides fragments. Gene expression did not differ between reef fragments, or as a consequence of acute exposure to heat or heat and disease, contrasting to results found in the field. Gene expression reported here indicates functional variation in populations of Symbiodinium spp. associated with P. astreoides in the Florida Keys, and is likely a result of localized adaptation. However, gene expression patterns observed in the lab imply that functional variation in zooxanthellae observed under conditions of chronic moderate stress is lost under the acute extreme conditions studied here.

Site-specific variation in gene expression from Symbiodinium spp. associated with offshore and inshore Porites astreoides in the lower Florida Keys is lost with bleaching and disease stress

PubMed Central

Haslun, Joshua A.; Strychar, Kevin B.; Ostrom, Peggy H.; Cervino, James M.

2017-01-01

Scleractinian coral are experiencing unprecedented rates of mortality due to increases in sea surface temperatures in response to global climate change. Some coral species however, survive high temperature events due to a reduced susceptibility to bleaching. We investigated the relationship between bleaching susceptibility and expression of five metabolically related genes of Symbiodinium spp. from the coral Porites astreoides originating from an inshore and offshore reef in the Florida Keys. The acclimatization potential of Symbiodinium spp. to changing temperature regimes was also measured via a two-year reciprocal transplant between the sites. Offshore coral fragments displayed significantly higher expression in Symbiodinium spp. genes PCNA, SCP2, G3PDH, PCP and psaE than their inshore counterparts (p<0.05), a pattern consistent with increased bleaching susceptibility in offshore corals. Additionally, gene expression patterns in Symbiodinium spp. from site of origin were conserved throughout the two-year reciprocal transplant, indicating acclimatization did not occur within this multi-season time frame. Further, laboratory experiments were used to investigate the influence of acute high temperature (32°C for eight hours) and disease (lipopolysaccharide of Serratia marcescens) on the five metabolically related symbiont genes from the same offshore and inshore P. astreoides fragments. Gene expression did not differ between reef fragments, or as a consequence of acute exposure to heat or heat and disease, contrasting to results found in the field. Gene expression reported here indicates functional variation in populations of Symbiodinium spp. associated with P. astreoides in the Florida Keys, and is likely a result of localized adaptation. However, gene expression patterns observed in the lab imply that functional variation in zooxanthellae observed under conditions of chronic moderate stress is lost under the acute extreme conditions studied here. PMID:28355291

Investigating Extreme Heat and Humidity in the Northeast United States from a Joint Hazard Perspective

NASA Astrophysics Data System (ADS)

Horton, R. M.; Coffel, E.; Kushnir, Y.

2014-12-01

Recent years have seen an increasing focus on extreme high temperature events, as our understanding of societal vulnerability to such extremes has grown. Less climate research has been devoted to heat indices that consider the joint hazard posed by high temperatures and high humidity, even though heat indices are being prioritized by utility providers and public health officials. This paper evaluates how well CMIP5 models are able to reproduce the large-scale features and surface conditions associated with joint high heat and humidity events in the Northeast U.S. Projected changes in heat indices are also shown both for the full set of CMIP5 models and for a subset of models that best reproduce the statistics of historical high heat index events. The importance of considering the relationship between 1) temperature and humidity extremes and 2) projected changes in extreme temperature and humidity extremes, rather than investigating each variable independently, will be emphasized. Potential impacts of the findings on human mortality and energy consumption will be briefly discussed.

Extremal black holes in dynamical Chern-Simons gravity

NASA Astrophysics Data System (ADS)

McNees, Robert; Stein, Leo C.; Yunes, Nicolás

2016-12-01

Rapidly rotating black hole (BH) solutions in theories beyond general relativity (GR) play a key role in experimental gravity, as they allow us to compute observables in extreme spacetimes that deviate from the predictions of GR. Such solutions are often difficult to find in beyond-general-relativity theories due to the inclusion of additional fields that couple to the metric nonlinearly and non-minimally. In this paper, we consider rotating BH solutions in one such theory, dynamical Chern-Simons (dCS) gravity, where the Einstein-Hilbert action is modified by the introduction of a dynamical scalar field that couples to the metric through the Pontryagin density. We treat dCS gravity as an effective field theory and work in the decoupling limit, where corrections are treated as small perturbations from GR. We perturb about the maximally rotating Kerr solution, the so-called extremal limit, and develop mathematical insight into the analysis techniques needed to construct solutions for generic spin. First we find closed-form, analytic expressions for the extremal scalar field, and then determine the trace of the metric perturbation, giving both in terms of Legendre decompositions. Retaining only the first three and four modes in the Legendre representation of the scalar field and the trace, respectively, suffices to ensure a fidelity of over 99% relative to full numerical solutions. The leading-order mode in the Legendre expansion of the trace of the metric perturbation contains a logarithmic divergence at the extremal Kerr horizon, which is likely to be unimportant as it occurs inside the perturbed dCS horizon. The techniques employed here should enable the construction of analytic, closed-form expressions for the scalar field and metric perturbations on a background with arbitrary rotation.

Molecular cloning and functional analysis of the FLOWERING LOCUS T (FT) homolog GhFT1 from Gossypium hirsutum.

PubMed

Guo, Danli; Li, Chao; Dong, Rui; Li, Xiaobo; Xiao, Xiangwen; Huang, Xianzhong

2015-06-01

FLOWERING LOCUS T (FT) encodes a member of the phosphatidylethanolamine-binding protein (PEBP) family that functions as the mobile floral signal, playing an important role in regulating the floral transition in angiosperms. We isolated an FT-homolog (GhFT1) from Gossypium hirsutum L. cultivar, Xinluzao 33 GhFT1 was predominantly expressed in stamens and sepals, and had a relatively higher expression level during the initiation stage of fiber development. GhFT1 mRNA displayed diurnal oscillations in both long-day and short-day condition, suggesting that the expression of this gene may be under the control of the circadian clock. Subcellular analysis revealed that GhFT1 protein located in the cytoplasm and nucleus. Ectopic expression of GhFT1 in transgenic arabidopsis plants resulted in early flowering compared with wild-type plants. In addition, ectopic expression of GhFT1 in arabidopsis ft-10 mutants partially rescued the extremely late flowering phenotype. Finally, several flowering related genes functioning downstream of AtFT were highly upregulated in the 35S::GhFT1 transgenic arabidopsis plants. In summary, GhFT1 is an FT-homologous gene in cotton that regulates flower transition similar to its orthologs in other plant species and thus it may be a candidate target for promoting early maturation in cotton breeding. © 2014 Institute of Botany, Chinese Academy of Sciences.

The progression of CD56+ myeloid sarcoma: A case report and literature review

PubMed Central

WANG, XIN; LI, WEN-SHENG; ZHENG, YAN; YING, ZHAO-XIA; WANG, YONG-XIAN; WANG, YING-MEI; ZHENG, JUN-FENG; XIAO, SHENG-XIANG

2016-01-01

The current study presents a case of cluster of differentiation (CD)56+ myeloid sarcoma in a patient that initially presented with skin lesions, and provides evidence for the clinical and differential diagnosis of myeloid sarcoma. The patient of the present case report was a 65-year-old man who was admitted to hospital with a six-month history of bilateral purple-red papules and nodules, which were present on the upper limbs of the patient and had spread over his whole body one month prior to admission to the hospital. Pathological examination demonstrated a diffuse infusion of primitive round cells at the papillary dermis and subcutaneous tissues. The infiltrated cells were 40–60 µm in diameter and morphologically identical. Immunohistochemical examination revealed that the cells expressed myeloperoxidase, CD56, CD43 and T-cell intracytoplasmic antigen. In addition, several cells expressed CD34, and 90% of the cells expressed Ki67. While the majority of cells in myeloid sarcoma do not express CD56, the present case was a myeloid sarcoma that expressed CD56, which is extremely rare. The sarcoma in the present patient progressed rapidly, and the patient died eight months following the onset of disease. Clinicians should be aware of CD56+ myeloid sarcoma, which is easily misdiagnosed and inappropriately treated. Consequently, myeloid sarcoma may have a high malignancy and poor outcome for patients. PMID:27123069

Risk for Mania and Positive Emotional Responding: Too Much of a Good Thing?

PubMed Central

Gruber, June; Oveis, Christopher; Keltner, Dacher; Johnson, Sheri L.

2010-01-01

Although positive emotion research has begun to flourish, the extremes of positive emotion remain understudied. The present research used a multimethod approach to examine positive emotional disturbance by comparing participants at high and low risk for episodes of mania, which involves elevations in positive emotionality. Ninety participants were recruited into a high or low mania risk group according to responses on the Hypomanic Personality Scale. Participants’ subjective, expressive, and physiological emotional responses were gathered while they watched two positive, two negative, and one neutral film clip. Results suggested that participants at high risk for mania reported elevated positive emotion and irritability and also exhibited elevated cardiac vagal tone across positive, negative, and neutral films. Discussion focuses on the implications these findings have for the diagnosis and prevention of bipolar disorder, as well as for the general study of positive emotion. PMID:18266513

Risk for mania and positive emotional responding: too much of a good thing?

PubMed

Gruber, June; Johnson, Sheri L; Oveis, Christopher; Keltner, Dacher

2008-02-01

Although positive emotion research has begun to flourish, the extremes of positive emotion remain understudied. The present research used a multimethod approach to examine positive emotional disturbance by comparing participants at high and low risk for episodes of mania, which involves elevations in positive emotionality. Ninety participants were recruited into a high or low mania risk group according to responses on the Hypomanic Personality Scale. Participants' subjective, expressive, and physiological emotional responses were gathered while they watched two positive, two negative, and one neutral film clip. Results suggested that participants at high risk for mania reported elevated positive emotion and irritability and also exhibited elevated cardiac vagal tone across positive, negative, and neutral films. Discussion focuses on the implications these findings have for the diagnosis and prevention of bipolar disorder, as well as for the general study of positive emotion.

Suppression of p53-inducible gene 3 is significant for glioblastoma progression and predicts poor patient prognosis.

PubMed

Quan, Jishu; Li, Yong; Jin, Meihua; Chen, Dunfu; Yin, Xuezhe; Jin, Ming

2017-03-01

Glioblastoma is the most malignant and invasive brain tumor with extremely poor prognosis. p53-inducible gene 3, a downstream molecule of the tumor suppressor p53, has been found involved in apoptosis and oxidative stress response. However, the functions of p53-inducible gene 3(PIG3) in cancer are far from clear including glioblastoma. In this study, we found that p53-inducible gene 3 expression was suppressed in glioblastoma tissues compared with normal tissues. And the expression of p53-inducible gene 3 was significantly associated with the World Health Organization grade. Patients with high p53-inducible gene 3 expression have a significantly longer median survival time (15 months) than those with low p53-inducible gene 3 expression (8 months). According to Cox regression analysis, p53-inducible gene 3 was an independent prognostic factor with multivariate hazard ratio of 0.578 (95% confidence interval, 0.352-0.947; p = 0.030) for overall survival. Additionally, gain and loss of function experiments showed that knockdown of p53-inducible gene 3 significantly increased the proliferation and invasion ability of glioblastoma cells while overexpression of p53-inducible gene 3 inhibited the proliferation and invasion ability. The results of in vivo glioblastoma models further confirmed that p53-inducible gene 3 suppression promoted glioblastoma progression. Altogether, our data suggest that high expression of p53-inducible gene 3 is significant for glioblastoma inhibition and p53-inducible gene 3 independently indicates good prognosis in patients, which might be a novel prognostic biomarker or potential therapeutic target in glioblastoma.

Flower-predominant expression of a gene encoding a novel class I chitinase in rice (Oryza sativa L.).

PubMed

Takakura, Y; Ito, T; Saito, H; Inoue, T; Komari, T; Kuwata, S

2000-04-01

A flower-predominant cDNA for a gene, termed OsChia 1;175, was isolated from a cDNA library of rice pistils. Northern blot and RT-PCR analyses revealed that the OsChia 1;175 gene is highly expressed in floral organs (pistils, stamens and lodicules at the heading stage) but not or at an extremely low level in vegetative organs. OsChia 1;175 encodes a protein that consists of 340 amino acid residues, and the putative mature protein shows 52% to 63% amino acid identity to class I chitinases of rice or other plants. The phylogenetic tree shows that the OsChia 1;175 protein is a new type of plant class I chitinase in rice. The expression of OsChia 1;175 in vegetative organs is not induced by several chemicals, UV, and wounding. The soluble putative mature OsChia 1;175 protein expressed in Escherichia coli exhibited chitinase activity in the assay with colloidal chitin as a substrate. Genomic Southern analysis revealed that the OsChia 1;175 gene was organized as a low-copy gene family. The rice genomic library was screened and a genome clone corresponding to OsChia 1;175 was isolated. The transcription start sites of the OsChia 1;175 gene were mapped by primer extension analysis. The 1.2 kb putative promoter region of the OsChia 1;175 gene was fused to the GUS (beta-glucuronidase) gene, and this chimeric gene was introduced to rice by Agrobacterium-mediated transformation. The flower-predominant gene expression was identified also in the transgenic rice plants. The high promoter activity was detected in the stigmas, styles, stamens and lodicules in transgenic plants. The possible functions of OsChia 1;175 are discussed.

Effects of Extreme Temperatures on Cause-Specific Cardiovascular Mortality in China

PubMed Central

Wang, Xuying; Li, Guoxing; Liu, Liqun; Westerdahl, Dane; Jin, Xiaobin; Pan, Xiaochuan

2015-01-01

Objective: Limited evidence is available for the effects of extreme temperatures on cause-specific cardiovascular mortality in China. Methods: We collected data from Beijing and Shanghai, China, during 2007–2009, including the daily mortality of cardiovascular disease, cerebrovascular disease, ischemic heart disease and hypertensive disease, as well as air pollution concentrations and weather conditions. We used Poisson regression with a distributed lag non-linear model to examine the effects of extremely high and low ambient temperatures on cause-specific cardiovascular mortality. Results: For all cause-specific cardiovascular mortality, Beijing had stronger cold and hot effects than those in Shanghai. The cold effects on cause-specific cardiovascular mortality reached the strongest at lag 0–27, while the hot effects reached the strongest at lag 0–14. The effects of extremely low and high temperatures differed by mortality types in the two cities. Hypertensive disease in Beijing was particularly susceptible to both extremely high and low temperatures; while for Shanghai, people with ischemic heart disease showed the greatest relative risk (RRs = 1.16, 95% CI: 1.03, 1.34) to extremely low temperature. Conclusion: People with hypertensive disease were particularly susceptible to extremely low and high temperatures in Beijing. People with ischemic heart disease in Shanghai showed greater susceptibility to extremely cold days. PMID:26703637

Effects of Extreme Temperatures on Cause-Specific Cardiovascular Mortality in China.

PubMed

Wang, Xuying; Li, Guoxing; Liu, Liqun; Westerdahl, Dane; Jin, Xiaobin; Pan, Xiaochuan

2015-12-21

Limited evidence is available for the effects of extreme temperatures on cause-specific cardiovascular mortality in China. We collected data from Beijing and Shanghai, China, during 2007-2009, including the daily mortality of cardiovascular disease, cerebrovascular disease, ischemic heart disease and hypertensive disease, as well as air pollution concentrations and weather conditions. We used Poisson regression with a distributed lag non-linear model to examine the effects of extremely high and low ambient temperatures on cause-specific cardiovascular mortality. For all cause-specific cardiovascular mortality, Beijing had stronger cold and hot effects than those in Shanghai. The cold effects on cause-specific cardiovascular mortality reached the strongest at lag 0-27, while the hot effects reached the strongest at lag 0-14. The effects of extremely low and high temperatures differed by mortality types in the two cities. Hypertensive disease in Beijing was particularly susceptible to both extremely high and low temperatures; while for Shanghai, people with ischemic heart disease showed the greatest relative risk (RRs = 1.16, 95% CI: 1.03, 1.34) to extremely low temperature. People with hypertensive disease were particularly susceptible to extremely low and high temperatures in Beijing. People with ischemic heart disease in Shanghai showed greater susceptibility to extremely cold days.

A web-based study of bipolarity and impulsivity in athletes engaging in extreme and high-risk sports.

PubMed

Dudek, Dominika; Siwek, Marcin; Jaeschke, Rafał; Drozdowicz, Katarzyna; Styczeń, Krzysztof; Arciszewska, Aleksandra; Chrobak, Adrian A; Rybakowski, Janusz K

2016-06-01

We hypothesised that men and women who engage in extreme or high-risk sports would score higher on standardised measures of bipolarity and impulsivity compared to age and gender matched controls. Four-hundred and eighty extreme or high-risk athletes (255 males and 225 females) and 235 age-matched control persons (107 males and 128 females) were enrolled into the web-based case-control study. The Mood Disorder Questionnaire (MDQ) and Barratt Impulsiveness Scale (BIS-11) were administered to screen for bipolarity and impulsive behaviours, respectively. Results indicated that extreme or high-risk athletes had significantly higher scores of bipolarity and impulsivity, and lower scores on cognitive complexity of the BIS-11, compared to controls. Further, there were positive correlations between the MDQ and BIS-11 scores. These results showed greater rates of bipolarity and impulsivity, in the extreme or high-risk athletes, suggesting these measures are sensitive to high-risk behaviours.

Gene expression and molecular phylogenetic analyses of beta-glucosidase in the termite Reticulitermes speratus (Isoptera: Rhinotermitidae).

PubMed

Shimada, Keisuke; Maekawa, Kiyoto

2014-06-01

Beta-glucosidase (BG) is known as a multifunctional enzyme for social maintenance in terms of both cellulose digestion and social communication in termites. However, the expression profiles of each BG gene and their evolutionary history are not well understood. First, we cloned two types of BG homologs (RsBGI and RsBGII) from the termite Reticulitermes speratus (Kolbe). Gene expression analyses showed that RsBGI expression levels of primary queens and kings from 30 to 100 days after colony foundation were high, but those of reproductives dropped after day 400. Extremely low gene expression levels of RsBGI were observed in eggs, whereas workers had significantly higher expression levels than those of soldiers and other colony members. Consequently, RsBGI gene expression levels changed among each developmental stage, and RsBGI was shown to be involved in cellulose digestion. On the other hand, the RsBGII gene was consistently expressed in all castes and developmental stages examined, and notable expression changes were not observed among them, including in eggs. It was indicated that RsBGII is a main component involved in social communication, for example, the egg-recognition pheromone shown in this species previously. Finally, we obtained partial gene homologs from other termite and cockroach species, including the woodroach (genus Cryptocercus), which is the sister group to termites, and performed molecular phylogenetic analyses. The results showed that the origin of the BG gene homologs preceded the divergence of termites and cockroaches, suggesting that the acquisition of multifunctionality of the BG gene also occurred in cockroach lineages. Copyright © 2014 Elsevier Ltd. All rights reserved.

Proteome analysis of Physcomitrella patens exposed to progressive dehydration and rehydration.

PubMed

Cui, Suxia; Hu, Jia; Guo, Shilei; Wang, Jie; Cheng, Yali; Dang, Xinxing; Wu, Lili; He, Yikun

2012-01-01

Physcomitrella patens is an extremely dehydration-tolerant moss. However, the molecular basis of its responses to loss of cellular water remains unclear. A comprehensive proteomic analysis of dehydration- and rehydration-responsive proteins has been conducted using quantitative two-dimensional difference in-gel electrophoresis (2D-DIGE), and traditional 2-D gel electrophoresis (2-DE) combined with MALDI TOF/TOF MS. Of the 216 differentially-expressed protein spots, 112 and 104 were dehydration- and rehydration-responsive proteins, respectively. The functional categories of the most differentially-expressed proteins were seed maturation, defence, protein synthesis and quality control, and energy production. Strikingly, most of the late embryogenesis abundant (LEA) proteins were expressed at a basal level under control conditions and their synthesis was strongly enhanced by dehydration, a pattern that was confirmed by RT-PCR. Actinoporins, phosphatidylethanolamine-binding protein, arabinogalactan protein, and phospholipase are the likely dominant players in the defence system. In addition, 24 proteins of unknown function were identified as novel dehydration- or rehydration-responsive proteins. Our data indicate that Physcomitrella adopts a rapid protein response mechanism to cope with dehydration in its leafy-shoot and basal expression levels of desiccation-tolerant proteins are rapidly upgraded at high levels under stress. This mechanism appears similar to that seen in angiosperm seeds.

Proteome analysis of Physcomitrella patens exposed to progressive dehydration and rehydration

PubMed Central

Cui, Suxia; Hu, Jia; Guo, Shilei; Wang, Jie; Cheng, Yali; Dang, Xinxing; Wu, Lili; He, Yikun

2012-01-01

Physcomitrella patens is an extremely dehydration-tolerant moss. However, the molecular basis of its responses to loss of cellular water remains unclear. A comprehensive proteomic analysis of dehydration- and rehydration-responsive proteins has been conducted using quantitative two-dimensional difference in-gel electrophoresis (2D-DIGE), and traditional 2-D gel electrophoresis (2-DE) combined with MALDI TOF/TOF MS. Of the 216 differentially-expressed protein spots, 112 and 104 were dehydration- and rehydration-responsive proteins, respectively. The functional categories of the most differentially-expressed proteins were seed maturation, defence, protein synthesis and quality control, and energy production. Strikingly, most of the late embryogenesis abundant (LEA) proteins were expressed at a basal level under control conditions and their synthesis was strongly enhanced by dehydration, a pattern that was confirmed by RT-PCR. Actinoporins, phosphatidylethanolamine-binding protein, arabinogalactan protein, and phospholipase are the likely dominant players in the defence system. In addition, 24 proteins of unknown function were identified as novel dehydration- or rehydration-responsive proteins. Our data indicate that Physcomitrella adopts a rapid protein response mechanism to cope with dehydration in its leafy-shoot and basal expression levels of desiccation-tolerant proteins are rapidly upgraded at high levels under stress. This mechanism appears similar to that seen in angiosperm seeds. PMID:21994173

Genome Structures and Transcriptomes Signify Niche Adaptation for the Multiple-Ion-Tolerant Extremophyte Schrenkiella parvula1[C][W][OPEN

PubMed Central

Oh, Dong-Ha; Hong, Hyewon; Lee, Sang Yeol; Yun, Dae-Jin; Bohnert, Hans J.; Dassanayake, Maheshi

2014-01-01

Schrenkiella parvula (formerly Thellungiella parvula), a close relative of Arabidopsis (Arabidopsis thaliana) and Brassica crop species, thrives on the shores of Lake Tuz, Turkey, where soils accumulate high concentrations of multiple-ion salts. Despite the stark differences in adaptations to extreme salt stresses, the genomes of S. parvula and Arabidopsis show extensive synteny. S. parvula completes its life cycle in the presence of Na+, K+, Mg2+, Li+, and borate at soil concentrations lethal to Arabidopsis. Genome structural variations, including tandem duplications and translocations of genes, interrupt the colinearity observed throughout the S. parvula and Arabidopsis genomes. Structural variations distinguish homologous gene pairs characterized by divergent promoter sequences and basal-level expression strengths. Comparative RNA sequencing reveals the enrichment of ion-transport functions among genes with higher expression in S. parvula, while pathogen defense-related genes show higher expression in Arabidopsis. Key stress-related ion transporter genes in S. parvula showed increased copy number, higher transcript dosage, and evidence for subfunctionalization. This extremophyte offers a framework to identify the requisite adjustments of genomic architecture and expression control for a set of genes found in most plants in a way to support distinct niche adaptation and lifestyles. PMID:24563282

Resource quality affects weapon and testis size and the ability of these traits to respond to selection in the leaf-footed cactus bug, Narnia femorata.

PubMed

Sasson, Daniel A; Munoz, Patricio R; Gezan, Salvador A; Miller, Christine W

2016-04-01

The size of weapons and testes can be central to male reproductive success. Yet, the expression of these traits is often extremely variable. Studies are needed that take a more complete organism perspective, investigating the sources of variation in both traits simultaneously and using developmental conditions that mimic those in nature. In this study, we investigated the components of variation in weapon and testis sizes using the leaf-footed cactus bug, Narnia femorata (Hemiptera: Coreidae) on three natural developmental diets. We show that the developmental diet has profound effects on both weapon and testis expression and scaling. Intriguingly, males in the medium-quality diet express large weapons but have relatively tiny testes, suggesting complex allocation decisions. We also find that heritability, evolvability, and additive genetic variation are highest in the high-quality diet for testis and body mass. This result suggests that these traits may have an enhanced ability to respond to selection during a small window of time each year when this diet is available. Taken together, these results illustrate that normal, seasonal fluctuations in the nutritional environment may play a large role in the expression of sexually selected traits and the ability of these traits to respond to selection.

Different levels of hsp70 and hsc70 mRNA expression in Iberian fish exposed to distinct river conditions

PubMed Central

Jesus, Tiago F.; Inácio, Ângela; Coelho, Maria M.

2013-01-01

Comprehension of the mechanisms by which ectotherms, such as fish, respond to thermal stress is paramount for understanding the threats that environmental changes may pose to wild populations. Heat shock proteins are molecular chaperones with an important role in several stress conditions such as high temperatures. In the Iberian Peninsula, particularly in Portugal, freshwater fish of the genus Squalius are subject to daily and seasonal temperature variations. To examine the extent to which different thermal regimes influence the expression patterns of hsp70 and hsc70 transcripts we exposed two species of Squalius (S. torgalensis and S. carolitertii) to different temperatures (20, 25, 30 and 35 °C). At 35 °C, there was a significant increase in the expression of hsp70 and hsc70 in the southern species, S. torgalensis, while the northern species, S. carolitertii, showed no increase in the expression of these genes; however, some individuals of the latter species died when exposed to 35 °C. These results suggest that S. torgalensis may cope better with harsher temperatures that are characteristic of this species natural environment; S. carolitertii, on the other hand, may be unable to deal with the extreme temperatures faced by the southern species. PMID:23569409

Adaptation potential of naturally ventilated barns to high temperature extremes: The OptiBarn project

NASA Astrophysics Data System (ADS)

Menz, Christoph

2016-04-01

Climate change interferes with various aspects of the socio-economic system. One important aspect is its influence on animal husbandry, especially dairy faming. Dairy cows are usually kept in naturally ventilated barns (NVBs) which are particular vulnerable to extreme events due to their low adaptation capabilities. An effective adaptation to high outdoor temperatures for example, is only possible under certain wind and humidity conditions. High temperature extremes are expected to increase in number and strength under climate change. To assess the impact of this change on NVBs and dairy cows also the changes in wind and humidity needs to be considered. Hence we need to consider the multivariate structure of future temperature extremes. The OptiBarn project aims to develop sustainable adaptation strategies for dairy housings under climate change for Europe, by considering the multivariate structure of high temperature extremes. In a first step we identify various multivariate high temperature extremes for three core regions in Europe. With respect to dairy cows in NVBs we will focus on the wind and humidity field during high temperature events. In a second step we will use the CORDEX-EUR-11 ensemble to evaluate the capability of the RCMs to model such events and assess their future change potential. By transferring the outdoor conditions to indoor climate and animal wellbeing the results of this assessment can be used to develop technical, architectural and animal specific adaptation strategies for high temperature extremes.

Metatranscriptomic analysis of lignocellulolytic microbial communities involved in high-solids decomposition of rice straw

DOE PAGES

Simmons, Christopher W.; Reddy, Amitha P.; D’haeseleer, Patrik; ...

2014-12-31

New lignocellulolytic enzymes are needed that maintain optimal activity under the harsh conditions present during industrial enzymatic deconstruction of biomass, including high temperatures, the absence of free water, and the presence of inhibitors from the biomass. Enriching lignocellulolytic microbial communities under these conditions provides a source of microorganisms that may yield robust lignocellulolytic enzymes tolerant to the extreme conditions needed to improve the throughput and efficiency of biomass enzymatic deconstruction. Identification of promising enzymes from these systems is challenging due to complex substrate-enzyme interactions and requirements to assay for activity. In this study, metatranscriptomes from compost-derived microbial communities enriched onmore » rice straw under thermophilic and mesophilic conditions were sequenced and analyzed to identify lignocellulolytic enzymes overexpressed under thermophilic conditions. To determine differential gene expression across mesophilic and thermophilic treatments, a method was developed which pooled gene expression by functional category, as indicated by Pfam annotations, since microbial communities performing similar tasks are likely to have overlapping functions even if they share no specific genes. Differential expression analysis identified enzymes from glycoside hydrolase family 48, carbohydrate binding module family 2, and carbohydrate binding module family 33 domains as significantly overexpressed in the thermophilic community. Overexpression of these protein families in the thermophilic community resulted from expression of a small number of genes not currently represented in any protein database. Genes in overexpressed protein families were predominantly expressed by a single Actinobacteria genus, Micromonospora. In conclusion, coupling measurements of deconstructive activity with comparative analyses to identify overexpressed enzymes in lignocellulolytic communities provides a targeted approach for discovery of candidate enzymes for more efficient biomass deconstruction. Furthermore, glycoside hydrolase family 48 cellulases and carbohydrate binding module family 33 polysaccharide monooxygenases with carbohydrate binding module family 2 domains may improve saccharification of lignocellulosic biomass under high-temperature and low moisture conditions relevant to industrial biofuel production.« less

Metatranscriptomic analysis of lignocellulolytic microbial communities involved in high-solids decomposition of rice straw

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simmons, Christopher W.; Reddy, Amitha P.; D’haeseleer, Patrik

New lignocellulolytic enzymes are needed that maintain optimal activity under the harsh conditions present during industrial enzymatic deconstruction of biomass, including high temperatures, the absence of free water, and the presence of inhibitors from the biomass. Enriching lignocellulolytic microbial communities under these conditions provides a source of microorganisms that may yield robust lignocellulolytic enzymes tolerant to the extreme conditions needed to improve the throughput and efficiency of biomass enzymatic deconstruction. Identification of promising enzymes from these systems is challenging due to complex substrate-enzyme interactions and requirements to assay for activity. In this study, metatranscriptomes from compost-derived microbial communities enriched onmore » rice straw under thermophilic and mesophilic conditions were sequenced and analyzed to identify lignocellulolytic enzymes overexpressed under thermophilic conditions. To determine differential gene expression across mesophilic and thermophilic treatments, a method was developed which pooled gene expression by functional category, as indicated by Pfam annotations, since microbial communities performing similar tasks are likely to have overlapping functions even if they share no specific genes. Differential expression analysis identified enzymes from glycoside hydrolase family 48, carbohydrate binding module family 2, and carbohydrate binding module family 33 domains as significantly overexpressed in the thermophilic community. Overexpression of these protein families in the thermophilic community resulted from expression of a small number of genes not currently represented in any protein database. Genes in overexpressed protein families were predominantly expressed by a single Actinobacteria genus, Micromonospora. In conclusion, coupling measurements of deconstructive activity with comparative analyses to identify overexpressed enzymes in lignocellulolytic communities provides a targeted approach for discovery of candidate enzymes for more efficient biomass deconstruction. Furthermore, glycoside hydrolase family 48 cellulases and carbohydrate binding module family 33 polysaccharide monooxygenases with carbohydrate binding module family 2 domains may improve saccharification of lignocellulosic biomass under high-temperature and low moisture conditions relevant to industrial biofuel production.« less

Sex differences in autism: a resting-state fMRI investigation of functional brain connectivity in males and females.

PubMed

Alaerts, Kaat; Swinnen, Stephan P; Wenderoth, Nicole

2016-06-01

Autism spectrum disorders (ASD) are far more prevalent in males than in females. Little is known however about the differential neural expression of ASD in males and females. We used a resting-state fMRI-dataset comprising 42 males/42 females with ASD and 75 male/75 female typical-controls to examine whether autism-related alterations in intrinsic functional connectivity are similar or different in males and females, and particularly whether alterations reflect 'neural masculinization', as predicted by the Extreme Male Brain theory. Males and females showed a differential neural expression of ASD, characterized by highly consistent patterns of hypo-connectivity in males with ASD (compared to typical males), and hyper-connectivity in females with ASD (compared to typical females). Interestingly, patterns of hyper-connectivity in females with ASD reflected a shift towards the (high) connectivity levels seen in typical males (neural masculinization), whereas patterns of hypo-connectivity observed in males with ASD reflected a shift towards the (low) typical feminine connectivity patterns (neural feminization). Our data support the notion that ASD is a disorder of sexual differentiation rather than a disorder characterized by masculinization in both genders. Future work is needed to identify underlying factors such as sex hormonal alterations that drive these sex-specific neural expressions of ASD. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Natural variation reveals that OsSAP16 controls low-temperature germination in rice.

