Metagenomics: A Call for Bringing a New Science into the Classroom (While It's Still New)

ERIC Educational Resources Information Center

Jurkowski, Anne; Reid, Ann H.; Labov, Jay B.

2007-01-01

This article describes the emerging field of metagenomics, a potent new tool that vastly expands the ability of scientists to study the myriad capabilities of microbial communities and the as yet unrecognized relationships and interactions of microbes with other forms of life and the environment. The birth of this exciting new field provides the…

Unrecognized heart failure and chronic obstructive pulmonary disease (COPD) in frail elderly detected through a near-home targeted screening strategy.

PubMed

van Mourik, Yvonne; Bertens, Loes C M; Cramer, Maarten J M; Lammers, Jan-Willem J; Reitsma, Johannes B; Moons, Karel G M; Hoes, Arno W; Rutten, Frans H

2014-01-01

Reduced exercise tolerance and dyspnea are common in older people, and heart failure (HF) and chronic obstructive pulmonary disease (COPD) are the main causes. We want to determine the prevalence of previously unrecognized HF, COPD, and other chronic diseases in frail older people using a near-home targeted screening strategy. Community-dwelling frail persons aged ≥65 years underwent a 2-step screening strategy. First, they received a questionnaire inquiring about dyspnea and exercise tolerance. Those with exercise intolerance and/or dyspnea were invited to visit their primary care physician's office for a screening program, including medical history taking, physical examination, blood tests, electrocardiography, spirometry, and echocardiography. The final diagnosis of every patient was determined by a panel consisting of 3 physicians. Of the 570 elderly who filled out the questionnaire, 395 (69%) had reduced exercise tolerance or dyspnea. Of these, 389 underwent the screening program: 127 (33.5%, 95% confidence interval, 28.9-38.4%) were newly diagnosed with HF (mainly HF with a preserved ejection fraction [23.5%]), and previously unrecognized COPD was detected in 16.8% (95% confidence interval, 13.4-20.9%). In total, 165 patients (43.9%) received a new diagnosis of either HF, COPD, or both. Other new diagnoses (in 32.7% of the screening program patients) included atrial fibrillation (1.8%), valvular disease (21.4%), (persisting) asthma (3.1%), anemia (12.7%), and thyroid disease (0.6%). No clear explanation for the complaints of 47 patients (12.2%) was found using our strategy. Unrecognized chronic diseases might be detected in community-dwelling frail elderly using a near-home screening strategy that is simple to implement. It remains to be proven, however, whether optimizing treatment of the newly detected diagnoses in this fragile population with multimorbidities and polypharmacy improves quality of life and reduces morbidity and mortality. © Copyright 2014 by the American Board of Family Medicine.

Lobectomy is a more Cost-Effective Option than Total Thyroidectomy for 1 to 4 cm Papillary Thyroid Carcinoma that do not Possess Clinically Recognizable High-Risk Features.

PubMed

Lang, Brian Hung-Hin; Wong, Carlos K H

2016-10-01

Although lobectomy is a viable alternative to total thyroidectomy (TT) in low-risk 1 to 4 cm papillary thyroid carcinoma (PTC), lobectomy is associated with higher locoregional recurrence risk and need for completion TT upon discovery of a previously unrecognized histologic high-risk feature (HRF). The present study evaluated long-term cost-effectiveness between lobectomy and TT. Our base case was a hypothetical female cohort aged 40 years with a low-risk 2.5 cm PTC. A Markov decision tree model was constructed to compare cost-effectiveness between lobectomy and TT after 25 years. Patients with an unrecognized HRF (including aggressive histology, microscopic extrathyroidal extension, lymphovascular invasion, positive resection margin, nodal metastasis >5 mm, and multifocality) underwent completion TT after lobectomy. Outcome probabilities, utilities, and costs were estimated from the literature. The threshold for cost-effectiveness was set at US$50,000/quality-adjusted life-year (QALY). Sensitivity and threshold analyses were used to examine model uncertainty. After 25 years, each patient who underwent lobectomy instead of TT cost an extra US$772.08 but gained an additional 0.300 QALY. The incremental cost-effectiveness ratio was US$2577.65/QALY. In the sensitivity analysis, the lobectomy arm began to become cost-effective only after 3 years. Despite varying the reported prevalence of clinically unrecognized HRFs, complication from surgical procedures, annualized recurrence rates, unit cost of surgical procedure or complication, and utility score, lobectomy remained more cost-effective than TT. Despite the higher locoregional recurrence risk and having almost half of the patients undergoing completion TT after lobectomy upon discovery of a previously unrecognized HRF, initial lobectomy was a more cost-effective long-term option than initial TT for 1 to 4 cm PTCs without clinically recognized HRFs.

Bilateral pheochromocytoma during the postpartum period.

PubMed

Wattanachanya, Lalita; Bunworasate, Udomsak; Plengpanich, Wanee; Houngngam, Natnicha; Buranasupkajorn, Patinut; Sunthornyothin, Sarat; Shotelersuk, Vorasuk; Snabboon, Thiti

2009-12-01

Pheochromocytoma manifesting during pregnancy is uncommon but it is responsible for a high maternal and fetal mortality rate, especially when unrecognized. Most cases of pheochromocytoma are sporadic but they can be part of hereditary autosomal dominant syndromes. We describe a case of bilateral pheochromocytoma in a term-pregnant patient with a previous history of medullary thyroid carcinoma (MTC). Her genetic study revealed a heterozygous mutation, c.1900T>C, in the RET proto-oncogene which confirmed the diagnosis of multiple endocrine neoplasia type 2A (MEN2A). Unrecognized, the tumors caused a crisis with fatal outcome in the mother during the postpartum period. This event might have been prevented if the tumor had been detected previously. MEN2A affected pregnancy is an unusual condition. This syndrome should be suspected when a pregnant patient has a history of MTC. Early detection and appropriate management can prevent serious maternal and fetal complications. We also reviewed the literature of MEN2A-affected pregnancies.

36 CFR 60.14 - Changes and revisions to properties listed in the National Register.

Code of Federal Regulations, 2013 CFR

2013-07-01

... previously unrecognized significance in American history, architecture, archeology, engineering or culture... would be adversely affected by the intrusion of the property; and (iv) Photographs showing the proposed... adversely affected by intrusion of the property. In addition, new photographs, acreage, verbal boundary...

36 CFR 60.14 - Changes and revisions to properties listed in the National Register.

Code of Federal Regulations, 2014 CFR

2014-07-01

... previously unrecognized significance in American history, architecture, archeology, engineering or culture... would be adversely affected by the intrusion of the property; and (iv) Photographs showing the proposed... adversely affected by intrusion of the property. In addition, new photographs, acreage, verbal boundary...

36 CFR 60.14 - Changes and revisions to properties listed in the National Register.

Code of Federal Regulations, 2011 CFR

2011-07-01

... previously unrecognized significance in American history, architecture, archeology, engineering or culture... would be adversely affected by the intrusion of the property; and (iv) Photographs showing the proposed... adversely affected by intrusion of the property. In addition, new photographs, acreage, verbal boundary...

36 CFR 60.14 - Changes and revisions to properties listed in the National Register.

Code of Federal Regulations, 2012 CFR

2012-07-01

... previously unrecognized significance in American history, architecture, archeology, engineering or culture... would be adversely affected by the intrusion of the property; and (iv) Photographs showing the proposed... adversely affected by intrusion of the property. In addition, new photographs, acreage, verbal boundary...

Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease.

PubMed

Kumar, Manoj; Sharma, Barjesh C; Sarin, Shiv K

2008-06-01

Hepatitis E virus (HEV) has recently been implicated in episodes of acute decompensation in patients having underlying chronic liver disease (CLD) of varying etiology. However, HEV as a cause of acute exacerbation of previously asymptomatic and unrecognized hepatitis B virus (HBV)-infected patients is less well described. The aim of the present study was to investigate the etiology of acute exacerbation of previously asymptomatic and unrecognized HBV-infected patients and to evaluate the relative role of HEV. We also investigated the effect of superinfection on the clinical spectrum of underlying HBV infection. Forty-three patients presented with the following were retrospectively analyzed: (i) clinical features suggestive of acute hepatitis; (ii) with hepatitis B surface antigen (HBsAg) (+); (iii) IgM hepatitis B core antibody (IgM anti-HBc) (-); (iv) no previous history of liver disease; (v) no features suggestive of CLD at presentation; (vi) HBsAg remaining (+) for at least 12 months on follow up; and (vii) having a follow-up biopsy during the convalescent phase showing evidence of chronic hepatitis B. Of the 43 patients, 21 were hepatitis e antigen (HBeAg) (+) (Gr.1) and 22 HBeAg (-) (Gr.2) at presentation. In Gr.1, only two (9.5%) had superinfection (both with hepatitis A virus), whereas in Gr.2, 11 (50%) had superinfection (27.3% hepatitis E, 13.6% hepatitis A and 9.1% both) (P = 0.007). In Gr.1, the remaining 19 (90.5%) patients had spontaneous exacerbation (immune clearance with spontaneous seroconversion) whereas in Gr.2, the remaining 11 (50%) had spontaneous exacerbation (due to reactivation). Overall, HEV superinfection contributed to 20% of acute exacerbation episodes and, in particular, 36% of episodes in initially HBeAg (-) patients. Time to alanine aminotransferase normalization was longer in patients with superinfection (n = 13) as compared to spontaneous exacerbation (n = 30) (median [range] 36 [8-48]vs 16 [6-36] weeks, P = 0.001). During convalescence, there was no significant difference between histological activity index score (median [range] 8 [4-11]vs 8 [4-16] weeks, P = 0.629) and fibrosis scores (median [range] 3.5 [1-4]vs 2 [1-4] weeks, P = 0.099] on liver biopsy after recovery among patients with acute exacerbation due to superinfection and spontaneous exacerbation. Acute exacerbations in HBeAg (+) patients are most often due to spontaneous viral activation, while in HBeAg (-) patients, superinfection with non-B hepatitis viruses and spontaneous viral activation are equally common. HEV is an important cause of acute exacerbation in previously asymptomatic and unrecognized patients with HBV-related CLD.

Contrast, contours and the confusion effect in dazzle camouflage.

PubMed

Hogan, Benedict G; Scott-Samuel, Nicholas E; Cuthill, Innes C

2016-07-01

'Motion dazzle camouflage' is the name for the putative effects of highly conspicuous, often repetitive or complex, patterns on parameters important in prey capture, such as the perception of speed, direction and identity. Research into motion dazzle camouflage is increasing our understanding of the interactions between visual tracking, the confusion effect and defensive coloration. However, there is a paucity of research into the effects of contrast on motion dazzle camouflage: is maximal contrast a prerequisite for effectiveness? If not, this has important implications for our recognition of the phenotype and understanding of the function and mechanisms of potential motion dazzle camouflage patterns. Here we tested human participants' ability to track one moving target among many identical distractors with surface patterns designed to test the influence of these factors. In line with previous evidence, we found that targets with stripes parallel to the object direction of motion were hardest to track. However, reduction in contrast did not significantly influence this result. This finding may bring into question the utility of current definitions of motion dazzle camouflage, and means that some animal patterns, such as aposematic or mimetic stripes, may have previously unrecognized multiple functions.

The Impact of Repeated Health Checks for Adults with Intellectual Disabilities

ERIC Educational Resources Information Center

Felce, David; Baxter, Helen; Lowe, Kathy; Dunstan, Frank; Houston, Helen; Jones, Glyn; Felce, Janet; Kerr, Michael

2008-01-01

Background: An earlier study (Baxter "et al." 2006) found that a structured health check conducted in primary care identified clinically significant previously unrecognized morbidity among adults with intellectual disabilities. The aim here was to examine whether follow-up health checks would identify equally significant newly identified morbidity…

Diversity at the Holarctic nexus: species of Arostrilepis (Eucestoda: Hymenolepididae) in arvicoline rodents (Cricetidae: Arvicolinae) from greater Beringia

USDA-ARS?s Scientific Manuscript database

Previously unrecognized species of hymenolepidid cestodes attributable to Arostrilepis Mas-Coma & Tenora, 1997 in arvicoline rodents from the greater Beringian region and western North America are described. Discovery and characterization of these tapeworms contributes to the recognition of a compl...

Cosmetics, categories, and the future.

PubMed

Draelos, Zoe Diana

2012-01-01

Cosmetics is an interesting unregulated category of over-the-counter products designed to enhance appearance and skin health. The coloring agents used in cosmetics are regulated along with their preservative constituents. New understandings of skin physiology have allowed cosmetics to advance beyond appearance issues into the functional arena. Cosmeceuticals is an unrecognized term from a regulatory perspective that conveys the new cosmetic formulations ability to improve skin health. © 2012 Wiley Periodicals, Inc.

Naringenin is a novel inhibitor of Dictyostelium cell proliferation and cell migration

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

Russ, Misty; Martinez, Raquel; Ali, Hind

2006-06-23

Naringenin is a flavanone compound that alters critical cellular processes such as cell multiplication, glucose uptake, and mitochondrial activity. In this study, we used the social amoeba, Dictyostelium discoideum, as a model system for examining the cellular processes and signaling pathways affected by naringenin. We found that naringenin inhibited Dictyostelium cell division in a dose-dependent manner (IC{sub 5} {approx} 20 {mu}M). Assays of Dictyostelium chemotaxis and multicellular development revealed that naringenin possesses a previously unrecognized ability to suppress amoeboid cell motility. We also found that naringenin, which is known to inhibit phosphatidylinositol 3-kinase activity, had no apparent effect on phosphatidylinositolmore » 3,4,5-trisphosphate synthesis in live Dictyostelium cells; suggesting that this compound suppresses cell growth and migration via alternative signaling pathways. In another context, the discoveries described here highlight the value of using the Dictyostelium model system for identifying and characterizing the mechanisms by which naringenin, and related compounds, exert their effects on eukaryotic cells.« less

Effects of paraquat on Escherichia coli: Differences between B and K-12 strains

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

Kitzler, J.W.; Minakami, H.; Fridovich, I.

1990-02-01

Escherichia coli B and K-12 are equally susceptible to the bacteriostatic effects of aerobic paraquat, but they differed strikingly when the lethality of paraquat was evaluated. E. coli B suffered an apparent loss of viability when briefly exposed to paraquat, whereas E. coli K-12 did not. This difference depended on the ability of the B-strain, but not the K-12 strain, to retain internalized paraquat; the B strain was killed on aerobic tryptic soy-yeast extract plates during the incubation which preceded the counting of colonies. This difference in retention of paraquat between strains was demonstrated by delayed loss of viability, bymore » growth inhibition, and by cyanide-resistant respiration after brief exposure to paraquat, washing, and testing in fresh medium. This difference was also shown by using ({sup 14}C)paraquat. This previously unrecognized difference between E. coli B and K-12 has been the cause of apparently contradictory reports and should lead to some reevaluation of the pertinent literature.« less

Carbonic anhydrase enzymes regulate mast cell–mediated inflammation

PubMed Central

Soteropoulos, Patricia

2016-01-01

Type 2 cytokine responses are necessary for the development of protective immunity to helminth parasites but also cause the inflammation associated with allergies and asthma. Recent studies have found that peripheral hematopoietic progenitor cells contribute to type 2 cytokine–mediated inflammation through their enhanced ability to develop into mast cells. In this study, we show that carbonic anhydrase (Car) enzymes are up-regulated in type 2–associated progenitor cells and demonstrate that Car enzyme inhibition is sufficient to prevent mouse mast cell responses and inflammation after Trichinella spiralis infection or the induction of food allergy–like disease. Further, we used CRISPR/Cas9 technology and illustrate that genetically editing Car1 is sufficient to selectively reduce mast cell development. Finally, we demonstrate that Car enzymes can be targeted to prevent human mast cell development. Collectively, these experiments identify a previously unrecognized role for Car enzymes in regulating mast cell lineage commitment and suggest that Car enzyme inhibitors may possess therapeutic potential that can be used to treat mast cell–mediated inflammation. PMID:27526715

Allelopathic interactions of linoleic acid and nitric oxide increase the competitive ability of Microcystis aeruginosa.

PubMed

Song, Hao; Lavoie, Michel; Fan, Xiaoji; Tan, Hana; Liu, Guangfu; Xu, Pengfei; Fu, Zhengwei; Paerl, Hans W; Qian, Haifeng

2017-08-01

The frequency and intensity of cyanobacterial blooms are increasing worldwide with major societal and economic costs. Interactions between toxic cyanobacteria and eukaryotic algal competitors can affect toxic bloom formation, but the exact mechanisms of interspecies interactions remain unknown. Using metabolomic and proteomic profiling of co-cultures of the toxic cyanobacterium Microcystis aeruginosa with a green alga as well as of microorganisms collected in a Microcystis spp. bloom in Lake Taihu (China), we disentangle novel interspecies allelopathic interactions. We describe an interspecies molecular network in which M. aeruginosa inhibits growth of Chlorella vulgaris, a model green algal competitor, via the release of linoleic acid. In addition, we demonstrate how M. aeruginosa takes advantage of the cell signaling compound nitric oxide produced by C. vulgaris, which stimulates a positive feedback mechanism of linoleic acid release by M. aeruginosa and its toxicity. Our high-throughput system-biology approach highlights the importance of previously unrecognized allelopathic interactions between a broadly distributed toxic cyanobacterial bloom former and one of its algal competitors.

Deep-sea vent chemoautotrophs: diversity, biochemistry and ecological significance.

PubMed

Nakagawa, Satoshi; Takai, Ken

2008-07-01

Deep-sea vents support productive ecosystems driven primarily by chemoautotrophs. Chemoautotrophs are organisms that are able to fix inorganic carbon using a chemical energy obtained through the oxidation of reduced compounds. Following the discovery of deep-sea vent ecosystems in 1977, there has been an increasing knowledge that deep-sea vent chemoautotrophs display remarkable physiological and phylogenetic diversity. Cultivation-dependent and -independent studies have led to an emerging view that the majority of deep-sea vent chemoautotrophs have the ability to derive energy from a variety of redox couples other than the conventional sulfur-oxygen couple, and fix inorganic carbon via the reductive tricarboxylic acid cycle. In addition, recent genomic, metagenomic and postgenomic studies have considerably accelerated the comprehensive understanding of molecular mechanisms of deep-sea vent chemoautotrophy, even in yet uncultivable endosymbionts of vent fauna. Genomic analysis also suggested that there are previously unrecognized evolutionary links between deep-sea vent chemoautotrophs and important human/animal pathogens. This review summarizes chemoautotrophy in deep-sea vents, highlighting recent biochemical and genomic discoveries.

Male songbirds provide indirect parental care by guarding females during incubation

USGS Publications Warehouse

Fedy, B.C.; Martin, T.E.

2009-01-01

Across many taxa, guarding of fertile mates is a widespread tactic that enhances paternity assurance. However, guarding of mates can also occur during the nonfertile period, and the fitness benefits of this behavior are unclear. Male songbirds, for example, sometimes guard nonfertile females during foraging recesses from incubation. We hypothesized that guarding postreproductive mates may have important, but unrecognized, benefits by enhancing female foraging efficiency, thereby increasing time spent incubating eggs. We tested the hypothesis in 2 songbird species by examining female behavior during natural and experimentally induced absences of males. Male absence caused increased vigilance in foraging females that decreased their efficiency and resulted in less time spent incubating eggs. Male guarding of nonfertile females can thus provide a previously unrecognized form of indirect parental care.

Xyleborus bispinatus reared on artificial media using sawdust from avocado or silkbay in presence or absence of the laurel wilt pathogen (Raffaelea lauricola)

USDA-ARS?s Scientific Manuscript database

Xyleborus bispinatus Eichhoff (Coleoptera: Curculionidae: Scolytinae) was reported in Florida for the first time in 2013. Previously, it was unrecognized and not distinguished from the morphologically similar Xyleborus ferrugineus (F.). Like other members of the tribe Xyleborini, X. ferrugineus (and...

Edge-Region Grouping in Figure-Ground Organization and Depth Perception

ERIC Educational Resources Information Center

Palmer, Stephen E.; Brooks, Joseph L.

2008-01-01

Edge-region grouping (ERG) is proposed as a unifying and previously unrecognized class of relational information that influences figure-ground organization and perceived depth across an edge. ERG occurs when the edge between two regions is differentially grouped with one region based on classic principles of similarity grouping. The ERG hypothesis…

Neurodevelopment and Chronic Illness: Mechanisms of Disease and Treatment

ERIC Educational Resources Information Center

Armstrong, F. Daniel

2006-01-01

Successful treatment of many childhood diseases once considered terminal has resulted in the emergence of long-term effects of the disease or consequences of treatment that were previously unrecognized. Many of these long-term effects involve the central nervous system (CNS) and are developmental in the way that they emerge over time. Because we…

New Hepatitis E Virus Genotype in Camels, the Middle East

PubMed Central

Lau, Susanna K.P.; Teng, Jade L.L.; Tsang, Alan K. L.; Joseph, Marina; Wong, Emily Y.M.; Tang, Ying; Sivakumar, Saritha; Xie, Jun; Bai, Ru; Wernery, Renate; Wernery, Ulrich; Yuen, Kwok-Yung

2014-01-01

In a molecular epidemiology study of hepatitis E virus (HEV) in dromedaries in Dubai, United Arab Emirates, HEV was detected in fecal samples from 3 camels. Complete genome sequencing of 2 strains showed >20% overall nucleotide difference to known HEVs. Comparative genomic and phylogenetic analyses revealed a previously unrecognized HEV genotype. PMID:24856611

Fatal Metacestode Infection in Bornean Orangutan Caused by Unknown Versteria Species

PubMed Central

Gendron-Fitzpatrick, Annette; Deering, Kathleen M.; Wallace, Roberta S.; Clyde, Victoria L.; Lauck, Michael; Rosen, Gail E.; Bennett, Andrew J.; Greiner, Ellis C.; O’Connor, David H.

2014-01-01

A captive juvenile Bornean orangutan (Pongo pygmaeus) died from an unknown disseminated parasitic infection. Deep sequencing of DNA from infected tissues, followed by gene-specific PCR and sequencing, revealed a divergent species within the newly proposed genus Versteria (Cestoda: Taeniidae). Versteria may represent a previously unrecognized risk to primate health. PMID:24377497

Erythema after laser skin resurfacing.

PubMed

Ruiz-Esparza, J; Barba Gomez, J M; Gomez de la Torre, O L; David, L

1998-01-01

Erythema after laser skin resurfacing is seen by many as a necessary evil in order to get good results from the procedure. A critical review of widely accepted concepts may lead to diminishing the length of postoperative erythema in patients undergoing laser resurfacing. The authors report on two previously unrecognized factors in the causation of this problem.

Community-acquired adult Escherichia coli meningitis leading to diagnosis of unrecognized retropharyngeal abscess and cervical spondylodiscitis: a case report.

PubMed

Kohlmann, Rebekka; Nefedev, Andrey; Kaase, Martin; Gatermann, Sören G

2015-12-12

Escherichia coli is a rare cause of community-acquired meningitis in adults unless predisposing factors are present (e.g., previous penetrating cranio-cerebral injury or neurosurgery, immunosuppression, chronic alcoholism, history of cancer, diabetes mellitus, advanced age). We describe the case of a 53-year-old woman, resident in Germany, suffering from community-acquired bacterial meningitis caused by CTX-M-9 type extended spectrum β-lactamase producing Escherichia coli. Because typical predisposing factors were not apparent, pathogen identification resulted in expanded diagnostics to exclude a distant or contiguous primary focus. By magnetic resonance tomography, a previously unrecognized large retropharyngeal abscess with cervical spondylodiscitis was detected. In retrospect, the patient had complained about neck pain for a few weeks prior to meningitis onset, but the symptoms were interpreted as being related to a herniated disk. Meningitis and osteomyelitis resolved completely under surgical treatment and meropenem therapy. In case of adult Escherichia coli meningitis, underlying diseases should always be carefully excluded, especially if predisposing factors are not apparent.

Isolation of carbohydrate-metabolizing, extremely halophilic bacteria.

NASA Technical Reports Server (NTRS)

Tomlinson, G. A.; Hochstein, L. I.

1972-01-01

Four previously unrecognized strains of extremely halophilic bacteria that utilize carbohydrates have been isolated. Gas production proved an unreliable index of carbohydrate metabolism; therefore, carbohydrate utilization was measured by determining acid formation and sugar disappearance during growth. By these procedures, carbohydrate utilization was readily detected. The results suggest that carbohydrate dissimilation by extremely halophilic bacteria may be more common than previously thought and that the apparent rarity of carbohydrate-metabolizing halophiles may be an artifact of the isolation procedures used.

Miscellaneous neurologic or neuromuscular disorders in horses.

PubMed

Aleman, Monica

2011-12-01

NMD is an important cause of morbidity in horses. Signs of dysfunction could be variable depending on the specific area affected. NM disease can go unrecognized if a thorough evaluation is not performed in diseased horses. Electrodiagnostic testing is an area that has the potential to document and improve our understanding of NM disease yet is uncommonly performed. Keeping an open and observant mind will enhance our ability to search and find answers.

Myeloproliferative neoplasms in five multiple sclerosis patients☆

PubMed Central

Thorsteinsdottir, Sigrun; Bjerrum, Ole Weis; Hasselbalch, Hans Carl

2013-01-01

The concurrence of myeloproliferative neoplasms (MPNs) and multiple sclerosis (MS) is unusual. We report five patients from a localized geographic area in Denmark with both MS and MPN; all the patients were diagnosed with MPNs in the years 2007–2012. We describe the patients' history and treatment. A potential link between MS and MPNs has not been previously recognized. This observation calls attention to potential environmental factors and/or previously unrecognized genetic factors predisposing these patients to both MS and MPNs. PMID:24371783

Small and large vessel disease in persons with unrecognized compared to recognized myocardial infarction: The Tromsø Study 2007-2008.

PubMed

Øhrn, Andrea Milde; Schirmer, Henrik; von Hanno, Therese; Mathiesen, Ellisiv B; Arntzen, Kjell Arne; Bertelsen, Geir; Njølstad, Inger; Løchen, Maja-Lisa; Wilsgaard, Tom; Bairey Merz, C Noel; Lindekleiv, Haakon

2018-02-15

Unrecognized myocardial infarction (MI) is a frequent condition with unknown underlying reason. We hypothesized the lack of recognition of MI is related to pathophysiology, specifically differences in underlying small and large vessel disease. 6128 participants were examined with retinal photography, ultrasound of the carotid artery and a 12‑lead electrocardiography (ECG). Small vessel disease was defined as narrower retinal arterioles and/or wider retinal venules measured on retinal photographs. Large vessel disease was defined as carotid artery pathology. We defined unrecognized MI as ECG-evidence of MI without a clinically recognized event. We analyzed the cross-sectional relationship between MI recognition and markers of small and large vessel disease, adjusted for age and sex. Unrecognized MI was present in 502 (8.2%) and recognized MI in 326 (5.3%) of the 6128 participants. Compared to recognized MI, unrecognized MI was associated with small vessel disease indicated by narrower retinal arterioles (OR 1.66, 95% CI 1.05-2.62, highest vs. lowest quartile). Unrecognized MI was less associated with wider retinal venules (OR 0.55, 95% CI 0.35-0.87, lowest vs. highest quartile). Compared to recognized MI, unrecognized MI was less associated with large vessel disease indicated by presence of plaque in the carotid artery (OR for presence of carotid artery plaque in unrecognized MI 0.51, 95% CI 0.37-0.69). No significant sex interaction was present. Unrecognized MI was more associated with small vessel disease and less associated with large vessel disease compared to recognized MI. These findings suggest that the pathophysiology behind unrecognized and recognized MI may differ. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Xyleborus bispinatus (Coleoptera: Curculionidae) reared on artificial media using sawdust from avocado or silkbay in presence or absence of the laurel wilt pathogen (Raffaelea lauricola).

USDA-ARS?s Scientific Manuscript database

Xyleborus bispinatus Eichhoff (Coleoptera: Curculionidae) was reported in Florida for the first time in 2013. Previously, it was unrecognized and not distinguished from the morphologically similar Xyleborus ferrugineus (F.). Like other members of the tribe Xyleborini, X. ferrugineus (and possibly X....

Consistent negative temperature sensitivity and positive influence of precipitation on growth of floodplain Picea glauca in Interior Alaska

Treesearch

Glenn Patrick Juday; Claire. Alix

2012-01-01

This paper calibrates climate controls over radial growth of floodplain white spruce (Picea glauca (Moench) Voss) and examines whether growth in these populations responds similarly to climate as upland trees in Interior Alaska. Floodplain white spruce trees hold previously unrecognized potential for long-term climate reconstruction because they...

Using a Critical Reflection Framework and Collaborative Inquiry to Improve Teaching Practice: An Action Research Project

ERIC Educational Resources Information Center

Briscoe, Patricia

2017-01-01

This action research reports on a three-year collaborative learning process among three teachers. We used current literature and a critical reflection framework to understand why our teaching approaches were not resulting in increased student learning. This allowed us to examine our previously unrecognized and uninterrupted--and often,…

Hymenolepis folkertsi n. sp. (Eucestoda: Hymenolepididae) in the oldfield mouse Peromyscus polionotus from the southeastern Nearctic with comments on tapeworm faunal diversity among deer mice

USDA-ARS?s Scientific Manuscript database

A previously unrecognized species of hymenolepidid cestode attributable to Hymenolepis Weinland, 1858 is described based on specimens in Peromyscus polionotus, oldfield mouse, from Georgia near the southeastern coast of continental North America. Specimens of Hymenolepis folkertsi n. sp. differ from...

Prevalence of diabetes and unrecognized diabetes in hypertensive patients aged 40 to 79 years in southwest China

PubMed Central

Liu, Ya; Hu, Rong; Ouyang, Ling-yun; Liu, Jian-xiong; Li, Xiu-jun; Yi, Yan-jing; Wang, Tzung-Dau; Zhao, Shui-ping

2017-01-01

This study aimed to assess the prevalence of diabetes and unrecognized diabetes in hypertensive patients aged 40 to 79 years in Southwest China. From September 2013 to March 2014, a cross-sectional survey was conducted in 4021 hypertensive patients aged 40 to 79 years living in Chengdu and Chongqing, China. Fasting plasma glucose (FPG) and 2h plasma glucose (2-hPG) in an oral glucose-tolerance test (OGTT) were used for assessments. Whether the patients previously had diabetes (DM) was determined by their own reports. The survey was carried out by the same questionnaire for all respondents. DM prevalence was 32.0% in hypertensive patients aged 40 to 79 years in Southwest China, with the rates of 29.6% and 33.5% in men and women, respectively (P<0.001). DM prevalence increased with age age and body-mass index. DM prevalence rates were 16.9%, 24.7%, 38.2% and 41.9% in hypertensive patients aged 40–49, 50–59, 60–69 and over 70, respectively. DM prevalence were 30.6%, 27.9%, 37.1%, and 37.4%, for BMI<18.5, 18.5–24.9, 25.0–29.9, and ≥30, respectively. Prevalence of unrecognized DM were 20.8% in hypertensive patients aged 40 to 79 years in Southwest China. Using only fasting blood glucose testing without OGTT would have resulted in 65.0% of missed DM diagnosis in these newly diagnosed patients. The prevalence of DM and unrecognized DM were high in hypertensive patients aged 40 to 79 years in Southwest China.These findings indicate that hypertensive patients aged 40 to 79 years should regularly submit to community-based OGTT screening for timely DM diagnosis. PMID:28192474

Transport and collision dynamics in periodic asymmetric obstacle arrays: Rational design of microfluidic rare-cell immunocapture devices

NASA Astrophysics Data System (ADS)

Gleghorn, Jason P.; Smith, James P.; Kirby, Brian J.

2013-09-01

Microfluidic obstacle arrays have been used in numerous applications, and their ability to sort particles or capture rare cells from complex samples has broad and impactful applications in biology and medicine. We have investigated the transport and collision dynamics of particles in periodic obstacle arrays to guide the design of convective, rather than diffusive, transport-based immunocapture microdevices. Ballistic and full computational fluid dynamics simulations are used to understand the collision modes that evolve in cylindrical obstacle arrays with various geometries. We identify previously unrecognized collision mode structures and differential size-based collision frequencies that emerge from these arrays. Previous descriptions of transverse displacements that assume unidirectional flow in these obstacle arrays cannot capture mode transitions properly as these descriptions fail to capture the dependence of the mode transitions on column spacing and the attendant change in the flow field. Using these analytical and computational simulations, we elucidate design parameters that induce high collision rates for all particles larger than a threshold size or selectively increase collision frequencies for a narrow range of particle sizes within a polydisperse population. Furthermore, we investigate how the particle Péclet number affects collision dynamics and mode transitions and demonstrate that experimental observations from various obstacle array geometries are well described by our computational model.

Timing is everything

PubMed Central

Carr, Heather S; Frost, Jeffrey A

2013-01-01

Cell adhesion to the extracellular matrix elicits a temporal reorganization of the actin cytoskeleton that is regulated first by Rac1 and later by RhoA. The signaling mechanisms controlling late stage RhoA activation are incompletely understood. Net1A is a RhoA/RhoB-specific guanine nucleotide exchange factor that is required for cancer cell motility. The ability of Net1A to stimulate RhoA activation is negatively regulated by nuclear sequestration. However, mechanisms controlling the plasma membrane localization of Net1A had not previously been reported. Recently we have shown that Rac1 activation stimulates plasma membrane relocalization and activation of Net1A. Net1A relocalization is independent of its catalytic activity and does not require its C-terminal pleckstrin homology or PDZ interacting domains. Rac1 activation during cell adhesion stimulates a transient relocalization of Net1A that is terminated by proteasomal degradation of Net1A. Importantly, plasma membrane localization of Net1A is required for efficient myosin light chain phosphorylation, focal adhesion maturation, and cell spreading. These data show for the first time a physiological mechanism controlling Net1A relocalization from the nucleus. They also demonstrate a previously unrecognized role for Net1A in controlling actomyosin contractility and focal adhesion dynamics during cell adhesion. PMID:23792411

New technologies, human-microbe interactions, and the search for previously unrecognized pathogens.

PubMed

Relman, David A

2002-12-01

Evidence suggests that a significant number of clinically important microbial pathogens remain unrecognized. Observations from the natural world, from patterns of disease in human populations, from the bedside, and from the clinical laboratory all contribute to this body of evidence. A variety of acute and chronic neurologic syndromes illustrate this point; despite features of infection, most cases of aseptic meningitis, encephalitis, and cerebral vasculitis cannot be assigned a microbiologic diagnosis. The development and clinical application of molecular methods have led to the discovery of novel members of the endogenous normal flora as well as putative disease agents. Current challenges include the establishment of criteria for disease causation and further characterization of the human microbiome during states of health. These challenges and the goal of understanding microbial contributions to inflammatory disease may be addressed effectively through the thoughtful integration of modern technologies and clinical insight.

Hypertension among Oral Contraceptive Users in El Paso, Texas

PubMed Central

White, Kari; Potter, Joseph E.; Hopkins, Kristine; Amastae, Jon; Grossman, Daniel

2015-01-01

On the U.S.-Mexico border, residents frequently cross into Mexico to obtain medications or medical care. We previously reported relatively high prevalence of hypertension among Latina oral contraceptive users in El Paso, particularly those obtaining pills over the counter (OTC) in Mexico. Here, we examine factors associated with having hypertension among 411 OTC users and 399 clinic users. We also assess hypertension awareness and interest in using blood pressure kiosks. Women age 35 to 44 and who had BMI ≥ 30 kg/m2 had higher odds of having hypertension. 59% of hypertensive women had unrecognized hypertension, and 77% of all participants would use a blood pressure kiosk; there were no significant differences between clinic and OTC users. Alternative approaches to increase access to health screenings are needed in this setting, where OTC pill use among women with unrecognized hypertension confers unique health risks. PMID:24185148

Shifting from Implicit to Explicit Knowledge: Different Roles of Early- and Late-Night Sleep

ERIC Educational Resources Information Center

Yordanova, Juliana; Kolev, Vasil; Verleger, Rolf; Bataghva, Zhamak; Born, Jan; Wagner, Ullrich

2008-01-01

Sleep has been shown to promote the generation of explicit knowledge as indicated by the gain of insight into previously unrecognized task regularities. Here, we explored whether this generation of explicit knowledge depends on pre-sleep implicit knowledge, and specified the differential roles of slow-wave sleep (SWS) vs. rapid eye movement (REM)…

γδ T cells recognize a microbial encoded B cell antigen to initiate a rapid antigen specific Interleukin 17 response

PubMed Central

Zeng, Xun; Wei, Yu-ling; Huang, Jun; Newell, Evan W.; Yu, Hongxiang; Kidd, Brian A.; Kuhns, Michael S.; Waters, Ray W.; Davis, Mark M.; Weaver, Casey T.; Chien, Yueh-hsiu

2012-01-01

Summary γδ T cells contribute uniquely to host immune defense. However, how they function remains an enigma. Although it is unclear what most γδ T cells recognize, common dogma asserts that they recognize self-antigens. While they are the major initial Interleukin-17 (IL-17) producers in infections, it is unclear what is required to trigger these cells to act. Here, we report that a noted B cell antigen, the algae protein-phycoerythrin (PE) is an antigen for murine and human γδ T cells. PE also stained specific bovine γδ T cells. Employing this specificity, we demonstrated that antigen recognition, but not extensive clonal expansion, was required to activate naïve γδ T cells to make IL-17. In this activated state, γδ T cells gained the ability to respond to cytokine signals that perpetuated the IL-17 production. These results underscore the adaptability of lymphocyte antigen receptors and suggest a previously unrecognized antigen-driven rapid response in protective immunity prior to the maturation of classical adaptive immunity. PMID:22960222

Allelopathic interactions of linoleic acid and nitric oxide increase the competitive ability of Microcystis aeruginosa

PubMed Central

Song, Hao; Lavoie, Michel; Fan, Xiaoji; Tan, Hana; Liu, Guangfu; Xu, Pengfei; Fu, Zhengwei; Paerl, Hans W; Qian, Haifeng

2017-01-01

The frequency and intensity of cyanobacterial blooms are increasing worldwide with major societal and economic costs. Interactions between toxic cyanobacteria and eukaryotic algal competitors can affect toxic bloom formation, but the exact mechanisms of interspecies interactions remain unknown. Using metabolomic and proteomic profiling of co-cultures of the toxic cyanobacterium Microcystis aeruginosa with a green alga as well as of microorganisms collected in a Microcystis spp. bloom in Lake Taihu (China), we disentangle novel interspecies allelopathic interactions. We describe an interspecies molecular network in which M. aeruginosa inhibits growth of Chlorella vulgaris, a model green algal competitor, via the release of linoleic acid. In addition, we demonstrate how M. aeruginosa takes advantage of the cell signaling compound nitric oxide produced by C. vulgaris, which stimulates a positive feedback mechanism of linoleic acid release by M. aeruginosa and its toxicity. Our high-throughput system-biology approach highlights the importance of previously unrecognized allelopathic interactions between a broadly distributed toxic cyanobacterial bloom former and one of its algal competitors. PMID:28398349

Sp5 induces the expression of Nanog to maintain mouse embryonic stem cell self-renewal.

PubMed

Tang, Ling; Wang, Manman; Liu, Dahai; Gong, Mengting; Ying, Qi-Long; Ye, Shoudong

2017-01-01

Activation of signal transducer and activator of transcription 3 (STAT3) by leukemia inhibitory factor (LIF) maintains mouse embryonic stem cell (mESC) self-renewal. Our previous study showed that trans-acting transcription factor 5 (Sp5), an LIF/STAT3 downstream target, supports mESC self-renewal. However, the mechanism by which Sp5 exerts these effects remains elusive. Here, we found that Nanog is a direct target of Sp5 and mediates the self-renewal-promoting effect of Sp5 in mESCs. Overexpression of Sp5 induced Nanog expression, while knockdown or knockout of Sp5 decreased the Nanog level. Moreover, chromatin immunoprecipitation (ChIP) assays showed that Sp5 directly bound to the Nanog promoter. Functional studies revealed that knockdown of Nanog eliminated the mESC self-renewal-promoting ability of Sp5. Finally, we demonstrated that the self-renewal-promoting function of Sp5 was largely dependent on its zinc finger domains. Taken together, our study provides unrecognized functions of Sp5 in mESCs and will expand our current understanding of the regulation of mESC pluripotency.

Sialylated multivalent antigens engage CD22 in trans and inhibit B cell activation.

PubMed

Courtney, Adam H; Puffer, Erik B; Pontrello, Jason K; Yang, Zhi-Qiang; Kiessling, Laura L

2009-02-24

CD22 is an inhibitory coreceptor on the surface of B cells that attenuates B cell antigen receptor (BCR) signaling and, therefore, B cell activation. Elucidating the molecular mechanisms underlying the inhibitory activity of CD22 is complicated by the ubiquity of CD22 ligands. Although antigens can display CD22 ligands, the receptor is known to bind to sialylated glycoproteins on the cell surface. The propinquity of CD22 and cell-surface glycoprotein ligands has led to the conclusion that the inhibitory properties of the receptor are due to cis interactions. Here, we examine the functional consequences of trans interactions by employing sialylated multivalent antigens that can engage both CD22 and the BCR. Exposure of B cells to sialylated antigens results in the inhibition of key steps in BCR signaling. These results reveal that antigens bearing CD22 ligands are powerful suppressors of B cell activation. The ability of sialylated antigens to inhibit BCR signaling through trans CD22 interactions reveals a previously unrecognized role for the Siglec-family of receptors as modulators of immune signaling.

Biotic homogenization can decrease landscape-scale forest multifunctionality.

PubMed

van der Plas, Fons; Manning, Pete; Soliveres, Santiago; Allan, Eric; Scherer-Lorenzen, Michael; Verheyen, Kris; Wirth, Christian; Zavala, Miguel A; Ampoorter, Evy; Baeten, Lander; Barbaro, Luc; Bauhus, Jürgen; Benavides, Raquel; Benneter, Adam; Bonal, Damien; Bouriaud, Olivier; Bruelheide, Helge; Bussotti, Filippo; Carnol, Monique; Castagneyrol, Bastien; Charbonnier, Yohan; Coomes, David Anthony; Coppi, Andrea; Bastias, Cristina C; Dawud, Seid Muhie; De Wandeler, Hans; Domisch, Timo; Finér, Leena; Gessler, Arthur; Granier, André; Grossiord, Charlotte; Guyot, Virginie; Hättenschwiler, Stephan; Jactel, Hervé; Jaroszewicz, Bogdan; Joly, François-Xavier; Jucker, Tommaso; Koricheva, Julia; Milligan, Harriet; Mueller, Sandra; Muys, Bart; Nguyen, Diem; Pollastrini, Martina; Ratcliffe, Sophia; Raulund-Rasmussen, Karsten; Selvi, Federico; Stenlid, Jan; Valladares, Fernando; Vesterdal, Lars; Zielínski, Dawid; Fischer, Markus

2016-03-29

Many experiments have shown that local biodiversity loss impairs the ability of ecosystems to maintain multiple ecosystem functions at high levels (multifunctionality). In contrast, the role of biodiversity in driving ecosystem multifunctionality at landscape scales remains unresolved. We used a comprehensive pan-European dataset, including 16 ecosystem functions measured in 209 forest plots across six European countries, and performed simulations to investigate how local plot-scale richness of tree species (α-diversity) and their turnover between plots (β-diversity) are related to landscape-scale multifunctionality. After accounting for variation in environmental conditions, we found that relationships between α-diversity and landscape-scale multifunctionality varied from positive to negative depending on the multifunctionality metric used. In contrast, when significant, relationships between β-diversity and landscape-scale multifunctionality were always positive, because a high spatial turnover in species composition was closely related to a high spatial turnover in functions that were supported at high levels. Our findings have major implications for forest management and indicate that biotic homogenization can have previously unrecognized and negative consequences for large-scale ecosystem multifunctionality.

Biotic homogenization can decrease landscape-scale forest multifunctionality

PubMed Central

van der Plas, Fons; Manning, Pete; Soliveres, Santiago; Allan, Eric; Scherer-Lorenzen, Michael; Verheyen, Kris; Wirth, Christian; Zavala, Miguel A.; Ampoorter, Evy; Baeten, Lander; Barbaro, Luc; Bauhus, Jürgen; Benavides, Raquel; Benneter, Adam; Bonal, Damien; Bouriaud, Olivier; Bruelheide, Helge; Bussotti, Filippo; Carnol, Monique; Castagneyrol, Bastien; Charbonnier, Yohan; Coppi, Andrea; Bastias, Cristina C.; Dawud, Seid Muhie; De Wandeler, Hans; Domisch, Timo; Finér, Leena; Granier, André; Grossiord, Charlotte; Guyot, Virginie; Hättenschwiler, Stephan; Jactel, Hervé; Jaroszewicz, Bogdan; Joly, François-xavier; Jucker, Tommaso; Koricheva, Julia; Milligan, Harriet; Mueller, Sandra; Muys, Bart; Nguyen, Diem; Pollastrini, Martina; Ratcliffe, Sophia; Raulund-Rasmussen, Karsten; Selvi, Federico; Stenlid, Jan; Valladares, Fernando; Vesterdal, Lars; Zielínski, Dawid; Fischer, Markus

2016-01-01

Many experiments have shown that local biodiversity loss impairs the ability of ecosystems to maintain multiple ecosystem functions at high levels (multifunctionality). In contrast, the role of biodiversity in driving ecosystem multifunctionality at landscape scales remains unresolved. We used a comprehensive pan-European dataset, including 16 ecosystem functions measured in 209 forest plots across six European countries, and performed simulations to investigate how local plot-scale richness of tree species (α-diversity) and their turnover between plots (β-diversity) are related to landscape-scale multifunctionality. After accounting for variation in environmental conditions, we found that relationships between α-diversity and landscape-scale multifunctionality varied from positive to negative depending on the multifunctionality metric used. In contrast, when significant, relationships between β-diversity and landscape-scale multifunctionality were always positive, because a high spatial turnover in species composition was closely related to a high spatial turnover in functions that were supported at high levels. Our findings have major implications for forest management and indicate that biotic homogenization can have previously unrecognized and negative consequences for large-scale ecosystem multifunctionality. PMID:26979952

Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes.

PubMed

Markstein, Michele; Pitsouli, Chrysoula; Villalta, Christians; Celniker, Susan E; Perrimon, Norbert

2008-04-01

A major obstacle to creating precisely expressed transgenes lies in the epigenetic effects of the host chromatin that surrounds them. Here we present a strategy to overcome this problem, employing a Gal4-inducible luciferase assay to systematically quantify position effects of host chromatin and the ability of insulators to counteract these effects at phiC31 integration loci randomly distributed throughout the Drosophila genome. We identify loci that can be exploited to deliver precise doses of transgene expression to specific tissues. Moreover, we uncover a previously unrecognized property of the gypsy retrovirus insulator to boost gene expression to levels severalfold greater than at most or possibly all un-insulated loci, in every tissue tested. These findings provide the first opportunity to create a battery of transgenes that can be reliably expressed at high levels in virtually any tissue by integration at a single locus, and conversely, to engineer a controlled phenotypic allelic series by exploiting several loci. The generality of our approach makes it adaptable to other model systems to identify and modify loci for optimal transgene expression.

Discovery of Novel Nonactive Site Inhibitors of the Prothrombinase Enzyme Complex.

PubMed

Kapoor, Karan; McGill, Nicole; Peterson, Cynthia B; Meyers, Harold V; Blackburn, Michael N; Baudry, Jerome

2016-03-28

The risk of serious bleeding is a major liability of anticoagulant drugs that are active-site competitive inhibitors targeting the Factor Xa (FXa) prothrombin (PT) binding site. The present work identifies several new classes of small molecule anticoagulants that can act as nonactive site inhibitors of the prothrombinase (PTase) complex composed of FXa and Factor Va (FVa). These new classes of anticoagulants were identified, using a novel agnostic computational approach to identify previously unrecognized binding pockets at the FXa-FVa interface. From about three million docking calculations of 281,128 compounds in a conformational ensemble of FXa heavy chains identified by molecular dynamics (MD) simulations, 97 compounds and their structural analogues were selected for experimental validation, through a series of inhibition assays. The compound selection was based on their predicted binding affinities to FXa and their ability to successfully bind to multiple protein conformations while showing selectivity for particular binding sites at the FXa/FVa interface. From these, thirty-one (31) compounds were experimentally identified as nonactive site inhibitors. Concentration-based assays further identified 10 compounds represented by four small-molecule families of inhibitors that achieve dose-independent partial inhibition of PTase activity in a nonactive site-dependent and self-limiting mechanism. Several compounds were identified for their ability to bind to protein conformations only seen during MD, highlighting the importance of accounting for protein flexibility in structure-based drug discovery approaches.

A new worm infiltrating the human cornea: A report of three cases.

PubMed

McBurney-Lin, Shan; Khorram, David; Gee, Stephen; Hoberg, Eric P; Klassen-Fischer, Mary K; Neafie, Ronald C

2018-03-01

To characterize a new species of parasitic nematode that triggers uveitis. Three previously healthy, relatively young people each contracted a corneal stromal nematode that, upon surgical removal and examination, did not match any known nematodes. Clinical ocular findings included corneal opacification, visible corneal worms, conjunctival injection, and uveitis. The three cases presented here represent a previously undescribed parasitic infection of the cornea by an unidentified nematode. These findings may represent a previously unrecognized zoonotic infection from wildlife sources and potentially a newly documented nematode requiring description. Future clinical findings regarding this newly described nematode are needed to further develop our understanding of the disease.

Whole-genome sequencing of genotype VI Newcastle disease viruses from formalin-fixed paraffin-embedded tissues from wild pigeons reveals continuous evolution and previously unrecognized genetic diversity in the U.S.

USDA-ARS?s Scientific Manuscript database

Background: Newcastle disease viruses (NDV) are highly contagious and cause disease in both wild birds and poultry. A pigeon-adapted variant of genotype VI NDV, often termed pigeon paramyxovirus 1, is commonly isolated from columbids in the United States and worldwide. Complete genomic characterizat...

Neuro-Immune Mechanisms in Response to Venezuelan equine encephalitis Virus Infection

DTIC Science & Technology

2000-05-01

horses . They were subsequently shown to be previously unrecognized viral agents of severe equine encephalitis (Smith et al., 1997). One member of...iii ABSTRACT NEURO-IMMUNE MECHANISMS IN RESPONSE TO VENEZUELAN EQUINE ENCEPHALITIS VIRUS INFECTION Major Bruce A. Schoneboom directed by Franziska B...Grieder, DVM, Ph.D., Assistant Professor of Microbiology and Immunology, Molecular and Cellular Biology, and Neuroscience Venezuelan equine

26 CFR 1.860A-0 - Outline of REMIC provisions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... foreign persons. § 1.860C-2Determination of REMIC taxable income or net loss. (a) Treatment of gain or... gain or loss. (3) Basis of contributed assets allocated among interests. (i) In general. (ii...) Treatment of unrecognized gain or loss. (i) Unrecognized gain on regular interests. (ii) Unrecognized loss...

26 CFR 1.1092(b)-5T - Definitions (temporary).

Code of Federal Regulations, 2010 CFR

2010-04-01

... defined in sections 1092(d)(4) (B) and (C) respectively. (k) Section 1256 contract. The term section 1256... referred to in paragraph (n)(1) of this section. (o) Unrecognized gain. The term unrecognized gain means unrecognized gain as defined in section 1092(a)(3)(A). (p) Substantially identical. The term substantially...

26 CFR 1.1092(b)-5T - Definitions (temporary).

Code of Federal Regulations, 2012 CFR

2012-04-01

... defined in sections 1092(d)(4) (B) and (C) respectively. (k) Section 1256 contract. The term section 1256... referred to in paragraph (n)(1) of this section. (o) Unrecognized gain. The term unrecognized gain means unrecognized gain as defined in section 1092(a)(3)(A). (p) Substantially identical. The term substantially...

26 CFR 1.1092(b)-5T - Definitions (temporary).

Code of Federal Regulations, 2014 CFR

2014-04-01

... defined in sections 1092(d)(4) (B) and (C) respectively. (k) Section 1256 contract. The term section 1256... referred to in paragraph (n)(1) of this section. (o) Unrecognized gain. The term unrecognized gain means unrecognized gain as defined in section 1092(a)(3)(A). (p) Substantially identical. The term substantially...

26 CFR 1.1092(b)-5T - Definitions (temporary).

Code of Federal Regulations, 2013 CFR

2013-04-01

... defined in sections 1092(d)(4) (B) and (C) respectively. (k) Section 1256 contract. The term section 1256... referred to in paragraph (n)(1) of this section. (o) Unrecognized gain. The term unrecognized gain means unrecognized gain as defined in section 1092(a)(3)(A). (p) Substantially identical. The term substantially...

26 CFR 1.1092(b)-5T - Definitions (temporary).

Code of Federal Regulations, 2011 CFR

2011-04-01

... defined in sections 1092(d)(4) (B) and (C) respectively. (k) Section 1256 contract. The term section 1256... referred to in paragraph (n)(1) of this section. (o) Unrecognized gain. The term unrecognized gain means unrecognized gain as defined in section 1092(a)(3)(A). (p) Substantially identical. The term substantially...

Viscotaxis: Microswimmer Navigation in Viscosity Gradients

NASA Astrophysics Data System (ADS)

Liebchen, Benno; Monderkamp, Paul; ten Hagen, Borge; Löwen, Hartmut

2018-05-01

The survival of many microorganisms, like Leptospira or Spiroplasma bacteria, can depend on their ability to navigate towards regions of favorable viscosity. While this ability, called viscotaxis, has been observed in several bacterial experiments, the underlying mechanism remains unclear. We provide a framework to study viscotaxis of biological or synthetic self-propelled swimmers in slowly varying viscosity fields and show that suitable body shapes create viscotaxis based on a systematic asymmetry of viscous forces acting on a microswimmer. Our results shed new light on viscotaxis in Spiroplasma and Leptospira and suggest that dynamic body shape changes exhibited by both types of microorganisms may have an unrecognized functionality: to prevent them from drifting to low viscosity regions where they swim poorly. The present theory classifies microswimmers regarding their ability to show viscotaxis and can be used to design synthetic viscotactic swimmers, e.g., for delivering drugs to a target region distinguished by viscosity.

NCI Helps Children’s Hospital of Philadelphia to Identify and Treat New Target in Pediatric Cancer | Poster

Cancer.gov

There may be a new, more effective method for treating high-risk neuroblastoma, according to scientists at the Children’s Hospital of Philadelphia and collaborators in the Cancer and Inflammation Program at NCI at Frederick. Together, the groups published a study describing a previously unrecognized protein on neuroblastoma cells, called GPC2, as well as the creation of a

A Cluster of Legionella-Associated Pneumonia Cases in a Population of Military Recruits

DTIC Science & Technology

2007-06-01

this cluster may suggest a previously unrecognized suscep- FIG. 1. Phylogenic analysis of the training center strain (represented by the MCRD consensus...military recruits during population- based surveillance for pneumonia pathogens. Results were confirmed by sequence analysis . Cases cluster tightly...17 April 2007 A Legionella cluster was identified through retrospective PCR analysis of 240 throat swab samples from X-ray-confirmed pneumonia cases

Exploring the SDSS Dataset with Linked Scatter Plots: I. EMP, CEMP, and CV Stars

NASA Technical Reports Server (NTRS)

Carbon, Duane F.; Henze, Christopher; Nelson, Bron C.

2017-01-01

We present the results of a search for EMP, CEMP, and cataclysmic variable stars using a new exploration tool based on linked scatter plots (LSPs). Our approach is especially designed to work with very large spectrum data sets such as the SDSS, LAMOST, RAVE, and Gaia data sets and can be applied to stellar, galaxy, and quasar spectra. As a demonstration, we conduct a search for EMP, CEMP, and cataclysmic variable stars in the SDSS DR10 data set. We first created a 3326-dimensional phase space containing nearly 2 billion measures of the strengths of over 1600 spectral features in 569,738 SDSS stars. These measures capture essentially all the stellar atomic and molecular species visible at the resolution of SDSS spectra. We show how LSPs can be used to quickly isolate and examine interesting portions of this phase space. To illustrate, we use LSPs coupled with cuts in selected portions of phase space to extract EMP stars, C-rich EMP stars, and CV stars. We present identifications for 59 previously unrecognized candidate EMP stars and 11 previously unrecognized candidate CEMP stars. We also call attention to 2 candidate He II emission CV stars found by the LSP approach that have not yet been discussed in the literature.

Owls may use faeces and prey feathers to signal current reproduction.

PubMed

Penteriani, Vincenzo; Delgado, Maria del Mar

2008-08-20

Many animals communicate by marking focal elements of their home range with different kinds of materials. Visual signaling has been demonstrated to play a previously unrecognized role in the intraspecific communication of eagle owls (Bubo bubo), in both territorial and parent-offspring contexts. Visual signals may play a role in a variety of circumstances in this crepuscular and nocturnal species. Here, we report that a large amount of extremely visible white faeces and prey feathers appear during the breeding season on posts and plucking sites in proximity to the nest, potentially representing a way for eagle owls to mark their territory. We present descriptive and experimental evidence showing that faeces and prey remains could act as previously unrecognized visual signals in a nocturnal avian predator. This novel signaling behavior could indicate the owls' current reproductive status to potential intruders, such as other territorial owls or non-breeding floaters. Faeces and prey feather markings may also advertise an owl's reproductive status or function in mate-mate communication. We speculate that faeces marks and plucking may represent an overlooked but widespread method for communicating current reproduction to conspecifics. Such marking behavior may be common in birds, and we may now be exploring other questions and mechanisms in territoriality.