PubMed

Wang, Xiang; Zou, Baohong; Shao, Qiaolin; Cui, Yongmei; Lu, Shan; Zhang, Yan; Huang, Quansheng; Huang, Ji; Hua, Jian

2018-01-23

Low temperature affects seed germination in plants, and low-temperature germination (LTG) is an important agronomic trait. Natural variation of LTG has been reported in rice, but the molecular basis for this variation is largely unknown. Here we report the phenotypic analysis of LTG in 187 rice natural accessions and a genome-wide association study (GWAS) of LTG in this collection. A total of 53 quantitative trait loci (QTLs) were found to be associated with LTG, of which 20 were located in previously reported QTLs. We further identified Stress-Associated Protein 16 (OsSAP16), coding for a zinc-finger domain protein, as a causal gene for one of the major LTG QTLs. Loss of OsSAP16 function reduces germination while greater expression of OsSAP16 enhances germination at low temperature. In addition, accessions with extremely high and low LTG values have correspondingly high and low OsSAP16 expression at low temperatures, suggesting that variation in expression of the OsSAP16 gene contributes to LTG variation. As the first case of identification of an LTG gene through GWAS, this study indicates that GWAS of natural accessions is an effective strategy in genetically dissecting LTG processes and gaining molecular understanding of low-temperature response and germination. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

The nonstationary impact of local temperature changes and ENSO on extreme precipitation at the global scale

NASA Astrophysics Data System (ADS)

Sun, Qiaohong; Miao, Chiyuan; Qiao, Yuanyuan; Duan, Qingyun

2017-12-01

The El Niño-Southern Oscillation (ENSO) and local temperature are important drivers of extreme precipitation. Understanding the impact of ENSO and temperature on the risk of extreme precipitation over global land will provide a foundation for risk assessment and climate-adaptive design of infrastructure in a changing climate. In this study, nonstationary generalized extreme value distributions were used to model extreme precipitation over global land for the period 1979-2015, with ENSO indicator and temperature as covariates. Risk factors were estimated to quantify the contrast between the influence of different ENSO phases and temperature. The results show that extreme precipitation is dominated by ENSO over 22% of global land and by temperature over 26% of global land. With a warming climate, the risk of high-intensity daily extreme precipitation increases at high latitudes but decreases in tropical regions. For ENSO, large parts of North America, southern South America, and southeastern and northeastern China are shown to suffer greater risk in El Niño years, with more than double the chance of intense extreme precipitation in El Niño years compared with La Niña years. Moreover, regions with more intense precipitation are more sensitive to ENSO. Global climate models were used to investigate the changing relationship between extreme precipitation and the covariates. The risk of extreme, high-intensity precipitation increases across high latitudes of the Northern Hemisphere but decreases in middle and lower latitudes under a warming climate scenario, and will likely trigger increases in severe flooding and droughts across the globe. However, there is some uncertainties associated with the influence of ENSO on predictions of future extreme precipitation, with the spatial extent and risk varying among the different models.

Transcriptome analysis in tardigrade species reveals specific molecular pathways for stress adaptations.

PubMed

Förster, Frank; Beisser, Daniela; Grohme, Markus A; Liang, Chunguang; Mali, Brahim; Siegl, Alexander Matthias; Engelmann, Julia C; Shkumatov, Alexander V; Schokraie, Elham; Müller, Tobias; Schnölzer, Martina; Schill, Ralph O; Frohme, Marcus; Dandekar, Thomas

2012-01-01

Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade Milnesium tardigradum were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from Hypsibius dujardini, revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for M. tardigradum are different from typical motifs known from higher animals. M. tardigradum and H. dujardini protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of M. tardigradum. These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and M. tardigradum in particular so highly stress resistant.

Native xylose-inducible promoter expands the genetic tools for the biomass-degrading, extremely thermophilic bacterium Caldicellulosiruptor bescii.

PubMed

Williams-Rhaesa, Amanda M; Awuku, Nanaakua K; Lipscomb, Gina L; Poole, Farris L; Rubinstein, Gabriel M; Conway, Jonathan M; Kelly, Robert M; Adams, Michael W W

2018-07-01

Regulated control of both homologous and heterologous gene expression is essential for precise genetic manipulation and metabolic engineering of target microorganisms. However, there are often no options available for inducible promoters when working with non-model microorganisms. These include extremely thermophilic, cellulolytic bacteria that are of interest for renewable lignocellulosic conversion to biofuels and chemicals. In fact, improvements to the genetic systems in these organisms often cease once transformation is achieved. This present study expands the tools available for genetically engineering Caldicellulosiruptor bescii, the most thermophilic cellulose-degrader known growing up to 90 °C on unpretreated plant biomass. A native xylose-inducible (P xi ) promoter was utilized to control the expression of the reporter gene (ldh) encoding lactate dehydrogenase. The P xi -ldh construct resulted in a both increased ldh expression (20-fold higher) and lactate dehydrogenase activity (32-fold higher) in the presence of xylose compared to when glucose was used as a substrate. Finally, lactate production during growth of the recombinant C. bescii strain was proportional to the initial xylose concentration, showing that tunable expression of genes is now possible using this xylose-inducible system. This study represents a major step in the use of C. bescii as a potential platform microorganism for biotechnological applications using renewable biomass.

Microbial diversity of extreme habitats in human homes.

PubMed

Savage, Amy M; Hills, Justin; Driscoll, Katherine; Fergus, Daniel J; Grunden, Amy M; Dunn, Robert R

2016-01-01

High-throughput sequencing techniques have opened up the world of microbial diversity to scientists, and a flurry of studies in the most remote and extreme habitats on earth have begun to elucidate the key roles of microbes in ecosystems with extreme conditions. These same environmental extremes can also be found closer to humans, even in our homes. Here, we used high-throughput sequencing techniques to assess bacterial and archaeal diversity in the extreme environments inside human homes (e.g., dishwashers, hot water heaters, washing machine bleach reservoirs, etc.). We focused on habitats in the home with extreme temperature, pH, and chemical environmental conditions. We found a lower diversity of microbes in these extreme home environments compared to less extreme habitats in the home. However, we were nonetheless able to detect sequences from a relatively diverse array of bacteria and archaea. Habitats with extreme temperatures alone appeared to be able to support a greater diversity of microbes than habitats with extreme pH or extreme chemical environments alone. Microbial diversity was lowest when habitats had both extreme temperature and one of these other extremes. In habitats with both extreme temperatures and extreme pH, taxa with known associations with extreme conditions dominated. Our findings highlight the importance of examining interactive effects of multiple environmental extremes on microbial communities. Inasmuch as taxa from extreme environments can be both beneficial and harmful to humans, our findings also suggest future work to understand both the threats and opportunities posed by the life in these habitats.

Modulation of gene expression in heart and liver of hibernating black bears (Ursus americanus)

PubMed Central

2011-01-01

Background Hibernation is an adaptive strategy to survive in highly seasonal or unpredictable environments. The molecular and genetic basis of hibernation physiology in mammals has only recently been studied using large scale genomic approaches. We analyzed gene expression in the American black bear, Ursus americanus, using a custom 12,800 cDNA probe microarray to detect differences in expression that occur in heart and liver during winter hibernation in comparison to summer active animals. Results We identified 245 genes in heart and 319 genes in liver that were differentially expressed between winter and summer. The expression of 24 genes was significantly elevated during hibernation in both heart and liver. These genes are mostly involved in lipid catabolism and protein biosynthesis and include RNA binding protein motif 3 (Rbm3), which enhances protein synthesis at mildly hypothermic temperatures. Elevated expression of protein biosynthesis genes suggests induction of translation that may be related to adaptive mechanisms reducing cardiac and muscle atrophies over extended periods of low metabolism and immobility during hibernation in bears. Coordinated reduction of transcription of genes involved in amino acid catabolism suggests redirection of amino acids from catabolic pathways to protein biosynthesis. We identify common for black bears and small mammalian hibernators transcriptional changes in the liver that include induction of genes responsible for fatty acid β oxidation and carbohydrate synthesis and depression of genes involved in lipid biosynthesis, carbohydrate catabolism, cellular respiration and detoxification pathways. Conclusions Our findings show that modulation of gene expression during winter hibernation represents molecular mechanism of adaptation to extreme environments. PMID:21453527

Mechanical characterization of alloys in extreme conditions of high strain rates and high temperature

NASA Astrophysics Data System (ADS)

Cadoni, Ezio

2018-03-01

The aim of this paper is the description of the mechanical characterization of alloys under extreme conditions of temperature and loading. In fact, in the frame of the Cost Action CA15102 “Solutions for Critical Raw Materials Under Extreme Conditions (CRM-EXTREME)” this aspect is crucial and many industrial applications have to consider the dynamic response of materials. Indeed, for a reduction and substitution of CRMs in alloys is necessary to design the materials and understand if the new materials behave better or if the substitution or reduction badly affect their performance. For this reason, a deep knowledge of the mechanical behaviour at high strain-rates of considered materials is required. In general, machinery manufacturing industry or transport industry as well as energy industry have important dynamic phenomena that are simultaneously affected by extended strain, high strain-rate, damage and pressure, as well as conspicuous temperature gradients. The experimental results in extreme conditions of high strain rate and high temperature of an austenitic stainless steel as well as a high-chromium tempered martensitic reduced activation steel Eurofer97 are presented.

Morphological and transcriptional response of an anhydrobiotic insect to ionizing radiation and desiccation: steps forward in understanding molecular background of extreme radioresistance in higher eukaryotes

NASA Astrophysics Data System (ADS)

Gusev, Oleg; Novikova, Nataliya; Sychev, Vladimir; Okuda, Takashi; Kikawada, Takahiro; Sakashita, Tetsuya; Mukae, Kyosuke

2012-07-01

Life in extreme or drastically changing environments in many cases leads to evolutionary evolvement of mechanisms of cross-resistance to different abiotic stresses, often never actually faced by the organism in its natural habitat. Larvae of the sleeping chironomidPolypedilum vanderplanki (Diptera) are able to resist complete desiccation and in the dry form survive under excess of various abiotic stresses, including exposure to space environment. One of the most intriguing features of the anhydrobiotic larvae is resistance to extremely high doses of different types of ionizing radiation. To understand the cross-tolerance mechanism, we have analyzed the structural changes in the nuclear DNA using transmission electron microscopy and DNA comet assays in relation to anhydrobiosis and radiation. We find that dehydration causes alterations in chromatin structure and a severe fragmentation of nuclear DNA in the cells of the larvae despite successful anhydrobiosis. The DNA fragmentation level and the recovery of DNA integrity in the rehydrated after anhydrobiosis larvae were similar to those of hydrated larvae irradiated with 70 Gy of high-linear energy transfer (LET) ions (4He+). In comparison, low-LET radiation (gamma rays) of the same dose causes less initial damage to the larvae, and recovery of DNA repair is complete within 24 h. Genome-wide analysis of mRNA expression in the larvae revealed that a large group of genes (including antioxidants, anhydrobiosis-specific biomolecules and protein-reparation enzymes) showed a similar patterns of activity in response to both desiccation and ionizing radiation. We conclude that t one of the factors explaining the relationship between the resistance to ionizing radiation and the ability to undergo anhydrobiosis in the sleeping chironomid would be an adaptation to desiccation-inflicted proteins and nuclear DNA damage.

Functional diversity of arbuscular mycorrhizas extends to the expression of plant genes involved in P nutrition.

PubMed

Burleigh, Stephen H; Cavagnaro, Tim; Jakobsen, Iver

2002-07-01

This study of functional diversity considers symbiotic associations between two plant species, Medicago truncatula and Lycopersicon esculentum, and seven species of arbuscular mycorrhizal fungi (AMF). The objective was to integrate physiological analyses with molecular techniques to test whether functional diversity between AMF species is not only apparent at the level of mycorrhiza formation, plant nutrient uptake and plant growth, but also at the molecular level as observed by variation in the root expression of plant genes involved in the plant's P-starvation response. The seven species of AMF varied widely in their influence on the root expression of MtPT2 and Mt4 from M. truncatula and LePT1 and TPSI1 from L. esculentum. At one extreme was Glomus mosseae, whereby its colonization of M. truncatula resulted in the greatest reduction in MtPT2 and Mt4 gene expression and the highest level of P uptake and growth, while at the other extreme was Gigaspora rosea, whereby colonization resulted in the highest levels of MtPT2 and Mt4 gene expression and the lowest P uptake and growth. The expression of LePT1 and TPSI1 within the roots of L. esculentum was low and relatively uniform across the seven mycorrhizas, reflecting the ability of this cultivar to maintain low and constant shoot P levels despite root colonization by a broad selection of AMF. This study extends current understanding of functional diversity and shows that plants can respond differently to AMF, not only at the level of colonization, nutrient uptake and growth, but also at the level of gene expression.

Extreme High-Temperature Events Over East Asia in 1.5°C and 2°C Warmer Futures: Analysis of NCAR CESM Low-Warming Experiments

NASA Astrophysics Data System (ADS)

Li, Donghuan; Zhou, Tianjun; Zou, Liwei; Zhang, Wenxia; Zhang, Lixia

2018-02-01

Extreme high-temperature events have large socioeconomic and human health impacts. East Asia (EA) is a populous region, and it is crucial to assess the changes in extreme high-temperature events in this region under different climate change scenarios. The Community Earth System Model low-warming experiment data were applied to investigate the changes in the mean and extreme high temperatures in EA under 1.5°C and 2°C warming conditions above preindustrial levels. The results show that the magnitude of warming in EA is approximately 0.2°C higher than the global mean. Most populous subregions, including eastern China, the Korean Peninsula, and Japan, will see more intense, more frequent, and longer-lasting extreme temperature events under 1.5°C and 2°C warming. The 0.5°C lower warming will help avoid 35%-46% of the increases in extreme high-temperature events in terms of intensity, frequency, and duration in EA with maximal avoidance values (37%-49%) occurring in Mongolia. Thus, it is beneficial for EA to limit the warming target to 1.5°C rather than 2°C.

Trends in body mass index and prevalence of extreme high obesity among Pennsylvania children and adolescents, 2007-2011: promising but cautionary.

PubMed

Lohrmann, David; YoussefAgha, Ahmed; Jayawardene, Wasantha

2014-04-01

We determined current trends and patterns in overweight, obesity, and extreme high obesity among Pennsylvania pre-kindergarten (pre-K) to 12th grade students and simulated future trends. We analyzed body mass index (BMI) of pre-K to 12th grade students from 43 of 67 Pennsylvania counties in 2007 to 2011 to determine trends and to discern transition patterns among BMI status categories for 2009 to 2011. Vinsem simulation, confirmed by Markov chain modeling, generated future prevalence trends. Combined rates of overweight, obesity, and extreme high obesity decreased among secondary school students across the 5 years, and among elementary students, first increased and then markedly decreased. BMI status remained constant for approximately 80% of normal and extreme high obese students, but both decreased and increased among students who initially were overweight and obese; the increase in BMI remained significant. Overall trends in child and adolescent BMI status seemed positive. BMI transition patterns indicated that although overweight and obesity prevalence leveled off, extreme high obesity, especially among elementary students, is projected to increase substantially over time. If current transition patterns continue, the prevalence of overweight, obesity, and extreme high obesity among Pennsylvania students in 2031 is projected to be 16.0%, 6.6%, and 23.2%, respectively.

Heat shock protein expression enhances heat tolerance of reptile embryos

PubMed Central

Gao, Jing; Zhang, Wen; Dang, Wei; Mou, Yi; Gao, Yuan; Sun, Bao-Jun; Du, Wei-Guo

2014-01-01

The role of heat shock proteins (HSPs) in heat tolerance has been demonstrated in cultured cells and animal tissues, but rarely in whole organisms because of methodological difficulties associated with gene manipulation. By comparing HSP70 expression patterns among representative species of reptiles and birds, and by determining the effect of HSP70 overexpression on embryonic development and hatchling traits, we have identified the role of HSP70 in the heat tolerance of amniote embryos. Consistent with their thermal environment, and high incubation temperatures and heat tolerance, the embryos of birds have higher onset and maximum temperatures for induced HSP70 than do reptiles, and turtles have higher onset and maximum temperatures than do lizards. Interestingly, the trade-off between benefits and costs of HSP70 overexpression occurred between life-history stages: when turtle embryos developed at extreme high temperatures, HSP70 overexpression generated benefits by enhancing embryo heat tolerance and hatching success, but subsequently imposed costs by decreasing heat tolerance of surviving hatchlings. Taken together, the correlative and causal links between HSP70 and heat tolerance provide, to our knowledge, the first unequivocal evidence that HSP70 promotes thermal tolerance of embryos in oviparous amniotes. PMID:25080340

Physiological and Transcriptional Responses of Different Industrial Microbes at Near-Zero Specific Growth Rates.

PubMed

Ercan, Onur; Bisschops, Markus M M; Overkamp, Wout; Jørgensen, Thomas R; Ram, Arthur F; Smid, Eddy J; Pronk, Jack T; Kuipers, Oscar P; Daran-Lapujade, Pascale; Kleerebezem, Michiel

2015-09-01

The current knowledge of the physiology and gene expression of industrially relevant microorganisms is largely based on laboratory studies under conditions of rapid growth and high metabolic activity. However, in natural ecosystems and industrial processes, microbes frequently encounter severe calorie restriction. As a consequence, microbial growth rates in such settings can be extremely slow and even approach zero. Furthermore, uncoupling microbial growth from product formation, while cellular integrity and activity are maintained, offers perspectives that are economically highly interesting. Retentostat cultures have been employed to investigate microbial physiology at (near-)zero growth rates. This minireview compares information from recent physiological and gene expression studies on retentostat cultures of the industrially relevant microorganisms Lactobacillus plantarum, Lactococcus lactis, Bacillus subtilis, Saccharomyces cerevisiae, and Aspergillus niger. Shared responses of these organisms to (near-)zero growth rates include increased stress tolerance and a downregulation of genes involved in protein synthesis. Other adaptations, such as changes in morphology and (secondary) metabolite production, were species specific. This comparison underlines the industrial and scientific significance of further research on microbial (near-)zero growth physiology. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The evolution of insecticide resistance in the brown planthopper (Nilaparvata lugens Stål) of China in the period 2012-2016.

PubMed

Wu, Shun-Fan; Zeng, Bin; Zheng, Chen; Mu, Xi-Chao; Zhang, Yong; Hu, Jun; Zhang, Shuai; Gao, Cong-Fen; Shen, Jin-Liang

2018-03-15

The brown planthopper, Nilaparvata lugens, is an economically important pest on rice in Asia. Chemical control is still the most efficient primary way for rice planthopper control. However, due to the intensive use of insecticides to control this pest over many years, resistance to most of the classes of chemical insecticides has been reported. In this article, we report on the status of eight insecticides resistance in Nilaparvata lugens (Stål) collected from China over the period 2012-2016. All of the field populations collected in 2016 had developed extremely high resistance to imidacloprid, thiamethoxam, and buprofezin. Synergism tests showed that piperonyl butoxide (PBO) produced a high synergism of imidacloprid, thiamethoxam, and buprofezin effects in the three field populations, YA2016, HX2016, and YC2016. Functional studies using both double-strand RNA (dsRNA)-mediated knockdown in the expression of CYP6ER1 and transgenic expression of CYP6ER1 in Drosophila melanogaster showed that CYP6ER1 confers imidacloprid, thiamethoxam and buprofezin resistance. These results will be beneficial for effective insecticide resistance management strategies to prevent or delay the development of insecticide resistance in brown planthopper populations.

Transcriptome sequencing for identification of diapause-associated genes in fall webworm, Hyphantria cunea Drury.

PubMed

Deng, Yu; Li, Fei; Rieske, Lynne K; Sun, Li-Li; Sun, Shou-Hui

2018-08-20

Fall webworm, Hyphantria cunea Drury (Lepidoptera: Arctiidae) is extremely adaptable and highly invasive in China as a defoliator of ornamental and forest trees. Both voltinism and diapause strategies of fall webworm in China are variable, and this variability contributes to it invasiveness. Little is known about molecular regulation of diapause in fall webworm. To gain insight into possible mechanisms of diapause induction, high-throughput RNA-seq data were generated from non-diapause pupae (NDP) and diapause pupae (DP). A total of 58,151 unigenes were assembled and researched against nine public databases. In total, 29,013 up-regulated and 3451 down-regulated unigenes were differentially expressed by DP when compared with those of NDP. Genes encoding proteins such as UDP-glycosyl transferase (UGT), cytochrome P450 and Hsp70 were predicted to be involved in diapause. Moreover, GO function and KEGG pathway enrichments were performed on all differentially expressed genes (DEGs) and showed that cell cycle and insulin signaling pathways may be related to the diapause of the fall webworm. This study provides valuable information about the fall webworm transcriptome for future gene function research, especially as it relates to diapause. Copyright © 2018 Elsevier B.V. All rights reserved.

Adoptive immunotherapy utilizing anti-CD19 chimeric antigen receptor T-cells for B-cell malignancies.

PubMed

Oh, Iekuni; Oh, Yukiko; Ohmine, Ken

2016-01-01

Genetically modified T-cells with forced expression of anti-CD19 chimeric antigen receptor (CD19 CAR) have demonstrated promising clinical results for relapsed and refractory B cell malignancies in early clinical trial settings. The first beneficial tumor regressions were identified among approximately half of CLL patients in 2011. Similarly, CD19 CAR T-cells achieved remissions in about 80% of aggressive B-cell lymphomas in 2012. Furthermore, in 2013 this cellular therapy showed an extremely high rate of efficacy against refractory CD19 positive acute lymphoid leukemia, which had been regarded as the most difficult to treat hematologic disease. Recently, despite the absence of CD19 expression by neoplastic plasma cells, patients with refractory multiple myeloma achieved stringent complete remission after this therapy coupled with high dose chemotherapy and autologous stem cell transplantation. However, there are significant toxicities. Cytokine releasing syndrome and neurotoxicity are recognized as life-threatening adverse events. Although phase I/II clinical trials have just started in Japan, given the exciting results obtained to date, this cellular therapy is expected to be a novel breakthrough immunotherapy for treating refractory B-cell malignancies.

The Complete Genome Sequence of Hyperthermophile Dictyoglomus turgidum DSM 6724™ Reveals a Specialized Carbohydrate Fermentor

PubMed Central

Brumm, Phillip J.; Gowda, Krishne; Robb, Frank T.; Mead, David A.

2016-01-01

Here we report the complete genome sequence of the chemoorganotrophic, extremely thermophilic bacterium, Dictyoglomus turgidum, which is a Gram negative, strictly anaerobic bacterium. D. turgidum and D. thermophilum together form the Dictyoglomi phylum. The two Dictyoglomus genomes are highly syntenic, and both are distantly related to Caldicellulosiruptor spp. D. turgidum is able to grow on a wide variety of polysaccharide substrates due to significant genomic commitment to glycosyl hydrolases, 16 of which were cloned and expressed in our study. The GH5, GH10, and GH42 enzymes characterized in this study suggest that D. turgidum can utilize most plant-based polysaccharides except crystalline cellulose. The DNA polymerase I enzyme was also expressed and characterized. The pure enzyme showed improved amplification of long PCR targets compared to Taq polymerase. The genome contains a full complement of DNA modifying enzymes, and an unusually high copy number (4) of a new, ancestral family of polB type nucleotidyltransferases designated as MNT (minimal nucleotidyltransferases). Considering its optimal growth at 72°C, D. turgidum has an anomalously low G+C content of 39.9% that may account for the presence of reverse gyrase, usually associated with hyperthermophiles. PMID:28066333

Diversifying evolution of competitiveness.

PubMed

Baldauf, Sebastian A; Engqvist, Leif; Weissing, Franz J

2014-10-29

In many species, individuals express phenotypic characteristics that enhance their competitiveness, that is, the ability to acquire resources in competition with others. Moreover, the degree of competitiveness varies considerably across individuals and in time. By means of an evolutionary model, we provide an explanation for this finding. We make the assumption that investment into competitiveness enhances the probability to acquire a high-quality resource, but at the same time reduces the ability of exploiting acquired resources with maximal efficiency. The model reveals that under a broad range of conditions competitiveness either converges to a polymorphic state, where individuals differing in competitive ability stably coexist, or is subject to perpetual transitions between periods of high and low competitiveness. The dynamics becomes even more complex if females can evolve preferences for (or against) competitive males. In extreme cases, such preferences can even drive the population to extinction.

Lower extremity muscle activation during baseball pitching.

PubMed

Campbell, Brian M; Stodden, David F; Nixon, Megan K

2010-04-01

The purpose of this study was to investigate muscle activation levels of select lower extremity muscles during the pitching motion. Bilateral surface electromyography data on 5 lower extremity muscles (biceps femoris, rectus femoris, gluteus maximus, vastus medialis, and gastrocnemius) were collected on 11 highly skilled baseball pitchers and compared with individual maximal voluntary isometric contraction (MVIC) data. The pitching motion was divided into 4 distinct phases: phase 1, initiation of pitching motion to maximum stride leg knee height; phase 2, maximum stride leg knee height to stride foot contact (SFC); phase 3, SFC to ball release; and phase 4, ball release to 0.5 seconds after ball release (follow-through). Results indicated that trail leg musculature elicited moderate to high activity levels during phases 2 and 3 (38-172% of MVIC). Muscle activity levels of the stride leg were moderate to high during phases 2-4 (23-170% of MVIC). These data indicate a high demand for lower extremity strength and endurance. Specifically, coaches should incorporate unilateral and bilateral lower extremity exercises for strength improvement or maintenance and to facilitate dynamic stabilization of the lower extremities during the pitching motion.

Generalist genes and high cognitive abilities.

PubMed

Haworth, Claire M A; Dale, Philip S; Plomin, Robert

2009-07-01

The concept of generalist genes operating across diverse domains of cognitive abilities is now widely accepted. Much less is known about the etiology of the high extreme of performance. Is there more specialization at the high extreme? Using a representative sample of 4,000 12-year-old twin pairs from the UK Twins Early Development Study, we investigated the genetic and environmental overlap between web-based tests of general cognitive ability, reading, mathematics and language performance for the top 15% of the distribution using DF extremes analysis. Generalist genes are just as evident at the high extremes of performance as they are for the entire distribution of abilities and for cognitive disabilities. However, a smaller proportion of the phenotypic intercorrelations appears to be explained by genetic influences for high abilities.

Generalist genes and high cognitive abilities

PubMed Central

Haworth, Claire M.A.; Dale, Philip S.; Plomin, Robert

2014-01-01

The concept of generalist genes operating across diverse domains of cognitive abilities is now widely accepted. Much less is known about the etiology of the high extreme of performance. Is there more specialization at the high extreme? Using a representative sample of 4000 12-year-old twin pairs from the UK Twins Early Development Study, we investigated the genetic and environmental overlap between web-based tests of general cognitive ability, reading, mathematics and language performance for the top 15% of the distribution using DF extremes analysis. Generalist genes are just as evident at the high extremes of performance as they are for the entire distribution of abilities and for cognitive disabilities. However, a smaller proportion of the phenotypic intercorrelations appears to be explained by genetic influences for high abilities. PMID:19377870

Preliminary analysis of cold stress responsive proteins in Mesocestoides corti larvae.

PubMed

Canclini, Lucía; Esteves, Adriana

2007-07-01

Many parasites undergo sudden changes in environmental conditions at some stage during their life cycle. The molecular response to this variation is characterised by a rapid transcriptional activation of a specific set of genes coding for proteins generically known as stress proteins. They appear to be also involved in various biological processes including cell proliferation and differentiation. The platyhelminth parasite, Mesocestoides corti (Cestoda) presents important properties as a model organism. Under stress conditions, key molecules involved in metabolic pathways as well as in the growth and differentiation of the parasite can be identified. 2D protein expression profile of tetrathyridia of M. corti, submitted to nutritional starvation and cold stress is described, as well as the recovery pattern. A set of specifically expressed proteins was observed in each experimental condition. Quantitative and qualitative differences and stress recovery pattern are also reported. This work makes evident the high plasticity and resistance to extreme environmental conditions of these parasites at the molecular level.

Pleomorphic leiomyosarcoma with a dedifferentiation-like appearance in the kidney: case report and literature review.

PubMed

Tajima, Shogo; Waki, Michihiko; Fukuyama, Masashi

2016-12-01

Although primary leiomyosarcoma of the kidney is extremely rare, it is the most common sarcoma of the kidney. Leiomyosarcoma with a large pleomorphic component is designated as pleomorphic leiomyosarcoma. The pleomorphic component is usually similar to undifferentiated high-grade pleomorphic sarcoma, although it variably expresses smooth muscle markers on immunohistochemistry. In the few reported cases of pleomorphic leiomyosarcoma of the kidney, cases with the pleomorphic component showing distinct nodularity similar to dedifferentiated leiomyosarcoma have not been described, to the best of our knowledge. Herein, we present a case of a 49-year-old woman with pleomorphic leiomyosarcoma in the kidney showing distinct nodularity of smooth muscle marker-expressing pleomorphic cells within a background of classic leiomyosarcoma. Along with the classification as a pleomorphic leiomyosarcoma, suggesting aggressive clinical behavior, the renal origin itself might also be a predictor of poor prognosis, as shown in a previous study. This case also involved concomitant distant metastases, already present during the initial detection of the renal tumor.

Production of Hev b5 as a fluorescent biotin-binding tripartite fusion protein in insect cells.

PubMed

Nordlund, Henri R; Laitinen, Olli H; Uotila, Sanna T H; Kulmala, Minna; Kalkkinen, Nisse; Kulomaa, Markku S

2005-10-14

The presented green fluorescent protein and streptavidin core-based tripartite fusion system provides a simple and efficient way for the production of proteins fused to it in insect cells. This fusion protein forms a unique tag, which serves as a multipurpose device enabling easy optimization of production, one-step purification via streptavidin-biotin interaction, and visualization of the fusion protein during downstream processing and in applications. In the present study, we demonstrate the successful production, purification, and detection of a natural rubber latex allergen Hev b5 with this system. We also describe the production of another NRL allergen with the system, Hev b1, which formed large aggregates and gave small yields in purification. The aggregates were detected at early steps by microscopical inspection of the infected insect cells producing this protein. Therefore, this fusion system can also be utilized as a fast indicator of the solubility of the expressed fusion proteins and may therefore be extremely useful in high-throughput expression approaches.

The national aero-space plane

NASA Technical Reports Server (NTRS)

Mendez, Bruce

1988-01-01

The National Aerospace Plane is an extremely versatile and adaptable aircraft. It can be developed into an Orient Express that would dramatically improve trade with countries in Asia and elsewhere: a commuter transport to ferry men and materials to space, an advanced tactical fighter or bomber, and an unparalleled high altitude spy-plane to observe troubled spots all over the globe. Utilizing the technology developed by this pilot program, it will be possible to quickly and easily get to low Earth orbit, go halfway around the world in a fraction of the time it previously took, and lead the world in the development of advanced technology to improve our lives and the lives of many others.

Ultra-sparse dielectric nanowire grids as wideband reflectors and polarizers.

PubMed

Yoon, Jae Woong; Lee, Kyu Jin; Magnusson, Robert

2015-11-02

Engaging both theory and experiment, we investigate resonant photonic lattices in which the duty cycle tends to zero. Corresponding dielectric nanowire grids are mostly empty space if operated as membranes in vacuum or air. These grids are shown to be effective wideband reflectors with impressive polarizing properties. We provide computed results predicting nearly complete reflection and attendant polarization extinction in multiple spectral regions. Experimental results with Si nanowire arrays with 10% duty cycle show ~200-nm-wide band of high reflection for one polarization state and free transmission for the orthogonal state. These results agree quantitatively with theoretical predictions. It is fundamentally extremely significant that the wideband spectral expressions presented can be generated in these minimal systems.

Application of laser-wakefield-based x-ray source to global food security issues

NASA Astrophysics Data System (ADS)

Kieffer, J. C.; Fourmaux, S.; Hallin, E.; Arnison, P.; Brereton, N.; Pitre, F.; Dixon, M.; Tran, N.

2017-05-01

We present the development of a high throughput phase contrast screening system based on LWFA Xray sources for plant imaging. We upgraded the INRS laser-betatron beam line and we illustrate its imaging potential through the innovative development of new tools for addressing issues relevant to global food security. This initiative, led by the Global Institute of Food Security (GIFS) at the U of Saskatchewan, aims to elucidate that part of the function that maps environmental inputs onto specific plant phenotypes. The prospect of correlating phenotypic expression with adaptation to environmental stresses will provide researchers with a new tool to assess breeding programs for crops meant to thrive under the climate extremes.

NIPA1 Gene Mutations Cause Autosomal Dominant Hereditary Spastic Paraplegia (SPG6)

PubMed Central

Rainier, Shirley; Chai, Jing-Hua; Tokarz, Debra; Nicholls, Robert D.; Fink, John K.

2003-01-01

The hereditary spastic paraplegias (HSPs) are genetically heterogeneous disorders characterized by progressive lower-extremity weakness and spasticity. The molecular pathogenesis is poorly understood. We report discovery of a dominant negative mutation in the NIPA1 gene in a kindred with autosomal dominant HSP (ADHSP), linked to chromosome 15q11-q13 (SPG6 locus); and precisely the same mutation in an unrelated kindred with ADHSP that was too small for meaningful linkage analysis. NIPA1 is highly expressed in neuronal tissues and encodes a putative membrane transporter or receptor. Identification of the NIPA1 function and ligand will aid an understanding of axonal neurodegeneration in HSP and may have important therapeutic implications. PMID:14508710

The Ogaden Insurrection: Implications for Islamist Extremism and U.S. National Security

DTIC Science & Technology

2011-02-16

DISTRIBUTION A. Approved for public release: distribution unlimited i DISCLAIMER The views expressed in this academic research paper are those of...23 Terrence Lyons, “Avoiding Conflict in the Horn of Africa, U.S. Policy Toward Ethiopia and Eritrea,” Council on Foreign Relations, CSR No. 21...ballot box and [the EPRDF regards] the expression of differing views and interests as a form of betrayal,” and are therefore repressed. International

Absence of classical heat shock response in the citrus pathogen Xylella fastidiosa.

PubMed

Martins-de-Souza, Daniel; Martins, Daniel; Astua-Monge, Gustavo; Coletta-Filho, Helvécio Della; Winck, Flavia Vischi; Baldasso, Paulo Aparecido; de Oliveira, Bruno Menezes; Marangoni, Sérgio; Machado, Marcos Antônio; Novello, José Camillo; Smolka, Marcus Bustamante

2007-02-01

The fastidious bacterium Xylella fastidiosa is associated with important crop diseases worldwide. We have recently shown that X. fastidiosa is a peculiar organism having unusually low values of gene codon bias throughout its genome and, unexpectedly, in the group of the most abundant proteins. Here, we hypothesized that the lack of codon usage optimization in X. fastidiosa would incapacitate this organism to undergo quick and massive changes in protein expression as occurs in a classical stress response. Proteomic analysis of the response to heat stress in X. fastidiosa revealed that no changes in protein expression can be detected. Moreover, stress-inducible proteins identified in the closely related citrus pathogen Xanthomonas axonopodis pv citri were found to be constitutively expressed in X. fastidiosa. These proteins have extremely high codon bias values in the X. citri and other well-studied organisms, but low values in X. fastidiosa. Because biased codon usage is well known to correlate to the rate of protein synthesis, we speculate that the peculiar codon bias distribution in X. fastidiosa is related to the absence of a classical stress response, and, probably, alternative strategies for survival of X. fastidiosa under stressfull conditions.

Paraganglioma of the vulva: a case report and review of the literature

PubMed Central

Liu, Yong-Qiao; Yue, Jun-Qiu

2013-01-01

Paraganglioma is a neuroendocrine neoplasm, which is extremely rare in the vulva and only one case has been reported. Here we present a case of vulvar paraganglioma in a 48-year-old woman and a literature review. The patient found a lump located in the genitals below the symphysis pubis 3 months before presentation when she complained that the lump was increasing in size. A 3.2 cm x 2.3 cm x 1.5 cm nodule was excised from subcutaneous soft tissue in the vulva. Microscopy showed a diversity of cell morphologies and structures in the rich vascular network of the tumor separated the chief cells into round cell nests (Zellballen pattern). Some areas of the tumor presented epithelioid and spindle-shaped cells with increased cell density and indistinct structural characteristics. Hyaline degeneration of collagen fibers or mucoid degeneration was found in tumor interstitium. Immunohistochemical staining showed diffused expression of synaptophysin in the chief cells, focal expression of S-100 protein in the sustentacular cells and high expression of CD34 in the vascular components. Based on morphological and immunohistochemical results, a rare paraganglioma of the vulva was diagnosed. PMID:24133606

Paraganglioma of the vulva: a case report and review of the literature.

PubMed

Liu, Yong-Qiao; Yue, Jun-Qiu

2013-01-01

Paraganglioma is a neuroendocrine neoplasm, which is extremely rare in the vulva and only one case has been reported. Here we present a case of vulvar paraganglioma in a 48-year-old woman and a literature review. The patient found a lump located in the genitals below the symphysis pubis 3 months before presentation when she complained that the lump was increasing in size. A 3.2 cm x 2.3 cm x 1.5 cm nodule was excised from subcutaneous soft tissue in the vulva. Microscopy showed a diversity of cell morphologies and structures in the rich vascular network of the tumor separated the chief cells into round cell nests (Zellballen pattern). Some areas of the tumor presented epithelioid and spindle-shaped cells with increased cell density and indistinct structural characteristics. Hyaline degeneration of collagen fibers or mucoid degeneration was found in tumor interstitium. Immunohistochemical staining showed diffused expression of synaptophysin in the chief cells, focal expression of S-100 protein in the sustentacular cells and high expression of CD34 in the vascular components. Based on morphological and immunohistochemical results, a rare paraganglioma of the vulva was diagnosed.

A rapid, ratiometric, enzyme-free, and sensitive single-step miRNA detection using three-way junction based FRET probes

NASA Astrophysics Data System (ADS)

Luo, Qingying; Liu, Lin; Yang, Cai; Yuan, Jing; Feng, Hongtao; Chen, Yan; Zhao, Peng; Yu, Zhiqiang; Jin, Zongwen

2018-03-01

MicroRNAs (miRNAs) are single stranded endogenous molecules composed of only 18-24 nucleotides which are critical for gene expression regulating the translation of messenger RNAs. Conventional methods based on enzyme-assisted nucleic acid amplification techniques have many problems, such as easy contamination, high cost, susceptibility to false amplification, and tendency to have sequence mismatches. Here we report a rapid, ratiometric, enzyme-free, sensitive, and highly selective single-step miRNA detection using three-way junction assembled (or self-assembled) FRET probes. The developed strategy can be operated within the linear range from subnanomolar to hundred nanomolar concentrations of miRNAs. In comparison with the traditional approaches, our method showed high sensitivity for the miRNA detection and extreme selectivity for the efficient discrimination of single-base mismatches. The results reveal that the strategy paved a new avenue for the design of novel highly specific probes applicable in diagnostics and potentially in microscopic imaging of miRNAs in real biological environments.

Intra-seasonal Characteristics of Wintertime Extreme Cold Events over South Korea

NASA Astrophysics Data System (ADS)

Park, Taewon; Jeong, Jeehoon; Choi, Jahyun

2017-04-01

The present study reveals the changes in the characteristics of extreme cold events over South Korea for boreal winter (November to March) in terms of the intra-seasonal variability of frequency, duration, and atmospheric circulation pattern. Influences of large-scale variabilities such as the Siberian High activity, the Arctic Oscillation (AO), and the Madden-Julian Oscillation (MJO) on extreme cold events are also investigated. In the early and the late of the winter during November and March, the upper-tropospheric wave-train for a life-cycle of the extreme cold events tends to pass quickly over East Asia. In addition, compared with the other months, the intensity of the Siberian High is weaker and the occurrences of strong negative AO are less frequent. It lead to events with weak amplitude and short duration. On the other hand, the amplified Siberian High and the strong negative AO occur more frequently in the mid of the winter from December to February. The extreme cold events are mainly characterized by a well-organized anticyclonic blocking around the Ural Mountain and the Subarctic. These large-scale circulation makes the extreme cold events for the midwinter last long with strong amplitude. The MJO phases 2-3 which provide a suitable condition for the amplification of extreme cold events occur frequently for November to January when the frequencies are more than twice those for February and March. While the extreme cold events during March have the least frequency, the weakest amplitude, and the shortest duration due to weak impacts of the abovementioned factors, the strong activities of the factors for January force the extreme cold events to be the most frequent, the strongest, and the longest among the boreal winter. Keywords extreme cold event, wave-train, blocking, Siberian High, AO, MJO

Dominant-Negative Regulation of Cell Surface Expression by a Pentapeptide Motif at the Extreme COOH Terminus of an Slo1 Calcium-Activated Potassium Channel Splice Variant

PubMed Central

Chiu, Yu-Hsin; Alvarez-Baron, Claudia; Kim, Eun Young

2010-01-01

Large-conductance Ca2+-activated K+ (BKCa) channels regulate the physiology of many cell types. A single vertebrate gene variously known as Slo1, KCa1.1, or KCNMA1 encodes the pore-forming subunits of BKCa channel but is expressed in a potentially very large number of alternative splice variants. Two splice variants of Slo1, Slo1VEDEC and Slo1QEERL, which differ at the extreme COOH terminus, show markedly different steady-state expression levels on the cell surface. Here we show that Slo1VEDEC and Slo1QEERL can reciprocally coimmunoprecipitate, indicating that they form heteromeric complexes. Moreover, coexpression of even small amounts of Slo1VEDEC markedly reduces surface expression of Slo1QEERL and total Slo1 as indicated by cell-surface biotinylation assays. The effects of Slo1VEDEC on steady-state surface expression can be attributed primarily to the last five residues of the protein based on surface expression of motif-swapped constructs of Slo1 in human embryonic kidney (HEK) 293T cells. In addition, the presence of the VEDEC motif at the COOH terminus of Slo1 channels is sufficient to confer a dominant-negative effect on cell surface expression of itself or other types of Slo1 subunits. Treating cells with short peptides containing the VEDEC motif increased surface expression of Slo1VEDEC channels transiently expressed in HEK293T cells and increased current through endogenous BKCa channels in mouse podocytes. Slo1VEDEC and Slo1QEERL channels are removed from the HEK293T cell surface with similar kinetics and to a similar extent, which suggests that the inhibitory effect of the VEDEC motif is exerted primarily on forward trafficking into the plasma membrane. PMID:20051533

A quantitative and high-throughput assay of human papillomavirus DNA replication.

PubMed

Gagnon, David; Fradet-Turcotte, Amélie; Archambault, Jacques

2015-01-01

Replication of the human papillomavirus (HPV) double-stranded DNA genome is accomplished by the two viral proteins E1 and E2 in concert with host DNA replication factors. HPV DNA replication is an established model of eukaryotic DNA replication and a potential target for antiviral therapy. Assays to measure the transient replication of HPV DNA in transfected cells have been developed, which rely on a plasmid carrying the viral origin of DNA replication (ori) together with expression vectors for E1 and E2. Replication of the ori-plasmid is typically measured by Southern blotting or PCR analysis of newly replicated DNA (i.e., DpnI digested DNA) several days post-transfection. Although extremely valuable, these assays have been difficult to perform in a high-throughput and quantitative manner. Here, we describe a modified version of the transient DNA replication assay that circumvents these limitations by incorporating a firefly luciferase expression cassette in cis of the ori. Replication of this ori-plasmid by E1 and E2 results in increased levels of firefly luciferase activity that can be accurately quantified and normalized to those of Renilla luciferase expressed from a control plasmid, thus obviating the need for DNA extraction, digestion, and analysis. We provide a detailed protocol for performing the HPV type 31 DNA replication assay in a 96-well plate format suitable for small-molecule screening and EC50 determinations. The quantitative and high-throughput nature of the assay should greatly facilitate the study of HPV DNA replication and the identification of inhibitors thereof.

Establishment of ultra long-lived cell lines by transfection of TERT into normal human fibroblast TIG-1 and their characterization.

PubMed

Kamada, Mizuna; Kumazaki, Tsutomu; Matsuo, Taira; Mitsui, Youji; Takahashi, Tomoko

2012-06-01

To establish useful human normal cell lines, TERT (telomerase reverse transcriptase) cDNA was transfected into normal female lung fibroblast, TIG-1. After long-term-sub-cultivation of 74 individual clones selected for resistance to G418, we obtained 55 cultures with normal range of life span [75 PDL (population doubling level)], 16 cultures with extended life span (75-140 PDL). In addition, 3 immortal cell strains and unexpectedly, one ultra long-lived cell line (ULT-1) with life span of 166 PDL were established. IMT-1, one of the immortal cell strains was confirmed to maintain long telomere length, high telomerase activity and an extremely low level of p16INK4A. They also showed moderate p53 and p21CIP1 expression, keeping vigorous growth rate even at 450 PDL. High level of fibronectin and collagen 1α expression confirmed IMT-1 as normal fibroblasts, although one X chromosome had been lost. ULT-1, however, kept a near normal karyotypes and had shortening of telomere length, high expression of p16INK4A, moderate levels of senescence associated-β-galactosidase positive cells and decreased growth rate only after 150 PDs (population doublings), and finally reached senescence at 166 PDL with morphology of normal senescent fibroblasts. As resources of standard normal human cell, abundant vials of early and middle passages of ULT-1 have been stocked. The use of the cell line is discussed, focusing on isograft of artificial skin and screening of anti-aging or safe chemical agents.

The novel extremely psychrophilic luciferase from Metridia longa: Properties of a high-purity protein produced in insect cells.

PubMed

Larionova, Marina D; Markova, Svetlana V; Vysotski, Eugene S

2017-01-29

The bright bioluminescence of copepod Metridia longa is conditioned by a small secreted coelenterazine-dependent luciferase (MLuc). To date, three isoforms of MLuc differing in length, sequences, and some properties were cloned and successfully applied as high sensitive bioluminescent reporters. In this work, we report cloning of a novel group of genes from M. longa encoding extremely psychrophilic isoforms of MLuc (MLuc2-type). The novel isoforms share only ∼54-64% of protein sequence identity with the previously cloned isoforms and, consequently, are the product of a separate group of paralogous genes. The MLuc2 isoform with consensus sequence was produced as a natively folded protein using baculovirus/insect cell expression system, purified, and characterized. The MLuc2 displays a very high bioluminescent activity and high thermostability similar to those of the previously characterized M. longa luciferase isoform MLuc7. However, in contrast to MLuc7 revealing the highest activity at 12-17 °C and 0.5 M NaCl, the bioluminescence optima of MLuc2 isoforms are at ∼5 °C and 1 M NaCl. The MLuc2 adaptation to cold is also accompanied by decrease of melting temperature and affinity to substrate suggesting a more conformational flexibility of a protein structure. The luciferase isoforms with different temperature optima may provide adaptability of the M. longa bioluminescence to the changes of water temperature during diurnal vertical migrations. Copyright © 2016 Elsevier Inc. All rights reserved.

Reparameterization of PAM50 Expression Identifies Novel Breast Tumor Dimensions and Leads to Discovery of a Genome-Wide Significant Breast Cancer Locus at 12q15.

PubMed

Madsen, Michael J; Knight, Stacey; Sweeney, Carol; Factor, Rachel; Salama, Mohamed; Stijleman, Inge J; Rajamanickam, Venkatesh; Welm, Bryan E; Arunachalam, Sasi; Jones, Brandt; Rachamadugu, Rakesh; Rowe, Kerry; Cessna, Melissa H; Thomas, Alun; Kushi, Lawrence H; Caan, Bette J; Bernard, Philip S; Camp, Nicola J

2018-06-01

Background: Breast tumor subtyping has failed to provide impact in susceptibility genetics. The PAM50 assay categorizes breast tumors into: Luminal A, Luminal B, HER2-enriched and Basal-like. However, tumors are often more complex than simple categorization can describe. The identification of heritable tumor characteristics has potential to decrease heterogeneity and increase power for gene finding. Methods: We used 911 sporadic breast tumors with PAM50 expression data to derive tumor dimensions using principal components (PC). Dimensions in 238 tumors from high-risk pedigrees were compared with the sporadic tumors. Proof-of-concept gene mapping, informed by tumor dimension, was performed using Shared Genomic Segment (SGS) analysis. Results: Five dimensions (PC1-5) explained the majority of the PAM50 expression variance: three captured intrinsic subtype, two were novel (PC3, PC5). All five replicated in 745 TCGA tumors. Both novel dimensions were significantly enriched in the high-risk pedigrees (intrinsic subtypes were not). SGS gene-mapping in a pedigree identified a 0.5 Mb genome-wide significant region at 12q15 This region segregated through 32 meioses to 8 breast cancer cases with extreme PC3 tumors ( P = 2.6 × 10 -8 ). Conclusions: PC analysis of PAM50 gene expression revealed multiple independent, quantitative measures of tumor diversity. These tumor dimensions show evidence for heritability and potential as powerful traits for gene mapping. Impact: Our study suggests a new approach to describe tumor expression diversity, provides new avenues for germline studies, and proposes a new breast cancer locus. Similar reparameterization of expression patterns may inform other studies attempting to model the effects of tumor heterogeneity. Cancer Epidemiol Biomarkers Prev; 27(6); 644-52. ©2018 AACR . ©2018 American Association for Cancer Research.

Molecular characteristics of the HSP70 gene and its differential expression in female and male golden apple snails (Pomacea canaliculata) under temperature stimulation.

PubMed

Song, Hong-Mei; Mu, Xi-Dong; Gu, Dang-En; Luo, Du; Yang, Ye-Xin; Xu, Meng; Luo, Jian-Ren; Zhang, Jia-En; Hu, Yin-Chang

2014-07-01

Heat-shock protein 70 (HSP70) is one of the most important heat-shock proteins that helps organisms to modulate stress response via over-expression. The HSP70 gene from Pomacea canaliculata was cloned using the RACE approach; the gene is 2,767 bp in length and contains an open reading frame of 1,932 bp, which is encoded by a polypeptide of 643 amino acids. BLAST analysis showed that the predicted amino acid sequence of the P. canaliculata HSP70 gene shared a relatively high similarity with that of other known eukaryotic species that display conserved HSP characteristics. The phylogeny demonstrated a separate clustering of the apple snail HSP70 with other constitutive members from other mollusk species. Quantitative real-time RT-PCR was used to detect the differential expression of HSP70 in both sexes of P. canaliculata at different temperature conditions. These results showed that HSP70 transcript levels decreased slightly under cold shock and increased significantly under heat-shock conditions in both sexes compared to normal temperatures (26 °C). Under cold-shock treatment, the sex effect was not significant. With heat treatment, HSP70 expression could be induced at 36 °C in both females and males, and it peaked at 42 and 39 °C in females and males, respectively. In addition, a clear time-dependent HSP70 expression pattern of the apple snail exposed to the same high temperature (36 °C) was observed at different time points. The maximal induction of HSP70 expression appeared at 12 and 48 h in males and females after heat shock, respectively. The maximal induction in females was significantly higher compared to males under heat stimulus. Taken together, these results strongly suggested that males were more susceptible to heat than females and provided useful molecular information for the ecological adaptability of P. canaliculata against extreme environmental stress.

Different culture conditions affect the growth of human tendon stem/progenitor cells (TSPCs) within a mixed tendon cells (TCs) population.

PubMed

Viganò, M; Perucca Orfei, C; Colombini, A; Stanco, D; Randelli, P; Sansone, V; de Girolamo, L

2017-12-01

Tendon resident cells (TCs) are a mixed population made of terminally differentiated tenocytes and tendon stem/progenitor cells (TSPCs). Since the enrichment of progenitors proportion could enhance the effectiveness of treatments based on these cell populations, the interest on the effect of culture conditions on the TSPCs is growing. In this study the clonal selection and the culture in presence or absence of basic fibroblast growth factor (bFGF) were used to assess their influences on the stemness properties and phenotype specific features of tendon cells. Cells cultured with the different methods were analyzed in terms of clonogenic and differentiation abilities, stem and tendon specific genes expression and immunophenotype at passage 2 and passage 4. The clonal selection allowed to isolate cells with a higher multi-differentiation potential, but at the same time a lower proliferation rate in comparison to the whole population. Moreover, the clones express a higher amounts of stemness marker OCT4 and tendon specific transcription factor Scleraxis (SCX) mRNA, but a lower level of decorin (DCN). On the other hand, the number of cells obtained by clonal selection was extremely low and most of the clones were unable to reach a high number of passages in cultures. The presence of bFGF influences TCs morphology, enhance their proliferation rate and reduce their clonogenic ability. Interestingly, the expression of CD54, a known mesenchymal stem cell marker, is reduced in presence of bFGF at early passages. Nevertheless, bFGF does not affect the chondrogenic and osteogenic potential of TCs and the expression of tendon specific markers, while it was able to downregulate the OCT4 expression. This study showed that clonal selection enhance progenitors content in TCs populations, but the extremely low number of cells produced with this method could represent an insurmountable obstacle to its application in clinical approaches. We observed that the addition of bFGF to the culture medium promotes the maintenance of a higher number of differentiated cells, reducing the proportion of progenitors within the whole population. Overall our findings demonstrated the importance of the use of specific culture protocols to obtain tendon cells for possible clinical applications.

The Imprint of Extreme Climate Events in Century-Long Time Series of Wood Anatomical Traits in High-Elevation Conifers

PubMed Central

Carrer, Marco; Brunetti, Michele; Castagneri, Daniele

2016-01-01

Extreme climate events are of key importance for forest ecosystems. However, both the inherent infrequency, stochasticity and multiplicity of extreme climate events, and the array of biological responses, challenges investigations. To cope with the long life cycle of trees and the paucity of the extreme events themselves, our inferences should be based on long-term observations. In this context, tree rings and the related xylem anatomical traits represent promising sources of information, due to the wide time perspective and quality of the information they can provide. Here we test, on two high-elevation conifers (Larix decidua and Picea abies sampled at 2100 m a.s.l. in the Eastern Alps), the associations among temperature extremes during the growing season and xylem anatomical traits, specifically the number of cells per ring (CN), cell wall thickness (CWT), and cell diameter (CD). To better track the effect of extreme events over the growing season, tree rings were partitioned in 10 sectors. Climate variability has been reconstructed, for 1800–2011 at monthly resolution and for 1926–2011 at daily resolution, by exploiting the excellent availability of very long and high quality instrumental records available for the surrounding area, and taking into account the relationship between meteorological variables and site topographical settings. Summer temperature influenced anatomical traits of both species, and tree-ring anatomical profiles resulted as being associated to temperature extremes. Most of the extreme values in anatomical traits occurred with warm (positive extremes) or cold (negative) conditions. However, 0–34% of occurrences did not match a temperature extreme event. Specifically, CWT and CN extremes were more clearly associated to climate than CD, which presented a bias to track cold extremes. Dendroanatomical analysis, coupled to high-quality daily-resolved climate records, seems a promising approach to study the effects of extreme events on trees, but further investigations are needed to improve our comprehension of the critical role of such elusive events in forest ecosystems. PMID:27242880

Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda.

PubMed

Prasher, Bhavana; Negi, Sapna; Aggarwal, Shilpi; Mandal, Amit K; Sethi, Tav P; Deshmukh, Shailaja R; Purohit, Sudha G; Sengupta, Shantanu; Khanna, Sangeeta; Mohammad, Farhan; Garg, Gaurav; Brahmachari, Samir K; Mukerji, Mitali

2008-09-09

Ayurveda is an ancient system of personalized medicine documented and practiced in India since 1500 B.C. According to this system an individual's basic constitution to a large extent determines predisposition and prognosis to diseases as well as therapy and life-style regime. Ayurveda describes seven broad constitution types (Prakritis) each with a varying degree of predisposition to different diseases. Amongst these, three most contrasting types, Vata, Pitta, Kapha, are the most vulnerable to diseases. In the realm of modern predictive medicine, efforts are being directed towards capturing disease phenotypes with greater precision for successful identification of markers for prospective disease conditions. In this study, we explore whether the different constitution types as described in Ayurveda has molecular correlates. Normal individuals of the three most contrasting constitutional types were identified following phenotyping criteria described in Ayurveda in Indian population of Indo-European origin. The peripheral blood samples of these individuals were analysed for genome wide expression levels, biochemical and hematological parameters. Gene Ontology (GO) and pathway based analysis was carried out on differentially expressed genes to explore if there were significant enrichments of functional categories among Prakriti types. Individuals from the three most contrasting constitutional types exhibit striking differences with respect to biochemical and hematological parameters and at genome wide expression levels. Biochemical profiles like liver function tests, lipid profiles, and hematological parameters like haemoglobin exhibited differences between Prakriti types. Functional categories of genes showing differential expression among Prakriti types were significantly enriched in core biological processes like transport, regulation of cyclin dependent protein kinase activity, immune response and regulation of blood coagulation. A significant enrichment of housekeeping, disease related and hub genes were observed in these extreme constitution types. Ayurveda based method of phenotypic classification of extreme constitutional types allows us to uncover genes that may contribute to system level differences in normal individuals which could lead to differential disease predisposition. This is a first attempt towards unraveling the clinical phenotyping principle of a traditional system of medicine in terms of modern biology. An integration of Ayurveda with genomics holds potential and promise for future predictive medicine.

Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda

PubMed Central

Prasher, Bhavana; Negi, Sapna; Aggarwal, Shilpi; Mandal, Amit K; Sethi, Tav P; Deshmukh, Shailaja R; Purohit, Sudha G; Sengupta, Shantanu; Khanna, Sangeeta; Mohammad, Farhan; Garg, Gaurav; Brahmachari, Samir K; Mukerji, Mitali

2008-01-01

Background Ayurveda is an ancient system of personalized medicine documented and practiced in India since 1500 B.C. According to this system an individual's basic constitution to a large extent determines predisposition and prognosis to diseases as well as therapy and life-style regime. Ayurveda describes seven broad constitution types (Prakritis) each with a varying degree of predisposition to different diseases. Amongst these, three most contrasting types, Vata, Pitta, Kapha, are the most vulnerable to diseases. In the realm of modern predictive medicine, efforts are being directed towards capturing disease phenotypes with greater precision for successful identification of markers for prospective disease conditions. In this study, we explore whether the different constitution types as described in Ayurveda has molecular correlates. Methods Normal individuals of the three most contrasting constitutional types were identified following phenotyping criteria described in Ayurveda in Indian population of Indo-European origin. The peripheral blood samples of these individuals were analysed for genome wide expression levels, biochemical and hematological parameters. Gene Ontology (GO) and pathway based analysis was carried out on differentially expressed genes to explore if there were significant enrichments of functional categories among Prakriti types. Results Individuals from the three most contrasting constitutional types exhibit striking differences with respect to biochemical and hematological parameters and at genome wide expression levels. Biochemical profiles like liver function tests, lipid profiles, and hematological parameters like haemoglobin exhibited differences between Prakriti types. Functional categories of genes showing differential expression among Prakriti types were significantly enriched in core biological processes like transport, regulation of cyclin dependent protein kinase activity, immune response and regulation of blood coagulation. A significant enrichment of housekeeping, disease related and hub genes were observed in these extreme constitution types. Conclusion Ayurveda based method of phenotypic classification of extreme constitutional types allows us to uncover genes that may contribute to system level differences in normal individuals which could lead to differential disease predisposition. This is a first attempt towards unraveling the clinical phenotyping principle of a traditional system of medicine in terms of modern biology. An integration of Ayurveda with genomics holds potential and promise for future predictive medicine. PMID:18782426

pH regulates genes for flagellar motility, catabolism, and oxidative stress in Escherichia coli K-12.

PubMed

Maurer, Lisa M; Yohannes, Elizabeth; Bondurant, Sandra S; Radmacher, Michael; Slonczewski, Joan L

2005-01-01

Gene expression profiles of Escherichia coli K-12 W3110 were compared as a function of steady-state external pH. Cultures were grown to an optical density at 600 nm of 0.3 in potassium-modified Luria-Bertani medium buffered at pH 5.0, 7.0, and 8.7. For each of the three pH conditions, cDNA from RNA of five independent cultures was hybridized to Affymetrix E. coli arrays. Analysis of variance with an alpha level of 0.001 resulted in 98% power to detect genes showing a twofold difference in expression. Normalized expression indices were calculated for each gene and intergenic region (IG). Differential expression among the three pH classes was observed for 763 genes and 353 IGs. Hierarchical clustering yielded six well-defined clusters of pH profiles, designated Acid High (highest expression at pH 5.0), Acid Low (lowest expression at pH 5.0), Base High (highest at pH 8.7), Base Low (lowest at pH 8.7), Neutral High (highest at pH 7.0, lower in acid or base), and Neutral Low (lowest at pH 7.0, higher at both pH extremes). Flagellar and chemotaxis genes were repressed at pH 8.7 (Base Low cluster), where the cell's transmembrane proton potential is diminished by the maintenance of an inverted pH gradient. High pH also repressed the proton pumps cytochrome o (cyo) and NADH dehydrogenases I and II. By contrast, the proton-importing ATP synthase F1Fo and the microaerophilic cytochrome d (cyd), which minimizes proton export, were induced at pH 8.7. These observations are consistent with a model in which high pH represses synthesis of flagella, which expend proton motive force, while stepping up electron transport and ATPase components that keep protons inside the cell. Acid-induced genes, on the other hand, were coinduced by conditions associated with increased metabolic rate, such as oxidative stress. All six pH-dependent clusters included envelope and periplasmic proteins, which directly experience external pH. Overall, this study showed that (i) low pH accelerates acid consumption and proton export, while coinducing oxidative stress and heat shock regulons; (ii) high pH accelerates proton import, while repressing the energy-expensive flagellar and chemotaxis regulons; and (iii) pH differentially regulates a large number of periplasmic and envelope proteins.

Projected timing of perceivable changes in climate extremes for terrestrial and marine ecosystems.

PubMed

Tan, Xuezhi; Gan, Thian Yew; Horton, Daniel E

2018-05-26

Human and natural systems have adapted to and evolved within historical climatic conditions. Anthropogenic climate change has the potential to alter these conditions such that onset of unprecedented climatic extremes will outpace evolutionary and adaptive capabilities. To assess whether and when future climate extremes exceed their historical windows of variability within impact-relevant socioeconomic, geopolitical, and ecological domains, we investigate the timing of perceivable changes (time of emergence; TOE) for 18 magnitude-, frequency-, and severity-based extreme temperature (10) and precipitation (8) indices using both multimodel and single-model multirealization ensembles. Under a high-emission scenario, we find that the signal of frequency- and severity-based temperature extremes is projected to rise above historical noise earliest in midlatitudes, whereas magnitude-based temperature extremes emerge first in low and high latitudes. Precipitation extremes demonstrate different emergence patterns, with severity-based indices first emerging over midlatitudes, and magnitude- and frequency-based indices emerging earliest in low and high latitudes. Applied to impact-relevant domains, simulated TOE patterns suggest (a) unprecedented consecutive dry day occurrence in >50% of 14 terrestrial biomes and 12 marine realms prior to 2100, (b) earlier perceivable changes in climate extremes in countries with lower per capita GDP, and (c) emergence of severe and frequent heat extremes well-before 2030 for the 590 most populous urban centers. Elucidating extreme-metric and domain-type TOE heterogeneities highlights the challenges adaptation planners face in confronting the consequences of elevated twenty-first century radiative forcing. © 2018 John Wiley & Sons Ltd.

The Peak Structure and Future Changes of the Relationships Between Extreme Precipitation and Temperature

NASA Technical Reports Server (NTRS)

Wang, Guiling; Wang, Dagang; Trenberth, Kevin E.; Erfanian, Amir; Yu, Miao; Bosilovich, Michael G.; Parr, Dana T.

2017-01-01

Theoretical models predict that, in the absence of moisture limitation, extreme precipitation intensity could exponentially increase with temperatures at a rate determined by the Clausius-Clapeyron (C-C) relationship. Climate models project a continuous increase of precipitation extremes for the twenty-first century over most of the globe. However, some station observations suggest a negative scaling of extreme precipitation with very high temperatures, raising doubts about future increase of precipitation extremes. Here we show for the present-day climate over most of the globe,the curve relating daily precipitation extremes with local temperatures has a peak structure, increasing as expected at the low medium range of temperature variations but decreasing at high temperatures. However, this peak-shaped relationship does not imply a potential upper limit for future precipitation extremes. Climate models project both the peak of extreme precipitation and the temperature at which it peaks (T(sub peak)) will increase with warming; the two increases generally conform to the C-C scaling rate in mid- and high-latitudes,and to a super C-C scaling in most of the tropics. Because projected increases of local mean temperature (T(sub mean)) far exceed projected increases of T(sub peak) over land, the conventional approach of relating extreme precipitation to T(sub mean) produces a misleading sub-C-C scaling rate.

Changes in extreme cold tolerance, membrane composition and cardiac transcriptome during the first day of thermal acclimation in the porcelain crab Petrolisthes cinctipes.

PubMed

Ronges, Daria; Walsh, Jillian P; Sinclair, Brent J; Stillman, Jonathon H

2012-06-01

Intertidal zone organisms can experience transient freezing temperatures during winter low tides, but their extreme cold tolerance mechanisms are not known. Petrolisthes cinctipes is a temperate mid-high intertidal zone crab species that can experience wintertime habitat temperatures below the freezing point of seawater. We examined how cold tolerance changed during the initial phase of thermal acclimation to cold and warm temperatures, as well as the persistence of cold tolerance during long-term thermal acclimation. Thermal acclimation for as little as 6 h at 8°C enhanced cold tolerance during a 1 h exposure to -2°C relative to crabs acclimated to 18°C. Potential mechanisms for this enhanced tolerance were elucidated using cDNA microarrays to probe for differences in gene expression in cardiac tissue of warm- and cold-acclimated crabs during the first day of thermal acclimation. No changes in gene expression were detected until 12 h of thermal acclimation. Genes strongly upregulated in warm-acclimated crabs represented immune response and extracellular/intercellular processes, suggesting that warm-acclimated crabs had a generalized stress response and may have been remodelling tissues or altering intercellular processes. Genes strongly upregulated in cold-acclimated crabs included many that are involved in glucose production, suggesting that cold acclimation involves increasing intracellular glucose as a cryoprotectant. Structural cytoskeletal proteins were also strongly represented among the genes upregulated in only cold-acclimated crabs. There were no consistent changes in composition or the level of unsaturation of membrane phospholipid fatty acids with cold acclimation, which suggests that neither short- nor long-term changes in cold tolerance are mediated by changes in membrane fatty acid composition. Overall, our study demonstrates that initial changes in cold tolerance are likely not regulated by transcriptomic responses, but that gene-expression-related changes in homeostasis begin within 12 h, the length of a tidal cycle.

Spatial and temporal analysis of extreme sea level and storm surge events around the coastline of the UK

PubMed Central

Haigh, Ivan D.; Wadey, Matthew P.; Wahl, Thomas; Ozsoy, Ozgun; Nicholls, Robert J.; Brown, Jennifer M.; Horsburgh, Kevin; Gouldby, Ben

2016-01-01

In this paper we analyse the spatial footprint and temporal clustering of extreme sea level and skew surge events around the UK coast over the last 100 years (1915–2014). The vast majority of the extreme sea level events are generated by moderate, rather than extreme skew surges, combined with spring astronomical high tides. We distinguish four broad categories of spatial footprints of events and the distinct storm tracks that generated them. There have been rare events when extreme levels have occurred along two unconnected coastal regions during the same storm. The events that occur in closest succession (<4 days) typically impact different stretches of coastline. The spring/neap tidal cycle prevents successive extreme sea level events from happening within 4–8 days. Finally, the 2013/14 season was highly unusual in the context of the last 100 years from an extreme sea level perspective. PMID:27922630

Probability modeling of high flow extremes in Yingluoxia watershed, the upper reaches of Heihe River basin

NASA Astrophysics Data System (ADS)

Li, Zhanling; Li, Zhanjie; Li, Chengcheng

2014-05-01

Probability modeling of hydrological extremes is one of the major research areas in hydrological science. Most basins in humid and semi-humid south and east of China are concerned for probability modeling analysis of high flow extremes. While, for the inland river basin which occupies about 35% of the country area, there is a limited presence of such studies partly due to the limited data availability and a relatively low mean annual flow. The objective of this study is to carry out probability modeling of high flow extremes in the upper reach of Heihe River basin, the second largest inland river basin in China, by using the peak over threshold (POT) method and Generalized Pareto Distribution (GPD), in which the selection of threshold and inherent assumptions for POT series are elaborated in details. For comparison, other widely used probability distributions including generalized extreme value (GEV), Lognormal, Log-logistic and Gamma are employed as well. Maximum likelihood estimate is used for parameter estimations. Daily flow data at Yingluoxia station from 1978 to 2008 are used. Results show that, synthesizing the approaches of mean excess plot, stability features of model parameters, return level plot and the inherent independence assumption of POT series, an optimum threshold of 340m3/s is finally determined for high flow extremes in Yingluoxia watershed. The resulting POT series is proved to be stationary and independent based on Mann-Kendall test, Pettitt test and autocorrelation test. In terms of Kolmogorov-Smirnov test, Anderson-Darling test and several graphical diagnostics such as quantile and cumulative density function plots, GPD provides the best fit to high flow extremes in the study area. The estimated high flows for long return periods demonstrate that, as the return period increasing, the return level estimates are probably more uncertain. The frequency of high flow extremes exhibits a very slight but not significant decreasing trend from 1978 to 2008, while the intensity of such flow extremes is comparatively increasing especially for the higher return levels.