Exploring the SDSS Dataset with Linked Scatter Plots: I. EMP, CEMP, and CV Stars.

PubMed

Carbon, Duane F; Henze, Christopher; Nelson, Bron C

2017-02-01

We present the results of a search for EMP, CEMP, and cataclysmic variable stars using a new exploration tool based on linked scatter plots (LSPs). Our approach is especially designed to work with very large spectrum data sets such as the SDSS, LAMOST, RAVE, and Gaia data sets and can be applied to stellar, galaxy, and quasar spectra. As a demonstration, we conduct a search for EMP, CEMP, and cataclysmic variable stars in the SDSS DR10 data set. We first created a 3326-dimensional phase space containing nearly 2 billion measures of the strengths of over 1600 spectral features in 569,738 SDSS stars. These measures capture essentially all the stellar atomic and molecular species visible at the resolution of SDSS spectra. We show how LSPs can be used to quickly isolate and examine interesting portions of this phase space. To illustrate, we use LSPs coupled with cuts in selected portions of phase space to extract EMP stars, C-rich EMP stars, and CV stars. We present identifications for 59 previously unrecognized candidate EMP stars and 11 previously unrecognized candidate CEMP stars. We also call attention to 2 candidate He II emission CV stars found by the LSP approach that have not yet been discussed in the literature.

Owls May Use Faeces and Prey Feathers to Signal Current Reproduction

PubMed Central

Penteriani, Vincenzo; del Mar Delgado, Maria

2008-01-01

Background Many animals communicate by marking focal elements of their home range with different kinds of materials. Visual signaling has been demonstrated to play a previously unrecognized role in the intraspecific communication of eagle owls (Bubo bubo), in both territorial and parent-offspring contexts. Visual signals may play a role in a variety of circumstances in this crepuscular and nocturnal species. Methodology/Principal Findings Here, we report that a large amount of extremely visible white faeces and prey feathers appear during the breeding season on posts and plucking sites in proximity to the nest, potentially representing a way for eagle owls to mark their territory. We present descriptive and experimental evidence showing that faeces and prey remains could act as previously unrecognized visual signals in a nocturnal avian predator. This novel signaling behavior could indicate the owls' current reproductive status to potential intruders, such as other territorial owls or non-breeding floaters. Faeces and prey feather markings may also advertise an owl's reproductive status or function in mate-mate communication. Conclusions/Significance We speculate that faeces marks and plucking may represent an overlooked but widespread method for communicating current reproduction to conspecifics. Such marking behavior may be common in birds, and we may now be exploring other questions and mechanisms in territoriality. PMID:18714382

Exploring the SDSS Data Set with Linked Scatter Plots. I. EMP, CEMP, and CV Stars

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

Carbon, Duane F.; Henze, Christopher; Nelson, Bron C., E-mail: Duane.F.Carbon@nasa.gov

We present the results of a search for extremely metal-poor (EMP), carbon-enhanced metal-poor (CEMP), and cataclysmic variable (CV) stars using a new exploration tool based on linked scatter plots (LSPs). Our approach is especially designed to work with very large spectrum data sets such as the SDSS, LAMOST, RAVE, and Gaia data sets, and it can be applied to stellar, galaxy, and quasar spectra. As a demonstration, we conduct our search using the SDSS DR10 data set. We first created a 3326-dimensional phase space containing nearly 2 billion measures of the strengths of over 1600 spectral features in 569,738 SDSSmore » stars. These measures capture essentially all the stellar atomic and molecular species visible at the resolution of SDSS spectra. We show how LSPs can be used to quickly isolate and examine interesting portions of this phase space. To illustrate, we use LSPs coupled with cuts in selected portions of phase space to extract EMP stars, CEMP stars, and CV stars. We present identifications for 59 previously unrecognized candidate EMP stars and 11 previously unrecognized candidate CEMP stars. We also call attention to 2 candidate He ii emission CV stars found by the LSP approach that have not yet been discussed in the literature.« less

VizieR Online Data Catalog: Exploring the SDSS data set. I. EMP & CV stars (Carbon+, 2017)

NASA Astrophysics Data System (ADS)

Carbon, D. F.; Henze, C.; Nelson, B. C.

2017-08-01

We present the results of a search for extremely metal-poor (EMP), carbon-enhanced metal-poor (CEMP), and cataclysmic variable (CV) stars using a new exploration tool based on linked scatter plots (LSPs). Our approach is especially designed to work with very large spectrum data sets such as the SDSS, LAMOST, RAVE, and Gaia data sets, and it can be applied to stellar, galaxy, and quasar spectra. As a demonstration, we conduct our search using the SDSS DR10 data set. We first created a 3326-dimensional phase space containing nearly 2 billion measures of the strengths of over 1600 spectral features in 569738 SDSS stars. These measures capture essentially all the stellar atomic and molecular species visible at the resolution of SDSS spectra. We show how LSPs can be used to quickly isolate and examine interesting portions of this phase space. To illustrate, we use LSPs coupled with cuts in selected portions of phase space to extract EMP stars, CEMP stars, and CV stars. We present identifications for 59 previously unrecognized candidate EMP stars and 11 previously unrecognized candidate CEMP stars. We also call attention to 2 candidate He II emission CV stars found by the LSP approach that have not yet been discussed in the literature. (3 data files).

Exploring the SDSS Dataset with Linked Scatter Plots: I. EMP, CEMP, and CV Stars

PubMed Central

Carbon, Duane F.; Henze, Christopher; Nelson, Bron C.

2017-01-01

We present the results of a search for EMP, CEMP, and cataclysmic variable stars using a new exploration tool based on linked scatter plots (LSPs). Our approach is especially designed to work with very large spectrum data sets such as the SDSS, LAMOST, RAVE, and Gaia data sets and can be applied to stellar, galaxy, and quasar spectra. As a demonstration, we conduct a search for EMP, CEMP, and cataclysmic variable stars in the SDSS DR10 data set. We first created a 3326-dimensional phase space containing nearly 2 billion measures of the strengths of over 1600 spectral features in 569,738 SDSS stars. These measures capture essentially all the stellar atomic and molecular species visible at the resolution of SDSS spectra. We show how LSPs can be used to quickly isolate and examine interesting portions of this phase space. To illustrate, we use LSPs coupled with cuts in selected portions of phase space to extract EMP stars, C-rich EMP stars, and CV stars. We present identifications for 59 previously unrecognized candidate EMP stars and 11 previously unrecognized candidate CEMP stars. We also call attention to 2 candidate He II emission CV stars found by the LSP approach that have not yet been discussed in the literature. PMID:28684884

Exploring the SDSS Data Set with Linked Scatter Plots. I. EMP, CEMP, and CV Stars

NASA Astrophysics Data System (ADS)

Carbon, Duane F.; Henze, Christopher; Nelson, Bron C.

2017-02-01

We present the results of a search for extremely metal-poor (EMP), carbon-enhanced metal-poor (CEMP), and cataclysmic variable (CV) stars using a new exploration tool based on linked scatter plots (LSPs). Our approach is especially designed to work with very large spectrum data sets such as the SDSS, LAMOST, RAVE, and Gaia data sets, and it can be applied to stellar, galaxy, and quasar spectra. As a demonstration, we conduct our search using the SDSS DR10 data set. We first created a 3326-dimensional phase space containing nearly 2 billion measures of the strengths of over 1600 spectral features in 569,738 SDSS stars. These measures capture essentially all the stellar atomic and molecular species visible at the resolution of SDSS spectra. We show how LSPs can be used to quickly isolate and examine interesting portions of this phase space. To illustrate, we use LSPs coupled with cuts in selected portions of phase space to extract EMP stars, CEMP stars, and CV stars. We present identifications for 59 previously unrecognized candidate EMP stars and 11 previously unrecognized candidate CEMP stars. We also call attention to 2 candidate He II emission CV stars found by the LSP approach that have not yet been discussed in the literature.

Origin, antigenicity, and function of a secreted form of ORF2 in hepatitis E virus infection.

PubMed

Yin, Xin; Ying, Dong; Lhomme, Sébastien; Tang, Zimin; Walker, Christopher M; Xia, Ningshao; Zheng, Zizheng; Feng, Zongdi

2018-05-01

The enterically transmitted hepatitis E virus (HEV) adopts a unique strategy to exit cells by cloaking its capsid (encoded by the viral ORF2 gene) and circulating in the blood as "quasi-enveloped" particles. However, recent evidence suggests that the majority of the ORF2 protein present in the patient serum and supernatants of HEV-infected cell culture exists in a free form and is not associated with virus particles. The origin and biological functions of this secreted form of ORF2 (ORF2 S ) are unknown. Here we show that production of ORF2 S results from translation initiated at the previously presumed AUG start codon for the capsid protein, whereas translation of the actual capsid protein (ORF2 C ) is initiated at a previously unrecognized internal AUG codon (15 codons downstream of the first AUG). The addition of 15 amino acids to the N terminus of the capsid protein creates a signal sequence that drives ORF2 S secretion via the secretory pathway. Unlike ORF2 C , ORF2 S is glycosylated and exists as a dimer. Nonetheless, ORF2 S exhibits substantial antigenic overlap with the capsid, but the epitopes predicted to bind the putative cell receptor are lost. Consistent with this, ORF2 S does not block HEV cell entry but inhibits antibody-mediated neutralization. These results reveal a previously unrecognized aspect in HEV biology and shed new light on the immune evasion mechanisms and pathogenesis of this virus.

Timing is everything: Rac1 controls Net1A localization to regulate cell adhesion.

PubMed

Carr, Heather S; Frost, Jeffrey A

2013-01-01

Cell adhesion to the extracellular matrix elicits a temporal reorganization of the actin cytoskeleton that is regulated first by Rac1 and later by RhoA. The signaling mechanisms controlling late stage RhoA activation are incompletely understood. Net1A is a RhoA/RhoB-specific guanine nucleotide exchange factor that is required for cancer cell motility. The ability of Net1A to stimulate RhoA activation is negatively regulated by nuclear sequestration. However, mechanisms controlling the plasma membrane localization of Net1A had not previously been reported. Recently we have shown that Rac1 activation stimulates plasma membrane relocalization and activation of Net1A. Net1A relocalization is independent of its catalytic activity and does not require its C-terminal pleckstrin homology or PDZ interacting domains. Rac1 activation during cell adhesion stimulates a transient relocalization of Net1A that is terminated by proteasomal degradation of Net1A. Importantly, plasma membrane localization of Net1A is required for efficient myosin light chain phosphorylation, focal adhesion maturation, and cell spreading. These data show for the first time a physiological mechanism controlling Net1A relocalization from the nucleus. They also demonstrate a previously unrecognized role for Net1A in controlling actomyosin contractility and focal adhesion dynamics during cell adhesion.

Wall teichoic acids prevent antibody binding to epitopes within the cell wall of Staphylococcus aureus.

PubMed

Gautam, Samir; Kim, Taehan; Lester, Evan; Deep, Deeksha; Spiegel, David A

2016-01-15

Staphylococcus aureus is a Gram-positive bacterial pathogen that produces a range of infections including cellulitis, pneumonia, and septicemia. The principle mechanism in antistaphylococcal host defense is opsonization with antibodies and complement proteins, followed by phagocytic clearance. Here we use a previously developed technique for installing chemical epitopes in the peptidoglycan cell wall to show that surface glycopolymers known as wall teichoic acids conceal cell wall epitopes, preventing their recognition and opsonization by antibodies. Thus, our results reveal a previously unrecognized immunoevasive role for wall teichoic acids in S. aureus: repulsion of peptidoglycan-targeted antibodies.

Cathodoluminescent bimineralic ooids from the Pleistocene of the Florida continental shelf

USGS Publications Warehouse

Major, R. P.; Halley, Robert B.; Lukas, Karen J.

1988-01-01

  The ooid grainstone underwent an episode of meteoric diagenesis. but ooid cortices were not affected by the event. We propose a previously unrecognized process by which the magnesian calcite cortex layers underwent diagenetic alteration in oxygen-depleted seawater. During this diagenesis, magnesium was lost and manganese was incorporated without apparent textural alteration and without mineralogical stabilization. Thus, we Suggest that cathodoluminescence may result from diagenetic alteration on the sea-floor.

Turbulent shear spurs settlement in larval sea urchins

PubMed Central

Gaylord, Brian; Hodin, Jason; Ferner, Matthew C.

2013-01-01

Marine invertebrates commonly produce larvae that disperse in ocean waters before settling into adult shoreline habitat. Chemical and other seafloor-associated cues often facilitate this latter transition. However, the range of effectiveness of such cues is limited to small spatial scales, creating challenges for larvae in finding suitable sites at which to settle, especially given that they may be carried many kilometers by currents during their planktonic phase. One possible solution is for larvae to use additional, broader-scale environmental signposts to first narrow their search to the general vicinity of a candidate settlement location. Here we demonstrate strong effects of just such a habitat-scale cue, one with the potential to signal larvae that they have arrived in appropriate coastal areas. Larvae of the purple sea urchin (Strongylocentrotus purpuratus) exhibit dramatic enhancement in settlement following stimulation by turbulent shear typical of wave-swept shores where adults of this species live. This response manifests in an unprecedented fashion relative to previously identified cues. Turbulent shear does not boost settlement by itself. Instead, it drives a marked developmental acceleration that causes “precompetent” larvae refractory to chemical settlement inducers to immediately become “competent” and thereby reactive to such inducers. These findings reveal an unrecognized ability of larval invertebrates to shift the trajectory of a major life history event in response to fluid-dynamic attributes of a target environment. Such an ability may improve performance and survival in marine organisms by encouraging completion of their life cycle in advantageous locations. PMID:23572585

The Single-Nucleotide Resolution Transcriptome of Pseudomonas aeruginosa Grown in Body Temperature

PubMed Central

Dandekar, Ajai A.; Edelheit, Sarit; Greenberg, E. Peter; Sorek, Rotem; Lory, Stephen

2012-01-01

One of the hallmarks of opportunistic pathogens is their ability to adjust and respond to a wide range of environmental and host-associated conditions. The human pathogen Pseudomonas aeruginosa has an ability to thrive in a variety of hosts and cause a range of acute and chronic infections in individuals with impaired host defenses or cystic fibrosis. Here we report an in-depth transcriptional profiling of this organism when grown at host-related temperatures. Using RNA-seq of samples from P. aeruginosa grown at 28°C and 37°C we detected genes preferentially expressed at the body temperature of mammalian hosts, suggesting that they play a role during infection. These temperature-induced genes included the type III secretion system (T3SS) genes and effectors, as well as the genes responsible for phenazines biosynthesis. Using genome-wide transcription start site (TSS) mapping by RNA-seq we were able to accurately define the promoters and cis-acting RNA elements of many genes, and uncovered new genes and previously unrecognized non-coding RNAs directly controlled by the LasR quorum sensing regulator. Overall we identified 165 small RNAs and over 380 cis-antisense RNAs, some of which predicted to perform regulatory functions, and found that non-coding RNAs are preferentially localized in pathogenicity islands and horizontally transferred regions. Our work identifies regulatory features of P. aeruginosa genes whose products play a role in environmental adaption during infection and provides a reference transcriptional landscape for this pathogen. PMID:23028334

Microbiological, Geochemical and Hydrologic Processes Controlling Uranium Mobility: An Integrated Field Scale Subsurface Research Challenge Site at Rifle, Colorado, February 2011 to January 2012

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

Long, Philip E.; Banfield, Jill; Chandler, Darrell P.

The Rifle IFRC continued to make excellent progress during the last 12 months. As noted above, a key field experiment (Best Western) was performed during 2011 as a logical follow-on to the Super 8 field experiment preformed in 2010. In the Super 8 experiment, we successfully combined desorption and bioreduction and deployed a number of novel tracer techniques to enhance our ability to interpret the biogeochemistry of the experiment. In the Best Western experiment, we used the same experimental plot (Plot C) as was used for Super 8. The overarching objective of the Best Western field experiment was to comparedmore » the impacts of abiotic vs. biotic increases in alkalinity and to assess the mass of the sorbed pool of U(VI) at Rifle at the field scale. Both of these objectives were met. Preliminary analysis of the data indicate that the underlying biogeochemical data sets were obtained that will support a mechanistic understanding of the underlying processes, including remarkable insight into previously unrecognized microbial processes taking place during acetate amendment of the subsurface for a second time.« less

The role of IQSEC2 in syndromic intellectual disability: Narrowing the diagnostic odyssey.

PubMed

Helm, Benjamin M; Powis, Zoe; Prada, Carlos E; Casasbuenas-Alarcon, Olga L; Balmakund, Tonya; Schaefer, G B; Kahler, Stephen G; Kaylor, Julie; Winter, Susan; Zarate, Yuri A; Schrier Vergano, Samantha A

2017-10-01

While X-linked intellectual disability (XLID) syndromes pose a diagnostic challenge for clinicians, an increasing number of recognized disorders and their genetic etiologies are providing answers for patients and their families. The availability of clinical exome sequencing is broadening the ability to identify mutations in genes previously unrecognized as causing XLID. In recent years, the IQSEC2 gene, located at Xp11.22, has emerged as the cause of multiple cases of both nonsyndromic and syndromic XLID. Herein we present a case series of six individuals (five males, one female) with intellectual disability and seizures found to have alterations in IQSEC2. In all cases, the diagnostic odyssey was extensive and expensive, often including invasive testing such as muscle biopsies, before ultimately reaching the diagnosis. We report these cases to demonstrate the exhaustive work-up prior to finding the changes in IQSEC2 gene, recommend that this gene be considered earlier in the diagnostic evaluation of individuals with global developmental delay, microcephaly, and severe, intractable epilepsy, and support the use of intellectual disability panels including IQSEC2 in the first-line evaluation of these patients. © 2017 Wiley Periodicals, Inc.

Genetic Identification of a PilT Motor in Geobacter sulfurreducens Reveals a Role for Pilus Retraction in Extracellular Electron Transfer

PubMed Central

Speers, Allison M.; Schindler, Bryan D.; Hwang, Jihwan; Genc, Aycin; Reguera, Gemma

2016-01-01

The metal-reducing bacterium Geobacter sulfurreducens requires the expression of conductive pili to reduce iron oxides and to wire electroactive biofilms, but the role of pilus retraction in these functions has remained elusive. Here we show that of the four PilT proteins encoded in the genome of G. sulfurreducens, PilT3 powered pilus retraction in planktonic cells of a PilT-deficient strain of P. aeruginosa and restored the dense mutant biofilms to wild-type levels. Furthermore, PilT3 and PilT4 rescued the twitching motility defect of the PilT-deficient mutant. However, PilT4 was the only paralog whose inactivation in G. sulfurreducens lead to phenotypes associated with the hyperpiliation of non-retractile mutants such as enhanced adhesion and biofilm-forming abilities. In addition, PilT4 was required to reduce iron oxides. Taken together, the results indicate that PilT4 is the motor ATPase of G. sulfurreducens pili and reveal a previously unrecognized role for pilus retraction in extracellular electron transfer, a strategy that confers on Geobacter spp. an adaptive advantage for metal reduction in the natural environment. PMID:27799920

Phylogenetic Inferences Reveal a Large Extent of Novel Biodiversity in Chemically Rich Tropical Marine Cyanobacteria

PubMed Central

Gunasekera, Sarath P.; Gerwick, William H.

2013-01-01

Benthic marine cyanobacteria are known for their prolific biosynthetic capacities to produce structurally diverse secondary metabolites with biomedical application and their ability to form cyanobacterial harmful algal blooms. In an effort to provide taxonomic clarity to better guide future natural product drug discovery investigations and harmful algal bloom monitoring, this study investigated the taxonomy of tropical and subtropical natural product-producing marine cyanobacteria on the basis of their evolutionary relatedness. Our phylogenetic inferences of marine cyanobacterial strains responsible for over 100 bioactive secondary metabolites revealed an uneven taxonomic distribution, with a few groups being responsible for the vast majority of these molecules. Our data also suggest a high degree of novel biodiversity among natural product-producing strains that was previously overlooked by traditional morphology-based taxonomic approaches. This unrecognized biodiversity is primarily due to a lack of proper classification systems since the taxonomy of tropical and subtropical, benthic marine cyanobacteria has only recently been analyzed by phylogenetic methods. This evolutionary study provides a framework for a more robust classification system to better understand the taxonomy of tropical and subtropical marine cyanobacteria and the distribution of natural products in marine cyanobacteria. PMID:23315747

Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans

PubMed Central

Chou, Meng-Yun; Fogelstrand, Linda; Hartvigsen, Karsten; Hansen, Lotte F.; Woelkers, Douglas; Shaw, Peter X.; Choi, Jeomil; Perkmann, Thomas; Bäckhed, Fredrik; Miller, Yury I.; Hörkkö, Sohvi; Corr, Maripat; Witztum, Joseph L.; Binder, Christoph J.

2009-01-01

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of oxidized lipoproteins and apoptotic cells. Adaptive immune responses to various oxidation-specific epitopes play an important role in atherogenesis. However, accumulating evidence suggests that these epitopes are also recognized by innate receptors, such as scavenger receptors on macrophages, and plasma proteins, such as C-reactive protein (CRP). Here, we provide multiple lines of evidence that oxidation-specific epitopes constitute a dominant, previously unrecognized target of natural Abs (NAbs) in both mice and humans. Using reconstituted mice expressing solely IgM NAbs, we have shown that approximately 30% of all NAbs bound to model oxidation-specific epitopes, as well as to atherosclerotic lesions and apoptotic cells. Because oxidative processes are ubiquitous, we hypothesized that these epitopes exert selective pressure to expand NAbs, which in turn play an important role in mediating homeostatic functions consequent to inflammation and cell death, as demonstrated by their ability to facilitate apoptotic cell clearance. These findings provide novel insights into the functions of NAbs in mediating host homeostasis and into their roles in health and diseases, such as chronic inflammatory diseases and atherosclerosis. PMID:19363291

Central serous choroidopathy in the Hallermann-Streiff Syndrome.

PubMed

Blair, N P; Brockhurst, R J; Lee, W

1981-08-01

Central serous choroidopathy was observed in a young patient with the Hallermann-Streiff syndrome. Typical features of this syndrome include microphthalmos, proportionate dwarfism, dyscephaly with birdlike facies, dental abnormalities, and hypotrichosis. Exceptional aspects of this case include age of onset (11 years), high hyperopic refractive error (+ 13.00 sphere), and multiple recurrences caused by six separate documented leaks from the choroid. Fundus changes previously reported in the Hallermann-Streiff syndrome, interpreted as chorioretinal pigmentary changes, may have been secondary to previous undiagnosed central serous choroidopathy. Periodic ophthalmoscopy should be performed and may detect unrecognized episodes of central serous choroidopathy for which photocoagulation would be beneficial.

Unsuspected glucose-6-phosphate dehydrogenase deficiency presenting as symptomatic methemoglobinemia with severe hemolysis after fava bean ingestion in a 6-year-old boy.

PubMed

Odièvre, Marie-Hélène; Danékova, Névéna; Mesples, Bettina; Chemouny, Myriam; Couque, Nathalie; Parez, Nathalie; Ducrocq, Rolande; Elion, Jacques

2011-05-01

We report the occurrence of symptomatic methemoglobinemia in a previously healthy boy, who presented with severe acute hemolysis after fava bean ingestion. The methemoglobinemia revealed a previously unrecognized glucose-6-phosphate dehydrogenase (G6PD) deficiency. We discuss the pathophysiology of severe methemoglobinemia when associated with acute hemolysis, favism, and the common African G6PD A-variant [G6PD, VAL68MET, ASN126ASP]. In conclusion, screening for G6PD deficiency must be considered in symptomatic methemoglobinemia, especially in young boys, when associated with intravascular hemolysis.

Rasburicase-induced Hemolytic Anemia in an Adolescent With Unknown Glucose-6-Phosphate Dehydrogenase Deficiency.

PubMed

Akande, Manzilat; Audino, Anthony N; Tobias, Joseph D

2017-01-01

Rasburicase, used in the prevention and treatment of tumor lysis syndrome (TLS), may cause hemolytic anemia and methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Although routine screening for G6PD deficiency has been recommended, given the turnaround time for test results and the urgency to treat TLS, such screening may not be feasible. We report a case of rasburicase-induced hemolytic anemia without methemoglobinemia in an adolescent with T-cell lymphoblastic lymphoma, TLS, and previously unrecognized G6PD deficiency. Previous reports of hemolytic anemia with rasburicase are reviewed, mechanisms discussed, and preventative strategies presented.

Use of court records for supplementing occupational disease surveillance.

PubMed Central

Schwartz, E; Landrigan, P

1987-01-01

To conduct surveillance of occupationally related health events, the New Hampshire Division of Public Health Services analyzes death certificates and workers' compensation claims. In an effort to bolster these limited data sources, a previously unrecognized data-set comprised of court records was explored. Court records obtained from the Federal District Court proved to be a readily accessible and detailed source of information for identifying suspected cases of asbestos-related disease and potential sources of asbestos exposure. PMID:2959164

Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages

PubMed Central

Gizard, Florence; Heywood, Elizabeth B.; Findeisen, Hannes M.; Zhao, Yue; Jones, Karrie L.; Cudejko, Cèline; Post, Ginell R.; Staels, Bart; Bruemmer, Dennis

2010-01-01

Objective Telomerase serves as a critical regulator of tissue renewal. Although telomerase activity is inducible in response to various environmental cues, it remains unknown whether telomerase is activated during the inflammatory remodeling underlying atherosclerosis formation. To address this question, we investigated in the present study the regulation of telomerase in macrophages and during atherosclerosis development in LDL-receptor-deficient mice. Methods and Results We demonstrate that inflammatory stimuli activate telomerase in macrophages by inducing the expression of the catalytic subunit telomerase reverse transcriptase (TERT). Reporter and chromatin immunoprecipitation assays identified a previously unrecognized NF-κB response element in the TERT promoter, to which NF-κB is recruited during inflammation. Inhibition of NF-κB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-κB target gene. Furthermore, functional experiments revealed that TERT-deficiency results in a senescent cell phenotype. Finally, we demonstrate high levels of TERT expression in macrophages of human atherosclerotic lesions and establish that telomerase is activated during atherosclerosis development in LDL-receptor-deficient mice. Conclusion These results characterize TERT as a previously unrecognized NF-κB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis. This induction of TERT expression prevents macrophage senescence and may have important implications for the development of atherosclerosis. PMID:21106948

Emotional memory: No source memory without old-new recognition.

PubMed

Bell, Raoul; Mieth, Laura; Buchner, Axel

2017-02-01

Findings reported in the memory literature suggest that the emotional components of an encoding episode can be dissociated from nonemotional memory. In particular, it has been found that the previous association with threatening events can be retrieved in aversive conditioning even in the absence of item identification. In the present study, we test whether emotional source memory can be independent of item recognition. Participants saw pictures of snakes paired with threatening and nonthreatening context information (poisonousness or nonpoisonousness). In the source memory test, participants were required to remember whether a snake was associated with poisonousness or nonpoisonousness. A simple extension of a well-established multinomial source monitoring model was used to measure source memory for unrecognized items. By using this model, it was possible to assess directly whether participants were able to associate a previously seen snake with poisonousness or nonpoisonousness even if the snake itself was not recognized as having been presented during the experiment. In 3 experiments, emotional source memory was only found for recognized items. While source memory for recognized items differed between emotional and nonemotional information, source memory for unrecognized items was equally absent for emotional and nonemotional information. We conclude that emotional context information is bound to item representations and cannot be retrieved in the absence of item recognition. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Biocontainment laboratory risk assessment: perspectives and considerations.

PubMed

Patterson, Amy; Fennington, Kelly; Bayha, Ryan; Wax, Diane; Hirschberg, Rona; Boyd, Nancy; Kurilla, Michael

2014-07-01

The ability to respond to public health emergencies involving infectious diseases as well as our ability to adequately prepare for as yet unknown or unrecognized emerging infectious diseases requires suitable facilities within which scientific investigations can take place. To ensure the safe conduct of such investigations so that laboratory workers and the general public are protected from potential consequences of accidental or intentional release of high consequence pathogens, special containment facilities have been designed and constructed. Evaluation of the adequacy of containment for these types of investigations requires a risk assessment (RA) as part of the overall construction project for these types of laboratories. A discussion of the RA process along with considerations that impact the design of such studies and the overall results is presented. Published 2014. This article is a US Government work and is in the public domain in the USA.

Preeclampsia: is it because of the asymptomatic, unrecognized renal scars caused by urinary tract infections in childhood that become symptomatic with pregnancy?

PubMed

Ozlü, Tülay; Alçelik, Aytekin; Calişkan, Billur; Dönmez, Melahat Emine

2012-11-01

Preeclampsia is an important disease of pregnancy whose exact etiology is still unknown despite continuing developments in medicine. Although most commonly it is believed to be caused by a defective placentation, in this paper, we hypothesize that the primary underlying problem in the development of preeclampsia can be in kidneys in a greater proportion of cases than it is believed today. The increased intravascular volume and the increased work load of kidneys together with the resulting glomerular hypertrophy may precipitate nephrotic syndrome, which in this case is called "preeclampsia" in a previously affected kidney. Urinary tract infections in childhood leaving silent, unrecognized small scars in the kidneys may be the underlying renal cause which disrupts its silence with an increased work load of kidneys prominently occurring after the midtrimester. The histopathologic finding in kidneys with renal scars after childhood urinary tract infections and in preeclampsia is focal segmental glomerulosclerosis in the majority of cases and this similarity strengthens our hypothesis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Interpretation of the Last Chance thrust, Death Valley region, California, as an Early Permian décollement in a previously undeformed shale basin

USGS Publications Warehouse

Stevens, Calvin H.; Stone, Paul

2005-01-01

We interpret the Last Chance thrust as similar in many ways to Appalachian-type décollements in which the zone of thrusting is localized along a shale interval. The Last Chance thrust, however, has been dismembered during later geologic events so that its original geometry has been obscured. Our model may have unrecognized analogs in other structurally complex shale basins in which the initial deformation was along a major shale unit.

Gregory the Great's metaphor of the physician of the heart as a model for pastoral identity.

PubMed

McGrath-Merkle, Clare

2011-06-01

The identity of the Roman Catholic priesthood remains in serious crisis. Scholars have called for a return to traditional sources to find possible solutions, including the Early Church Fathers and the Hebrew Bible. Following Oden, this article further explores Pope Gregory the Great's The Book of Pastoral Rule and his ideals regarding pastoral identity. Of unique importance is his notion of the pastor as a "physician of the heart," unrecognized previously as central to his project.

On the derivation of selection functions from redshift survey data

NASA Technical Reports Server (NTRS)

Strauss, Michael A.; Yahil, Amos; Davis, Marc

1991-01-01

A previously unrecognized effect is described in the derivation of luminosity functions and selection functions from existing redshift survey data, due to binning of quoted magnitudes and diameters. Corrections are made for this effect in the Center for Astrophysics (CfA) and Southern Sky (SSRS) Redshift Surveys. The correction makes subtle but systematic changes in the derived density fields of the CfA survey, especially within 2000 km/s of the Local Group. The effect on the density field of the SSRS survey is negligible.

Constraints on formation processes of two coarse-grained calcium- aluminum-rich inclusions: a study of mantles, islands and cores

USGS Publications Warehouse

Meeker, G.P.

1995-01-01

Many coarse-grained calcium- aluminum-rich inclusions (CAIs) contain features that are inconsistent with equilibrium liquid crystallization models of origin. Spinel-free islands (SFIs) in spinel-rich cores of Type B CAIs are examples of such features. One model previously proposed for the origin of Allende 5241, a Type B1 CAI containing SFIs, involves the capture and assimilation of xenoliths by a liquid droplet in the solar nebula (El Goresy et al, 1985; MacPherson et al 1989). This study reports new textural and chemical zoning data from 5241 and identifies previously unrecognized chemical zoning patterns in the melilite mantle and in a SFI. -from Author

Prevalence and Significance of Unrecognized Lower Extremity Peripheral Arterial Disease in General Medicine Practice

PubMed Central

McGrae McDermott, Mary; Kerwin, Diana R; Liu, Kiang; Martin, Gary J; O'Brien, Erin; Kaplan, Heather; Greenland, Philip

2001-01-01

OBJECTIVE To determine the prevalence of unrecognized lower extremity peripheral arterial disease (PAD) among men and women aged 55 years and older in a general internal medicine (GIM) practice and to identify characteristics and functional performance associated with unrecognized PAD. DESIGN Cross-sectional. SETTING Academic medical center. PARTICIPANTS We identified 143 patients with known PAD from the noninvasive vascular laboratory, and 239 men and women aged 55 and older with no prior PAD history from a GIM practice. Group 1 consisted of patients with PAD consecutively identified from the noninvasive vascular laboratory (n = 143). Group 2 included GIM practice patients found to have an ankle brachial index less than 0.90, consistent with PAD (n = 34). Group 3 consisted of GIM practice patients without PAD (n = 205). MEASUREMENTS AND MAIN RESULTS Leg functioning was assessed with the 6-minute walk, 4-meter walking velocity, and Walking Impairment Questionnaire (WIQ). Of GIM practice patients, 14% had unrecognized PAD. Only 44% of patients in Group 2 had exertional leg symptoms. Distances achieved in the 6-minute walk were 1,130, 1,362, and 1,539 feet for Groups 1, 2, and 3, respectively, adjusting for age, gender, and race (P < .001). The degree of difficulty walking due to leg symptoms as reported on the WIQ was comparable between Groups 2 and 3 and significantly greater in Group 1 than Group 2. In multiple logistic regression analysis including Groups 2 and 3, current cigarette smoking was associated independently with unrecognized PAD (odds ratio [OR], 6.82; 95% confidence interval [95% CI], 1.55 to 29.93). Aspirin therapy was nearly independently associated with absence of PAD (OR, 0.37; 95% CI, 0.12 to 1.12). CONCLUSION Unrecognized PAD is common among men and women aged 55 years and older in GIM practice and is associated with impaired lower extremity functioning. Ankle brachial index screening may be necessary to diagnose unrecognized PAD in a GIM practice. PMID:11422635

Incidental germline variants in 1000 advanced cancers on a prospective somatic genomic profiling protocol.

PubMed

Meric-Bernstam, F; Brusco, L; Daniels, M; Wathoo, C; Bailey, A M; Strong, L; Shaw, K; Lu, K; Qi, Y; Zhao, H; Lara-Guerra, H; Litton, J; Arun, B; Eterovic, A K; Aytac, U; Routbort, M; Subbiah, V; Janku, F; Davies, M A; Kopetz, S; Mendelsohn, J; Mills, G B; Chen, K

2016-05-01

Next-generation sequencing in cancer research may reveal germline variants of clinical significance. We report patient preferences for return of results and the prevalence of incidental pathogenic germline variants (PGVs). Targeted exome sequencing of 202 genes was carried out in 1000 advanced cancers using tumor and normal DNA in a research laboratory. Pathogenic variants in 18 genes, recommended for return by The American College of Medical Genetics and Genomics, as well as PALB2, were considered actionable. Patient preferences of return of incidental germline results were collected. Return of results was initiated with genetic counseling and repeat CLIA testing. Of the 1000 patients who underwent sequencing, 43 had likely PGVs: APC (1), BRCA1 (11), BRCA2 (10), TP53 (10), MSH2 (1), MSH6 (4), PALB2 (2), PTEN (2), TSC2 (1), and RB1 (1). Twenty (47%) of 43 variants were previously known based on clinical genetic testing. Of the 1167 patients who consented for a germline testing protocol, 1157 (99%) desired to be informed of incidental results. Twenty-three previously unrecognized mutations identified in the research environment were confirmed with an orthogonal CLIA platform. All patients approached decided to proceed with formal genetic counseling; in all cases where formal genetic testing was carried out, the germline variant of concern validated with clinical genetic testing. In this series, 2.3% patients had previously unrecognized pathogenic germline mutations in 19 cancer-related genes. Thus, genomic sequencing must be accompanied by a plan for return of germline results, in partnership with genetic counseling. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Cirrhosis is Under-recognized in Patients Subsequently Diagnosed with Hepatocellular Cancer

PubMed Central

Walker, Megan; El-Serag, Hashem B.; Sada, Yvonne; Mittal, Sahil; Ying, Jun; Duan, Zhigang; Richardson, Peter; Davila, Jessica A.; Kanwal, Fasiha

2015-01-01

Background Most clinical practice guidelines recommend screening for HCC in patients with cirrhosis. However, patients with compensated cirrhosis are often asymptomatic and may remain unrecognized for years. Aims To determine the extent to which cirrhosis is unrecognized in a US Veteran population with HCC and to evaluate the association between lack of cirrhosis recognition and stage of HCC at diagnosis. Methods We reviewed the electronic medical records of a random sample of HCC cases diagnosed in the national Veterans Affairs system between 2005 and 2011. We conducted multivariable analyses adjusting for patients’ demographics, comorbidity, etiology of underlying disease, and healthcare utilization including HCC surveillance. Results Of 1201 patients with HCC and cirrhosis, 24.6% had unrecognized cirrhosis prior to HCC diagnosis. Older patients (>65yr, odds ratio [OR] 2.32), African Americans (OR 1.93), patients with alcoholic or NAFLD liver disease (OR 1.69 and 4.77 respectively), HIV (OR 3.02), and fewer comorbidities (Deyo 0 vs. 3, OR 2.42) had significantly higher odds of having unrecognized cirrhosis than comparison groups. Furthermore, patients with unrecognized cirrhosis were 6.5 times more likely to have advanced stage HCC at diagnosis. The effect of cirrhosis recognition on HCC stage remained significant after adjusting for pre-specified covariates (OR 3.37). Conclusions In one fourth of patients, cirrhosis was unrecognized prior to HCC diagnosis, and this group was significantly more likely to have advanced stage HCC. These findings emphasize the importance of timely evaluation for cirrhosis in at-risk populations as a critical step to improving outcomes for HCC patients. PMID:26784271

Anaerobic biodegradation of methyl esters by Acetobacterium woodii and Eubacterium limosum

USGS Publications Warehouse

Liu, Shi; Suflita, Joseph M.

1994-01-01

The ability ofAcetobacterium woodii andEubacterium limosum to degrade methyl esters of acetate, propionate, butyrate, and isobutyrate was examined under growing and resting-cell conditions. Both bacteria hydrolyzed the esters to the corresponding carboxylates and methanol under either condition. Methanol was further oxidized to formate under growing but not resting conditions. Unlike the metabolism of phenylmethylethers, no H2 requirement was evident for ester biotransformation. The hydrolysis of methyl carboxylates is thermodynamically favorable under standard conditions and the mixotrophic metabolism of ester/CO2 allowed for bacterial growth. These results suggest that the degradation of methyl carboxylates may be a heretofore unrecognized nutritional option for acetogenic bacteria.

Evolvable Neuronal Paths: A Novel Basis for Information and Search in the Brain

PubMed Central

Fernando, Chrisantha; Vasas, Vera; Szathmáry, Eörs; Husbands, Phil

2011-01-01

We propose a previously unrecognized kind of informational entity in the brain that is capable of acting as the basis for unlimited hereditary variation in neuronal networks. This unit is a path of activity through a network of neurons, analogous to a path taken through a hidden Markov model. To prove in principle the capabilities of this new kind of informational substrate, we show how a population of paths can be used as the hereditary material for a neuronally implemented genetic algorithm, (the swiss-army knife of black-box optimization techniques) which we have proposed elsewhere could operate at somatic timescales in the brain. We compare this to the same genetic algorithm that uses a standard ‘genetic’ informational substrate, i.e. non-overlapping discrete genotypes, on a range of optimization problems. A path evolution algorithm (PEA) is defined as any algorithm that implements natural selection of paths in a network substrate. A PEA is a previously unrecognized type of natural selection that is well suited for implementation by biological neuronal networks with structural plasticity. The important similarities and differences between a standard genetic algorithm and a PEA are considered. Whilst most experiments are conducted on an abstract network model, at the conclusion of the paper a slightly more realistic neuronal implementation of a PEA is outlined based on Izhikevich spiking neurons. Finally, experimental predictions are made for the identification of such informational paths in the brain. PMID:21887266

Computational and transcriptional evidence for microRNAs in the honey bee genome

PubMed Central

Weaver, Daniel B; Anzola, Juan M; Evans, Jay D; Reid, Jeffrey G; Reese, Justin T; Childs, Kevin L; Zdobnov, Evgeny M; Samanta, Manoj P; Miller, Jonathan; Elsik, Christine G

2007-01-01

Background Non-coding microRNAs (miRNAs) are key regulators of gene expression in eukaryotes. Insect miRNAs help regulate the levels of proteins involved with development, metabolism, and other life history traits. The recently sequenced honey bee genome provides an opportunity to detect novel miRNAs in both this species and others, and to begin to infer the roles of miRNAs in honey bee development. Results Three independent computational surveys of the assembled honey bee genome identified a total of 65 non-redundant candidate miRNAs, several of which appear to have previously unrecognized orthologs in the Drosophila genome. A subset of these candidate miRNAs were screened for expression by quantitative RT-PCR and/or genome tiling arrays and most predicted miRNAs were confirmed as being expressed in at least one honey bee tissue. Interestingly, the transcript abundance for several known and novel miRNAs displayed caste or age-related differences in honey bees. Genes in proximity to miRNAs in the bee genome are disproportionately associated with the Gene Ontology terms 'physiological process', 'nucleus' and 'response to stress'. Conclusion Computational approaches successfully identified miRNAs in the honey bee and indicated previously unrecognized miRNAs in the well-studied Drosophila melanogaster genome despite the 280 million year distance between these insects. Differentially transcribed miRNAs are likely to be involved in regulating honey bee development, and arguably in the extreme developmental switch between sterile worker bees and highly fertile queens. PMID:17543122

Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population.

PubMed

Tatlisumak, Turgut; Putaala, Jukka; Innilä, Markus; Enzinger, Christian; Metso, Tiina M; Curtze, Sami; von Sarnowski, Bettina; Amaral-Silva, Alexandre; Jungehulsing, Gerhard Jan; Tanislav, Christian; Thijs, Vincent; Rolfs, Arndt; Norrving, Bo; Fazekas, Franz; Suomalainen, Anu; Kolodny, Edwin H

2016-02-01

Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

Mutations in the Gene Encoding IFT Dynein Complex Component WDR34 Cause Jeune Asphyxiating Thoracic Dystrophy

PubMed Central

Schmidts, Miriam; Vodopiutz, Julia; Christou-Savina, Sonia; Cortés, Claudio R.; McInerney-Leo, Aideen M.; Emes, Richard D.; Arts, Heleen H.; Tüysüz, Beyhan; D’Silva, Jason; Leo, Paul J.; Giles, Tom C.; Oud, Machteld M.; Harris, Jessica A.; Koopmans, Marije; Marshall, Mhairi; Elçioglu, Nursel; Kuechler, Alma; Bockenhauer, Detlef; Moore, Anthony T.; Wilson, Louise C.; Janecke, Andreas R.; Hurles, Matthew E.; Emmet, Warren; Gardiner, Brooke; Streubel, Berthold; Dopita, Belinda; Zankl, Andreas; Kayserili, Hülya; Scambler, Peter J.; Brown, Matthew A.; Beales, Philip L.; Wicking, Carol; Duncan, Emma L.; Mitchison, Hannah M.

2013-01-01

Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery. PMID:24183451

Utility of multiple rule out CT screening of high-risk atraumatic patients in an emergency department-a feasibility study.

PubMed

Pries-Heje, Mia M; Hasselbalch, Rasmus B; Raaschou, Henriette; Rezanavaz-Gheshlagh, Bijan; Heebøll, Hanne; Rehman, Shazia; Kristensen, Mariana; Andersen, Erik Henning; Ravn, Lisbet; Nèmery, Michel C; Lind, Morten N; Boel, Thomas; Ulriksen, Peter Sommer; Iversen, Kasper K

2018-02-17

Several large trials have evaluated the effect of CT screening based on specific symptoms, with varying outcomes. Screening of patients with CT based on their prognosis alone has not been examined before. For moderate-to-high risk patients presenting in the emergency department (ED), the potential gain from a CT scan might outweigh the risk of radiation exposure. We hypothesized that an accelerated "multiple rule out" CT screening of moderate-to-high risk patients will detect many clinically unrecognized diagnoses that affect change in treatment. Patients ≥ 40 years, triaged as high-risk or moderate-to-high risk according to vital signs, were eligible for inclusion. Patients were scanned with a combined ECG-gated and dual energy CT scan of cerebrum, thorax, and abdomen. The impact of the CT scan on patient diagnosis and treatment was examined prospectively by an expert panel. A total of 100 patients were included in the study, (53% female, mean age 73 years [age range, 43-93]). The scan lead to change in treatment or additional examinations in 37 (37%) patients, of which 24 (24%) were diagnostically significant, change in acute treatment in 11 (11%) cases and previously unrecognized malignant tumors in 10 (10%) cases. The mean size specific radiation dose was 15.9 mSv (± 3.1 mSv). Screening with a multi-rule out CT scan of high-risk patients in an ED is feasible and result in discovery of clinically unrecognized diagnoses and malignant tumors, but at the cost of radiation exposure and downstream examinations. The clinical impact of these findings should be evaluated in a larger randomized cohort.

Interactome analyses identify ties of PrP and its mammalian paralogs to oligomannosidic N-glycans and endoplasmic reticulum-derived chaperones.

PubMed

Watts, Joel C; Huo, Hairu; Bai, Yu; Ehsani, Sepehr; Jeon, Amy Hye Won; Won, Amy Hye; Shi, Tujin; Daude, Nathalie; Lau, Agnes; Young, Rebecca; Xu, Lei; Carlson, George A; Williams, David; Westaway, David; Schmitt-Ulms, Gerold

2009-10-01

The physiological environment which hosts the conformational conversion of the cellular prion protein (PrP(C)) to disease-associated isoforms has remained enigmatic. A quantitative investigation of the PrP(C) interactome was conducted in a cell culture model permissive to prion replication. To facilitate recognition of relevant interactors, the study was extended to Doppel (Prnd) and Shadoo (Sprn), two mammalian PrP(C) paralogs. Interestingly, this work not only established a similar physiological environment for the three prion protein family members in neuroblastoma cells, but also suggested direct interactions amongst them. Furthermore, multiple interactions between PrP(C) and the neural cell adhesion molecule, the laminin receptor precursor, Na/K ATPases and protein disulfide isomerases (PDI) were confirmed, thereby reconciling previously separate findings. Subsequent validation experiments established that interactions of PrP(C) with PDIs may extend beyond the endoplasmic reticulum and may play a hitherto unrecognized role in the accumulation of PrP(Sc). A simple hypothesis is presented which accounts for the majority of interactions observed in uninfected cells and suggests that PrP(C) organizes its molecular environment on account of its ability to bind to adhesion molecules harboring immunoglobulin-like domains, which in turn recognize oligomannose-bearing membrane proteins.

Fidelity of the representation of value in decision-making

PubMed Central

Dowding, Ben A.

2017-01-01

The ability to make optimal decisions depends on evaluating the expected rewards associated with different potential actions. This process is critically dependent on the fidelity with which reward value information can be maintained in the nervous system. Here we directly probe the fidelity of value representation following a standard reinforcement learning task. The results demonstrate a previously-unrecognized bias in the representation of value: extreme reward values, both low and high, are stored significantly more accurately and precisely than intermediate rewards. The symmetry between low and high rewards pertained despite substantially higher frequency of exposure to high rewards, resulting from preferential exploitation of more rewarding options. The observed variation in fidelity of value representation retrospectively predicted performance on the reinforcement learning task, demonstrating that the bias in representation has an impact on decision-making. A second experiment in which one or other extreme-valued option was omitted from the learning sequence showed that representational fidelity is primarily determined by the relative position of an encoded value on the scale of rewards experienced during learning. Both variability and guessing decreased with the reduction in the number of options, consistent with allocation of a limited representational resource. These findings have implications for existing models of reward-based learning, which typically assume defectless representation of reward value. PMID:28248958

Engineered fusokine GIFT4 licenses the ability of B cells to trigger a tumoricidal T cell response

PubMed Central

Deng, Jiusheng; Yuan, Shala; Pennati, Andrea; Murphy, Jordan; Wu, Jian Hui; Lawson, David; Galipeau, Jacques

2014-01-01

Engineered chimeric cytokines can generate gain-of-function activity in immune cells. Here we report potent antitumor activity for a novel fusion cytokine generated by N-terminal coupling of GM-CSF to IL-4, generating a fusokine termed GIFT4. B cells treated with GIFT4 clustered GM-CSF and IL-4 receptors on the cell surface and displayed a pan-STAT hyperphosphorylation associated with acquisition of a distinct phenotype and function described to date. In C57BL/6J mice, administration of GIFT4 expanded endogenous B cells and suppressed the growth of B16F0 melanoma cells. Further, B16F0 melanoma cells engineered to secrete GIFT4 were rejected immunologically in a B cell-dependent manner. This effect was abolished when GIFT4-expressing B16F0 cells were implanted in B cell-deficient mice, confirming a B cell-dependent antitumor effect. Human GIFT4-licensed B cells primed cytotoxic T cells and specifically killed melanoma cells in vitro and in vivo. Taken together, our results demonstrated that GIFT4 could mediate expansion of B cells with potent antigen-specific effector function. GIFT4 may offer a novel immunotherapeutic tool and define a previously unrecognized potential for B cells in melanoma immunotherapy. PMID:24938765

Persistently high prevalence and unrecognized HIV infection among men who have sex with men in Baltimore: the BESURE Study

PubMed Central

German, Danielle; Sifakis, Frangiscos; Maulsby, Cathy; Towe, Vivian L.; Flynn, Colin P.; Latkin, Carl A.; Celentano, David D.; Hauck, Heather; Holtgrave, David R.

2017-01-01

Background Given high rates of HIV among Baltimore MSM, we examined characteristics associated with HIV prevalence and unrecognized HIV infection among Baltimore MSM at two time points. Methods Cross-sectional behavioral surveys and HIV testing in 2004–2005 and 2008 using venue-based sampling among adult Baltimore men at MSM-identified locations. MSM was defined as sex with a male partner in the past year. Bivariate and backwards stepwise regression identified characteristics associated with HIV and unrecognized infection. Findings HIV prevalence was 37.7% overall in 2004–2005 (n=645) and 37.5% in 2008 (n=448), 51.4% and 44.7% among Black MSM, and 12.9% and 18.3% among non-Hispanic White MSM. Compared to non-Hispanic White MSM, Black MSM were 4.0 times (95% C.I.: 2.3, 7.0) more likely to be HIV-positive in 2004–2005 and 2.5 times (95% C.I.: 1.5, 4.0) more likely in 2008. Prevalence of unrecognized HIV infection was 58.4% overall in 2004–2005 and 74.4% in 2008, 63.8% and 76.9% among Black MSM, and 15.4% and 47.4% among non-Hispanic White MSM. In adjusted models, unrecognized infection was significantly associated with minority race/ethnicity, younger age, and no prior year doctor visits in 2004–5 and with younger age and no prior year doctor visits in 2008. Conclusion High rates of HIV infection and substantial rates of unrecognized HIV infection among Baltimore MSM, particularly men of color and young men, require urgent public and private sector attention and increased prevention response. PMID:21297479

Ripple Ring Basins on Ganymede and Callisto

NASA Technical Reports Server (NTRS)

Croft, S. K.

1985-01-01

The unusual morphology of the Valhalla multiple or ripple-ring basin in Callisto was totally unexpected in light of the morphologies of large impact structures on the terrestrial planets. Two other ripple-ring basins (RRB's), Asgard and a smaller structure near the crater Adlinda are also described. Several additional RRB's were found on Callisto, an example of which is shown. A previously unrecognized RRB on Ganymede was also found. An image and geologic sketch map of this RRB are shown. Morphometric and positional data for all known RRB's are given.

Inflammatory arthritis and systemic bone loss are attenuated by gastrointestinal helminth parasites.

PubMed

Sarter, Kerstin; Kulagin, Manuel; Schett, Georg; Harris, Nicola L; Zaiss, Mario M

2017-05-01

Infections with different helminth species have been observed to ameliorate a variety of chronic inflammatory diseases. Herein, we show that the natural murine helminth species, Heligmosomoides polygyrus bakeri (Hp) is capable of attenuating disease severity in two different inflammatory arthritis models. Furthermore, we show that excretory-secretory (ES) products from Hp directly suppress osteoclast differentiation in vitro. Taken together, these results demonstrate that helminth infections can dampen autoimmune diseases and highlight a previously unrecognized and important role for ES products, by directly impacting on bone destruction.

Mask induction despite circuit obstruction: an unrecognized hazard of relying on automated machine check technology.

PubMed

Yang, Kamie K; Lewis, Ian H

2014-06-15

Various equipment malfunctions of anesthesia gas delivery systems have been previously reported. Our profession increasingly uses technology as a means to prevent these errors. We report a case of a near-total anesthesia circuit obstruction that went undetected before the induction of anesthesia despite the use of automated machine check technology. This case highlights that automated machine check modules can fail to detect severe equipment failure and demonstrates how, even in this era of expanding technology, manual checks still remain essential components of safe care.

New features of global climatology revealed by satellite-derived oceanic rainfall maps

NASA Technical Reports Server (NTRS)

Rao, M. S. V.; Theon, J. S.

1977-01-01

Quantitative rainfall maps over the oceanic areas of the globe were derived from the Nimbus 5 Electrically Scanning Microwave Radiometer (ESMR) data. Analysis of satellite derived oceanic rainfall maps reveal certain distinctive characteristics of global patterns for the years 1973-74. The main ones are (1) the forking of the Intertropical Convergence Zone in the Pacific, (2) a previously unrecognized rain area in the South Atlantic, (3) the bimodal behavior of rainbelts in the Indian Ocean and (4) the large interannual variability in oceanic rainfall. These features are discussed.

[Antimicrobial resistance testing in clinical practice].

PubMed

Doi, Yohei

2012-02-01

Previously unrecognized or underrecognized antimicrobial resistant bacteria, including NDM-1-producing Enterobacteriaceae and multidrug-resistant Acinetobacter baumannii, were recently identified in health care facilities in Japan. Vigilance in the clinical microbiology laboratory for these organisms is the key to early recognition of their emergence. Many of these organisms can be confirmed or at least suspected through routine susceptibility testing, which can then be referred to reference laboratories for further phenotypic or genetic testing. Antimicrobial resistance testing plays a crucial role in patient management, infection control and monitoring of local as well as national and international epidemiology.

Milankovitch wobble?

NASA Astrophysics Data System (ADS)

Mitchell, R. N.; Thissen, C.; Kirschvink, J. L.; Schrag, D. P.; Montanari, A.; Coccioni, R.; Slotznick, S. P.; Yamazaki, T.; Penserini, B. D.; Abrahams, J. N. H.; Cruz-Heredia, M.; Evans, D. A.

2015-12-01

High-resolution paleomagnetism of Cretaceous-aged limestone in Italy reveals evidence for a previously unrecognized ~10˚ directional variation, or "wobble", of either the geographic or magnetic pole on a 106-year, "Milankovitch" time scale. Ten ~1 million year (Myr) wobbles of magnetic inclination can be identified and correlated across Italy from 87-74 Myr ago, potentially refining the global polarity time scale and seafloor spreading rates. Milankovitch wobble is an omnipresent geophysical process that represents, irrespective of its mechanism, a new chronometer for age calibration with paleomagnetism. If Milankovitch wobble is interpreted as a geomagnetic artifact—the long-considered but still unproven idea that astronomical variations influence the geodynamo—the geocentric-axial dipole hypothesis would only be viable when averaged over time scales 100 times greater than currently thought, making present-day geocentricity largely coincidental. If interpreted as true geographic change, Milankovitch wobble implies an unrecognized, rapid time scale (~10˚ Myr-1) of true polar wander, possibly due to ice sheet dynamics driven by the 1.2 Myr modulation of Earth's rotational obliquity. Stable isotope data co-vary with the Milankovitch wobble, possibly favoring the polar wander mechanism that predicts rapid environmental change where the geomagnetic artifact hypothesis does not.

The Growth-Suppressive Function of the Polycomb Group Protein Polyhomeotic Is Mediated by Polymerization of Its Sterile Alpha Motif (SAM) Domain*

PubMed Central

Robinson, Angela K.; Leal, Belinda Z.; Chadwell, Linda V.; Wang, Renjing; Ilangovan, Udayar; Kaur, Yogeet; Junco, Sarah E.; Schirf, Virgil; Osmulski, Pawel A.; Gaczynska, Maria; Hinck, Andrew P.; Demeler, Borries; McEwen, Donald G.; Kim, Chongwoo A.

2012-01-01

Polyhomeotic (Ph), a member of the Polycomb Group (PcG), is a gene silencer critical for proper development. We present a previously unrecognized way of controlling Ph function through modulation of its sterile alpha motif (SAM) polymerization leading to the identification of a novel target for tuning the activities of proteins. SAM domain containing proteins have been shown to require SAM polymerization for proper function. However, the role of the Ph SAM polymer in PcG-mediated gene silencing was uncertain. Here, we first show that Ph SAM polymerization is indeed required for its gene silencing function. Interestingly, the unstructured linker sequence N-terminal to Ph SAM can shorten the length of polymers compared with when Ph SAM is individually isolated. Substituting the native linker with a random, unstructured sequence (RLink) can still limit polymerization, but not as well as the native linker. Consequently, the increased polymeric Ph RLink exhibits better gene silencing ability. In the Drosophila wing disc, Ph RLink expression suppresses growth compared with no effect for wild-type Ph, and opposite to the overgrowth phenotype observed for polymer-deficient Ph mutants. These data provide the first demonstration that the inherent activity of a protein containing a polymeric SAM can be enhanced by increasing SAM polymerization. Because the SAM linker had not been previously considered important for the function of SAM-containing proteins, our finding opens numerous opportunities to manipulate linker sequences of hundreds of polymeric SAM proteins to regulate a diverse array of intracellular functions. PMID:22275371

Hurt but still alive: Residual activity in the parahippocampal cortex conditions the recognition of familiar places in a patient with topographic agnosia.