Numerical modeling of macrodispersion in heterogeneous media: a comparison of multi-Gaussian and non-multi-Gaussian models

NASA Astrophysics Data System (ADS)

Wen, Xian-Huan; Gómez-Hernández, J. Jaime

1998-03-01

The macrodispersion of an inert solute in a 2-D heterogeneous porous media is estimated numerically in a series of fields of varying heterogeneity. Four different random function (RF) models are used to model log-transmissivity (ln T) spatial variability, and for each of these models, ln T variance is varied from 0.1 to 2.0. The four RF models share the same univariate Gaussian histogram and the same isotropic covariance, but differ from one another in terms of the spatial connectivity patterns at extreme transmissivity values. More specifically, model A is a multivariate Gaussian model for which, by definition, extreme values (both high and low) are spatially uncorrelated. The other three models are non-multi-Gaussian: model B with high connectivity of high extreme values, model C with high connectivity of low extreme values, and model D with high connectivities of both high and low extreme values. Residence time distributions (RTDs) and macrodispersivities (longitudinal and transverse) are computed on ln T fields corresponding to the different RF models, for two different flow directions and at several scales. They are compared with each other, as well as with predicted values based on first-order analytical results. Numerically derived RTDs and macrodispersivities for the multi-Gaussian model are in good agreement with analytically derived values using first-order theories for log-transmissivity variance up to 2.0. The results from the non-multi-Gaussian models differ from each other and deviate largely from the multi-Gaussian results even when ln T variance is small. RTDs in non-multi-Gaussian realizations with high connectivity at high extreme values display earlier breakthrough than in multi-Gaussian realizations, whereas later breakthrough and longer tails are observed for RTDs from non-multi-Gaussian realizations with high connectivity at low extreme values. Longitudinal macrodispersivities in the non-multi-Gaussian realizations are, in general, larger than in the multi-Gaussian ones, while transverse macrodispersivities in the non-multi-Gaussian realizations can be larger or smaller than in the multi-Gaussian ones depending on the type of connectivity at extreme values. Comparing the numerical results for different flow directions, it is confirmed that macrodispersivities in multi-Gaussian realizations with isotropic spatial correlation are not flow direction-dependent. Macrodispersivities in the non-multi-Gaussian realizations, however, are flow direction-dependent although the covariance of ln T is isotropic (the same for all four models). It is important to account for high connectivities at extreme transmissivity values, a likely situation in some geological formations. Some of the discrepancies between first-order-based analytical results and field-scale tracer test data may be due to the existence of highly connected paths of extreme conductivity values.

The 2010 Pakistan floods: high-resolution simulations with the WRF model

NASA Astrophysics Data System (ADS)

Viterbo, Francesca; Parodi, Antonio; Molini, Luca; Provenzale, Antonello; von Hardenberg, Jost; Palazzi, Elisa

2013-04-01

Estimating current and future water resources in high mountain regions with complex orography is a difficult but crucial task. In particular, the French-Italian project PAPRIKA is focused on two specific regions in the Hindu-Kush -- Himalaya -- Karakorum (HKKH)region: the Shigar basin in Pakistan, at the feet of K2, and the Khumbu valley in Nepal, at the feet of Mount Everest. In this framework, we use the WRF model to simulate precipitation and meteorological conditions with high resolution in areas with extreme orographic slopes, comparing the model output with station and satellite data. Once validated the model, we shall run a set of three future time-slices at very high spatial resolution, in the periods 2046-2050, 2071-2075 and 2096-2100, nested in different climate change scenarios (EXtreme PREcipitation and Hydrological climate Scenario Simulations -EXPRESS-Hydro project). As a prelude to this study, here we discuss the simulation of specific, high-intensity rainfall events in this area. In this paper we focus on the 2010 Pakistan floods which began in late July 2010, producing heavy monsoon rains in the Khyber Pakhtunkhwa, Sindh, Punjab and Balochistan regions of Pakistan and affecting the Indus River basin. Approximately one-fifth of Pakistan's total land area was underwater, with a death toll of about 2000 people. This event has been simulated with the WRF model (version 3.3.) in cloud-permitting mode (d01 14 km and d02 3.5 km): different convective closures and microphysics parameterization have been used. A deeper understanding of the processes responsible for this event has been gained through comparison with rainfall depth observations, radiosounding data and geostationary/polar satellite images.

Winter storms drive rapid phenotypic, regulatory, and genomic shifts in the green anole lizard.

PubMed

Campbell-Staton, Shane C; Cheviron, Zachary A; Rochette, Nicholas; Catchen, Julian; Losos, Jonathan B; Edwards, Scott V

2017-08-04

Extreme environmental perturbations offer opportunities to observe the effects of natural selection in wild populations. During the winter of 2013-2014, the southeastern United States endured an extreme cold event. We used thermal performance, transcriptomics, and genome scans to measure responses of lizard populations to storm-induced selection. We found significant increases in cold tolerance at the species' southern limit. Gene expression in southern survivors shifted toward patterns characteristic of northern populations. Comparing samples before and after the extreme winter, 14 genomic regions were differentiated in the surviving southern population; four also exhibited signatures of local adaptation across the latitudinal gradient and implicate genes involved in nervous system function. Together, our results suggest that extreme winter events can rapidly produce strong selection on natural populations at multiple biological levels that recapitulate geographic patterns of local adaptation. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Oxidative stress induces vascular heme oxygenase-1 expression in ovariectomized rats.

PubMed

Lee, Yen-Mei; Cheng, Pao-Yun; Hong, Su-Fen; Chen, Shu-Ying; Lam, Kwok-Keung; Sheu, Joen-Rong; Yen, Mao-Hsiung

2005-07-01

Heme oxygenase-1 (HO-1), an inducible stress protein, has been implicated in cytoprotection against oxidative stress in vitro and in vivo. Estrogens also have antioxidant effects. This study investigated the time course of HO-1 and inducible nitric oxide synthase (iNOS) expression in the aortas of ovariectomized rats, and the regulatory relationship between the NO/NOS and the carbon monoxide/HO systems. HO-1 and iNOS protein expression was induced by ovariectomy (Ovx) and was extremely high 2-6 weeks after Ovx compared with the sham-operated group. Expression of the constitutive enzymes HO-2 and endothelial NOS did not differ significantly between sham-operated and Ovx rats. 17beta-Estradiol (E(2)) replacement reversed these changes in rats after Ovx. Long-term treatment with the antioxidant tempol significantly inhibited HO-1 and iNOS expression. The iNOS inhibitor aminoguanidine significantly suppressed the induction of HO-1. Oxidized glutathione in the hearts of Ovx rats increased gradually, with significant elevation at 3-6 weeks after Ovx compared with the sham-operated group, whereas plasma levels of NO metabolites were significantly reduced 4-6 weeks after Ovx. Treatment with the HO inhibitor zinc protoporphyrin IX blocked HO-1 induction, but significantly increased the plasma levels of NO metabolites. In conclusion, HO-1 is induced by oxidative stress resulting from E(2) depletion. The NO/iNOS system contributes to the induction of HO-1, which may subsequently suppress iNOS activity to modulate vasculoprotective effects after menopause.

Identification of a distinct population of CD133+CXCR4+ cancer stem cells in ovarian cancer

PubMed Central

Cioffi, Michele; D’Alterio, Crescenzo; Camerlingo, Rosalba; Tirino, Virginia; Consales, Claudia; Riccio, Anna; Ieranò, Caterina; Cecere, Sabrina Chiara; Losito, Nunzia Simona; Greggi, Stefano; Pignata, Sandro; Pirozzi, Giuseppe; Scala, Stefania

2015-01-01

CD133 and CXCR4 were evaluated in the NCI-60 cell lines to identify cancer stem cell rich populations. Screening revealed that, ovarian OVCAR-3, -4 and -5 and colon cancer HT-29, HCT-116 and SW620 over expressed both proteins. We aimed to isolate cells with stem cell features sorting the cells expressing CXCR4+CD133+ within ovarian cancer cell lines. The sorted population CD133+CXCR4+ demonstrated the highest efficiency in sphere formation in OVCAR-3, OVCAR-4 and OVCAR-5 cells. Moreover OCT4, SOX2, KLF4 and NANOG were highly expressed in CD133+CXCR4+ sorted OVCAR-5 cells. Most strikingly CXCR4+CD133+ sorted OVCAR-5 and -4 cells formed the highest number of tumors when inoculated in nude mice compared to CD133−CXCR4−, CD133+CXCR4−, CD133−CXCR4+ cells. CXCR4+CD133+ OVCAR-5 cells were resistant to cisplatin, overexpressed the ABCG2 surface drug transporter and migrated toward the CXCR4 ligand, CXCL12. Moreover, when human ovarian cancer cells were isolated from 37 primary ovarian cancer, an extremely variable level of CXCR4 and CD133 expression was detected. Thus, in human ovarian cancer cells CXCR4 and CD133 expression identified a discrete population with stem cell properties that regulated tumor development and chemo resistance. This cell population represents a potential therapeutic target. PMID:26020117

Molecular mechanisms of phenotypic plasticity in social insects

USDA-ARS?s Scientific Manuscript database

Polyphenism in insects, whereby a single genome expresses different phenotypes in response to environmental cues, is a fascinating biological phenomenon. Social insects are especially intriguing examples of phenotypic plasticity because division of labor results in the development of extreme morphol...

Metronidazole as a protector of cells from electromagnetic radiation of extremely high frequencies

NASA Astrophysics Data System (ADS)

Kuznetsov, Pavel E.; Malinina, Ulia A.; Popyhova, Era B.; Rogacheva, Svetlana M.; Somov, Alexander U.

2006-08-01

It is well known that weak electromagnetic fields of extremely high frequencies cause significant modification of the functional status of biological objects of different levels of organization. The aim of the work was to study the combinatory effect of metronidazole - the drug form of 1-(2'hydroxiethil)-2-methil-5-nitroimidazole - and electromagnetic radiation of extremely high frequencies (52...75 GHz) on the hemolytic stability of erythrocytes and hemotaxis activity of Infusoria Paramecium caudatum.

Are recent severe floods in Xiang River basin of China linked with the increase extreme precipitation?

NASA Astrophysics Data System (ADS)

Cheng, L.; Du, J.

2015-12-01

The Xiang River, a main tributary of the Yangtze River, is subjected to high floods frequently in recent twenty years. Climate change, including abrupt shifts and fluctuations in precipitation is an important factor influencing hydrological extreme conditions. In addition, human activities are widely recognized as another reasons leading to high flood risk. With the effects of climate change and human interventions on hydrological cycle, there are several questions that need to be addressed. Are floods in the Xiang River basin getting worse? Whether the extreme streamflow shows an increasing tendency? If so, is it because the extreme rainfall events have predominant effect on floods? To answer these questions, the article detected existing trends in extreme precipitation and discharge using Mann-Kendall test. Continuous wavelet transform method was employed to identify the consistency of changes in extreme precipitation and discharge. The Pearson correlation analysis was applied to investigate how much degree of variations in extreme discharge can be explained by climate change. The results indicate that slightly upward trends can be detected in both extreme rainfalls and discharge in the upper region of Xiang River basin. For the most area of middle and lower river basin, the extreme rainfalls show significant positive trends, but the extreme discharge displays slightly upward trends with no significance at 90% confidence level. Wavelet transform analysis results illustrate that highly similar patterns of signal changes can be seen between extreme precipitation and discharge in upper section of the basin, while the changes in extreme precipitation for the middle and lower reaches do not always coincide with the extreme streamflow. The correlation coefficients of the wavelet transforms for the precipitation and discharge signals in most area of the basin pass the significance test. The conclusion may be drawn that floods in recent years are not getting worse in Xiang River basin. The similar signal patterns and positive correlation between extreme discharge and precipitation indicate that the variability of extreme precipitation has an important effect on extreme discharge of flood, although the intensity of human impacts in lower section of Xiang River basin has increased markedly.

The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm.

PubMed

Jensen, Elizabeth T; van der Burg, Jelske W; O'Shea, Thomas M; Joseph, Robert M; Allred, Elizabeth N; Heeren, Tim; Leviton, Alan; Kuban, Karl C K

2017-08-01

To assess the association between maternal prepregnancy body mass index and adequacy of pregnancy weight gain in relation to neurocognitive function in school-aged children born extremely preterm. Study participants were 535 ten-year-old children enrolled previously in the prospective multicenter Extremely Low Gestational Age Newborns cohort study who were products of singleton pregnancies. Soon after delivery, mothers provided information about prepregnancy weight. Prepregnancy body mass index and adequacy of weight gain were characterized based on this information. Children underwent a neurocognitive evaluation at 10 years of age. Maternal prepregnancy obesity was associated with increased odds of a lower score for Differential Ability Scales-II Verbal IQ, for Developmental Neuropsychological Assessment-II measures of processing speed and visual fine motor control, and for Wechsler Individual Achievement Test-III Spelling. Children born to mothers who gained an excessive amount of weight were at increased odds of a low score on the Oral and Written Language Scales Oral Expression assessment. Conversely, children whose mother did not gain an adequate amount of weight were at increased odds of a lower score on the Oral and Written Language Scales Oral Expression and Wechsler Individual Achievement Test-III Word Reading assessments. In this cohort of infants born extremely preterm, maternal obesity was associated with poorer performance on some assessments of neurocognitive function. Our findings are consistent with the observational and experimental literature and suggest that opportunities may exist to mitigate risk through education and behavioral intervention before pregnancy. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between stress and pain in work-related upper extremity disorders: the hidden role of chronic multisymptom illnesses.

PubMed

Clauw, Daniel J; Williams, David A

2002-05-01

Pain and fatigue are commonly associated with work-related upper extremity disorders. Occasionally these symptoms persist beyond a reasonable healing period. One potential explanation for prolonged symptom expression is the concurrent development of a stress-mediated illness or CMI (Chronic Multi-Symptom Illness). In such a scenario, the chronic regional pain and other symptoms that the individual is experiencing would be attributable to the CMI rather than to tissue damage or a biomechanical dysfunction of the upper-extremity. This article critically reviews the case definitions of the new class of CMI disorders and evaluates the existing evidence supporting centrally mediated physiological changes (e.g., sensory hypervigilance, dysautonomia) that manifest as symptoms of pain and fatigue in some individuals experiencing chronic stressors. While explanations for prolonged pain and fatigue have historically focused on mechanisms involving peripheral pathology or psychiatric explanations, ample evidences support the role of altered Central Nervous System function in accounting for symptom manifestation in CMI. A model is presented that unites seemingly disparate findings across numerous investigations and provides a framework for understanding how genetics, triggering events, stressors, and early life events can affect CNS activity. Resultant symptom expression (e.g., pain and fatigue) from central dysregulation would be expected to occur in a subset of individuals in the population, including a subset of individuals with work-related upper extremity disorders. Thus when symptoms such as pain and fatigue persist beyond a reasonable period, consideration of CMI and associated assessment and interventions focused on central mechanisms may be worthwhile.

Effects of massage on the expression of proangiogenic markers in rat skin.

PubMed

Ratajczak-Wielgomas, Katarzyna; Kassolik, Krzysztof; Grzegrzolka, Jedrzej; Halski, Tomasz; Piotrowska, Aleksandra; Mieszala, Katarzyna; Wilk, Iwona; Podhorska-Okolow, Marzenna; Dziegiel, Piotr; Andrzejewski, Waldemar

2018-05-17

Massage is a physiotherapeutic treatment, commonly used in both therapy and restoration of normal body functions. The aim of this work was to determine the effects of skin massage on stimulating the expression of angiogenesis-initiating factors, i.e. VEGF-A, FGF-2 (bFGF) and CD34 and on skin regeneration processes. The study was conducted on 48 Buffalo strain rats, randomly divided into two groups. In the first group (M, the massaged group), massage was applied five times a week for 7 weeks. In the second study group (C, the control group), the massage was omitted. Massage consisted of spiral movements at the plantar surface of skin for 5 min on each rear extremity. The gene expression of proangiogenic factors, including VEGF-A, FGF-2, CD34 at the mRNA level was determined using real-time PCR. Immunohistochemistry was performed on paraffin sections of rat skin to determine VEGF-A, FGF-2 CD34 and Ki-67expression. An increase in mRNA expression in the skin of the rat's rear extremity for VEGF-A and FGF-2 in the first week of the experiment was shown in the M group compared with the control rats. The upregulation of CD34 mRNA expression was also observed in the M group. We observed positive correlations between VEGF-A mRNA expression and the expression of mRNA for FGF-2 and CD34, as well as correlation between the expression of mRNA for FGF-2 and CD34. The immunohistochemical expression of VEGF-A, FGF-2 and CD34 was at a much lower level in the skin of control rats relative to the skin of massaged animals. Moreover, significantly higher immunoreactivity was shown for nuclear protein Ki-67 in epidermal cells in the M group compared with the C group. Rat skin massage increased the expression of the main angiogenesis-stimulating factors and the proliferative activity of epidermal cells, which can stimulate skin regeneration and tissue repairing processes.

Faster-X evolution of gene expression is driven by recessive adaptive cis-regulatory variation in Drosophila.

PubMed

Llopart, Ana

2018-05-01

The hemizygosity of the X (Z) chromosome fully exposes the fitness effects of mutations on that chromosome and has evolutionary consequences on the relative rates of evolution of X and autosomes. Specifically, several population genetics models predict increased rates of evolution in X-linked loci relative to autosomal loci. This prediction of faster-X evolution has been evaluated and confirmed for both protein coding sequences and gene expression. In the case of faster-X evolution for gene expression divergence, it is often assumed that variation in 5' noncoding sequences is associated with variation in transcript abundance between species but a formal, genomewide test of this hypothesis is still missing. Here, I use whole genome sequence data in Drosophila yakuba and D. santomea to evaluate this hypothesis and report positive correlations between sequence divergence at 5' noncoding sequences and gene expression divergence. I also examine polymorphism and divergence in 9,279 noncoding sequences located at the 5' end of annotated genes and detected multiple signals of positive selection. Notably, I used the traditional synonymous sites as neutral reference to test for adaptive evolution, but I also used bases 8-30 of introns <65 bp, which have been proposed to be a better neutral choice. X-linked genes with high degree of male-biased expression show the most extreme adaptive pattern at 5' noncoding regions, in agreement with faster-X evolution for gene expression divergence and a higher incidence of positively selected recessive mutations. © 2018 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Extreme-volatility dynamics in crude oil markets

NASA Astrophysics Data System (ADS)

Jiang, Xiong-Fei; Zheng, Bo; Qiu, Tian; Ren, Fei

2017-02-01

Based on concepts and methods from statistical physics, we investigate extreme-volatility dynamics in the crude oil markets, using the high-frequency data from 2006 to 2010 and the daily data from 1986 to 2016. The dynamic relaxation of extreme volatilities is described by a power law, whose exponents usually depend on the magnitude of extreme volatilities. In particular, the relaxation before and after extreme volatilities is time-reversal symmetric at the high-frequency time scale, but time-reversal asymmetric at the daily time scale. This time-reversal asymmetry is mainly induced by exogenous events. However, the dynamic relaxation after exogenous events exhibits the same characteristics as that after endogenous events. An interacting herding model both with and without exogenous driving forces could qualitatively describe the extreme-volatility dynamics.

Bright high-repetition-rate source of narrowband extreme-ultraviolet harmonics beyond 22 eV

PubMed Central

Wang, He; Xu, Yiming; Ulonska, Stefan; Robinson, Joseph S.; Ranitovic, Predrag; Kaindl, Robert A.

2015-01-01

Novel table-top sources of extreme-ultraviolet light based on high-harmonic generation yield unique insight into the fundamental properties of molecules, nanomaterials or correlated solids, and enable advanced applications in imaging or metrology. Extending high-harmonic generation to high repetition rates portends great experimental benefits, yet efficient extreme-ultraviolet conversion of correspondingly weak driving pulses is challenging. Here, we demonstrate a highly-efficient source of femtosecond extreme-ultraviolet pulses at 50-kHz repetition rate, utilizing the ultraviolet second-harmonic focused tightly into Kr gas. In this cascaded scheme, a photon flux beyond ≈3 × 1013 s−1 is generated at 22.3 eV, with 5 × 10−5 conversion efficiency that surpasses similar harmonics directly driven by the fundamental by two orders-of-magnitude. The enhancement arises from both wavelength scaling of the atomic dipole and improved spatio-temporal phase matching, confirmed by simulations. Spectral isolation of a single 72-meV-wide harmonic renders this bright, 50-kHz extreme-ultraviolet source a powerful tool for ultrafast photoemission, nanoscale imaging and other applications. PMID:26067922

Observed and predicted sensitivities of extreme surface ozone to meteorological drivers in three US cities

NASA Astrophysics Data System (ADS)

Fix, Miranda J.; Cooley, Daniel; Hodzic, Alma; Gilleland, Eric; Russell, Brook T.; Porter, William C.; Pfister, Gabriele G.

2018-03-01

We conduct a case study of observed and simulated maximum daily 8-h average (MDA8) ozone (O3) in three US cities for summers during 1996-2005. The purpose of this study is to evaluate the ability of a high resolution atmospheric chemistry model to reproduce observed relationships between meteorology and high or extreme O3. We employ regional coupled chemistry-transport model simulations to make three types of comparisons between simulated and observational data, comparing (1) tails of the O3 response variable, (2) distributions of meteorological predictor variables, and (3) sensitivities of high and extreme O3 to meteorological predictors. This last comparison is made using two methods: quantile regression, for the 0.95 quantile of O3, and tail dependence optimization, which is used to investigate even higher O3 extremes. Across all three locations, we find substantial differences between simulations and observational data in both meteorology and meteorological sensitivities of high and extreme O3.

Early Diagnosis and Intervention Strategies for Post-Traumatic Heterotopic Ossification in Severely Injured Extremities

DTIC Science & Technology

2014-10-01

Adipoq, BMP4, Col4a3, IGF2, MyoD1, Smad3); 3-20 fold lower elevation of expression of Col1a1 ; and 3-10 fold higher expression of MMP9 and Spp1...XI, alpha 1 COL1A1 collagen, type I, alpha 1 COL2A1 collagen, type II, alpha 1 COL4A3 collagen, type IV, alpha 3 COMP cartilage oligomeric matrix

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cooperstock, F.I., E-mail: cooperst@uvic.ca; Dupre, M.J., E-mail: mdupre@tulane.edu

We introduce a naturally-defined totally invariant spacetime energy expression for general relativity incorporating the contribution from gravity. The extension links seamlessly to the action integral for the gravitational field. The demand that the general expression for arbitrary systems reduces to the Tolman integral in the case of stationary bounded distributions, leads to the matter-localized Ricci integral for energy–momentum in support of the energy localization hypothesis. The role of the observer is addressed and as an extension of the special relativistic case, the field of observers comoving with the matter is seen to compute the intrinsic global energy of a system.more » The new localized energy supports the Bonnor claim that the Szekeres collapsing dust solutions are energy-conserving. It is suggested that in the extreme of strong gravity, the Heisenberg Uncertainty Principle be generalized in terms of spacetime energy–momentum. -- Highlights: •We present a totally invariant spacetime energy expression for general relativity incorporating the contribution from gravity. •Demand for the general expression to reduce to the Tolman integral for stationary systems supports the Ricci integral as energy–momentum. •Localized energy via the Ricci integral is consistent with the energy localization hypothesis. •New localized energy supports the Bonnor claim that the Szekeres collapsing dust solutions are energy-conserving. •Suggest the Heisenberg Uncertainty Principle be generalized in terms of spacetime energy–momentum in strong gravity extreme.« less

Emotional word usage in groups at risk for schizophrenia-spectrum disorders: An objective investigation of attention to emotion

PubMed Central

Fung, Christie K.; Moore, Melody M.; Karcher, Nicole R.; Kerns, John G.; Martin, Elizabeth A.

2017-01-01

Both extreme levels of social anhedonia (SocAnh) and extreme levels of perceptual aberration/magical ideation (PerMag) indicate increased risk for schizophrenia-spectrum disorders and are associated with emotional deficits. For SocAnh, there is evidence of self-reported decreased trait positive affect and abnormalities in emotional attention. For PerMag, there is evidence of increased trait negative affect and increased attention to negative emotion. Yet, the nature of more objective emotional abnormalities in these groups is unclear. The goal of this study was to assess attention to emotions more objectively in a SocAnh, PerMag, and control group by using a positive (vs. neutral) mood induction procedure followed by a free writing period. Linguistic analyses revealed that the SocAnh group used fewer positive emotion words than the control group, with the PerMag group falling in between the others. In addition, both at-risk groups used more negative emotion words than the control group. Also, for the control group only, those in the positive mood induction used more positive emotion words, suggesting their emotions influenced their linguistic expression. Overall, SocAnh is associated with decreased positive emotional expression and at-risk groups are associated with increased negative emotional expression and a decreased influence of emotions on linguistic expression. PMID:28242515

RADIATION-INDUCED GENETIC DAMAGE IN THE MEXICAN TOAD (BUFO VALLICEPS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blair, W.F.

1960-10-01

Lines of Mexican toads (Bufo valliceps) bearing x-ray induced genetic damage were established by mating normal females with males that had received gonadal x-ray doses ranging from 300 to 3000 r. Survival in the first generation was inversely proportional to dose,-as was expected. Toads of the 300-r and l000- r lines were inbred, and toads of these lines and of the 700-r line were outcrossed to normal ones. Two crosses were made between toads of the 500-r and 1000-r lines. Developmental abnormalities of various kinds appeared at life history stages rangthg from early embryonic development to post-metamorphic life in bothmore » inbred and outcross generations. These included abnormal gastrulation and neurulation, larval and post-metamorphic edema, abnormally positioned or missing limbs, optical deficiencies, prognathous jaw due to excessive elongation of the lower jaw, and melanin deficiency. The prognathous jaw, in its extreme expression, would probably be lethal in natural populations because of difficulty of feeding. The melanin deficiency, in its extreme expression, is lethal as metamorphosis fails to occur, and in lesser expression, it appears to be lethal or detrimental. The various abnormalities do not appear to be inherited in any simple way, but instead they vary in expression both within and between generations, possibly in relation to genotype and environment. (auth)« less

Emotional word usage in groups at risk for schizophrenia-spectrum disorders: An objective investigation of attention to emotion.

PubMed

Fung, Christie K; Moore, Melody M; Karcher, Nicole R; Kerns, John G; Martin, Elizabeth A

2017-06-01

Both extreme levels of social anhedonia (SocAnh) and extreme levels of perceptual aberration/magical ideation (PerMag) indicate increased risk for schizophrenia-spectrum disorders and are associated with emotional deficits. For SocAnh, there is evidence of self-reported decreased trait positive affect and abnormalities in emotional attention. For PerMag, there is evidence of increased trait negative affect and increased attention to negative emotion. Yet, the nature of more objective emotional abnormalities in these groups is unclear. The goal of this study was to assess attention to emotions more objectively in a SocAnh, PerMag, and control group by using a positive (vs. neutral) mood induction procedure followed by a free writing period. Linguistic analyses revealed that the SocAnh group used fewer positive emotion words than the control group, with the PerMag group falling in between the others. In addition, both at-risk groups used more negative emotion words than the control group. Also, for the control group only, those in the positive mood induction used more positive emotion words, suggesting their emotions influenced their linguistic expression. Overall, SocAnh is associated with decreased positive emotional expression and at-risk groups are associated with increased negative emotional expression and a decreased influence of emotions on linguistic expression. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Cloning and expression analysis of tps, and cryopreservation research of trehalose from Antarctic strain Pseudozyma sp.

PubMed

Yin, Hua; Wang, Yibin; He, Yingying; Xing, Lei; Zhang, Xiufang; Wang, Shuai; Qi, Xiaoqing; Zheng, Zhou; Lu, Jian; Miao, Jinlai

2017-10-01

Trehalose is a non-reducing disaccharide sugar that widely exists in a variety of organisms, such as bacteria and eukaryotes except the vertebrates. It plays an important role in a number of critical metabolic functions especially in response to stressful environmental conditions. However, the biosynthetic pathways of trehalose in cold-adapted yeast and its responses to temperature and salinity changes remain little understood. In this study, the genome of Antarctic-isolated Pseudozyma sp. NJ7 was generated from which we identified the gene coding for trehalose phosphate synthase (TPS1) and trehalose phosphate phosphatase (TPS2), the two enzymes most critical for trehalose production. The whole draft genome length of Pseudozyma sp. NJ7 was 18,021,233 bp, and encoded at least 34 rRNA operons and 72 tRNAs. The open reading frame of tps1 contained 1827 nucleotide encoding 608 amino acids with a molecular weight of 67.64 kDa, and an isoelectric point of 5.54, while tps2 contained 3948 nucleotide encoding 1315 amino acids with a molecular weight of 144.47 kDa and an isoelectric point of 6.36. The TPS1 and TPS2 protein sequences were highly homologous to Moesziomyces antarcticus T-34, but TPS2 had obvious specificity and differently with others which suggest species specificity and different evolutionary history. Expression level of tps1 gene was strongly influenced by temperature and high salinity. In addition, addition of 0.5% trehalose preserved yeast cells in the short term but was not effective for cryopreservation for more than 5 days, but still suggesting that exogenous trehalose could indeed significantly improve the survival of yeast cells under freezing conditions. Our results provided new insights on the molecular basis of cold adaptations of Antarctic Pseudozyma sp., and also generated new information on the roles trehalose play in yeast tolerance to extreme conditions in the extreme Antarctic environments.

Escherichia coli growth changes by the mediated effects after low-intensity electromagnetic irradiation of extremely high frequencies.

PubMed

Torgomyan, Heghine; Hovnanyan, Karlen; Trchounian, Armen

2013-04-01

Water is the major constituent of environmental medium and biological systems. The effects occurring in water as a result of low-intensity electromagnetic irradiation (EMI) in extremely high frequencies are supposed to be the primary mechanism to create conditions for biological responses. The EMI effects on Escherichia coli, after irradiation of their suspension, are most probably water-mediated. Indirect effects of EMI at 51.8, 53, 70.6, and 73 GHz frequencies on bacteria, through water, assay buffer (Tris-phosphate buffer with inorganic salts at low or moderate concentrations), or peptone growth medium were studied. The mediated effects of 70.6 and 73 GHz irradiated water, assay buffer, and growth medium on E. coli growth characteristics were insignificant. But the results were different for 51.8 and 53 GHz. EMI mediated effects on bacterial growth were clearly demonstrated. The effects were more strongly expressed with 53 GHz. Moreover, it was shown that 70.6 and 73 GHz similarly suppressed the cell growth after direct irradiation of E. coli in water or on solid medium. Interestingly, for 51.8 and 53 GHz the bacterial growth decreases after suspension irradiation was less, compared to the direct irradiation of bacteria on solid medium. Especially, it was also more expressed in case of 53 GHz. Also with electron microscopy, EMI-induced bacterial cell sizes and structure different changes were detected. In addition, the distinguished changes in surface tension, oxidation-reduction potential and pH of water, assay buffer, growth medium, and bacterial suspension were determined. They depended on EMI frequency used. The differences could be associated with the partial absorbance of EMI energy by the surrounding medium, which depends on a specific frequency. The results are crucial to understand biophysical mechanisms of EMI effects on bacteria.

Projected Changes in Hydrological Extremes in a Cold Region Watershed: Sensitivity of Results to Statistical Methods of Analysis

NASA Astrophysics Data System (ADS)

Dibike, Y. B.; Eum, H. I.; Prowse, T. D.

2017-12-01

Flows originating from alpine dominated cold region watersheds typically experience extended winter low flows followed by spring snowmelt and summer rainfall driven high flows. In a warmer climate, there will be temperature- induced shift in precipitation from snow towards rain as well as changes in snowmelt timing affecting the frequency of extreme high and low flow events which could significantly alter ecosystem services. This study examines the potential changes in the frequency and severity of hydrologic extremes in the Athabasca River watershed in Alberta, Canada based on the Variable Infiltration Capacity (VIC) hydrologic model and selected and statistically downscaled climate change scenario data from the latest Coupled Model Intercomparison Project (CMIP5). The sensitivity of these projected changes is also examined by applying different extreme flow analysis methods. The hydrological model projections show an overall increase in mean annual streamflow in the watershed and a corresponding shift in the freshet timing to earlier period. Most of the streams are projected to experience increases during the winter and spring seasons and decreases during the summer and early fall seasons, with an overall projected increases in extreme high flows, especially for low frequency events. While the middle and lower parts of the watershed are characterised by projected increases in extreme high flows, the high elevation alpine region is mainly characterised by corresponding decreases in extreme low flow events. However, the magnitude of projected changes in extreme flow varies over a wide range, especially for low frequent events, depending on the climate scenario and period of analysis, and sometimes in a nonlinear way. Nonetheless, the sensitivity of the projected changes to the statistical method of analysis is found to be relatively small compared to the inter-model variability.

Coherence Volume of an Optical Wave Field with Broad Frequency and Angular Spectra

NASA Astrophysics Data System (ADS)

Lyakin, D. V.; Mysina, N. Yu.; Ryabukho, V. P.