PubMed

van Assche, Mitsouko; Kebets, Valeria; Lopez, Ursula; Saj, Arnaud; Goldstein, Rachel; Bernasconi, Françoise; Vuilleumier, Patrik; Assal, Frédéric

2016-01-01

The parahippocampal cortex (PHC) participates in both perception and memory. However, the way perceptual and memory processes cooperate when we navigate in our everyday life environment remains poorly understood. We studied a stroke patient presenting a brain lesion in the right PHC, which resulted in a mild and quantifiable topographic agnosia, and allowed us to investigate the role of this structure in overt place recognition. Photographs of personally familiar and unfamiliar places were displayed during functional magnetic resonance imaging (fMRI). Familiar places were either recognized or unrecognized by the patient and 6 age- and education-matched controls in a visual post-scan recognition test. In fMRI, recognized places were associated with a network comprising the fusiform gyrus in the intact side, but also the right anterior PHC, which included the lesion site. Moreover, this right PHC showed increased connectivity with the left homologous PHC in the intact hemisphere. By contrasting recognized with unrecognized familiar places, we replicate the finding of the joint involvement of the retrosplenial cortex, occipito-temporal areas, and posterior parietal cortex in place recognition. This study shows that the ability for left and right anterior PHC to communicate despite the neurological damage conditioned place recognition success in this patient. It further highlights a hemispheric asymmetry in this process, by showing the fundamental role of the right PHC in topographic agnosia.

Recognition of incident diabetes mellitus during an acute myocardial infarction.

PubMed

Arnold, Suzanne V; Stolker, Joshua M; Lipska, Kasia J; Jones, Philip G; Spertus, John A; McGuire, Darren K; Inzucchi, Silvio E; Goyal, Abhinav; Maddox, Thomas M; Lind, Marcus; Gumber, Divya; Shore, Supriya; Kosiborod, Mikhail

2015-05-01

Diabetes mellitus (DM) is common in patients hospitalized with an acute myocardial infarction (AMI), representing in some cases the first opportunity to recognize and treat DM. We report the incidence of new DM and its recognition among patients with AMI. Patients in a 24-site US AMI registry (2005-08) had glycosylated hemoglobin assessed at a core laboratory, with results blinded to clinicians and local clinical measurements left to the discretion of the treating providers. Among 2854 AMI patients without known DM on admission, 287 patients (10%) met criteria for previously unknown DM, defined by a core laboratory glycosylated hemoglobin of ≥6.5%. Among these, 186 (65%) were unrecognized by treating clinicians, receiving neither DM education, glucose-lowering medications at discharge, nor documentation of DM in the chart (median glycosylated hemoglobin of unrecognized patients, 6.7%; range, 6.5-12.3%). Six months after discharge, only 5% of those not recognized as having DM during hospitalization had been initiated on glucose-lowering medications versus 66% of those recognized (P<0.001). Underlying DM that has not been previously diagnosed is common among AMI patients, affecting 1 in 10 patients, yet is recognized by the care team only one third of the time. Given its frequency and therapeutic implications, including but extending beyond the initiation of glucose-lowering treatment, consideration should be given to screening all AMI patients for DM during hospitalization. Inexpensive, ubiquitous, and endorsed as an acceptable screen for DM, glycosylated hemoglobin testing should be considered for this purpose. © 2015 American Heart Association, Inc.

The bhuQ Gene Encodes a Heme Oxygenase That Contributes to the Ability of Brucella abortus 2308 To Use Heme as an Iron Source and Is Regulated by Irr

PubMed Central

Ojeda, Jenifer F.; Martinson, David A.; Menscher, Evan A.

2012-01-01

The Brucella BhuQ protein is a homolog of the Bradyrhizobium japonicum heme oxygenases HmuD and HmuQ. To determine if this protein plays a role in the ability of Brucella abortus 2308 to use heme as an iron source, an isogenic bhuQ mutant was constructed and its phenotype evaluated. Although the Brucella abortus bhuQ mutant DCO1 did not exhibit a defect in its capacity to use heme as an iron source or evidence of increased heme toxicity in vitro, this mutant produced increased levels of siderophore in response to iron deprivation compared to 2308. Introduction of a bhuQ mutation into the B. abortus dhbC mutant BHB2 (which cannot produce siderophores) resulted in a severe growth defect in the dhbC bhuQ double mutant JFO1 during cultivation under iron-restricted conditions, which could be rescued by the addition of FeCl3, but not heme, to the growth medium. The bhuQ gene is cotranscribed with the gene encoding the iron-responsive regulator RirA, and both of these genes are repressed by the other major iron-responsive regulator in the alphaproteobacteria, Irr. The results of these studies suggest that B. abortus 2308 has at least one other heme oxygenase that works in concert with BhuQ to allow this strain to efficiently use heme as an iron source. The genetic organization of the rirA-bhuQ operon also provides the basis for the proposition that BhuQ may perform a previously unrecognized function by allowing the transcriptional regulator RirA to recognize heme as an iron source. PMID:22636783

Impact of Design Effects in Large-Scale District and State Assessments

ERIC Educational Resources Information Center

Phillips, Gary W.

2015-01-01

This article proposes that sampling design effects have potentially huge unrecognized impacts on the results reported by large-scale district and state assessments in the United States. When design effects are unrecognized and unaccounted for they lead to underestimating the sampling error in item and test statistics. Underestimating the sampling…

Damage Control: Cellular Mechanisms of Plasma Membrane Repair

PubMed Central

Andrews, Norma W.; de Almeida, Patricia E.; Corrotte, Matthias

2014-01-01

Summary When wounded, eukaryotic cells reseal in a few seconds. Ca2+ influx induces exocytosis of lysosomes, a process previously thought to promote repair by “patching” wounds. New evidence suggests that resealing involves direct wound removal. Exocytosis of lysosomal acid sphingomyelinase triggers endocytosis of lesions, followed by intracellular degradation. Characterization of injury-induced endosomes revealed a role for caveolae, sphingolipid-enriched plasma membrane invaginations that internalize toxin pores and are abundant in mechanically stressed cells. These findings provide a novel mechanistic explanation for the muscle pathology associated with mutations in caveolar proteins. Membrane remodeling by the ESCRT complex was also recently shown to participate in small wound repair, emphasizing that cell resealing involves previously unrecognized mechanisms for lesion removal, which are distinct from the “patch” model. PMID:25150593

A pharyngeal jaw evolutionary innovation facilitated extinction in Lake Victoria cichlids.

PubMed

McGee, Matthew D; Borstein, Samuel R; Neches, Russell Y; Buescher, Heinz H; Seehausen, Ole; Wainwright, Peter C

2015-11-27

Evolutionary innovations, traits that give species access to previously unoccupied niches, may promote speciation and adaptive radiation. Here, we show that such innovations can also result in competitive inferiority and extinction. We present evidence that the modified pharyngeal jaws of cichlid fishes and several marine fish lineages, a classic example of evolutionary innovation, are not universally beneficial. A large-scale analysis of dietary evolution across marine fish lineages reveals that the innovation compromises access to energy-rich predator niches. We show that this competitive inferiority shaped the adaptive radiation of cichlids in Lake Tanganyika and played a pivotal and previously unrecognized role in the mass extinction of cichlid fishes in Lake Victoria after Nile perch invasion. Copyright © 2015, American Association for the Advancement of Science.

Development of unauthorized airborne emission source identification procedure

NASA Astrophysics Data System (ADS)

Shtripling, L. O.; Bazhenov, V. V.; Varakina, N. S.; Kupriyanova, N. P.

2018-01-01

The paper presents the procedure for searching sources of unauthorized airborne emissions. To make reasonable regulation decisions on airborne pollutant emissions and to ensure the environmental safety of population, the procedure provides for the determination of a pollutant mass emission value from the source being the cause of high pollution level and the search of a previously unrecognized contamination source in a specified area. To determine the true value of mass emission from the source, the minimum of the mean-root-square mismatch criterion between the computed and measured pollutant concentration in the given location is used.

Identification of mineral resources in Afghanistan-Detecting and mapping resource anomalies in prioritized areas using geophysical and remote sensing (ASTER and HyMap) data

USGS Publications Warehouse

King, Trude V.V.; Johnson, Michaela R.; Hubbard, Bernard E.; Drenth, Benjamin J.

2011-01-01

During the independent analysis of the geophysical, ASTER, and imaging spectrometer (HyMap) data by USGS scientists, previously unrecognized targets of potential mineralization were identified using evaluation criteria most suitable to the individual dataset. These anomalous zones offer targets of opportunity that warrant additional field verification. This report describes the standards used to define the anomalies, summarizes the results of the evaluations for each type of data, and discusses the importance and implications of regions of anomaly overlap between two or three of the datasets.

Atlantoaxial dislocation in a patient with nonsyndromic symmetrical dwarfism: Report of a rare case

PubMed Central

Ram, Duvuru; Madhugiri, Venkatesh S.; Roopesh Kumar, V. R.; Gulati, Reena; Sasidharan, Gopalakrishnan M.; Gundamaneni, Sudheer Kumar

2015-01-01

Congenital anomalies of the craniovertebral junction (CVJ) are complex developmental defects. We describe a patient with atlantoaxial dislocation (AAD) and short stature whose morphopathologydid not fit into any of the previously described syndromic constellations. The patient underwent a reduction of the AAD followed by fixation with C1-C2 transarticular screws. Although numerous syndromes have been linked to both dwarfism and craniovertebral junction anomalies, this patient did not fit into any of these patterns. It is possible that this may be one of the many as yet unrecognized patterns of congenital anomalies. PMID:25788820

NASA Technology Takes Center Stage

NASA Technical Reports Server (NTRS)

2004-01-01

In today's fast-paced business world, there is often more information available to researchers than there is time to search through it. Data mining has become the answer to finding the proverbial "needle in a haystack," as companies must be able to quickly locate specific pieces of information from large collections of data. Perilog, a suite of data-mining tools, searches for hidden patterns in large databases to determine previously unrecognized relationships. By retrieving and organizing contextually relevant data from any sequence of terms - from genetic data to musical notes - the software can intelligently compile information about desired topics from databases.

NCI Helps Children’s Hospital of Philadelphia to Identify and Treat New Target in Pediatric Cancer | Poster

Cancer.gov

There may be a new, more effective method for treating high-risk neuroblastoma, according to scientists at the Children’s Hospital of Philadelphia and collaborators in the Cancer and Inflammation Program at NCI at Frederick. Together, the groups published a study describing a previously unrecognized protein on neuroblastoma cells, called GPC2, as well as the creation of a novel antibody-drug conjugate, a combination of a human antibody and a naturally occurring anticancer drug, that locates and binds to GPC2 in a highly efficient way.

Extraterrestrial platinum group nuggets in deep-sea sediments

NASA Technical Reports Server (NTRS)

Brownlee, D. E.; Bates, B. A.; Wheelock, M. M.

1984-01-01

A previously unrecognized property of iron cosmic spheres is reported. The most common spheres larger than 300 microns do not, in fact, contain FeNi metal cores, but instead contain a micrometer-sized nugget composed almost entirely of platinum group elements. These elements appear to have been concentrated by the oxidation of molten meteoritic metal during atmospheric entry. This process is critically dependent on the relative abundance of oxygen in the atmosphere, and the first appearance of the nuggets in the geological record may provide a marker indicating when the oxygen abundance attained half of its present level.

Platelets: versatile effector cells in hemostasis, inflammation, and the immune continuum

PubMed Central

Vieira-de-Abreu, Adriana; Campbell, Robert A.; Weyrich, Andrew S.

2015-01-01

Platelets are chief effector cells in hemostasis. In addition, however, their specializations include activities and intercellular interactions that make them key effectors in inflammation and in the continuum of innate and adaptive immunity. This review focuses on the immune features of human platelets and platelets from experimental animals and on interactions between inflammatory, immune, and hemostatic activities of these anucleate but complex and versatile cells. The experimental findings and evidence for physiologic immune functions include previously unrecognized biologic characteristics of platelets and are paralleled by new evidence for unique roles of platelets in inflammatory, immune, and thrombotic diseases. PMID:21818701

An Unusual Cause of GI Bleeding in a Quadriplegic: Report of a Case and Review of the Literature

PubMed Central

Joseph, Raymond E.; Epsten, Robert; Kowlessar, O. Dhodanand

1982-01-01

The authors report a case of upper gastrointestinal hemorrhage in a quadriplegic. The cause was a Mallory-Weiss tear, a previously unrecognized problem in these patients. The incidence of bleeding in patients with spinal cord injury is as high as 25 percent in the few reported series. We feel that with the increased risk of gastrointestinal bleeding in the spinal cord patient and the accompanying significant mortality, early endoscopy is essential for accurate diagnosis since clues to the presence, etiology, and severity of the bleeding are often lacking. PMID:6981707

Progranulin, lysosomal regulation and neurodegenerative disease.

PubMed

Kao, Aimee W; McKay, Andrew; Singh, Param Priya; Brunet, Anne; Huang, Eric J

2017-06-01

The discovery that heterozygous and homozygous mutations in the gene encoding progranulin are causally linked to frontotemporal dementia and lysosomal storage disease, respectively, reveals previously unrecognized roles of the progranulin protein in regulating lysosome biogenesis and function. Given the importance of lysosomes in cellular homeostasis, it is not surprising that progranulin deficiency has pleiotropic effects on neural circuit development and maintenance, stress response, innate immunity and ageing. This Progress article reviews recent advances in progranulin biology emphasizing its roles in lysosomal function and brain innate immunity, and outlines future avenues of investigation that may lead to new therapeutic approaches for neurodegeneration.

Signs of essential blepharospasm: a motion-picture analysis.

PubMed

Coles, W H

1977-06-01

Motion pictures of 15 patients with essential blepharospasm were studied. Previously unrecognized signs indicated multiple cranial nerve involvement. These signs include impersistence of gaze, lid retraction, tongue thrust, head tilts, head jerks, vertical gaze spasms, and asymmetry. The sugns were also observed in a patient with bilateral blepharospasm who had a history of Bell's palsy suggesting facial nerve injury as a possible factor in blepharospasm. The presence of these signs can be explained by known neural pathways, but the site, or sites, of the lesion remains obscure. These signs may be important in assessing severity and in treatment evaluation.

On the Lienard-Wiechert potentials

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

Whitney, C.K.

1988-09-01

Very recently, questions have started to surface concerning the well-known Lienard-Wiechert potentials describing relativistically moving point sources in classical electrodynamics. The existence of questions prompts a review of the original derivations by Lienard and Wiechert. These were done at the turn of the present century, and so predate the development of relevant modern techniques from special relativity theory and generalized function theory. Only purely geometric reasoning was used. That reasoning is reviewed here, and a previously unrecognized flaw is noted. When this flaw is remedied, the potentials are slightly altered and become consistent with other new results reported elsewhere.

Complete genome sequence of Methanospirillum hungatei type strain JF1

DOE PAGES

Gunsalus, Robert; Cook, Lauren E.; Crable, Bryan R.; ...

2016-01-06

Methanospirillum hungatei strain JF1 (DSM 864) is a methane-producing archaeon and is the type species of the genus Methanospirillum, which belongs to the family Methanospirillaceae within the order Methanomicrobiales. Its genome was selected for sequencing due to its ability to utilize hydrogen and carbon dioxide and/or formate as a sole source of energy. Ecologically, M. hungatei functions as the hydrogen- and/or formate-using partner with many species of syntrophic bacteria. Its morphology is distinct from other methanogens with the ability to form long chains of cells (up to 100 m in length), which are enclosed within a sheath-like structure, and terminalmore » cells with polar flagella. The genome of M. hungatei strain JF1 is the first completely sequenced genome of the family Methanospirillaceae, and it has a circular genome of 3,544,738 bp containing 3,239 protein coding and 68 RNA genes. Furthermore, the large genome of M. hungatei JF1 suggests the presence of unrecognized biochemical/physiological properties that likely extend to the other Methanospirillaceae and include the ability to form the unusual sheath-like structure and to successfully interact with syntrophic bacteria.« less

Erythrocyte shape abnormalities, membrane oxidative damage, and β-actin alterations: an unrecognized triad in classical autism.

PubMed

Ciccoli, Lucia; De Felice, Claudio; Paccagnini, Eugenio; Leoncini, Silvia; Pecorelli, Alessandra; Signorini, Cinzia; Belmonte, Giuseppe; Guerranti, Roberto; Cortelazzo, Alessio; Gentile, Mariangela; Zollo, Gloria; Durand, Thierry; Valacchi, Giuseppe; Rossi, Marcello; Hayek, Joussef

2013-01-01

Autism spectrum disorders (ASDs) are a complex group of neurodevelopment disorders steadily rising in frequency and treatment refractory, where the search for biological markers is of paramount importance. Although red blood cells (RBCs) membrane lipidomics and rheological variables have been reported to be altered, with some suggestions indicating an increased lipid peroxidation in the erythrocyte membrane, to date no information exists on how the oxidative membrane damage may affect cytoskeletal membrane proteins and, ultimately, RBCs shape in autism. Here, we investigated RBC morphology by scanning electron microscopy in patients with classical autism, that is, the predominant ASDs phenotype (age range: 6-26 years), nonautistic neurodevelopmental disorders (i.e., "positive controls"), and healthy controls (i.e., "negative controls"). A high percentage of altered RBCs shapes, predominantly elliptocytes, was observed in autistic patients, but not in both control groups. The RBCs altered morphology in autistic subjects was related to increased erythrocyte membrane F2-isoprostanes and 4-hydroxynonenal protein adducts. In addition, an oxidative damage of the erythrocyte membrane β-actin protein was evidenced. Therefore, the combination of erythrocyte shape abnormalities, erythrocyte membrane oxidative damage, and β-actin alterations constitutes a previously unrecognized triad in classical autism and provides new biological markers in the diagnostic workup of ASDs.

Erythrocyte Shape Abnormalities, Membrane Oxidative Damage, and β-Actin Alterations: An Unrecognized Triad in Classical Autism

PubMed Central

Ciccoli, Lucia; De Felice, Claudio; Pecorelli, Alessandra; Belmonte, Giuseppe; Guerranti, Roberto; Cortelazzo, Alessio; Durand, Thierry; Valacchi, Giuseppe; Rossi, Marcello; Hayek, Joussef

2013-01-01

Autism spectrum disorders (ASDs) are a complex group of neurodevelopment disorders steadily rising in frequency and treatment refractory, where the search for biological markers is of paramount importance. Although red blood cells (RBCs) membrane lipidomics and rheological variables have been reported to be altered, with some suggestions indicating an increased lipid peroxidation in the erythrocyte membrane, to date no information exists on how the oxidative membrane damage may affect cytoskeletal membrane proteins and, ultimately, RBCs shape in autism. Here, we investigated RBC morphology by scanning electron microscopy in patients with classical autism, that is, the predominant ASDs phenotype (age range: 6–26 years), nonautistic neurodevelopmental disorders (i.e., “positive controls”), and healthy controls (i.e., “negative controls”). A high percentage of altered RBCs shapes, predominantly elliptocytes, was observed in autistic patients, but not in both control groups. The RBCs altered morphology in autistic subjects was related to increased erythrocyte membrane F2-isoprostanes and 4-hydroxynonenal protein adducts. In addition, an oxidative damage of the erythrocyte membrane β-actin protein was evidenced. Therefore, the combination of erythrocyte shape abnormalities, erythrocyte membrane oxidative damage, and β-actin alterations constitutes a previously unrecognized triad in classical autism and provides new biological markers in the diagnostic workup of ASDs. PMID:24453417

Simulator-induced spatial disorientation: effects of age, sleep deprivation, and type of conflict.

PubMed

Previc, Fred H; Ercoline, William R; Evans, Richard H; Dillon, Nathan; Lopez, Nadia; Daluz, Christina M; Workman, Andrew

2007-05-01

Spatial disorientation mishaps are greater at night and with greater time on task, and sleep deprivation is known to decrease cognitive and overall flight performance. However, the ability to perceive and to be influenced by physiologically appropriate simulated SD conflicts has not previously been studied in an automated simulator flight profile. A set of 10 flight profiles were flown by 10 U.S. Air Force (USAF) pilots over a period of 28 h in a specially designed flight simulator for spatial disorientation research and training. Of the 10 flights, 4 had a total of 7 spatial disorientation (SD) conflicts inserted into each of them, 5 simulating motion illusions and 2 involving visual illusions. The percentage of conflict reports was measured along with the effects of four conflicts on flight performance. The results showed that, with one exception, all motion conflicts were reported over 60% of the time, whereas the two visual illusions were reported on average only 25% of the time, although they both significantly affected flight performance. Pilots older than 35 yr of age were more likely to report conflicts than were those under 30 yr of age (63% vs. 38%), whereas fatigue had little effect overall on either recognized or unrecognized SD. The overall effects of these conflicts on perception and performance were generally not altered by sleep deprivation, despite clear indications of fatigue in our pilots.

Quantitative Phospho-proteomic Analysis of TNFα/NFκB Signaling Reveals a Role for RIPK1 Phosphorylation in Suppressing Necrotic Cell Death.

PubMed

Mohideen, Firaz; Paulo, Joao A; Ordureau, Alban; Gygi, Steve P; Harper, J Wade

2017-07-01

TNFα is a potent inducer of inflammation due to its ability to promote gene expression, in part via the NFκB pathway. Moreover, in some contexts, TNFα promotes Caspase-dependent apoptosis or RIPK1/RIPK3/MLKL-dependent necrosis. Engagement of the TNF Receptor Signaling Complex (TNF-RSC), which contains multiple kinase activities, promotes phosphorylation of several downstream components, including TAK1, IKKα/IKKβ, IκBα, and NFκB. However, immediate downstream phosphorylation events occurring in response to TNFα signaling are poorly understood at a proteome-wide level. Here we use Tandem Mass Tagging-based proteomics to quantitatively characterize acute TNFα-mediated alterations in the proteome and phosphoproteome with or without inhibition of the cIAP-dependent survival arm of the pathway with a SMAC mimetic. We identify and quantify over 8,000 phosphorylated peptides, among which are numerous known sites in the TNF-RSC, NFκB, and MAP kinase signaling systems, as well as numerous previously unrecognized phosphorylation events. Functional analysis of S320 phosphorylation in RIPK1 demonstrates a role for this event in suppressing its kinase activity, association with CASPASE-8 and FADD proteins, and subsequent necrotic cell death during inflammatory TNFα stimulation. This study provides a resource for further elucidation of TNFα-dependent signaling pathways. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Novobiocin: redesigning a DNA gyrase inhibitor for selective inhibition of hsp90.

PubMed

Burlison, Joseph A; Neckers, Len; Smith, Andrew B; Maxwell, Anthony; Blagg, Brian S J

2006-12-06

Novobiocin is a member of the coumermycin family of antibiotics and is a well-established inhibitor of DNA gyrase. Recent studies have shown that novobiocin binds to a previously unrecognized ATP-binding site at the C-terminus of Hsp90 and induces degradation of Hsp90-dependent client proteins at approximately 700 microM. In an effort to develop more efficacious inhibitors of the C-terminal binding site, a library of novobiocin analogues was prepared and initial structure-activity relationships revealed. These data suggested that the 4-hydroxy moiety of the coumarin ring and the 3'-carbamate of the noviose appendage were detrimental to Hsp90 inhibitory activity. In an effort to confirm these findings, 4-deshydroxy novobiocin (DHN1) and 3'-descarbamoyl-4-deshydroxynovobiocin (DHN2) were prepared and evaluated against Hsp90. Both compounds were significantly more potent than the natural product, and DHN2 proved to be more active than DHN1. In an effort to determine whether these moieties are important for DNA gyrase inhibition, these compounds were tested for their ability to inhibit DNA gyrase and found to exhibit significant reduction in gyrase activity. Thus, we have established the first set of compounds that clearly differentiate between the C-terminus of Hsp90 and DNA gyrase, converted a well-established gyrase inhibitor into a selective Hsp90 inhibitor, and confirmed essential structure-activity relationships for the coumermycin family of antibiotics.

Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy

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

Que, Emily L.; Duncan, Francesca E.; Bayer, Amanda R.

During fertilization or chemically-induced egg activation, the mouse egg releases billions of zinc atoms in brief bursts known as ‘zinc sparks.’ The zona pellucida (ZP), a glycoprotein matrix surrounding the egg, is the first structure zinc ions encounter as they diffuse away from the plasma membrane. Following fertilization, the ZP undergoes changes described as ‘hardening’, which prevent multiple sperm from fertilizing the egg and thereby establish a block to polyspermy. A major event in zona hardening is cleavage of ZP2 proteins by ovastacin; however, the overall physiochemical changes contributing to zona hardening are not well understood. Using x-ray fluorescence microscopy,more » transmission and scanning electron microscopy, and biological function assays, we tested the hypothesis that zinc release contributes to ZP hardening. We found that the zinc content in the ZP increases by 300% following activation and that zinc exposure modulates the architecture of the ZP matrix. Importantly, zinc-induced structural changes of the ZP have a direct biological consequence; namely, they reduce the ability of sperm to bind to the ZP. These results provide a paradigm-shifting model in which fertilization-induced zinc sparks contribute to the polyspermy block by altering conformations of the ZP matrix. Finally, this adds a previously unrecognized factor, namely zinc, to the process of ZP hardening.« less

Engineered fusokine GIFT4 licenses the ability of B cells to trigger a tumoricidal T-cell response.

PubMed

Deng, Jiusheng; Yuan, Shala; Pennati, Andrea; Murphy, Jordan; Wu, Jian Hui; Lawson, David; Galipeau, Jacques

2014-08-01

Engineered chimeric cytokines can generate gain-of-function activity in immune cells. Here, we report potent antitumor activity for a novel fusion cytokine generated by N-terminal coupling of GM-CSF to IL4, generating a fusokine termed GIFT4. B cells treated with GIFT4 clustered GM-CSF and IL4 receptors on the cell surface and displayed a pan-STAT hyperphosphorylation associated with acquisition of a distinct phenotype and function described to date. In C57BL/6J mice, administration of GIFT4 expanded endogenous B cells and suppressed the growth of B16F0 melanoma cells. Furthermore, B16F0 melanoma cells engineered to secrete GIFT4 were rejected immunologically in a B-cell-dependent manner. This effect was abolished when GIFT4-expressing B16F0 cells were implanted in B-cell-deficient mice, confirming a B-cell-dependent antitumor effect. Human GIFT4-licensed B cells primed cytotoxic T cells and specifically killed melanoma cells in vitro and in vivo. Taken together, our results demonstrated that GIFT4 could mediate expansion of B cells with potent antigen-specific effector function. GIFT4 may offer a novel immunotherapeutic tool and define a previously unrecognized potential for B cells in melanoma immunotherapy. ©2014 American Association for Cancer Research.

What's hot, what's new in basic science: report from the American Transplant Congress 2015.

PubMed

Heeger, P S

2015-11-01

Research reports presented at the American Transplant Congress 2015 provided an array of basic science findings of relevance to the transplant community. Among key themes is the concept that ischemia-reperfusion injury and early posttransplantation inflammation is linked to adaptive alloimmunity and transplant injury. Molecular and cellular mechanisms contributing to these interactions were highlighted. The relevance of understanding how blocking costimulation, including CD40/CD154 interactions, affects various aspects of the alloimmune response was enhanced by the description of preclinical studies demonstrating efficacy of a unique, blocking anti-CD40 monoclonal antibody that could potentially be used in humans. The identification of mechanisms underlying interactions among T cell subsets and B cells, including follicular helper T cells, regulatory T cells, effector B cells, and regulatory B cells, provides multiple previously unrecognized targets for future therapeutic interventions. Additional reports of interest include novel insights into effects of the gut microbiome on graft survival and the ability to differentiate insulin-secreting, islet-like cells from induced pluripotent stem cells. Overall, the reported basic science findings from American Transplant Congress 2015 add to the fundamental understanding of innate and adaptive alloimmunity and provide novel and testable hypotheses that have the potential to be translated into improved clinical care of transplant patients. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy

DOE PAGES

Que, Emily L.; Duncan, Francesca E.; Bayer, Amanda R.; ...

2017-01-19

During fertilization or chemically-induced egg activation, the mouse egg releases billions of zinc atoms in brief bursts known as ‘zinc sparks.’ The zona pellucida (ZP), a glycoprotein matrix surrounding the egg, is the first structure zinc ions encounter as they diffuse away from the plasma membrane. Following fertilization, the ZP undergoes changes described as ‘hardening’, which prevent multiple sperm from fertilizing the egg and thereby establish a block to polyspermy. A major event in zona hardening is cleavage of ZP2 proteins by ovastacin; however, the overall physiochemical changes contributing to zona hardening are not well understood. Using x-ray fluorescence microscopy,more » transmission and scanning electron microscopy, and biological function assays, we tested the hypothesis that zinc release contributes to ZP hardening. We found that the zinc content in the ZP increases by 300% following activation and that zinc exposure modulates the architecture of the ZP matrix. Importantly, zinc-induced structural changes of the ZP have a direct biological consequence; namely, they reduce the ability of sperm to bind to the ZP. These results provide a paradigm-shifting model in which fertilization-induced zinc sparks contribute to the polyspermy block by altering conformations of the ZP matrix. Finally, this adds a previously unrecognized factor, namely zinc, to the process of ZP hardening.« less

The Role of DNA Barcodes in Understanding and Conservation of Mammal Diversity in Southeast Asia

PubMed Central

Francis, Charles M.; Borisenko, Alex V.; Ivanova, Natalia V.; Eger, Judith L.; Lim, Burton K.; Guillén-Servent, Antonio; Kruskop, Sergei V.; Mackie, Iain; Hebert, Paul D. N.

2010-01-01

Background Southeast Asia is recognized as a region of very high biodiversity, much of which is currently at risk due to habitat loss and other threats. However, many aspects of this diversity, even for relatively well-known groups such as mammals, are poorly known, limiting ability to develop conservation plans. This study examines the value of DNA barcodes, sequences of the mitochondrial COI gene, to enhance understanding of mammalian diversity in the region and hence to aid conservation planning. Methodology and Principal Findings DNA barcodes were obtained from nearly 1900 specimens representing 165 recognized species of bats. All morphologically or acoustically distinct species, based on classical taxonomy, could be discriminated with DNA barcodes except four closely allied species pairs. Many currently recognized species contained multiple barcode lineages, often with deep divergence suggesting unrecognized species. In addition, most widespread species showed substantial genetic differentiation across their distributions. Our results suggest that mammal species richness within the region may be underestimated by at least 50%, and there are higher levels of endemism and greater intra-specific population structure than previously recognized. Conclusions DNA barcodes can aid conservation and research by assisting field workers in identifying species, by helping taxonomists determine species groups needing more detailed analysis, and by facilitating the recognition of the appropriate units and scales for conservation planning. PMID:20838635

Global functions of extracellular, transmembrane and cytoplasmic domains of organic solute transporter β-subunit.

PubMed

Christian, Whitney V; Hinkle, Patricia M

2017-05-25

Transport of bile acids across the basolateral membrane of the intestinal enterocyte is carried out by the organic solute transporter (Ost) composed of a seven-transmembrane domain (TMD) subunit (Ostα) and an ancillary single TMD subunit (Ostβ). Although previous investigations have demonstrated the importance of the TMD of Ostβ for its activity, further studies were conducted to assess the contributions of other regions of the Ostβ subunit. Transport activity was retained when Ostβ was truncated to contain only the TMD with 15 additional residues on each side and co-expressed with Ostα, whereas shorter fragments were inactive. To probe the broader functions of Ostβ segments, chimeric proteins were constructed in which N-terminal, TMD or C-terminal regions of Ostβ were fused to corresponding regions of receptor activity-modifying protein (RAMP1), a single TMD protein required by several seven-TMD G-protein-coupled receptors including the calcitonin receptor-like receptor (CLR). Ostβ/RAMP1 chimeras were expressed with Ostα and CLR. As expected, replacing the Ostβ TMD abolished transport activity; however, replacing either the entire N-terminal or entire C-terminal domain of Ostβ with RAMP1 sequences did not prevent plasma membrane localization or the ability to support [ 3 H]taurocholate uptake. Co-immunoprecipitation experiments revealed that the C-terminus of Ostβ is a previously unrecognized site of interaction with Ostα. All chimeras containing N-terminal RAMP1 segments allowed co-expressed CLR to respond to agonists with strong increases in cyclic AMP. These results provide new insights into the structure and function of the heteromeric Ost transporter complex. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Pentose sugars inhibit metabolism and increase expression of an AgrD-type cyclic pentapeptide in Clostridium thermocellum

DOE PAGES

Verbeke, Tobin J.; Giannone, Richard J.; Klingeman, Dawn M.; ...

2017-02-23

Significant hurdles exist in efforts to domesticate and industrialize a microbial species for biotechnological application as specific metabolic functions found in natural communities disappear in axenic cultures. For the lignocellulose-deconstructing specialist Clostridium thermocellum, the catabolism of hemicellulose-derived pentoses, which the bacterium cannot ferment, is one such function. Here, we report that various xylo-oligomers significantly inhibit C. thermocellum metabolism and growth and that microbe-sugar interactions occur across multiple dimensions. First, stable isotope metabolomics confirmed C. thermocellum s ability to transport and metabolize pentose sugars. This transport occurs, at least in part, through the ATP-dependent transporter, CbpD. Secondly, xylose is an electronmore » sink for C. thermocellum metabolism leading to the production of xylitol. Deletion of Clo1313_0076, annotated as a xylitol dehydrogenase, reduced the total production and molar xylitol yields by 41% and 46%, respectively. However, it also altered the relative end-product distribution patterns confirming that external electron acceptors may influence the bacterium s redox metabolism to a greater extent than previously considered. Finally, xylose-induced inhibition corresponds with the up-regulation and biogenesis of an AgrD-type, lactone cyclized pentapeptide signaling molecule; which is the first report of an AgrD-type signaling peptide in any thermophile. Addition of synthetic versions of the cyclic peptide inhibited cultures grown in the absence of xylose, but had no effect on cultures already inhibited by the pentose sugar. Together, our findings identify that C. thermocellum has evolved previously unrecognized strategies to cope with C5-sugars, but the absence of a native catabolic sink negatively affects strain metabolism and growth.« less

Pentose sugars inhibit metabolism and increase expression of an AgrD-type cyclic pentapeptide in Clostridium thermocellum

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

Verbeke, Tobin J.; Giannone, Richard J.; Klingeman, Dawn M.

Significant hurdles exist in efforts to domesticate and industrialize a microbial species for biotechnological application as specific metabolic functions found in natural communities disappear in axenic cultures. For the lignocellulose-deconstructing specialist Clostridium thermocellum, the catabolism of hemicellulose-derived pentoses, which the bacterium cannot ferment, is one such function. Here, we report that various xylo-oligomers significantly inhibit C. thermocellum metabolism and growth and that microbe-sugar interactions occur across multiple dimensions. First, stable isotope metabolomics confirmed C. thermocellum s ability to transport and metabolize pentose sugars. This transport occurs, at least in part, through the ATP-dependent transporter, CbpD. Secondly, xylose is an electronmore » sink for C. thermocellum metabolism leading to the production of xylitol. Deletion of Clo1313_0076, annotated as a xylitol dehydrogenase, reduced the total production and molar xylitol yields by 41% and 46%, respectively. However, it also altered the relative end-product distribution patterns confirming that external electron acceptors may influence the bacterium s redox metabolism to a greater extent than previously considered. Finally, xylose-induced inhibition corresponds with the up-regulation and biogenesis of an AgrD-type, lactone cyclized pentapeptide signaling molecule; which is the first report of an AgrD-type signaling peptide in any thermophile. Addition of synthetic versions of the cyclic peptide inhibited cultures grown in the absence of xylose, but had no effect on cultures already inhibited by the pentose sugar. Together, our findings identify that C. thermocellum has evolved previously unrecognized strategies to cope with C5-sugars, but the absence of a native catabolic sink negatively affects strain metabolism and growth.« less

Evidence of infection with H4 and H11 avian influenza viruses among Lebanese chicken growers.

PubMed

Kayali, Ghazi; Barbour, Elie; Dbaibo, Ghassan; Tabet, Carelle; Saade, Maya; Shaib, Houssam A; Debeauchamp, Jennifer; Webby, Richard J

2011-01-01

Human infections with H5, H7, and H9 avian influenza viruses are well documented. Exposure to poultry is the most important risk factor for humans becoming infected with these viruses. Data on human infection with other low pathogenicity avian influenza viruses is sparse but suggests that such infections may occur. Lebanon is a Mediterranean country lying under two major migratory birds flyways and is home to many wild and domestic bird species. Previous reports from this country demonstrated that low pathogenicity avian influenza viruses are in circulation but highly pathogenic H5N1 viruses were not reported. In order to study the extent of human infection with avian influenza viruses in Lebanon, we carried out a seroprevalence cross-sectional study into which 200 poultry-exposed individuals and 50 non-exposed controls were enrolled. We obtained their sera and tested it for the presence of antibodies against avian influenza viruses types H4 through H16 and used a questionnaire to collect exposure data. Our microneutralization assay results suggested that backyard poultry growers may have been previously infected with H4 and H11 avian influenza viruses. We confirmed these results by using a horse red blood cells hemagglutination inhibition assay. Our data also showed that farmers with antibodies against each virus type clustered in a small geographic area suggesting that unrecognized outbreaks among birds may have led to these human infections. In conclusion, this study suggests that occupational exposure to chicken is a risk factor for infection with avian influenza especially among backyard growers and that H4 and H11 influenza viruses may possess the ability to cross the species barrier to infect humans.

Quid est Clea helena? Evidence for a previously unrecognized radiation of assassin snails (Gastropoda: Buccinoidea: Nassariidae)

PubMed Central

Galindo, Lee Ann; Kantor, Yuri I.

2017-01-01

The genus Clea from SE Asia is from one of only two unrelated families among the megadiverse predatory marine Neogastropoda to have successfully conquered continental waters. While little is known about their anatomy, life history and ecology, interest has grown exponentially in recent years owing to their increasing popularity as aquarium pets. However, the systematic affinities of the genus and the validity of the included species have not been robustly explored. Differences in shell, operculum and radula characters support separation of Clea as presently defined into two distinct genera: Clea, for the type species Clea nigricans and its allies, and Anentome for Clea helena and allies. A five-gene mitochondrial (COI, 16S, 12S) and nuclear (H3, 28S) gene dataset confirms the placement of Anentome as a somewhat isolated offshoot of the family Nassariidae and sister to the estuarine Nassodonta. Anatomical data corroborate this grouping and, in conjunction with their phylogenetic placement, support their recognition as a new subfamily, the Anentominae. The assassin snail Anentome helena, a popular import through the aquarium trade so named for their voracious appetite for other snails, is found to comprise a complex of at least four species. None of these likely represents true Anentome helena described from Java, including a specimen purchased through the aquarium trade under this name in the US and one that was recently found introduced in Singapore, both of which were supported as conspecific with a species from Thailand. The introduction of Anentome “helena” through the aquarium trade constitutes a significant threat to native aquatic snail faunas which are often already highly imperiled. Comprehensive systematic revision of this previously unrecognized species complex is urgently needed to facilitate communication and manage this emerging threat. PMID:28828249

Src homology 2 domain-containing phosphatase 2 (Shp2) is a component of the A-kinase-anchoring protein (AKAP)-Lbc complex and is inhibited by protein kinase A (PKA) under pathological hypertrophic conditions in the heart.

PubMed

Burmeister, Brian T; Taglieri, Domenico M; Wang, Li; Carnegie, Graeme K

2012-11-23

AKAP-Lbc is a scaffold protein that coordinates cardiac hypertrophic signaling. AKAP-Lbc interacts with Shp2, facilitating its regulation by PKA. AKAP-Lbc integrates PKA and Shp2 signaling in the heart. Under pathological hypertrophic conditions Shp2 is phosphorylated by PKA, and phosphatase activity is inhibited. Inhibition of Shp2 activity through AKAP-Lbc-anchored PKA is a previously unrecognized mechanism that may promote pathological cardiac hypertrophy. Pathological cardiac hypertrophy (an increase in cardiac mass resulting from stress-induced cardiac myocyte growth) is a major factor underlying heart failure. Our results identify a novel mechanism of Shp2 inhibition that may promote cardiac hypertrophy. We demonstrate that the tyrosine phosphatase, Shp2, is a component of the A-kinase-anchoring protein (AKAP)-Lbc complex. AKAP-Lbc facilitates PKA phosphorylation of Shp2, which inhibits its protein-tyrosine phosphatase activity. Given the important cardiac roles of both AKAP-Lbc and Shp2, we investigated the AKAP-Lbc-Shp2 interaction in the heart. AKAP-Lbc-tethered PKA is implicated in cardiac hypertrophic signaling; however, mechanism of PKA action is unknown. Mutations resulting in loss of Shp2 catalytic activity are also associated with cardiac hypertrophy and congenital heart defects. Our data indicate that AKAP-Lbc integrates PKA and Shp2 signaling in the heart and that AKAP-Lbc-associated Shp2 activity is reduced in hypertrophic hearts in response to chronic β-adrenergic stimulation and PKA activation. Thus, while induction of cardiac hypertrophy is a multifaceted process, inhibition of Shp2 activity through AKAP-Lbc-anchored PKA is a previously unrecognized mechanism that may promote compensatory cardiac hypertrophy.

Viral Surveillance in Serum Samples From Patients With Acute Liver Failure By Metagenomic Next-Generation Sequencing.

PubMed

Somasekar, Sneha; Lee, Deanna; Rule, Jody; Naccache, Samia N; Stone, Mars; Busch, Michael P; Sanders, Corron; Lee, William M; Chiu, Charles Y

2017-10-16

Twelve percent of all acute liver failure (ALF) cases are of unknown origin, often termed indeterminate. A previously unrecognized hepatotropic virus has been suspected as a potential etiologic agent. We compared the performance of metagenomic next-generation sequencing (mNGS) with confirmatory nucleic acid testing (NAT) to routine clinical diagnostic testing in detection of known or novel viruses associated with ALF. Serum samples from 204 adult ALF patients collected from 1998 to 2010 as part of a nationwide registry were analyzed. One hundred eighty-seven patients (92%) were classified as indeterminate, while the remaining 17 patients (8%) served as controls, with infections by either hepatitis A virus or hepatitis B virus (HBV), or a noninfectious cause for their ALF. Eight cases of infection from previously unrecognized viral pathogens were detected by mNGS (4 cases of herpes simplex virus type 1, including 1 case of coinfection with HBV, and 1 case each of HBV, parvovirus B19, cytomegalovirus, and human herpesvirus 7). Several missed dual or triple infections were also identified, and assembled viral genomes provided additional information on genotyping and drug resistance mutations. Importantly, no sequences corresponding to novel viruses were detected. These results suggest that ALF patients should be screened for the presence of uncommon viruses and coinfections, and that most cases of indeterminate ALF in the United States do not appear to be caused by novel viral pathogens. In the future, mNGS testing may be useful for comprehensive diagnosis of viruses associated with ALF, or to exclude infectious etiologies. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

A carbon isotopic and sedimentological record of the latest Devonian (Famennian) from the Western U.S. and Germany

USGS Publications Warehouse

Myrow, P.M.; Strauss, J.V.; Creveling, J.R.; Sicard, K.R.; Ripperdan, R.; Sandberg, C.A.; Hartenfels, S.

2011-01-01

New carbon isotopic data from upper Famennian deposits in the western United States reveal two previously unrecognized major positive isotopic excursions. The first is an abrupt ~. 3??? positive excursion, herein referred to as ALFIE (A Late Famennian Isotopic Excursion), recorded in two sections of the Pinyon Peak Limestone of north-central Utah. Integration of detailed chemostratigraphic and biostratigraphic data suggests that ALFIE is the Laurentian record of the Dasberg Event, which has been linked to transgression in Europe and Morocco. Sedimentological data from the Chaffee Group of western Colorado also record transgression at a similar biostratigraphic position, with a shift from restricted to open-marine lithofacies. ALFIE is not evident in chemostratigraphic data from age-equivalent strata in Germany studied herein and in southern Europe, either because it is a uniquely North American phenomenon, or because the German sections are too condensed relative to those in Laurentia. A second positive carbon isotopic excursion from the upper Chaffee Group of Colorado is recorded in transgressive strata deposited directly above a previously unrecognized paleokarst interval. The age of this excursion, and the duration of the associated paleokarst hiatus, are not well constrained, although the events occurred sometime after the Late Famennian Middle expansa Zone. The high positive values recorded in this excursion are consistent with those associated with the youngest Famennian Middle to Late praesulcata Hangenberg Isotopic Excursion in Europe, the isotopic expression of the Hangenberg Event, which included mass extinction, widespread black shale deposition, and a glacio-eustatic fall and rise. If correct, this would considerably revise the age of the Upper Chaffee Group strata of western Colorado. ?? 2011 Elsevier B.V.

Evidence for a previously unrecognized species of owlet-nightjar

USGS Publications Warehouse

Pratt, T.K.

2000-01-01

I studied the systematic relationships of the three large owlet-nightjars (Aegothelidae) to determine the taxonomic status of a fawn-colored lowland form currently classified as Aegotheles insignis tatei. I examined most of the existing specimens of A. i. insignis (n = 158) and A. crinifrons (n = 23) and all known specimens of A. i. tatei (n = 4). I also examined specimens of A. albertisi (n = 70), A. archboldi (n = 25), A. bennettii (n = 55), A. cristatus (n = 50), A. savesi (n = 1), and A. wallacii (n = 21). Aegotheles i. tatei was distinguishable from A. i. insignis and A. crinifrons by its small size and in seven plumage characters. Aegotheles i. tatei was further distinguishable from one or the other of these taxa by four additional characters. Unique among owlet-nightjars, A. i. tatei has the shortest tarsi, does not have recurved filamentous tips on its facial feathers, and has stiffer feathers on the auricular area and throat. My search of museums revealed two new specimens of A. i. tatei, expanding the known geographic range of this taxon 1,000 km eastward along the southern coast of Papua New Guinea from the upper Fly River to Nunumai, near the Ulamanu River. Unlike the montane A. i. insignis, A. i. tatei inhabits lowland forests where rivers emerge from foothills of the main cordillera. I propose that tatei be elevated to species status and that the name Starry Owlet-Nightjar be adopted based on the bird's markings. Aegotheles crinifrons, A. insignis, and A. tatei pass through a previously unrecognized but distinctive rufous juvenal plumage. These are the only owlet-nightjars known to exhibit this plumage, which calls for reexamination of generic limits within the Aegothelidae.

MUC1-C Represses the Crumbs Complex Polarity Factor CRB3 and Downregulates the Hippo Pathway

PubMed Central

Alam, Maroof; Bouillez, Audrey; Tagde, Ashujit; Ahmad, Rehan; Rajabi, Hasan; Maeda, Takahiro; Hiraki, Masayuki; Suzuki, Yozo; Kufe, Donald

2016-01-01

Apical-basal polarity and epithelial integrity are maintained in part by the Crumbs (CRB) complex. The C-terminal subunit of MUC1 (MUC1-C) is a transmembrane protein that is expressed at the apical border of normal epithelial cells and aberrantly at high levels over the entire surface of their transformed counterparts. However, it is not known if MUC1-C contributes to this loss of polarity that is characteristic of carcinoma cells. Here it is demonstrated that MUC1-C downregulates expression of the Crumbs complex CRB3 protein in triple-negative breast cancer (TNBC) cells. MUC1-C associates with ZEB1 on the CRB3 promoter and represses CRB3 transcription. Notably, CRB3 activates the core kinase cassette of the Hippo pathway, which includes LATS1 and LATS2. In this context, targeting MUC1-C was associated with increased phosphorylation of LATS1, consistent with activation of the Hippo pathway, which is critical for regulating cell contact, tissue repair, proliferation and apoptosis. Also shown is that MUC1-C-mediated suppression of CRB3 and the Hippo pathway is associated with dephosphorylation and activation of the oncogenic YAP protein. In turn, MUC1-C interacts with YAP, promotes formation of YAP/β-catenin complexes and induces the WNT target gene MYC. These data support a previously unrecognized model in which targeting MUC1-C in TNBC cells (i) induces CRB3 expression, (ii) activates the CRB3-driven Hippo pathway, (iii) inactivates YAP, and thereby (iv) suppresses YAP/β-catenin-mediated induction of MYC expression. Implications These findings demonstrate a previously unrecognized role for the MUC1-C oncoprotein in the regulation of polarity and the Hippo pathway in breast cancer. PMID:27658423

Unexpected tautomeric equilibria of the carbanion-enamine intermediate in pyruvate oxidase highlight unrecognized chemical versatility of thiamin

PubMed Central

Meyer, Danilo; Neumann, Piotr; Koers, Eline; Sjuts, Hanno; Lüdtke, Stefan; Sheldrick, George M.; Ficner, Ralf; Tittmann, Kai

2012-01-01

Thiamin diphosphate, the vitamin B1 coenzyme, plays critical roles in fundamental metabolic pathways that require acyl carbanion equivalents. Studies on chemical models and enzymes had suggested that these carbanions are resonance-stabilized as enamines. A crystal structure of this intermediate in pyruvate oxidase at 1.1 Å resolution now challenges this paradigm by revealing that the enamine does not accumulate. Instead, the intermediate samples between the ketone and the carbanion both interlocked in a tautomeric equilibrium. Formation of the keto tautomer is associated with a loss of aromaticity of the cofactor. The alternate confinement of electrons to neighboring atoms rather than π-conjugation seems to be of importance for the enzyme-catalyzed, redox-coupled acyl transfer to phosphate, which requires a dramatic inversion of polarity of the reacting substrate carbon in two subsequent catalytic steps. The ability to oscillate between a nucleophilic (carbanion) and an electrophilic (ketone) substrate center highlights a hitherto unrecognized versatility of the thiamin cofactor. It remains to be studied whether formation of the keto tautomer is a general feature of all thiamin enzymes, as it could provide for stable storage of the carbanion state, or whether this feature represents a specific trait of thiamin oxidases. In addition, the protonation state of the two-electron reduced flavin cofactor can be fully assigned, demonstrating the power of high-resolution cryocrystallography for elucidation of enzymatic mechanisms. PMID:22730460

Structural geologic analysis of Nevada using ERTS-1 images: A preliminary report

NASA Technical Reports Server (NTRS)

Rowan, L. C.; Wetlaufer, P. H.

1973-01-01

Structural analysis of Nevada using ERTS-1 images showns several previously unrecognized lineaments which may be the surface manifestations of major fault or fracture zones. Principle trends are NE, NW, NNE-NNW, and ENE. Two lineament zones, the Walker Lane and Midas Trench lineament system, transect the predominantly NNE-NNW trending mountain ranges for more than 500 km. 50 circular features have been delineated. Comparison with known Tertiary volcanic centers and reference to geologic maps suggest 8 new centers. Preferred distribution of mines and Tertiary volcanic centers along some of the major lineament suggests a genetic relationship. The intersection of three previously unmapped lineaments in northwestern Nevada is the location of a highly productive metallogenic district. In the Walker Lane, ENE-trending lineament appear to be related to the occurrence of productive ore deposits.

Solving the shrinkage-induced PDMS alignment registration issue in multilayer soft lithography

NASA Astrophysics Data System (ADS)

Moraes, Christopher; Sun, Yu; Simmons, Craig A.

2009-06-01

Shrinkage of polydimethylsiloxane (PDMS) complicates alignment registration between layers during multilayer soft lithography fabrication. This often hinders the development of large-scale microfabricated arrayed devices. Here we report a rapid method to construct large-area, multilayered devices with stringent alignment requirements. This technique, which exploits a previously unrecognized aspect of sandwich mold fabrication, improves device yield, enables highly accurate alignment over large areas of multilayered devices and does not require strict regulation of fabrication conditions or extensive calibration processes. To demonstrate this technique, a microfabricated Braille display was developed and characterized. High device yield and accurate alignment within 15 µm were achieved over three layers for an array of 108 Braille units spread over a 6.5 cm2 area, demonstrating the fabrication of well-aligned devices with greater ease and efficiency than previously possible.

Unrecognised ventriculitis/meningitis presenting as hydrocephalus in infancy.

PubMed

Udani, Vrajesh; Udani, Soonu; Merani, Rohan; Bavdekar, Manisha

2003-09-01

Infantile hydrocephalus due to unrecognized neonatal-onset meningitis/ventriculitis, was studied retrospectively using 1991-1998 chart review. Seventy two patients with hydrocephalus were reviewed. Thirteen infants had hydrocephalus associated with active meningitis/ventriculitis which had remained unrecognized. Active meningitis/ventriculitis was confirmed by the finding of an abnormal lumbar and ventricular CSF with or without positive culture. All had perinatal risk factors and 10/13 had been given antibiotics in the postnatal period. 6/13 infants appeared to be well. The most common presentation was increasing head size. All lumbar and ventricular CSFs were abnormal and 10/13 had positive cultures as well. Imaging revealed hydrocephalus in all. The infants were treated with antibiotics for a mean of 32.8 days before VP shunting. 7/11 were severely disabled. Unrecognized active meningitis/ventriculitis is an important cause of infantile hydrocephalus.

Characteristic illness behaviour in assault patients: DATES syndrome.

PubMed Central

Shepherd, J P; Peak, J D; Haria, S; Sleeman, F

1995-01-01

Violent crime has become a public health issue, not least because the needs of victims have been neglected in the criminal justice system. Since this group suffer more psychological distress than victims of accidents, we compared illness experience in 433 adult assault victims with paired victims of accidents in a case control study. In the 10 year period prior to injury, there was a significant excess of hospital contacts in the assault group in relation to trauma, elective surgery and drug abuse but not to other psychiatric or medical conditions. This spectrum of disorders constitutes a previously unrecognized syndrome in young adults, probably representing the manifestations of antisocial personality. PMID:7769600

Alpha Trianguli Australis (K2 II-III) - Hybrid or composite?

NASA Technical Reports Server (NTRS)

Ayres, T. R.

1985-01-01

The prototype hybrid-spectrum giant Alpha Trianguli Australis exhibits a far-ultraviolet continuum which is considerably bluer than would be expected of a star of its optical colors, suggesting the presence of a previously unrecognized companion. If the K-type primary is as luminous as indicated by the widths of its Ca II and H-alpha lines, the companion could be an early F-type dwarf that only recently has arrived on the main sequence. Indeed, the flux of C IV from Alpha TrA - an important measure of hybridness - would not be inconsistent with that expected from a very young chromospherically active F star.

Antibacterial activity of silver-killed bacteria: the "zombies" effect

NASA Astrophysics Data System (ADS)

Wakshlak, Racheli Ben-Knaz; Pedahzur, Rami; Avnir, David

2015-04-01

We report a previously unrecognized mechanism for the prolonged action of biocidal agents, which we denote as the zombies effect: biocidally-killed bacteria are capable of killing living bacteria. The concept is demonstrated by first killing Pseudomonas aeruginosa PAO1 with silver nitrate and then challenging, with the dead bacteria, a viable culture of the same bacterium: Efficient antibacterial activity of the killed bacteria is observed. A mechanism is suggested in terms of the action of the dead bacteria as a reservoir of silver, which, due to Le-Chatelier's principle, is re-targeted to the living bacteria. Langmuirian behavior, as well as deviations from it, support the proposed mechanism.

Predatory Dinosaurs from the Sahara and Late Cretaceous Faunal Differentiation

PubMed

Sereno; Dutheil; Iarochene; Larsson; Lyon; Magwene; Sidor; Varricchio; Wilson

1996-05-17

Late Cretaceous (Cenomanian) fossils discovered in the Kem Kem region of Morocco include large predatory dinosaurs that inhabited Africa as it drifted into geographic isolation. One, represented by a skull approximately 1.6 meters in length, is an advanced allosauroid referable to the African genus Carcharodontosaurus. Another, represented by a partial skeleton with slender proportions, is a new basal coelurosaur closely resembling the Egyptian genus Bahariasaurus. Comparisons with Cretaceous theropods from other continents reveal a previously unrecognized global radiation of carcharodontosaurid predators. Substantial geographic differentiation of dinosaurian faunas in response to continental drift appears to have arisen abruptly at the beginning of the Late Cretaceous.

Puzzling questions about excited superdeformed rotational bands of atomic nuclei are answered by the two-revolving-cluster model.

PubMed Central

Pauling, L

1992-01-01

The two-revolving-cluster model provides explanations of several questions about excited superdeformed bands: restriction to the lanthanons and the Hg-Tl-Pb region and to the smaller values of the neutron number for each element, truncation of the gamma-ray cascades, differences in shape of the lanthanon and Hg-Tl-Pb bands, alignment of quantified spins, and the existence of pairs of bands with nearly identical gamma-ray sequences. A previously unrecognized kind of pairing (intercalation of gamma-ray values) is also reported and a discussion is given of the values of electric quadrupole moments. PMID:11607327

Phencyclidine and Chemical “Stroking”

PubMed Central

Alexander, Ranya L.

1980-01-01

The current wave of drug abuse is but the latest manifestation of the real human need for “stroking.” Drugs which affect the pleasure center of the brain are prime objects of abuse. Phencyclidine (“PCP” or “angel dust”) is a cyclohexylamine which has properties of the amphetamine-stimulants, the narcotic-depressants and the hallucinogens. Previously unrecognized population groups include children less than six years of age and pregnant women and their intoxicated offspring. Successful treatment of present and future patients must be multidisciplinary and will ultimately depend upon a clear understanding of the pharmacology, social psychology, politics, and economics of drugs of abuse. PMID:7191444

Seafloor character and sedimentary processes in eastern Long Island Sound and western Block Island Sound

USGS Publications Warehouse

Poppe, Lawrence J.; Cohen-DiGiacomo, M. L.; Smith, S.M.; Stewart, H.F.; Forfinski, N.A.

2006-01-01

Multibeam bathymetric data and seismic-reflection profiles collected in eastern Long Island Sound and western Block Island Sound reveal previously unrecognized glacial features and modern bedforms. Glacial features include an ice-sculptured bedrock surface, a newly identified recessional moraine, exposed glaciolacustrine sediments, and remnants of stagnant-ice-contact deposits. Modern bedforms include fields of transverse sand waves, barchanoid waves, giant scour depressions, and pockmarks. Bedform asymmetry and scour around obstructions indicate that net sediment transport is westward across the northern part of the study area near Fishers Island, and eastward across the southern part near Great Gull Island.

MULTIFOCAL RETINAL INFILTRATES WITH PHLEBITIS AND OPTIC NEUROPATHY IN AN HIV-POSITIVE PEDIATRIC PATIENT.

PubMed

Kasi, Sundeep K; Vora, Robin A; Martin, Taliva; Cunningham, Emmett T

2015-01-01

To describe an unusual presentation of bilateral HIV-associated multifocal retinal infiltrates with phlebitis and optic neuropathy in a pediatric patient from Zimbabwe, Africa. Retrospective case report of a 15-year-old boy from Zimbabwe, Africa. The patient was found to have bilateral vitritis, multifocal retinitis with phlebitis, and optic neuropathy in the setting of previously unrecognized HIV infection. Vision improved and the clinical findings resolved after treatment with intravenous corticosteroids and highly active retroviral therapy (HAART). The authors describe the occurrence and treatment of bilateral, HIV-associated multifocal retinal infiltrates with phlebitis and HIV-associated optic neuropathy in a pediatric patient from Zimbabwe, Africa.

The 2002 Denali fault earthquake, Alaska: A large magnitude, slip-partitioned event

USGS Publications Warehouse

Eberhart-Phillips, D.; Haeussler, Peter J.; Freymueller, J.T.; Frankel, A.D.; Rubin, C.M.; Craw, P.; Ratchkovski, N.A.; Anderson, G.; Carver, G.A.; Crone, A.J.; Dawson, T.E.; Fletcher, H.; Hansen, R.; Harp, E.L.; Harris, R.A.; Hill, D.P.; Hreinsdottir, S.; Jibson, R.W.; Jones, L.M.; Kayen, R.; Keefer, D.K.; Larsen, C.F.; Moran, S.C.; Personius, S.F.; Plafker, G.; Sherrod, B.; Sieh, K.; Sitar, N.; Wallace, W.K.

2003-01-01

The MW (moment magnitude) 7.9 Denali fault earthquake on 3 November 2002 was associated with 340 kilometers of surface rupture and was the largest strike-slip earthquake in North America in almost 150 years. It illuminates earthquake mechanics and hazards of large strike-slip faults. It began with thrusting on the previously unrecognized Susitna Glacier fault, continued with right-slip on the Denali fault, then took a right step and continued with right-slip on the Totschunda fault. There is good correlation between geologically observed and geophysically inferred moment release. The earthquake produced unusually strong distal effects in the rupture propagation direction, including triggered seismicity.

A Statistical Test of the Relationship between Galactic HI Structure and Small-scale Structure in the Cosmic Microwave Background

NASA Astrophysics Data System (ADS)

Verschuur, Gerrit L.

2014-06-01

The archive of IRIS, PLANCK and WMAP data available at the IRSA website of IPAC allows the apparent associations between galactic neutral hydrogen (HI) features and small-scale structure in WMAP and PLANCK data to be closely examined. In addition, HI new observations made with the Green Bank Telescope are used to perform a statistical test of putative associations. It is concluded that attention should be paid to the possibility that some of the small-scale structure found in WMAP and PLANCK data harbors the signature of a previously unrecognized source of high-frequency continuum emission in the Galaxy.

Leg regeneration stunts wing growth and hinders flight performance in a stick insect (Sipyloidea sipylus).

PubMed

Maginnis, Tara L

2006-07-22

Major morphological structures are sometimes produced not once, but twice. For example, stick insects routinely shed legs to escape a predator or tangled moult, and these legs are subsequently re-grown. Here, I show that in Sipyloidea sipylus, re-growth of a leg during development causes adults to have disproportionately smaller wings and increases wing loading. These morphological consequences of leg regeneration led to significant reductions in several biologically relevant measures of individual flight performance. This previously unrecognized tradeoff between legs and wings reveals the integrated nature of phasmid phenotypes, and I propose how this tradeoff may have shaped phasmid evolution.

Changes in Central Walker Lane Strain Accommodation near Bridgeport, California; as told by the Stanislaus Group

NASA Astrophysics Data System (ADS)

Carlson, C. W.; Pluhar, C. J.; Glen, J. M.; Farner, M. J.

2012-12-01

Accommodating ~20-25% of the dextral-motion between the Pacific and North American plates the Walker Lane is represented as an elongate, NW oriented, region of active tectonics positioned between the northwesterly-translating Sierra Nevada microplate and the east-west extension of the Basin and Range. This region of transtension is being variably accommodated on regional-scale systems of predominantly strike-slip faulting. At the western edge of the central Walker Lane (ca. 38°-39°N latitude) is a region of crustal-scale blocks bounded by wedge-shaped depositional-basins and normal-fault systems, here defined as the west-central Walker Lane (WCWL). Devoid of obvious strike-slip faulting, the presence of tectonic-block vertical-axis rotations in the WCWL represents unrecognized components of dextral-shearing and/or changes of strain-accommodation over time. We use paleomagnetic reference directions for Eureka Valley Tuff (EVT) members of the late Miocene Stanislaus Group as spatial and temporal markers for documentation of tectonic-block vertical-axis rotations near Bridgeport, CA. Study-site rotations revealed discrete rotational domains of mean vertical-axis rotation ranging from ~10°-30° with heterogeneous regional distribution. Additionally, the highest measured magnitudes of vertical-axis rotation (~50°-60° CW) define a 'Region of High Strain' that includes the wedge-shaped Bridgeport Valley (Basin). This study revealed previously-unrecognized tectonic rotation of reference direction sites from prior studies for two (By-Day and Upper) of the three members of the EVT, resulting in under-estimates of regional strain accommodation by these studies. Mean remanent directions and virtual geomagnetic poles utilized in our study yielded a recalculated reference direction for the By-Day member of: Dec.=353.2°; Inc.= 43.7°; α95=10.1, in agreement with new measurements in the stable Sierra Nevada. This recalculated direction confirmed the presence of previously unrecognized reference site rotations, and provided an additional reference direction for determining vertical-axis rotation magnitudes. We present a kinematic model based on mean rotation magnitudes of ~30° CW for the Sweetwater Mountains and Bodie Hills that accounts for rotational-strain accommodation of dextral shear in the WCWL since the late Miocene. This model considers rotational magnitudes, paleostrain indicators, edge-effects, and strain-accommodating structures of rotating crustal blocks to represent changes in regional strain accommodation over time. The results and models presented here elucidate the complicated and evolving nature of the WCWL, and further understanding of variations in strain accommodation for the Walker Lane.

Coordinated regulation of accessory genetic elements produces cyclic di-nucleotides for V. cholerae virulence.

PubMed

Davies, Bryan W; Bogard, Ryan W; Young, Travis S; Mekalanos, John J

2012-04-13

The function of the Vibrio 7(th) pandemic island-1 (VSP-1) in cholera pathogenesis has remained obscure. Utilizing chromatin immunoprecipitation sequencing and RNA sequencing to map the regulon of the master virulence regulator ToxT, we identify a TCP island-encoded small RNA that reduces the expression of a previously unrecognized VSP-1-encoded transcription factor termed VspR. VspR modulates the expression of several VSP-1 genes including one that encodes a novel class of di-nucleotide cyclase (DncV), which preferentially synthesizes a previously undescribed hybrid cyclic AMP-GMP molecule. We show that DncV is required for efficient intestinal colonization and downregulates V. cholerae chemotaxis, a phenotype previously associated with hyperinfectivity. This pathway couples the actions of previously disparate genomic islands, defines VSP-1 as a pathogenicity island in V. cholerae, and implicates its occurrence in 7(th) pandemic strains as a benefit for host adaptation through the production of a regulatory cyclic di-nucleotide. Copyright © 2012 Elsevier Inc. All rights reserved.

A single macrolichen constitutes hundreds of unrecognized species.

PubMed

Lücking, Robert; Dal-Forno, Manuela; Sikaroodi, Masoumeh; Gillevet, Patrick M; Bungartz, Frank; Moncada, Bibiana; Yánez-Ayabaca, Alba; Chaves, José Luis; Coca, Luis Fernando; Lawrey, James D

2014-07-29

The number of Fungi is estimated at between 1.5 and 3 million. Lichenized species are thought to make up a comparatively small portion of this figure, with unrecognized species richness hidden among little-studied, tropical microlichens. Recent findings, however, suggest that some macrolichens contain a large number of unrecognized taxa, increasing known species richness by an order of magnitude or more. Here we report the existence of at least 126 species in what until recently was believed to be a single taxon: the basidiolichen fungus Dictyonema glabratum, also known as Cora pavonia. Notably, these species are not cryptic but morphologically distinct. A predictive model suggests an even larger number, with more than 400 species. These results call into question species concepts in presumably well-known macrolichens and demonstrate the need for accurately documenting such species richness, given the importance of these lichens in endangered ecosystems such as paramos and the alarming potential for species losses throughout the tropics.

Misleading hallucinations in unrecognized narcolepsy.

PubMed

Szucs, A; Janszky, J; Holló, A; Migléczi, G; Halász, P

2003-10-01

To describe psychosis-like hallucinatory states in unrecognized narcolepsy. Two patients with hypnagogic/hypnapompic hallucinations are presented. Both patients had realistic and complex - multi-modal and scenic-daytime sexual hallucinations leading, in the first case, to a legal procedure because of false accusation, and in the second, to serious workplace conflicts. Both patients were convinced of the reality of their hallucinatory experiences but later both were able to recognize their hallucinatory character. Clinical data, a multiple sleep latency test, polysomnography, and HLA typing revealed that both patients suffered from narcolepsy. We suggest that in unrecognized narcolepsy with daytime hypnagogic/hypnapompic hallucinations the diagnostic procedure may mistakenly incline towards delusional psychoses. Daytime realistic hypnagogic/hypnapompic hallucinations may also have forensic consequences and mislead legal evaluation. Useful clinical features in differentiating narcolepsy from psychoses are: the presence of other narcoleptic symptoms, features of hallucinations, and response to adequate medication.

Improved high-throughput quantification of luminescent microplate assays using a common Western-blot imaging system.

PubMed

Hawkins, Liam J; Storey, Kenneth B

2017-01-01

Common Western-blot imaging systems have previously been adapted to measure signals from luminescent microplate assays. This can be a cost saving measure as Western-blot imaging systems are common laboratory equipment and could substitute a dedicated luminometer if one is not otherwise available. One previously unrecognized limitation is that the signals captured by the cameras in these systems are not equal for all wells. Signals are dependent on the angle of incidence to the camera, and thus the location of the well on the microplate. Here we show that: •The position of a well on a microplate significantly affects the signal captured by a common Western-blot imaging system from a luminescent assay.•The effect of well position can easily be corrected for.•This method can be applied to commercially available luminescent assays, allowing for high-throughput quantification of a wide range of biological processes and biochemical reactions.

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

Wrighton, Kelly C.; Thomas, Brian C.; Sharon, I.

BD1-5, OP11, and OD1 bacteria have been widely detected in anaerobic environments, but their metabolisms remain unclear owing to lack of cultivated representatives and minimal genomic sampling. We uncovered metabolic characteristics for members of these phyla, and a new lineage, PER, via cultivation-independent recovery of 49 partial to near-complete genomes from an acetate-amended aquifer. All organisms were nonrespiring anaerobes predicted to ferment. Three augment fermentation with archaeal-like type II and III ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBisCO) that couples adenosine monophosphate salvage with CO2 fixation, a pathway previously not described in Bacteria. Members of OD1 reduce sulfur and may pump protons using archaeal-typemore » hydrogenases. For six organisms, the UGA stop codon is translated as tryptophan. All bacteria studied here may play previously unrecognized roles in hydrogen production, sulfur cycling, and fermentation of refractory sedimentary carbon.« less

The Role of Depression in the Differential Effect of Childhood Parental Divorce on Male and Female Adult Offspring Suicide Attempt Risk

PubMed Central

Lizardi, Dana; Thompson, Ronald G.; Keyes, Katherine; Hasin, Deborah

2013-01-01

In previous studies by our group, we found that female offspring of parental divorce and parental remarriage are more susceptible to suicide attempt than male offspring. In this study, we examine whether these findings remain even after controlling for offspring depression. The sample consists of respondents from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. Multivariable regressions controlled for offspring depression, parental depression, age, race/ethnicity, income, and marital status. Our previous findings that female offspring of parental divorce and parental remarriage are more likely to report a lifetime suicide attempt than male offspring remained even after controlling for offspring depression. Findings suggest that focusing on engaging female offspring who demonstrate symptoms of depression is not sufficient to reduce suicide attempt risk in this group as many at risk individuals will remain unrecognized. PMID:20823733

A new small-eared shrew of the Cryptotis nigrescens-group from Colombia (Mammalia: Soricomorpha: Soricidae)

USGS Publications Warehouse

Woodman, N.

2003-01-01

Cryptotis colombiana Woodman & Timm, 1993 previously was known from few specimens from two isolated regions in the Cordillera Central and Cordillera Oriental of Colombia. Recent collecting in the northern Cordillera Central and review of older collections from the central Cordillera Oriental in the vicinity of Bogota yielded additional specimens that permit reevaluation of the two geographic populations of these small-eared shrews. Morphological and morphometrical studies indicate that the population inhabiting the Cordillera Oriental represents a distinct, previously unrecognized species that I describe herein as Cryptotis brachyonyx. Study of 54 specimens of shrews from the Cordillera Oriental in systematic collections in North America, South America, and Europe yielded only four specimens of the new species, all collected before 1926. The paucity of modern specimens suggests that C. brachyonyx may be extremely restricted in distribution, or possibly extinct.

The role of depression in the differential effect of childhood parental divorce on male and female adult offspring suicide attempt risk.

PubMed

Lizardi, Dana; Thompson, Ronald G; Keyes, Katherine; Hasin, Deborah

2010-09-01

In previous studies by our group, we found that female offspring of parental divorce and parental remarriage are more susceptible to suicide attempt than male offspring. In this study, we examine whether these findings remain even after controlling for offspring depression. The sample consists of respondents from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. Multivariable regressions controlled for offspring depression, parental depression, age, race/ethnicity, income, and marital status. Our previous findings that female offspring of parental divorce and parental remarriage are more likely to report a lifetime suicide attempt than male offspring remained even after controlling for offspring depression. Findings suggest that focusing on engaging female offspring who demonstrate symptoms of depression is not sufficient to reduce suicide attempt risk in this group as many at risk individuals will remain unrecognized.

Machine Learning for Characterization of Insect Vector Feeding

PubMed Central

Willett, Nora S.; Stelinski, Lukasz L.; Lapointe, Stephen L.

2016-01-01

Insects that feed by ingesting plant and animal fluids cause devastating damage to humans, livestock, and agriculture worldwide, primarily by transmitting pathogens of plants and animals. The feeding processes required for successful pathogen transmission by sucking insects can be recorded by monitoring voltage changes across an insect-food source feeding circuit. The output from such monitoring has traditionally been examined manually, a slow and onerous process. We taught a computer program to automatically classify previously described insect feeding patterns involved in transmission of the pathogen causing citrus greening disease. We also show how such analysis contributes to discovery of previously unrecognized feeding states and can be used to characterize plant resistance mechanisms. This advance greatly reduces the time and effort required to analyze insect feeding, and should facilitate developing, screening, and testing of novel intervention strategies to disrupt pathogen transmission affecting agriculture, livestock and human health. PMID:27832081

Carving out turf in a biodiversity hotspot: multiple, previously unrecognized shrew species co-occur on Java Island, Indonesia.

PubMed

Esselstyn, Jacob A; Maharadatunkamsi; Achmadi, Anang S; Siler, Cameron D; Evans, Ben J

2013-10-01

In theory, competition among species in a shared habitat results in niche separation. In the case of small recondite mammals such as shrews, little is known about their autecologies, leaving open questions regarding the degree to which closely related species co-occur and how or whether ecological niches are partitioned. The extent to which species are able to coexist may depend on the degree to which they exploit different features of their habitat, which may in turn influence our ability to recognize them as species. We explored these issues in a biodiversity hotspot, by surveying shrew (genus Crocidura) diversity on the Indonesian island of Java. We sequenced portions of nine unlinked genes in 100-117 specimens of Javan shrews and incorporated homologous data from most known Crocidura species from other parts of island South-East Asia. Current taxonomy recognizes four Crocidura species on Java, including two endemics. However, our phylogenetic, population genetic and species delimitation analyses identify five species on the island, and all are endemic to Java. While the individual ranges of these species may not overlap in their entirety, we found up to four species living syntopically and all five species co-occurring on one mountain. Differences in species' body size, use of above ground-level habitats by one species and habitat partitioning along ecological gradients may have facilitated species diversification and coexistence. © 2013 John Wiley & Sons Ltd.

From Peptides to Proteins: Systematic Control of Net Molecular Charge and Hydrophilicity on the Kinetics of Calcite Growth

NASA Astrophysics Data System (ADS)

Elhadj, S.; de Yoreo, J. J.; Hoyer, J. J.; Dove, P. M.

2006-12-01

The compartment-specific compositions of biologic molecules isolated from biominerals suggest that control of mineral growth may be linked to biochemical features. Here we define a systematic relationship between the ability of biomolecules in solution to promote the growth of calcite (CaCO3) and their net negative molecular charge and hydrophilicity. The degree of enhancement is dependent on peptide composition, but not on peptide sequence. Data analysis shows that this rate enhancement arises from an increase in the kinetic coefficient. We interpret the mechanism of growth enhancement to be a catalytic process whereby biomolecules reduce the magnitude of the diffusive barrier, Ek, by perturbations that displace water molecules- a water shell destruction mechanism. The result is a decrease in the repulsive barrier for attachment of solutes to the solid phase. This previously unrecognized relationship also rationalizes recently reported data showing acceleration of calcite growth rates over rates measured in the pure system by nanomolar levels of abalone nacre proteins. These findings show that the growth-modifying properties of small model peptides may be scaled up to analyze mineralization processes that are mediated by more complex proteins. We suggest that enhancement of calcite growth may now be estimated a priori from the composition of peptide sequences and the calculated values of hydrophilicity and net molecular charge without need for detailed tests for each biomolecule. This insight may contribute to an improved understanding of mineralization in diverse systems of biomineralization.

Millennial-scale ocean acidification and late Quaternary decline of cryptic bacterial crusts in tropical reefs.

PubMed

Riding, R; Liang, L; Braga, J C

2014-09-01

Ocean acidification by atmospheric carbon dioxide has increased almost continuously since the last glacial maximum (LGM), 21,000 years ago. It is expected to impair tropical reef development, but effects on reefs at the present day and in the recent past have proved difficult to evaluate. We present evidence that acidification has already significantly reduced the formation of calcified bacterial crusts in tropical reefs. Unlike major reef builders such as coralline algae and corals that more closely control their calcification, bacterial calcification is very sensitive to ambient changes in carbonate chemistry. Bacterial crusts in reef cavities have declined in thickness over the past 14,000 years with largest reduction occurring 12,000-10,000 years ago. We interpret this as an early effect of deglacial ocean acidification on reef calcification and infer that similar crusts were likely to have been thicker when seawater carbonate saturation was increased during earlier glacial intervals, and thinner during interglacials. These changes in crust thickness could have substantially affected reef development over glacial cycles, as rigid crusts significantly strengthen framework and their reduction would have increased the susceptibility of reefs to biological and physical erosion. Bacterial crust decline reveals previously unrecognized millennial-scale acidification effects on tropical reefs. This directs attention to the role of crusts in reef formation and the ability of bioinduced calcification to reflect changes in seawater chemistry. It also provides a long-term context for assessing anticipated anthropogenic effects. © 2014 John Wiley & Sons Ltd.

ToxReporter: viewing the genome through the eyes of a toxicologist.

PubMed

Gosink, Mark

2016-01-01

One of the many roles of a toxicologist is to determine if an observed adverse event (AE) is related to a previously unrecognized function of a given gene/protein. Towards that end, he or she will search a variety of public and propriety databases for information linking that protein to the observed AE. However, these databases tend to present all available information about a protein, which can be overwhelming, limiting the ability to find information about the specific toxicity being investigated. ToxReporter compiles information from a broad selection of resources and limits display of the information to user-selected areas of interest. ToxReporter is a PERL-based web-application which utilizes a MySQL database to streamline this process by categorizing public and proprietary domain-derived information into predefined safety categories according to a customizable lexicon. Users can view gene information that is 'red-flagged' according to the safety issue under investigation. ToxReporter also uses a scoring system based on relative counts of the red-flags to rank all genes for the amount of information pertaining to each safety issue and to display their scored ranking as an easily interpretable 'Tox-At-A-Glance' chart. Although ToxReporter was originally developed to display safety information, its flexible design could easily be adapted to display disease information as well.Database URL: ToxReporter is freely available at https://github.com/mgosink/ToxReporter. © The Author(s) 2016. Published by Oxford University Press.

Discovery of cellular substrates for protein kinase A using a peptide array screening protocol.

PubMed

Smith, F Donelson; Samelson, Bret K; Scott, John D

2011-08-15

Post-translational modification of proteins is a universal form of cellular regulation. Phosphorylation on serine, threonine, tyrosine or histidine residues by protein kinases is the most widespread and versatile form of covalent modification. Resultant changes in activity, localization or stability of phosphoproteins drives cellular events. MS and bioinformatic analyses estimate that ~30% of intracellular proteins are phosphorylated at any given time. Multiple approaches have been developed to systematically define targets of protein kinases; however, it is likely that we have yet to catalogue the full complement of the phosphoproteome. The amino acids that surround a phosphoacceptor site are substrate determinants for protein kinases. For example, basophilic enzymes such as PKA (protein kinase A), protein kinase C and calmodulin-dependent kinases recognize basic side chains preceding the target serine or threonine residues. In the present paper we describe a strategy using peptide arrays and motif-specific antibodies to identify and characterize previously unrecognized substrate sequences for protein kinase A. We found that the protein kinases PKD (protein kinase D) and MARK3 [MAP (microtubule-associated protein)-regulating kinase 3] can both be phosphorylated by PKA. Furthermore, we show that the adapter protein RIL [a product of PDLIM4 (PDZ and LIM domain protein 4)] is a PKA substrate that is phosphorylated on Ser(119) inside cells and that this mode of regulation may control its ability to affect cell growth. © The Authors Journal compilation © 2011 Biochemical Society

Millennial-scale ocean acidification and late Quaternary

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

Riding, Dr Robert E; Liang, Liyuan; Braga, Dr Juan Carlos

Ocean acidification by atmospheric carbon dioxide has increased almost continuously since the last glacial maximum (LGM), 21 000 years ago. It is expected to impair tropical reef development, but effects on reefs at the present day and in the recent past have proved difficult to evaluate. We present evidence that acidification has already significantly reduced the formation of calcified bacterial crusts in tropical reefs. Unlike major reef builders such as coralline algae and corals that more closely control their calcification, bacterial calcification is very sensitive to ambient changes in carbonate chemistry. Bacterial crusts in reef cavities have declined in thicknessmore » over the past 14 000 years with largest reduction occurring 12 000 10 000 years ago. We interpret this as an early effect of deglacial ocean acidification on reef calcification and infer that similar crusts were likely to have been thicker when seawater carbonate saturation was increased during earlier glacial intervals, and thinner during interglacials. These changes in crust thickness could have substantially affected reef development over glacial cycles, as rigid crusts significantly strengthen framework and their reduction would have increased the susceptibility of reefs to biological and physical erosion. Bacterial crust decline reveals previously unrecognized millennial-scale acidification effects on tropical reefs. This directs attention to the role of crusts in reef formation and the ability of bioinduced calcification to reflect changes in seawater chemistry. It also provides a long-term context for assessing anticipated anthropogenic effects.« less

Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury.

PubMed

Brosius Lutz, Amanda; Chung, Won-Suk; Sloan, Steven A; Carson, Glenn A; Zhou, Lu; Lovelett, Emilie; Posada, Sean; Zuchero, J Bradley; Barres, Ben A

2017-09-19

Ineffective myelin debris clearance is a major factor contributing to the poor regenerative ability of the central nervous system. In stark contrast, rapid clearance of myelin debris from the injured peripheral nervous system (PNS) is one of the keys to this system's remarkable regenerative capacity, but the molecular mechanisms driving PNS myelin clearance are incompletely understood. We set out to discover new pathways of PNS myelin clearance to identify novel strategies for activating myelin clearance in the injured central nervous system, where myelin debris is not cleared efficiently. Here we show that Schwann cells, the myelinating glia of the PNS, collaborate with hematogenous macrophages to clear myelin debris using TAM (Tyro3, Axl, Mer) receptor-mediated phagocytosis as well as autophagy. In a mouse model of PNS nerve crush injury, Schwann cells up-regulate TAM phagocytic receptors Axl and Mertk following PNS injury, and Schwann cells lacking both of these phagocytic receptors exhibit significantly impaired myelin phagocytosis both in vitro and in vivo. Autophagy-deficient Schwann cells also display reductions in myelin clearance after mouse nerve crush injury, as has been recently shown following nerve transection. These findings add a mechanism, Axl/Mertk-mediated myelin clearance, to the repertoire of cellular machinery used to clear myelin in the injured PNS. Given recent evidence that astrocytes express Axl and Mertk and have previously unrecognized phagocytic potential, this pathway may be a promising avenue for activating myelin clearance after CNS injury.

Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells.

PubMed

Hu Frisk, Jun Mei; Kjellén, Lena; Kaler, Stephen G; Pejler, Gunnar; Öhrvik, Helena

2017-12-15

Copper has previously been implicated in the regulation of immune responses, but the impact of this metal on mast cells is poorly understood. In this article, we address this issue and show that copper starvation of mast cells causes increased granule maturation, as indicated by higher proteoglycan content, stronger metachromatic staining, and altered ultrastructure in comparison with nontreated cells, whereas copper overload has the opposite effects. In contrast, copper status did not impact storage of histamine in mast cells, nor did alterations in copper levels affect the ability of mast cells to degranulate in response to IgER cross-linking. A striking finding was decreased tryptase content in mast cells with copper overload, whereas copper starvation increased tryptase content. These effects were associated with corresponding shifts in tryptase mRNA levels, suggesting that copper affects tryptase gene regulation. Mechanistically, we found that alterations in copper status affected the expression of microphthalmia-associated transcription factor, a transcription factor critical for driving tryptase expression. We also found evidence supporting the concept that the effects on microphthalmia-associated transcription factor are dependent on copper-mediated modulation of MAPK signaling. Finally, we show that, in MEDNIK syndrome, a condition associated with low copper levels and a hyperallergenic skin phenotype, including pruritis and dermatitis, the number of tryptase-positive mast cells is increased. Taken together, our findings reveal a hitherto unrecognized role for copper in the regulation of mast cell gene expression and maturation. Copyright © 2017 by The American Association of Immunologists, Inc.

Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor.

PubMed

Fernández-Del-Río, Lucía; Nag, Anish; Gutiérrez Casado, Elena; Ariza, Julia; Awad, Agape M; Joseph, Akil I; Kwon, Ohyun; Verdin, Eric; de Cabo, Rafael; Schneider, Claus; Torres, Jorge Z; Burón, María I; Clarke, Catherine F; Villalba, José M

2017-09-01

Coenzyme Q (Q) is a lipid-soluble antioxidant essential in cellular physiology. Patients with Q deficiencies, with few exceptions, seldom respond to treatment. Current therapies rely on dietary supplementation with Q 10 , but due to its highly lipophilic nature, Q 10 is difficult to absorb by tissues and cells. Plant polyphenols, present in the human diet, are redox active and modulate numerous cellular pathways. In the present study, we tested whether treatment with polyphenols affected the content or biosynthesis of Q. Mouse kidney proximal tubule epithelial (Tkpts) cells and human embryonic kidney cells 293 (HEK 293) were treated with several types of polyphenols, and kaempferol produced the largest increase in Q levels. Experiments with stable isotope 13 C-labeled kaempferol demonstrated a previously unrecognized role of kaempferol as an aromatic ring precursor in Q biosynthesis. Investigations of the structure-function relationship of related flavonols showed the importance of two hydroxyl groups, located at C3 of the C ring and C4' of the B ring, both present in kaempferol, as important determinants of kaempferol as a Q biosynthetic precursor. Concurrently, through a mechanism not related to the enhancement of Q biosynthesis, kaempferol also augmented mitochondrial localization of Sirt3. The role of kaempferol as a precursor that increases Q levels, combined with its ability to upregulate Sirt3, identify kaempferol as a potential candidate in the design of interventions aimed on increasing endogenous Q biosynthesis, particularly in kidney. Copyright © 2017 Elsevier Inc. All rights reserved.

Biopsychosocial function analyses changes the assessment of the ability to work in patients on long-term sick-leave due to chronic musculoskeletal pain: the role of undiagnosed mental health comorbidity.

PubMed

Olaya-Contreras, Patricia; Styf, Jorma

2013-05-01

To study the prevalence of somatic and mental health comorbidity and the use of opioid medication among patients on long-term sick-leave due to chronic musculoskeletal pain (CMP); to compare an orthopaedic-based assessment of ability to work with a team assessment; to investigate the relationship between intensity of pain and psychosocial characteristics in this group. A cross-sectional study was carried out with 174 consecutive patients on sick-leave for a mean of 21 months. All were referred from the Social Insurance Office for orthopaedic evaluation and assessment of the ability to work. Of them, only 83/174 patients were referred by the Office for psychiatric evaluation. Neck pain was the main cause of disability. Patients with neck pain often suffered pain in more than two sites, and greater intensity of pain. Thirty-four percent of all participants had been prescribed opioid medication before consultation. Degrees of disability, unemployment, low degree of education and to be an immigrant were related to intensity of pain. Unrecognized psychiatric disorders changed the main cause of inability to work in 69% of patients who underwent both orthopaedic and psychiatric evaluation. An evaluation based on biopsychosocial function is valuable in reaching an accurate assessment of the patient's diagnosis, and ability to work in CMP. Ability to work and degree of sick-leave in patients on long-term sick-leave is determined to a large extent by undiagnosed mental health comorbidities, and not solely somatic complaints.

Utilizing OODB schema modeling for vocabulary management.

PubMed Central

Gu, H.; Cimino, J. J.; Halper, M.; Geller, J.; Perl, Y.

1996-01-01

Comprehension of complex controlled vocabularies is often difficult. We present a method, facilitated by an object-oriented database, for depicting such a vocabulary (the Medical Entities Dictionary (MED) from the Columbia-Presbyterian Medical Center) in a schematic way which uses a sparse inheritance network of area classes. The resulting Object Oriented Health Vocabulary repository (OOHVR) allows visualization of the 43,000 MED concepts as 90 area classes. This view has provided valuable information to those responsible with maintaining the MED. As a result, the MED organization has been improved and some previously-unrecognized errors and inconsistencies have been removed. We believe that this schematic approach allows improved comprehension of the gestalt of large controlled medical vocabulary. PMID:8947671

GiniClust: detecting rare cell types from single-cell gene expression data with Gini index.

PubMed

Jiang, Lan; Chen, Huidong; Pinello, Luca; Yuan, Guo-Cheng

2016-07-01

High-throughput single-cell technologies have great potential to discover new cell types; however, it remains challenging to detect rare cell types that are distinct from a large population. We present a novel computational method, called GiniClust, to overcome this challenge. Validation against a benchmark dataset indicates that GiniClust achieves high sensitivity and specificity. Application of GiniClust to public single-cell RNA-seq datasets uncovers previously unrecognized rare cell types, including Zscan4-expressing cells within mouse embryonic stem cells and hemoglobin-expressing cells in the mouse cortex and hippocampus. GiniClust also correctly detects a small number of normal cells that are mixed in a cancer cell population.

Distribution of trace elements in drilling chip samples around a roll-type uranium deposit, San Juan Basin, New Mexico

USGS Publications Warehouse

Day, H.C.; Spirakis, C.S.; Zech, R.S.; Kirk, A.R.

1983-01-01

Chip samples from rotary drilling in the vicinity of a roll-type uranium deposit in the southwestern San Juan Basin were split into a whole-washed fraction, a clay fraction, and a heavy mineral concentrate fraction. Analyses of these fractions determined that cutting samples could be used to identify geochemical halos associated with this ore deposit. In addition to showing a distribution of selenium, uranium, vanadium, and molybdenum similar to that described by Harshman (1974) in uranium roll-type deposits in Wyoming, South Dakota, and Texas, the chemical data indicate a previously unrecognized zinc anomaly in the clay fraction downdip of the uranium ore.

Asteroid Systems: Binaries, Triples, and Pairs

NASA Astrophysics Data System (ADS)

Margot, J.-L.; Pravec, P.; Taylor, P.; Carry, B.; Jacobson, S.

In the past decade, the number of known binary near-Earth asteroids has more than quadrupled and the number of known large main-belt asteroids with satellites has doubled. Half a dozen triple asteroids have been discovered, and the previously unrecognized populations of asteroid pairs and small main-belt binaries have been identified. The current observational evidence confirms that small (≲20 km) binaries form by rotational fission and establishes that the Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect powers the spin-up process. A unifying paradigm based on rotational fission and post-fission dynamics can explain the formation of small binaries, triples, and pairs. Large (>~20 km) binaries with small satellites are most likely created during large collisions.

Beyond the Laboratory, Into the Clinic: What Dogs with Disk Disease Have Taught Us About Photobiomodulation for Spinal Cord Injury.

PubMed

Robinson, Narda G

2017-11-01

For spinal-cord-injured (SCI) patients, integrative medicine approaches such as photomedicine and acupuncture can renew hope and offer previously unrecognized ways to help regain function and improve quality of life. By understanding the mechanisms of action that these two modalities share, practitioners can better target specific attributes of spinal cord pathophysiology that are limiting recovery. Naturally occurring intervertebral disk disease (IVDD) in dogs affords unparalleled translational opportunities to develop treatment strategies involving photobiomodulation and acupuncture. Insights derived through clinical trials of dogs with IVDD have the potential to raise the standard of care for both human and canine SCI patients.

Equations of motion for the gravitational two-body problem

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

Whitney, C.K.

1988-01-01

This paper reinvestigates the well-known gravitational two-body problem, in light of new information concerning the electrodynamic version of the problem. The well-known Lienard-Wiechert potentials, and the fields derived from them, are suspected to be time-shifted, anticipating the true potentials and fields by the time required for signal propagation from the source to the observer. This time shift is significant because it implies field directions different to first order in v/c. In the gravitational problem, the resulting observer accelerations become correlated with retarded source positions, rather than with present, unretarded source positions as was previously believed. This means there exist previouslymore » unrecognized first-order effects in gravitational systems.« less

CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells.

PubMed

Taghizadeh, Rouzbeh; Noh, Minsoo; Huh, Yang Hoon; Ciusani, Emilio; Sigalotti, Luca; Maio, Michele; Arosio, Beatrice; Nicotra, Maria R; Natali, PierGiorgio; Sherley, James L; La Porta, Caterina A M

2010-12-22

A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs) from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+. We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone. The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.

Monomeric Alpha-Synuclein Exerts a Physiological Role on Brain ATP Synthase

PubMed Central

Ludtmann, Marthe H.R.; Angelova, Plamena R.; Ninkina, Natalia N.; Gandhi, Sonia

2016-01-01

Misfolded α-synuclein is a key factor in the pathogenesis of Parkinson's disease (PD). However, knowledge about a physiological role for the native, unfolded α-synuclein is limited. Using brains of mice lacking α-, β-, and γ-synuclein, we report that extracellular monomeric α-synuclein enters neurons and localizes to mitochondria, interacts with ATP synthase subunit α, and modulates ATP synthase function. Using a combination of biochemical, live-cell imaging and mitochondrial respiration analysis, we found that brain mitochondria of α-, β-, and γ-synuclein knock-out mice are uncoupled, as characterized by increased mitochondrial respiration and reduced mitochondrial membrane potential. Furthermore, synuclein deficiency results in reduced ATP synthase efficiency and lower ATP levels. Exogenous application of low unfolded α-synuclein concentrations is able to increase the ATP synthase activity that rescues the mitochondrial phenotypes observed in synuclein deficiency. Overall, the data suggest that α-synuclein is a previously unrecognized physiological regulator of mitochondrial bioenergetics through its ability to interact with ATP synthase and increase its efficiency. This may be of particular importance in times of stress or PD mutations leading to energy depletion and neuronal cell toxicity. SIGNIFICANCE STATEMENT Misfolded α-synuclein aggregations in the form of Lewy bodies have been shown to be a pathological hallmark in histological staining of Parkinson's disease (PD) patient brains. It is known that misfolded α-synuclein is a key driver in PD pathogenesis, but the physiological role of unfolded monomeric α-synuclein remains unclear. Using neuronal cocultures and isolated brain mitochondria of α-, β-, and γ-synuclein knock-out mice and monomeric α-synuclein, this current study shows that α-synuclein in its unfolded monomeric form improves ATP synthase efficiency and mitochondrial function. The ability of monomeric α-synuclein to enhance ATP synthase efficiency under physiological conditions may be of importance when α-synuclein undergoes the misfolding and aggregation reported in PD. PMID:27733604

Quaternary geology of the Duck Hawk Bluffs, southwest Banks Island, Arctic Canada: a re-investigation of a critical terrestrial type locality for glacial and interglacial events bordering the Arctic Ocean

NASA Astrophysics Data System (ADS)

Evans, David J. A.; England, John H.; La Farge, Catherine; Coulthard, Roy D.; Lakeman, Thomas R.; Vaughan, Jessica M.

2014-05-01

Duck Hawk Bluffs, southwest Banks Island, is a primary section (8 km long and 60 m high) in the western Canadian Arctic Archipelago exposing a long record of Quaternary sedimentation adjacent to the Arctic Ocean. A reinvestigation of Duck Hawk Bluffs demonstrates that it is a previously unrecognized thrust-block moraine emplaced from the northeast by Laurentide ice. Previous stratigraphic models of Duck Hawk Bluffs reported a basal unit of preglacial fluvial sand and gravel (Beaufort Fm, forested Arctic), overlain by a succession of three glaciations and at least two interglacials. Our observations dismiss the occurrence of preglacial sediments and amalgamate the entire record into three glacial intervals and one prominent interglacial. The first glacigenic sedimentation is recorded by an ice-contact sandur containing redeposited allochthonous organics previously assigned to the Beaufort Fm. This is overlain by fine-grained sediments with ice wedge pseudomorphs and well-preserved bryophyte assemblages corresponding to an interglacial environment similar to modern. The second glacial interval is recorded by ice-proximal mass flows and marine rhythmites that were glacitectonized when Laurentide ice overrode the site from Amundsen Gulf to the south. Sediments of this interval have been reported to be magnetically reversed (>780 ka). The third interval of glacigenic sedimentation includes glacifluvial sand and gravel recording the arrival of Laurentide ice that overrode the site from the northeast (island interior) depositing a glacitectonite and constructing the thrust block moraine that comprises Duck Hawk Bluffs. Sediments of this interval have been reported to be magnetically normal (<780 ka). The glacitectonite contains a highly deformed melange of pre-existing sediments that were previously assigned to several formally named, marine and interglacial deposits resting in an undeformed sequence. In contrast, the tectonism associated with the thrust block moraine imparted pervasive deformation throughout all underlying units, highlighted by a previously unrecognized raft of Cretaceous bedrock. During this advance, Laurentide ice from the interior of Banks Island coalesced with an ice stream in Amundsen Gulf, depositing the interlobate Sachs Moraine that contains shells as young as ˜24 cal ka BP (Late Wisconsinan). During deglaciation, meltwater emanating from these separating ice lobes deposited outwash that extended to deglacial marine limit (11 m asl) along the west coast of Banks Island. Our new stratigraphic synthesis fundamentally revises and simplifies the record of past Quaternary environments preserved on southwest Banks Island, which serves as a key terrestrial archive for palaeoenvironmental change.

Endocrine and Hypertensive Disorders of Potassium Regulation: Primary Aldosteronism

PubMed Central

Weiner, I. David

2013-01-01

The identification that primary aldosteronism is a common cause of resistant hypertension is a significant advance in our ability to care for patients with hypertension. Primary aldosteronism is common, and when unrecognized is associated with increased incidence of adverse cardiovascular outcomes. Identification of primary aldosteronism is based upon use of the plasma aldosterone level, plasma renin activity and the aldosterone:renin ratio (ARR). Differentiation between unilateral and bilateral autonomous adrenal aldosterone production then guides further therapy, with use of mineralocorticoid receptor blockers for those with bilateral autonomous adrenal aldosterone production and laparoscopic adrenalectomy for those with unilateral autonomous aldosterone production. In this review, we discuss in detail the pathogenesis of primary aldosteronism-induced hypertension and potassium disorders, the evaluation of the patient with suspected primary aldosteronism and the management of primary aldosteronism, both through medications and through surgery. PMID:23953804

A single macrolichen constitutes hundreds of unrecognized species

PubMed Central

Lücking, Robert; Dal-Forno, Manuela; Sikaroodi, Masoumeh; Gillevet, Patrick M.; Bungartz, Frank; Moncada, Bibiana; Yánez-Ayabaca, Alba; Chaves, José Luis; Coca, Luis Fernando; Lawrey, James D.

2014-01-01

The number of Fungi is estimated at between 1.5 and 3 million. Lichenized species are thought to make up a comparatively small portion of this figure, with unrecognized species richness hidden among little-studied, tropical microlichens. Recent findings, however, suggest that some macrolichens contain a large number of unrecognized taxa, increasing known species richness by an order of magnitude or more. Here we report the existence of at least 126 species in what until recently was believed to be a single taxon: the basidiolichen fungus Dictyonema glabratum, also known as Cora pavonia. Notably, these species are not cryptic but morphologically distinct. A predictive model suggests an even larger number, with more than 400 species. These results call into question species concepts in presumably well-known macrolichens and demonstrate the need for accurately documenting such species richness, given the importance of these lichens in endangered ecosystems such as paramos and the alarming potential for species losses throughout the tropics. PMID:24982168

Anatomy of a Hotspot: Chain and Seroepidemiology of Ebola Virus Transmission, Sukudu, Sierra Leone, 2015-16.

PubMed

Kelly, J Daniel; Barrie, Mohamed Bailor; Mesman, Annelies W; Karku, Sahr; Quiwa, Komba; Drasher, Michael; Schlough, Gabriel Warren; Dierberg, Kerry; Koedoyoma, Songor; Lindan, Christina P; Jones, James Holland; Chamie, Gabriel; Worden, Lee; Greenhouse, Bryan; Weiser, Sheri D; Porco, Travis C; Rutherford, George W; Richardson, Eugene T

2018-03-28

Studies have yet to include minimally symptomatic Ebola virus (EBOV) infections and unrecognized Ebola virus disease (EVD) in Ebola-related transmission chains and epidemiologic risk estimates. We conducted a cross-sectional, sero-epidemiological survey from October 2015 to January 2016 among 221 individuals living in quarantined households from November 2014 to February 2015 during the Ebola outbreak in the village of Sukudu, Sierra Leone. Of 48 EBOV-infected persons, 25% (95% confidence interval [CI], 14%-40%) had minimally symptomatic EBOV infections and 4% (95% CI, 1%-14%) were unrecognized EVD cases. The pattern of minimally symptomatic EBOV infections in the transmission chain was nonrandom (P < .001, permutation test). Not having lived in the same house as an EVD case was significantly associated with minimally symptomatic infection. This is the first study to investigate a chain of EBOV transmission inclusive of minimally symptomatic EBOV infections and unrecognized EVD. Our findings provide new insights into Ebola transmission dynamics and quarantine practices.

Functional Metagenomics Reveals Previously Unrecognized Diversity of Antibiotic Resistance Genes in Gulls

PubMed Central

Martiny, Adam C.; Martiny, Jennifer B. H.; Weihe, Claudia; Field, Andrew; Ellis, Julie C.

2011-01-01

Wildlife may facilitate the spread of antibiotic resistance (AR) between human-dominated habitats and the surrounding environment. Here, we use functional metagenomics to survey the diversity and genomic context of AR genes in gulls. Using this approach, we found a variety of AR genes not previously detected in gulls and wildlife, including class A and C β-lactamases as well as six tetracycline resistance gene types. An analysis of the flanking sequences indicates that most of these genes are present in Enterobacteriaceae and various Gram-positive bacteria. In addition to finding known gene types, we detected 31 previously undescribed AR genes. These undescribed genes include one most similar to an uncharacterized gene in Verrucomicrobium and another to a putative DNA repair protein in Lactobacillus. Overall, the study more than doubled the number of clinically relevant AR gene types known to be carried by gulls or by wildlife in general. Together with the propensity of gulls to visit human-dominated habitats, this high diversity of AR gene types suggests that gulls could facilitate the spread of AR. PMID:22347872

Fracture trends identified by ERTS-1 imagery in Utah and Nevada

NASA Technical Reports Server (NTRS)

Jensen, M. L. (Principal Investigator); Erickson, M. P.; Smith, M. R.

1973-01-01

The author has identified the following significant results. In the Utah-Nevada area, linear structural trends recorded on ERTS-1 imagery conform in part to previously recognized structures. In addition, the ERTS-1 imagery reveals cryptic structures not previously identified and not readily apparent in other imagery. These structures are illustrated by prominent east-west trending structures which appear to be concentrated in pre-volcanic rocks. This suggests that the structures are older than many of those with other trends which are equally prominent in volcanic and non-volcanic terrain. Since the older east-west structures may have controlled early Tertiary emplacement of magma or the ascent of mineralizing fluids, their recognition is important in minerial exploration. Soil-gas sampling and analysis for mercury content is being continued over structures, and projected trends of buried structures which appear, from studies of ERTS-1 imagery, to be favorable to mineralization. Comparison of ERTS-1 and Skylab imagery indicated that ERTS-1 imagery records more previously unrecognized linear structures than the Skylab imagery. In differentiating and identifying different rock types, the Skylab imagery appears to be more effective.

MUC1-C Represses the Crumbs Complex Polarity Factor CRB3 and Downregulates the Hippo Pathway.

PubMed

Alam, Maroof; Bouillez, Audrey; Tagde, Ashujit; Ahmad, Rehan; Rajabi, Hasan; Maeda, Takahiro; Hiraki, Masayuki; Suzuki, Yozo; Kufe, Donald

2016-12-01

Apical-basal polarity and epithelial integrity are maintained in part by the Crumbs (CRB) complex. The C--terminal subunit of MUC1 (MUC1-C) is a transmembrane protein that is expressed at the apical border of normal epithelial cells and aberrantly at high levels over the entire surface of their transformed counterparts. However, it is not known whether MUC1-C contributes to this loss of polarity that is characteristic of carcinoma cells. Here it is demonstrated that MUC1-C downregulates expression of the Crumbs complex CRB3 protein in triple-negative breast cancer (TNBC) cells. MUC1-C associates with ZEB1 on the CRB3 promoter and represses CRB3 transcription. Notably, CRB3 activates the core kinase cassette of the Hippo pathway, which includes LATS1 and LATS2. In this context, targeting MUC1-C was associated with increased phosphorylation of LATS1, consistent with activation of the Hippo pathway, which is critical for regulating cell contact, tissue repair, proliferation, and apoptosis. Also shown is that MUC1-C--mediated suppression of CRB3 and the Hippo pathway is associated with dephosphorylation and activation of the oncogenic YAP protein. In turn, MUC1-C interacts with YAP, promotes formation of YAP/β-catenin complexes, and induces the WNT target gene MYC. These data support a previously unrecognized pathway in which targeting MUC1-C in TNBC cells (i) induces CRB3 expression, (ii) activates the CRB3-driven Hippo pathway, (iii) inactivates YAP, and thereby (iv) suppresses YAP/β-catenin-mediated induction of MYC expression. These findings demonstrate a previously unrecognized role for the MUC1-C oncoprotein in the regulation of polarity and the Hippo pathway in breast cancer. Mol Cancer Res; 14(12); 1266-76. ©2016 AACR. ©2016 American Association for Cancer Research.

IκB kinaseα/β control biliary homeostasis and hepatocarcinogenesis in mice by phosphorylating the cell-death mediator receptor-interacting protein kinase 1.

PubMed

Koppe, Christiane; Verheugd, Patricia; Gautheron, Jérémie; Reisinger, Florian; Kreggenwinkel, Karina; Roderburg, Christoph; Quagliata, Luca; Terracciano, Luigi; Gassler, Nikolaus; Tolba, René H; Boege, Yannick; Weber, Achim; Karin, Michael; Luedde, Mark; Neumann, Ulf P; Weiskirchen, Ralf; Tacke, Frank; Vucur, Mihael; Trautwein, Christian; Lüscher, Bernhard; Preisinger, Christian; Heikenwalder, Mathias; Luedde, Tom

2016-10-01

The IκB-Kinase (IKK) complex-consisting of the catalytic subunits, IKKα and IKKβ, as well as the regulatory subunit, NEMO-mediates activation of the nuclear factor κB (NF-κB) pathway, but previous studies suggested the existence of NF-κB-independent functions of IKK subunits with potential impact on liver physiology and disease. Programmed cell death is a crucial factor in the progression of liver diseases, and receptor-interacting kinases (RIPKs) exerts strategic control over multiple pathways involved in regulating novel programmed cell-death pathways and inflammation. We hypothesized that RIPKs might be unrecognized targets of the catalytic IKK-complex subunits, thereby regulating hepatocarcinogenesis and cholestasis. In this present study, mice with specific genetic inhibition of catalytic IKK activity in liver parenchymal cells (LPCs; IKKα/β(LPC-KO) ) were intercrossed with RIPK1(LPC-KO) or RIPK3(-/-) mice to examine whether RIPK1 or RIPK3 might be downstream targets of IKKs. Moreover, we performed in vivo phospho-proteome analyses and in vitro kinase assays, mass spectrometry, and mutagenesis experiments. These analyses revealed that IKKα and IKKβ-in addition to their known function in NF-κB activation-directly phosphorylate RIPK1 at distinct regions of the protein, thereby regulating cell viability. Loss of this IKKα/β-dependent RIPK1 phosphorylation in LPCs inhibits compensatory proliferation of hepatocytes and intrahepatic biliary cells, thus impeding HCC development, but promoting biliary cell paucity and lethal cholestasis. IKK-complex subunits transmit a previously unrecognized signal through RIPK1, which is fundamental for the long-term consequences of chronic hepatic inflammation and might have potential implications for future pharmacological strategies against cholestatic liver disease and cancer. (Hepatology 2016;64:1217-1231). © 2016 by the American Association for the Study of Liver Diseases.

Nursing Home Use Across The Spectrum of Cognitive Decline: Merging Mayo Clinic Study of Aging With CMS MDS Assessments.

PubMed

Emerson, Jane A; Smith, Carin Y; Long, Kirsten H; Ransom, Jeanine E; Roberts, Rosebud O; Hass, Steven L; Duhig, Amy M; Petersen, Ronald C; Leibson, Cynthia L

2017-10-01

Objective, complete estimates of nursing home (NH) use across the spectrum of cognitive decline are needed to help predict future care needs and inform economic models constructed to assess interventions to reduce care needs. Retrospective longitudinal study. Olmsted County, MN. Mayo Clinic Study of Aging participants assessed as cognitively normal (CN), mild cognitive impairment (MCI), previously unrecognized dementia, or prevalent dementia (age = 70-89 years; N = 3,545). Participants were followed in Centers for Medicare and Medicaid Services (CMS) Minimum Data Set (MDS) NH records and in Rochester Epidemiology Project provider-linked medical records for 1-year after assessment of cognition for days of observation, NH use (yes/no), NH days, NH days/days of observation, and mortality. In the year after cognition was assessed, for persons categorized as CN, MCI, previously unrecognized dementia, and prevalent dementia respectively, the percentages who died were 1.0%, 2.6%, 4.2%, 21%; the percentages with any NH use were 3.8%, 8.7%, 19%, 40%; for persons with any NH use, median NH days were 27, 38, 120, 305, and median percentages of NH days/days of observation were 7.8%, 12%, 33%, 100%. The year after assessment, among persons with prevalent dementia and any NH use, >50% were a NH resident all days of observation. Pairwise comparisons revealed that each increase in cognitive impairment category exhibited significantly higher proportions with any NH use. One-year mortality was especially high for persons with prevalent dementia and any NH use (30% vs 13% for those with no NH use); 58% of all deaths among persons with prevalent dementia occurred while a NH resident. Findings suggest reductions in NH use could result from quality alternatives to NH admission, both among persons with MCI and persons with dementia, together with suitable options for end-of-life care among persons with prevalent dementia. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Natural Variation in the Promoter of GSE5 Contributes to Grain Size Diversity in Rice.

PubMed

Duan, Penggen; Xu, Jinsong; Zeng, Dali; Zhang, Baolan; Geng, Mufan; Zhang, Guozheng; Huang, Ke; Huang, Luojiang; Xu, Ran; Ge, Song; Qian, Qian; Li, Yunhai

2017-05-01

The utilization of natural genetic variation greatly contributes to improvement of important agronomic traits in crops. Understanding the genetic basis for natural variation of grain size can help breeders develop high-yield rice varieties. In this study, we identify a previously unrecognized gene, named GSE5, in the qSW5/GW5 locus controlling rice grain size by combining the genome-wide association study with functional analyses. GSE5 encodes a plasma membrane-associated protein with IQ domains, which interacts with the rice calmodulin protein, OsCaM1-1. We found that loss of GSE5 function caused wide and heavy grains, while overexpression of GSE5 resulted in narrow grains. We showed that GSE5 regulates grain size predominantly by influencing cell proliferation in spikelet hulls. Three major haplotypes of GSE5 (GSE5, GSE5 DEL1+IN1 , and GSE5 DEL2 ) in cultivated rice were identified based on the deletion/insertion type in its promoter region. We demonstrated that a 950-bp deletion (DEL1) in indica varieties carrying the GSE5 DEL1+IN1 haplotype and a 1212-bp deletion (DEL2) in japonica varieties carrying the GSE5 DEL2 haplotype associated with decreased expression of GSE5, resulting in wide grains. Further analyses indicate that wild rice accessions contain all three haplotypes of GSE5, suggesting that the GSE5 haplotypes present in cultivated rice are likely to have originated from different wild rice accessions during rice domestication. Taken together, our results indicate that the previously unrecognized GSE5 gene in the qSW5/GW5 locus, which is widely utilized by rice breeders, controls grain size, and reveal that natural variation in the promoter region of GSE5 contributes to grain size diversity in rice. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Constraining the India-Asia collision by retrieving the paleolatitude from partially remagnetized Paleogene volcanics in the Nanmulin Basin (southern Tibet)

NASA Astrophysics Data System (ADS)

Huang, Wentao; Dupont-Nivet, Guillaume; van Hinsbergen, Douwe; Lippert, Peter; Dekkers, Mark; Guo, Zhaojie; Li, Xiaochun; Zhang, Xiaoran

2014-05-01

Determining paleolatitudes of the Lhasa terrane (southern Tibet) using paleomagnetic inclinations is key to constraining the paleogeography and timing of the collision between India and Asia. However, paleolatitude estimates vary widely from 5°N to 30°N due to unrecognized rock magnetic biases such as inclination shallowing in sedimentary rocks or poor averaging of secular variation in volcanic rocks. Here, we investigated Paleogene volcanics of the Linzizong Group from southern Tibet in the Nanmulin Basin that had previously yielded low paleomagnetic inclinations ca. 10°N. Using proper paleomagnetic sampling and measurement protocols we observe similar shallow inclinations. However, sampled sections with different bedding attitudes yield a negative fold test indicating that the isolated remanent magnetizations do not have a primary origin. Detailed rock magnetic analysis, end-member modeling, and petrographic investigation reveal that most of the section has been variably remagnetized due to low-temperature alteration of magmatic titanomagnetite and formation of secondary hematite, which occurred after tilting of the strata. We show that the observed paleomagnetic inclinations vary according to a linear trend with the degree of remagnetization. Accordingly, we can estimate that the primary pre-tilting thermoremanent magnetization has an inclination of 38.1° ([35.7°, 40.5°] within 95% confidence limit), corresponding to a paleolatitude of 21.4° ([19.8°, 23.1°] within 95% confidence limit). This is consistent with results from pristine volcanic units and inclination-shallowing corrected sediments of the upper Linzizong Group ~200 km to the east [Dupont-Nivet et al., Geophysical Journal International, 182, 1189-1198; Huang et al., Geophysical Journal International, 194, 1390-1411]. Our results demonstrate that previously reported low paleolatitudes of the Lhasa terrane can be an artifact of unrecognized remagnetization. Furthermore, we show that original paleolatitudes can be recovered from partially remagnetized volcanics. Collectively, these results suggest that the India-Asia collision began at ~20°N by 45-55 Ma.