2018-03-01

We consider the sizes of a region in a three-dimensional space in which an optical wave field excites mutually coherent perturbations. We discuss the conditions under which the length of this region along the direction of propagation of the wave field and, correspondingly, its volume are determined either by the width of the frequency spectrum of the field or by the width of its angular spectrum, or by the parameters of these spectra simultaneously. We obtain expressions for estimating extremely small values of the coherence volume of the fields with a broad frequency spectrum and an extremely broad angular spectrum. Using the notion of instantaneous speckle-modulation of the wave field, we give a physical interpretation to the occurrence of a limited coherence volume of the field. The length of the spatiotemporal coherence region in which mutually coherent perturbations occur at different times is determined. The coherence volume of a wave field that illuminates an object in high-resolution microscopy with frequency broadband light is considered. The conditions for the dominant influence of the angular or frequency spectra on the longitudinal length of the coherence region are given, and the conditions for the influence of the frequency spectrum width on the transverse coherence of the wave field are examined. We show that, when using fields with broad and ultrabroad spectra in high-resolution microscopy, this influence should be taken into account.

Model methodology for estimating pesticide concentration extremes based on sparse monitoring data

USGS Publications Warehouse

Vecchia, Aldo V.

2018-03-22

This report describes a new methodology for using sparse (weekly or less frequent observations) and potentially highly censored pesticide monitoring data to simulate daily pesticide concentrations and associated quantities used for acute and chronic exposure assessments, such as the annual maximum daily concentration. The new methodology is based on a statistical model that expresses log-transformed daily pesticide concentration in terms of a seasonal wave, flow-related variability, long-term trend, and serially correlated errors. Methods are described for estimating the model parameters, generating conditional simulations of daily pesticide concentration given sparse (weekly or less frequent) and potentially highly censored observations, and estimating concentration extremes based on the conditional simulations. The model can be applied to datasets with as few as 3 years of record, as few as 30 total observations, and as few as 10 uncensored observations. The model was applied to atrazine, carbaryl, chlorpyrifos, and fipronil data for U.S. Geological Survey pesticide sampling sites with sufficient data for applying the model. A total of 112 sites were analyzed for atrazine, 38 for carbaryl, 34 for chlorpyrifos, and 33 for fipronil. The results are summarized in this report; and, R functions, described in this report and provided in an accompanying model archive, can be used to fit the model parameters and generate conditional simulations of daily concentrations for use in investigations involving pesticide exposure risk and uncertainty.

Abnormal Positioning of Diencephalic Cell Types in Neocortical Tissue in the Dorsal Telencephalon of Mice Lacking Functional Gli3

PubMed Central

Fotaki, Vassiliki; Yu, Tian; Zaki, Paulette A.; Mason, John O.; Price, David J.

2008-01-01

The transcription factor Gli3 (glioma-associated oncogene homolog) is essential for normal development of the mammalian forebrain. One extreme requirement for Gli3 is at the dorsomedial telencephalon, which does not form in Gli3Xt/Xt mutant mice lacking functional Gli3. In this study, we analyzed expression of Gli3 in the wild-type telencephalon and observed a highdorsal-to-lowventral gradient of Gli3 expression and predominance of the cleaved form of the Gli3 protein dorsally. This graded expression correlates with the severedorsal-to-mildventral telencephalic phenotype observed in Gli3Xt/Xt mice. We characterized the abnormal joining of the telencephalon to the diencephalon and defined the medial limit of the dorsal telencephalon in Gli3Xt/Xt mice early in corticogenesis. Based on this analysis, we concluded that some of the abnormal expression of ventral telencephalic markers previously described as being in the dorsal telencephalon is, in fact, expression in adjacent diencephalic tissue, which expresses many of the same genes that mark the ventral telencephalon. We observed occasional cells with diencephalic character in the Foxg1 (forkhead box)-expressing Gli3Xt/Xt telencephalon at embryonic day 10.5, a day after the anatomical subdivision of the forebrain vesicle. Large clusters of such cells appear in the Gli3Xt/Xt neocortical region at later ages, when the neocortex becomes highly disorganized, forming rosettes comprising mainly neural progenitors. We propose that Gli3 is indispensable for formation of an intact telencephalic-diencephalic boundary and for preventing the abnormal positioning of diencephalic cells in the dorsal telencephalon. PMID:16957084

Insulin-like growth factor (IGF) signalling is required for early dorso-anterior development of the zebrafish embryo.

PubMed

Eivers, Edward; McCarthy, Karena; Glynn, Catherine; Nolan, Catherine M; Byrnes, Lucy

2004-12-01

The insulin-like growth factor (IGF) signalling pathway has been highly conserved in animal evolution and, in mammals and Xenopus, plays a key role in embryonic growth and development, with the IGF-1 receptor (IGF-1R) being a crucial regulator of the signalling cascade. Here we report the first functional role for the IGF pathway in zebrafish. Expression of mRNA coding for a dominant negative IGF-1R resulted in embryos that were small in size compared to controls and had disrupted head and CNS development. At its most extreme, this phenotype was characterized by a complete loss of head and eye structures, an absence of notochord and the presence of abnormal somites. In contrast, up-regulation of IGF signalling following injection of IGF-1 mRNA, resulted in a greatly expanded development of anterior structures at the expense of trunk and tail. IGF-1R knockdown caused a significant decrease in the expression of Otx2, Rx3, FGF8, Pax6.2 and Ntl, while excess IGF signalling expanded Otx2 expression in presumptive forebrain tissue and widened the Ntl expression domain in the developing notochord. The observation that IGF-1R knockdown reduced expression of two key organizer genes (chordin and goosecoid) suggests that IGF signalling plays a role in regulating zebrafish organizer activity. This is supported by the expression of IGF-1, IGF-2 and IGF-1R in shield-stage zebrafish embryos and the demonstration that IGF signalling influences expression of BMP2b, a gene that plays an important role in zebrafish pattern formation. Our data is consistent with a common pathway for integration of IGF, FGF8 and anti-BMPs in early vertebrate development.

Effects of elevated mean and extremely high temperatures on the physio-ecological characteristics of geographically distinctive populations of Cunninghamia lanceolata

NASA Astrophysics Data System (ADS)

Zhou, Ting; Jia, Xiaorong; Liao, Huixuan; Peng, Shijia; Peng, Shaolin

2016-12-01

Conventional models for predicting species distribution under global warming scenarios often treat one species as a homogeneous whole. In the present study, we selected Cunninghamia lanceolata (C. lanceolata), a widely distributed species in China, to investigate the physio-ecological responses of five populations under different temperature regimes. The results demonstrate that increased mean temperatures induce increased growth performance among northern populations, which exhibited the greatest germination capacity and largest increase in the overlap between the growth curve and the monthly average temperature. However,tolerance of the southern population to extremely high temperatures was stronger than among the population from the northern region,shown by the best growth and the most stable photosynthetic system of the southern population under extremely high temperature. This result indicates that the growth advantage among northern populations due to increased mean temperatures may be weakened by lower tolerance to extremely high temperatures. This finding is antithetical to the predicted results. The theoretical coupling model constructed here illustrates that the difference in growth between populations at high and low latitudes and altitudes under global warming will decrease because of the frequent occurrence of extremely high temperatures.

Variability of hydrological extreme events in East Asia and their dynamical control: a comparison between observations and two high-resolution global climate models

NASA Astrophysics Data System (ADS)

Freychet, N.; Duchez, A.; Wu, C.-H.; Chen, C.-A.; Hsu, H.-H.; Hirschi, J.; Forryan, A.; Sinha, B.; New, A. L.; Graham, T.; Andrews, M. B.; Tu, C.-Y.; Lin, S.-J.

2017-02-01

This work investigates the variability of extreme weather events (drought spells, DS15, and daily heavy rainfall, PR99) over East Asia. It particularly focuses on the large scale atmospheric circulation associated with high levels of the occurrence of these extreme events. Two observational datasets (APHRODITE and PERSIANN) are compared with two high-resolution global climate models (HiRAM and HadGEM3-GC2) and an ensemble of other lower resolution climate models from CMIP5. We first evaluate the performance of the high resolution models. They both exhibit good skill in reproducing extreme events, especially when compared with CMIP5 results. Significant differences exist between the two observational datasets, highlighting the difficulty of having a clear estimate of extreme events. The link between the variability of the extremes and the large scale circulation is investigated, on monthly and interannual timescales, using composite and correlation analyses. Both extreme indices DS15 and PR99 are significantly linked to the low level wind intensity over East Asia, i.e. the monsoon circulation. It is also found that DS15 events are strongly linked to the surface temperature over the Siberian region and to the land-sea pressure contrast, while PR99 events are linked to the sea surface temperature anomalies over the West North Pacific. These results illustrate the importance of the monsoon circulation on extremes over East Asia. The dependencies on of the surface temperature over the continent and the sea surface temperature raise the question as to what extent they could affect the occurrence of extremes over tropical regions in future projections.

Estimating extreme stream temperatures by the standard deviate method

NASA Astrophysics Data System (ADS)

Bogan, Travis; Othmer, Jonathan; Mohseni, Omid; Stefan, Heinz

2006-02-01

It is now widely accepted that global climate warming is taking place on the earth. Among many other effects, a rise in air temperatures is expected to increase stream temperatures indefinitely. However, due to evaporative cooling, stream temperatures do not increase linearly with increasing air temperatures indefinitely. Within the anticipated bounds of climate warming, extreme stream temperatures may therefore not rise substantially. With this concept in mind, past extreme temperatures measured at 720 USGS stream gauging stations were analyzed by the standard deviate method. In this method the highest stream temperatures are expressed as the mean temperature of a measured partial maximum stream temperature series plus its standard deviation multiplied by a factor KE (standard deviate). Various KE-values were explored; values of KE larger than 8 were found physically unreasonable. It is concluded that the value of KE should be in the range from 7 to 8. A unit error in estimating KE translates into a typical stream temperature error of about 0.5 °C. Using a logistic model for the stream temperature/air temperature relationship, a one degree error in air temperature gives a typical error of 0.16 °C in stream temperature. With a projected error in the enveloping standard deviate dKE=1.0 (range 0.5-1.5) and an error in projected high air temperature d Ta=2 °C (range 0-4 °C), the total projected stream temperature error is estimated as d Ts=0.8 °C.

Some ideas on the choice of designs and materials for cooled mirrors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howells, M.R.

1994-12-01

This paper expresses some views on the fabrication of future synchrotron beam-line optics; more particularly the metallurgical issues in high-quality metal mirrors. A simple mirror with uniform cooling channels is first analyzed theoretically, followed by the cullular-pin-post system with complex coolant flow path. Choice of mirror material is next considered. For the most challenging situations (need for intensive cooling), the present practice is to use nickel-plated glidcop or silicon; for less severe challenges, Si carbide may be used and cooling may be direct or indirect; and for the mildest heat loads, fused silica or ulf are popular. For the highestmore » performance mirrors (extreme heat load), the glidcop developments should be continued perhaps to cellular-pin-post systems. For extreme distortion, Si is indicated and invar offers both improved performance and lower price. For less extreme challenges but still with cooling, Ni-plated metals have the cost advantage and SXA and other Al alloys can be added to glidcop and invar. For mirrors with mild cooling requirements, stainless steel would have many advantages. Once the internal cooling designs are established, they will be seen as more cost-effective and reliable than clamp-on schemes. Where no cooling is needed, Si, Si carbide, and the glasses can be used. For the future, the effect of electroless Ni layers on cooling design need study, and a way to finish nickel that is compatible with multilayers should be developed.« less

Phage Lambda P Protein: Trans-Activation, Inhibition Phenotypes and their Suppression

PubMed Central

Hayes, Sidney; Erker, Craig; Horbay, Monique A.; Marciniuk, Kristen; Wang, Wen; Hayes, Connie

2013-01-01

The initiation of bacteriophage λ replication depends upon interactions between the oriλ DNA site, phage proteins O and P, and E. coli host replication proteins. P exhibits a high affinity for DnaB, the major replicative helicase for unwinding double stranded DNA. The concept of P-lethality relates to the hypothesis that P can sequester DnaB and in turn prevent cellular replication initiation from oriC. Alternatively, it was suggested that P-lethality does not involve an interaction between P and DnaB, but is targeted to DnaA. P-lethality is assessed by examining host cells for transformation by ColE1-type plasmids that can express P, and the absence of transformants is attributed to a lethal effect of P expression. The plasmid we employed enabled conditional expression of P, where under permissive conditions, cells were efficiently transformed. We observed that ColE1 replication and plasmid establishment upon transformation is extremely sensitive to P, and distinguish this effect from P-lethality directed to cells. We show that alleles of dnaB protect the variant cells from P expression. P-dependent cellular filamentation arose in ΔrecA or lexA[Ind-] cells, defective for SOS induction. Replication propagation and restart could represent additional targets for P interference of E. coli replication, beyond the oriC-dependent initiation step. PMID:23389467

Myocardial Adiponectin Isoform Shift in Dogs with Congestive Heart Failure—A Comparison to Hibernating Brown Bears (Ursus arctos horribilis)

PubMed Central

Nelson, O. Lynne; Wood, Rachael M.; Häggström, Jens; Kvart, Clarence; Robbins, Charles T.

2017-01-01

Adiponectin is the most abundant plasma adipokine, and is well known for its role in energy homeostasis and cardiac protection. In humans with dilated cardiomyopathy, myocardial adiponectin protein expression is reduced compared to normal hearts and has been implicated in the pathology of cardiomyopathy. Serum adiponectin levels are often conflicting, with higher levels associated with poor survival in humans with congestive heart failure (CHF). We evaluated adiponectin serum concentrations and myocardial protein expression in dogs with naturally occurring myxomatous mitral valve disease and CHF. We compared the findings to active and hibernating brown bears as bears are adapted to endure an extreme period of low cardiac output during their annual hibernation. Bears exhibited largely the active high-molecular weight (HMW) versus the low-molecular weight isoforms of myocardial adiponectin (HMW:LMW = 6.3) during both the active period and hibernation, while healthy dogs exhibited a more balanced mix of isoforms. Dogs with CHF expressed predominately HMW isoforms of adiponectin (HMW:LMW = 12.5), appearing more similar to bears. In contrast to humans, serum adiponectin was significantly lower in dogs with CHF and lowest levels in the severest CHF class. In both dogs and bears, myocardial adiponectin was expressed independent of circulating adiponectin concentrations, suggesting a local regulatory mechanism within the heart. PMID:29056695

Did Androgen-Binding Protein Paralogs Undergo Neo- and/or Subfunctionalization as the Abp Gene Region Expanded in the Mouse Genome?

PubMed Central

Karn, Robert C.; Chung, Amanda G.; Laukaitis, Christina M.

2014-01-01

The Androgen-binding protein (Abp) region of the mouse genome contains 30 Abpa genes encoding alpha subunits and 34 Abpbg genes encoding betagamma subunits, their products forming dimers composed of an alpha and a betagamma subunit. We endeavored to determine how many Abp genes are expressed as proteins in tears and saliva, and as transcripts in the exocrine glands producing them. Using standard PCR, we amplified Abp transcripts from cDNA libraries of C57BL/6 mice and found fifteen Abp gene transcripts in the lacrimal gland and five in the submandibular gland. Proteomic analyses identified proteins corresponding to eleven of the lacrimal gland transcripts, all of them different from the three salivary ABPs reported previously. Our qPCR results showed that five of the six transcripts that lacked corresponding proteins are expressed at very low levels compared to those transcripts with proteins. We found 1) no overlap in the repertoires of expressed Abp paralogs in lacrimal gland/tears and salivary glands/saliva; 2) substantial sex-limited expression of lacrimal gland/tear expressed-paralogs in males but no sex-limited expression in females; and 3) that the lacrimal gland/tear expressed-paralogs are found exclusively in ancestral clades 1, 2 and 3 of the five clades described previously while the salivary glands/saliva expressed-paralogs are found only in clade 5. The number of instances of extremely low levels of transcription without corresponding protein production in paralogs specific to tears and saliva suggested the role of subfunctionalization, a derived condition wherein genes that may have been expressed highly in both glands ancestrally were down-regulated subsequent to duplication. Thus, evidence for subfunctionalization can be seen in our data and we argue that the partitioning of paralog expression between lacrimal and salivary glands that we report here occurred as the result of adaptive evolution. PMID:25531410

Did androgen-binding protein paralogs undergo neo- and/or Subfunctionalization as the Abp gene region expanded in the mouse genome?

PubMed

Karn, Robert C; Chung, Amanda G; Laukaitis, Christina M

2014-01-01

The Androgen-binding protein (Abp) region of the mouse genome contains 30 Abpa genes encoding alpha subunits and 34 Abpbg genes encoding betagamma subunits, their products forming dimers composed of an alpha and a betagamma subunit. We endeavored to determine how many Abp genes are expressed as proteins in tears and saliva, and as transcripts in the exocrine glands producing them. Using standard PCR, we amplified Abp transcripts from cDNA libraries of C57BL/6 mice and found fifteen Abp gene transcripts in the lacrimal gland and five in the submandibular gland. Proteomic analyses identified proteins corresponding to eleven of the lacrimal gland transcripts, all of them different from the three salivary ABPs reported previously. Our qPCR results showed that five of the six transcripts that lacked corresponding proteins are expressed at very low levels compared to those transcripts with proteins. We found 1) no overlap in the repertoires of expressed Abp paralogs in lacrimal gland/tears and salivary glands/saliva; 2) substantial sex-limited expression of lacrimal gland/tear expressed-paralogs in males but no sex-limited expression in females; and 3) that the lacrimal gland/tear expressed-paralogs are found exclusively in ancestral clades 1, 2 and 3 of the five clades described previously while the salivary glands/saliva expressed-paralogs are found only in clade 5. The number of instances of extremely low levels of transcription without corresponding protein production in paralogs specific to tears and saliva suggested the role of subfunctionalization, a derived condition wherein genes that may have been expressed highly in both glands ancestrally were down-regulated subsequent to duplication. Thus, evidence for subfunctionalization can be seen in our data and we argue that the partitioning of paralog expression between lacrimal and salivary glands that we report here occurred as the result of adaptive evolution.

About climate variabilitiy leading the hydric condition of the soil in the rainfed region of Argentina

NASA Astrophysics Data System (ADS)

Pántano, V. C.; Penalba, O. C.

2013-05-01

Extreme events of temperature and rainfall have a socio-economic impact in the rainfed agriculture production region in Argentina. The magnitude of the impact can be analyzed through the water balance which integrates the characteristics of the soil and climate conditions. Changes observed in climate variables during the last decades affected the components of the water balance. As a result, a displacement of the agriculture border towards the west was produced, improving the agricultural production of the region. The objective of this work is to analyze how the variability of rainfall and temperature leads the hydric condition of the soil, with special focus on extreme events. The hydric conditions of the soil (HC= Excess- Deficit) were estimated from the monthly water balance (Thornthwaite and Mather method, 1957), using monthly potential evapotranspiration (PET) and monthly accumulated rainfall (R) for 33 stations (period 1970-2006). Information of temperature and rainfall was provided by National Weather Service and the effective capacity of soil water was considered from Forte Lay and Spescha (2001). An agricultural extreme condition occurs when soil moisture and rainfall are inadequate or excessive for the development of the crops. In this study, we define an extreme event when the variable is less (greater) than its 20% and 10% (80% and 90%) percentile. In order to evaluate how sensitive is the HC to water and heat stress in the region, different conditional probabilities were evaluated. There is a weaker response of HC to extreme low PET while extreme low R leads high values of HC. However, this behavior is not always observed, especially in the western region where extreme high and low PET show a stronger influence over the HC. Finally, to analyze the temporal variability of extreme PET and R, leading hydric condition of the soil, the number of stations presenting extreme conditions was computed for each month. As an example, interesting results were observed for April. During this month, the water recharge of the soil is crucial to let the winter crops manage with the scarce rainfalls occurring in the following months. In 1970, 1974, 1977, 1978 and 1997 more than 50% of the stations were under extreme high PET; while 1970, 1974, 1978 and 1988 presented more than 40% under extreme low R. Thus, the 70s was the more threatened decade of the period. Since the 80s (except for 1997), extreme dry events due to one variable or the other are mostly presented separately, over smaller areas. The response of the spatial distribution of HC is stronger when both variables present extreme conditions. In particular, during 1997 the region presents extreme low values of HC as a consequence of extreme low R and high PET. Communities dependent on agriculture are highly sensitive to climate variability and its extremes. In the studied region, it was shown that scarce water and heat stress contribute to the resulting hydric condition, producing strong impact over different productive activities. Extreme temperature seems to have a stronger influence over extreme unfavorable hydric conditions.

Divergence of Iron Metabolism in Wild Malaysian Yeast

PubMed Central

Lee, Hana N.; Mostovoy, Yulia; Hsu, Tiffany Y.; Chang, Amanda H.; Brem, Rachel B.

2013-01-01

Comparative genomic studies have reported widespread variation in levels of gene expression within and between species. Using these data to infer organism-level trait divergence has proven to be a key challenge in the field. We have used a wild Malaysian population of S. cerevisiae as a test bed in the search to predict and validate trait differences based on observations of regulatory variation. Malaysian yeast, when cultured in standard medium, activated regulatory programs that protect cells from the toxic effects of high iron. Malaysian yeast also showed a hyperactive regulatory response during culture in the presence of excess iron and had a unique growth defect in conditions of high iron. Molecular validation experiments pinpointed the iron metabolism factors AFT1, CCC1, and YAP5 as contributors to these molecular and cellular phenotypes; in genome-scale sequence analyses, a suite of iron toxicity response genes showed evidence for rapid protein evolution in Malaysian yeast. Our findings support a model in which iron metabolism has diverged in Malaysian yeast as a consequence of a change in selective pressure, with Malaysian alleles shifting the dynamic range of iron response to low-iron concentrations and weakening resistance to extreme iron toxicity. By dissecting the iron scarcity specialist behavior of Malaysian yeast, our work highlights the power of expression divergence as a signpost for biologically and evolutionarily relevant variation at the organismal level. Interpreting the phenotypic relevance of gene expression variation is one of the primary challenges of modern genomics. PMID:24142925

Divergence of iron metabolism in wild Malaysian yeast.

PubMed

Lee, Hana N; Mostovoy, Yulia; Hsu, Tiffany Y; Chang, Amanda H; Brem, Rachel B

2013-12-09

Comparative genomic studies have reported widespread variation in levels of gene expression within and between species. Using these data to infer organism-level trait divergence has proven to be a key challenge in the field. We have used a wild Malaysian population of S. cerevisiae as a test bed in the search to predict and validate trait differences based on observations of regulatory variation. Malaysian yeast, when cultured in standard medium, activated regulatory programs that protect cells from the toxic effects of high iron. Malaysian yeast also showed a hyperactive regulatory response during culture in the presence of excess iron and had a unique growth defect in conditions of high iron. Molecular validation experiments pinpointed the iron metabolism factors AFT1, CCC1, and YAP5 as contributors to these molecular and cellular phenotypes; in genome-scale sequence analyses, a suite of iron toxicity response genes showed evidence for rapid protein evolution in Malaysian yeast. Our findings support a model in which iron metabolism has diverged in Malaysian yeast as a consequence of a change in selective pressure, with Malaysian alleles shifting the dynamic range of iron response to low-iron concentrations and weakening resistance to extreme iron toxicity. By dissecting the iron scarcity specialist behavior of Malaysian yeast, our work highlights the power of expression divergence as a signpost for biologically and evolutionarily relevant variation at the organismal level. Interpreting the phenotypic relevance of gene expression variation is one of the primary challenges of modern genomics.

Projected regional changes in the characteristics of dry and moist heat waves in the United States derived from downscaled CMIP5 models

NASA Astrophysics Data System (ADS)

Schoof, J. T.

2017-12-01

Extreme temperatures affect society in multiple ways, but the impacts are often different depending on the concurrent humidity. For example, the greatest impacts on human morbidity and mortality result when the temperature and humidity are both elevated. Conversely, high temperatures coupled with low humidity often lead to agricultural impacts resulting in lower yields. Despite the importance of humidity in determining heat wave impacts, relatively few students of future temperature extremes have also considered possible changes in humidity. In a recent study, we investigated recent historical changes in the frequency and intensity and low humidity and high humidity extreme temperature events using a framework based on isobaric equivalent temperature. Here, we extend this approach to climate projections from CMIP5 models to explore possible regional changes in extreme heat characteristics. After using quantile mapping to bias correct and downscale the CMIP5 model outputs, we analyze results from two future periods (2031-2055 and 2061-2085) and two representative concentration pathways, RCP 4.5 and RCP 8.5, corresponding to moderate and high levels of radiative forcing from greenhouse gases. For each of seven US regions, we consider changes in extreme temperature frequency, changes in the proportion of extreme temperature days characterized by high humidity, and changes in the magnitude of temperature and humidity on extreme temperature days.

The critical role of uncertainty in projections of hydrological extremes

NASA Astrophysics Data System (ADS)

Meresa, Hadush K.; Romanowicz, Renata J.

2017-08-01

This paper aims to quantify the uncertainty in projections of future hydrological extremes in the Biala Tarnowska River at Koszyce gauging station, south Poland. The approach followed is based on several climate projections obtained from the EURO-CORDEX initiative, raw and bias-corrected realizations of catchment precipitation, and flow simulations derived using multiple hydrological model parameter sets. The projections cover the 21st century. Three sources of uncertainty are considered: one related to climate projection ensemble spread, the second related to the uncertainty in hydrological model parameters and the third related to the error in fitting theoretical distribution models to annual extreme flow series. The uncertainty of projected extreme indices related to hydrological model parameters was conditioned on flow observations from the reference period using the generalized likelihood uncertainty estimation (GLUE) approach, with separate criteria for high- and low-flow extremes. Extreme (low and high) flow quantiles were estimated using the generalized extreme value (GEV) distribution at different return periods and were based on two different lengths of the flow time series. A sensitivity analysis based on the analysis of variance (ANOVA) shows that the uncertainty introduced by the hydrological model parameters can be larger than the climate model variability and the distribution fit uncertainty for the low-flow extremes whilst for the high-flow extremes higher uncertainty is observed from climate models than from hydrological parameter and distribution fit uncertainties. This implies that ignoring one of the three uncertainty sources may cause great risk to future hydrological extreme adaptations and water resource planning and management.

Regional-Scale High-Latitude Extreme Geoelectric Fields Pertaining to Geomagnetically Induced Currents

NASA Technical Reports Server (NTRS)

Pulkkinen, Antti; Bernabeu, Emanuel; Eichner, Jan; Viljanen, Ari; Ngwira, Chigomezyo

2015-01-01

Motivated by the needs of the high-voltage power transmission industry, we use data from the high-latitude IMAGE magnetometer array to study characteristics of extreme geoelectric fields at regional scales. We use 10-s resolution data for years 1993-2013, and the fields are characterized using average horizontal geoelectric field amplitudes taken over station groups that span about 500-km distance. We show that geoelectric field structures associated with localized extremes at single stations can be greatly different from structures associated with regionally uniform geoelectric fields, which are well represented by spatial averages over single stations. Visual extrapolation and rigorous extreme value analysis of spatially averaged fields indicate that the expected range for 1-in-100-year extreme events are 3-8 V/km and 3.4-7.1 V/km, respectively. The Quebec reference ground model is used in the calculations.

Whole blood transcriptome comparison of pigs with extreme production of in vivo dsRNA-induced serum IFN-a.

PubMed

Liu, Xiangdong; Huang, Jing; Yang, Songbai; Zhao, Yunxia; Xiang, Anjing; Cao, Jianhua; Fan, Bin; Wu, Zhenfang; Zhao, Junlong; Zhao, Shuhong; Zhu, Mengjin

2014-05-01

Interferon (IFN) is one of the major regulators of innate immunity, it also mediates the adaptive immune responses to a broad spectrum of pathogens. This study aims in identifying differences between high vs. low INF-a responders which were chosen based on serum INF-a levels at 4 h post poly I:C treatment. A transcriptomic analysis was designed to describe the whole blood differential transcriptomal response to poly I:C by pigs with high vs. low IFN alpha levels. The capability of producing dsRNA (poly I:C)-induced serum IFN-a is highly variable in pig population. The high INF-a responders had 328 unique differentially expressed genes, suggesting that the HIGH pigs have greater responsiveness upon the dsRNA simulation. Based on the results, the interferon-dependent antiviral responsiveness through the IFN-stimulated genes (ISGs) is likely more effective in HIGH pigs. Inferring from the known organization of IFN pathways, the reason for the more IFN-a production in the HIGH pigs was likely due to the enhanced expression of IRF-7 in TLR or RIG- I/MDA5 signaling pathways. Furthermore, the larger number of the altered genes in the HIGH pigs after simulation is also possibly because of the greater number of the altered transcription factors. To our knowledge, this is the first report of comparative transcriptomic analysis to advance our understanding of whole blood immune response in pigs with different in vivo poly I:C-inducted IFN-a levels. The paper significantly expands our knowledge of how pigs respond to poly I:C which is highly relevant for understanding resistance to viral infections and also for vaccine development. Copyright © 2013 Elsevier Ltd. All rights reserved.

Brief Report: A mass spectrometry assay to simultaneously analyze ROS1 and RET fusion gene expression in non-small cell lung cancer

PubMed Central

Wijesinghe, Priyanga; Bepler, Gerold

2014-01-01

Introduction ROS1 and RET gene fusions were recently discovered in non-small cell lung cancer (NSCLC) as potential therapeutic targets with small molecule kinase inhibitors. The conventional screening methods of these fusions are time consuming and require samples of high quality and quantity. Here, we describe a novel and efficient method by coupling the power of multiplexing PCR and the sensitivity of mass spectrometry. Methods The multiplex mass spectrometry platform simultaneously tests samples for the expression of nine ROS1 and six RET fusion genes. The assay incorporates detection of wild-type exon junctions immediately upstream and downstream of the fusion junction to exclude false negative results. To flag false positives, the system also comprises two independent assays for each fusion gene junction. Results The characteristic mass spectrometric peaks of the gene fusions were obtained using engineered plasmid constructs. Specific assays targeting the wild-type gene exon junctions were validated using cDNA from lung tissue of healthy individuals. The system was further validated using cDNA derived from NSCLC cell lines that express endogenous fusion genes. The expressed ROS1-SLC34A2 and CCDC6-RET gene fusions from the NSCLC cell lines HCC78 and LC-2/ad, respectively, were accurately detected by the novel assay. The assay is extremely sensitive, capable of detecting an event in test specimens containing 0.5% positive tumors. Conclusion The novel multiplexed assay is robustly capable of detecting 15 different clinically relevant RET and ROS1 fusion variants. The benefits of this detection method include exceptionally low sample input, high cost efficiency, flexibility, and rapid turnover. PMID:25384172

Analysis of porcine adipose tissue transcriptome reveals differences in de novo fatty acid synthesis in pigs with divergent muscle fatty acid composition.

PubMed

Corominas, Jordi; Ramayo-Caldas, Yuliaxis; Puig-Oliveras, Anna; Estellé, Jordi; Castelló, Anna; Alves, Estefania; Pena, Ramona N; Ballester, Maria; Folch, Josep M

2013-12-01

In pigs, adipose tissue is one of the principal organs involved in the regulation of lipid metabolism. It is particularly involved in the overall fatty acid synthesis with consequences in other lipid-target organs such as muscles and the liver. With this in mind, we have used massive, parallel high-throughput sequencing technologies to characterize the porcine adipose tissue transcriptome architecture in six Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition (three per group). High-throughput RNA sequencing was used to generate a whole characterization of adipose tissue (backfat) transcriptome. A total of 4,130 putative unannotated protein-coding sequences were identified in the 20% of reads which mapped in intergenic regions. Furthermore, 36% of the unmapped reads were represented by interspersed repeats, SINEs being the most abundant elements. Differential expression analyses identified 396 candidate genes among divergent animals for intramuscular fatty acid composition. Sixty-two percent of these genes (247/396) presented higher expression in the group of pigs with higher content of intramuscular SFA and MUFA, while the remaining 149 showed higher expression in the group with higher content of PUFA. Pathway analysis related these genes to biological functions and canonical pathways controlling lipid and fatty acid metabolisms. In concordance with the phenotypic classification of animals, the major metabolic pathway differentially modulated between groups was de novo lipogenesis, the group with more PUFA being the one that showed lower expression of lipogenic genes. These results will help in the identification of genetic variants at loci that affect fatty acid composition traits. The implications of these results range from the improvement of porcine meat quality traits to the application of the pig as an animal model of human metabolic diseases.

Mathematical Justification of Expression-Based Pathway Activation Scoring (PAS).

PubMed

Aliper, Alexander M; Korzinkin, Michael B; Kuzmina, Natalia B; Zenin, Alexander A; Venkova, Larisa S; Smirnov, Philip Yu; Zhavoronkov, Alex A; Buzdin, Anton A; Borisov, Nikolay M

2017-01-01

Although modeling of activation kinetics for various cell signaling pathways has reached a high grade of sophistication and thoroughness, most such kinetic models still remain of rather limited practical value for biomedicine. Nevertheless, recent advancements have been made in application of signaling pathway science for real needs of prescription of the most effective drugs for individual patients. The methods for such prescription evaluate the degree of pathological changes in the signaling machinery based on two types of data: first, on the results of high-throughput gene expression profiling, and second, on the molecular pathway graphs that reflect interactions between the pathway members. For example, our algorithm OncoFinder evaluates the activation of molecular pathways on the basis of gene/protein expression data in the objects of the interest.Yet, the question of assessment of the relative importance for each gene product in a molecular pathway remains unclear unless one call for the methods of parameter sensitivity /stiffness analysis in the interactomic kinetic models of signaling pathway activation in terms of total concentrations of each gene product.Here we show two principal points: 1. First, the importance coefficients for each gene in pathways that were obtained using the extremely time- and labor-consuming stiffness analysis of full-scaled kinetic models generally differ from much easier-to-calculate expression-based pathway activation score (PAS) not more than by 30%, so the concept of PAS is kinetically justified. 2. Second, the use of pathway-based approach instead of distinct gene analysis, due to the law of large numbers, allows restoring the correlation between the similar samples that were examined using different transcriptome investigation techniques.

Microbiota diversity and gene expression dynamics in human oral biofilms

PubMed Central

2014-01-01

Background Micro-organisms inhabiting teeth surfaces grow on biofilms where a specific and complex succession of bacteria has been described by co-aggregation tests and DNA-based studies. Although the composition of oral biofilms is well established, the active portion of the bacterial community and the patterns of gene expression in vivo have not been studied. Results Using RNA-sequencing technologies, we present the first metatranscriptomic study of human dental plaque, performed by two different approaches: (1) A short-reads, high-coverage approach by Illumina sequencing to characterize the gene activity repertoire of the microbial community during biofilm development; (2) A long-reads, lower-coverage approach by pyrosequencing to determine the taxonomic identity of the active microbiome before and after a meal ingestion. The high-coverage approach allowed us to analyze over 398 million reads, revealing that microbial communities are individual-specific and no bacterial species was detected as key player at any time during biofilm formation. We could identify some gene expression patterns characteristic for early and mature oral biofilms. The transcriptomic profile of several adhesion genes was confirmed through qPCR by measuring expression of fimbriae-associated genes. In addition to the specific set of gene functions overexpressed in early and mature oral biofilms, as detected through the short-reads dataset, the long-reads approach detected specific changes when comparing the metatranscriptome of the same individual before and after a meal, which can narrow down the list of organisms responsible for acid production and therefore potentially involved in dental caries. Conclusions The bacteria changing activity during biofilm formation and after meal ingestion were person-specific. Interestingly, some individuals showed extreme homeostasis with virtually no changes in the active bacterial population after food ingestion, suggesting the presence of a microbial community which could be associated to dental health. PMID:24767457

Microbiota diversity and gene expression dynamics in human oral biofilms.

PubMed

Benítez-Páez, Alfonso; Belda-Ferre, Pedro; Simón-Soro, Aurea; Mira, Alex

2014-04-27

Micro-organisms inhabiting teeth surfaces grow on biofilms where a specific and complex succession of bacteria has been described by co-aggregation tests and DNA-based studies. Although the composition of oral biofilms is well established, the active portion of the bacterial community and the patterns of gene expression in vivo have not been studied. Using RNA-sequencing technologies, we present the first metatranscriptomic study of human dental plaque, performed by two different approaches: (1) A short-reads, high-coverage approach by Illumina sequencing to characterize the gene activity repertoire of the microbial community during biofilm development; (2) A long-reads, lower-coverage approach by pyrosequencing to determine the taxonomic identity of the active microbiome before and after a meal ingestion. The high-coverage approach allowed us to analyze over 398 million reads, revealing that microbial communities are individual-specific and no bacterial species was detected as key player at any time during biofilm formation. We could identify some gene expression patterns characteristic for early and mature oral biofilms. The transcriptomic profile of several adhesion genes was confirmed through qPCR by measuring expression of fimbriae-associated genes. In addition to the specific set of gene functions overexpressed in early and mature oral biofilms, as detected through the short-reads dataset, the long-reads approach detected specific changes when comparing the metatranscriptome of the same individual before and after a meal, which can narrow down the list of organisms responsible for acid production and therefore potentially involved in dental caries. The bacteria changing activity during biofilm formation and after meal ingestion were person-specific. Interestingly, some individuals showed extreme homeostasis with virtually no changes in the active bacterial population after food ingestion, suggesting the presence of a microbial community which could be associated to dental health.

Prepubertal unilateral gynecomastia: report of 2 cases.

PubMed

Demirbilek, Hüseyin; Bacak, Gökhan; Baran, Rıza Taner; Avcı, Yahya; Baran, Ahmet; Keleş, Ayşenur; Özbek, Mehmet Nuri; Alanay, Yasemin; Hussain, Khalid

2014-12-01

Prepubertal unilateral gynecomastia is an extremely rare condition. At present, its etiology and management strategy are not well known. Two unrelated prepubertal boys of ages 8 and 9 who presented with complaints of unilateral enlargement of breast tissue are reported. Physical examination, biochemical, hormonal and oncologic work-up findings were normal. Both patients were treated with peripheral liposuction successfully. Histopathological and immunohistochemical examinations showed benign fibroglandular gynecomastia and intensive (3+) estrogen receptor expression in 100% of periductal epithelial cells. Although an extremely rare and generally benign condition, patients with prepubertal unilateral gynecomastia should have a full endocrine and oncologic work-up.

Prepubertal Unilateral Gynecomastia: Report of 2 Cases

PubMed Central

Demirbilek, Hüseyin; Bacak, Gökhan; Baran, Rıza Taner; Avcı, Yahya; Baran, Ahmet; Keleş, Ayşenur; Özbek, Mehmet Nuri; Alanay, Yasemin; Hussain, Khalid

2014-01-01

Prepubertal unilateral gynecomastia is an extremely rare condition. At present, its etiology and management strategy are not well known. Two unrelated prepubertal boys of ages 8 and 9 who presented with complaints of unilateral enlargement of breast tissue are reported. Physical examination, biochemical, hormonal and oncologic work-up findings were normal. Both patients were treated with peripheral liposuction successfully. Histopathological and immunohistochemical examinations showed benign fibroglandular gynecomastia and intensive (3+) estrogen receptor expression in 100% of periductal epithelial cells. Although an extremely rare and generally benign condition, patients with prepubertal unilateral gynecomastia should have a full endocrine and oncologic work-up. PMID:25541897

[Experimental evaluation of actoprotective activity of nitrogen-containing heterocyclic compounds derivatives in extreme conditions].

PubMed

Tsublova, E G; Ivanova, T G; Ivanova, T N; Iasnetsov, V V

2013-07-01

In experiments on nonlinear male mice the ability of new derivatives of nitrogen-containing heterocyclic compounds to increase the physical working capacity in conditions of hyperthermia, hypothermia and acute normobaric hypoxia and hypercapnia has been investigated. It is established, that pyridine derivative IBHF-11 has more expressed positive action in the said conditions. It provided increase of the working capacity of animals at all kinds of extreme influence, and the value of positive action was comparable, and in conditions of acute normobaric hypoxia and hypercapnia exceeded those at the reference products bemitil and bromantan.

Evaluation of uncertainty in capturing the spatial variability and magnitudes of extreme hydrological events for the uMngeni catchment, South Africa

NASA Astrophysics Data System (ADS)

Kusangaya, Samuel; Warburton Toucher, Michele L.; van Garderen, Emma Archer

2018-02-01

Downscaled General Circulation Models (GCMs) output are used to forecast climate change and provide information used as input for hydrological modelling. Given that our understanding of climate change points towards an increasing frequency, timing and intensity of extreme hydrological events, there is therefore the need to assess the ability of downscaled GCMs to capture these extreme hydrological events. Extreme hydrological events play a significant role in regulating the structure and function of rivers and associated ecosystems. In this study, the Indicators of Hydrologic Alteration (IHA) method was adapted to assess the ability of simulated streamflow (using downscaled GCMs (dGCMs)) in capturing extreme river dynamics (high and low flows), as compared to streamflow simulated using historical climate data from 1960 to 2000. The ACRU hydrological model was used for simulating streamflow for the 13 water management units of the uMngeni Catchment, South Africa. Statistically downscaled climate models obtained from the Climate System Analysis Group at the University of Cape Town were used as input for the ACRU Model. Results indicated that, high flows and extreme high flows (one in ten year high flows/large flood events) were poorly represented both in terms of timing, frequency and magnitude. Simulated streamflow using dGCMs data also captures more low flows and extreme low flows (one in ten year lowest flows) than that captured in streamflow simulated using historical climate data. The overall conclusion was that although dGCMs output can reasonably be used to simulate overall streamflow, it performs poorly when simulating extreme high and low flows. Streamflow simulation from dGCMs must thus be used with caution in hydrological applications, particularly for design hydrology, as extreme high and low flows are still poorly represented. This, arguably calls for the further improvement of downscaling techniques in order to generate climate data more relevant and useful for hydrological applications such as in design hydrology. Nevertheless, the availability of downscaled climatic output provide the potential of exploring climate model uncertainties in different hydro climatic regions at local scales where forcing data is often less accessible but more accurate at finer spatial scales and with adequate spatial detail.

Social interactions in massively multiplayer online role-playing gamers.

PubMed

Cole, Helena; Griffiths, Mark D

2007-08-01

To date, most research into massively multiplayer online role-playing games (MMORPGs) has examined the demographics of play. This study explored the social interactions that occur both within and outside of MMORPGs. The sample consisted of 912 self-selected MMORPG players from 45 countries. MMORPGs were found to be highly socially interactive environments providing the opportunity to create strong friendships and emotional relationships. The study demonstrated that the social interactions in online gaming form a considerable element in the enjoyment of playing. The study showed MMORPGs can be extremely social games, with high percentages of gamers making life-long friends and partners. It was concluded that virtual gaming may allow players to express themselves in ways they may not feel comfortable doing in real life because of their appearance, gender, sexuality, and/or age. MMORPGs also offer a place where teamwork, encouragement, and fun can be experienced.

The seco-iridoid pathway from Catharanthus roseus

PubMed Central

Miettinen, Karel; Dong, Lemeng; Navrot, Nicolas; Schneider, Thomas; Burlat, Vincent; Pollier, Jacob; Woittiez, Lotte; van der Krol, Sander; Lugan, Raphaël; Ilc, Tina; Verpoorte, Robert; Oksman-Caldentey, Kirsi-Marja; Martinoia, Enrico; Bouwmeester, Harro; Goossens, Alain; Memelink, Johan; Werck-Reichhart, Danièle

2014-01-01

The (seco)iridoids and their derivatives, the monoterpenoid indole alkaloids (MIAs), form two large families of plant-derived bioactive compounds with a wide spectrum of high-value pharmacological and insect-repellent activities. Vinblastine and vincristine, MIAs used as anticancer drugs, are produced by Catharanthus roseus in extremely low levels, leading to high market prices and poor availability. Their biotechnological production is hampered by the fragmentary knowledge of their biosynthesis. Here we report the discovery of the last four missing steps of the (seco)iridoid biosynthesis pathway. Expression of the eight genes encoding this pathway, together with two genes boosting precursor formation and two downstream alkaloid biosynthesis genes, in an alternative plant host, allows the heterologous production of the complex MIA strictosidine. This confirms the functionality of all enzymes of the pathway and highlights their utility for synthetic biology programmes towards a sustainable biotechnological production of valuable (seco)iridoids and alkaloids with pharmaceutical and agricultural applications. PMID:24710322

Extremely low-level microwaves attenuate immune imbalance induced by inhalation exposure to low-level toluene in mice.

PubMed

Novoselova, Elena G; Glushkova, Olga V; Khrenov, Maxim O; Novoselova, Tatyana V; Lunin, Sergey M; Fesenko, Eugeny E

2017-05-01

To clarify whether extremely low-level microwaves (MW) alone or in combination with p38 inhibitor affect immune cell responses to inhalation exposure of mice to low-level toluene. The cytokine profile, heat shock proteins expression, and the activity of several signal cascades, namely, NF-κB, SAPK/JNK, IRF-3, p38 MAPK, and TLR4 were measured in spleen lymphocytes of mice treated to air-delivered toluene (0.6 mg/m 3 ) or extremely low-level microwaves (8.15-18 GHz, 1μW/cm 2 , 1 Hz swinging frequency) or combined action of these two factors. A single exposure to air-delivered low-level toluene induced activation of NF-κB, SAPK/JNK, IFR-3, p38 MAPK and TLR4 pathways. Furthermore, air toluene induced the expression of Hsp72 and enhanced IL-1, IL-6, and TNF-α in blood plasma, which is indicative of a pro-inflammatory response. Exposure to MW alone also resulted in the enhancement of the plasma cytokine values (e.g. IL-6, TNF-α, and IFN-γ) and activation of the NF-κB, MAPK p38, and especially the TLR4 pathways in splenic lymphocytes. Paradoxically, pre-exposure to MW partially recovered or normalized the lymphocyte parameters in the toluene-exposed mice, while the p38 inhibitor XI additionally increased protective activity of microwaves by down regulating MAPKs (JNK and p38), IKK, as well as expression of TLR4 and Hsp90-α. The results suggest that exposure to low-intensity MW at specific conditions may recover immune parameters in mice undergoing inhalation exposure to low-level toluene via mechanisms involving cellular signaling.

Emotion regulation strategies mediate the associations of positive and negative affect to upper extremity physical function.

PubMed

Talaei-Khoei, Mojtaba; Nemati-Rezvani, Hora; Fischerauer, Stefan F; Ring, David; Chen, Neal; Vranceanu, Ana-Maria

2017-05-01

The Gross process model of emotion regulation holds that emotion-eliciting situations (e.g. musculoskeletal illness) can be strategically regulated to determine the final emotional and behavioral response. Also, there is some evidence that innate emotional traits may predispose an individual to a particular regulating coping style. We enrolled 107 patients with upper extremity musculoskeletal illness in this cross-sectional study. They completed self-report measures of positive and negative affect, emotion regulation strategies (cognitive reappraisal and expressive suppression), upper extremity physical function, pain intensity, and demographics. We used Preacher and Hayes' bootstrapping approach to process analysis to infer the direct effect of positive and negative affect on physical function as well as their indirect effects through activation of emotion regulation strategies. Negative affect was associated with decreased physical function. The association was partly mediated by expressive suppression (b (SE)=-.10 (.05), 95% BCa CI [-.21, -.02]). Positive affect was associated with increased physical function. Cognitive reappraisal partially mediated this association (b (SE)=.11 (.05), 95% BCa CI [.03, .24]). After controlling for pain intensity, the ratio of the mediated effect to total effect grew even larger in controlled model comparing to uncontrolled model (33% vs. 26% for expressive suppression and 32% vs. 30% for cognitive reappraisal). The relationships between affect, emotion regulation strategies and physical function appear to be more dependent on the emotional response to an orthopedic condition rather than the intensity of the nociceptive stimulation of the pain. Findings support integration of emotion regulation training in skill-based psychotherapy in this population to mitigate the effect of negative affect and enhance the influence of positive affect on physical function. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of regional slopes on local structure and exploration of tilted paleo-highs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nazarov, D.A.; Chernobrov, B.S.

1986-06-01

Prospects for discovering local highs in old petroleum-producing regions have by now been substantially exhausted. Hence it is of great importance at this stage to seek non-anticlinal accumulations of hydrocarbons, including those in traps genetically associated with tilted paleo-highs, often represented in the modern structural plan by structural noses and terraces. Appropriate exploration for such types of deposits may soon become important in Ciscaucasia and other old petroleum-producing regions. Consequently, problems of the scientific basis for prospecting paleo-highs tilted in the modern structural plan, and developing procedures both for revealing and also for assessing their expression in the structural planmore » during different stages of geological history, and establishing the time and depth of changes in aspect, will become extremely topical. In order to discover possible local highs and to study their features within the margins of the platformal basins and the platformal edges of the marginal troughs, the authors use the method of removing the effect of the regional slope on the local structural plan. This paper describes this method. 13 references.« less

Combination of carbon ion beam and gemcitabine causes irreparable DNA damage and death of radioresistant pancreatic cancer stem-like cells in vitro and in vivo

PubMed Central

Sai, Sei; Wakai, Toshifumi; Vares, Guillaume; Yamada, Shigeru; Kamijo, Takehiko; Kamada, Tadashi; Shirai, Toshiyuki

2015-01-01

We try to elucidate whether a carbon ion beam alone or in combination with gemcitabine has advantages over X-ray in targeting putative pancreatic cancer stem-like cells (CSCs) in vitro and in vivo. Colony, spheroid formation and tumorigenicity assays confirmed that CD44+/ESA+ cells sorted from PANC1 and PK45 cells have more CSC properties than CD44−/ESA− cells. The number of colonies and spheroids formed from CSCs after carbon ion beam irradiation was significantly reduced compared to after X-ray irradiation, and they were extremely highly suppressed when carbon ion beam combined with gemcitabine. The relative biological effectiveness (RBE) values for the carbon ion beam relative to X-ray at the D10 levels for CSCs were 2.23-2.66. Expressions of multiple cell death-related genes were remarkably highly induced, and large numbers of γH2AX foci in CSCs were formed after carbon ion beam combined with gemcitabine. The highly expressed CSC markers were significantly inhibited after 30 Gy of carbon ion beam and almost lost after 25 Gy carbon ion beam combined with 50 mg/kg gemcitabine. In conclusion, a carbon ion beam combined with gemcitabine has superior potential to kill pancreatic CSCs via irreparable clustered DSB compared to a carbon ion alone or X-rays combined with gemcitabine. PMID:25849939

Myxofibrosarcoma primary cultures: molecular and pharmacological profile

PubMed Central

De Vita, Alessandro; Recine, Federica; Mercatali, Laura; Miserocchi, Giacomo; Liverani, Chiara; Spadazzi, Chiara; Casadei, Roberto; Bongiovanni, Alberto; Pieri, Federica; Riva, Nada; Amadori, Dino; Ibrahim, Toni

2017-01-01

Background: Myxofibrosarcoma (MFS), formerly considered as a myxoid variant of malignant fibrous histiocytoma, is the most common sarcoma of the extremities in adults and is characterized by a high frequency of local recurrence. The clinical behavior of MFS is unpredictable and the efficacy of chemotherapy is still not well documented. Furthermore, given the relatively recent recognition of MFS as a distinct pathologic entity its cellular and molecular biology has still not been extensively studied in patient-derived preclinical models. We examined the molecular biology and treatment outcomes of high-grade, patient-derived MFS primary cultures. Methods: A total of three patient-derived MFS primary cultures were analyzed. We evaluated the role of CD109 expression and also looked for a correlation between transforming growth factor-beta (TGF-β) expression and sensitivity of the primary cultures to different drugs. Results: CD109 was a promising marker for the identification of more aggressive high-grade MFS and a potential therapeutic target. The results also highlighted the potential role of TGF-β in chemoresistance. Pharmacological analysis confirmed the sensitivity of the cultures to chemotherapy. The most active treatments were epirubicin alone and epirubicin in combination with ifosfamide, the latter representing the current standard of care for soft tissue sarcomas (STSs), including MFS. Conclusions: Our results provide a starting point for further research aimed at improving the management of MFS patients undergoing chemotherapy. PMID:29449896

Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma.

PubMed

Elloul, Sivan; Elstrand, Mari Bukholt; Nesland, Jahn M; Tropé, Claes G; Kvalheim, Gunnar; Goldberg, Iris; Reich, Reuven; Davidson, Ben

2005-04-15

It was demonstrated previously that the Snail family of transcription factors and Smad-interacting protein 1 (Sip1) regulate E-cadherin and matrix metalloproteinase 2 (MMP-2) expression, cellular morphology, and invasion in carcinoma. For the current study, the authors analyzed the relation between the expression of Snail, Slug, and Sip1; the expression of MMP-2 and E-cadherin; and clinical parameters in patients with metastatic ovarian and breast carcinoma. One hundred one fresh-frozen, malignant effusions from patients who were diagnosed with gynecologic carcinomas (78 ovarian carcinomas and 23 breast carcinomas) were studied for mRNA expression of Snail, Slug, Sip1, MMP-2, and E-cadherin using reverse transcriptase-polymerase chain reaction analysis. Snail mRNA and E-cadherin protein expression levels also were studied in ovarian carcinoma effusions using in situ hybridization and immunocytochemistry. The results were analyzed for possible correlation with clinicopathologic parameters in both tumor types. E-cadherin mRNA expression was lower in breast carcinoma (P = 0.001), whereas Snail expression was higher (P = 0.003). The Snail/E-cadherin ratio (P < 0.001) and the Sip1/E-cadherin ratio (P = 0.002) were higher in breast carcinomas. Sip1 mRNA expression (P < 0.001) and Slug mRNA expression (P < 0.001) were correlated with the expression of MMP-2 in ovarian carcinomas. The Sip1/E-cadherin ratio was higher in primary ovarian carcinomas at the time of diagnosis compared with postchemotherapy ovarian carcinoma effusions (P = 0.003), higher in Stage IV tumors compared with Stage III tumors (P = 0.049), and higher in pleural effusions compared with peritoneal effusions (P = 0.044). In a univariate survival analysis of patients with ovarian carcinoma, a high Sip1/E-cadherin ratio predicted poor overall survival (P = 0.018). High E-cadherin mRNA expression predicted better disease-free survival (P = 0.023), with a similar trend for a low Slug/E-cadherin ratio (P = 0.07). High Snail mRNA expression predicted shorter effusion-free survival (P = 0.008), disease-free survival (P = 0.03), and overall survival (P = 0.008) in patients with breast carcinoma. Transcription factors that regulate E-cadherin were expressed differentially in metastatic ovarian and breast carcinoma. Snail may predict a poor outcome in patients who have breast carcinoma metastatic to effusions. E-cadherin expression generally was conserved in effusions from patients with ovarian carcinoma, but the subset of patients with postulated Sip1-induced repression of this adhesion molecule had a significantly worse outcome. This finding was in agreement with the stronger suppression of E-cadherin by Snail and Sip1 in breast carcinoma effusions, a clinical condition associated with extremely poor survival. (c) 2005 American Cancer Society.

Gene-expression signatures of Atlantic salmon's plastic life cycle.

PubMed

Aubin-Horth, Nadia; Letcher, Benjamin H; Hofmann, Hans A

2009-09-15

How genomic expression differs as a function of life history variation is largely unknown. Atlantic salmon exhibits extreme alternative life histories. We defined the gene-expression signatures of wild-caught salmon at two different life stages by comparing the brain expression profiles of mature sneaker males and immature males, and early migrants and late migrants. In addition to life-stage-specific signatures, we discovered a surprisingly large gene set that was differentially regulated-at similar magnitudes, yet in opposite direction-in both life history transitions. We suggest that this co-variation is not a consequence of many independent cellular and molecular switches in the same direction but rather represents the molecular equivalent of a physiological shift orchestrated by one or very few master regulators.

Physiological and psychological fatigue in extreme conditions: the military example.

PubMed

Weeks, Sharon R; McAuliffe, Caitlin L; Durussel, David; Pasquina, Paul F

2010-05-01

The extreme conditions causing fatigue in military service members in combat and combat training deserve special consideration. The collective effects of severe exertion, limited caloric intake, and sleep deprivation, combined with the inherent stressors of combat, lead to both physiological and psychological fatigue that may significantly impair performance. Studies of combat training have revealed a myriad of endocrine, cognitive, and neurological changes that occur as a result of exposure to extreme conditions. Further contributory effects of multiple military deployments, post-traumatic stress disorder, and traumatic brain injury may also influence both the susceptibility to and expression of fatigue states. Further research is needed to explore these effects to enhance military readiness and performance as well as prevent injuries. Copyright (c) 2010 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

BPS counting for knots and combinatorics on words

NASA Astrophysics Data System (ADS)

Kucharski, Piotr; Sułkowski, Piotr

2016-11-01

We discuss relations between quantum BPS invariants defined in terms of a product decomposition of certain series, and difference equations (quantum A-polynomials) that annihilate such series. We construct combinatorial models whose structure is encoded in the form of such difference equations, and whose generating functions (Hilbert-Poincaré series) are solutions to those equations and reproduce generating series that encode BPS invariants. Furthermore, BPS invariants in question are expressed in terms of Lyndon words in an appropriate language, thereby relating counting of BPS states to the branch of mathematics referred to as combinatorics on words. We illustrate these results in the framework of colored extremal knot polynomials: among others we determine dual quantum extremal A-polynomials for various knots, present associated combinatorial models, find corresponding BPS invariants (extremal Labastida-Mariño-Ooguri-Vafa invariants) and discuss their integrality.

Effects of diurnal temperature range on mortality in Hefei city, China

NASA Astrophysics Data System (ADS)

Tang, Jing; Xiao, Chang-chun; Li, Yu-rong; Zhang, Jun-qing; Zhai, Hao-yuan; Geng, Xi-ya; Ding, Rui; Zhai, Jin-xia

2017-12-01

Although several studies indicated an association between diurnal temperature range (DTR) and mortality, the results about modifiers are inconsistent, and few studies were conducted in developing inland country. This study aims to evaluate the effects of DTR on cause-specific mortality and whether season, gender, or age might modify any association in Hefei city, China, during 2007-2016. Quasi-Poisson generalized linear regression models combined with a distributed lag non-linear model (DLNM) were applied to evaluate the relationships between DTR and non-accidental, cardiovascular, and respiratory mortality. We observed a J-shaped relationship between DTR and cause-specific mortality. With a DTR of 8.3 °C as the reference, the cumulative effects of extremely high DTR were significantly higher for all types of mortality than effects of lower or moderate DTR in full year. When stratified by season, extremely high DTR in spring had a greater impact on all cause-specific mortality than other three seasons. Male and the elderly (≥ 65 years) were consistently more susceptible to extremely high DTR effect than female and the youth (< 65 years) for non-accidental and cardiovascular mortality. To the contrary, female and the youth were more susceptible to extremely high DTR effect than male and the elderly for respiratory morality. The study suggests that extremely high DTR is a potential trigger for non-accidental mortality in Hefei city, China. Our findings also highlight the importance of protecting susceptible groups from extremely high DTR especially in the spring.

Effects of diurnal temperature range on mortality in Hefei city, China

NASA Astrophysics Data System (ADS)

Tang, Jing; Xiao, Chang-chun; Li, Yu-rong; Zhang, Jun-qing; Zhai, Hao-yuan; Geng, Xi-ya; Ding, Rui; Zhai, Jin-xia

2018-05-01

Although several studies indicated an association between diurnal temperature range (DTR) and mortality, the results about modifiers are inconsistent, and few studies were conducted in developing inland country. This study aims to evaluate the effects of DTR on cause-specific mortality and whether season, gender, or age might modify any association in Hefei city, China, during 2007-2016. Quasi-Poisson generalized linear regression models combined with a distributed lag non-linear model (DLNM) were applied to evaluate the relationships between DTR and non-accidental, cardiovascular, and respiratory mortality. We observed a J-shaped relationship between DTR and cause-specific mortality. With a DTR of 8.3 °C as the reference, the cumulative effects of extremely high DTR were significantly higher for all types of mortality than effects of lower or moderate DTR in full year. When stratified by season, extremely high DTR in spring had a greater impact on all cause-specific mortality than other three seasons. Male and the elderly (≥ 65 years) were consistently more susceptible to extremely high DTR effect than female and the youth (< 65 years) for non-accidental and cardiovascular mortality. To the contrary, female and the youth were more susceptible to extremely high DTR effect than male and the elderly for respiratory morality. The study suggests that extremely high DTR is a potential trigger for non-accidental mortality in Hefei city, China. Our findings also highlight the importance of protecting susceptible groups from extremely high DTR especially in the spring.

Cloning, expression, and crystallization of Cpn60 proteins from Thermococcus litoralis.

PubMed

Osipiuk, J; Sriram, M; Mai, X; Adams, M W; Joachimiak, A

2000-01-01

Two genes of the extreme thermophilic archaeon Thermococcus litoralis homologous to those that code for Cpn60 chaperonins were cloned and expressed in Escherichia coli. Each of the Cpn60 subunits as well as the entire Cpn60 complex crystallize in a variety of morphological forms. The best crystals diffract to 3.6 A resolution at room temperature and belong to the space group 1422 with unit cell parameters a = b = 193.5 A, c = 204.2 A.

Closed-Form Evaluation of Mutual Coupling in a Planar Array of Circular Apertures

NASA Technical Reports Server (NTRS)

Bailey, M. C.

1996-01-01

The integral expression for the mutual admittance between circular apertures in a planar array is evaluated in closed form. Very good accuracy is realized when compared with values that were obtained by numerical integration. Utilization of this closed-form expression, for all element pairs that are separated by more than one element spacing, yields extremely accurate results and significantly reduces the computation time that is required to analyze the performance of a large electronically scanning antenna array.

Detection of early primary colorectal cancer with upconversion luminescent NP-based molecular probes

NASA Astrophysics Data System (ADS)

Liu, Chunyan; Qi, Yifei; Qiao, Ruirui; Hou, Yi; Chan, Kaying; Li, Ziqian; Huang, Jiayi; Jing, Lihong; Du, Jun; Gao, Mingyuan

2016-06-01

Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation.Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation. Electronic supplementary information (ESI) available: (1) Molecular structure of Jeffamine-modified FA; (2) immunohistochemical analysis of FR expression in the colorectal tissue derived from mice treated with NaCl at different weeks; (3) biodistributions of probes of NP-FA and NP-IgG in the main organs of mice. See DOI: 10.1039/c5nr07858j

De novo assembling and primary analysis of genome and transcriptome of gray whale Eschrichtius robustus.

PubMed

Moskalev, Alexey А; Kudryavtseva, Anna V; Graphodatsky, Alexander S; Beklemisheva, Violetta R; Serdyukova, Natalya A; Krutovsky, Konstantin V; Sharov, Vadim V; Kulakovskiy, Ivan V; Lando, Andrey S; Kasianov, Artem S; Kuzmin, Dmitry A; Putintseva, Yuliya A; Feranchuk, Sergey I; Shaposhnikov, Mikhail V; Fraifeld, Vadim E; Toren, Dmitri; Snezhkina, Anastasia V; Sitnik, Vasily V

2017-12-28

Gray whale, Eschrichtius robustus (E. robustus), is a single member of the family Eschrichtiidae, which is considered to be the most primitive in the class Cetacea. Gray whale is often described as a "living fossil". It is adapted to extreme marine conditions and has a high life expectancy (77 years). The assembly of a gray whale genome and transcriptome will allow to carry out further studies of whale evolution, longevity, and resistance to extreme environment. In this work, we report the first de novo assembly and primary analysis of the E. robustus genome and transcriptome based on kidney and liver samples. The presented draft genome assembly is complete by 55% in terms of a total genome length, but only by 24% in terms of the BUSCO complete gene groups, although 10,895 genes were identified. Transcriptome annotation and comparison with other whale species revealed robust expression of DNA repair and hypoxia-response genes, which is expected for whales. This preliminary study of the gray whale genome and transcriptome provides new data to better understand the whale evolution and the mechanisms of their adaptation to the hypoxic conditions.

Historical Underpinnings of Bipolar Disorder Diagnostic Criteria

PubMed Central

Mason, Brittany L.; Brown, E. Sherwood; Croarkin, Paul E.

2016-01-01

Mood is the changing expression of emotion and can be described as a spectrum. The outermost ends of this spectrum highlight two states, the lowest low, melancholia, and the highest high, mania. These mood extremes have been documented repeatedly in human history, being first systematically described by Hippocrates. Nineteenth century contemporaries Falret and Baillarger described two forms of an extreme mood disorder, with the validity and accuracy of both debated. Regardless, the concept of a cycling mood disease was accepted before the end of the 19th century. Kraepelin then described “manic depressive insanity” and presented his description of a full spectrum of mood dysfunction which could be exhibited through single episodes of mania or depression or a complement of many episodes of each. It was this concept which was incorporated into the first DSM and carried out until DSM-III, in which the description of episodic mood dysfunction was used to build a diagnosis of bipolar disorder. Criticism of this approach is explored through discussion of the bipolar spectrum concept and some recent examinations of the clinical validity of these DSM diagnoses are presented. The concept of bipolar disorder in children is also explored. PMID:27429010

Transcriptome Analysis in Tardigrade Species Reveals Specific Molecular Pathways for Stress Adaptations

PubMed Central

Förster, Frank; Beisser, Daniela; Grohme, Markus A.; Liang, Chunguang; Mali, Brahim; Siegl, Alexander Matthias; Engelmann, Julia C.; Shkumatov, Alexander V.; Schokraie, Elham; Müller, Tobias; Schnölzer, Martina; Schill, Ralph O.; Frohme, Marcus; Dandekar, Thomas

2012-01-01

Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade Milnesium tardigradum were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from Hypsibius dujardini, revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for M. tardigradum are different from typical motifs known from higher animals. M. tardigradum and H. dujardini protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of M. tardigradum. These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and M. tardigradum in particular so highly stress resistant. PMID:22563243

Author Correction: Ultra-thin high-efficiency mid-infraredtransmissive Huygens meta-optics.

PubMed

Zhang, Li; Ding, Jun; Zheng, Hanyu; An, Sensong; Lin, Hongtao; Zheng, Bowen; Du, Qingyang; Yin, Gufan; Michon, Jerome; Zhang, Yifei; Fang, Zhuoran; Shalaginov, Mikhail Y; Deng, Longjiang; Gu, Tian; Zhang, Hualiang; Hu, Juejun

2018-06-14

The original version of this Article omitted the following from the Acknowledgements:'J.D. and H. Zhang acknowledge initial funding for design of the meta-atoms provided by the National Science Foundation under award CMMI-1266251. Z.L. and H. Zheng contributed to the Device Fabrication section and were independently funded as visiting scholars by the National Natural Science Foundation of China under award 51772042 and the "111" project (No. B13042) led by Professor Huaiwu Zhang. Later work contained within the Device Modeling and Device Characterization sections and some revisions to the manuscript were funded under Defense Advanced Research Projects Agency Defense Sciences Office (DSO) Program: EXTREME Optics and Imaging (EXTREME) under Agreement No. HR00111720029. The authors also acknowledge fabrication facility support by the Harvard University Center for Nanoscale Systems funded by the National Science Foundation under award 0335765. The views, opinions and/or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government.' This has been corrected in both the PDF and HTML versions of the Article.