X-exome sequencing in Finnish families with Intellectual Disability - four novel mutations and two novel syndromic phenotypes

PubMed Central

2014-01-01

Background X-linked intellectual disability (XLID) is a group of genetically heterogeneous disorders characterized by substantial impairment in cognitive abilities, social and behavioral adaptive skills. Next generation sequencing technologies have become a powerful approach for identifying molecular gene mutations relevant for diagnosis. Methods & objectives Enrichment of X-chromosome specific exons and massively parallel sequencing was performed for identifying the causative mutations in 14 Finnish families, each of them having several males affected with intellectual disability of unknown cause. Results We found four novel mutations in known XLID genes. Two mutations; one previously reported missense mutation (c.1111C > T), and one novel frameshift mutation (c. 990_991insGCTGC) were identified in SLC16A2, a gene that has been linked to Allan-Herndon-Dudley syndrome (AHDS). One novel missense mutation (c.1888G > C) was found in GRIA3 and two novel splice donor site mutations (c.357 + 1G > C and c.985 + 1G > C) were identified in the DLG3 gene. One missense mutation (c.1321C > T) was identified in the candidate gene ZMYM3 in three affected males with a previously unrecognized syndrome characterized by unique facial features, aortic stenosis and hypospadia was detected. All of the identified mutations segregated in the corresponding families and were absent in > 100 Finnish controls and in the publicly available databases. In addition, a previously reported benign variant (c.877G > A) in SYP was identified in a large family with nine affected males in three generations, who have a syndromic phenotype. Conclusions All of the mutations found in this study are being reported for the first time in Finnish families with several affected male patients whose etiological diagnoses have remained unknown to us, in some families, for more than 30 years. This study illustrates the impact of X-exome sequencing to identify rare gene mutations and the challenges of interpreting the results. Further functional studies are required to confirm the cause of the syndromic phenotypes associated with ZMYM3 and SYP in this study. PMID:24721225

Substitutions of short heterologous DNA segments of intragenomic or extragenomic origins produce clustered genomic polymorphisms

PubMed Central

Harms, Klaus; Lunnan, Asbjørn; Hülter, Nils; Mourier, Tobias; Vinner, Lasse; Andam, Cheryl P.; Marttinen, Pekka; Fridholm, Helena; Hansen, Anders Johannes; Hanage, William P.; Nielsen, Kaare Magne; Willerslev, Eske; Johnsen, Pål Jarle

2016-01-01

In a screen for unexplained mutation events we identified a previously unrecognized mechanism generating clustered DNA polymorphisms such as microindels and cumulative SNPs. The mechanism, short-patch double illegitimate recombination (SPDIR), facilitates short single-stranded DNA molecules to invade and replace genomic DNA through two joint illegitimate recombination events. SPDIR is controlled by key components of the cellular genome maintenance machinery in the gram-negative bacterium Acinetobacter baylyi. The source DNA is primarily intragenomic but can also be acquired through horizontal gene transfer. The DNA replacements are nonreciprocal and locus independent. Bioinformatic approaches reveal occurrence of SPDIR events in the gram-positive human pathogen Streptococcus pneumoniae and in the human genome. PMID:27956618

Astrocytic GABA transporter activity modulates excitatory neurotransmission

PubMed Central

Boddum, Kim; Jensen, Thomas P.; Magloire, Vincent; Kristiansen, Uffe; Rusakov, Dmitri A.; Pavlov, Ivan; Walker, Matthew C.

2016-01-01

Astrocytes are ideally placed to detect and respond to network activity. They express ionotropic and metabotropic receptors, and can release gliotransmitters. Astrocytes also express transporters that regulate the extracellular concentration of neurotransmitters. Here we report a previously unrecognized role for the astrocytic GABA transporter, GAT-3. GAT-3 activity results in a rise in astrocytic Na+ concentrations and a consequent increase in astrocytic Ca2+ through Na+/Ca2+ exchange. This leads to the release of ATP/adenosine by astrocytes, which then diffusely inhibits neuronal glutamate release via activation of presynaptic adenosine receptors. Through this mechanism, increases in astrocytic GAT-3 activity due to GABA released from interneurons contribute to 'diffuse' heterosynaptic depression. This provides a mechanism for homeostatic regulation of excitatory transmission in the hippocampus. PMID:27886179

Ecological Guild Evolution and the Discovery of the World's Smallest Vertebrate

PubMed Central

Rittmeyer, Eric N.; Allison, Allen; Gründler, Michael C.; Thompson, Derrick K.; Austin, Christopher C.

2012-01-01

Living vertebrates vary drastically in body size, yet few taxa reach the extremely minute size of some frogs and teleost fish. Here we describe two new species of diminutive terrestrial frogs from the megadiverse hotspot island of New Guinea, one of which represents the smallest known vertebrate species, attaining an average body size of only 7.7 mm. Both new species are members of the recently described genus Paedophryne, the four species of which are all among the ten smallest known frog species, making Paedophryne the most diminutive genus of anurans. This discovery highlights intriguing ecological similarities among the numerous independent origins of diminutive anurans, suggesting that minute frogs are not mere oddities, but represent a previously unrecognized ecological guild. PMID:22253785

Strain-induced phase and oxygen-vacancy stability in ionic interfaces from first-principles calculations

DOE PAGES

Aidhy, Dilpuneet S.; Liu, Bin; Zhang, Yanwen; ...

2014-12-03

Understanding interfacial chemistry is becoming crucial in materials design for heterointerfaces. Using density functional theory, we elucidate the effect of strained interfaces on phase and oxygen-vacancy stability for CeO2 | ZrO2, ThO2 | ZrO2 and CeO2 | ThO2 interfaces. The calculations show that ZrO2 transforms from cubic fluorite to the orthorhombic columbite under tensile strain providing evidence of a previous experimental speculation of an unrecognized ZrO2 phase. We also show that oxygen vacancies could be preferably stabilized on either side of the interface by manipulating strain. We predict that they are stable in tensile-strain, and unstable in compressivestrained materials.

A new species of small-eared shrew from Colombia and Venezuela (Mammalia: Soricomorpha: Soricidae: Genus Cryptotis)

USGS Publications Warehouse

Woodman, N.

2002-01-01

Populations of small-eared shrews inhabiting the northern Cordillera Oriental of Colombia and adjoining Venezuelan highlands in the vicinity of Paramo de Tama have been referred alternatively to Cryptotis thomssi or Cryptotis meridensis. Morphological and morphometrical study of this population indicates that it belongs to neither taxon, but represents a distinct, previously unrecognized species. I describe this new species as Cryptotis tamensis and redescribe C. meridensis. Recognition of the population at Paramo de Tama as a separate taxon calls into question the identities of populations of shrews currently represented only by single specimens from Cerro Pintado in the Sierra de Perija, Colombia, and near El Junquito in the coastal highlands of Venezuela.

Degradation of curcumin: From mechanism to biological implications

PubMed Central

Schneider, Claus; Gordon, Odaine N.; Edwards, Rebecca L.; Luis, Paula B.

2016-01-01

Curcumin is the main bioactive ingredient in turmeric extract and widely consumed as part of the spice mix curry or as dietary supplement. Turmeric has a long history of therapeutic application in traditional Asian medicine. Biomedical studies conducted in the past two decades have identified a large number of cellular targets and effects of curcumin. In vitro curcumin rapidly degrades in an autoxidative transformation to diverse chemical species, formation of which has only recently been appreciated. We discuss how degradation and metabolism of curcumin, through products and their mechanism of formation, provide a basis for the interpretation of preclinical data and clinical studies. We suggest that the previously unrecognized diversity of its degradation products could be an important factor in explaining the polypharmacology of curcumin. PMID:25817068

Innate immunity, insulin resistance and type 2 diabetes.

PubMed

Fernández-Real, José Manuel; Pickup, John C

2008-01-01

Recent evidence has disclosed previously unrecognized links among insulin resistance, obesity, circulating immune markers, immunogenetic susceptibility, macrophage function and chronic infection. Genetic variations leading to altered production or function of circulating innate immune proteins, cellular pattern-recognition receptors and inflammatory cytokines have been linked with insulin resistance, type 2 diabetes, obesity and atherosclerosis. Cellular innate immune associations with obesity and insulin resistance include increased white blood cell count and adipose tissue macrophage numbers. The innate immune response is modulated possibly by both predisposition (genetic or fetal programming), perhaps owing to evolutionary pressures caused by acute infections at the population level (pandemics), and chronic low exposure to environmental products or infectious agents. The common characteristics shared among innate immunity activation, obesity and insulin resistance are summarized.

ALGERIAN IVY DERMATITIS—A California Disease

PubMed Central

Dorsey, Clete S.

1959-01-01

A hitherto unrecognized cause of contact dermatitis in California is the widely cultivated plant known as Algerian ivy. This plant, which grows in California (and its close relative, English ivy) causes a dermatitis which is similar to although milder than that caused by poison oak. Dermatitis from this cause occurs most frequently when persons who have become sensitive to it by previous contact trim the plant back in the spring after its seasonal spurt of growth. For persons whose occupations require repeated contact with the plant, dermatitis from this cause is an occupational hazard. Dermatitis from this plant is easily diagnosed by means of a simple patch test. In a series of 12 cases the only effective treatment was with corticosteroid agents. ImagesFigure 1.Figure 2. PMID:13629356

Catheter-Directed Thrombolysis of Lower Limb Thrombosis

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

Pianta, Marcus J.; Thomson, Kenneth R., E-mail: k.thomson@alfred.org.au

2011-02-15

Late complications of thrombosis of the deep veins in the region between the popliteal vein termination and the confluence of the common iliac veins and inferior vena cava (suprapopliteal deep-vein thrombosis) are common and often unrecognized by those responsible for the initial management. Pharmacomechanical-assisted clearance of the thrombus at the time of first presentation provides the best opportunity for complete recovery with preservation of normal venous valve function and avoidance of recurrent deep-vein thrombosis and postthrombotic syndrome. Recent interventional radiology methods provide for rapid and complete thrombolysis even in some patients in whom thrombolysis was previously considered contraindicated. This reviewmore » describes the methods, safety, and efficacy of acute interventional treatment of suprapopliteal deep-vein thrombosis.« less

Optical Coherence Tomography Identifies Lower Labial Salivary Gland Surface Density in Cystic Fibrosis

PubMed Central

Nowak, Jan K.; Grulkowski, Ireneusz; Karnowski, Karol; Wojtkowski, Maciej; Walkowiak, Jaroslaw

2015-01-01

The labial minor salivary glands (LSGs) are easily accessible mucus-secreting structures of the alimentary tract that may provide new information on the basis of gastrointestinal complications of cystic fibrosis (CF). It was shown that they are destructed in the course of cystic fibrosis. We employed wide-field, micrometer resolution in vivo optical coherence tomography to assess the surface density of LSGs in 18 patients with CF and 18 healthy subjects. The median LSGs’ surface densities in CF patients, and in the control group were 4.32 glands/cm2 and 6.58 glands/cm2, respectively (p = 0.006; Mann-Whitney U test). A lower LSG surface density is a previously unrecognized CF-related pathology of the alimentary tract. PMID:25622042

Overweight individuals are at increased risk for thrombotic thrombocytopenic purpura.

PubMed

Nicol, Kathleen K; Shelton, Brent J; Knovich, Mary Ann; Owen, John

2003-11-01

Our understanding of the pathophysiology of thrombotic thrombocytopenic purpura, TTP, has increased dramatically in the past few years with the identification of the role of ADAMTS13. Nonetheless, risk factors for the development of acute TTP are few. Informally, obesity was felt to be common in patients with TTP and so a formal study was undertaken to further define this association. We report our data in 105 patients with classical TTP as defined by thrombocytopenia and microangiopathic hemolytic anemia. We found that marked obesity is a previously unrecognized risk factor with an associated odds ratio of 7.6. Interestingly, despite this increased risk, obesity might well be associated with lower mortality, although this did not reach statistical significance. Copyright 2003 Wiley-Liss, Inc.

Canonical DNA Repair Pathways Influence R-Loop-Driven Genome Instability.

PubMed

Stirling, Peter C; Hieter, Philip

2017-10-27

DNA repair defects create cancer predisposition in humans by fostering a higher rate of mutations. While DNA repair is quite well characterized, recent studies have identified previously unrecognized relationships between DNA repair and R-loop-mediated genome instability. R-loops are three-stranded nucleic acid structures in which RNA binds to genomic DNA to displace a loop of single-stranded DNA. Mutations in homologous recombination, nucleotide excision repair, crosslink repair, and DNA damage checkpoints have all now been linked to formation and function of transcription-coupled R-loops. This perspective will summarize recent literature linking DNA repair to R-loop-mediated genomic instability and discuss how R-loops may contribute to mutagenesis in DNA-repair-deficient cancers. Copyright © 2016 Elsevier Ltd. All rights reserved.

An active atmospheric methane sink in high Arctic mineral cryosols

DOE PAGES

Lau, Maggie C.Y.; Stackhouse, B.; Layton, Alice C.; ...

2015-01-01

The transition of Arctic carbon-rich cryosols into methane (CH₄)-emitting wetlands due to global warming is a rising concern. However, the spatially predominant mineral cryosols and their CH₄ emission potential are poorly understood. Fluxes measured in situ and estimated under laboratory conditions coupled with -omics analysis indicate (1) mineral cryosols in the Canadian high Arctic contain atmospheric CH₄-oxidizing bacteria; (2) the atmospheric CH⁺ uptake flux increases with ground temperature; and, as a result, (3) the atmospheric CH₄ sink strength will increase by a factor of 5-30 as the Arctic warms by 5-15 °C over a century. We demonstrated that acidic mineralmore » cryosols have previously unrecognized potential of negative CH₄ feedback.« less

Cluster-Expansion Model for Complex Quinary Alloys: Application to Alnico Permanent Magnets

NASA Astrophysics Data System (ADS)

Nguyen, Manh Cuong; Zhou, Lin; Tang, Wei; Kramer, Matthew J.; Anderson, Iver E.; Wang, Cai-Zhuang; Ho, Kai-Ming

2017-11-01

An accurate and transferable cluster-expansion model for complex quinary alloys is developed. Lattice Monte Carlo simulation enabled by this cluster-expansion model is used to investigate temperature-dependent atomic structure of alnico alloys, which are considered as promising high-performance non-rare-earth permanent-magnet materials for high-temperature applications. The results of the Monte Carlo simulations are consistent with available experimental data and provide useful insights into phase decomposition, selection, and chemical ordering in alnico. The simulations also reveal a previously unrecognized D 03 alloy phase. This phase is very rich in Ni and exhibits very weak magnetization. Manipulating the size and location of this phase provides a possible route to improve the magnetic properties of alnico, especially coercivity.

Changing partners: moving from non-homologous to homologous centromere pairing in meiosis

PubMed Central

Stewart, Mara N.; Dawson, Dean S.

2010-01-01

Reports of centromere pairing in early meiotic cells have appeared sporadically over the past thirty years. Recent experiments demonstrate that early centromere pairing occurs between non-homologous centromeres. As meiosis proceeds, centromeres change partners, becoming arranged in homologous pairs. Investigations of these later centromere pairs indicate that paired homologous centromeres are actively associated rather than positioned passively, side-by-side. Meiotic centromere pairing has been observed in organisms as diverse as mice, wheat and yeast, indicating that non-homologous centromere pairing in early meiosis and active homologous centromere pairing in later meiosis might be themes in meiotic chromosome behavior. Moreover, such pairing could have previously unrecognized roles in mediating chromosome organization or architecture that impact meiotic segregation fidelity. PMID:18804891

Terraces on the Florida escarpment: Implications for erosional processes

USGS Publications Warehouse

Twichell, D.C.; Paull, C.K.; Parson, L.M.

1991-01-01

SeaBeam bathymetric data and GLORIA (Geologic LOng-Range Inclined Asdic) sidescan sonar images of a 175-km-long section of the Florida escarpment in the eastern Guff of Mexico show that this carbonate escarpment has been eroded since its initial formation, but its morphology suggests that erosional processes have not acted uniformly on the escarpment. Parts of the escarpment are notched by box canyons that have extremely steep headwalls and may be sites off active ground-water sapping. The intercanyon areas commonly have previously unrecognized terraces below 2600 m. Above 2600 m, the escarpment is steeper and has no terraces. The terraces may reflect differences in platform strata exposed at the escarpment that are responding differently to erosional processes.

Two middle-age-onset hemochromatosis patients with heterozygous mutations in the hemojuvelin gene in a Chinese family.

PubMed

Li, Shufeng; Xue, Jun; Chen, Baojun; Wang, Qiwei; Shi, Minke; Xie, Xiaojing; Zhang, Liang

2014-04-01

Hereditary hemochromatosis is a disorder characterized by enhanced intestinal absorption of dietary iron. Here, we report a heterozygous genotype at two mutation sites in hemojuvelin (HJV) present in two brothers with middle-age-onset hemochromatosis in a Chinese family. To date, only homozygous or compound heterozygous states of HJV gene have been reported as associated with iron overload. However, the patients here were heterozygous for two mutations in one HJV allele in cis: a premature termination mutation (962G>A and 963C>A; C321X) and a mutation in the signal peptide (18G>C; Q6H). Previously unrecognized environmental or other genetic factors may have interacted with the heterozygous genotype in these patients.

Neutrophils alter the inflammatory milieu by signal-dependent translation of constitutive messenger RNAs

NASA Astrophysics Data System (ADS)

Lindemann, Stephan W.; Yost, Christian C.; Denis, Melvin M.; McIntyre, Thomas M.; Weyrich, Andrew S.; Zimmerman, Guy A.

2004-05-01

The mechanisms by which neutrophils, key effector cells of the innate immune system, express new gene products in inflammation are largely uncharacterized. We found that they rapidly translate constitutive mRNAs when activated, a previously unrecognized response. One of the proteins synthesized without a requirement for transcription is the soluble IL-6 receptor , which translocates to endothelial cells and induces a temporal switch to mononuclear leukocyte recruitment. Its synthesis is regulated by a specialized translational control pathway that is inhibited by rapamycin, a bacterial macrolide with therapeutic efficacy in transplantation, inflammatory syndromes, and neoplasia. Signal-dependent translation in activated neutrophils may be a critical mechanism for alteration of the inflammatory milieu and a therapeutic target.

Reevaluation of mid-Pliocene North Atlantic sea surface temperatures

USGS Publications Warehouse

Robinson, Marci M.; Dowsett, Harry J.; Dwyer, Gary S.; Lawrence, Kira T.

2008-01-01

Multiproxy temperature estimation requires careful attention to biological, chemical, physical, temporal, and calibration differences of each proxy and paleothermometry method. We evaluated mid-Pliocene sea surface temperature (SST) estimates from multiple proxies at Deep Sea Drilling Project Holes 552A, 609B, 607, and 606, transecting the North Atlantic Drift. SST estimates derived from faunal assemblages, foraminifer Mg/Ca, and alkenone unsaturation indices showed strong agreement at Holes 552A, 607, and 606 once differences in calibration, depth, and seasonality were addressed. Abundant extinct species and/or an unrecognized productivity signal in the faunal assemblage at Hole 609B resulted in exaggerated faunal-based SST estimates but did not affect alkenone-derived or Mg/Ca–derived estimates. Multiproxy mid-Pliocene North Atlantic SST estimates corroborate previous studies documenting high-latitude mid-Pliocene warmth and refine previous faunal-based estimates affected by environmental factors other than temperature. Multiproxy investigations will aid SST estimation in high-latitude areas sensitive to climate change and currently underrepresented in SST reconstructions.

Molecular Taxonomy Provides New Insights into Anopheles Species of the Neotropical Arribalzagia Series

PubMed Central

Gómez, Giovan F.; Bickersmith, Sara A.; González, Ranulfo; Conn, Jan E.; Correa, Margarita M.

2015-01-01

Phylogenetic analysis of partial mitochondrial cytochrome oxidase c subunit I (COI) and nuclear internal transcribed spacer 2 (ITS2) sequences were used to evaluate initial identification and to investigate phylogenetic relationships of seven Anopheles morphospecies of the Arribalzagia Series from Colombia. Phylogenetic trees recovered highly supported clades for An. punctimaculas.s., An. calderoni, An. malefactor s.l., An. neomaculipalpus, An. apicimacula s.l., An. mattogrossensis and An. peryassui. This study provides the first molecular confirmation of An. malefactorfrom Colombia and discovered conflicting patterns of divergence for the molecular markers among specimens from northeast and northern Colombia suggesting the presence of two previously unrecognized Molecular Operational Taxonomic Units (MOTUs). Furthermore, two highly differentiated An. apicimacula MOTUs previously found in Panama were detected. Overall, the combined molecular dataset facilitated the detection of known and new Colombian evolutionary lineages, and constitutes the baseline for future research on their bionomics, ecology and potential role as malaria vectors. PMID:25774795

Indoor Air Quality and Asthma

PubMed Central

Holm, Stewart

2017-01-01

Numerous contaminants in indoor air and their potential to cause or exacerbate asthma continue to be a subject of public health concern. Many agents are causally associated with or can exacerbate asthma, particularly in children. For formaldehyde, an established respiratory irritant based on numerous studies, the evidence for an association with asthma is still considered only limited or suggestive. However, there is no evidence that indicates increased sensitivity to sensory irritation to formaldehyde in people often regarded as susceptible such as asthmatics. Acrolein, but not formaldehyde, was significantly associated with asthma in a large cohort of children. This prompted an evaluation of this highly irritating chemical that had never previously been considered in the context of the indoor air/childhood asthma issue. Because acrolein is more potent than formaldehyde as a respiratory irritant and ubiquitous in indoor air, it is plausible that previous studies on potential risk factors and childhood asthma may be confounded by formaldehyde acting as an unrecognized proxy for acrolein. PMID:28250718

High REE and Y concentrations in Co-Cu-Au ores of the Blackbird district, Idaho

USGS Publications Warehouse

Slack, J.F.

2006-01-01

Analysis of 11 samples of strata-bound Co-Cu-Au ore from the Blackbird district in Idaho shows previously unknown high concentrations of rare earth elements (REE) and Y, averaging 0.53 wt percent ???REE + Y oxides. Scanning electron microscopy indicates REE and Y residence in monazite, xenotime, and allanite that form complex intergrowths with cobaltite, suggesting coeval Co and REE + Y mineralization during the Mesoproterozoic. Occurrence of high REE and Y concentrations in the Blackbird ores, together with previously documented saline-rich fluid inclusions and Cl-rich biotite, suggest that these are not volcanogenic massive sulfide or sedimentary exhalative deposits but instead are iron oxide-copper-gold (IOCG) deposits. Other strata-bound Co deposits of Proterozoic age in the North American Cordillera and elsewhere in the world may have potential for REE and Y resources. IOCG deposits with abundant light REE should also be evaluated for possible unrecognized heavy REE and Y mineralization. ?? 2006 by Economic Geology.

Rainfall-enhanced blooming in typhoon wakes

PubMed Central

Lin, Y.-C.; Oey, L.-Y.

2016-01-01

Strong phytoplankton blooming in tropical-cyclone (TC) wakes over the oligotrophic oceans potentially contributes to long-term changes in global biogeochemical cycles. Yet blooming has traditionally been discussed using anecdotal events and its biophysical mechanics remain poorly understood. Here we identify dominant blooming patterns using 16 years of ocean-color data in the wakes of 141 typhoons in western North Pacific. We observe right-side asymmetric blooming shortly after the storms, attributed previously to sub-mesoscale re-stratification, but thereafter a left-side asymmetry which coincides with the left-side preference in rainfall due to the large-scale wind shear. Biophysical model experiments and observations demonstrate that heavier rainfall freshens the near-surface water, leading to stronger stratification, decreased turbulence and enhanced blooming. Our results suggest that rainfall plays a previously unrecognized, critical role in TC-induced blooming, with potentially important implications for global biogeochemical cycles especially in view of the recent and projected increases in TC-intensity that harbingers stronger mixing and heavier rain under the storm. PMID:27545899

Fragmentation of Andes-to-Amazon connectivity by hydropower dams

PubMed Central

Anderson, Elizabeth P.; Jenkins, Clinton N.; Heilpern, Sebastian; Maldonado-Ocampo, Javier A.; Carvajal-Vallejos, Fernando M.; Encalada, Andrea C.; Rivadeneira, Juan Francisco; Hidalgo, Max; Cañas, Carlos M.; Ortega, Hernan; Salcedo, Norma; Maldonado, Mabel; Tedesco, Pablo A.

2018-01-01

Andes-to-Amazon river connectivity controls numerous natural and human systems in the greater Amazon. However, it is being rapidly altered by a wave of new hydropower development, the impacts of which have been previously underestimated. We document 142 dams existing or under construction and 160 proposed dams for rivers draining the Andean headwaters of the Amazon. Existing dams have fragmented the tributary networks of six of eight major Andean Amazon river basins. Proposed dams could result in significant losses in river connectivity in river mainstems of five of eight major systems—the Napo, Marañón, Ucayali, Beni, and Mamoré. With a newly reported 671 freshwater fish species inhabiting the Andean headwaters of the Amazon (>500 m), dams threaten previously unrecognized biodiversity, particularly among endemic and migratory species. Because Andean rivers contribute most of the sediment in the mainstem Amazon, losses in river connectivity translate to drastic alteration of river channel and floodplain geomorphology and associated ecosystem services. PMID:29399629

Fragmentation of Andes-to-Amazon connectivity by hydropower dams.

PubMed

Anderson, Elizabeth P; Jenkins, Clinton N; Heilpern, Sebastian; Maldonado-Ocampo, Javier A; Carvajal-Vallejos, Fernando M; Encalada, Andrea C; Rivadeneira, Juan Francisco; Hidalgo, Max; Cañas, Carlos M; Ortega, Hernan; Salcedo, Norma; Maldonado, Mabel; Tedesco, Pablo A

2018-01-01

Andes-to-Amazon river connectivity controls numerous natural and human systems in the greater Amazon. However, it is being rapidly altered by a wave of new hydropower development, the impacts of which have been previously underestimated. We document 142 dams existing or under construction and 160 proposed dams for rivers draining the Andean headwaters of the Amazon. Existing dams have fragmented the tributary networks of six of eight major Andean Amazon river basins. Proposed dams could result in significant losses in river connectivity in river mainstems of five of eight major systems-the Napo, Marañón, Ucayali, Beni, and Mamoré. With a newly reported 671 freshwater fish species inhabiting the Andean headwaters of the Amazon (>500 m), dams threaten previously unrecognized biodiversity, particularly among endemic and migratory species. Because Andean rivers contribute most of the sediment in the mainstem Amazon, losses in river connectivity translate to drastic alteration of river channel and floodplain geomorphology and associated ecosystem services.

Botulism from chopped garlic: delayed recognition of a major outbreak.

PubMed

St Louis, M E; Peck, S H; Bowering, D; Morgan, G B; Blatherwick, J; Banerjee, S; Kettyls, G D; Black, W A; Milling, M E; Hauschild, A H

1988-03-01

Diagnosis of botulism in two teenaged sisters in Montreal led to the identification of 36 previously unrecognized cases of type B botulism in persons who had eaten at a restaurant in Vancouver, British Columbia, during the preceding 6 weeks. A case-control study implicated a new vehicle for botulism, commercial chopped garlic in soybean oil (P less than 10(-4)). Relatively mild and slowly progressive illness, dispersion of patients over at least eight provinces and states in three countries, and a previously unsuspected vehicle had contributed to prolonged misdiagnoses, including myasthenia gravis (six patients), psychiatric disorders (four), stroke (three), and others. Ethnic background influenced severity of illness: 60% of Chinese patients but only 4% of others needed mechanical ventilation (P less than 10(-3]. Trypsinization of serum was needed to show toxemia in one patient. Electromyography results with high-frequency repetitive stimulation corroborated the diagnosis of botulism up to 2 months after onset. Although botulism is a life-threatening disease, misdiagnosis may be common and large outbreaks can escape recognition completely.

CD44 deficiency leads to decreased proinflammatory cytokine production in lung induced by PCV2 in mice.

PubMed

Fu, Qiang; Hou, Linbing; Xiao, Pingping; Guo, Chunhe; Chen, Yaosheng; Liu, Xiaohong

2014-12-01

Porcine circovirus type 2 (PCV2) is the primary etiological agent of postweaning multisystemic wasting syndrome (PMWS). CD44 is a widely expressed class I transmembrane glycoprotein implicated in immunological and inflammatory responses. In previous studies, the role of CD44 in host defense against microorganism infection remains controversial. The role of CD44 in host defense against PCV2 infection has never been studied before. In this study, we investigated the role of CD44 in the development of pneumonia induced by PCV2 in mice model. Upon infection, CD44 mRNA level in lung tissue was upregulated, and we confirmed a detrimental role of CD44 in host defense against PCV2 infection. The results demonstrated that CD44 deficiency could result in decreased proinflammatory cytokine production in lung induced by PCV2 in mice, suggesting a previously unrecognized role for CD44 in the development of pneumonia response to PCV2 infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

Alternative Splicing of Four Trafficking Genes Regulates Myofiber Structure and Skeletal Muscle Physiology.

PubMed

Giudice, Jimena; Loehr, James A; Rodney, George G; Cooper, Thomas A

2016-11-15

During development, transcriptional and post-transcriptional networks are coordinately regulated to drive organ maturation. Alternative splicing contributes by producing temporal-specific protein isoforms. We previously found that genes undergoing splicing transitions during mouse postnatal heart development are enriched for vesicular trafficking and membrane dynamics functions. Here, we show that adult trafficking isoforms are also expressed in adult skeletal muscle and hypothesize that striated muscle utilizes alternative splicing to generate specific isoforms required for function of adult tissue. We deliver morpholinos into flexor digitorum brevis muscles in adult mice to redirect splicing of four trafficking genes to the fetal isoforms. The splicing switch results in multiple structural and functional defects, including transverse tubule (T-tubule) disruption and dihydropyridine receptor alpha (DHPR) and Ryr1 mislocalization, impairing excitation-contraction coupling, calcium handling, and force generation. The results demonstrate a previously unrecognized role for trafficking functions in adult muscle tissue homeostasis and a specific requirement for the adult splice variants. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Enterococcus faecalis Ebp pili are important for cell-cell aggregation and intraspecies gene transfer

PubMed Central

Leanti La Rosa, Sabina; Camila Montealegre, Maria; Singh, Kavindra V.

2016-01-01

Enterococcus faecalis is an opportunistic pathogen that ranks among the leading causes of biofilm-associated infections. We previously demonstrated that the endocarditis- and biofilm-associated pili (Ebp) of E. faecalis play a major role in biofilm formation, adherence to abiotic surfaces and experimental infections. In this study, derivatives of E. faecalis strain OG1 were engineered to further characterize functions of Ebp pili. Loss of pili resulted in a 36-fold decrease in the number of closely associated cells when OG1RFΔebpABC was mixed with OG1SSpΔebpABC, compared with mixing the Ebp+ parental strains. In addition, using the Ebp+ parental strains as donor and recipient, we found a statistically significant increase (280–360 %, P < 0.05) in the frequency of plasmid transfer versus using Ebp−  mutants in the conjugation experiments. These results demonstrate a previously unrecognized role of Ebp pili, namely, as important contributors to microscale cell aggregation and horizontal spread of genetic material. PMID:26967674

Systematics of Vampyressa melissa Thomas, 1926 (Chiroptera, Phyllostomidae), with descriptions of two new species of Vampyressa

USGS Publications Warehouse

Tavares, Valéria da C.; Gardner, Alfred L.; Ramírez-Chaves, Héctor E.; Velazco, Paúl M.

2014-01-01

Vampyressa melissa is a poorly known phyllostomid bat listed as vulnerable by the International Union for Conservation of Nature (IUCN). Since its description in 1926, fewer than 40 V. melissa have been reported in the literature, and less than half of these may have been correctly identified. During revisionary studies of Vampyressa, we uncovered two previously unrecognized species related to V. melissa, all associated with higher elevation habitats (>1400 m), one from the Andes of Colombia (Vampyressa sinchi, new species) and the other from western Panama (Vampyressa elisabethae, new species) revealing that V. melissa, as traditionally defined, is a composite of at least three species. In this paper, we provide a restricted diagnosis for the genus Vampyressa, an emended diagnosis of V. melissa, and descriptions of the two new species. The separation of these frugivorous bats, previously identified as V. melissa, into three isolated upper-elevation species, each having restricted distributions further highlights their fragile conservation status.

Rainfall-enhanced blooming in typhoon wakes.

PubMed

Lin, Y-C; Oey, L-Y

2016-08-22

Strong phytoplankton blooming in tropical-cyclone (TC) wakes over the oligotrophic oceans potentially contributes to long-term changes in global biogeochemical cycles. Yet blooming has traditionally been discussed using anecdotal events and its biophysical mechanics remain poorly understood. Here we identify dominant blooming patterns using 16 years of ocean-color data in the wakes of 141 typhoons in western North Pacific. We observe right-side asymmetric blooming shortly after the storms, attributed previously to sub-mesoscale re-stratification, but thereafter a left-side asymmetry which coincides with the left-side preference in rainfall due to the large-scale wind shear. Biophysical model experiments and observations demonstrate that heavier rainfall freshens the near-surface water, leading to stronger stratification, decreased turbulence and enhanced blooming. Our results suggest that rainfall plays a previously unrecognized, critical role in TC-induced blooming, with potentially important implications for global biogeochemical cycles especially in view of the recent and projected increases in TC-intensity that harbingers stronger mixing and heavier rain under the storm.

Rainfall-enhanced blooming in typhoon wakes

NASA Astrophysics Data System (ADS)

Lin, Y.-C.; Oey, L.-Y.

2016-08-01

Strong phytoplankton blooming in tropical-cyclone (TC) wakes over the oligotrophic oceans potentially contributes to long-term changes in global biogeochemical cycles. Yet blooming has traditionally been discussed using anecdotal events and its biophysical mechanics remain poorly understood. Here we identify dominant blooming patterns using 16 years of ocean-color data in the wakes of 141 typhoons in western North Pacific. We observe right-side asymmetric blooming shortly after the storms, attributed previously to sub-mesoscale re-stratification, but thereafter a left-side asymmetry which coincides with the left-side preference in rainfall due to the large-scale wind shear. Biophysical model experiments and observations demonstrate that heavier rainfall freshens the near-surface water, leading to stronger stratification, decreased turbulence and enhanced blooming. Our results suggest that rainfall plays a previously unrecognized, critical role in TC-induced blooming, with potentially important implications for global biogeochemical cycles especially in view of the recent and projected increases in TC-intensity that harbingers stronger mixing and heavier rain under the storm.

Rainfall-enhanced blooming in typhoon wakes

NASA Astrophysics Data System (ADS)

Lin, Y.; Oey, L. Y.

2016-12-01

Strong phytoplankton blooming in tropical-cyclone (TC) wakes over the oligotrophic oceans potentially contributes to long-term changes in global biogeochemical cycles. Yet blooming has traditionally been discussed using anecdotal events and its biophysical mechanics remain poorly understood. Here we identify dominant blooming patterns using 16 years of ocean-color data in the wakes of 141 typhoons in western North Pacific. We observe right-side asymmetric blooming shortly after the storms, attributed previously to sub-mesoscale re-stratification, but thereafter a left-side asymmetry which coincides with the left-side preference in rainfall due to the large-scale wind shear. Biophysical model experiments and observations demonstrate that heavier rainfall freshens the near-surface water, leading to stronger stratification, decreased turbulence and enhanced blooming. Our results suggest that rainfall plays a previously unrecognized, critical role in TC-induced blooming, with potentially important implications for global biogeochemical cycles especially in view of the recent and projected increases in TC-intensity that harbingers stronger mixing and heavier rain under the storm.

Inducing amnesia through systemic suppression

PubMed Central

Hulbert, Justin C.; Henson, Richard N.; Anderson, Michael C.

2016-01-01

Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma. PMID:26977589

A comparative study of family functioning, health, and mental health awareness and utilization among female Bedouin-Arabs from recognized and unrecognized villages in the Negev.

PubMed

Al-Krenawi, Alean; Graham, John R

2006-02-01

A good portion of geography is contested by the Israeli state and the country's Bedouin-Arab population. There are two categories of Bedouin villages: those areas that are "officially" recognized by the state and those that are not. In this article we determine utilization and awareness of health and mental health services among 376 Bedouin-Arab women in recognized and unrecognized villages in the Negev. Although there are differences between them, primary health care (PHC) services usually are available within recognized villages, accessible to those from unrecognized villages, and tend to precipitate user satisfaction. We conclude with various suggestions for improving health service delivery and making PHC and mental health delivery more accessible. Through this article we intend to help mental health practitioners on two levels: the policy level, regarding the design of mental health services for societies in transition, such as the Bedouin Arab, and the practical level by helping practitioners better appreciate the psychosocial status of women in Bedouin-Arab societies and the factors associated with Bedouin-Arab PHC utilization.

Dissimilatory Fe(III) reduction by the marine microorganism Desulfuromonas acetoxidans

USGS Publications Warehouse

Roden, E.E.; Lovley, D.R.

1993-01-01

The ability of the marine microorganism Desulfuromonas acetoxidans to reduce Fe(III) was investigated because of its close phylogenetic relationship with the freshwater dissimilatory Fe(III) reducer Geobacter metallireducens. Washed cell suspensions of the type strain of D. acetoxidans reduced soluble Fe(III)-citrate and Fe(III) complexed with nitriloacetic acid. The c-type cytochrome(s) of D. acetoxidans was oxidized by Fe(III)- citrate and Mn(IV)-oxalate, as well as by two electron acceptors known to support growth, colloidal sulfur and malate. D. acetoxidans grew in defined anoxic, bicarbonate-buffered medium with acetate as the sole electron donor and poorly crystalline Fe(III) or Mn(IV) as the sole electron acceptor. Magnetite (Fe3O4) and siderite (FeCO3) were the major end products of Fe(III) reduction, whereas rhodochrosite (MnCO3) was the end product of Mn(IV) reduction. Ethanol, propanol, pyruvate, and butanol also served as electron donors for Fe(III) reduction. In contrast to D. acetoxidans, G. metallireducens could only grow in freshwater medium and it did not conserve energy to support growth from colloidal S0 reduction. D. acetoxidans is the first marine microorganism shown to conserve energy to support growth by coupling the complete oxidation of organic compounds to the reduction of Fe(III) or Mn(IV). Thus, D. acetoxidans provides a model enzymatic mechanism for Fe(III) or Mn(IV) oxidation of organic compounds in marine and estuarine sediments. These findings demonstrate that 16S rRNA phylogenetic analyses can suggest previously unrecognized metabolic capabilities of microorganisms.

Tumor-extrinsic discoidin domain receptor 1 promotes mammary tumor growth by regulating adipose stromal interleukin 6 production in mice.

PubMed

Sun, Xiujie; Gupta, Kshama; Wu, Bogang; Zhang, Deyi; Yuan, Bin; Zhang, Xiaowen; Chiang, Huai-Chin; Zhang, Chi; Curiel, Tyler J; Bendeck, Michelle P; Hursting, Stephen; Hu, Yanfen; Li, Rong

2018-02-23

Discoidin domain receptor 1 (DDR1) is a collagen receptor that mediates cell communication with the extracellular matrix (ECM). Aberrant expression and activity of DDR1 in tumor cells are known to promote tumor growth. Although elevated DDR1 levels in the stroma of breast tumors are associated with poor patient outcome, a causal role for tumor-extrinsic DDR1 in cancer promotion remains unclear. Here we report that murine mammary tumor cells transplanted to syngeneic recipient mice in which Ddr1 has been knocked out (KO) grow less robustly than in WT mice. We also found that the tumor-associated stroma in Ddr1- KO mice exhibits reduced collagen deposition compared with the WT controls, supporting a role for stromal DDR1 in ECM remodeling of the tumor microenvironment. Furthermore, the stromal-vascular fraction (SVF) of Ddr1 knockout adipose tissue, which contains committed adipose stem/progenitor cells and preadipocytes, was impaired in its ability to stimulate tumor cell migration and invasion. Cytokine array-based screening identified interleukin 6 (IL-6) as a cytokine secreted by the SVF in a DDR1-dependent manner. SVF-produced IL-6 is important for SVF-stimulated tumor cell invasion in vitro , and, using antibody-based neutralization, we show that tumor promotion by IL-6 in vivo requires DDR1. In conclusion, our work demonstrates a previously unrecognized function of DDR1 in promoting tumor growth. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Nipah Virus V Protein Evades Alpha and Gamma Interferons by Preventing STAT1 and STAT2 Activation and Nuclear Accumulation

PubMed Central

Rodriguez, Jason J.; Parisien, Jean-Patrick; Horvath, Curt M.

2002-01-01

Characterization of recent outbreaks of fatal encephalitis in southeast Asia identified the causative agent to be a previously unrecognized enveloped negative-strand RNA virus of the Paramyxoviridae family, Nipah virus. One feature linking Nipah virus to this family is a conserved cysteine-rich domain that is the hallmark of paramyxovirus V proteins. The V proteins of other paramyxovirus species have been linked with evasion of host cell interferon (IFN) signal transduction and subsequent antiviral responses by inducing proteasomal degradation of the IFN-responsive transcription factors, STAT1 or STAT2. Here we demonstrate that Nipah virus V protein escapes IFN by a distinct mechanism involving direct inhibition of STAT protein function. Nipah virus V protein differs from other paramyxovirus V proteins in its subcellular distribution but not in its ability to inhibit cellular IFN responses. Nipah virus V protein does not induce STAT degradation but instead inhibits IFN responses by forming high-molecular-weight complexes with both STAT1 and STAT2. We demonstrate that Nipah virus V protein accumulates in the cytoplasm by a Crm1-dependent mechanism, alters the STAT protein subcellular distribution in the steady state, and prevents IFN-stimulated STAT redistribution. Consistent with the formation of complexes, STAT protein tyrosine phosphorylation is inhibited in cells expressing the Nipah virus V protein. As a result, Nipah virus V protein efficiently prevents STAT1 and STAT2 nuclear translocation in response to IFN, inhibiting cellular responses to both IFN-α and IFN-γ. PMID:12388709

The Earth's Biosphere

NASA Technical Reports Server (NTRS)

2002-01-01

In the last five years, scientists have been able to monitor our changing planet in ways never before possible. The Sea-viewing Wide Field-of-View Sensor (SeaWiFS), aboard the OrbView-2 satellite, has given researchers an unprecedented view of the biological engine that drives life on Earth-the countless forms of plants that cover the land and fill the oceans. 'There is no question the Earth is changing. SeaWiFS has enabled us, for the first time, to monitor the biological consequences of that change-to see how the things we do, as well as natural variability, affect the Earth's ability to support life,' said Gene Carl Feldman, SeaWiFS project manager at NASA's Goddard Space Flight Center, Greenbelt, Md. SeaWiFS data, based on continuous daily global observations, have helped scientists make a more accurate assessment of the oceans' role in the global carbon cycle. The data provide a key parameter in a number of ecological and environmental studies as well as global climate-change modeling. The images of the Earth's changing land, ocean and atmosphere from SeaWiFS have documented many previously unrecognized phenomena. The image above shows the global biosphere from June 2002 measured by SeaWiFS. Data in the oceans is chlorophyll concentration, a measure of the amount of phytoplankton (microscopic plants) living in the ocean. On land SeaWiFS measures Normalized Difference Vegetation Index, an indication of the density of plant growth. For more information and images, read: SeaWiFS Sensor Marks Five Years Documenting Earth'S Dynamic Biosphere Image courtesy SeaWiFS project and copyright Orbimage.

BMP15 Mutations Associated With Primary Ovarian Insufficiency Reduce Expression, Activity, or Synergy With GDF9.

PubMed

Patiño, Liliana C; Walton, Kelly L; Mueller, Thomas D; Johnson, Katharine E; Stocker, William; Richani, Dulama; Agapiou, David; Gilchrist, Robert B; Laissue, Paul; Harrison, Craig A

2017-03-01

Bone morphogenetic protein (BMP)15 is an oocyte-specific growth factor, which, together with growth differentiation factor (GDF) 9, regulates folliculogenesis and ovulation rate. Multiple mutations in BMP15 have been identified in women with primary ovarian insufficiency (POI), supporting a pathogenic role; however, the underlying biological mechanism of many of these mutants remains unresolved. To determine how mutations associated with ovarian dysfunction alter the biological activity of human BMP15. The effects of 10 mutations in BMP15 on protein production, activation of granulosa cells, and synergy with GDF9 were assessed. Sequencing of 35 patients with POI identified both an unrecognized BMP15 variant (c.986G>A, R329H) and a variant (c.581T>C, F194S) previously associated with the condition. Assessing expression and activity of these and 8 other BMP15 mutants identified: (1) multiple variants, including L148P, F194S, and Y235C, with reduced mature protein production; (2) three variants (R138H, A180T, and R329H) with ∼fourfold lower activity than wild-type BMP15; and (3) 3 variants (R68W, F194S, and N196K) with a significantly reduced ability to synergize with GDF9. Mutations in BMP15 associated with POI reduce mature protein production, activity, or synergy with GDF9. The latter effect is perhaps most interesting given that interactions with GDF9 most likely underlie the physiology of BMP15 in the human ovary. Copyright © 2017 by the Endocrine Society

An interplay between the serotonin transporter (SERT) and 5-HT receptors controls stimulus-secretion coupling in sympathoadrenal chromaffin cells.

PubMed

Brindley, Rebecca L; Bauer, Mary Beth; Blakely, Randy D; Currie, Kevin P M

2016-11-01

Adrenal chromaffin cells (ACCs), the neuroendocrine arm of the sympathetic nervous system, secrete catecholamines to mediate the physiological response to stress. Although ACCs do not synthesize 5-HT, they express the serotonin transporter (SERT). Genetic variations in SERT are linked to several CNS disorders but the role(s) of SERT/5-HT in ACCs has remained unclear. Adrenal glands from wild-type mice contained 5-HT at ≈ 750 fold lower abundance than adrenaline, and in SERT(-/-) mice this was reduced by ≈80% with no change in catecholamines. Carbon fibre amperometry showed that SERT modulated the ability of 5-HT1A receptors to inhibit exocytosis. 5-HT reduced the number of amperometric spikes (vesicular fusion events) evoked by KCl in SERT(-/-) cells and wild-type cells treated with escitalopram, a SERT antagonist. The 5-HT1A receptor antagonist WAY100635 blocked the inhibition by 5-HT which was mimicked by the 5-HT1A agonist 8-OH-DPAT but not the 5-HT1B agonist CP93129. There was no effect on voltage-gated Ca(2+) channels, K(+) channels, or intracellular [Ca(2+)] handling, showing the 5-HT receptors recruit an atypical inhibitory mechanism. Spike charge and kinetics were not altered by 5-HT receptors but were reduced in SERT(-/-) cells compared to wild-type cells. Our data reveal a novel role for SERT and suggest that adrenal chromaffin cells might be a previously unrecognized hub for serotonergic control of the sympathetic stress response. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intestinal Perforation Following Ileoscopy Through a Prolapsed Stoma in an Pediatric Intestinal Transplant Recipient With an Unrecognized Parastomal Hernia

PubMed Central

Yeh, Joanna; Hall, Theodore R.; Agopian, Vatche G.; Farmer, Douglas G.; Marcus, Elizabeth A.; Venick, Robert S.; Wozniak, Laura J.

2016-01-01

Ileoscopy with mucosal biopsy is fundamental in the management and surveillance of inflammatory bowel disease patients and intestinal transplant recipients. There is a paucity of data describing the risks of ileoscopy in the presence of a prolapsed stoma. Parastomal hernias are frequently associated with prolapsed stomas. We report the first case of perforation during ileoscopy in the setting of a prolapsed stoma and unrecognized parastomal hernia. Recognition of parastomal hernia associated with stoma prolapse is of paramount importance in patients undergoing ileoscopy as it may increase the risk of perforation. PMID:27807575

Chronic sinusitis associated with the use of unrecognized bone substitute: a case report.

PubMed

Beklen, Arzu; Pihakari, Antti; Rautemaa, Riina; Hietanen, Jarkko; Ali, Ahmed; Konttinen, Yrjö T

2008-05-01

Bone grafts are used for bone augmentation to ensure optimal implant placement. However, this procedure may sometimes cause sinusitis. The case of a 44-year-old woman with the diagnosis of recurrent and chronic sinusitis of her right maxillary sinus with a history of dental implant surgery is presented. After several attempts with normal standard sinusitis therapy, unrecognized bone substitute was removed from the sinus cavity, which finally led to resolution of the sinusitis. This case reiterates the importance of a careful examination, consultation, and second opinion for the selection of optimal treatment.

Behavior problems in children at time of first recognized seizure and changes over the following 3 years.

PubMed

Austin, J K; Perkins, S M; Johnson, C S; Fastenau, P S; Byars, A W; deGrauw, T J; Dunn, D W

2011-08-01

The purposes of this 36-month study of children with first recognized seizures were: (1) to describe baseline differences in behavior problems between children with and without prior unrecognized seizures; (2) to identify differences over time in behavior problems between children with seizures and their healthy siblings; (3) to identify the proportions of children with seizures and healthy siblings who were consistently at risk for behavior problems for 36 months; and (4) to identify risk factors for behavior problems 36 months following the first recognized seizure. Risk factors explored included demographic (child age and gender, caregiver education), neuropsychological (IQ, processing speed), seizure (epileptic syndrome, use of antiepileptic drug, seizure recurrence), and family (family mastery, satisfaction with family relationships, parent response) variables. Participants were 300 children aged 6 through 14 years with a first recognized seizure and 196 healthy siblings. Data were collected from medical records, structured interviews, self-report questionnaires, and neuropsychological testing. Behavior problems were measured using the Child Behavior Checklist and the Teacher's Report Form. Data analyses included descriptive statistics and linear mixed models. Children with prior unrecognized seizures were at higher risk for behavior problems at baseline. As a group, children with seizures showed a steady reduction in behavior problems over time. Children with seizures were found to have significantly more behavior problems than their siblings over time, and significantly more children with seizures (11.3%) than siblings (4.6%) had consistent behavior problems over time. Key risk factors for child behavior problems based on both caregivers and teachers were: less caregiver education, slower initial processing speed, slowing of processing speed over the first 36 months, and a number of family variables including lower levels of family mastery or child satisfaction with family relationships, lower parent support of the child's autonomy, and lower parent confidence in their ability to discipline their child. Children with new-onset seizures who are otherwise developing normally have higher rates of behavior problems than their healthy siblings; however, behavior problems are not consistently in the at-risk range in most children during the first 3 years after seizure onset. When children show behavior problems, family variables that might be targeted include family mastery, parent support of child autonomy, and parents' confidence in their ability to handle their children's behavior.

The attention habit: how reward learning shapes attentional selection.

PubMed

Anderson, Brian A

2016-04-01

There is growing consensus that reward plays an important role in the control of attention. Until recently, reward was thought to influence attention indirectly by modulating task-specific motivation and its effects on voluntary control over selection. Such an account was consistent with the goal-directed (endogenous) versus stimulus-driven (exogenous) framework that had long dominated the field of attention research. Now, a different perspective is emerging. Demonstrations that previously reward-associated stimuli can automatically capture attention even when physically inconspicuous and task-irrelevant challenge previously held assumptions about attentional control. The idea that attentional selection can be value driven, reflecting a distinct and previously unrecognized control mechanism, has gained traction. Since these early demonstrations, the influence of reward learning on attention has rapidly become an area of intense investigation, sparking many new insights. The result is an emerging picture of how the reward system of the brain automatically biases information processing. Here, I review the progress that has been made in this area, synthesizing a wealth of recent evidence to provide an integrated, up-to-date account of value-driven attention and some of its broader implications. © 2015 New York Academy of Sciences.

ISOFORMS OF VITAMIN E DIFFERENTIALLY REGULATE INFLAMMATION

PubMed Central

Cook-Mills, Joan M.; McCary, Christine A.

2011-01-01

Vitamin E regulation of disease has been extensively studied in humans, animal models and cell systems. Most of these studies focus on the α-tocopherol isoform of vitamin E. These reports indicate contradictory outcomes for anti-inflammatory functions of the α-tocopherol isoform of vitamin E, especially with regards to clinical studies of asthma and atherosclerosis. These seemingly disparate clinical results are consistent with recently reported unrecognized properties of isoforms of vitamin E. Recently, it has been reported that physiological levels of purified natural forms of vitamin E have opposing regulatory functions during inflammation. These opposing regulatory functions by physiological levels of vitamin E isoforms impact interpretations of previous studies on vitamin E. Moreover, additional recent studies also indicate that the effects of vitamin E isoforms on inflammation are only partially reversible using physiological levels of a vitamin E isoform with opposing immunoregulatory function. Thus, this further influences interpretations of previous studies with vitamin E in which there was inflammation and substantial vitamin E isoforms present before the initiation of the study. In summary, this review will discuss regulation of inflammation by vitamin E, including alternative interpretations of previous studies in the literature with regards to vitamin E isoforms. PMID:20923401

Stress, burnout, and maladaptive coping: strategies for surgeon well-being.

PubMed

Bittner, James G; Khan, Zarrish; Babu, Maya; Hamed, Osama

2011-08-01

Practicing physicians and surgeons, medical and surgical residents, and medical students dedicate their lives to providing optimum patient care, but doing so places them at significant risk for personal and professional stress and, ultimately, burnout. Of great concern is the fact that unrecognized stress and unmanaged burnout are more prevalent among residents than previously believed. Research shows that stress without conflict resolution may lead to burnout, which can contribute to impaired technical performance, medical errors, physical and mental health problems, and even increase the risk of suicide. Therefore, it is crucial that surgeons, and the organizations that train and employ them, recognize the early signs of stress and burnout, adopt adaptive coping strategies, and maintain a culture wherein work-life balance and surgeon well-being are shared goals.

Prevalent Glucocorticoid and Androgen Activity in US Water Sources

PubMed Central

Stavreva, Diana A.; George, Anuja A.; Klausmeyer, Paul; Varticovski, Lyuba; Sack, Daniel; Voss, Ty C.; Schiltz, R. Louis; Blazer, Vicki S.; Iwanowicz, Luke R.; Hager, Gordon L.

2012-01-01

Contamination of the environment with endocrine disrupting chemicals (EDCs) is a major health concern. The presence of estrogenic compounds in water and their deleterious effect are well documented. However, detection and monitoring of other classes of EDCs is limited. Here we utilize a high-throughput live cell assay based on sub-cellular relocalization of GFP-tagged glucocorticoid and androgen receptors (GFP-GR and GFP-AR), in combination with gene transcription analysis, to screen for glucocorticoid and androgen activity in water samples. We report previously unrecognized glucocorticoid activity in 27%, and androgen activity in 35% of tested water sources from 14 states in the US. Steroids of both classes impact body development, metabolism, and interfere with reproductive, endocrine, and immune systems. This prevalent contamination could negatively affect wildlife and human populations. PMID:23226835

Prevalent glucocorticoid and androgen activity in US water sources.

PubMed

Stavreva, Diana A; George, Anuja A; Klausmeyer, Paul; Varticovski, Lyuba; Sack, Daniel; Voss, Ty C; Schiltz, R Louis; Blazer, Vicki S; Iwanowicz, Luke R; Hager, Gordon L

2012-01-01

Contamination of the environment with endocrine disrupting chemicals (EDCs) is a major health concern. The presence of estrogenic compounds in water and their deleterious effect are well documented. However, detection and monitoring of other classes of EDCs is limited. Here we utilize a high-throughput live cell assay based on sub-cellular relocalization of GFP-tagged glucocorticoid and androgen receptors (GFP-GR and GFP-AR), in combination with gene transcription analysis, to screen for glucocorticoid and androgen activity in water samples. We report previously unrecognized glucocorticoid activity in 27%, and androgen activity in 35% of tested water sources from 14 states in the US. Steroids of both classes impact body development, metabolism, and interfere with reproductive, endocrine, and immune systems. This prevalent contamination could negatively affect wildlife and human populations.

Early scattering of the solar protoplanetary disk recorded in meteoritic chondrules

PubMed Central

Marrocchi, Yves; Chaussidon, Marc; Piani, Laurette; Libourel, Guy

2016-01-01

Meteoritic chondrules are submillimeter spherules representing the major constituent of nondifferentiated planetesimals formed in the solar protoplanetary disk. The link between the dynamics of the disk and the origin of chondrules remains enigmatic. Collisions between planetesimals formed at different heliocentric distances were frequent early in the evolution of the disk. We show that the presence, in some chondrules, of previously unrecognized magnetites of magmatic origin implies the formation of these chondrules under impact-generated oxidizing conditions. The three oxygen isotopes systematic of magmatic magnetites and silicates can only be explained by invoking an impact between silicate-rich and ice-rich planetesimals. This suggests that these peculiar chondrules are by-products of the early mixing in the disk of populations of planetesimals from the inner and outer solar system. PMID:27419237

Optimized knock-in of point mutations in zebrafish using CRISPR/Cas9.

PubMed

Prykhozhij, Sergey V; Fuller, Charlotte; Steele, Shelby L; Veinotte, Chansey J; Razaghi, Babak; Robitaille, Johane M; McMaster, Christopher R; Shlien, Adam; Malkin, David; Berman, Jason N

2018-06-14

We have optimized point mutation knock-ins into zebrafish genomic sites using clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 reagents and single-stranded oligodeoxynucleotides. The efficiency of knock-ins was assessed by a novel application of allele-specific polymerase chain reaction and confirmed by high-throughput sequencing. Anti-sense asymmetric oligo design was found to be the most successful optimization strategy. However, cut site proximity to the mutation and phosphorothioate oligo modifications also greatly improved knock-in efficiency. A previously unrecognized risk of off-target trans knock-ins was identified that we obviated through the development of a workflow for correct knock-in detection. Together these strategies greatly facilitate the study of human genetic diseases in zebrafish, with additional applicability to enhance CRISPR-based approaches in other animal model systems.

Effect of sound on gap-junction-based intercellular signaling: Calcium waves under acoustic irradiation.

PubMed

Deymier, P A; Swinteck, N; Runge, K; Deymier-Black, A; Hoying, J B

2015-01-01

We present a previously unrecognized effect of sound waves on gap-junction-based intercellular signaling such as in biological tissues composed of endothelial cells. We suggest that sound irradiation may, through temporal and spatial modulation of cell-to-cell conductance, create intercellular calcium waves with unidirectional signal propagation associated with nonconventional topologies. Nonreciprocity in calcium wave propagation induced by sound wave irradiation is demonstrated in the case of a linear and a nonlinear reaction-diffusion model. This demonstration should be applicable to other types of gap-junction-based intercellular signals, and it is thought that it should be of help in interpreting a broad range of biological phenomena associated with the beneficial therapeutic effects of sound irradiation and possibly the harmful effects of sound waves on health.

Bioresorbable Electronic Stent Integrated with Therapeutic Nanoparticles for Endovascular Diseases.

PubMed

Son, Donghee; Lee, Jongha; Lee, Dong Jun; Ghaffari, Roozbeh; Yun, Sumin; Kim, Seok Joo; Lee, Ji Eun; Cho, Hye Rim; Yoon, Soonho; Yang, Shixuan; Lee, Seunghyun; Qiao, Shutao; Ling, Daishun; Shin, Sanghun; Song, Jun-Kyul; Kim, Jaemin; Kim, Taeho; Lee, Hakyong; Kim, Jonghoon; Soh, Min; Lee, Nohyun; Hwang, Cheol Seong; Nam, Sangwook; Lu, Nanshu; Hyeon, Taeghwan; Choi, Seung Hong; Kim, Dae-Hyeong

2015-06-23

Implantable endovascular devices such as bare metal, drug eluting, and bioresorbable stents have transformed interventional care by providing continuous structural and mechanical support to many peripheral, neural, and coronary arteries affected by blockage. Although effective in achieving immediate restoration of blood flow, the long-term re-endothelialization and inflammation induced by mechanical stents are difficult to diagnose or treat. Here we present nanomaterial designs and integration strategies for the bioresorbable electronic stent with drug-infused functionalized nanoparticles to enable flow sensing, temperature monitoring, data storage, wireless power/data transmission, inflammation suppression, localized drug delivery, and hyperthermia therapy. In vivo and ex vivo animal experiments as well as in vitro cell studies demonstrate the previously unrecognized potential for bioresorbable electronic implants coupled with bioinert therapeutic nanoparticles in the endovascular system.

Hippocampal ripples down-regulate synapses.

PubMed

Norimoto, Hiroaki; Makino, Kenichi; Gao, Mengxuan; Shikano, Yu; Okamoto, Kazuki; Ishikawa, Tomoe; Sasaki, Takuya; Hioki, Hiroyuki; Fujisawa, Shigeyoshi; Ikegaya, Yuji

2018-03-30

The specific effects of sleep on synaptic plasticity remain unclear. We report that mouse hippocampal sharp-wave ripple oscillations serve as intrinsic events that trigger long-lasting synaptic depression. Silencing of sharp-wave ripples during slow-wave states prevented the spontaneous down-regulation of net synaptic weights and impaired the learning of new memories. The synaptic down-regulation was dependent on the N -methyl-d-aspartate receptor and selective for a specific input pathway. Thus, our findings are consistent with the role of slow-wave states in refining memory engrams by reducing recent memory-irrelevant neuronal activity and suggest a previously unrecognized function for sharp-wave ripples. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Anterior Cruciate Ligament Injury, Reconstruction, and the Optimization of Outcome

PubMed Central

Bliss, James Philip

2017-01-01

Anterior cruciate ligament reconstruction (ACLR) provides an established surgical intervention to control pathological tibiofemoral translational and rotational movement. ACLR is a safe and reproducible intervention, but there remains an underlying rate of failure to return to preinjury sporting activity levels. Postoperative pathological laxity and graft reinjury remain concerns. Previously, unrecognized meniscal lesions, disruption of the lateral capsule, and extracapsular structures offer potential avenues to treat and to therefore improve kinematic outcome and functional results, following reconstruction. Addressing laterally based injuries may also improve the durability of intraarticular ACLR. Improving the anterior cruciate ligament (ACL) graft replication of the normal ACL attachment points on the femur and the tibia, using either double bundle or anatomical single bundle techniques, improves kinematics, which may benefit outcome and functionality, following reconstruction. PMID:28966384

Prevalent flucocorticoid and androgen activity in US water sources

USGS Publications Warehouse

Stavreva, Diana A.; George, Anuja A.; Klausmeyer, Paul; Varticovski, Lyuba; Sack, Daniel; Voss, Ty C.; Schiltz, R. Louis; Blazer, Vicki; Iwanowiczl, Luke R.; Hager, Gordon L.

2012-01-01

Contamination of the environment with endocrine disrupting chemicals (EDCs) is a major health concern. The presence of estrogenic compounds in water and their deleterious effect are well documented. However, detection and monitoring of other classes of EDCs is limited. Here we utilize a high-throughput live cell assay based on sub-cellular relocalization of GFP-tagged glucocorticoid and androgen receptors (GFP-GR and GFP-AR), in combination with gene transcription analysis, to screen for glucocorticoid and androgen activity in water samples. We report previously unrecognized glucocorticoid activity in 27%, and androgen activity in 35% of tested water sources from 14 states in the US. Steroids of both classes impact body development, metabolism, and interfere with reproductive, endocrine, and immune systems. This prevalent contamination could negatively affect wildlife and human populations.

A Republican Egalitarian Approach to Bioethics: The Case of the Unrecognized Bedouin Villages in Israel.

PubMed

Filc, Dani; Davidovich, Nadav; Gottlieb, Nora

2016-10-01

This article argues that current, mainstream, liberal approaches to the right to health and to bioethics are not adequately aware of the structural and political character of health and illness. We propose a radical egalitarian definition of the right to health as the basis for the discussion of a republican egalitarian perspective on bioethics that redefines autonomy and stresses the importance of equality, political participation, and the common good. The violations of the right to health in unrecognized Bedouin villages in Israel are analyzed to exemplify the possibilities opened by the republican egalitarian approach. © The Author(s) 2015.

Unrecognized pediatric and adult family members of children with acute brucellosis.

PubMed

Çiftdoğan, Dilek Yılmaz; Aslan, Selda

Brucellosis is an infectious, contagious and zoonotic disease that occurs worldwide. The family members of an index case of brucellosis may be especially susceptible, due to sharing the same source of infection and similar risk factors for brucellosis. In this study, we propose to screen pediatric and adult family members of brucellosis index cases for detecting additional unrecognized infected family members. 114 family members of 41 pediatric patients with brucellosis were evaluated. All family members completed a brief questionnaire and were tested by a standard tube agglutination test (STA). The majority of family members (n=96, 84.2%) were children. Among the 114 family members, 42 (36.8%) were seropositive, and 15 (35.7%) were symptomatic. The majority of the symptomatic seropositive family members (n=12, 80%) had STA titers (≥1:640) higher than asymptomatic seropositive family members (n=9, 33%; p=0.004). The routine screening of both pediatric and adult family members of index cases is a priority in endemic areas. Using this screening approach, unrecognized family members who are seropositive for brucellosis will be identified earlier and be able to receive prompt treatment. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Delivery of tobramycin coupled to iron oxide nanoparticles across the biofilm of mucoidal Pseudonomas aeruginosa and investigation of its efficacy

NASA Astrophysics Data System (ADS)

Armijo, Leisha M.; Kopciuch, Michael; Olszá½¹wka, Zuzia; Wawrzyniec, Stephen J.; Rivera, Antonio C.; Plumley, John B.; Cook, Nathaniel C.; Brandt, Yekaterina I.; Huber, Dale L.; Smolyakov, Gennady A.; Adolphi, Natalie L.; Smyth, Hugh D. C.; Osiński, Marek

2014-03-01

Pseudomonas aeruginosa bacterium is a deadly pathogen, leading to respiratory failure in cystic fibrosis and nosocomial pneumonia, and responsible for high mortality rates in these diseases. P. aeruginosa has inherent as well as acquired resistance to many drug classes. In this paper, we investigate the effectiveness of two classes; aminoglycoside (tobramycin) and fluoroquinolone (ciprofloxacin) administered alone, as well as conjugated to iron oxide (magnetite) nanoparticles. P. aeruginosa possesses the ability to quickly alter its genetics to impart resistance to the presence of new, unrecognized treatments. As a response to this impending public health threat, we have synthesized and characterized magnetite nanoparticles capped with biodegradable short-chain carboxylic acid derivatives conjugated to common antibiotic drugs. The functionalized nanoparticles may carry the drug past the mucus and biofilm layers to target the bacterial colonies via magnetic gradient-guided transport. Additionally, the magnetic ferrofluid may be used under application of an oscillating magnetic field to raise the local temperature, causing biofilm disruption, slowed growth, and mechanical disruption. These abilities of the ferrofluid would also treat multi-drug resistant strains, which appear to be increasing in many nosocomial as well as acquired opportunistic infections. In this in vitro model, we show that the iron oxide alone can also inhibit bacterial growth and biofilm formation.

Src-homology 2 domain-containing tyrosine phosphatase 2 promotes oral cancer invasion and metastasis

PubMed Central

2014-01-01

Background Tumor invasion and metastasis represent a major unsolved problem in cancer pathogenesis. Recent studies have indicated the involvement of Src-homology 2 domain-containing tyrosine phosphatase 2 (SHP2) in multiple malignancies; however, the role of SHP2 in oral cancer progression has yet to be elucidated. We propose that SHP2 is involved in the progression of oral cancer toward metastasis. Methods SHP2 expression was evaluated in paired oral cancer tissues by using immunohistochemical staining and real-time reverse transcription polymerase chain reaction. Isogenic highly invasive oral cancer cell lines from their respective low invasive parental lines were established using a Boyden chamber assay, and changes in the hallmarks of the epithelial-mesenchymal transition (EMT) were assessed to evaluate SHP2 function. SHP2 activity in oral cancer cells was reduced using si-RNA knockdown or enforced expression of a catalytically deficient mutant to analyze migratory and invasive ability in vitro and metastasis toward the lung in mice in vivo. Results We observed the significant upregulation of SHP2 in oral cancer tissues and cell lines. Following SHP2 knockdown, the oral cancer cells markedly attenuated migratory and invasion ability. We observed similar results in phosphatase-dead SHP2 C459S mutant expressing cells. Enhanced invasiveness was associated with significant upregulation of E-cadherin, vimentin, Snail/Twist1, and matrix metalloproteinase-2 in the highly invasive clones. In addition, we determined that SHP2 activity is required for the downregulation of phosphorylated ERK1/2, which modulates the downstream effectors, Snail and Twist1 at a transcript level. In lung tissue sections of mice, we observed that HSC3 tumors with SHP2 deletion exhibited significantly reduced metastatic capacity, compared with tumors administered control si-RNA. Conclusions Our data suggest that SHP2 promotes the invasion and metastasis of oral cancer cells. These results provide a rationale for further investigating the effects of small-molecule SHP2 inhibitors on the progression of oral cancer, and indicate a previously unrecognized SHP2-ERK1/2-Snail/Twist1 pathway that is likely to play a crucial role in oral cancer invasion and metastasis. PMID:24931737

Mutational analysis uncovers monogenic bone disorders in women with pregnancy-associated osteoporosis: three novel mutations in LRP5, COL1A1, and COL1A2.

PubMed

Butscheidt, S; Delsmann, A; Rolvien, T; Barvencik, F; Al-Bughaili, M; Mundlos, S; Schinke, T; Amling, M; Kornak, U; Oheim, R

2018-03-29

Pregnancy was found to be a skeletal risk factor promoting the initial onset of previously unrecognized monogenic bone disorders, thus explaining a proportion of cases with pregnancy-associated osteoporosis. Therapeutic measures should focus in particular on the normalization of the disturbed calcium homeostasis in order to enable the partial skeletal recovery. Pregnancy-associated osteoporosis (PAO) is a rare skeletal condition, which is characterized by a reduction in bone mineral density (BMD) in the course of pregnancy and lactation. Typical symptoms include vertebral compression fractures and transient osteoporosis of the hip. Since the etiology is not well understood, this prospective study was conducted in order to elucidate the relevance of pathogenic gene variants for the development of PAO. Seven consecutive cases with the diagnosis of PAO underwent a skeletal assessment (blood tests, DXA, HR-pQCT) and a comprehensive genetic analysis using a custom-designed gene panel. All cases showed a reduced BMD (DXA T-score, lumbar spine - 3.2 ± 1.0; left femur - 2.2 ± 0.5; right femur - 1.9 ± 0.5), while the spine was affected more severely (p < 0.05). The trabecular and cortical thickness was overall reduced in HR-pQCT, while the trabecular number showed no alterations in most cases. The genetic analysis revealed three novel mutations in LRP5, COL1A1, and COL1A2. Our data show that previously unrecognized monogenic bone disorders play an important role in PAO. Pregnancy should be considered a skeletal risk factor, which can promote the initial clinical onset of such skeletal disorders. The underlying increased calcium demand is essential in terms of prophylactic and therapeutic measures, which are especially required in individuals with a genetically determined low bone mass. The implementation of this knowledge in clinical practice can enable the partial recovery of the skeleton. Consistent genetic studies are needed to analyze the frequency of pathogenic variants in women with PAO.

Transient asymptomatic pulmonary opacities occurring during osimertinib treatment

PubMed Central

Noonan, Sinead A.; Sachs, Peter B.; Camidge, D. Ross

2017-01-01

Introduction Osimertinib is an Epidermal Growth Factor Receptor (EGFR) Inhibitor licensed for the treatment of EGFR mutant, T790M positive, non-small cell lung cancer (NSCLC). Previously unreported, common, transient asymptomatic pulmonary opacities (TAPOs) were noted at the University of Colorado in patients during osimertinib therapy. Methods CT imaging and clinical notes of NSCLC patients treated at the University of Colorado with osimertinib were retrospectively reviewed. Results Seven of twenty patients (35%), developed TAPOs while on osimertinib. The radiological patterns seen included ground-glass opacities with/without nodular consolidation. The median time to first lesion development was 8.7 weeks (range: 1.6 – 43 weeks) and 6 weeks (range: 1 – 11 weeks) to resolution during continued osimertinib. Conclusions TAPOs may be a previously unrecognized, benign feature associated with osimertinib therapy, which may be mistaken for isolated pulmonary progression or the beginning of more severe pneumonitis. If new onset pulmonary lesions, especially those associated with ground-glass appearances, are asymptomatic, localized and there is no evidence of disease progression elsewhere it may be reasonable to continue treatment with osimertinib and monitor these lesions for resolution. PMID:27618759

The double auditory meatus--a rare first branchial cleft anomaly: clinical presentation and treatment.

PubMed

Stokroos, R J; Manni, J J

2000-11-01

To discuss the embryology, classification, clinical experience with, and management of first branchial cleft anomalies. Retrospective case review. Tertiary referral center. Patients with a first branchial cleft anomaly. Surgery or revision surgery. Classifications according to Work, Olsen, Chilla; previous diagnostic and therapeutic pitfalls; outcome of intervention (including facial nerve function). Between 1984 and 1999, first branchial cleft anomalies were diagnosed in 18 patients. Surgical treatment was the treatment of choice. The authors' approach in Work type I and type 2 lesions is described, and surgical aspects of revision surgery are discussed. The importance of early establishment of the relationship of the anomaly to the facial nerve is stressed. In 8 patients, previous surgical attempts had been undertaken without establishment of the diagnosis first. After intervention, the outcome was favorable. First branchial cleft anomalies occur sporadically in ordinary clinical practice. They may go unrecognized or may be mistaken for tumors or other inflammatory lesions of in the periauricular region. However, the distinct clinical features, which can be derived from embryologic development, usually lead to the correct diagnosis. This avoids both treatment delay and eventual failure.

Global Maps of ProQ Binding In Vivo Reveal Target Recognition via RNA Structure and Stability Control at mRNA 3' Ends.

PubMed

Holmqvist, Erik; Li, Lei; Bischler, Thorsten; Barquist, Lars; Vogel, Jörg

2018-05-15

The conserved RNA-binding protein ProQ has emerged as the centerpiece of a previously unknown third large network of post-transcriptional control in enterobacteria. Here, we have used in vivo UV crosslinking and RNA sequencing (CLIP-seq) to map hundreds of ProQ binding sites in Salmonella enterica and Escherichia coli. Our analysis of these binding sites, many of which are conserved, suggests that ProQ recognizes its cellular targets through RNA structural motifs found in small RNAs (sRNAs) and at the 3' end of mRNAs. Using the cspE mRNA as a model for 3' end targeting, we reveal a function for ProQ in protecting mRNA against exoribonucleolytic activity. Taken together, our results underpin the notion that ProQ governs a post-transcriptional network distinct from those of the well-characterized sRNA-binding proteins, CsrA and Hfq, and suggest a previously unrecognized, sRNA-independent role of ProQ in stabilizing mRNAs. Copyright © 2018 Elsevier Inc. All rights reserved.

Deciphering functional diversification within the lichen microbiota by meta-omics.

PubMed

Cernava, Tomislav; Erlacher, Armin; Aschenbrenner, Ines Aline; Krug, Lisa; Lassek, Christian; Riedel, Katharina; Grube, Martin; Berg, Gabriele

2017-07-19

Recent evidence of specific bacterial communities extended the traditional concept of fungal-algal lichen symbioses by a further organismal kingdom. Although functional roles were already assigned to dominant members of the highly diversified microbiota, a substantial fraction of the ubiquitous colonizers remained unexplored. We employed a multi-omics approach to further characterize functional guilds in an unconventional model system. The general community structure of the lichen-associated microbiota was shown to be highly similar irrespective of the employed omics approach. Five highly abundant bacterial orders-Sphingomonadales, Rhodospirillales, Myxococcales, Chthoniobacterales, and Sphingobacteriales-harbor functions that are of substantial importance for the holobiome. Identified functions range from the provision of vitamins and cofactors to the degradation of phenolic compounds like phenylpropanoid, xylenols, and cresols. Functions that facilitate the persistence of Lobaria pulmonaria under unfavorable conditions were present in previously overlooked fractions of the microbiota. So far, unrecognized groups like Chthoniobacterales (Verrucomicrobia) emerged as functional protectors in the lichen microbiome. By combining multi-omics and imaging techniques, we highlight previously overlooked participants in the complex microenvironment of the lichens.

Yeast three-hybrid screen identifies TgBRADIN/GRA24 as a negative regulator of Toxoplasma gondii bradyzoite differentiation.

PubMed

Odell, Anahi V; Tran, Fanny; Foderaro, Jenna E; Poupart, Séverine; Pathak, Ravi; Westwood, Nicholas J; Ward, Gary E

2015-01-01

Differentiation of the protozoan parasite Toxoplasma gondii into its latent bradyzoite stage is a key event in the parasite's life cycle. Compound 2 is an imidazopyridine that was previously shown to inhibit the parasite lytic cycle, in part through inhibition of parasite cGMP-dependent protein kinase. We show here that Compound 2 can also enhance parasite differentiation, and we use yeast three-hybrid analysis to identify TgBRADIN/GRA24 as a parasite protein that interacts directly or indirectly with the compound. Disruption of the TgBRADIN/GRA24 gene leads to enhanced differentiation of the parasite, and the TgBRADIN/GRA24 knockout parasites show decreased susceptibility to the differentiation-enhancing effects of Compound 2. This study represents the first use of yeast three-hybrid analysis to study small-molecule mechanism of action in any pathogenic microorganism, and it identifies a previously unrecognized inhibitor of differentiation in T. gondii. A better understanding of the proteins and mechanisms regulating T. gondii differentiation will enable new approaches to preventing the establishment of chronic infection in this important human pathogen.

Synthesis of instrumentally and historically recorded earthquakes and studying their spatial statistical relationship (A case study: Dasht-e-Biaz, Eastern Iran)

NASA Astrophysics Data System (ADS)

Jalali, Mohammad; Ramazi, Hamidreza

2018-06-01

Earthquake catalogues are the main source of statistical seismology for the long term studies of earthquake occurrence. Therefore, studying the spatiotemporal problems is important to reduce the related uncertainties in statistical seismology studies. A statistical tool, time normalization method, has been determined to revise time-frequency relationship in one of the most active regions of Asia, Eastern Iran and West of Afghanistan, (a and b were calculated around 8.84 and 1.99 in the exponential scale, not logarithmic scale). Geostatistical simulation method has been further utilized to reduce the uncertainties in the spatial domain. A geostatistical simulation produces a representative, synthetic catalogue with 5361 events to reduce spatial uncertainties. The synthetic database is classified using a Geographical Information System, GIS, based on simulated magnitudes to reveal the underlying seismicity patterns. Although some regions with highly seismicity correspond to known faults, significantly, as far as seismic patterns are concerned, the new method highlights possible locations of interest that have not been previously identified. It also reveals some previously unrecognized lineation and clusters in likely future strain release.

Sub-lethal behavioral and physiological effects of the biomedical bleeding process on the American horseshoe crab, Limulus polyphemus

PubMed Central

Anderson, Rebecca L.; Watson, Winsor H.; Chabot, Christopher C.

2014-01-01

The hemolymph of the American horseshoe crab, Limulus polyphemus, is harvested from over 500,000 animals annually to produce Limulus Amebocyte Lysate, a medically important product used to detect pathogenic bacteria. Declining abundance of spawning Limulus females in heavily harvested regions suggests deleterious effects of this activity and, while mortality rates of the harvest process are known to be 10–30%, sub-lethal behavioral and physiological effects are not known. In this study, we determined the impact of the harvest process on locomotion and hemocyanin levels of 28 female horseshoe crabs. While mortality rates after bleeding (18%) were similar to previous studies, we found significant decreases in the linear and angular velocity of freely moving animals, as well as changes in their activity levels and expression of circatidal behavioral rhythms. Further, we found reductions in hemocyanin levels, which may alter immune function and cuticle integrity. These previously unrecognized behavioral and physiological deficits suggest that the harvest of Limulus Amebocyte Lysate may decrease female fitness, and thus may contribute to the current population decline. PMID:24445440

Schizophrenia: What's Arc Got to Do with It?

PubMed

Managò, Francesca; Papaleo, Francesco

2017-01-01

Human studies of schizophrenia are now reporting a previously unidentified genetic convergence on postsynaptic signaling complexes such as the activity-regulated cytoskeletal-associated (Arc) gene. However, because this evidence is still very recent, the neurobiological implication of Arc in schizophrenia is still scattered and unrecognized. Here, we first review current and developing findings connecting Arc in schizophrenia. We then highlight recent and previous findings from preclinical mouse models that elucidate how Arc genetic modifications might recapitulate schizophrenia-relevant behavioral phenotypes following the novel Research Domain Criteria (RDoC) framework. Building on this, we finally compare and evaluate several lines of evidence demonstrating that Arc genetics can alter both glutamatergic and dopaminergic systems in a very selective way, again consistent with molecular alterations characteristic of schizophrenia. Despite being only initial, accumulating and compelling data are showing that Arc might be one of the primary biological players in schizophrenia. Synaptic plasticity alterations in the genetic architecture of psychiatric disorders might be a rule, not an exception. Thus, we anticipate that additional evidence will soon emerge to clarify the Arc-dependent mechanisms involved in the psychiatric-related dysfunctional behavior.

HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine.

PubMed

Asea, A; Kraeft, S K; Kurt-Jones, E A; Stevenson, M A; Chen, L B; Finberg, R W; Koo, G C; Calderwood, S K

2000-04-01

Here, we demonstrate a previously unknown function for the 70-kDa heat-shock protein (HSP70) as a cytokine. HSP70 bound with high affinity to the plasma membrane, elicited a rapid intracellular calcium flux, activated nuclear factor (NF)-kappaB and upregulated the expression of pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in human monocytes. Furthermore, two different signal transduction pathways were activated by exogenous HSP70: one dependent on CD14 and intracellular calcium, which resulted in increased IL-1beta, IL-6 and TNF-alpha; and the other independent of CD14 but dependent on intracellular calcium, which resulted in an increase in TNF-alpha but not IL-1beta or IL-6. These findings indicate that CD14 is a co-receptor for HSP70-mediated signaling in human monocytes and are indicative of an previously unrecognized function for HSP70 as an extracellular protein with regulatory effects on human monocytes, having a dual role as chaperone and cytokine.

The Expression Pattern of the Cell Cycle Inhibitor p19INK4d by Progenitor Cells of the Rat Embryonic Telencephalon and Neonatal Anterior Subventricular Zone

PubMed Central

Coskun, Volkan; Luskin, Marla B.

2014-01-01

In this study we investigated whether the pattern of expression of the cyclin-dependent kinase inhibitor p19INK4d by the unique progenitor cells of the neonatal anterior subventricular zone (SVZa) can account for their ability to divide even though they express phenotypic characteristics of differentiated neurons. p19INK4d was chosen for analysis because it usually acts to block permanently the cell cycle at the G1 phase. p19INK4d immunoreactivity and the incorporation of bromodeoxyuridine (BrdU) by SVZa cells were compared with that of the more typical progenitor cells of the prenatal telencephalic ventricular zone. In the developing telencephalon, p19INK4d is expressed by postmitotic cells and has a characteristic perinuclear distribution depending on the laminar position and state of differentiation of a cell. Moreover, the laminar-specific staining of the developing cerebral cortex revealed that the ventricular zone (VZ) is divided into p19INK4d(+) and p19INK4d(−) sublaminae, indicating that the VZ has a previously unrecognized level of functional organization. Furthermore, the rostral migratory stream, traversed by the SVZa-derived cells, exhibits an anteriorhigh–posteriorlow gradient of p19INK4d expression. On the basis of the p19INK4d immunoreactivity and BrdU incorporation, SVZa-derived cells appear to exit and reenter the cell cycle successively. Thus, in contrast to telencephalic VZ cells, SVZa cells continue to undergo multiple rounds of division and differentiation before becoming postmitotic. PMID:11312294

Curcumin Chemosensitizes 5-Fluorouracil Resistant MMR-Deficient Human Colon Cancer Cells in High Density Cultures

PubMed Central

Shakibaei, Mehdi; Buhrmann, Constanze; Kraehe, Patricia; Shayan, Parviz; Lueders, Cora; Goel, Ajay

2014-01-01

Objective Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50–60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC activity in 3D cultures of CRC cells. Methods High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3) and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R) were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. Results Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. Conclusion Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population. (246 words in abstract). PMID:24404205

Curcumin chemosensitizes 5-fluorouracil resistant MMR-deficient human colon cancer cells in high density cultures.

PubMed

Shakibaei, Mehdi; Buhrmann, Constanze; Kraehe, Patricia; Shayan, Parviz; Lueders, Cora; Goel, Ajay

2014-01-01

Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50-60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC activity in 3D cultures of CRC cells. High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3) and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R) were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population. (246 words in abstract).

(Pentamethylcyclopentadienato)rhodium complexes for delivery of the curcumin anticancer drug [Rhodium pentamethylcyclopentadienato complexes for delivery of the curcumin anti-cancer drug

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

Markham, Jack; Liang, Jun; Levina, Aviva

[RhIII(*Cp)Cl(X,Y)] n+ complexes {X, Y = Cl, PTA, n = 0 (2); X, Y = en, n = 1 (3, Cl– salt; 4, PF 6– salt); X, Y = acac, n = 0 (5); X, Y = cur, n = 0 (6), where *Cp = pentamethylcyclopentadienato, curH = curcumin; PTA = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane; en = 1,2-ethanediamine; acac = acetylacetonato = 2,4-pentanedionato(1–)} were synthesized from [Rh(*Cp)(µ-Cl)Cl] 2 (1). While 2–5 were inactive against human epithelial A549 lung-cancer cells in assays of cytotoxicity, and antimetastatic and proapoptotic behaviors, 6 had a cytotoxic activity similar to that of curH over 72 h, but atmore » 24 h in real-time cell migration assays, it was less active, showing slow release of curH. All complexes underwent ligand-exchange reactions with biomolecules and cells within the timeframes of the assays (X-ray absorption spectroscopy). Intracellular elemental distributions (X-ray fluorescence microscopy) showed that 6 effectively delivered curH to cells, where it was released. Other elemental distributions and caspase activities were consistent with preapoptotic activities. As such, 6 is a promising delivery agent for bioactive ligands, such as curH. However, pure curcumin itself showed a previously unrecognized ability to promote migration of A549 cells at subtoxic concentrations in the presence of endothelial growth factor, which may be a concern for its widespread use as a nutritional supplement and as a potential drug. As a result, this aspect warrants further research.« less

A Novel Functional Role of Collagen Glycosylation

PubMed Central

Jürgensen, Henrik J.; Madsen, Daniel H.; Ingvarsen, Signe; Melander, Maria C.; Gårdsvoll, Henrik; Patthy, Laszlo; Engelholm, Lars H.; Behrendt, Niels

2011-01-01

Collagens make up the most abundant component of interstitial extracellular matrices and basement membranes. Collagen remodeling is a crucial process in many normal physiological events and in several pathological conditions. Some collagen subtypes contain specific carbohydrate side chains, the function of which is poorly known. The endocytic collagen receptor urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180 plays an important role in matrix remodeling through its ability to internalize collagen for lysosomal degradation. uPARAP/Endo180 is a member of the mannose receptor protein family. These proteins all include a fibronectin type II domain and a series of C-type lectin-like domains, of which only a minor part possess carbohydrate recognition activity. At least two of the family members, uPARAP/Endo180 and the mannose receptor, interact with collagens. The molecular basis for this interaction is known to involve the fibronectin type II domain but nothing is known about the function of the lectin domains in this respect. In this study, we have investigated a possible role of the single active lectin domain of uPARAP/Endo180 in the interaction with collagens. By expressing truncated recombinant uPARAP/Endo180 proteins and analyzing their interaction with collagens with high and low levels of glycosylation we demonstrated that this lectin domain interacts directly with glycosylated collagens. This interaction is functionally important because it was found to modulate the endocytic efficiency of the receptor toward highly glycosylated collagens such as basement membrane collagen IV. Surprisingly, this property was not shared by the mannose receptor, which internalized glycosylated collagens independently of its lectin function. This role of modulating its uptake efficiency by a specific receptor is a previously unrecognized function of collagen glycosylation. PMID:21768090

The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch.

PubMed

Oberst, Andrew; Malatesta, Martina; Aqeilan, Rami I; Rossi, Mario; Salomoni, Paolo; Murillas, Rodolfo; Sharma, Prashant; Kuehn, Michael R; Oren, Moshe; Croce, Carlo M; Bernassola, Francesca; Melino, Gerry

2007-07-03

Nedd4-binding partner-1 (N4BP1) has been identified as a protein interactor and a substrate of the homologous to E6AP C terminus (HECT) domain-containing E3 ubiquitin-protein ligase (E3), Nedd4. Here, we describe a previously unrecognized functional interaction between N4BP1 and Itch, a Nedd4 structurally related E3, which contains four WW domains, conferring substrate-binding activity. We show that N4BP1 association with the second WW domain (WW2) of Itch interferes with E3 binding to its substrates. In particular, we found that N4BP1 and p73 alpha, a target of Itch-mediated ubiquitin/proteasome proteolysis, share the same binding site. By competing with p73 alpha for binding to the WW2 domain, N4BP1 reduces the ability of Itch to recruit and ubiquitylate p73 alpha and inhibits Itch autoubiquitylation activity both in in vitro and in vivo ubiquitylation assays. Similarly, both c-Jun and p63 polyubiquitylation by Itch are inhibited by N4BP1. As a consequence, genetic and RNAi knockdown of N4BP1 diminish the steady-state protein levels and significantly impair the transcriptional activity of Itch substrates. Notably, stress-induced induction of c-Jun was impaired in N4BP1(-/-) cells. These results demonstrate that N4BP1 functions as a negative regulator of Itch. In addition, because inhibition of Itch by N4BP1 results in the stabilization of crucial cell death regulators such as p73 alpha and c-Jun, it is conceivable that N4BP1 may have a role in regulating tumor progression and the response of cancer cells to chemotherapy.

IL-4/IL-13 Heteroreceptor Influences Th17 Cell Conversion and Sensitivity to Regulatory T Cell Suppression To Restrain Experimental Allergic Encephalomyelitis.

PubMed

Barik, Subhasis; Ellis, Jason S; Cascio, Jason A; Miller, Mindy M; Ukah, Tobechukwu K; Cattin-Roy, Alexis N; Zaghouani, Habib

2017-10-01

IL-4 and IL-13 have been defined as anti-inflammatory cytokines that can counter myelin-reactive T cells and modulate experimental allergic encephalomyelitis. However, it is not known whether endogenous IL-4 and IL-13 contribute to the maintenance of peripheral tolerance and whether their function is coordinated with T regulatory cells (Tregs). In this study, we used mice in which the common cytokine receptor for IL-4 and IL-13, namely the IL-4Rα/IL-13Rα1 (13R) heteroreceptor (HR), is compromised and determined whether the lack of signaling by endogenous IL-4 and IL-13 through the HR influences the function of effector Th1 and Th17 cells in a Treg-dependent fashion. The findings indicate that mice-deficient for the HR (13R -/- ) are more susceptible to experimental allergic encephalomyelitis than mice sufficient for the HR (13R +/+ ) and develop early onset and more severe disease. Moreover, Th17 cells from 13R -/- mice had reduced ability to convert to Th1 cells and displayed reduced sensitivity to suppression by Tregs relative to Th17 effectors from 13R +/+ mice. These observations suggest that IL-4 and IL-13 likely operate through the HR and influence Th17 cells to convert to Th1 cells and to acquire increased sensitivity to suppression, leading to control of immune-mediated CNS inflammation. These previously unrecognized findings shed light on the intricacies underlying the contribution of cytokines to peripheral tolerance and control of autoimmunity. Copyright © 2017 by The American Association of Immunologists, Inc.

(Pentamethylcyclopentadienato)rhodium complexes for delivery of the curcumin anticancer drug [Rhodium pentamethylcyclopentadienato complexes for delivery of the curcumin anti-cancer drug

DOE PAGES

Markham, Jack; Liang, Jun; Levina, Aviva; ...

2017-01-23

[RhIII(*Cp)Cl(X,Y)] n+ complexes {X, Y = Cl, PTA, n = 0 (2); X, Y = en, n = 1 (3, Cl– salt; 4, PF 6– salt); X, Y = acac, n = 0 (5); X, Y = cur, n = 0 (6), where *Cp = pentamethylcyclopentadienato, curH = curcumin; PTA = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane; en = 1,2-ethanediamine; acac = acetylacetonato = 2,4-pentanedionato(1–)} were synthesized from [Rh(*Cp)(µ-Cl)Cl] 2 (1). While 2–5 were inactive against human epithelial A549 lung-cancer cells in assays of cytotoxicity, and antimetastatic and proapoptotic behaviors, 6 had a cytotoxic activity similar to that of curH over 72 h, but atmore » 24 h in real-time cell migration assays, it was less active, showing slow release of curH. All complexes underwent ligand-exchange reactions with biomolecules and cells within the timeframes of the assays (X-ray absorption spectroscopy). Intracellular elemental distributions (X-ray fluorescence microscopy) showed that 6 effectively delivered curH to cells, where it was released. Other elemental distributions and caspase activities were consistent with preapoptotic activities. As such, 6 is a promising delivery agent for bioactive ligands, such as curH. However, pure curcumin itself showed a previously unrecognized ability to promote migration of A549 cells at subtoxic concentrations in the presence of endothelial growth factor, which may be a concern for its widespread use as a nutritional supplement and as a potential drug. As a result, this aspect warrants further research.« less

Effects of Orientation on Recognition of Facial Affect

NASA Technical Reports Server (NTRS)

Cohen, M. M.; Mealey, J. B.; Hargens, Alan R. (Technical Monitor)

1997-01-01

The ability to discriminate facial features is often degraded when the orientation of the face and/or the observer is altered. Previous studies have shown that gross distortions of facial features can go unrecognized when the image of the face is inverted, as exemplified by the 'Margaret Thatcher' effect. This study examines how quickly erect and supine observers can distinguish between smiling and frowning faces that are presented at various orientations. The effects of orientation are of particular interest in space, where astronauts frequently view one another in orientations other than the upright. Sixteen observers viewed individual facial images of six people on a computer screen; on a given trial, the image was either smiling or frowning. Each image was viewed when it was erect and when it was rotated (rolled) by 45 degrees, 90 degrees, 135 degrees, 180 degrees, 225 degrees and 270 degrees about the line of sight. The observers were required to respond as rapidly and accurately as possible to identify if the face presented was smiling or frowning. Measures of reaction time were obtained when the observers were both upright and supine. Analyses of variance revealed that mean reaction time, which increased with stimulus rotation (F=18.54, df 7/15, p (is less than) 0.001), was 22% longer when the faces were inverted than when they were erect, but that the orientation of the observer had no significant effect on reaction time (F=1.07, df 1/15, p (is greater than) .30). These data strongly suggest that the orientation of the image of a face on the observer's retina, but not its orientation with respect to gravity, is important in identifying the expression on the face.

Anti-sphingosine-1-phosphate monoclonal antibodies inhibit angiogenesis and sub-retinal fibrosis in a murine model of laser-induced choroidal neovascularization

PubMed Central

Caballero, Sergio; Swaney, James; Moreno, Kelli; Afzal, Aqeela; Kielczewski, Jennifer; Stoller, Glenn; Cavalli, Amy; Garland, William; Hansen, Geneviève; Sabbadini, Roger; Grant, Maria B.

2013-01-01

The efficacy of novel monoclonal antibodies that neutralize the pro-angiogenic mediator, sphingosine-1-phosphate (S1P), were tested using in vitro and in vivo angiogenesis models, including choroidal neovascularization (CNV) induced by laser disruption of Bruch’s membrane. S1P receptor levels in human brain choroid plexus endothelial cells (CPEC), human lung microvascular endothelial cells, human retinal vascular endothelial cells, and circulating endothelial progenitor cells were examined by semi-quantitative PCR. The ability of murine or humanized anti-S1P monoclonal antibodies (mAbs) to inhibit S1P-mediated microvessel tube formation by CPEC on Matrigel was evaluated and capillary density in subcutaneous growth factor-loaded Matrigel plugs was determined following anti-S1P treatment. S1P promoted in vitro capillary tube formation in CPEC consistent with the presence of cognate S1P1–5 receptor expression by these cells and the S1P antibody induced a dose-dependent reduction in microvessel tube formation. In a murine model of laser-induced rupture of Bruch’s membrane, S1P was detected in posterior cups of mice receiving laser injury, but not in uninjured controls. Intravitreous injection of anti-S1P mAbs dramatically inhibited CNV formation and sub-retinal collagen deposition in all treatment groups (p < 0.05 compared to controls), thereby identifying S1P as a previously unrecognized mediator of angiogenesis and subretinal fibrosis in this model. These findings suggest that neutralizing S1P with anti-S1P mAbs may be a novel method of treating patients with exudative age-related macular degeneration by reducing angiogenesis and sub-retinal fibrosis, which are responsible for visual acuity loss in this disease. PMID:18723015

Calcineurin Regulates Homologous Desensitization of Natriuretic Peptide Receptor-A and Inhibits ANP-Induced Testosterone Production in MA-10 Cells

PubMed Central

Henesy, Michelle B.; Britain, Andrea L.; Zhu, Bing; Amable, Lauren; Honkanen, Richard E.; Corbin, Jackie D.; Francis, Sharron H.; Rich, Thomas C.

2012-01-01

Receptor desensitization is a ubiquitous regulatory mechanism that defines the activatable pool of receptors, and thus, the ability of cells to respond to environmental stimuli. In recent years, the molecular mechanisms controlling the desensitization of a variety of receptors have been established. However, little is known about the molecular mechanisms that underlie desensitization of natriuretic peptide receptors, including natriuretic peptide receptor-A (NPR-A). Here we report that calcineurin (protein phosphatase 2B, PP2B, PPP3C) regulates homologous desensitization of NPR-A in murine Leydig tumor (MA-10) cells. We demonstrate that both pharmacological inhibition of calcineurin activity and siRNA-mediated suppression of calcineurin expression potentiate atrial natriuretic peptide (ANP)-induced cGMP synthesis. Treatment of MA-10 cells with inhibitors of other phosphoprotein phosphatases had little or no effect on ANP-induced cGMP accumulation. In addition, overexpression of calcineurin blunts ANP-induced cGMP synthesis. We also present data indicating that the inhibition of calcineurin potentiates ANP-induced testosterone production. To better understand the contribution of calcineurin in the regulation of NPR-A activity, we examined the kinetics of ANP-induced cGMP signals. We observed transient ANP-induced cGMP signals, even in the presence of phosphodiesterase inhibitors. Inhibition of both calcineurin and phosphodiesterase dramatically slowed the decay in the response. These observations are consistent with a model in which calcineurin mediated dephosphorylation and desensitization of NPR-A is associated with significant inhibition of cGMP synthesis. PDE activity hydrolyzes cGMP, thus lowering intracellular cGMP toward the basal level. Taken together, these data suggest that calcineurin plays a previously unrecognized role in the desensitization of NPR-A and, thereby, inhibits ANP-mediated increases in testosterone production. PMID:22876290

The genesis and source of the H7N9 influenza viruses causing human infections in China.

PubMed

Lam, Tommy Tsan-Yuk; Wang, Jia; Shen, Yongyi; Zhou, Boping; Duan, Lian; Cheung, Chung-Lam; Ma, Chi; Lycett, Samantha J; Leung, Connie Yin-Hung; Chen, Xinchun; Li, Lifeng; Hong, Wenshan; Chai, Yujuan; Zhou, Linlin; Liang, Huyi; Ou, Zhihua; Liu, Yongmei; Farooqui, Amber; Kelvin, David J; Poon, Leo L M; Smith, David K; Pybus, Oliver G; Leung, Gabriel M; Shu, Yuelong; Webster, Robert G; Webby, Richard J; Peiris, Joseph S M; Rambaut, Andrew; Zhu, Huachen; Guan, Yi

2013-10-10

A novel H7N9 influenza A virus first detected in March 2013 has since caused more than 130 human infections in China, resulting in 40 deaths. Preliminary analyses suggest that the virus is a reassortant of H7, N9 and H9N2 avian influenza viruses, and carries some amino acids associated with mammalian receptor binding, raising concerns of a new pandemic. However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully known. Using a combination of active surveillance, screening of virus archives, and evolutionary analyses, here we show that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions. We show that the H7 viruses subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at live poultry markets, which are thought to be the immediate source of human infections. Whether the H7N9 outbreak lineage has, or will, become enzootic in China and neighbouring regions requires further investigation. The discovery here of a related H7N7 influenza virus in chickens that has the ability to infect mammals experimentally, suggests that H7 viruses may pose threats beyond the current outbreak. The continuing prevalence of H7 viruses in poultry could lead to the generation of highly pathogenic variants and further sporadic human infections, with a continued risk of the virus acquiring human-to-human transmissibility.

Fluorescence in situ hybridization analyses of hematologic malignancies reveal frequent cytogenetically unrecognized 12p rearrangements.

PubMed

Andreasson, P; Johansson, B; Billström, R; Garwicz, S; Mitelman, F; Höglund, M

1998-03-01

Thirty-two hematologic malignancies--nine with cytogenetically identified 12p abnormalities and 23 with whole or partial losses of chromosome 12--were selected for fluorescence in situ hybridization (FISH) investigations of 12p. These analyses revealed structural 12p changes, such as translocations, deletions, insertions, inversions and amplification, in 20 cases. ETV6 rearrangements were detected in three acute leukemias. One acute undifferentiated leukemia had t(4;12)(q12;p13) as the sole anomaly. The second case, an acute myeloid leukemia (AML), displayed complex abnormalities involving, among others, chromosomes 9 and 12. The third case, also an AML, had an insertion of the distal part of ETV6 into chromosome arm 11q and into multiple ring chromosomes, which also contained chromosome 11 material, resulting in an amplification of a possible fusion gene. The fusion partners in these cases remain to be identified. Thirty-one additional breakpoints on 12p could be characterized in detail. The majority of these breaks were shown to result in interchromosomal rearrangements, possibly indicating the location of hitherto unrecognized genes of importance in the pathogenesis of hematologic malignancies. The FISH analyses disclosed terminal or interstitial 12p deletions in 18 cases. Seven myeloid malignancies showed deletions restricted to a region, including ETV6 and CDKN1B, which has been reported to be frequently lost in leukemias. In four cases, the deletions involved both these genes, whereas two AML displayed loss of CDKN1B but not ETV6, supporting previously reported findings indicating a region of deletion not including this gene. However, one myelodysplastic syndrome lacked one copy of ETV6 but not CDKN1B. Hence, we suggest a minimal region of deletion on 12p located between the ETV6 and CDKN1B genes.

Combinatorial phenotypic screen uncovers unrecognized family of extended thiourea inhibitors with copper-dependent anti-staphylococcal activity.

PubMed

Dalecki, Alex G; Malalasekera, Aruni P; Schaaf, Kaitlyn; Kutsch, Olaf; Bossmann, Stefan H; Wolschendorf, Frank

2016-04-01

The continuous rise of multi-drug resistant pathogenic bacteria has become a significant challenge for the health care system. In particular, novel drugs to treat infections of methicillin-resistant Staphylococcus aureus strains (MRSA) are needed, but traditional drug discovery campaigns have largely failed to deliver clinically suitable antibiotics. More than simply new drugs, new drug discovery approaches are needed to combat bacterial resistance. The recently described phenomenon of copper-dependent inhibitors has galvanized research exploring the use of metal-coordinating molecules to harness copper's natural antibacterial properties for therapeutic purposes. Here, we describe the results of the first concerted screening effort to identify copper-dependent inhibitors of Staphylococcus aureus. A standard library of 10 000 compounds was assayed for anti-staphylococcal activity, with hits defined as those compounds with a strict copper-dependent inhibitory activity. A total of 53 copper-dependent hit molecules were uncovered, similar to the copper independent hit rate of a traditionally executed campaign conducted in parallel on the same library. Most prominent was a hit family with an extended thiourea core structure, termed the NNSN motif. This motif resulted in copper-dependent and copper-specific S. aureus inhibition, while simultaneously being well tolerated by eukaryotic cells. Importantly, we could demonstrate that copper binding by the NNSN motif is highly unusual and likely responsible for the promising biological qualities of these compounds. A subsequent chemoinformatic meta-analysis of the ChEMBL chemical database confirmed the NNSNs as an unrecognized staphylococcal inhibitor, despite the family's presence in many chemical screening libraries. Thus, our copper-biased screen has proven able to discover inhibitors within previously screened libraries, offering a mechanism to reinvigorate exhausted molecular collections.

Evidence for post-1620 Ma Proterozoic regional deformation, Lucy Gray Range, southern Nevada

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

Duebendorfer, E.M.; Christensen, C.H.; Shafiqullah, M.

1993-04-01

Major mylonite zones in the northern Lucy Gray Range, Nevada, deform and are spatially associated with the 1,425 Ma Beer Bottle Pass pluton, Mylonitic granite yielded a K-Ar biotite date of 1,400 [+-] 30 Ma and is overlain nonconformably by the Cambrian Tapeats Sandstone, thus constraining deformation to the Proterozoic. The mylonites may therefore represent an unrecognized period of Proterozoic deformation in the Southwest. Field and microstructural studies were undertaken to evaluate between 3 possible models for the apparent spatial association of granite and mylonites: (1) deformation directly related to pluton emplacement (ballooning); (2) synkinematic pluton emplacement; or (3) post-emplacementmore » deformation. Mylonite zones up to 50 meters thick strike north to northeast, dip moderately to steeply northwest, and contain a remarkably consistent west-plunging mineral lineation. Mylonites are present locally at the granite-wall rock contact; however, less than 30% of the exposed contact is mylonitic. The authors reject a pluton-emplacement origin for the mylonites because (1) mylonite zones within wall rocks locally strike at high angles to an undeformed pluton-wall rock contact, (2) the consistent (pluton-side-down) shear sense is more compatible with a uniform-sense simple shear zone than a ballooning pluton, (3) plane strain fabrics dominate over flattening fabrics, and (4) mylonites adjacent to pluton contacts lack annealing textures predicted by the ballooning model. If so, the conventional interpretation of 1,400 Ga granitoids as anorogenic may need to be re-evaluated. The authors cannot, however, rule out the possibility that the mylonites completely postdate intrusion of the Beer Bottle Pass pluton. Future work is planned to delimit the regional extent of this previously unrecognized Proterozoic deformational event.« less

Random plasma glucose in serendipitous screening for glucose intolerance: screening for impaired glucose tolerance study 2.

PubMed

Ziemer, David C; Kolm, Paul; Foster, Jovonne K; Weintraub, William S; Vaccarino, Viola; Rhee, Mary K; Varughese, Rincy M; Tsui, Circe W; Koch, David D; Twombly, Jennifer G; Narayan, K M Venkat; Phillips, Lawrence S

2008-05-01

With positive results from diabetes prevention studies, there is interest in convenient ways to incorporate screening for glucose intolerance into routine care and to limit the need for fasting diagnostic tests. The aim of this study is to determine whether random plasma glucose (RPG) could be used to screen for glucose intolerance. This is a cross-sectional study. The participants of this study include a voluntary sample of 990 adults not known to have diabetes. RPG was measured, and each subject had a 75-g oral glucose tolerance test several weeks later. Glucose intolerance targets included diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose(110) (IFG(110); fasting glucose, 110-125 mg/dl, and 2 h glucose < 140 mg/dl). Screening performance was measured by area under receiver operating characteristic curves (AROC). Mean age was 48 years, and body mass index (BMI) was 30.4 kg/m(2); 66% were women, and 52% were black; 5.1% had previously unrecognized diabetes, and 24.0% had any "high-risk" glucose intolerance (diabetes or IGT or IFG(110)). The AROC was 0.80 (95% CI 0.74-0.86) for RPG to identify diabetes and 0.72 (0.68-0.75) to identify any glucose intolerance, both highly significant (p < 0.001). Screening performance was generally consistent at different times of the day, regardless of meal status, and across a range of risk factors such as age, BMI, high density lipoprotein cholesterol, triglycerides, and blood pressure. RPG values should be considered by health care providers to be an opportunistic initial screening test and used to prompt further evaluation of patients at risk of glucose intolerance. Such "serendipitous screening" could help to identify unrecognized diabetes and prediabetes.

General antibiotic exposure is associated with increased risk of developing chronic rhinosinusitis.

PubMed

Maxfield, Alice Z; Korkmaz, Hakan; Gregorio, Luciano L; Busaba, Nicolas Y; Gray, Stacey T; Holbrook, Eric H; Guo, Rong; Bleier, Benjamin S

2017-02-01

Antibiotic use and chronic rhinosinusitis (CRS) have been independently associated with microbiome diversity depletion and opportunistic infections. This study was undertaken to investigate whether antibiotic use may be an unrecognized risk factor for developing CRS. Case-control study of 1,162 patients referred to a tertiary sinus center for a range of sinonasal disorders. Patients diagnosed with CRS according to established consensus criteria (n = 410) were assigned to the case group (273 without nasal polyps [CRSsNP], 137 with nasal polyps [CRSwNP]). Patients with all other diagnoses (n = 752) were assigned to the control group. Chronic rhinosinusitis disease severity was determined using a validated quality of life (QOL) instrument. The class, diagnosis, and timing of previous nonsinusitis-related antibiotic exposures were recorded. Results were validated using a randomized administrative data review of 452 (38.9%) of patient charts. The odds ratio of developing CRS following antibiotic exposure were calculated, as well as the impact of antibiotic use on the subsequent QOL. Antibiotic use significantly increased the odds of developing CRSsNP (odds ratio: 2.21, 95% confidence interval, 1.66-2.93, P < 0.0001) as compared to nonusers. Antibiotic exposure was significantly associated with worse CRS QOL scores (P = 0.0009) over at least the subsequent 2 years. These findings were confirmed by the administrative data review. Use of antibiotics more than doubles the odds of developing CRSsNP and is associated with a worse QOL for at least 2 years following exposure. These findings expose an unrecognized and concerning consequence of general antibiotic use. 3b. Laryngoscope, 2016 127:296-302, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Metal exposures from aluminum cookware: An unrecognized public health risk in developing countries.

PubMed

Weidenhamer, Jeffrey D; Fitzpatrick, Meghann P; Biro, Alison M; Kobunski, Peter A; Hudson, Michael R; Corbin, Rebecca W; Gottesfeld, Perry

2017-02-01

Removing lead from gasoline has resulted in decreases in blood lead levels in most of the world, but blood lead levels remain elevated in low and middle-income countries compared to more developed countries. Several reasons for this difference have been investigated, but few studies have examined the potential contribution from locally-made aluminum cookware. In a previous study of cookware from a single African country, Cameroon, artisanal aluminum cookware that is made from scrap metal released significant quantities of lead. In this study, 42 intact aluminum cookware items from ten developing countries were tested for their potential to release lead and other metals during cooking. Fifteen items released ≥1 microgram of lead per serving (250mL) when tested by boiling with dilute acetic acid for 2h. One pot, from Viet Nam, released 33, 1126 and 1426 micrograms per serving in successive tests. Ten samples released >1 microgram of cadmium per serving, and fifteen items released >1 microgram of arsenic per serving. The mean exposure estimate for aluminum was 125mg per serving, more than six times the World Health Organization's Provisional Tolerable Weekly Intake of 20mg/day for a 70kg adult, and 40 of 42 items tested exceeded this level. We conducted preliminary assessments of three potential methods to reduce metal leaching from this cookware. Coating the cookware reduced aluminum exposure per serving by >98%, and similar reductions were seen for other metals as well. Potential exposure to metals by corrosion during cooking may pose a significant and largely unrecognized public health risk which deserves urgent attention. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification and characterization of unrecognized viruses in stool samples of non-polio acute flaccid paralysis children by simplified VIDISCA.

PubMed

Shaukat, Shahzad; Angez, Mehar; Alam, Muhammad Masroor; Jebbink, Maarten F; Deijs, Martin; Canuti, Marta; Sharif, Salmaan; de Vries, Michel; Khurshid, Adnan; Mahmood, Tariq; van der Hoek, Lia; Zaidi, Syed Sohail Zahoor

2014-08-12

The use of sequence independent methods combined with next generation sequencing for identification purposes in clinical samples appears promising and exciting results have been achieved to understand unexplained infections. One sequence independent method, Virus Discovery based on cDNA Amplified Fragment Length Polymorphism (VIDISCA) is capable of identifying viruses that would have remained unidentified in standard diagnostics or cell cultures. VIDISCA is normally combined with next generation sequencing, however, we set up a simplified VIDISCA which can be used in case next generation sequencing is not possible. Stool samples of 10 patients with unexplained acute flaccid paralysis showing cytopathic effect in rhabdomyosarcoma cells and/or mouse cells were used to test the efficiency of this method. To further characterize the viruses, VIDISCA-positive samples were amplified and sequenced with gene specific primers. Simplified VIDISCA detected seven viruses (70%) and the proportion of eukaryotic viral sequences from each sample ranged from 8.3 to 45.8%. Human enterovirus EV-B97, EV-B100, echovirus-9 and echovirus-21, human parechovirus type-3, human astrovirus probably a type-3/5 recombinant, and tetnovirus-1 were identified. Phylogenetic analysis based on the VP1 region demonstrated that the human enteroviruses are more divergent isolates circulating in the community. Our data support that a simplified VIDISCA protocol can efficiently identify unrecognized viruses grown in cell culture with low cost, limited time without need of advanced technical expertise. Also complex data interpretation is avoided thus the method can be used as a powerful diagnostic tool in limited resources. Redesigning the routine diagnostics might lead to additional detection of previously undiagnosed viruses in clinical samples of patients.

The alligator gut microbiome and implications for archosaur symbioses

PubMed Central

Keenan, Sarah W.; Engel, Annette Summers; Elsey, Ruth M.