Haloarchaea from the Andean Puna: Biological Role in the Energy Metabolism of Arsenic.

PubMed

Ordoñez, Omar Federico; Rasuk, María Cecilia; Soria, Mariana Noelia; Contreras, Manuel; Farías, María Eugenia

2018-03-08

Biofilms, microbial mats, and microbialites dwell under highly limiting conditions (high salinity, extreme aridity, pH, and elevated arsenic concentration) in the Andean Puna. Only recent pioneering studies have described the microbial diversity of different Altiplano lakes and revealed their unexpectedly diverse microbial communities. Arsenic metabolism is proposed to be an ancient mechanism to obtain energy by microorganisms. Members of Bacteria and Archaea are able to exploit arsenic as a bioenergetic substrate in either anaerobic arsenate respiration or chemolithotrophic growth on arsenite. Only six aioAB sequences coding for arsenite oxidase and three arrA sequences coding for arsenate reductase from haloarchaea were previously deposited in the NCBI database. However, no experimental data on their expression and function has been reported. Recently, our working group revealed the prevalence of haloarchaea in a red biofilm from Diamante Lake and microbial mat from Tebenquiche Lake using a metagenomics approach. Also, a surprisingly high abundance of genes used for anaerobic arsenate respiration (arr) and arsenite oxidation (aio) was detected in the Diamante's metagenome. In order to study in depth the role of arsenic in these haloarchaeal communities, in this work, we obtained 18 haloarchaea belonging to the Halorubrum genus, tolerant to arsenic. Furthermore, the identification and expression analysis of genes involved in obtaining energy from arsenic compounds (aio and arr) showed that aio and arr partial genes were detected in 11 isolates, and their expression was verified in two selected strains. Better growth of two isolates was obtained in presence of arsenic compared to control. Moreover, one of the isolates was able to oxidize As[III]. The confirmation of the oxidation of arsenic and the transcriptional expression of these genes by RT-PCR strongly support the hypothesis that the arsenic can be used in bioenergetics processes by the microorganisms flourishing in these environments.

Comparative Transcriptomics to Identify Novel Genes and Pathways in Dinoflagellates

NASA Astrophysics Data System (ADS)

Ryan, D.

2016-02-01

The unarmored dinoflagellate Karenia brevis is among the most prominent harmful, bloom-forming phytoplankton species in the Gulf of Mexico. During blooms, the polyketides PbTx-1 and PbTx-2 (brevetoxins) are produced by K. brevis. Brevetoxins negatively impact human health and the Gulf shellfish harvest. However, the genes underlying brevetoxin synthesis are currently unknown. Because the K. brevis genome is extremely large ( 1 × 1011 base pairs long), and with a high proportion of repetitive, non-coding DNA, it has not been sequenced. In fact, large, repetitive genomes are common among the dinoflagellate group. High-throughput RNA sequencing technology enabled us to assemble Karenia transcriptomes de novo and investigate potential genes in the brevetoxin pathway through comparative transcriptomics. The brevetoxin profile varies among K. brevis clonal cultures. For example, well-documented Wilson-CCFWC268 typically produces 8-10 pg PbTx per cell, whereas SP1 produces < 2 pg PbTx/cell, and the mutant low-toxin Wilson clone produces undetectable to low (<0.05 pg/cell) amounts. Further, PbTx-2 has been measured in Karenia papilionacea but not Karenia mikimotoi. We compared the transcriptomes of four K. brevis clones (Wilson-CCFWC268, SP3, SP1, and mutant low-toxin Wilson) with K. papilionacea and K. mikimotoi to investigate nucleotide-level genetic variations and differences in gene expression. Of the 85,000 transcripts in the K. brevis transcriptome, 4,600 transcripts, including novel unannotated orthologs and putative polyketide synthases (PKSs), were only expressed by brevetoxin-producing K. brevis and K. papilionacea, not K. mikimotoi. Examination of gene expression between the typical- and low-toxin Wilson clones identified about 3,500 genes with significantly different expression levels, including 2 putative PKSs. One of the 2 PKSs was only found in the brevetoxin-producing Karenia species. These transcriptomes could not have been characterized without high-throughput RNA sequencing.

Synoptic Conditions and Moisture Sources Actuating Extreme Precipitation in Nepal

NASA Astrophysics Data System (ADS)

Bohlinger, Patrik; Sorteberg, Asgeir; Sodemann, Harald

2017-12-01

Despite the vast literature on heavy-precipitation events in South Asia, synoptic conditions and moisture sources related to extreme precipitation in Nepal have not been addressed systematically. We investigate two types of synoptic conditions—low-pressure systems and midlevel troughs—and moisture sources related to extreme precipitation events. To account for the high spatial variability in rainfall, we cluster station-based daily precipitation measurements resulting in three well-separated geographic regions: west, central, and east Nepal. For each region, composite analysis of extreme events shows that atmospheric circulation is directed against the Himalayas during an extreme event. The direction of the flow is regulated by midtropospheric troughs and low-pressure systems traveling toward the respective region. Extreme precipitation events feature anomalous high abundance of total column moisture. Quantitative Lagrangian moisture source diagnostic reveals that the largest direct contribution stems from land (approximately 75%), where, in particular, over the Indo-Gangetic Plain moisture uptake was increased. Precipitation events occurring in this region before the extreme event likely provided additional moisture.

Method for reworkable packaging of high speed, low electrical parasitic power electronics modules through gate drive integration

DOEpatents

Passmore, Brandon; Cole, Zach; Whitaker, Bret; Barkley, Adam; McNutt, Ty; Lostetter, Alexander

2016-08-02

A multichip power module directly connecting the busboard to a printed-circuit board that is attached to the power substrate enabling extremely low loop inductance for extreme environments such as high temperature operation. Wire bond interconnections are taught from the power die directly to the busboard further enabling enable low parasitic interconnections. Integration of on-board high frequency bus capacitors provide extremely low loop inductance. An extreme environment gate driver board allows close physical proximity of gate driver and power stage to reduce overall volume and reduce impedance in the control circuit. Parallel spring-loaded pin gate driver PCB connections allows a reliable and reworkable power module to gate driver interconnections.

Advantageous Use of Hypnosis in a Case of Psychogenic Vomiting.

PubMed

Chandrashekhar, Roopa

2016-04-01

This case study describes in detail the role of hypnosis in treatment of a case of psychogenic vomiting. The patient, a 60-yearold woman, had been suffering for 9 months from episodes of vomiting which resulted in weight loss, dehydration, and hypokalemia. She was a conscientious woman with high standards of behavior, which did not allow an expression of the extreme hostility she felt toward her daughter-in-law. Hypnotherapeutic sessions reduced her anxiety, restored her sleep, improved mood, and helped deepen rapport, all of which created the ideal setting for Gestalt's empty chair technique. Integrating hypnosis greatly enhanced the quality of the empty chair dialogue, which by bringing about a shift in the patient's emotions from hostility to sympathy, facilitated recovery.

The cost of tolerance for violence.

PubMed

Sigler, R T

1995-01-01

Our society evinces a high tolerance for violence. This acceptance of certain forms of violent behavior is ingrained in the American value system, established through our history in the simple struggle to survive. Beginning with the colonial era, through the settlement of the western frontier, and during the wave of immigrant arrivals, Americans often used violence to establish basic rights. Sociobiological explanations of individual violent tendencies focus on genetic predisposition established through natural selection--or survival of the fittest--while psychoanalytical perspectives define extreme violence as a deviant form of natural aggression. On the other hand, criminologists define all violence as deviant. In today's society, physical force is considered to be justifiable when expressing political dissent and protecting self and property, and less so during domestic disputes.

An Evaluation of Automotive Interior Packages Based on Human Ocular and Joint Motor Properties

NASA Astrophysics Data System (ADS)

Tanaka, Yoshiyuki; Rakumatsu, Takeshi; Horiue, Masayoshi; Miyazaki, Tooru; Nishikawa, Kazuo; Nouzawa, Takahide; Tsuji, Toshio

This paper proposes a new evaluation method of an automotive interior package based on human oculomotor and joint-motor properties. Assuming the long-term driving situation in the express high way, the three evaluation indices were designed on i) the ratio of head motion at gazing the driving items; ii) the load torque for maintaining the standard driving posture; and iii) the human force manipulability at the end-point of human extremities. Experiments were carried out for two different interior packages with four subjects who have the special knowledge on the automobile development. Evaluation results demonstrate that the proposed method can quantitatively analyze the driving interior in good agreement with the generally accepted subjective opinion in the automobile industry.

Predicting marching capacity while carrying extremely heavy loads.

PubMed

Koerhuis, Claudy L; Veenstra, Bertil J; van Dijk, Jos J; Delleman, Nico J

2009-12-01

The objective of this study was to establish the best prediction for endurance time of combat soldiers marching with extremely heavy loads. It was hypothesized that loads relative to individual characteristics (% maximal load carry capacity [MLCC], % body mass, % lean body mass) would better predict endurance time than load itself. Twenty-three male combat soldiers participated. MLCC was determined by increasing the load by 7.5 kg every 4 minutes until exhaustion. The marching velocity and gradient were 3 km.h(-1) and 5%, respectively. Endurance time was determined carrying 70, 80, and 90% of MLCC. MLCC was on average 102.6 kg +/- 11.6. Load expressed as % MLCC was the best predictor for endurance time (R2 = 0.45). Load expressed as % body mass, as % lean body mass, and absolute load predicted endurance time less well (R2 = 0.30, R2 = 0.24, and R2 = 0.23, respectively). On the basis of these results, it is recommended to assess the MLCC of individual combat soldiers.

Communities that thrive in extreme conditions captured from a freshwater lake.

PubMed

Low-Décarie, Etienne; Fussmann, Gregor F; Dumbrell, Alex J; Bell, Graham

2016-09-01

Organisms that can grow in extreme conditions would be expected to be confined to extreme environments. However, we were able to capture highly productive communities of algae and bacteria capable of growing in acidic (pH 2), basic (pH 12) and saline (40 ppt) conditions from an ordinary freshwater lake. Microbial communities may thus include taxa that are highly productive in conditions that are far outside the range of conditions experienced in their host ecosystem. The organisms we captured were not obligate extremophiles, but were capable of growing in both extreme and benign conditions. The ability to grow in extreme conditions may thus be a common functional attribute in microbial communities. © 2016 The Author(s).

Imaging of upper extremity stress fractures in the athlete.

PubMed

Anderson, Mark W

2006-07-01

Although it is much less common than injuries in the lower extremities, an upper extremity stress injury can have a significant impact on an athlete. If an accurate and timely diagnosis is to be made, the clinician must have a high index of suspicion of a stress fracture in any athlete who is involved in a throwing, weightlifting, or upper extremity weight-bearing sport and presents with chronic pain in the upper extremity. Imaging should play an integral role in the work-up of these patients; if initial radiographs are unrevealing, further cross-sectional imaging should be strongly considered. Although a three-phase bone scan is highly sensitive in this regard, MRI has become the study of choice at most centers.

Expression of K19 and K7 in dysplastic nodules and hepatocellular carcinoma.

PubMed

Bae, Jun Sang; Choi, Ha Na; Noh, Sang Jae; Park, Byung Hyun; Jang, Kyu Yun; Park, Cheol Keun; Moon, Woo Sung

2012-08-01

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors characterized by a multistep process of tumor development. Nodular lesions that differ from the surrounding liver parenchyma and are characterized by cytological or structural atypia are termed dysplastic nodules (DNs). DNs are well-known precancerous HCC lesions. Expression of keratin (K) 19 and K7, molecular markers of hepatic progenitor cells and cholangiocytes, has been reported in certain HCCs. However, it remains unclear whether K19-positive HCC cells are derived from true hepatic progenitor cells or mature cells that have undergone a dedifferentiation or a transdifferentiation process. In total, 107 tissue sections (13 low-grade DNs, 15 high-grade DNs, 27 small HCCs and 52 large HCCs) from resected liver samples and 132 HCC tissue microarray (TMA) cores were subjected to immunohistochemical analysis for K19 and K7. Clinicopathological data of the HCC patients were evaluated. K19 expression was found in 0% of DNs, 19% of small HCCs (≤2 cm), 8% of large HCCs (>2 cm) and 8% of TMA samples. K7 expression was found in 14% of DNs, 41% of small HCCs, 15% of large HCCs and 6% of TMA samples. Among the five K19-positive small HCCs, four were distinctly nodular and one tumor was an infiltrative type. No vaguely nodular HCC was positive for K19. K19 expression was significantly associated with histological grade (P=0.023), serum α-fetoprotein level (P=0.001) and K7 expression (P=0.001) in HCC. K19 expression was an independent prognostic factor for overall survival in non-viral HCC patients (P=0.003). K19 expression is extremely rare in DNs and occurs in progressed small HCCs. Our results suggest that K19 expression may be an acquired feature of carcinoma cells during HCC progression in certain HCCs.

Extreme positive and negative appraisals of activated states interact to discriminate bipolar disorder from unipolar depression and non-clinical controls.

PubMed

Kelly, Rebecca E; Mansell, Warren; Wood, Alex M; Alatiq, Yousra; Dodd, Alyson; Searson, Ruth

2011-11-01

This research aimed to test whether positive, negative, or conflicting appraisals about activated mood states (e.g., energetic and high states) predicted bipolar disorder. A sample of individuals from clinical and control groups (171 with bipolar disorder, 42 with unipolar depression, and 64 controls) completed a measure of appraisals of internal states. High negative appraisals related to a higher likelihood of bipolar disorder irrespective of positive appraisals. High positive appraisals related to a higher likelihood of bipolar disorder only when negative appraisals were also high. Individuals were most likely to have bipolar disorder, as opposed to unipolar depression or no diagnosis, when they endorsed both extremely positive and extremely negative appraisals of the same, activated states. Appraisals of internal states were based on self-report. The results indicate that individuals with bipolar disorder tend to appraise activated, energetic internal states in opposing or conflicting ways, interpreting these states as both extremely positive and extremely negative. This may lead to contradictory attempts to regulate these states, which may in turn contribute to mood swing symptoms. Psychological therapy for mood swings and bipolar disorder should address extreme and conflicting appraisals of mood states. Copyright © 2011 Elsevier B.V. All rights reserved.

Zinc-dependent global transcriptional control, transcriptional deregulation, and higher gene copy number for genes in metal homeostasis of the hyperaccumulator Arabidopsis halleri.

PubMed

Talke, Ina N; Hanikenne, Marc; Krämer, Ute

2006-09-01

The metal hyperaccumulator Arabidopsis halleri exhibits naturally selected zinc (Zn) and cadmium (Cd) hypertolerance and accumulates extraordinarily high Zn concentrations in its leaves. With these extreme physiological traits, A. halleri phylogenetically belongs to the sister clade of Arabidopsis thaliana. Using a combination of genome-wide cross species microarray analysis and real-time reverse transcription-PCR, a set of candidate genes is identified for Zn hyperaccumulation, Zn and Cd hypertolerance, and the adjustment of micronutrient homeostasis in A. halleri. Eighteen putative metal homeostasis genes are newly identified to be more highly expressed in A. halleri than in A. thaliana, and 11 previously identified candidate genes are confirmed. The encoded proteins include HMA4, known to contribute to root-shoot transport of Zn in A. thaliana. Expression of either AtHMA4 or AhHMA4 confers cellular Zn and Cd tolerance to yeast (Saccharomyces cerevisiae). Among further newly implicated proteins are IRT3 and ZIP10, which have been proposed to contribute to cytoplasmic Zn influx, and FRD3 required for iron partitioning in A. thaliana. In A. halleri, the presence of more than a single genomic copy is a hallmark of several highly expressed candidate genes with possible roles in metal hyperaccumulation and metal hypertolerance. Both A. halleri and A. thaliana exert tight regulatory control over Zn homeostasis at the transcript level. Zn hyperaccumulation in A. halleri involves enhanced partitioning of Zn from roots into shoots. The transcriptional regulation of marker genes suggests that in the steady state, A. halleri roots, but not the shoots, act as physiologically Zn deficient under conditions of moderate Zn supply.

Strategic Therapeutic Targeting to Overcome Venetoclax Resistance in Aggressive B-cell Lymphomas.

PubMed

Pham, Lan V; Huang, Shengjian; Zhang, Hui; Zhang, Jun; Bell, Taylor; Zhou, Shouhao; Pogue, Elizabeth; Ding, Zhiyong; Lam, Laura; Westin, Jason; Davis, R Eric; Young, Ken H; Medeiros, L Jeffrey; Ford, Richard J; Nomie, Krystle; Zhang, Leo; Wang, Michael

2018-04-17

Purpose: B-cell lymphoma-2 (BCL-2), an antiapoptotic protein often dysregulated in B-cell lymphomas, promotes cell survival and provides protection from stress. A recent phase I first-in-human study of the BCL-2 inhibitor venetoclax in non-Hodgkin lymphoma showed an overall response rate of 44%. These promising clinical results prompted our examination of the biological effects and mechanism of action underlying venetoclax activity in aggressive B-cell lymphoma, including mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL). Experimental Design: MCL and DLBCL cell lines, primary patient samples, and in vivo patient-derived xenograft (PDX) models were utilized to examine venetoclax efficacy. Furthermore, the mechanisms underlying venetoclax response and the development of venetoclax resistance were evaluated using proteomics analysis and Western blotting. Results: Potential biomarkers linked to venetoclax activity and targeted combination therapies that can augment venetoclax response were identified. We demonstrate that DLBCL and MCL cell lines, primary patient samples, and PDX mouse models expressing high BCL-2 levels are extremely sensitive to venetoclax treatment. Proteomics studies showed that venetoclax substantially alters the expression levels and phosphorylation status of key proteins involved in cellular processes, including the DNA damage response, cell metabolism, cell growth/survival, and apoptosis. Short- and long-term exposure to venetoclax inhibited PTEN expression, leading to enhanced AKT pathway activation and concomitant susceptibility to PI3K/AKT inhibition. Intrinsic venetoclax-resistant cells possess high AKT activation and are highly sensitive to PI3K/AKT inhibition. Conclusions: These findings demonstrate the on-target effect of venetoclax and offer potential mechanisms to overcome acquired and intrinsic venetoclax resistance through PI3K/AKT inhibition. Clin Cancer Res; 1-14. ©2018 AACR. ©2018 American Association for Cancer Research.

iGen: An automated generator of simplified models with provable error bounds.

NASA Astrophysics Data System (ADS)

Tang, D.; Dobbie, S.

2009-04-01

Climate models employ various simplifying assumptions and parameterisations in order to increase execution speed. However, in order to draw conclusions about the Earths climate from the results of a climate simulation it is necessary to have information about the error that these assumptions and parameterisations introduce. A novel computer program, called iGen, is being developed which automatically generates fast, simplified models by analysing the source code of a slower, high resolution model. The resulting simplified models have provable bounds on error compared to the high resolution model and execute at speeds that are typically orders of magnitude faster. iGen's input is a definition of the prognostic variables of the simplified model, a set of bounds on acceptable error and the source code of a model that captures the behaviour of interest. In the case of an atmospheric model, for example, this would be a global cloud resolving model with very high resolution. Although such a model would execute far too slowly to be used directly in a climate model, iGen never executes it. Instead, it converts the code of the resolving model into a mathematical expression which is then symbolically manipulated and approximated to form a simplified expression. This expression is then converted back into a computer program and output as a simplified model. iGen also derives and reports formal bounds on the error of the simplified model compared to the resolving model. These error bounds are always maintained below the user-specified acceptable error. Results will be presented illustrating the success of iGen's analysis of a number of example models. These extremely encouraging results have lead on to work which is currently underway to analyse a cloud resolving model and so produce an efficient parameterisation of moist convection with formally bounded error.

Resilience and Suicidality among Homeless Youth

ERIC Educational Resources Information Center

Cleverley, Kristin; Kidd, Sean A.

2011-01-01

Homeless and street-involved youth are considered an extremely high risk group, with many studies highlighting trajectories characterized by abusive, neglectful, and unstable family histories, victimization and criminal involvement while on the streets, high rates of physical and mental illness, and extremely high rates of mortality. While there…

High-Pressure Transvenous Perfusion of the Upper Extremity in Human Muscular Dystrophy: A Safety Study with 0.9% Saline.

PubMed

Fan, Zheng; Kocis, Keith; Valley, Robert; Howard, James F; Chopra, Manisha; Chen, Yasheng; An, Hongyu; Lin, Weili; Muenzer, Joseph; Powers, William

2015-09-01

We evaluated safety and feasibility of high-pressure transvenous limb perfusion in an upper extremity of adult patients with muscular dystrophy, after completing a similar study in a lower extremity. A dose escalation study of single-limb perfusion with 0.9% saline was carried out in nine adults with muscular dystrophies under intravenous analgesia. Our study demonstrates that it is feasible and definitely safe to perform high-pressure transvenous perfusion with 0.9% saline up to 35% of limb volume in the upper extremities of young adults with muscular dystrophy. Perfusion at 40% limb volume is associated with short-lived physiological changes in peripheral nerves without clinical correlates in one subject. This study provides the basis for a phase 1/2 clinical trial using pressurized transvenous delivery into upper limbs of nonambulatory patients with Duchenne muscular dystrophy. Furthermore, our results are applicable to other conditions such as limb girdle muscular dystrophy as a method for delivering regional macromolecular therapeutics in high dose to skeletal muscles of the upper extremity.

Exaggerated perception of facial expressions is increased in individuals with schizotypal traits

PubMed Central

Uono, Shota; Sato, Wataru; Toichi, Motomi

2015-01-01

Emotional facial expressions are indispensable communicative tools, and social interactions involving facial expressions are impaired in some psychiatric disorders. Recent studies revealed that the perception of dynamic facial expressions was exaggerated in normal participants, and this exaggerated perception is weakened in autism spectrum disorder (ASD). Based on the notion that ASD and schizophrenia spectrum disorder are at two extremes of the continuum with respect to social impairment, we hypothesized that schizophrenic characteristics would strengthen the exaggerated perception of dynamic facial expressions. To test this hypothesis, we investigated the relationship between the perception of facial expressions and schizotypal traits in a normal population. We presented dynamic and static facial expressions, and asked participants to change an emotional face display to match the perceived final image. The presence of schizotypal traits was positively correlated with the degree of exaggeration for dynamic, as well as static, facial expressions. Among its subscales, the paranoia trait was positively correlated with the exaggerated perception of facial expressions. These results suggest that schizotypal traits, specifically the tendency to over-attribute mental states to others, exaggerate the perception of emotional facial expressions. PMID:26135081

Exaggerated perception of facial expressions is increased in individuals with schizotypal traits.

PubMed

Uono, Shota; Sato, Wataru; Toichi, Motomi

2015-07-02

Emotional facial expressions are indispensable communicative tools, and social interactions involving facial expressions are impaired in some psychiatric disorders. Recent studies revealed that the perception of dynamic facial expressions was exaggerated in normal participants, and this exaggerated perception is weakened in autism spectrum disorder (ASD). Based on the notion that ASD and schizophrenia spectrum disorder are at two extremes of the continuum with respect to social impairment, we hypothesized that schizophrenic characteristics would strengthen the exaggerated perception of dynamic facial expressions. To test this hypothesis, we investigated the relationship between the perception of facial expressions and schizotypal traits in a normal population. We presented dynamic and static facial expressions, and asked participants to change an emotional face display to match the perceived final image. The presence of schizotypal traits was positively correlated with the degree of exaggeration for dynamic, as well as static, facial expressions. Among its subscales, the paranoia trait was positively correlated with the exaggerated perception of facial expressions. These results suggest that schizotypal traits, specifically the tendency to over-attribute mental states to others, exaggerate the perception of emotional facial expressions.

Multiple extreme environmental conditions of intermittent soda pans in the Carpathian Basin (Central Europe).

PubMed

Boros, Emil; Katalin, V-Balogh; Vörös, Lajos; Horváth, Zsófia

2017-01-01

Soda lakes and pans represent saline ecosystems with unique chemical composition, occurring on all continents. The purpose of this study was to identify and characterise the main environmental gradients and trophic state that prevail in the soda pans (n=84) of the Carpathian Basin in Central Europe. Underwater light conditions, dissolved organic matter, phosphorus and chlorophyll a were investigated in 84 pans during 2009-2010. Besides, water temperature was measured hourly with an automatic sensor throughout one year in a selected pan. The pans were very shallow (median depth: 15 cm), and their extremely high turbidity (Secchi depth median: 3 cm, min: 0.5 cm) was caused by high concentrations of inorganic suspended solids (median: 0.4 g L -1 , max: 16 g L -1 ), which was the dominant (>50%) contributing factor to the vertical attenuation coefficient in 67 pans (80%). All pans were polyhumic (median DOC: 47 mg L -1 ), and total phosphorus concentration was also extremely high (median: 2 mg L -1 , max: 32 mg L -1 ). The daily water temperature maximum (44 °C) and fluctuation maximum (28 °C) were extremely high during summertime. The combination of environmental boundaries: shallowness, daily water temperature fluctuation, intermittent hydroperiod, high turbidity, polyhumic organic carbon concentration, high alkalinity and hypertrophy represent a unique extreme aquatic ecosystem.

Polygenic determinants in extremes of high-density lipoprotein cholesterol[S

PubMed Central

Dron, Jacqueline S.; Wang, Jian; Low-Kam, Cécile; Khetarpal, Sumeet A.; Robinson, John F.; McIntyre, Adam D.; Ban, Matthew R.; Cao, Henian; Rhainds, David; Dubé, Marie-Pierre; Rader, Daniel J.; Lettre, Guillaume; Tardif, Jean-Claude

2017-01-01

HDL cholesterol (HDL-C) remains a superior biochemical predictor of CVD risk, but its genetic basis is incompletely defined. In patients with extreme HDL-C concentrations, we concurrently evaluated the contributions of multiple large- and small-effect genetic variants. In a discovery cohort of 255 unrelated lipid clinic patients with extreme HDL-C levels, we used a targeted next-generation sequencing panel to evaluate rare variants in known HDL metabolism genes, simultaneously with common variants bundled into a polygenic trait score. Two additional cohorts were used for validation and included 1,746 individuals from the Montréal Heart Institute Biobank and 1,048 individuals from the University of Pennsylvania. Findings were consistent between cohorts: we found rare heterozygous large-effect variants in 18.7% and 10.9% of low- and high-HDL-C patients, respectively. We also found common variant accumulation, indicated by extreme polygenic trait scores, in an additional 12.8% and 19.3% of overall cases of low- and high-HDL-C extremes, respectively. Thus, the genetic basis of extreme HDL-C concentrations encountered clinically is frequently polygenic, with contributions from both rare large-effect and common small-effect variants. Multiple types of genetic variants should be considered as contributing factors in patients with extreme dyslipidemia. PMID:28870971

Polygenic determinants in extremes of high-density lipoprotein cholesterol.

PubMed

Dron, Jacqueline S; Wang, Jian; Low-Kam, Cécile; Khetarpal, Sumeet A; Robinson, John F; McIntyre, Adam D; Ban, Matthew R; Cao, Henian; Rhainds, David; Dubé, Marie-Pierre; Rader, Daniel J; Lettre, Guillaume; Tardif, Jean-Claude; Hegele, Robert A

2017-11-01

HDL cholesterol (HDL-C) remains a superior biochemical predictor of CVD risk, but its genetic basis is incompletely defined. In patients with extreme HDL-C concentrations, we concurrently evaluated the contributions of multiple large- and small-effect genetic variants. In a discovery cohort of 255 unrelated lipid clinic patients with extreme HDL-C levels, we used a targeted next-generation sequencing panel to evaluate rare variants in known HDL metabolism genes, simultaneously with common variants bundled into a polygenic trait score. Two additional cohorts were used for validation and included 1,746 individuals from the Montréal Heart Institute Biobank and 1,048 individuals from the University of Pennsylvania. Findings were consistent between cohorts: we found rare heterozygous large-effect variants in 18.7% and 10.9% of low- and high-HDL-C patients, respectively. We also found common variant accumulation, indicated by extreme polygenic trait scores, in an additional 12.8% and 19.3% of overall cases of low- and high-HDL-C extremes, respectively. Thus, the genetic basis of extreme HDL-C concentrations encountered clinically is frequently polygenic, with contributions from both rare large-effect and common small-effect variants. Multiple types of genetic variants should be considered as contributing factors in patients with extreme dyslipidemia. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Overexpression of HO-1 assisted PM2.5-induced apoptosis failure and autophagy-related cell necrosis.

PubMed

Zhou, Wei; Yuan, Xiaoyan; Zhang, Li; Su, Baoting; Tian, Dongdong; Li, Yang; Zhao, Jun; Wang, Yimei; Peng, Shuangqing

2017-11-01

Severe smog/haze events accompanied by extremely high concentrations of airborne fine particulate matter (PM2.5) have emerged frequently in China and the potential health risks have attracted ever-growing attention. During these episodes, a surge in hospital visits for acute respiratory symptoms and respiratory diseases exacerbation has been reported to be associated with acute exposure to high-levels of particulate matters. To investigate cell fate determination and the underlying pathogenic mechanisms during severe haze episodes or smog events, we exposed human lung epithelial cells (BEAS-2B) to PM2.5 (0-400μg/mL) for 24h and found that high doses of PM2.5 caused cell necrosis and autophagy dysfunction, while co-treatment with the autophagy inhibitor 3-MA could partially reduce PM2.5-induced cell necrosis. Exposure to PM2.5 also increased the expression and mitochondrial transposition of heme oxygenase 1 (HO-1), which consequently reduced the release of cytochrome C from mitochondria to cytosol. Knockdown of HO-1 by siRNA attenuated the mitochondrial accumulation of HO-1, reversed HO-1-induced the reduction of cytochrome C release and promoted PM2.5-induced cell apoptosis. In contrast to necrosis, PM2.5-induced autophagy was independent of HO-1. In conclusion, our results demonstrate that acute exposure to high PM2.5 concentrations causes autophagy-related cell necrosis. The decrease in cytochrome C release and apoptosis by upregulation of HO-1 maybe assist PM2.5-induced autophagy-related cell necrosis. Further, this study reveals dual roles for HO-1 in PM2.5-induced cytotoxicity and presents a possible explanation for the onset of acute respiratory symptoms under extreme particulate air pollution. Copyright © 2017. Published by Elsevier Inc.

Genetic compensation of high dose radiation-induced damage in an anhydrobiotic insect

NASA Astrophysics Data System (ADS)

Gusev, Oleg; Nakahara, Yuichi; Sakashita, Tetsuya; Kikawada, Takahiro; Okuda, Takashi

Anhydrobiotic larvae of African chironomid Polypedilum vanderplanki are known to show an extremely high tolerance against a range of stresses. The tolerance against various extreme environments exhibited by that insect might be due to being almost completely desiccated replacing water with trehalose, a state where little or no chemical reactions occur. From 2005 dried larvae of this insect are being used in a number of space experiments, both inside and outside of ISS as a model organism for estimation the limits of higher organisms' resistance to space environment stresses and long-term storage of the alive anhydrobiotic organisms during continues spaceflight. We have shown previously that both hydrated and dried larvae of Polypedilum vanderplanki have very higher tolerance against both highand low-linear energy transfer (LET), surviving after 7000Gy irradiation. It was suggested that the larvae would have effective DNA-reparation system in addition to artificial protection provided by glass-stage without water. In the present study we conducted analysis of stress-related gene expression in the larvae after 70-2000 Gy irradiations. Both DNA damage level and activity of DNA-reparation, anti-apoptotic and protein-damage related genes were analyzed. Direct visualization of DNA damage in the larvae fat body cells using Comet Assay showed that fragmented by radiation DNA is re-arranged within 76-98 hours after exposure. We found that massive overexpression of hsp and anti-oxidant genes occur in larvae entering anhydrobiosis , and provides refolding of proteins after rehydration. In the irradiated larvae overexpression of DNA-reparation enzymes anti-apoptotic genes was confirmed, suggesting that survival after high-dose irradiation is a result of combination of highly effective blocking of entering the apoptosis after severe DNA damage and DNA reparation.

Purification and biochemical characterization of a novel ecto-apyrase, MP67, from Mimosa pudica.

PubMed

Okuhata, Riku; Takishima, Takeshi; Nishimura, Naoaki; Ueda, Shogo; Tsuchiya, Takahide; Kanzawa, Nobuyuki

2011-09-01

We have previously reported the presence of an apyrase in Mimosa pudica. However, only limited information is available for this enzyme. Thus, in this study, the apyrase was purified to homogeneity. The purified enzyme had a molecular mass of around 67 kD and was able to hydrolyze both nucleotide triphosphate and nucleotide diphosphate as substrates. The ratio of ATP to ADP hydrolysis velocity of the purified protein was 0.01 in the presence of calcium ion, showing extremely high substrate specificity toward ADP. Thus, we designated this novel apyrase as MP67. A cDNA clone of MP67 was obtained using primers designed from the amino acid sequence of trypsin-digested fragments of the protein. In addition, rapid amplification of cDNA ends-polymerase chain reaction was performed to clone a conventional apyrase (MpAPY2). Comparison of the deduced amino acid sequences showed that MP67 is similar to ecto-apyrases; however, it was distinct from conventional apyrase based on phylogenetic classification. MP67 and MpAPY2 were expressed in Escherichia coli, and the recombinant proteins were purified. The recombinant MP67 showed high substrate specificity toward ADP rather than ATP. A polyclonal antibody raised against the recombinant MP67 was used to examine the tissue distribution and localization of native MP67 in the plant. The results showed that MP67 was ubiquitously distributed in various tissues, most abundantly in leaves, and was localized to plasma membranes. Thus, MP67 is a novel ecto-apyrase with extremely high substrate specificity for ADP.