2013-01-01

Among vertebrate gastrointestinal microbiome studies, complete representation of taxa is limited, particularly among reptiles. Here, we provide evidence for previously unrecognized host-microbiome associations along the gastrointestinal tract from the American alligator, a crown archosaur with shared ancestry to extinct taxa, including dinosaurs. Microbiome compositional variations reveal that the digestive system consists of multiple, longitudinally heterogeneous microbiomes that strongly correlate to specific gastrointestinal tract organs, regardless of rearing histories or feeding status. A core alligator gut microbiome comprised of Fusobacteria, but depleted in Bacteroidetes and Proteobacteria common to mammalians, is compositionally unique from other vertebrate gut microbiomes, including other reptiles, fish, and herbivorous and carnivorous mammals. As such, modern alligator gut microbiomes advance our understanding of archosaur gut microbiome evolution, particularly if conserved host ecology has retained archosaur-specific symbioses over geologic time. PMID:24096888

A Simple Correlation for Neutron Capture Rates from Nuclear Masses

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

Couture, Aaron Joseph

Recent studies of neutron capture performed at LANL have revealed a previously unrecognized connection between nuclear masses and the average neutron capture cross section. A team of three scientists from Los Alamos (P-27), Yale Univ., and Istanbul Univ. (Turkey) recently discovered this connection and have published their results as a Rapid Communication in Physical Review C. Neutron capture is a reaction in which a free neutron is absorbed by the nucleus, keeping the element unchanged, but changing isotopes. This reaction is typically exothermic. As a result, the reaction can proceed even when many other reaction channels are closed. In anmore » astrophysical environment, this means that neutron capture is the primary mechanism by which all of the elements with atomic number greater than nickel are produced is neutron capture.« less

Epigenetic Regulation of the NR4A Orphan Nuclear Receptor NOR1 By Histone Acetylation

PubMed Central

Zhao, Yue; Nomiyama, Takashi; Findeisen, Hannes M.; Qing, Hua; Aono, Jun; Jones, Karrie L.; Heywood, Elizabeth B.; Bruemmer, Dennis

2014-01-01

The nuclear receptor NOR1 is an immediate-early response gene implicated in the transcriptional control of proliferation. Since the expression level of NOR1 is rapidly induced through cAMP response element binding (CREB) protein-dependent promoter activation, we investigated the contribution of histone acetylation to this transient induction. We demonstrate that NOR1 transcription is induced by histone deacetylase (HDAC) inhibition and by depletion of HDAC1 and HDAC3. HDAC inhibition activated the NOR1 promoter, increased histone acetylation and augmented the recruitment of phosphorylated CREB to the promoter. Furthermore, HDAC inhibition increased Ser133 phosphorylation of CREB and augmented NOR1 protein stability. These data outline previously unrecognized mechanisms of NOR1 regulation and illustrate a key role for histone acetylation in the rapid induction of NOR1. PMID:25451221

A national plan for assisting states, federal agencies, and tribes in managing white-nose syndrome in bats

USGS Publications Warehouse

,; ,; ,; ,; ,; ,; ,; ,; ,; ,; ,; ,; ,; ,

2011-01-01

White-nose syndrome (WNS) is a disease responsible for unprecedented mortality in hibernating bats in the northeastern U.S. This previously unrecognized disease has spread very rapidly since its discovery in January 2007, and poses a considerable threat to hibernating bats throughout North America. As WNS spreads, the challenges for understanding and managing the disease continue to increase. Given the escalating complexity of these challenges, a highly coordinated effort is required for State, Federal, and Tribal wildlife agencies, and private partners to respond effectively to WNS and conserve species of bats. The plan proposed herein details the elements that are critical to the investigation and management of WNS, identifies key action items to address stated goals, and outlines the role(s) of agencies and entities involved in this continental effort.

Need for new sensors to map lithologic units

USGS Publications Warehouse

Rowan, Lawrence C.; Barringer, Anthony R.

1980-01-01

One of the most important contributions that remote sensing can make to mineral energy explorations to provide data from satellites to augment regional geological mapping. Geologic maps, which show information on the subsurface, are the main basis for formulating models of resource genesis that guide exploration. However, conventional compilation procedures are time-consuming and therefore often slow the pace of exploration, especially in large, inaccessible areas. Landsat Multispectral Scanner (MSS) images have been applied to a wide variety of specific geological problems, including discrimination of lithologic and delineation of previously unrecognized tectonic features. However, these lithologic distinctions are based on brightness, spectral reflectance, and, less commonly, the morphology of the unit, which in the wavelength region of MSS images are only rarely diagnostic of specific mineralogical content. Limonite is the only lithological material that can be identified be analyzing MSS spectral radiance.

Mathematical Modeling of Intravascular Blood Coagulation under Wall Shear Stress

PubMed Central

Rukhlenko, Oleksii S.; Dudchenko, Olga A.; Zlobina, Ksenia E.; Guria, Georgy Th.

2015-01-01

Increased shear stress such as observed at local stenosis may cause drastic changes in the permeability of the vessel wall to procoagulants and thus initiate intravascular blood coagulation. In this paper we suggest a mathematical model to investigate how shear stress-induced permeability influences the thrombogenic potential of atherosclerotic plaques. Numerical analysis of the model reveals the existence of two hydrodynamic thresholds for activation of blood coagulation in the system and unveils typical scenarios of thrombus formation. The dependence of blood coagulation development on the intensity of blood flow, as well as on geometrical parameters of atherosclerotic plaque is described. Relevant parametric diagrams are drawn. The results suggest a previously unrecognized role of relatively small plaques (resulting in less than 50% of the lumen area reduction) in atherothrombosis and have important implications for the existing stenting guidelines. PMID:26222505

Anthrax in injecting drug users: the need for increased vigilance in the clinic.

PubMed

Ascough, Stephanie; Altmann, Daniel Martin

2015-06-01

The emergence of a previously unrecognized route of Bacillus anthracis infection over the last few years has led to concern: sporadic anthrax outbreaks among heroin users in northern Europe have demonstrated the severe pathology associated with the newly described 'injectional anthrax'. With a high case fatality rate and non-specific early symptoms, this is a novel clinical manifestation of an old disease. Lack of awareness of this syndrome among emergency room clinicians can lead to a delayed diagnosis among heroin users; indeed, for many health workers in developed countries, where infection by B. anthracis is rare, this may be the first time they have encountered anthrax infections. As the putative route of contamination of the heroin supply is potentially ongoing, it is important that clinicians and public health workers remain vigilant for early signs of injectional anthrax.

Cutis laxa and fatal pulmonary hypertension: a newly recognized syndrome?

PubMed Central

Brunetti-Pierri, Nicola; Piccolo, Pasquale; Morava, Eva; Wevers, Ron A.; McGuirk, Megan; Johnson, Yvette R.; Urban, Zsolt; Dishop, Megan K.; Potocki, Lorraine

2015-01-01

Cutis laxa is a connective tissue disorder with distinctive lax, redundant, and inelastic skin. It is a genetically heterogenous disorder with autosomal dominant and recessive patterns of inheritance. We report a patient with cutis laxa supported by clinical, microscopic, and ultrastructural findings. Molecular analysis of fibulin-4 and -5, of the α2 subunit of the V-type H+ ATPase, and of the component of the oligomeric Golgi complex 7 (COG7) genes excluded the type I and type II autosomal recessive forms of cutis laxa, and congenital disorders of glycosylation associated with cutis laxa. Remarkably, our patient also presented severe and lethal pulmonary hypertension as a newborn. This case with cutis laxa, severe pulmonary hypertension, and no detectable mutations in fibulin-4 and -5 genes may represent a previously unrecognized syndrome. PMID:21285876

Pathogen alarm behavior in a termite: A new form of communication in social insects

PubMed

Rosengaus; Jordan; Lefebvre; Traniello

1999-11-01

Dampwood termites, Zootermopsis angusticollis, show an alarm response after detecting the presence of spores of the pathogenic fungus Metarhizium anisopliae. Termites in direct contact with a high concentration of spores (10(7) spores/ml) show a striking vibratory display which appears to convey information about the presence of pathogens to nearby unexposed nestmates through substrate vibration. Nestmates not directly in contact with spores that perceive the vibrational signal increase significantly their distance from the spore-exposed vibrating termites, apparently to escape from the source of infection. The fleeing response is not induced by the presence of the spores alone or by pheromones, and requires the perception of the vibrations propagated through the substrate. This "pathogen alarm behavior" appears to be a previously unrecognized communication mechanism that allows termites to reduce disease risks within the nest.

Pathogen Alarm Behavior in a Termite: A New Form of Communication in Social Insects

NASA Astrophysics Data System (ADS)

Rosengaus, R. B.; Jordan, C.; Lefebvre, M. L.; Traniello, J. F. A.

Dampwood termites, Zootermopsis angusticollis, show an alarm response after detecting the presence of spores of the pathogenic fungus Metarhizium anisopliae. Termites in direct contact with a high concentration of spores (107 spores/ml) show a striking vibratory display which appears to convey information about the presence of pathogens to nearby unexposed nestmates through substrate vibration. Nestmates not directly in contact with spores that perceive the vibrational signal increase significantly their distance from the spore-exposed vibrating termites, apparently to escape from the source of infection. The fleeing response is not induced by the presence of the spores alone or by pheromones, and requires the perception of the vibrations propagated through the substrate. This "pathogen alarm behavior" appears to be a previously unrecognized communication mechanism that allows termites to reduce disease risks within the nest.

New insights into Prevotella diversity and medical microbiology.

PubMed

Alauzet, Corentine; Marchandin, Hélène; Lozniewski, Alain

2010-11-01

In light of recent studies based on cultivation-independent methods, it appears that the diversity of Prevotella in human microbiota is greater than was previously assumed from cultivation-based studies, and that the implication of these bacteria in several human diseases was unrecognized. While some Prevotella taxa were found during opportunistic infections, changes in Prevotella abundance and diversity were discovered during dysbiosis-associated diseases. As member of the microbiota, Prevotella may also be considered as a reservoir for resistance genes. Greater knowledge on Prevotella diversity, as well as new insights into its pathogenic potential and implication in dysbiosis are expected from the use of human microbe identification microarrays, from whole-genome sequence analyse, and from the NIH Human Microbiome Project data. New approaches, including molecular-based methods, could contribute to improve the diagnosis of Prevotella infections.

Buried penis: An unrecognized risk factor in the development of invasive penile cancer.

PubMed

Abdulla, Alym; Daya, Dean; Pinthus, Jehonathan; Davies, Timothy

2012-10-01

One of the documented benefits of neonatal circumcision is protection against invasive penile cancer. To date there have been a handful of published cases of invasive penile cancer in men circumcised as neonates. We report a case of a 73-year-old man, with a history of neonatal circumcision with no evidence of previous human papillomavirus exposure, who developed a buried penis secondary to obesity. He was diagnosed with Grade 2, pT3N0 squamous cell carcinoma of the penis. This report suggests that buried penis may pose a risk factor for the development of penile cancer despite the protective effects of neonatal circumcision. Thus periodic examination of a buried penis is warranted even in patients with no risk factors for penile cancer. A review of the literature is provided.

Integrating Oral and General Health Screening at Senior Centers for Minority Elders

PubMed Central

Cheng, Bin; Northridge, Mary E.; Kunzel, Carol; Huang, Catherine; Lamster, Ira B.

2013-01-01

Racial/ethnic and socioeconomic disparities regarding untreated oral disease exist for older adults, and poor oral health diminishes quality of life. The ElderSmile program integrated screening for diabetes and hypertension into its community-based oral health activities at senior centers in northern Manhattan. The program found a willingness among minority seniors (aged ≥ 50 years) to be screened for primary care sensitive conditions by dental professionals and a high level of unrecognized disease (7.8% and 24.6% of ElderSmile participants had positive screening results for previously undiagnosed diabetes and hypertension, respectively). Dental professionals may screen for primary care–sensitive conditions and refer patients to health care providers for definitive diagnosis and treatment. The ElderSmile program is a replicable model for community-based oral and general health screening. PMID:23597378

Uncovering an Existential Barrier to Breast Self-exam Behavior

PubMed Central

Goldenberg, Jamie L.; Arndt, Jamie; Hart, Joshua; Routledge, Clay

2008-01-01

The present research applies an analysis derived from terror management theory to the health domain of breast examination, and in doing so uncovers previously unrecognized factors that may contribute to women’s reluctance to perform breast self-examinations (BSEs). In Study 1, when concerns about mortality were primed, reminders of human beings’ physical nature (i.e., creatureliness) reduced intentions to conduct BSEs compared to reminders of humans’ uniqueness. In Study 2, women conducted shorter exams on a breast model (an experience found to increase death-thought accessibility) when creatureliness was primed compared to a uniqueness and no essay condition. In Study 3, after a creatureliness prime, women performed shorter BSEs when a placebo did not provide an alternative explanation for their discomfort compared to when it did. Advances for theory and breast self-exam promotion are discussed. PMID:19255593

Improved method for HPLC analysis of polyamines, agmatine and aromatic monoamines in plant tissue

NASA Technical Reports Server (NTRS)

Slocum, R. D.; Flores, H. E.; Galston, A. W.; Weinstein, L. H.

1989-01-01

The high performance liquid chromatographic (HPLC) method of Flores and Galston (1982 Plant Physiol 69: 701) for the separation and quantitation of benzoylated polyamines in plant tissues has been widely adopted by other workers. However, due to previously unrecognized problems associated with the derivatization of agmatine, this important intermediate in plant polyamine metabolism cannot be quantitated using this method. Also, two polyamines, putrescine and diaminopropane, also are not well resolved using this method. A simple modification of the original HPLC procedure greatly improves the separation and quantitation of these amines, and further allows the simulation analysis of phenethylamine and tyramine, which are major monoamine constituents of tobacco and other plant tissues. We have used this modified HPLC method to characterize amine titers in suspension cultured carrot (Daucas carota L.) cells and tobacco (Nicotiana tabacum L.) leaf tissues.

Parking lot sealcoat: An unrecognized source of urban polycyclic aromatic hydrocarbons

USGS Publications Warehouse

Mahler, B.J.; Van Metre, P.C.; Bashara, T.J.; Wilson, J.T.; Johns, D.A.

2005-01-01

Polycyclic aromatic hydrocarbons (PAHs) are a ubiquitous contaminant in urban environments. Although numerous sources of PAHs to urban runoff have been identified, their relative importance remains uncertain. We show that a previously unidentified source of urban PAHs, parking lot sealcoat, may dominate loading of PAHs to urban water bodies in the United States. Particles in runoff from parking lots with coal-tar emulsion sealcoat had mean concentrations of PAHs of 3500 mg/kg, 65 times higher than the mean concentration from unsealed asphalt and cement lots. Diagnostic ratios of individual PAHs indicating sources are similar for particles from coal-tar emulsion sealed lots and suspended sediment from four urban streams. Contaminant yields projected to the watershed scale for the four associated watersheds indicate that runoff from sealed parking lots could account for the majority of stream PAH loads.

Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation

PubMed Central

Haldar, Saptarsi M.; Jeyaraj, Darwin; Anand, Priti; Zhu, Han; Lu, Yuan; Prosdocimo, Domenick A.; Eapen, Betty; Kawanami, Daiji; Okutsu, Mitsuharu; Brotto, Leticia; Fujioka, Hisashi; Kerner, Janos; Rosca, Mariana G.; McGuinness, Owen P.; Snow, Rod J.; Russell, Aaron P.; Gerber, Anthony N.; Bai, Xiaodong; Yan, Zhen; Nosek, Thomas M.; Brotto, Marco; Hoppel, Charles L.; Jain, Mukesh K.

2012-01-01

The ability of skeletal muscle to enhance lipid utilization during exercise is a form of metabolic plasticity essential for survival. Conversely, metabolic inflexibility in muscle can cause organ dysfunction and disease. Although the transcription factor Kruppel-like factor 15 (KLF15) is an important regulator of glucose and amino acid metabolism, its endogenous role in lipid homeostasis and muscle physiology is unknown. Here we demonstrate that KLF15 is essential for skeletal muscle lipid utilization and physiologic performance. KLF15 directly regulates a broad transcriptional program spanning all major segments of the lipid-flux pathway in muscle. Consequently, Klf15-deficient mice have abnormal lipid and energy flux, excessive reliance on carbohydrate fuels, exaggerated muscle fatigue, and impaired endurance exercise capacity. Elucidation of this heretofore unrecognized role for KLF15 now implicates this factor as a central component of the transcriptional circuitry that coordinates physiologic flux of all three basic cellular nutrients: glucose, amino acids, and lipids. PMID:22493257

Biological and Organic Chemical Decomposition of Silicates. Chapter 7.2

NASA Technical Reports Server (NTRS)

Silverman, M. P.

1979-01-01

The weathering of silicate rocks and minerals, an important concern of geologists and geochemists for many years, traditionally has been approached from strictly physical and chemical points of view. Biological effects were either unrecognized, ignored, or were mentioned in passing to account for such phenomena as the accumulation of organic matter in sediments or the generation of reducing environments. A major exception occurred in soil science where agricultural scientists, studying the factors important in the development of soils and their ability to nourish and sustain various crops, laid the foundation for much of what is known of the biological breakdown of silicate rocks and minerals. The advent of the space age accelerated the realization that many environmental problems and geo- chemical processes on Earth can only be understood in terms of ecosystems. This in turn, spurred renewed interest and activity among modem biologists, geologists and soil scientists attempting to unravel the intimate relations between biology and the weathering of silicate rocks and minerals of the earth surface.

Biological and Organic Chemical Decomposition of Silicates. Chapter 7.2

NASA Technical Reports Server (NTRS)

Sliverman, M. P.

1979-01-01

The weathering of silicate rocks and minerals, an important concern of geologists and geochemists for many years, traditionally has been approached from strictly physical and chemical points of view. Biological effects were either unrecognized, ignored, or were mentioned in passing to account for such phenomena as the accumulation of organic matter in sediments or the generation of reducing environments. A major exception occurred in soil science where agricultural scientists, studying the factors important in the development of soils and their ability to nourish and sustain various crops, laid the foundation for much of what is known of the biological breakdown of silicate rocks and minerals. The advent of the space age accelerated the realization that many environmental problems and geochemical processes on Earth can only be understood in terms of ecosystems. This in turn, spurred renewed interest and activity among modem biologists, geologists and soil scientists attempting to unravel the intimate relations between biology and the weathering of silicate rocks and minerals of the earth's surface.

The role of identification in dynamic psychiatry and psychotherapy.

PubMed

Corradi, Richard B

2011-01-01

Identification-a psychic process in which a person takes on characteristics of another-is a concept important to the understanding of human nature. It plays an important role in how our personalities develop, in our ability to deal with life's stresses, and in how we interact with other people. Knowledge of its manifestations is essential to dynamic psychiatry and to its applications in psychotherapy. This article defines identification and reviews its role in development and as a defense. It discusses its role in the psychopathology of disorders commonly encountered in psychotherapy practice-depression and anxiety states reactive to losses in life, and borderline states. Clinical vignettes illustrate how identification functions in these conditions, and also how identifications reveal themselves in the transference and are utilized in psychotherapy. A teaching vignette illustrates how important it is that residents learning the art of psychotherapy appreciate the therapeutic potential of identification. The article maintains that, although it often goes unrecognized, identification with the therapist is one of the most effective therapeutic devices in the transference.

Timing of the Late Paleozoic Ice Age: A Review of the Status Quo and New U-Pb Zircon Ages From Southern Gondwana

NASA Astrophysics Data System (ADS)

Mundil, R.; Griffis, N. P.; Keller, C. B.; Fedorchuk, N.; Montanez, I. P.; Isbell, J.; Vesely, F.; Iannuzzi, R.

2017-12-01

Throughout the Carboniferous and Permian Late Paleozoic Ice Age (LPIA), glaciations in southern Gondwana exerted a profound influence on global climate and environment, ocean chemistry, and the nature of sedimentary processes. The LPIA is widely regarded as an analogue for Pleistocene glaciations. Our understanding of the latter, as well as the validity of predictions for the future global climate and environment, depends therefore on our ability to reconstruct the LPIA. A robust chronostratigraphic framework built on high precision/high accuracy geochronology is crucial for the reconstruction of events and processes that occurred during the LPIA, particularly in the absence of high-resolution terrestrial biostratigraphic constraints that apply to both near- and far-field proxy records. The occurrence of volcaniclastic layers containing primary volcanic zircon at many levels throughout southern Gondwana makes such a reconstruction feasible, but complications inevitably arise due to the mixing of older age components with primary volcanic crystals, as well as the potential of unrecognized open system behavior to produce spurious younger ages. These pitfalls cause age dispersion that may be difficult to interpret, or is unrecognized if low precision geochronological techniques are used, resulting in inaccurate radioisotopic ages. Our current efforts in the Parana Basin (Southern Brazil) and the Karoo Basin (South Africa/Namibia) concentrate on building a robust and exportable chronostratigraphic framework based on U-Pb zircon CA-TIMS ages with sub-permil level precision combined with Bayesian approaches for resolving the eruption age of dispersed age spectra to facilitate the reconstruction of glaciogenic processes through the Carboniferous-Permian transition, as well as their implications for global sea level, atmospheric pCO2 and ocean chemistry. We will also review currently available geochronological data from contemporaneous Australian successions and their potential for robust correlations and paleo-environmental reconstruction.

Burden of Systolic and Diastolic Left Ventricular Dysfunction among Hispanics in the United States: Insights from the Echocardiographic Study of Latinos (ECHO-SOL)

PubMed Central

Mehta, Hardik; Armstrong, Anderson; Swett, Katrina; Shah, Sanjiv J.; Allison, Matthew A.; Hurwitz, Barry; Bangdiwala, Shrikant; Dadhania, Rupal; Kitzman, Dalane W.; Arguelles, William; Lima, Joao; Youngblood, Marston; Schneiderman, Neil; Daviglus, Martha L.; Spevack, Daniel; Talavera, Greg A.; Raisinghani, Ajit; Kaplan, Robert; Rodriguez, Carlos J.

2016-01-01

Background Population-based estimates of cardiac dysfunction and clinical heart failure (HF) remain undefined among Hispanics/Latino adults. Methods and Results Participants of Hispanic/Latino origin across the US, aged 45–74 years were enrolled into the Echocardiographic Study of Latinos (ECHO-SOL) and underwent a comprehensive echocardiography exam to define left ventricular systolic dysfunction (LVSD) and left ventricular diastolic dysfunction (LVDD). Clinical HF was defined according to self-report; and those with cardiac dysfunction but without clinical HF were characterized as having subclinical or unrecognized cardiac dysfunction. Of 1,818 ECHO-SOL participants (mean age 56.4 years; 42.6% male) , 49.7% had LVSD and/or LVDD. LVSD prevalence was 3.6%, while LVDD was detected in 50.3%. Participants with LVSD were more likely to be males and current smokers (all p<0.05). Female sex, hypertension, diabetes, higher body-mass index and renal dysfunction were more common among those with LVDD (all p<0.05). In age-sex adjusted models, individuals of Central American and Cuban backgrounds were almost two-fold more likely to have LVDD compared to those of Mexican backgrounds. Prevalence of clinical HF with LVSD (HF with reduced EF) was 7.3%; prevalence of clinical HF with LVDD (HF with preserved EF) was 3.6%. 96.1% of the cardiac dysfunction seen was subclinical or unrecognized. Compared to those with clinical cardiac dysfunction, prevalent coronary heart disease was the only factor independently associated with subclinical or unrecognized cardiac dysfunction (odds ratio: 0.1; 95% confidence interval: 0.1–0.4). Conclusions Among Hispanics/Latinos, most cardiac dysfunction is subclinical or unrecognized, with a high prevalence of diastolic dysfunction. This identifies a high-risk population for the development of clinical HF. PMID:27048764

The earliest bird-line archosaurs and the assembly of the dinosaur body plan.

PubMed

Nesbitt, Sterling J; Butler, Richard J; Ezcurra, Martín D; Barrett, Paul M; Stocker, Michelle R; Angielczyk, Kenneth D; Smith, Roger M H; Sidor, Christian A; Niedźwiedzki, Grzegorz; Sennikov, Andrey G; Charig, Alan J

2017-04-27

The relationship between dinosaurs and other reptiles is well established, but the sequence of acquisition of dinosaurian features has been obscured by the scarcity of fossils with transitional morphologies. The closest extinct relatives of dinosaurs either have highly derived morphologies or are known from poorly preserved or incomplete material. Here we describe one of the stratigraphically lowest and phylogenetically earliest members of the avian stem lineage (Avemetatarsalia), Teleocrater rhadinus gen. et sp. nov., from the Middle Triassic epoch. The anatomy of T. rhadinus provides key information that unites several enigmatic taxa from across Pangaea into a previously unrecognized clade, Aphanosauria. This clade is the sister taxon of Ornithodira (pterosaurs and birds) and shortens the ghost lineage inferred at the base of Avemetatarsalia. We demonstrate that several anatomical features long thought to characterize Dinosauria and dinosauriforms evolved much earlier, soon after the bird-crocodylian split, and that the earliest avemetatarsalians retained the crocodylian-like ankle morphology and hindlimb proportions of stem archosaurs and early pseudosuchians. Early avemetatarsalians were substantially more species-rich, widely geographically distributed and morphologically diverse than previously recognized. Moreover, several early dinosauromorphs that were previously used as models to understand dinosaur origins may represent specialized forms rather than the ancestral avemetatarsalian morphology.

Prokaryotic diversity, distribution, and insights into their role in biogeochemical cycling in marine basalts

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

Mason, Olivia U.; Di Meo-Savoie, Carol A.; Van Nostrand, Joy D.

2008-09-30

We used molecular techniques to analyze basalts of varying ages that were collected from the East Pacific Rise, 9 oN, from the rift axis of the Juan de Fuca Ridge, and from neighboring seamounts. Cluster analysis of 16S rDNA Terminal Restriction Fragment Polymorphism data revealed that basalt endoliths are distinct from seawater and that communities clustered, to some degree, based on the age of the host rock. This age-based clustering suggests that alteration processes may affect community structure. Cloning and sequencing of bacterial and archaeal 16S rRNA genes revealed twelve different phyla and sub-phyla associated with basalts. These include themore » Gemmatimonadetes, Nitrospirae, the candidate phylum SBR1093 in the c, andin the Archaea Marine Benthic Group B, none of which have been previously reported in basalts. We delineated novel ocean crust clades in the gamma-Proteobacteria, Planctomycetes, and Actinobacteria that are composed entirely of basalt associated microflora, and may represent basalt ecotypes. Finally, microarray analysis of functional genes in basalt revealed that genes coding for previously unreported processes such as carbon fixation, methane-oxidation, methanogenesis, and nitrogen fixation are present, suggesting that basalts harbor previously unrecognized metabolic diversity. These novel processes could exert a profound influence on ocean chemistry.« less

Exchange protein activated by cAMP (Epac) mediates cAMP-dependent but protein kinase A-insensitive modulation of vascular ATP-sensitive potassium channels

PubMed Central

Purves, Gregor I; Kamishima, Tomoko; Davies, Lowri M; Quayle, John M; Dart, Caroline

2009-01-01

Exchange proteins directly activated by cyclic AMP (Epacs or cAMP-GEF) represent a family of novel cAMP-binding effector proteins. The identification of Epacs and the recent development of pharmacological tools that discriminate between cAMP-mediated pathways have revealed previously unrecognized roles for cAMP that are independent of its traditional target cAMP-dependent protein kinase (PKA). Here we show that Epac exists in a complex with vascular ATP-sensitive potassium (KATP) channel subunits and that cAMP-mediated activation of Epac modulates KATP channel activity via a Ca2+-dependent mechanism involving the activation of Ca2+-sensitive protein phosphatase 2B (PP-2B, calcineurin). Application of the Epac-specific cAMP analogue 8-pCPT-2′-O-Me-cAMP, at concentrations that activate Epac but not PKA, caused a 41.6 ± 4.7% inhibition (mean ±s.e.m.; n= 7) of pinacidil-evoked whole-cell KATP currents recorded in isolated rat aortic smooth muscle cells. Importantly, similar results were obtained when cAMP was elevated by addition of the adenylyl cyclase activator forskolin in the presence of the structurally distinct PKA inhibitors, Rp-cAMPS or KT5720. Activation of Epac by 8-pCPT-2′-O-Me-cAMP caused a transient 171.0 ± 18.0 nm (n= 5) increase in intracellular Ca2+ in Fura-2-loaded aortic myocytes, which persisted in the absence of extracellular Ca2+. Inclusion of the Ca2+-specific chelator BAPTA in the pipette-filling solution or preincubation with the calcineurin inhibitors, cyclosporin A or ascomycin, significantly reduced the ability of 8-pCPT-2′-O-Me-cAMP to inhibit whole-cell KATP currents. These results highlight a previously undescribed cAMP-dependent regulatory mechanism that may be essential for understanding the physiological and pathophysiological roles ascribed to arterial KATP channels in the control of vascular tone and blood flow. PMID:19491242

MULTIMODAL IMAGING OF SYPHILITIC MULTIFOCAL RETINITIS.

PubMed

Curi, Andre L; Sarraf, David; Cunningham, Emmett T

2015-01-01

To describe multimodal imaging of syphilitic multifocal retinitis. Observational case series. Two patients developed multifocal retinitis after treatment of unrecognized syphilitic uveitis with systemic corticosteroids in the absence of appropriate antibiotic therapy. Multimodal imaging localized the foci of retinitis within the retina in contrast to superficial retinal precipitates that accumulate on the surface of the retina in eyes with untreated syphilitic uveitis. Although the retinitis resolved after treatment with systemic penicillin in both cases, vision remained poor in the patient with multifocal retinitis involving the macula. Treatment of unrecognized syphilitic uveitis with corticosteroids in the absence of antitreponemal treatment can lead to the development of multifocal retinitis. Multimodal imaging, and optical coherence tomography in particular, can be used to distinguish multifocal retinitis from superficial retinal precipitates or accumulations.

Congenital rubella syndrome in Haiti (Short communication).

PubMed

Golden, Nancy; Kempker, Russell; Khator, Parul; Summerlee, Robert; Fournier, Arthur

2002-10-01

To determine if there is an unrecognized problem of congenital rubella syndrome (CRS) in Haiti, a country without a national rubella immunization program. During March 2001 and June 2001, screening physicals were conducted on approximately 80 orphans at three orphanages in Haiti that accept disabled children. Children were classified as probable CRS cases based on established clinical criteria. Photo documentation of findings was obtained whenever possible. Six children met the criteria for probable CRS. Using data from surrounding Caribbean countries and from the United States of America prior to rubella immunization, we estimated that there are between 163 and 440 new cases of CRS per year in Haiti. CRS exists in Haiti, but its presence is generally unrecognized. A national rubella immunization policy should be considered.

Extra-articular hip impingement: a narrative review of the literature

PubMed Central

Cheatham, Scott W.

2016-01-01

There is growing subgroup of patients with poor outcomes after hip arthroscopy for intra-articular pathology suggesting unrecognized cause(s) of impingement may exist. Extra-articular hip impingement (EHI) is an emerging group of conditions that have been associated with intra-articular causes of impingement and may be an unrecognized source of pain. EHI is caused by abnormal contact between the extra-articular regions of the proximal femur and pelvis. This review discusses the most common forms for EHI including: central iliopsoas impingement, subspine impingement, ischiofemoral impingement, and greater trochanteric-pelvic impingement. The clinical presentation of each pathology will be discussed since EHI conditions share similar clinical features as the intra-articular pathology but also contain some unique characteristics. PMID:27069266

Apparent mineralcorticoid excess syndrome, an often forgotten or unrecognized cause of hypokalemia and hypertension: case report and appraisal of the pathophysiology.

PubMed

Bisogni, Valeria; Rossi, Gian Paolo; Calò, Lorenzo A

2014-06-01

The glicyrrhizic acid, contained in licorice, has a mineralcorticoid-like effect. Chronic excess intake of licorice induces the rare syndrome of "apparent mineralcorticoid excess", due to the inhibitory effect of glicyrrhizic acid on 11 β-hydroxysteroid dehydrogenase type 2 determining clinical/biochemical manifestations as resistant hypertension, metabolic alkalosis and severe hypokalemia. We report a typical clinical case of licorice abuse to emphasize the importance of a detailed anamnesis, which is essential for the diagnosis, avoid unnecessary and expensive investigations, and reduce the duration of hospitalization. We also provide an appraisal of the pathophysiology of "apparent mineralcorticoid excess" syndrome, still an often forgotten or unrecognized cause of hypokalemia and hypertension.

Reprogramming of non-genomic estrogen signaling by the stemness factor SOX2 enhances the tumor-initiating capacity of breast cancer cells.

PubMed

Vazquez-Martin, Alejandro; Cufí, Sílvia; López-Bonet, Eugeni; Corominas-Faja, Bruna; Cuyàs, Elisabet; Vellon, Luciano; Iglesias, Juan Manuel; Leis, Olatz; Martín, Angel G; Menendez, Javier A

2013-11-15

The restoration of pluripotency circuits by the reactivation of endogenous stemness factors, such as SOX2, may provide a new paradigm in cancer development. The tumoral stem cell reprogramming hypothesis, i.e., the ability of stemness factors to redirect normal and differentiated tumor cells toward a less-differentiated and stem-like state, adds new layers of complexity to cancer biology, because the effects of such reprogramming may remain dormant until engaged later in response to (epi)genetic and/or (micro)environmental events. To test this hypothesis, we utilized an in vitro model of a SOX2-overexpressing cancer stem cell (CSC)-like cellular state that was recently developed in our laboratory by employing Yamanaka's nuclear reprogramming technology in the estrogen receptor α (ERα)-positive MCF-7 breast cancer cell line. Despite the acquisition of distinct molecular features that were compatible with a breast CSC-like cellular state, such as strong aldehyde dehydrogenase activity, as detected by ALDEFLUOR, and overexpression of the SSEA-4 and CD44 breast CSC markers, the tumor growth-initiating ability of SOX2-overexpressing CSC-like MCF-7 cells solely occurred in female nude mice supplemented with estradiol when compared with MCF-7 parental cells. Ser118 phosphorylation of estrogen receptor α (ERα), which is a pivotal integrator of the genomic and nongenomic E 2/ERα signaling pathways, drastically accumulated in nuclear speckles in the interphase nuclei of SOX2-driven CSC-like cell populations. Moreover, SOX2-positive CSC-like cells accumulated significantly higher numbers of actively dividing cells, and the highest levels of phospho-Ser118-ERα occurred when chromosomes lined up on a metaphase plate. The previously unrecognized link between E 2/ERα signaling and SOX2-driven stem cell circuitry may significantly impact our current understanding of breast cancer initiation and progression, i.e., SOX2 can promote non-genomic E 2 signaling that leads to nuclear phospho-Ser118-ERα, which ultimately exacerbates genomic ER signaling in response to E 2. Because E 2 stimulation has been recently shown to enhance breast tumor-initiating cell survival by downregulating miR-140, which targets SOX2, the establishment of a bidirectional cross-talk interaction between the stem cell self-renewal regulator, SOX2, and the local and systemic ability of E 2 to increase breast CSC activity may have profound implications for the development of new CSC-directed strategies for breast cancer prevention and therapy.

[Foundation of the science and society alliance in France. Towards a conscious and recognised collaboration between actors of research and civil society].

PubMed

Fellini, Nadia; Faroult, Elie

2015-01-01

In the last two decades, the debate on the meaning of science in relation to societies that create it, nourish it, and benefit from it, focused on civil society's ability to produce knowledge. This yielded first the concept of participatory science and later the wider concept of participatory research. Throughout Europe, numerous collective experimentations have generated countless interactions, and new interfaces between the world of research and civil society are constantly being created. But in spite of the proliferation of these experiences, a paradox slows down their acknowledgment and legitimation. On the one hand, these interactions often go unseen and unrecognized by the institutions, public policies, and even at times their very creators. On the other hand, scientists, are still overwhelmingly wary of civil society and, perceiving only its intellectual deficit and lack of comprehension, they fail to consider the study and development of these interactions as being of primary importance. The Sciences and Society Alliance, which was recently founded in France, provides a platform where these collaborative experiences can be collected, studied, supported, communicated, and institutionally acknowledged. The launch of this process,which is soon to be European in scope, answers the need to bring science into the democratic path tread by the societies that create it. In its ability to compose diversity, this process is an example of deep democracy.

Greatest soil microbial diversity found in micro-habitats

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

Bach, Elizabeth M.; Williams, Ryan J.; Hargreaves, Sarah K.

Microbial interactions occur in habitats much smaller than typically considered in classic ecological studies. This study uses soil aggregates to examine soil microbial community composition and structure of both bacteria and fungi at a microbially relevant scale. Aggregates were isolated from three land management systems in central Iowa, USA to test if aggregate-level microbial responses were sensitive to large-scale shifts in plant community and management practices. Bacteria and fungi exhibited similar patterns of community structure and diversity among soil aggregates, regardless of land management. Microaggregates supported more diverse microbial communities, both taxonomically and functionally. Calculation of a weighted proportional wholemore » soil diversity, which accounted for microbes found in aggregate fractions, resulted in 65% greater bacterial richness and 100% greater fungal richness over independently sampled whole soil. Our results show microaggregates support a previously unrecognized diverse microbial community that likely effects microbial access and metabolism of soil substrates.« less

KRAS as a Therapeutic Target.

PubMed

McCormick, Frank

2015-04-15

KRAS proteins play a major role in human cancer, but have not yielded to therapeutic attack. New technologies in drug discovery and insights into signaling pathways that KRAS controls have promoted renewed efforts to develop therapies through direct targeting of KRAS itself, new ways of blocking KRAS processing, or by identifying targets that KRAS cancers depend on for survival. Although drugs that block the well-established downstream pathways, RAF-MAPK and PI3K, are being tested in the clinic, new efforts are under way to exploit previously unrecognized vulnerabilities, such as altered metabolic networks, or novel pathways identified through synthetic lethal screens. Furthermore, new ways of suppressing KRAS gene expression and of harnessing the immune system offer further hope that new ways of treating KRAS are finally coming into view. These issues are discussed in this edition of CCR Focus. ©2015 American Association for Cancer Research.

Supervolcanoes Within an Ancient Volcanic Province in Arabia Terra, Mars

NASA Technical Reports Server (NTRS)

Michalski, Joseph. R.; Bleacher, Jacob E.

2014-01-01

Several irregularly shaped craters located within Arabia Terra, Mars represent a new type of highland volcanic construct and together constitute a previously unrecognized martian igneous province. Similar to terrestrial supervolcanoes, these low-relief paterae display a range of geomorphic features related to structural collapse, effusive volcanism, and explosive eruptions. Extruded lavas contributed to the formation of enigmatic highland ridged plains in Arabia Terra. Outgassed sulfur and erupted fine-grained pyroclastics from these calderas likely fed the formation of altered, layered sedimentary rocks and fretted terrain found throughout the equatorial region. Discovery of a new type of volcanic construct in the Arabia volcanic province fundamentally changes the picture of ancient volcanism and climate evolution on Mars. Other eroded topographic basins in the ancient Martian highlands that have been dismissed as degraded impact craters should be reconsidered as possible volcanic constructs formed in an early phase of widespread, disseminated magmatism on Mars.

Epigenetic regulation of the NR4A orphan nuclear receptor NOR1 by histone acetylation.

PubMed

Zhao, Yue; Nomiyama, Takashi; Findeisen, Hannes M; Qing, Hua; Aono, Jun; Jones, Karrie L; Heywood, Elizabeth B; Bruemmer, Dennis

2014-12-20

The nuclear receptor NOR1 is an immediate-early response gene implicated in the transcriptional control of proliferation. Since the expression level of NOR1 is rapidly induced through cAMP response element binding (CREB) protein-dependent promoter activation, we investigated the contribution of histone acetylation to this transient induction. We demonstrate that NOR1 transcription is induced by histone deacetylase (HDAC) inhibition and by depletion of HDAC1 and HDAC3. HDAC inhibition activated the NOR1 promoter, increased histone acetylation and augmented the recruitment of phosphorylated CREB to the promoter. Furthermore, HDAC inhibition increased Ser133 phosphorylation of CREB and augmented NOR1 protein stability. These data outline previously unrecognized mechanisms of NOR1 regulation and illustrate a key role for histone acetylation in the rapid induction of NOR1. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

HIV-1, Reactive Oxygen Species and Vascular Complications

PubMed Central

Porter, Kristi M.; Sutliff, Roy L.

2012-01-01

Over 1 million people in the United States and 33 million individuals worldwide suffer from HIV/AIDS. Since its discovery, HIV/AIDS has been associated with an increased susceptibility to opportunistic infection due to immune dysfunction. Highly active antiretroviral therapies (HAART) restore immune function and, as a result, people infected with HIV-1 are living longer. This improved survival of HIV-1 patients has revealed a previously unrecognized risk of developing vascular complications, such as atherosclerosis and pulmonary hypertension. The mechanisms underlying these HIV-associated vascular disorders are poorly understood. However, HIV-induced elevations in reactive oxygen species, including superoxide and hydrogen peroxide, may contribute to vascular disease development and progression by altering cell function and redox-sensitive signaling pathways. In this review, we summarize the clinical and experimental evidence demonstrating HIV- and HIV antiretroviral therapy-induced alterations in reactive oxygen species (ROS) and how these effects likely contribute to vascular dysfunction and disease. PMID:22564529

Emerging roles of post-translational modifications in signal transduction and angiogenesis.

PubMed

Rahimi, Nader; Costello, Catherine E

2015-01-01

The vascular endothelial growth factor receptor-2 (VEGFR-2) belongs to the family of receptor tyrosine kinases and is a key player in vasculogenesis and pathological angiogenesis. An emerging picture of PTMs of VEGFR-2 suggests that they play central roles in generating a highly dynamic and complex signaling system that regulates key angiogenic responses ranging from endothelial cell differentiation, proliferation, migration to permeability. Recent MS analysis of VEGFR-2 uncovered previously unrecognized PTMs on VEGFR-2 with a distinct function. The ligand binding extracellular domain of VEGFR-2 is composed of seven immunoglobulin-like domains highly decorated with N-glycosylation, while its cytoplasmic domain is subject to multiple PTMs including Tyr, Ser/Thr phosphorylation, Arg and Lys methylation, acetylation and ubiquitination. Here we review the PTMs on VEGFR-2, their importance in angiogenic signaling relays and possible novel therapeutic potentials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rpl13a small nucleolar RNAs regulate systemic glucose metabolism

PubMed Central

Lee, Jiyeon; Harris, Alexis N.; Holley, Christopher L.; Mahadevan, Jana; Pyles, Kelly D.; Lavagnino, Zeno; Scherrer, David E.; Fujiwara, Hideji; Sidhu, Rohini; Zhang, Jessie; Huang, Stanley Ching-Cheng; Piston, David W.; Remedi, Maria S.; Urano, Fumihiko; Ory, Daniel S.

2016-01-01

Small nucleolar RNAs (snoRNAs) are non-coding RNAs that form ribonucleoproteins to guide covalent modifications of ribosomal and small nuclear RNAs in the nucleus. Recent studies have also uncovered additional non-canonical roles for snoRNAs. However, the physiological contributions of these small RNAs are largely unknown. Here, we selectively deleted four snoRNAs encoded within the introns of the ribosomal protein L13a (Rpl13a) locus in a mouse model. Loss of Rpl13a snoRNAs altered mitochondrial metabolism and lowered reactive oxygen species tone, leading to increased glucose-stimulated insulin secretion from pancreatic islets and enhanced systemic glucose tolerance. Islets from mice lacking Rpl13a snoRNAs demonstrated blunted oxidative stress responses. Furthermore, these mice were protected against diabetogenic stimuli that cause oxidative stress damage to islets. Our study illuminates a previously unrecognized role for snoRNAs in metabolic regulation. PMID:27820699

Pleural innate response activator B cells protect against pneumonia via a GM-CSF-IgM axis

PubMed Central

Chousterman, Benjamin G.; Hilgendorf, Ingo; Robbins, Clinton S.; Theurl, Igor; Gerhardt, Louisa M.S.; Iwamoto, Yoshiko; Quach, Tam D.; Ali, Muhammad; Chen, John W.; Rothstein, Thomas L.; Nahrendorf, Matthias; Weissleder, Ralph

2014-01-01

Pneumonia is a major cause of mortality worldwide and a serious problem in critical care medicine, but the immunophysiological processes that confer either protection or morbidity are not completely understood. We show that in response to lung infection, B1a B cells migrate from the pleural space to the lung parenchyma to secrete polyreactive emergency immunoglobulin M (IgM). The process requires innate response activator (IRA) B cells, a transitional B1a-derived inflammatory subset which controls IgM production via autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. The strategic location of these cells, coupled with the capacity to produce GM-CSF–dependent IgM, ensures effective early frontline defense against bacteria invading the lungs. The study describes a previously unrecognized GM-CSF-IgM axis and positions IRA B cells as orchestrators of protective IgM immunity. PMID:24821911

Quantization improves stabilization of dynamical systems with delayed feedback

NASA Astrophysics Data System (ADS)

Stepan, Gabor; Milton, John G.; Insperger, Tamas

2017-11-01

We show that an unstable scalar dynamical system with time-delayed feedback can be stabilized by quantizing the feedback. The discrete time model corresponds to a previously unrecognized case of the microchaotic map in which the fixed point is both locally and globally repelling. In the continuous-time model, stabilization by quantization is possible when the fixed point in the absence of feedback is an unstable node, and in the presence of feedback, it is an unstable focus (spiral). The results are illustrated with numerical simulation of the unstable Hayes equation. The solutions of the quantized Hayes equation take the form of oscillations in which the amplitude is a function of the size of the quantization step. If the quantization step is sufficiently small, the amplitude of the oscillations can be small enough to practically approximate the dynamics around a stable fixed point.

Control of jasmonate biosynthesis and senescence by miR319 targets.

PubMed

Schommer, Carla; Palatnik, Javier F; Aggarwal, Pooja; Chételat, Aurore; Cubas, Pilar; Farmer, Edward E; Nath, Utpal; Weigel, Detlef

2008-09-23

Considerable progress has been made in identifying the targets of plant microRNAs, many of which regulate the stability or translation of mRNAs that encode transcription factors involved in development. In most cases, it is unknown, however, which immediate transcriptional targets mediate downstream effects of the microRNA-regulated transcription factors. We identified a new process controlled by the miR319-regulated clade of TCP (TEOSINTE BRANCHED/CYCLOIDEA/PCF) transcription factor genes. In contrast to other miRNA targets, several of which modulate hormone responses, TCPs control biosynthesis of the hormone jasmonic acid. Furthermore, we demonstrate a previously unrecognized effect of TCPs on leaf senescence, a process in which jasmonic acid has been proposed to be a critical regulator. We propose that miR319-controlled TCP transcription factors coordinate two sequential processes in leaf development: leaf growth, which they negatively regulate, and leaf senescence, which they positively regulate.

Stress fracture of the second proximal phalanx of the foot in teenage athletes: Unrecognized location of stress fracture.

PubMed

Yamaguchi, Satoshi; Taketomi, Shuji; Funakoshi, Yusei; Tsuchiya, Kan; Akagi, Ryuichiro; Kimura, Seiji; Sadamasu, Aya; Ohtori, Seiji

2017-10-01

Adolescent athletes are a high-risk population for stress fractures. We report four cases of stress fractures of the second proximal phalanx, which had not been previously diagnosed as the location of the stress fracture of the foot, in teenage athletes. All fractures were on the plantar side of the proximal phalangeal base, and the oblique images of the plain radiograph clearly depicted the fractures. Notably, three out of the four patients had histories of stress fracture of other locations. While three athletes with acute cases were able to make an early return to play with simple conservative management, the chronic case required surgical treatment for this rare injury. Although a rare injury, it is important that clinicians be aware of this type of stress fracture, as a timely diagnosis can avoid the need for surgical treatment and allow an early return to play.

Rapid laccolith intrusion driven by explosive volcanic eruption

NASA Astrophysics Data System (ADS)

Castro, Jonathan M.; Cordonnier, Benoit; Schipper, C. Ian; Tuffen, Hugh; Baumann, Tobias S.; Feisel, Yves

2016-11-01

Magmatic intrusions and volcanic eruptions are intimately related phenomena. Shallow magma intrusion builds subsurface reservoirs that are drained by volcanic eruptions. Thus, the long-held view is that intrusions must precede and feed eruptions. Here we show that explosive eruptions can also cause magma intrusion. We provide an account of a rapidly emplaced laccolith during the 2011 rhyolite eruption of Cordón Caulle, Chile. Remote sensing indicates that an intrusion began after eruption onset and caused severe (>200 m) uplift over 1 month. Digital terrain models resolve a laccolith-shaped body ~0.8 km3. Deformation and conduit flow models indicate laccolith depths of only ~20-200 m and overpressures (~1-10 MPa) that likely stemmed from conduit blockage. Our results show that explosive eruptions may rapidly force significant quantities of magma in the crust to build laccoliths. These iconic intrusions can thus be interpreted as eruptive features that pose unique and previously unrecognized volcanic hazards.

Parking lot sealcoat: an unrecognized source of urban polycyclic aromatic hydrocarbons

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

Barbara J. Mahler; Peter C. Van Metre; Thomas J. Bashara

2005-08-01

Polycyclic aromatic hydrocarbons (PAHs) are a ubiquitous contaminant in urban environments. Although numerous sources of PAHs to urban runoff have been identified, their relative importance remains uncertain. The authors show that a previously unidentified source of urban PAHs, parking lot sealcoat, may dominate loading of PAHs to urban water bodies in the United States. Particles in runoff from parking lots with coal-tar emulsion sealcoat had mean concentrations of PAHs of 3500 mg/kg, 65 times higher than the mean concentration from unsealed asphalt and cement lots. Diagnostic ratios of individual PAHs indicating sources are similar for particles from coal-tar emulsion sealedmore » lots and suspended sediment from four urban streams. Contaminant yields projected to the watershed scale for the four associated watersheds indicate that runoff from sealed parking lots could account for the majority of stream PAH loads. 35 refs., 6 figs., 2 tabs.« less

Bipolar affective disorder and Parkinson's disease: a rare, insidious and often unrecognized association.

PubMed

Cannas, A; Spissu, A; Floris, G L; Congia, S; Saddi, M V; Melis, M; Mascia, M M; Pinna, F; Tuveri, A; Solla, P; Milia, A; Giagheddu, M; Tacconi, P

2002-09-01

Five patients (4 women) with Parkinson's disease (PD) and primary major psychiatric disorder (PMPD) meeting DSM-IV criteria for the diagnosis of bipolar affective disorder (BAD) were studied. Four patients had early onset PD. Four developed a severe psychiatric disorder a few years after starting dopaminergic therapy in presence of a mild motor disability and a mild cognitive impairment, with no evidence of cerebral atrophy at CT or MRI. Two patients developed a clear manic episode; the other three presented a severe depressive episode (in one case featuring a Cotard syndrome). None showed previous signs of long term L-dopa treatment syndrome (LTS), hallucinosis or other minor psychiatric disorders. The two manic episodes occurred shortly after an increase of dopaminergic therapy and in one case rapid cyclic mood fluctuations were observed. At the onset of psychiatric symptoms, all patients had an unspecific diagnosis of chronic delusional hallucinatory psychosis (CDHP).

High prevalence of hepatitis E virus infection in goats.

PubMed

Long, Feiyan; Yu, Wenhai; Yang, Chenchen; Wang, Jue; Li, Yunlong; Li, Yi; Huang, Fen

2017-11-01

Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide, primarily transmitted by fecal-oral route. Zoonotic transmission of HEV from HEV-infected pigs (pork) or cows (milk) to human or non-human primate has been confirmed, but the risk of HEV in goat is still rarely assessed. In the present study, stool, blood, tissues, and milk of goat were collected for HEV infection investigation from Dali City of Yunnan Province in China, where raw mutton and goat milk are traditionally consumed. Surprisingly, a high prevalence of HEV infection in goat was found. Phylogenetic analysis revealed that all HEV isolates from goat belong to genotype 4 and subtype 4h, and shared a high similarity homology (>99.6%) with HEV isolated from human, swine, and cows in the same area. Results suggested that goats are a previously unrecognized HEV host. © 2017 Wiley Periodicals, Inc.

Cell birth, cell death, cell diversity and DNA breaks: how do they all fit together?

NASA Technical Reports Server (NTRS)

Gilmore, E. C.; Nowakowski, R. S.; Caviness, V. S. Jr; Herrup, K.

2000-01-01

Substantial death of migrating and differentiating neurons occurs within the developing CNS of mice that are deficient in genes required for repair of double-stranded DNA breaks. These findings suggest that large-scale, yet previously unrecognized, double-stranded DNA breaks occur normally in early postmitotic and differentiating neurons. Moreover, they imply that cell death occurs if the breaks are not repaired. The cause and natural function of such breaks remains a mystery; however, their occurrence has significant implications. They might be detected by histological methods that are sensitive to DNA fragmentation and mistakenly interpreted to indicate cell death when no relationship exists. In a broader context, there is now renewed speculation that DNA recombination might be occurring during neuronal development, similar to DNA recombination in developing lymphocytes. If this is true, the target gene(s) of recombination and their significance remain to be determined.

Unusually large tsunamis frequent a currently creeping part of the Aleutian megathrust

USGS Publications Warehouse

Witter, Robert C.; Carver, G.A.; Briggs, Richard; Gelfenbaum, Guy R.; Koehler, R.D.; La Selle, SeanPaul M.; Bender, Adrian M.; Engelhart, S.E.; Hemphill-Haley, E.; Hill, Troy D.

2016-01-01

Current models used to assess earthquake and tsunami hazards are inadequate where creep dominates a subduction megathrust. Here we report geological evidence for large tsunamis, occurring on average every 300–340 years, near the source areas of the 1946 and 1957 Aleutian tsunamis. These areas bookend a postulated seismic gap over 200 km long where modern geodetic measurements indicate that the megathrust is currently creeping. At Sedanka Island, evidence for large tsunamis includes six sand sheets that blanket a lowland facing the Pacific Ocean, rise to 15 m above mean sea level, contain marine diatoms, cap terraces, adjoin evidence for scour, and date from the past 1700 years. The youngest sheet, and modern drift logs found as far as 800 m inland and >18 m elevation, likely record the 1957 tsunami. Modern creep on the megathrust coexists with previously unrecognized tsunami sources along this part of the Aleutian Subduction Zone.

Central and Peripheral Molecular Targets for Anti-Obesity Pharmacotherapy

PubMed Central

Valentino, Michael A.; Lin, Jieru E.; Waldman, Scott A.

2011-01-01

Obesity has emerged as one of the principle worldwide health concerns of the modern era, and there exists a tremendous unmet clinical need for safe and effective therapies to combat this global pandemic. The prevalence of obesity and its associated co-morbidities, including cardiovascular and metabolic diseases, has focused drug discovery and development on generating effective modalities for the treatment and prevention of obesity. Early efforts in the field of obesity pharmacotherapy centered on agents with indeterminate mechanisms of action producing treatment paradigms characterized by significant off-target effects. During the past two decades, new insights have been made into the physiologic regulation of energy balance and the subordinate central and peripheral circuits coordinating appetite, metabolism, and lipogenesis. These studies have revealed previously unrecognized molecular targets for controlling appetite and managing weight from which has emerged a new wave of targeted pharmacotherapies to prevent and control obesity. PMID:20445536

Intrinsic paleointensity bias and the long-term history of the geodynamo.

PubMed

Smirnov, Aleksey V; Kulakov, Evgeniy V; Foucher, Marine S; Bristol, Katie E

2017-02-01

Many geodynamo models predict an inverse relationship between geomagnetic reversal frequency and field strength. However, most of the absolute paleointensity data, obtained predominantly by the Thellier method from bulk volcanic rocks, fail to confirm this relationship. Although low paleointensities are commonly observed during periods of high reversal rate (notably, in the late Jurassic), higher than present-day intensity values are rare during periods of no or few reversals (superchrons). We have identified a fundamental mechanism that results in a pervasive and previously unrecognized low-field bias that affects most paleointensity data in the global database. Our results provide an explanation for the discordance between the experimental data and numerical models, and lend additional support to an inverse relationship between the reversal rate and field strength as a fundamental property of the geodynamo. We demonstrate that the accuracy of future paleointensity analyses can be improved by integration of the Thellier protocol with low-temperature demagnetizations.

Circadian rhythms constrain leaf and canopy gas exchange in an Amazonian forest

NASA Astrophysics Data System (ADS)

Doughty, Christopher E.; Goulden, Michael L.; Miller, Scott D.; da Rocha, Humberto R.

2006-08-01

We used a controlled-environment leaf gas-exchange system and the micrometeorological technique eddy covariance to determine whether circadian rhythms constrain the rates of leaf and canopy gas exchange in an Amazonian forest over a day. When exposed to continuous and constant light for 20 to 48 hours leaves of eleven of seventeen species reduced their photosynthetic rates and closed their stomata during the normally dark period and resumed active gas exchange during the normally light period. Similarly, the rate of whole-forest CO2 uptake at a predetermined irradiance declined during the late afternoon and early morning and increased during the middle of the day. We attribute these cycles to circadian rhythms that are analogous to ones that have been reported for herbaceous plants in the laboratory. The importance of endogenous gas exchange rhythms presents a previously unrecognized challenge for efforts to both interpret and model land-atmosphere energy and mass exchange.

Pulling boat hands: a unique dermatosis from coastal New England.

PubMed

Toback, A C; Korson, R; Krusinski, P A

1985-04-01

We report a previously unrecognized hand dermatosis, pulling boat hands (PBH), occurring in thirteen participants at the Outward Bound School on Hurricane Island, Maine. Painful and pruritic macules, plaques, and vesicles developed exclusively while subjects lived aboard a pulling boat, the school's open rowing/sailing craft. Nine of those affected were women and eight had Raynaud's phenomenon or vasospasm. These subjects experienced thirty episodes of PBH during May through October, 1978 to 1982. Histopathology revealed a superficial and deep lymphohistiocytic perivascular infiltrate, subepidermal blister formation, red blood cell extravasation, and dermal capillary thrombosis compatible with cold injury to the skin. All patients experienced prolonged percussion to their hands while rowing as well as a continuous environmental exposure to cold air, wind, humidity, ocean spume, and precipitation. These clinical, histopathologic, and environmental findings suggest a unique syndrome that combines the vascular effects of mechanical trauma from rowing with those of nonfreezing cold injury.