Purification and Biochemical Characterization of a Novel Ecto-Apyrase, MP67, from Mimosa pudica1[C][W][OA

PubMed Central

Okuhata, Riku; Takishima, Takeshi; Nishimura, Naoaki; Ueda, Shogo; Tsuchiya, Takahide; Kanzawa, Nobuyuki

2011-01-01

We have previously reported the presence of an apyrase in Mimosa pudica. However, only limited information is available for this enzyme. Thus, in this study, the apyrase was purified to homogeneity. The purified enzyme had a molecular mass of around 67 kD and was able to hydrolyze both nucleotide triphosphate and nucleotide diphosphate as substrates. The ratio of ATP to ADP hydrolysis velocity of the purified protein was 0.01 in the presence of calcium ion, showing extremely high substrate specificity toward ADP. Thus, we designated this novel apyrase as MP67. A cDNA clone of MP67 was obtained using primers designed from the amino acid sequence of trypsin-digested fragments of the protein. In addition, rapid amplification of cDNA ends-polymerase chain reaction was performed to clone a conventional apyrase (MpAPY2). Comparison of the deduced amino acid sequences showed that MP67 is similar to ecto-apyrases; however, it was distinct from conventional apyrase based on phylogenetic classification. MP67 and MpAPY2 were expressed in Escherichia coli, and the recombinant proteins were purified. The recombinant MP67 showed high substrate specificity toward ADP rather than ATP. A polyclonal antibody raised against the recombinant MP67 was used to examine the tissue distribution and localization of native MP67 in the plant. The results showed that MP67 was ubiquitously distributed in various tissues, most abundantly in leaves, and was localized to plasma membranes. Thus, MP67 is a novel ecto-apyrase with extremely high substrate specificity for ADP. PMID:21788364

Resistance of the Extreme Halophile Halobacterium sp. NRC-1 to Multiple Stresses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gygli, Patrick E.; Prajapati, Surendra; DeVeaux, Linda C.

2009-03-10

The model Archaeon Halobacterium sp. NRC-1 is an extreme halophile known for its resistance to multiple stressors, including electron-beam and ultraviolet radiation. It is a well-developed system with a completely sequenced genome and extensive post-genomic tools for the study of a variety of biological processes. To further understand the mechanisms of Halobacterium's, radiation resistance, we previously reported the selection for multiple independent highly resistant mutants using repeated exposure to high doses of 18-20 MeV electrons using a medical S-band Linac. Molecular analysis of the transcriptional profile of several of these mutants revealed a single common change: upregulation of the rfa3more » operon. These genes encode proteins homologous to the subunits of eukaryotic Replication Protein A (RPA), a DNA binding protein with major roles in DNA replication, recombination, and repair. This operon has also been implicated in a somewhat lesser role in resistance of wild type Halobacterium to ultraviolet radiation, suggesting common mechanisms for resistance. To further understand the mechanism of radiation resistance in the mutant strains, we measured the survival after exposure to both electron-beam and ultraviolet radiation, UV-A, B, and C All mutant strains showed increased resistance to electrons when compared with the parent. However, the mutant strains do not display increased UV resistance, and in one case is more sensitive than the parent strain. Thus, the protective role of increased RPA expression within a cell may be specific to the DNA damage caused by the different physical effects induced by high energy electron-beam radiation.« less

Experiences and Psychosocial Impact of West Africa Ebola Deployment on US Health Care Volunteers

PubMed Central

Gershon, Robyn; Dernehl, Liza A.; Nwankwo, Ezinne; Zhi, Qi; Qureshi, Kristine

2016-01-01

Background: This qualitative study was designed to assess health care volunteers’ experiences and psychosocial impacts associated with deployment to the West Africa Ebola epidemic. Methods: In 2015, using snowball sampling, 16 US health care volunteers who had recently returned from West Africa were recruited for this study. Semi-structured interviews were conducted to collect information associated with each phase of deployment (pre, peri, and post). Results: Participants reported that they were motivated to volunteer because of a sense of responsibility and feelings of empathy and altruism. Immediately prior to deployment, most reported fear of contagion and death, as well as doubts regarding the adequacy of their training. Family members and close friends expressed high levels of concern regarding participants’ decisions to volunteer. During the deployment, participants were fearful of exposure and reported feeling emotionally and physically exhausted. They also reported feeling frustrated by extreme resource limitations, poor management of the mission, lack of clearly defined roles and responsibilities, and inability to provide high quality care. Upon return home, participants felt a sense of isolation, depression, stigmatization, interpersonal difficulties, and extreme stress. Conclusion: Preparedness of volunteers was suboptimal at each stage of deployment. All stakeholders, including volunteers, sponsoring organizations, government agencies, and professional organizations have a shared responsibility in ensuring that volunteers to medical missions are adequately prepared. This is especially critical for high risk deployments. Effective policies and practices need to be developed and implemented in order to protect the health and well-being of health care volunteers to the fullest extent possible. PMID:27803840

Extreme Population Differences in the Human Zinc Transporter ZIP4 (SLC39A4) Are Explained by Positive Selection in Sub-Saharan Africa

PubMed Central

Pybus, Marc; Andrews, Glen K.; Lalueza-Fox, Carles; Comas, David; Sekler, Israel; de la Rasilla, Marco; Rosas, Antonio; Stoneking, Mark; Valverde, Miguel A.; Vicente, Rubén; Bosch, Elena

2014-01-01

Extreme differences in allele frequency between West Africans and Eurasians were observed for a leucine-to-valine substitution (Leu372Val) in the human intestinal zinc uptake transporter, ZIP4, yet no further evidence was found for a selective sweep around the ZIP4 gene (SLC39A4). By interrogating allele frequencies in more than 100 diverse human populations and resequencing Neanderthal DNA, we confirmed the ancestral state of this locus and found a strong geographical gradient for the derived allele (Val372), with near fixation in West Africa. In extensive coalescent simulations, we show that the extreme differences in allele frequency, yet absence of a classical sweep signature, can be explained by the effect of a local recombination hotspot, together with directional selection favoring the Val372 allele in Sub-Saharan Africans. The possible functional effect of the Leu372Val substitution, together with two pathological mutations at the same codon (Leu372Pro and Leu372Arg) that cause acrodermatitis enteropathica (a disease phenotype characterized by extreme zinc deficiency), was investigated by transient overexpression of human ZIP4 protein in HeLa cells. Both acrodermatitis mutations cause absence of the ZIP4 transporter cell surface expression and nearly absent zinc uptake, while the Val372 variant displayed significantly reduced surface protein expression, reduced basal levels of intracellular zinc, and reduced zinc uptake in comparison with the Leu372 variant. We speculate that reduced zinc uptake by the ZIP4-derived Val372 isoform may act by starving certain pathogens of zinc, and hence may have been advantageous in Sub-Saharan Africa. Moreover, these functional results may indicate differences in zinc homeostasis among modern human populations with possible relevance for disease risk. PMID:24586184

A Bulk Segregant Gene Expression Analysis of a Peach Population Reveals Components of the Underlying Mechanism of the Fruit Cold Response

PubMed Central

Pons, Clara; Martí, Cristina; Forment, Javier; Crisosto, Carlos H.; Dandekar, Abhaya M.; Granell, Antonio

2014-01-01

Peach fruits subjected for long periods of cold storage are primed to develop chilling injury once fruits are shelf ripened at room temperature. Very little is known about the molecular changes occurring in fruits during cold exposure. To get some insight into this process a transcript profiling analyses was performed on fruits from a PopDG population segregating for chilling injury CI responses. A bulked segregant gene expression analysis based on groups of fruits showing extreme CI responses indicated that the transcriptome of peach fruits was modified already during cold storage consistently with eventual CI development. Most peach cold-responsive genes have orthologs in Arabidopsis that participate in cold acclimation and other stresses responses, while some of them showed expression patterns that differs in fruits according to their susceptibility to develop mealiness. Members of ICE1, CBF1/3 and HOS9 regulons seem to have a prominent role in differential cold responses between low and high sensitive fruits. In high sensitive fruits, an alternative cold response program is detected. This program is probably associated with dehydration/osmotic stress and regulated by ABA, auxins and ethylene. In addition, the observation that tolerant siblings showed a series of genes encoding for stress protective activities with higher expression both at harvest and during cold treatment, suggests that preprogrammed mechanisms could shape fruit ability to tolerate postharvest cold-induced stress. A number of genes differentially expressed were validated and extended to individual genotypes by medium-throughput RT-qPCR. Analyses presented here provide a global view of the responses of peach fruits to cold storage and highlights new peach genes that probably play important roles in the tolerance/sensitivity to cold storage. Our results provide a roadmap for further experiments and would help to develop new postharvest protocols and gene directed breeding strategies to better cope with chilling injury. PMID:24598973

A bulk segregant gene expression analysis of a peach population reveals components of the underlying mechanism of the fruit cold response.

PubMed

Pons, Clara; Martí, Cristina; Forment, Javier; Crisosto, Carlos H; Dandekar, Abhaya M; Granell, Antonio

2014-01-01

Peach fruits subjected for long periods of cold storage are primed to develop chilling injury once fruits are shelf ripened at room temperature. Very little is known about the molecular changes occurring in fruits during cold exposure. To get some insight into this process a transcript profiling analyses was performed on fruits from a PopDG population segregating for chilling injury CI responses. A bulked segregant gene expression analysis based on groups of fruits showing extreme CI responses indicated that the transcriptome of peach fruits was modified already during cold storage consistently with eventual CI development. Most peach cold-responsive genes have orthologs in Arabidopsis that participate in cold acclimation and other stresses responses, while some of them showed expression patterns that differs in fruits according to their susceptibility to develop mealiness. Members of ICE1, CBF1/3 and HOS9 regulons seem to have a prominent role in differential cold responses between low and high sensitive fruits. In high sensitive fruits, an alternative cold response program is detected. This program is probably associated with dehydration/osmotic stress and regulated by ABA, auxins and ethylene. In addition, the observation that tolerant siblings showed a series of genes encoding for stress protective activities with higher expression both at harvest and during cold treatment, suggests that preprogrammed mechanisms could shape fruit ability to tolerate postharvest cold-induced stress. A number of genes differentially expressed were validated and extended to individual genotypes by medium-throughput RT-qPCR. Analyses presented here provide a global view of the responses of peach fruits to cold storage and highlights new peach genes that probably play important roles in the tolerance/sensitivity to cold storage. Our results provide a roadmap for further experiments and would help to develop new postharvest protocols and gene directed breeding strategies to better cope with chilling injury.

Integration of somatic mutation, expression and functional data reveals potential driver genes predictive of breast cancer survival.

PubMed

Suo, Chen; Hrydziuszko, Olga; Lee, Donghwan; Pramana, Setia; Saputra, Dhany; Joshi, Himanshu; Calza, Stefano; Pawitan, Yudi

2015-08-15

Genome and transcriptome analyses can be used to explore cancers comprehensively, and it is increasingly common to have multiple omics data measured from each individual. Furthermore, there are rich functional data such as predicted impact of mutations on protein coding and gene/protein networks. However, integration of the complex information across the different omics and functional data is still challenging. Clinical validation, particularly based on patient outcomes such as survival, is important for assessing the relevance of the integrated information and for comparing different procedures. An analysis pipeline is built for integrating genomic and transcriptomic alterations from whole-exome and RNA sequence data and functional data from protein function prediction and gene interaction networks. The method accumulates evidence for the functional implications of mutated potential driver genes found within and across patients. A driver-gene score (DGscore) is developed to capture the cumulative effect of such genes. To contribute to the score, a gene has to be frequently mutated, with high or moderate mutational impact at protein level, exhibiting an extreme expression and functionally linked to many differentially expressed neighbors in the functional gene network. The pipeline is applied to 60 matched tumor and normal samples of the same patient from The Cancer Genome Atlas breast-cancer project. In clinical validation, patients with high DGscores have worse survival than those with low scores (P = 0.001). Furthermore, the DGscore outperforms the established expression-based signatures MammaPrint and PAM50 in predicting patient survival. In conclusion, integration of mutation, expression and functional data allows identification of clinically relevant potential driver genes in cancer. The documented pipeline including annotated sample scripts can be found in http://fafner.meb.ki.se/biostatwiki/driver-genes/. yudi.pawitan@ki.se Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hepatic Overexpression of Endothelial Lipase Lowers HDL (High-Density Lipoprotein) but Maintains Reverse Cholesterol Transport in Mice: Role of SR-BI (Scavenger Receptor Class B Type I)/ABCA1 (ATP-Binding Cassette Transporter A1)-Dependent Pathways.

PubMed

Takiguchi, Shunichi; Ayaori, Makoto; Yakushiji, Emi; Nishida, Takafumi; Nakaya, Kazuhiro; Sasaki, Makoto; Iizuka, Maki; Uto-Kondo, Harumi; Terao, Yoshio; Yogo, Makiko; Komatsu, Tomohiro; Ogura, Masatsune; Ikewaki, Katsunori

2018-05-10

Reverse cholesterol transport (RCT) is a major mechanism by which HDL (high-density lipoprotein) protects against atherosclerosis. Endothelial lipase (EL) reportedly reduces HDL levels, which, in theory, would increase atherosclerosis. However, it remains unclear whether EL affects RCT in vivo. Adenoviral vectors expressing EL or luciferase were intravenously injected into mice, and a macrophage RCT assay was performed. As expected, hepatic EL overexpression markedly reduced HDL levels. In parallel, plasma 3 H-cholesterol counts from the EL-expressing mice decreased by 85% compared with control. Surprisingly, there was no difference in fecal 3 H-cholesterol excretion between the groups. Kinetic studies revealed increased catabolism/hepatic uptake of 3 HDL-cholesteryl ether, resulting in no change in fecal HDL-cholesteryl ester excretion in the mice. To explore underlying mechanisms for the preservation of RCT despite low HDL levels in the EL-expressing mice, we investigated the effects of hepatic SR-BI (scavenger receptor class B type I) knockdown. RCT assay revealed that knockdown of SR-BI alone reduced fecal excretion of macrophage-derived 3 H-cholesterol. Interestingly, hepatic EL overexpression under SR-BI inhibition further attenuated fecal tracer counts as compared with control. Finally, we observed that EL overexpression enhanced in vivo RCT under pharmacological inhibition of hepatic ABCA1 (ATP-binding cassette transporter A1) by probucol. Hepatic EL expression compensates for reduced macrophage-derived cholesterol efflux to plasma because of low HDL levels by promoting cholesterol excretion to bile/feces via an SR-BI pathway, maintaining overall RCT in vivo. In contrast, EL-modified HDL might negatively regulate RCT via hepatic ABCA1. Despite extreme hypoalphalipoproteinemia, RCT is maintained in EL-expressing mice via SR-BI/ABCA1-dependent pathways. © 2018 American Heart Association, Inc.

Progesterone signalling in broiler skeletal muscle is associated with divergent feed efficiency.

PubMed

Bottje, Walter; Kong, Byung-Whi; Reverter, Antonio; Waardenberg, Ashley J; Lassiter, Kentu; Hudson, Nicholas J

2017-02-24

We contrast the pectoralis muscle transcriptomes of broilers selected from within a single genetic line expressing divergent feed efficiency (FE) in an effort to improve our understanding of the mechanistic basis of FE. Application of a virtual muscle model to gene expression data pointed to a coordinated reduction in slow twitch muscle isoforms of the contractile apparatus (MYH15, TPM3, MYOZ2, TNNI1, MYL2, MYOM3, CSRP3, TNNT2), consistent with diminishment in associated slow machinery (myoglobin and phospholamban) in the high FE animals. These data are in line with the repeated transition from red slow to white fast muscle fibres observed in agricultural species selected on mass and FE. Surprisingly, we found that the expression of 699 genes encoding the broiler mitoproteome is modestly-but significantly-biased towards the high FE group, suggesting a slightly elevated mitochondrial content. This is contrary to expectation based on the slow muscle isoform data and theoretical physiological capacity arguments. Reassuringly, the extreme 40 most DE genes can successfully cluster the 12 individuals into the appropriate FE treatment group. Functional groups contained in this DE gene list include metabolic proteins (including opposing patterns of CA3 and CA4), mitochondrial proteins (CKMT1A), oxidative status (SEPP1, HIG2A) and cholesterol homeostasis (APOA1, INSIG1). We applied a differential network method (Regulatory Impact Factors) whose aim is to use patterns of differential co-expression to detect regulatory molecules transcriptionally rewired between the groups. This analysis clearly points to alterations in progesterone signalling (via the receptor PGR) as the major driver. We show the progesterone receptor localises to the mitochondria in a quail muscle cell line. Progesterone is sometimes used in the cattle industry in exogenous hormone mixes that lead to a ~20% increase in FE. Because the progesterone receptor can localise to avian mitochondria, our data continue to point to muscle mitochondrial metabolism as an important component of the phenotypic expression of variation in broiler FE.

Extreme pressure differences at 0900 NZST and winds across New Zealand

NASA Astrophysics Data System (ADS)

Salinger, M. James; Griffiths, Georgina M.; Gosai, Ashmita

2005-07-01

Trends in extremes in station daily sea-level pressure differences at 0900 NZST are examined, and extreme daily wind gusts, across New Zealand, since the 1960s. Annual time series were examined (with indices of magnitude and frequency over threshold percentiles) from the daily indices selected. These follow from earlier indices of normalized monthly mean sea-level pressure differences between station pairs, except the daily indices are not normalized. The frequency statistics quantify the number of extreme zonal (westerly and easterly), or extreme meridional (southerly or northerly), pressure gradient events. The frequency and magnitude of extreme westerly episodes has increased slightly over New Zealand, with a significant increase in the westerly extremes to the south of New Zealand. In contrast, the magnitude and frequency of easterly extremes has decreased over New Zealand, but increased to the south, with some trends weakly significant. The frequency and magnitude of daily southerly extremes has decreased significantly in the region.Extreme daily wind gust events at key climate stations in New Zealand and at Hobart, Australia, are highly likely to be associated with an extreme daily pressure difference. The converse was less likely to hold: extreme wind gusts were not always observed on days with extreme daily pressure difference, probably due to the strong influence that topography has on localized station winds. Significant correlations exist between the frequency indices and both annual-average mean sea-level pressures around the Australasian region and annual-average sea surface temperature (SST) anomalies in the Southern Hemisphere. These correlations are generally stronger for indices of extreme westerly or extreme southerly airflows. Annual-average pressures in the Tasman Sea or Southern Ocean are highly correlated to zonal indices (frequency of extreme westerlies). SST anomalies in the NINO3 region or on either side of the South Island are significantly correlated with the frequency of extreme westerly airflows.

Recombinant Protein Production from TPO Gen Cloning and Expression for Early Detection of Autoimmune Thyroid Diseases

NASA Astrophysics Data System (ADS)

Aulanni'am, Aulanni'am; Kinasih Wuragil, Dyah; Wahono Soeatmadji, Djoko; Zulkarnain; Marhendra, Agung Pramana W.

2018-01-01

Autoimmune Thyroid Disease (AITD) is an autoimmune disease that has many clinical symptoms but is difficult to detect at the onset of disease progression. Most thyroid autoimmune disease patients are positive with high titre of thyroid autoantibodies, especially thyroid peroxidase (TPO). The detection AITD are still needed because these tests are extremely high cost and have not regularly been performed in most of clinical laboratories. In the past, we have explored the autoimmune disease marker and it has been developed as source of polyclonal antibodies from patient origin. In the current study, we develop recombinant protein which resulted from cloning and expression of TPO gene from normal person and AITD patients. This work flows involves: DNA isolation and PCR to obtain TPO gene from human blood, insertion of TPO gene to plasmid and transformation to E. coli BL21, Bacterial culture to obtain protein product, protein purification and product analysis. This products can use for application to immunochromatography based test. This work could achieved with the goal of producing autoimmune markers with a guaranteed quality, sensitive, specific and economically. So with the collaboration with industries these devices could be used for early detection. Keywords: recombinant protein, TPO gene, Autoimmune thyroid diseases (AITD)ction of the diseases in the community.

Heat shock protein expression enhances heat tolerance of reptile embryos.

PubMed

Gao, Jing; Zhang, Wen; Dang, Wei; Mou, Yi; Gao, Yuan; Sun, Bao-Jun; Du, Wei-Guo

2014-09-22

The role of heat shock proteins (HSPs) in heat tolerance has been demonstrated in cultured cells and animal tissues, but rarely in whole organisms because of methodological difficulties associated with gene manipulation. By comparing HSP70 expression patterns among representative species of reptiles and birds, and by determining the effect of HSP70 overexpression on embryonic development and hatchling traits, we have identified the role of HSP70 in the heat tolerance of amniote embryos. Consistent with their thermal environment, and high incubation temperatures and heat tolerance, the embryos of birds have higher onset and maximum temperatures for induced HSP70 than do reptiles, and turtles have higher onset and maximum temperatures than do lizards. Interestingly, the trade-off between benefits and costs of HSP70 overexpression occurred between life-history stages: when turtle embryos developed at extreme high temperatures, HSP70 overexpression generated benefits by enhancing embryo heat tolerance and hatching success, but subsequently imposed costs by decreasing heat tolerance of surviving hatchlings. Taken together, the correlative and causal links between HSP70 and heat tolerance provide, to our knowledge, the first unequivocal evidence that HSP70 promotes thermal tolerance of embryos in oviparous amniotes. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

The Complete Genome Sequence of Hyperthermophile Dictyoglomus turgidum DSM 6724™ Reveals a Specialized Carbohydrate Fermentor

DOE PAGES

Brumm, Phillip J.; Gowda, Krishne; Robb, Frank T.; ...

2016-12-20

In this study we report the complete genome sequence of the chemoorganotrophic, extremely thermophilic bacterium, Dictyoglomus turgidum, which is a Gram negative, strictly anaerobic bacterium. D. turgidum and D. thermophilum together form the Dictyoglomi phylum. The two Dictyoglomus genomes are highly syntenic, and both are distantly related to Caldicellulosiruptor spp. D. turgidum is able to grow on a wide variety of polysaccharide substrates due to significant genomic commitment to glycosyl hydrolases, 16 of which were cloned and expressed in our study. The GH5, GH10, and GH42 enzymes characterized in this study suggest that D. turgidum can utilize most plant-based polysaccharidesmore » except crystalline cellulose. The DNA polymerase I enzyme was also expressed and characterized. The pure enzyme showed improved amplification of long PCR targets compared to Taq polymerase. The genome contains a full complement of DNA modifying enzymes, and an unusually high copy number (4) of a new, ancestral family of polB type nucleotidyltransferases designated as MNT (minimal nucleotidyltransferases). Considering its optimal growth at 72°C, D. turgidum has an anomalously low G+C content of 39.9% that may account for the presence of reverse gyrase, usually associated with hyperthermophiles.« less

Heterologous expression of an active chitin synthase from Rhizopus oryzae.

PubMed

Salgado-Lugo, Holjes; Sánchez-Arreguín, Alejandro; Ruiz-Herrera, José

2016-12-01

Chitin synthases are highly important enzymes in nature, where they synthesize structural components in species belonging to different eukaryotic kingdoms, including kingdom Fungi. Unfortunately, their structure and the molecular mechanism of synthesis of their microfibrilar product remain largely unknown, probably because no fungal active chitin synthases have been isolated, possibly due to their extreme hydrophobicity. In this study we have turned to the heterologous expression of the transcript from a small chitin synthase of Rhizopus oryzae (RO3G_00942, Chs1) in Escherichia coli. The enzyme was active, but accumulated mostly in inclusion bodies. High concentrations of arginine or urea solubilized the enzyme, but their dilution led to its denaturation and precipitation. Nevertheless, use of urea permitted the purification of small amounts of the enzyme. The properties of Chs1 (Km, optimum temperature and pH, effect of GlcNAc) were abnormal, probably because it lacks the hydrophobic transmembrane regions characteristic of chitin synthases. The product of the enzyme showed that, contrasting with chitin made by membrane-bound Chs's and chitosomes, was only partially in the form of short microfibrils of low crystallinity. This approach may lead to future developments to obtain active chitin synthases that permit understanding their molecular mechanism of activity, and microfibril assembly. Copyright © 2016. Published by Elsevier Inc.

Inhibition of BMP signaling overcomes acquired resistance to cetuximab in oral squamous cell carcinomas.

PubMed

Yin, Jinlong; Jung, Ji-Eun; Choi, Sun Il; Kim, Sung Soo; Oh, Young Taek; Kim, Tae-Hoon; Choi, Eunji; Lee, Sun Joo; Kim, Hana; Kim, Eun Ok; Lee, Yu Sun; Chang, Hee Jin; Park, Joo Yong; Kim, Yeejeong; Yun, Tak; Heo, Kyun; Kim, Youn-Jae; Kim, Hyunggee; Kim, Yun-Hee; Park, Jong Bae; Choi, Sung Weon

2018-02-01

Despite expressing high levels of the epidermal growth factor receptor (EGFR), a majority of oral squamous cell carcinoma (OSCC) patients show limited response to cetuximab and ultimately develop drug resistance. However, mechanism underlying cetuximab resistance in OSCC is not clearly understood. Here, using a mouse orthotopic xenograft model of OSCC, we show that bone morphogenic protein-7-phosphorylated Smad-1, -5, -8 (BMP7-p-Smad1/5/8) signaling contributes to cetuximab resistance. Tumor cells isolated from the recurrent cetuximab-resistant xenograft models exhibited low EGFR expression but extremely high levels of p-Smad1/5/8. Treatment with the bone morphogenic protein receptor type 1 (BMPRI) inhibitor, DMH1 significantly reduced cetuximab-resistant OSCC tumor growth, and combined treatment of DMH1 and cetuximab remarkably reduced relapsed tumor growth in vivo. Importantly, p-Smad1/5/8 level was elevated in cetuximab-resistant patients and this correlated with poor prognosis. Collectively, our results indicate that the BMP7-p-Smad1/5/8 signaling is a key pathway to acquired cetuximab resistance, and demonstrate that combination therapy of cetuximab and a BMP signaling inhibitor as potentially a new therapeutic strategy for overcoming acquired resistance to cetuximab in OSCC. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigating circular patterns in linear polarization observations of Venus

NASA Astrophysics Data System (ADS)

Mahapatra, Gourav; Stam, Daphne; Rossi, Loic; Rodenhuis, Michiel; Snik, Frans

2017-04-01

ESA's Venus Express mission has revealed our neighbouring planet to be a highly dynamic world, with ever-changing cloud properties and structures, wind speeds that increase in time, and variable concentrations of atmospheric trace gases such as SO2. The SPICAV-IR instrument on Venus Express has provided us with close-up linear polarization data of sunlight reflected by Venus's clouds and hazes, that allows a characterisation of their composition and particle sizes. Here, we analyse linear polarization data of the planet at a distance, obtained with the Extreme Polarimeter (ExPo) on the William Herschel Telescope on La Palma. These spatially resolved, high-accuracy polarization observations of Venus show faint circular patterns centered on the sub-solar point that are absent in the flux observations. So far, careful analyses have ruled out instrumental effects which leaves us to wonder about atmospheric properties as the cause of the circular patterns. Using numerical simulations of the flux and polarization of sunlight that is reflected by Venus, we have investigated the relation between the observed patterns and several atmospheric properties, such as variations in particle sizes, composition, density and altitude. We discuss the plausibility of the possible causes in the view of the current knowledge of the composition and dynamical processes in Venus's atmosphere.

The Complete Genome Sequence of Hyperthermophile Dictyoglomus turgidum DSM 6724™ Reveals a Specialized Carbohydrate Fermentor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brumm, Phillip J.; Gowda, Krishne; Robb, Frank T.

In this study we report the complete genome sequence of the chemoorganotrophic, extremely thermophilic bacterium, Dictyoglomus turgidum, which is a Gram negative, strictly anaerobic bacterium. D. turgidum and D. thermophilum together form the Dictyoglomi phylum. The two Dictyoglomus genomes are highly syntenic, and both are distantly related to Caldicellulosiruptor spp. D. turgidum is able to grow on a wide variety of polysaccharide substrates due to significant genomic commitment to glycosyl hydrolases, 16 of which were cloned and expressed in our study. The GH5, GH10, and GH42 enzymes characterized in this study suggest that D. turgidum can utilize most plant-based polysaccharidesmore » except crystalline cellulose. The DNA polymerase I enzyme was also expressed and characterized. The pure enzyme showed improved amplification of long PCR targets compared to Taq polymerase. The genome contains a full complement of DNA modifying enzymes, and an unusually high copy number (4) of a new, ancestral family of polB type nucleotidyltransferases designated as MNT (minimal nucleotidyltransferases). Considering its optimal growth at 72°C, D. turgidum has an anomalously low G+C content of 39.9% that may account for the presence of reverse gyrase, usually associated with hyperthermophiles.« less

Seed desiccation mechanisms co-opted for vegetative desiccation in the resurrection grass Oropetium thomaeum.

PubMed

VanBuren, Robert; Wai, Ching Man; Zhang, Qingwei; Song, Xiaomin; Edger, Patrick P; Bryant, Doug; Michael, Todd P; Mockler, Todd C; Bartels, Dorothea

2017-10-01

Resurrection plants desiccate during periods of prolonged drought stress, then resume normal cellular metabolism upon water availability. Desiccation tolerance has multiple origins in flowering plants, and it likely evolved through rewiring seed desiccation pathways. Oropetium thomaeum is an emerging model for extreme drought tolerance, and its genome, which is the smallest among surveyed grasses, was recently sequenced. Combining RNA-seq, targeted metabolite analysis and comparative genomics, we show evidence for co-option of seed-specific pathways during vegetative desiccation. Desiccation-related gene co-expression clusters are enriched in functions related to seed development including several seed-specific transcription factors. Across the metabolic network, pathways involved in programmed cell death inhibition, ABA signalling and others are activated during dehydration. Oleosins and oil bodies that typically function in seed storage are highly abundant in desiccated leaves and may function for membrane stability and storage. Orthologs to seed-specific LEA proteins from rice and maize have neofunctionalized in Oropetium with high expression during desiccation. Accumulation of sucrose, raffinose and stachyose in drying leaves mirrors sugar accumulation patterns in maturing seeds. Together, these results connect vegetative desiccation with existing seed desiccation and drought responsive pathways and provide some key candidate genes for engineering improved drought tolerance in crop plants. © 2017 John Wiley & Sons Ltd.

D-ribulose-5-phosphate 3-epimerase: Cloning and heterologous expression of the spinach gene, and purification and characterization of the recombinant enzyme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Y.R.; Hartman, F.C.; Lu, T.Y.S.

The authors have achieved, to their knowledge, the first high-level heterologous expression of the gene encoding D-ribulose-5-phosphate 3-epimerase from any source, thereby permitting isolation and characterization of the epimerase as found in photosynthetic organisms. The extremely labile recombinant spinach (Spinacia oleracea L.) enzyme was stabilized by DL-{alpha}-glycerophosphate or ethanol and destabilized by D-ribulose-5-phosphate or 2-mercaptoethanol. Despite this lability, the unprecedentedly high specific activity of the purified material indicates that the structural integrity of the enzyme is maintained throughout isolation. Ethylenediaminetetraacetate and divalent metal cations did not affect epimerase activity, thereby excluding a requirement for the latter in catalysis. As deducedmore » from the sequence of the cloned spinach gene and the electrophoretic mobility under denaturing conditions of the purified recombinant enzyme, its 25-kD subunit size was about the same as that of the corresponding epimerases of yeast and mammals. However, in contrast to these other species, the recombinant spinach enzyme was octameric rather than dimeric, as assessed by gel filtration and polyacrylamide gel electrophoresis under nondenaturing conditions. Western-blot analyses with antibodies to the purified recombinant enzyme confirmed that the epimerase extracted from spinach leaves is also octameric.« less

Extreme Consumption Drinking Gaming and Prepartying among High School Students

ERIC Educational Resources Information Center

Tomaso, Cara C.; Zamboanga, Byron L.; Haas, Amie L.; Kenney, Shannon R.; Ham, Lindsay S.; Borsari, Brian

2016-01-01

Drinking games and prepartying (i.e., drinking before going to a social gathering/event) have emerged as high-risk drinking behaviors in high school students. The present study examines the current prepartying behaviors of high school students who report current participation in extreme-consumption games (e.g., chugging) with those who do not.…

Factors affecting the 7Be surface concentration and its extremely high occurrences over the Scandinavian Peninsula during autumn and winter.

PubMed

Ajtić, J; Brattich, E; Sarvan, D; Djurdjevic, V; Hernández-Ceballos, M A

2018-05-01

Relationships between the beryllium-7 activity concentrations in surface air and meteorological parameters (temperature, atmospheric pressure, and precipitation), teleconnection indices (Arctic Oscillation, North Atlantic Oscillation, and Scandinavian pattern) and number of sunspots are investigated using two multivariate statistical techniques: hierarchical cluster and factor analysis. The beryllium-7 surface measurements over 1995-2011, at four sampling sites located in the Scandinavian Peninsula, are obtained from the Radioactivity Environmental Monitoring Database. In all sites, the statistical analyses show that the beryllium-7 concentrations are strongly linked to temperature. Although the beryllium-7 surface concentration exhibits the well-characterised spring/summer maximum, our study shows that extremely high beryllium-7 concentrations, defined as the values exceeding the 90 th percentile in the data records for each site, also occur over the October-March period. Two types of autumn/winter extremes are distinguished: type-1 when the number of extremes in a given month is less than three, and type-2 when at least three extremes occur in a month. Factor analysis performed for these autumn/winter events shows a weaker effect of temperature and a stronger impact of the transport and production signal on the beryllium-7 concentrations. Further, the majority of the type-2 extremes are associated with a very high monthly Scandinavian teleconnection index. The type-2 extremes that occurred in January, February and March are also linked to sudden stratospheric warmings of the Arctic vortex. Our results indicate that the Scandinavian teleconnection index might be a good indicator of the meteorological conditions facilitating extremely high beryllium-7 surface concentrations over Scandinavia during autumn and winter. Copyright © 2018 Elsevier Ltd. All rights reserved.