Hypoxia induces copper stable isotope fractionation in hepatocellular carcinoma, in a HIF-independent manner.

PubMed

Bondanese, Victor P; Lamboux, Aline; Simon, Melanie; Lafont, Jérôme E; Albalat, Emmanuelle; Pichat, Sylvain; Vanacker, Jean-Marc; Telouk, Philippe; Balter, Vincent; Oger, Philippe; Albarède, Francis

2016-11-09

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, with increasing incidence worldwide. The unrestrained proliferation of tumour cells leads to tumour hypoxia which in turn promotes cancer aggressiveness. While changes in the concentration of copper (Cu) have long been observed upon cancerization, we have recently reported that the isotopic composition of copper is also altered in several types of cancer. In particular, we showed that in hepatocellular carcinoma, tumour tissue contains heavier copper compared to the surrounding parenchyma. However, the reasons behind such isotopic signature remained elusive. Here we show that hypoxia causes heavy copper enrichment in several human cell lines. We also demonstrate that this effect of hypoxia is pH, HIF-1 and -2 independent. Our data identify a previously unrecognized cellular process associated with hypoxia, and suggests that in vivo tumour hypoxia determines copper isotope fractionation in HCC and other solid cancers.

Molecular ecology of hydrothermal vent microbial communities.

PubMed

Jeanthon, C

2000-02-01

The study of the structure and diversity of hydrothermal vent microbial communities has long been restricted to the morphological description of microorganisms and the use of enrichment culture-based techniques. Until recently the identification of the culturable fraction required the isolation of pure cultures followed by testing for multiple physiological and biochemical traits. However, peculiar inhabitants of the hydrothermal ecosystem such as the invertebrate endosymbionts and the dense microbial mat filaments have eluded laboratory cultivation. Substantial progress has been achieved in recent years in techniques for the identification of microorganisms in natural environments. Application of molecular approaches has revealed the existence of unique and previously unrecognized microorganisms. These have provided fresh insight into the ecology, diversity and evolution of mesophilic and thermophilic microbial communities from the deep-sea hydrothermal ecosystem. This review reports the main discoveries made through the introduction of these powerful techniques in the study of deep-sea hydrothermal vent microbiology.

Intrinsic paleointensity bias and the long-term history of the geodynamo

PubMed Central

Smirnov, Aleksey V.; Kulakov, Evgeniy V.; Foucher, Marine S.; Bristol, Katie E.

2017-01-01

Many geodynamo models predict an inverse relationship between geomagnetic reversal frequency and field strength. However, most of the absolute paleointensity data, obtained predominantly by the Thellier method from bulk volcanic rocks, fail to confirm this relationship. Although low paleointensities are commonly observed during periods of high reversal rate (notably, in the late Jurassic), higher than present-day intensity values are rare during periods of no or few reversals (superchrons). We have identified a fundamental mechanism that results in a pervasive and previously unrecognized low-field bias that affects most paleointensity data in the global database. Our results provide an explanation for the discordance between the experimental data and numerical models, and lend additional support to an inverse relationship between the reversal rate and field strength as a fundamental property of the geodynamo. We demonstrate that the accuracy of future paleointensity analyses can be improved by integration of the Thellier protocol with low-temperature demagnetizations. PMID:28246644

Volcanic Structures Within Niger and Dao Valles, Mars, and Implications for Outflow Channel Evolution and Hellas Basin Rim Development

NASA Astrophysics Data System (ADS)

Korteniemi, J.; Kukkonen, S.

2018-04-01

Outflow channel formation on the eastern Hellas rim region is traditionally thought to have been triggered by activity phases of the nearby volcanoes Hadriacus and Tyrrhenus Montes: As a result of volcanic heating subsurface volatiles were mobilized. It is, however, under debate, whether eastern Hellas volcanism was in fact more extensive, and if there were volcanic centers separate from the identified central volcanoes. This work describes previously unrecognized structures in the Niger-Dao Valles outflow channel complex. We interpret them as volcanic edifices: cones, a shield, and a caldera. The structures provide evidence of an additional volcanic center within the valles and indicate volcanic activity both prior to and following the formation of the outflow events. They expand the extent, type, and duration of volcanic activity in the Circum-Hellas Volcanic Province and provide new information on interaction between volcanism and fluvial activity.

Multidrug Transport Protein NorM from Vibrio cholerae Simultaneously Couples to Sodium- and Proton-Motive Force*

PubMed Central

Jin, Yoonhee; Nair, Asha; van Veen, Hendrik W.

2014-01-01

Membrane transporters belonging to the multidrug and toxic compound extrusion family mediate the efflux of unrelated pharmaceuticals from the interior of the cell in organisms ranging from bacteria to human. These proteins are thought to fall into two classes that couple substrate efflux to the influx of either Na+ or H+. We studied the energetics of drug extrusion by NorM from Vibrio cholerae in proteoliposomes in which purified NorM protein was functionally reconstituted in an inside-out orientation. We establish that NorM simultaneously couples to the sodium-motive force and proton-motive force, and biochemically identify protein regions and residues that play important roles in Na+ or H+ binding. As the positions of protons are not available in current medium and high-resolution crystal structures of multidrug and toxic compound extrusion transporters, our findings add a previously unrecognized parameter to mechanistic models based of these structures. PMID:24711447

Voltage controlling mechanisms in low resistivity silicon solar cells: A unified approach

NASA Technical Reports Server (NTRS)

Weizer, V. G.; Swartz, C. K.; Hart, R. E.; Godlewski, M. P.

1984-01-01

An experimental technique capable of resolving the dark saturation current into its base and emitter components is used as the basis of an analysis in which the voltage limiting mechanisms were determined for a variety of high voltage, low resistivity silicon solar cells. The cells studied include the University of Florida hi-low emitter cell, the NASA and the COMSAT multi-step diffused cells, the Spire Corporation ion-implanted emitter cell, and the University of New South Wales MINMIS and MINP cells. The results proved to be, in general, at variance with prior expectations. Most surprising was the finding that the MINP and the MINMIS voltage improvements are due, to a considerable extent, to a previously unrecognized optimization of the base component of the saturation current. This result is substantiated by an independent analysis of the material used to fabricate these devices.

Voltage controlling mechanisms in low resistivity silicon solar cells - A unified approach

NASA Technical Reports Server (NTRS)

Weizer, V. G.; Swartz, C. K.; Hart, R. E.; Godlewski, M. P.

1984-01-01

An experimental technique capable of resolving the dark saturation current into its base and emitter components is used as the basis of an analysis in which the voltage limiting mechanisms were determined for a variety of high voltage, low resistivity silicon solar cells. The cells studied include the University of Florida hi-low emitter cell, the NASA and the COMSAT multi-step diffused cells, the Spire Corporation ion-implanted emitter cell, and the University of New South Wales MINMIS and MINP cells. The results proved to be, in general, at variance with prior expectations. Most surprising was the finding that the MINP and the MINMIS voltage improvements are due, to a considerable extent, to a previously unrecognized optimization of the base component of the saturation current. This result is substantiated by an independent analysis of the material used to fabricate these devices.

Peroxidasin contributes to lung host defense by direct binding and killing of gram-negative bacteria.

PubMed

Shi, Ruizheng; Cao, Zehong; Li, Hong; Graw, Jochen; Zhang, Guogang; Thannickal, Victor J; Cheng, Guangjie

2018-05-01

Innate immune recognition is classically mediated by the interaction of host pattern-recognition receptors and pathogen-associated molecular patterns; this triggers a series of downstream signaling events that facilitate killing and elimination of invading pathogens. In this report, we provide the first evidence that peroxidasin (PXDN; also known as vascular peroxidase-1) directly binds to gram-negative bacteria and mediates bactericidal activity, thus, contributing to lung host defense. PXDN contains five leucine-rich repeats and four immunoglobulin domains, which allows for its interaction with lipopolysaccharide, a membrane component of gram-negative bacteria. Bactericidal activity of PXDN is mediated via its capacity to generate hypohalous acids. Deficiency of PXDN results in a failure to eradicate Pseudomonas aeruginosa and increased mortality in a murine model of Pseudomonas lung infection. These observations indicate that PXDN mediates previously unrecognized host defense functions against gram-negative bacterial pathogens.

Elevated prostacyclin biosynthesis in mice impacts memory and anxiety-like behavior.

PubMed

Vollert, Craig; Ohia, Odochi; Akasaka, Hironari; Berridge, Casey; Ruan, Ke-He; Eriksen, Jason L

2014-01-01

Prostacyclin is an endogenous lipid metabolite with properties of vasodilation and anti-platelet aggregation. While the effects of prostacyclin on the vascular protection have been well-documented, the role of this eicosanoid in the central nervous system has not been extensively studied. Recently, a transgenic mouse containing a hybrid enzyme, of cyclooxygenase-1 linked to prostacyclin synthase, was developed that produces elevated levels of prostacyclin in vivo. The goal of this study was to investigate whether increased prostacyclin biosynthesis could affect behavioral phenotypes in mice. Our results uncovered that elevated levels of prostacyclin broadly affect both cognitive and non-cognitive behaviors, including decreased anxiety-like behavior and improved learning in the fear-conditioning memory test. This study demonstrates that prostacyclin plays an important, but previously unrecognized, role in central nervous system function and behavior. Copyright © 2013 Elsevier B.V. All rights reserved.

Estimation of the Rate of Unrecognized Cross-Contamination with Mycobacterium tuberculosis in London Microbiology Laboratories

PubMed Central

Ruddy, M.; McHugh, T. D.; Dale, J. W.; Banerjee, D.; Maguire, H.; Wilson, P.; Drobniewski, F.; Butcher, P.; Gillespie, S. H.

2002-01-01

Isolates from patients with confirmed tuberculosis from London were collected over 2.5 years between 1995 and 1997. Restriction fragment length polymorphism (RFLP) analysis was performed by the international standard technique as part of a multicenter epidemiological study. A total of 2,779 samples representing 2,500 individual patients from 56 laboratories were examined. Analysis of these samples revealed a laboratory cross-contamination rate of between 0.54%, when only presumed cases of cross-contamination were considered, and 0.93%, when presumed and possible cases were counted. Previous studies suggest an extremely wide range of laboratory cross-contamination rates of between 0.1 and 65%. These data indicate that laboratory cross-contamination has not been a common problem in routine practice in the London area, but in several incidents patients did receive full courses of therapy that were probably unnecessary. PMID:12409381

Marine environment pollution: The contribution of mass spectrometry to the study of seawater.

PubMed

Magi, Emanuele; Di Carro, Marina

2016-09-09

The study of marine pollution has been traditionally addressed to persistent chemicals, generally known as priority pollutants; a current trend in environmental analysis is a shift toward "emerging pollutants," defined as newly identified or previously unrecognized contaminants. The present review is focused on the peculiar contribution of mass spectrometry (MS) to the study of pollutants in the seawater compartment. The work is organized in five paragraphs where the most relevant groups of pollutants, both "classical" and "emerging," are presented and discussed, highlighting the relative data obtained by the means of different MS techniques. The hyphenation of MS and separative techniques, together with the development of different ion sources, makes MS and tandem MS the analytical tool of choice for the determination of trace organic contaminants in seawater. © 2016 Wiley Periodicals, Inc. Mass Spec Rev. © 2016 Wiley Periodicals, Inc.

Dietary cholesterol promotes repair of demyelinated lesions in the adult brain.

PubMed

Berghoff, Stefan A; Gerndt, Nina; Winchenbach, Jan; Stumpf, Sina K; Hosang, Leon; Odoardi, Francesca; Ruhwedel, Torben; Böhler, Carolin; Barrette, Benoit; Stassart, Ruth; Liebetanz, David; Dibaj, Payam; Möbius, Wiebke; Edgar, Julia M; Saher, Gesine

2017-01-24

Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes.

Dietary cholesterol promotes repair of demyelinated lesions in the adult brain

PubMed Central

Berghoff, Stefan A.; Gerndt, Nina; Winchenbach, Jan; Stumpf, Sina K.; Hosang, Leon; Odoardi, Francesca; Ruhwedel, Torben; Böhler, Carolin; Barrette, Benoit; Stassart, Ruth; Liebetanz, David; Dibaj, Payam; Möbius, Wiebke; Edgar, Julia M.; Saher, Gesine

2017-01-01

Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes. PMID:28117328

Celiac disease: progress towards diagnosis and definition of pathogenic mechanisms.

PubMed

Rossi, Mauro; Bot, Adrian

2011-08-01

The current issue of the International Reviews of Immunology is dedicated entirely to Celiac Disease (CD). Recent development of additional biomarkers and diagnostics resulted in a sharp revision of the prevalence of this condition, with a previously unrecognized subclinical occurrence in the adult population. This was paralleled by groundbreaking progress in understanding its molecular pathogenesis: while gluten-derived peptides activate the innate immunity, post-translationally modified gluten elicits an adaptive immunity. These arms amplify each other, resulting in a self- perpetuating autoimmune condition, influenced by disturbances of the gut flora and mucus chemistry. The process evolves dramatically in a subset of patients with vulnerable immune homeostasis (eg. Treg cells) explaining the progressive, aggravating syndrome in the clinically overt version of CD. In depth understanding of the pathogenesis of CD thus creates the premises of developing novel, more accurate animal models that should support a rationale development of new prophylactic and therapeutic interventions.

Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level

NASA Astrophysics Data System (ADS)

Swiers, Gemma; Baumann, Claudia; O'Rourke, John; Giannoulatou, Eleni; Taylor, Stephen; Joshi, Anagha; Moignard, Victoria; Pina, Cristina; Bee, Thomas; Kokkaliaris, Konstantinos D.; Yoshimoto, Momoko; Yoder, Mervin C.; Frampton, Jon; Schroeder, Timm; Enver, Tariq; Göttgens, Berthold; de Bruijn, Marella F. T. R.

2013-12-01

Haematopoietic stem cells (HSCs) are the founding cells of the adult haematopoietic system, born during ontogeny from a specialized subset of endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic transition (EHT). Although recently imaged in real time, the underlying mechanism of EHT is still poorly understood. We have generated a Runx1 +23 enhancer-reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout embryonic development. Here we perform functional analysis of over 1,800 and transcriptional analysis of 268 single 23GFP+ HE cells to explore the onset of EHT at the single-cell level. We show that initiation of the haematopoietic programme occurs in cells still embedded in the endothelial layer, and is accompanied by a previously unrecognized early loss of endothelial potential before HSCs emerge. Our data therefore provide important insights on the timeline of early haematopoietic commitment.

Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease

PubMed Central

Uderhardt, Stefan; Ackermann, Jochen A.; Fillep, Tobias; Hammond, Victoria J.; Willeit, Johann; Stark, Konstantin; Rossaint, Jan; Schubert, Irene; Mielenz, Dirk; Dietel, Barbara; Raaz-Schrauder, Dorette; Ay, Cihan; Thaler, Johannes; Heim, Christian; Collins, Peter W.; Schabbauer, Gernot; Mackman, Nigel; Voehringer, David; Nadler, Jerry L.; Lee, James J.; Massberg, Steffen; Rauh, Manfred; O’Donnell, Valerie B.

2017-01-01

Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase–derived hydroxyeicosatetraenoic acid–phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease. PMID:28566277

Nuclear and mitochondrial markers reveal evidence for genetically segregated cryptic speciation in giant Pacific octopuses from Prince William Sound, Alaska

USGS Publications Warehouse

Toussaint, Rebecca K.; Scheel, David; Sage, G.K.; Talbot, S.L.

2012-01-01

Multiple species of large octopus are known from the north Pacific waters around Japan, however only one large species is known in the Gulf of Alaska (the giant Pacific octopus, Enteroctopus dofleini). Current taxonomy of E. dofleini is based on geographic and morphological characteristics, although with advances in genetic technology that is changing. Here, we used two mitochondrial genes (cytochrome b and cytochrome oxidase I), three nuclear genes (rhodopsin, octopine dehydrogenase, and paired-box 6), and 18 microsatellite loci for phylogeographic and phylogenetic analyses of octopuses collected from across southcentral and the eastern Aleutian Islands (Dutch Harbor), Alaska. Our results suggest the presence of a cryptic Enteroctopus species that is allied to, but distinguished from E. dofleini in Prince William Sound, Alaska. Existence of an undescribed and previously unrecognized taxon raises important questions about the taxonomy of octopus in southcentral Alaska waters.

A chemical biology approach to interrogate quorum-sensing regulated behaviors at the molecular and cellular level.

PubMed

Lowery, Colin A; Matamouros, Susana; Niessen, Sherry; Zhu, Jie; Scolnick, Jonathan; Lively, Jenny M; Cravatt, Benjamin F; Miller, Samuel I; Kaufmann, Gunnar F; Janda, Kim D

2013-07-25

Small molecule probes have been used extensively to explore biologic systems and elucidate cellular signaling pathways. In this study, we use an inhibitor of bacterial communication to monitor changes in the proteome of Salmonella enterica serovar Typhimurium with the aim of discovering unrecognized processes regulated by AI-2-based quorum-sensing (QS), a mechanism of bacterial intercellular communication that allows for the coordination of gene expression in a cell density-dependent manner. In S. typhimurium, this system regulates the uptake and catabolism of intercellular signals and has been implicated in pathogenesis, including the invasion of host epithelial cells. We demonstrate that our QS antagonist is capable of selectively inhibiting the expression of known QS-regulated proteins in S. typhimurium, thus attesting that QS inhibitors may be used to confirm proposed and elucidate previously unidentified QS pathways without relying on genetic manipulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hot moments in spawning aggregations: implications for ecosystem-scale nutrient cycling

NASA Astrophysics Data System (ADS)

Archer, Stephanie K.; Allgeier, Jacob E.; Semmens, Brice X.; Heppell, Scott A.; Pattengill-Semmens, Christy V.; Rosemond, Amy D.; Bush, Phillippe G.; McCoy, Croy M.; Johnson, Bradley C.; Layman, Craig A.

2015-03-01

Biogeochemical hot moments occur when a temporary increase in availability of one or more limiting reactants results in elevated rates of biogeochemical reactions. Many marine fish form transient spawning aggregations, temporarily increasing their local abundance and thus nutrients supplied via excretion at the aggregation site. In this way, nutrients released by aggregating fish could create a biogeochemical hot moment. Using a combination of empirical and modeling approaches, we estimate nitrogen and phosphorus supplied by aggregating Nassau grouper ( Epinephelus striatus). Data suggest aggregating grouper supply up to an order-of-magnitude more nitrogen and phosphorus than daily consumer-derived nutrient supply on coral reefs without aggregating fish. Comparing current and historic aggregation-level excretion estimates shows that overfishing reduced nutrients supplied by aggregating fish by up to 87 %. Our study illustrates a previously unrecognized ecosystem viewpoint regarding fish spawning aggregations and provides an additional perspective on the repercussions of their overexploitation.

Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk

PubMed Central

Zhu, Weifei; Gregory, Jill C.; Org, Elin; Buffa, Jennifer A.; Gupta, Nilaksh; Wang, Zeneng; Li, Lin; Fu, Xiaoming; Wu, Yuping; Mehrabian, Margarete; Sartor, R. Balfour; McIntyre, Thomas M.; Silverstein, Roy L.; Tang, W.H. Wilson; DiDonato, Joseph A.; Brown, J. Mark; Lusis, Aldons J.; Hazen, Stanley L.

2016-01-01

SUMMARY Normal platelet function is critical to blood hemostasis and maintenance of a closed circulatory system. Heightened platelet reactivity, however, is associated with cardiometabolic diseases and enhanced potential for thrombotic events. We now show gut microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to platelet hyperreactivity and enhanced thrombosis potential. Plasma TMAO levels in subjects (N>4000) independently predicted incident (3 yr) thrombosis (heart attack, stroke) risk. Direct exposure of platelets to TMAO enhanced submaximal stimulus-dependent platelet activation from multiple agonists through augmented Ca2+ release from intracellular stores. Animal model studies employing dietary choline or TMAO, germ-free mice, and microbial transplantation, collectively confirm a role for gut microbiota and TMAO in modulating platelet hyperresponsiveness and thrombosis potential, and identify microbial taxa associated with plasma TMAO and thrombosis potential. Collectively, the present results reveal a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thrombosis risk. PMID:26972052

Structure of the non-redox-active tungsten/[4Fe:4S] enzyme acetylene hydratase.

PubMed

Seiffert, Grazyna B; Ullmann, G Matthias; Messerschmidt, Albrecht; Schink, Bernhard; Kroneck, Peter M H; Einsle, Oliver

2007-02-27

The tungsten-iron-sulfur enzyme acetylene hydratase stands out from its class because it catalyzes a nonredox reaction, the hydration of acetylene to acetaldehyde. Sequence comparisons group the protein into the dimethyl sulfoxide reductase family, and it contains a bis-molybdopterin guanine dinucleotide-ligated tungsten atom and a cubane-type [4Fe:4S] cluster. The crystal structure of acetylene hydratase at 1.26 A now shows that the tungsten center binds a water molecule that is activated by an adjacent aspartate residue, enabling it to attack acetylene bound in a distinct, hydrophobic pocket. This mechanism requires a strong shift of pK(a) of the aspartate, caused by a nearby low-potential [4Fe:4S] cluster. To access this previously unrecognized W-Asp active site, the protein evolved a new substrate channel distant from where it is found in other molybdenum and tungsten enzymes.

Supervolcanoes within an ancient volcanic province in Arabia Terra, Mars.

PubMed

Michalski, Joseph R; Bleacher, Jacob E

2013-10-03

Several irregularly shaped craters located within Arabia Terra, Mars, represent a new type of highland volcanic construct and together constitute a previously unrecognized Martian igneous province. Similar to terrestrial supervolcanoes, these low-relief paterae possess a range of geomorphic features related to structural collapse, effusive volcanism and explosive eruptions. Extruded lavas contributed to the formation of enigmatic highland ridged plains in Arabia Terra. Outgassed sulphur and erupted fine-grained pyroclastics from these calderas probably fed the formation of altered, layered sedimentary rocks and fretted terrain found throughout the equatorial region. The discovery of a new type of volcanic construct in the Arabia volcanic province fundamentally changes the picture of ancient volcanism and climate evolution on Mars. Other eroded topographic basins in the ancient Martian highlands that have been dismissed as degraded impact craters should be reconsidered as possible volcanic constructs formed in an early phase of widespread, disseminated magmatism on Mars.

Factoring stream turbulence into global assessments of nitrogen pollution.

PubMed

Grant, Stanley B; Azizian, Morvarid; Cook, Perran; Boano, Fulvio; Rippy, Megan A

2018-03-16

The discharge of excess nitrogen to streams and rivers poses an existential threat to both humans and ecosystems. A seminal study of headwater streams across the United States concluded that in-stream removal of nitrate is controlled primarily by stream chemistry and biology. Reanalysis of these data reveals that stream turbulence (in particular, turbulent mass transfer across the concentration boundary layer) imposes a previously unrecognized upper limit on the rate at which nitrate is removed from streams. The upper limit closely approximates measured nitrate removal rates in streams with low concentrations of this pollutant, a discovery that should inform stream restoration designs and efforts to assess the effects of nitrogen pollution on receiving water quality and the global nitrogen cycle. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Entropy of the Bose-Einstein-condensate ground state: Correlation versus ground-state entropy

NASA Astrophysics Data System (ADS)

Kim, Moochan B.; Svidzinsky, Anatoly; Agarwal, Girish S.; Scully, Marlan O.

2018-01-01

Calculation of the entropy of an ideal Bose-Einstein condensate (BEC) in a three-dimensional trap reveals unusual, previously unrecognized, features of the canonical ensemble. It is found that, for any temperature, the entropy of the Bose gas is equal to the entropy of the excited particles although the entropy of the particles in the ground state is nonzero. We explain this by considering the correlations between the ground-state particles and particles in the excited states. These correlations lead to a correlation entropy which is exactly equal to the contribution from the ground state. The correlations themselves arise from the fact that we have a fixed number of particles obeying quantum statistics. We present results for correlation functions between the ground and excited states in a Bose gas, so as to clarify the role of fluctuations in the system. We also report the sub-Poissonian nature of the ground-state fluctuations.

CD4 on CD8+ T cells directly enhances effector function and is a target for HIV infection

NASA Astrophysics Data System (ADS)

Kitchen, Scott G.; Jones, Nicole R.; Laforge, Stuart; Whitmire, Jason K.; Vu, Bien-Aimee; Galic, Zoran; Brooks, David G.; Brown, Stephen J.; Kitchen, Christina M. R.; Zack, Jerome A.

2004-06-01

Costimulation of purified CD8+ T lymphocytes induces de novo expression of CD4, suggesting a previously unrecognized function for this molecule in the immune response. Here, we report that the CD4 molecule plays a direct role in CD8+ T cell function by modulating expression of IFN- and Fas ligand, two important CD8+ T cell effector molecules. CD4 expression also allows infection of CD8 cells by HIV, which results in down-regulation of the CD4 molecule and impairs the induction of IFN-, Fas ligand, and the cytotoxic responses of activated CD8+ T cells. Thus, the CD4 molecule plays a direct role in CD8 T cell function, and infection of these cells by HIV provides an additional reservoir for the virus and also may contribute to the immunodeficiency seen in HIV disease.

Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics.

PubMed

Cowell, Annie N; Istvan, Eva S; Lukens, Amanda K; Gomez-Lorenzo, Maria G; Vanaerschot, Manu; Sakata-Kato, Tomoyo; Flannery, Erika L; Magistrado, Pamela; Owen, Edward; Abraham, Matthew; LaMonte, Gregory; Painter, Heather J; Williams, Roy M; Franco, Virginia; Linares, Maria; Arriaga, Ignacio; Bopp, Selina; Corey, Victoria C; Gnädig, Nina F; Coburn-Flynn, Olivia; Reimer, Christin; Gupta, Purva; Murithi, James M; Moura, Pedro A; Fuchs, Olivia; Sasaki, Erika; Kim, Sang W; Teng, Christine H; Wang, Lawrence T; Akidil, Aslı; Adjalley, Sophie; Willis, Paul A; Siegel, Dionicio; Tanaseichuk, Olga; Zhong, Yang; Zhou, Yingyao; Llinás, Manuel; Ottilie, Sabine; Gamo, Francisco-Javier; Lee, Marcus C S; Goldberg, Daniel E; Fidock, David A; Wirth, Dyann F; Winzeler, Elizabeth A

2018-01-12

Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 Plasmodium falciparum parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This exploration of the P. falciparum resistome and druggable genome will likely guide drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms available to the malaria parasite. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Decoding sORF translation - from small proteins to gene regulation.

PubMed

Cabrera-Quio, Luis Enrique; Herberg, Sarah; Pauli, Andrea

2016-11-01

Translation is best known as the fundamental mechanism by which the ribosome converts a sequence of nucleotides into a string of amino acids. Extensive research over many years has elucidated the key principles of translation, and the majority of translated regions were thought to be known. The recent discovery of wide-spread translation outside of annotated protein-coding open reading frames (ORFs) came therefore as a surprise, raising the intriguing possibility that these newly discovered translated regions might have unrecognized protein-coding or gene-regulatory functions. Here, we highlight recent findings that provide evidence that some of these newly discovered translated short ORFs (sORFs) encode functional, previously missed small proteins, while others have regulatory roles. Based on known examples we will also speculate about putative additional roles and the potentially much wider impact that these translated regions might have on cellular homeostasis and gene regulation.

Role of chiral quantum Hall edge states in nuclear spin polarization.

PubMed

Yang, Kaifeng; Nagase, Katsumi; Hirayama, Yoshiro; Mishima, Tetsuya D; Santos, Michael B; Liu, Hongwu

2017-04-20

Resistively detected NMR (RDNMR) based on dynamic nuclear polarization (DNP) in a quantum Hall ferromagnet (QHF) is a highly sensitive method for the discovery of fascinating quantum Hall phases; however, the mechanism of this DNP and, in particular, the role of quantum Hall edge states in it are unclear. Here we demonstrate the important but previously unrecognized effect of chiral edge modes on the nuclear spin polarization. A side-by-side comparison of the RDNMR signals from Hall bar and Corbino disk configurations allows us to distinguish the contributions of bulk and edge states to DNP in QHF. The unidirectional current flow along chiral edge states makes the polarization robust to thermal fluctuations at high temperatures and makes it possible to observe a reciprocity principle of the RDNMR response. These findings help us better understand complex NMR responses in QHF, which has important implications for the development of RDNMR techniques.

The Dilemma of Mountain Roads

EPA Science Inventory

Mountain roads and trails are proliferating throughout developing Southeast Asia with severe but largely unrecognized long-term consequences related to effects of landslides and surface erosion on communities and downstream resources.

A novel mode of enhancer evolution: The Tal1 stem cell enhancer recruited a MIR element to specifically boost its activity

PubMed Central

Smith, Aileen M.; Sanchez, Maria-Jose; Follows, George A.; Kinston, Sarah; Donaldson, Ian J.; Green, Anthony R.; Göttgens, Berthold

2008-01-01

Altered cis-regulation is thought to underpin much of metazoan evolution, yet the underlying mechanisms remain largely obscure. The stem cell leukemia TAL1 (also known as SCL) transcription factor is essential for the normal development of blood stem cells and we have previously shown that the Tal1 +19 enhancer directs expression to hematopoietic stem cells, hematopoietic progenitors, and to endothelium. Here we demonstrate that an adjacent region 1 kb upstream (+18 element) is in an open chromatin configuration and carries active histone marks but does not function as an enhancer in transgenic mice. Instead, it boosts activity of the +19 enhancer both in stable transfection assays and during differentiation of embryonic stem (ES) cells carrying single-copy reporter constructs targeted to the Hprt locus. The +18 element contains a mammalian interspersed repeat (MIR) which is essential for the +18 function and which was transposed to the Tal1 locus ∼160 million years ago at the time of the mammalian/marsupial branchpoint. Our data demonstrate a previously unrecognized mechanism whereby enhancer activity is modulated by a transposon exerting a “booster” function which would go undetected by conventional transgenic approaches. PMID:18687876

GDH3 encodes a glutamate dehydrogenase isozyme, a previously unrecognized route for glutamate biosynthesis in Saccharomyces cerevisiae.

PubMed Central

Avendaño, A; Deluna, A; Olivera, H; Valenzuela, L; Gonzalez, A

1997-01-01

It has been considered that the yeast Saccharomyces cerevisiae, like many other microorganisms, synthesizes glutamate through the action of NADP+-glutamate dehydrogenase (NADP+-GDH), encoded by GDH1, or through the combined action of glutamine synthetase and glutamate synthase (GOGAT), encoded by GLN1 and GLT1, respectively. A double mutant of S. cerevisiae lacking NADP+-GDH and GOGAT activities was constructed. This strain was able to grow on ammonium as the sole nitrogen source and thus to synthesize glutamate through an alternative pathway. A computer search for similarities between the GDH1 nucleotide sequence and the complete yeast genome was carried out. In addition to identifying its cognate sequence at chromosome XIV, the search found that GDH1 showed high identity with a previously recognized open reading frame (GDH3) of chromosome I. Triple mutants impaired in GDH1, GLT1, and GDH3 were obtained. These were strict glutamate auxotrophs. Our results indicate that GDH3 plays a significant physiological role, providing glutamate when GDH1 and GLT1 are impaired. This is the first example of a microorganism possessing three pathways for glutamate biosynthesis. PMID:9287019

Learning from Trending, Precursor Analysis, and System Failures

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

Youngblood, R. W.; Duffey, R. B.

2015-11-01

Models of reliability growth relate current system unreliability to currently accumulated experience. But “experience” comes in different forms. Looking back after a major accident, one is sometimes able to identify previous events or measurable performance trends that were, in some sense, signaling the potential for that major accident: potential that could have been recognized and acted upon, but was not recognized until the accident occurred. This could be a previously unrecognized cause of accidents, or underestimation of the likelihood that a recognized potential cause would actually operate. Despite improvements in the state of practice of modeling of risk and reliability,more » operational experience still has a great deal to teach us, and work has been going on in several industries to try to do a better job of learning from experience before major accidents occur. It is not enough to say that we should review operating experience; there is too much “experience” for such general advice to be considered practical. The paper discusses the following: 1. The challenge of deciding what to focus on in analysis of operating experience. 2. Comparing what different models of learning and reliability growth imply about trending and precursor analysis.« less

Relict or colonizer? Extinction and range expansion of penguins in southern New Zealand

PubMed Central

Boessenkool, Sanne; Austin, Jeremy J.; Worthy, Trevor H.; Scofield, Paul; Cooper, Alan; Seddon, Philip J.; Waters, Jonathan M.

2008-01-01

Recent human expansion into the Pacific initiated a dramatic avian extinction crisis, and surviving taxa are typically interpreted as declining remnants of previously abundant populations. As a case in point, New Zealand's endangered yellow-eyed penguin (Megadyptes antipodes) is widely considered to have been more abundant and widespread in the past. By contrast, our genetic and morphological analyses of prehistoric, historic and modern penguin samples reveal that this species expanded its range to the New Zealand mainland only in the last few hundred years. This range expansion was apparently facilitated by the extinction of M. antipodes' previously unrecognized sister species following Polynesian settlement in New Zealand. Based on combined genetic and morphological data, we describe this new penguin species, the first known to have suffered human-mediated extinction. The range expansion of M. antipodes so soon after the extinction of its sister species supports a historic paradigmatic shift in New Zealand Polynesian culture. Additionally, such a dynamic biological response to human predation reveals a surprising and less recognized potential for species to have benefited from the extinction of their ecologically similar sister taxa and highlights the complexity of large-scale extinction events. PMID:19019791

Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map.

PubMed

Hewett, Duncan; Samuelsson, Lena; Polding, Joanne; Enlund, Fredrik; Smart, Devi; Cantone, Kathryn; See, Chee Gee; Chadha, Sapna; Inerot, Annica; Enerback, Charlotta; Montgomery, Doug; Christodolou, Chris; Robinson, Phil; Matthews, Paul; Plumpton, Mary; Wahlstrom, Jan; Swanbeck, Gunnar; Martinsson, Tommy; Roses, Allen; Riley, John; Purvis, Ian

2002-03-01

Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Here we describe the creation of a single-nucleotide polymorphism (SNP) map spanning 900-1200 kb of chromosome 3q21, which had been previously recognized as containing a psoriasis susceptibility locus, PSORS5. We genotyped 644 individuals, from 195 Swedish psoriatic families, for 19 polymorphisms. Linkage disequilibrium (LD) between marker and disease was assessed using the transmission/disequilibrium test (TDT). In the TDT analysis, alleles of three of these SNPs showed significant association with disease (P<0.05). A 160-kb interval encompassing these three SNPs was sequenced, and a coding sequence consisting of 13 exons was identified. The predicted protein shares 30-40% homology with the family of cation/chloride cotransporters. A five-marker haplotype spanning the 3' half of this gene is associated with psoriasis to a P value of 3.8<10(-5). We have called this gene SLC12A8, coding for a member of the solute carrier family 12 proteins. It belongs to a class of genes that were previously unrecognized as playing a role in psoriasis pathogenesis.

Integrative Taxonomy of Southeast Asian Snail-Eating Turtles (Geoemydidae: Malayemys) Reveals a New Species and Mitochondrial Introgression

PubMed Central

Ihlow, Flora; Vamberger, Melita; Flecks, Morris; Hartmann, Timo; Cota, Michael; Makchai, Sunchai; Meewattana, Pratheep; Dawson, Jeffrey E.; Kheng, Long; Rödder, Dennis; Fritz, Uwe

2016-01-01

Based on an integrative taxonomic approach, we examine the differentiation of Southeast Asian snail-eating turtles using information from 1863 bp of mitochondrial DNA, 12 microsatellite loci, morphology and a correlative species distribution model. Our analyses reveal three genetically distinct groups with limited mitochondrial introgression in one group. All three groups exhibit distinct nuclear gene pools and distinct morphology. Two of these groups correspond to the previously recognized species Malayemys macrocephala (Chao Phraya Basin) and M. subtrijuga (Lower Mekong Basin). The third and genetically most divergent group from the Khorat Basin represents a previously unrecognized species, which is described herein. Although Malayemys are extensively traded and used for religious release, only few studied turtles appear to be translocated by humans. Historic fluctuations in potential distributions were assessed using species distribution models (SDMs). The Last Glacial Maximum (LGM) projection of the predictive SDMs suggests two distinct glacial distribution ranges, implying that the divergence of M. macrocephala and M. subtrijuga occurred in allopatry and was triggered by Pleistocene climate fluctuations. Only the projection derived from the global circulation model MIROC reveals a distinct third glacial distribution range for the newly discovered Malayemys species. PMID:27050302

Stratigraphic variation in petrographic composition of Nanushuk Group sandstones at Slope Mountain, North Slope, Alaska: A section in Geologic studies in Alaska by the U.S. Geological Survey, 1998

USGS Publications Warehouse

Johnsson, Mark J.; Sokol, Nikolas K.

2000-01-01

Fluvial, deltaic, and marine sediments of the Nanushuk Group (Albian to Cenomanian), North Slope, Alaska, record Early Cretaceous orogenic events in the Brooks Range to the south. The 1,060-m section at Slope Mountain is part of the Lower Cretaceous Umiat Delta, shed from the Endicott and De Long Mountains subterranes in the central Brooks Range. These sandstones are litharenites dominated by metasedimentary lithic fragments. Subtle and previously unrecognized stratigraphic variations in composition (up-section increases in metasedimentary lithic fragments, volcanic lithic fragments, and quartz interpreted to be of metamorphic origin) reflect a combination of facies migration and changes in provenance associated with unroofing of the ancestral Brooks Range. We recognize stratigraphic variation in sandstone composition at Slope Mountain whereas previous workers have not, probably because of our use of finely subdivided point-counting categories. The source of the volcanic lithic fragments in the Nanushuk Group remains enigmatic; the most likely candidate is a now-eroded volcanic arc, perhaps a volcanic superstructure to granitic rocks of the Ruby terrane to the south.

Retrograde air escape via the nasolacrimal system: a previously unrecognized complication of continuous positive airway pressure in the management of obstructive sleep apnea.

PubMed

Singh, Narinder Pal; Walker, Robbie James Eades; Cowan, Fiona; Davidson, Arthur Craig; Roberts, David Newton

2014-05-01

Continuous positive airway pressure (CPAP) is the gold standard treatment for moderate to severe obstructive sleep apnoea (OSA). Eye-related side effects of CPAP are commonly attributed to a poorly sealed mask, allowing leaked air to blow over the eye. We present 3 cases where attended polysomnography (A-PSG) demonstrated CPAP-associated retrograde air escape via the nasolacrimal system (CRANS) in the absence of any mask leaks. Symptoms included dry eye, epiphora, air escape from the medial canthus, and eyelid flutter. Symptoms were controlled with a variety of surgical and nonsurgical techniques. CRANS represents a previously undescribed clinical entity. CRANS may be responsible for some CPAP-related eye side effects and possibly for rarer secondary eye complications, including conjunctivitis and corneal ulceration. CRANS should be suspected in any patient on CPAP complaining of eye symptoms. CRANS may be diagnosed through careful observation during A-PSG and confirmed by performing a "saline bubble test." Management options include nonsurgical (mask alternatives, humidification, nasopharyngeal airway) and surgical techniques (nasal airway surgery, inferior turbinate out-fracture and adhesion, injection of bulking agent around Hasner's valve).

In the Information Age, do dementia caregivers get the information they need? Semi-structured interviews to determine informal caregivers' education needs, barriers, and preferences.

PubMed

Peterson, Kendra; Hahn, Howard; Lee, Amber J; Madison, Catherine A; Atri, Alireza

2016-09-23

Most patients with dementia or cognitive impairment receive care from family members, often untrained for this challenging role. Caregivers may not access publicly available caregiving information, and caregiver education programs are not widely implemented clinically. Prior large surveys yielded broad quantitative understanding of caregiver information needs, but do not illuminate the in-depth, rich, and nuanced caregiver perspectives that can be gleaned using qualitative methodology. We aimed to understand perspectives about information sources, barriers and preferences, through semi-structured interviews with 27 caregivers. Content analysis identified important themes. We interviewed 19 women, 8 men; mean age 58.5 years; most adult children (15) or spouses (8) of the care recipient. Dementia symptoms often developed insidiously, with delayed disease acknowledgement and caregiver self-identification. While memory loss was common, behavioral symptoms were most troublesome, often initially unrecognized as disease indicators. Emerging themes: 1.) Barriers to seeking information often result from knowledge gaps, rather than reluctance to assume the caregiver role; 2.) Most caregivers currently receive insufficient information. Caregivers are open to many information sources, settings, and technologies, including referrals to other healthcare professionals, print material, and community and internet resources, but expect the primary care provider (PCP) to recommend, endorse, and guide them to specific sources. These findings replicated and expanded on results from previous quantitative surveys and, importantly, revealed a previously unrecognized essential factor: despite receiving insufficient information, caregivers place critical value on their relationship with care recipient PCPs to receive recommendations, guidance and endorsement to sources of caregiving information. Implications include: 1.) Greater public education is needed to help caregivers identify and describe diverse cognitive, functional and behavioral symptoms that lead to dementia, and recognize the benefits of early detection in accessing information regarding multi-modality management and care; 2.) Improved methods are needed for PCPs to detect and manage cognitive and behavioral changes, as well as mechanisms that facilitate the busy PCP, either directly or via referral, to provide caregiver information, education, support, and services. The critical relationship between caregivers and PCPs should not be circumvented but should be facilitated to provide more effective guidance regarding dementia caregiver needs.

Sex chromosome-specific regulation in the Drosophila male germline but little evidence for chromosomal dosage compensation or meiotic inactivation.

PubMed

Meiklejohn, Colin D; Landeen, Emily L; Cook, Jodi M; Kingan, Sarah B; Presgraves, Daven C

2011-08-01

The evolution of heteromorphic sex chromosomes (e.g., XY in males or ZW in females) has repeatedly elicited the evolution of two kinds of chromosome-specific regulation: dosage compensation--the equalization of X chromosome gene expression in males and females--and meiotic sex chromosome inactivation (MSCI)--the transcriptional silencing and heterochromatinization of the X during meiosis in the male (or Z in the female) germline. How the X chromosome is regulated in the Drosophila melanogaster male germline is unclear. Here we report three new findings concerning gene expression from the X in Drosophila testes. First, X chromosome-wide dosage compensation appears to be absent from most of the Drosophila male germline. Second, microarray analysis provides no evidence for X chromosome-specific inactivation during meiosis. Third, we confirm the previous discovery that the expression of transgene reporters driven by autosomal spermatogenesis-specific promoters is strongly reduced when inserted on the X chromosome versus the autosomes; but we show that this chromosomal difference in expression is established in premeiotic cells and persists in meiotic cells. The magnitude of the X-autosome difference in transgene expression cannot be explained by the absence of dosage compensation, suggesting that a previously unrecognized mechanism limits expression from the X during spermatogenesis in Drosophila. These findings help to resolve several previously conflicting reports and have implications for patterns of genome evolution and speciation in Drosophila.

Flank vents and graben as indicators of Late Amazonian volcanotectonic activity on Olympus Mons

NASA Astrophysics Data System (ADS)

Peters, S. I.; Christensen, P. R.

2017-03-01

Previous studies have focused on large-scale features on Olympus Mons, such as its flank terraces, the summit caldera complex, and the basal escarpment and aureole deposits. Here we identify and characterize previously unrecognized and unmapped small scale features to help further understand the volcanotectonic evolution of this enormous volcano. Using Context Camera, High Resolution Imaging Science Experiment, Thermal Emission Imaging System, High Resolution Stereo Camera Digital Terrain Model, and Mars Orbiter Laser Altimeter data, we identified and characterized the morphology and distribution of 60 flank vents and 84 grabens on Olympus Mons. We find that effusive eruptions have dominated volcanic activity on Olympus Mons in the Late Amazonian. Explosive eruptions were rare, implying volatile-poor magmas and/or a lack of magma-water interactions during the Late Amazonian. The distribution of flank vents suggests dike propagation of hundreds of kilometers and shallow magma storage. Small grabens, not previously observed in lower-resolution data, occur primarily on the lower flanks of Olympus Mons and indicate late-stage extensional tectonism. Based on superposition relationships, we have concluded two stages of development for Olympus Mons during the Late Amazonian: (1) primarily effusive resurfacing and formation of flank vents followed by (2) waning effusive volcanism and graben formation and/or reactivation. This developmental sequence resembles that proposed for Ascraeus Mons and other large Martian shields, suggesting a similar geologic evolution for these volcanoes.

Discovery and validation of information theory-based transcription factor and cofactor binding site motifs.

PubMed

Lu, Ruipeng; Mucaki, Eliseos J; Rogan, Peter K

2017-03-17

Data from ChIP-seq experiments can derive the genome-wide binding specificities of transcription factors (TFs) and other regulatory proteins. We analyzed 765 ENCODE ChIP-seq peak datasets of 207 human TFs with a novel motif discovery pipeline based on recursive, thresholded entropy minimization. This approach, while obviating the need to compensate for skewed nucleotide composition, distinguishes true binding motifs from noise, quantifies the strengths of individual binding sites based on computed affinity and detects adjacent cofactor binding sites that coordinate with the targets of primary, immunoprecipitated TFs. We obtained contiguous and bipartite information theory-based position weight matrices (iPWMs) for 93 sequence-specific TFs, discovered 23 cofactor motifs for 127 TFs and revealed six high-confidence novel motifs. The reliability and accuracy of these iPWMs were determined via four independent validation methods, including the detection of experimentally proven binding sites, explanation of effects of characterized SNPs, comparison with previously published motifs and statistical analyses. We also predict previously unreported TF coregulatory interactions (e.g. TF complexes). These iPWMs constitute a powerful tool for predicting the effects of sequence variants in known binding sites, performing mutation analysis on regulatory SNPs and predicting previously unrecognized binding sites and target genes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Immortal time bias: a frequently unrecognized threat to validity in the evaluation of postoperative radiotherapy.

PubMed

Park, Henry S; Gross, Cary P; Makarov, Danil V; Yu, James B

2012-08-01

To evaluate the influence of immortal time bias on observational cohort studies of postoperative radiotherapy (PORT) and the effectiveness of sequential landmark analysis to account for this bias. First, we reviewed previous studies of the Surveillance, Epidemiology, and End Results (SEER) database to determine how frequently this bias was considered. Second, we used SEER to select three tumor types (glioblastoma multiforme, Stage IA-IVM0 gastric adenocarcinoma, and Stage II-III rectal carcinoma) for which prospective trials demonstrated an improvement in survival associated with PORT. For each tumor type, we calculated conditional survivals and adjusted hazard ratios of PORT vs. postoperative observation cohorts while restricting the sample at sequential monthly landmarks. Sixty-two percent of previous SEER publications evaluating PORT failed to use a landmark analysis. As expected, delivery of PORT for all three tumor types was associated with improved survival, with the largest associated benefit favoring PORT when all patients were included regardless of survival. Preselecting a cohort with a longer minimum survival sequentially diminished the apparent benefit of PORT. Although the majority of previous SEER articles do not correct for it, immortal time bias leads to altered estimates of PORT effectiveness, which are very sensitive to landmark selection. We suggest the routine use of sequential landmark analysis to account for this bias. Copyright © 2012 Elsevier Inc. All rights reserved.

Immortal Time Bias: A Frequently Unrecognized Threat to Validity in the Evaluation of Postoperative Radiotherapy

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

Park, Henry S.; Gross, Cary P.; Makarov, Danil V.

2012-08-01

Purpose: To evaluate the influence of immortal time bias on observational cohort studies of postoperative radiotherapy (PORT) and the effectiveness of sequential landmark analysis to account for this bias. Methods and Materials: First, we reviewed previous studies of the Surveillance, Epidemiology, and End Results (SEER) database to determine how frequently this bias was considered. Second, we used SEER to select three tumor types (glioblastoma multiforme, Stage IA-IVM0 gastric adenocarcinoma, and Stage II-III rectal carcinoma) for which prospective trials demonstrated an improvement in survival associated with PORT. For each tumor type, we calculated conditional survivals and adjusted hazard ratios of PORTmore » vs. postoperative observation cohorts while restricting the sample at sequential monthly landmarks. Results: Sixty-two percent of previous SEER publications evaluating PORT failed to use a landmark analysis. As expected, delivery of PORT for all three tumor types was associated with improved survival, with the largest associated benefit favoring PORT when all patients were included regardless of survival. Preselecting a cohort with a longer minimum survival sequentially diminished the apparent benefit of PORT. Conclusions: Although the majority of previous SEER articles do not correct for it, immortal time bias leads to altered estimates of PORT effectiveness, which are very sensitive to landmark selection. We suggest the routine use of sequential landmark analysis to account for this bias.« less

Reverberations on the watery element: A significant, tsunamigenic historical earthquake offshore the Carolina coast

USGS Publications Warehouse

Hough, Susan E.; Munsey, Jeffrey; Ward, Steven N.

2013-01-01

We investigate an early nineteenth‐century earthquake that has been previously cataloged but not previously investigated in detail or recognized as a significant event. The earthquake struck at approximately 4:30 a.m. LT on 8 January 1817 and was widely felt throughout the southeastern and mid‐Atlantic United States. Around 11:00 a.m. the same day, an eyewitness described a 12‐inch tide that rose abruptly and agitated boats on the Delaware River near Philadelphia. We show that the timing of this tide is consistent with the predicted travel time for a tsunami generated by an offshore earthquake 6–7 hours earlier. By combining constraints provided by the shaking intensity distribution and the tsunami observation, we conclude that the 1817 earthquake had a magnitude of low‐ to mid‐M 7 and a location 800–1000 km offshore of South Carolina. Our results suggest that poorly understood offshore source zones might represent a previously unrecognized hazard to the southern and mid‐Atlantic coast. Both observational and modeling results indicate that potential tsunami hazard within Delaware Bay merits consideration: the simple geometry of the bay appears to catch and focus tsunami waves. Our preferred location for the 1817 earthquake is along a diffuse northeast‐trending zone defined by instrumentally recorded and historical earthquakes. The seismotectonic framework for this region remains enigmatic.

Rapid Serial Naming Is a Unique Predictor of Spelling in Children

ERIC Educational Resources Information Center

Savage, Robert; Pillay, Vanitha; Melidona, Santo

2008-01-01

Some previous research has shown strong associations between spelling ability and rapid automatic naming (RAN) after controls for phonological processing and nonsense-word reading ability, consistent with the double-deficit hypothesis in reading and spelling. Previous studies did not, however, control for nonsense-word spelling ability before…

Executive Functioning and Visuospatial Abilities in Bulimia Nervosa with or without a Previous History of Anorexia Nervosa.

PubMed

Degortes, Daniela; Tenconi, Elena; Santonastaso, Paolo; Favaro, Angela

2016-03-01

The aim of the present study was to investigate executive functioning and visuospatial abilities in patients with bulimia nervosa (BN), with a particular interest in exploring the impact of a previous diagnosis of anorexia nervosa (AN). Several neuropsychological tasks were administered to 89 BN patients (52 with a previous history of AN and 37 without previous AN) and 160 healthy women. A poorer performance on set-shifting measures (Wisconsin Card Sorting Test) was found only in BN patients with a previous history of AN. Decision-making abilities (Iowa Gambling Task) were significantly impaired in the whole sample of BN patients, but difficulties were more pronounced in the subgroup with previous AN. Finally, we did not find any differences in response inhibition and visuospatial abilities between the two samples of BN patients and healthy women. Our findings support the idea that cognitive abilities in patients with BN are more impaired in the presence of a prior history of AN. The clinical and treatment implications of our findings should be explored in future studies. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Meta-Analysis of Cognitive Functioning in Breast Cancer Survivors Previously Treated With Standard-Dose Chemotherapy

PubMed Central

Jim, Heather S.L.; Phillips, Kristin M.; Chait, Sari; Anne Faul, Leigh; Popa, Mihaela A.; Lee, Yun-Hsiang; Hussin, Mallory G.; Jacobsen, Paul B.; Small, Brent J.

2012-01-01

Purpose Evidence is mixed regarding long-term cognitive deficits in patients treated with chemotherapy. Previous meta-analyses have not focused specifically on the postchemotherapy period and have not incorporated several recent studies. The goal of the current study was to conduct a meta-analysis of cognitive functioning in breast cancer survivors who were treated with chemotherapy ≥ 6 months previously. Methods A search of PubMed, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library yielded 2,751 abstracts, which were independently evaluated by pairs of raters. Meta-analysis was conducted on 17 studies of 807 patients previously treated with standard-dose chemotherapy for breast cancer. Neuropsychological tests were categorized according to eight cognitive domains: attention, executive functioning, information processing, motor speed, verbal ability, verbal memory, visual memory, and visuospatial ability. Results Deficits in cognitive functioning were observed in patients treated with chemotherapy relative to controls or prechemotherapy baseline in the domains of verbal ability (g = −0.19; P < .01) and visuospatial ability (g = −0.27; P < .01). Patients treated with chemotherapy performed worse than noncancer controls in verbal ability and worse than patients treated without chemotherapy in visuospatial ability (both P < .01). Age, education, time since treatment, and endocrine therapy did not moderate observed cognitive deficits in verbal ability or visuospatial ability (all P ≥ .51). Conclusion Results indicate that, on average, observed cognitive deficits in patients with breast cancer previously treated with chemotherapy are small in magnitude and limited to the domains of verbal ability and visuospatial ability. This information can be used to inform interventions to educate patients with breast cancer regarding the long-term impact of chemotherapy on cognitive functioning. PMID:22927526

Comorbid fibromyalgia: A qualitative review of prevalence and importance.

PubMed

Fitzcharles, M-A; Perrot, S; Häuser, W

2018-05-26

Fibromyalgia (FM) may be an unrecognized cause of suffering for persons with an array of medical conditions. This is especially true for illness that is characterized by pain of any nature. Once believed to be a unique diagnosis, FM is recently reported to occur concomitantly with various rheumatic diseases, and importantly adversely impacts global health status. However, there is increasing report of FM associated with other diseases that are not defined by chronic pain. This qualitative review examines the evidence for comorbid FM in illness, and where available the effect of FM on the primary disease. Other than for musculoskeletal disorders, the published literature reporting an association of FM with illness is limited with scanty reports for some neurological, gastrointestinal, mental health and other overlapping pain conditions. Comorbid FM adversely affects both health status and outcome for rheumatic diseases, but with limited study in other diseases. When unrecognized, comorbid FM may be mistaken as poor control of the primary disease, leading to incorrect treatment decisions. FM may be a neglected condition that pervades many conditions and may contribute to the burden of illness. Physicians should be alert to the possibility of comorbid FM, and symptoms of FM should be specifically addressed. Comorbid fibromyalgia (FM) in other medical conditions is largely unrecognized. When reported as accompanying rheumatic diseases, FM adversely affects global health status. With limited reports of comorbid FM with other conditions, neglect to diagnose comorbid FM may misdirect treatments. © 2018 European Pain Federation - EFIC®.

Should we reconsider the routine use of placebo controls in clinical research?

PubMed

Avins, Andrew L; Cherkin, Daniel C; Sherman, Karen J; Goldberg, Harley; Pressman, Alice

2012-04-27

Modern clinical-research practice favors placebo controls over usual-care controls whenever a credible placebo exists. An unrecognized consequence of this preference is that clinicians are more limited in their ability to provide the benefits of the non-specific healing effects of placebos in clinical practice. We examined the issues in choosing between placebo and usual-care controls. We considered why placebo controls place constraints on clinicians and the trade-offs involved in the choice of control groups. We find that, for certain studies, investigators should consider usual-care controls, even if an adequate placebo is available. Employing usual-care controls would be of greatest value for pragmatic trials evaluating treatments to improve clinical care and for which threats to internal validity can be adequately managed without a placebo-control condition. Intentionally choosing usual-care controls, even when a satisfactory placebo exists, would allow clinicians to capture the value of non-specific therapeutic benefits that are common to all interventions. The result could be more effective, patient-centered care that makes the best use of both specific and non-specific benefits of medical interventions.

Long-term memory of heterospecific vocalizations by African lions

NASA Astrophysics Data System (ADS)

Grinnell, Jon; van Dyk, Gus; Slotow, Rob

2005-09-01

Animals that use and evaluate long-distance signals have the potential to glean valuable information about others in their environment via eavesdropping. In those areas where they coexist, African lions (Panthera leo) are a significant eavesdropper on spotted hyenas (Crocuta crocuta), often using hyena vocalizations to locate and scavenge from hyena kills. This relationship was used to test African lions' long-term memory of the vocalizations of spotted hyenas via playback experiments. Hyena whoops and a control sound (Canis lupus howls) were played to three populations of lions in South Africa: (1) lions with past experience of spotted hyenas; (2) lions with current experience; and (3) lions with no experience. The results strongly suggest that lions have the cognitive ability to remember the vocalizations of spotted hyenas even after 10 years with no contact of any kind with them. Such long-term memory of heterospecific vocalizations may be widespread in species that gain fitness benefits from eavesdropping on others, but where such species are sympatric and often interact it may pass unrecognized as short-term memory instead.

Case studies of power and control related to tobacco use during pregnancy.

PubMed

Greaves, Lorraine; Kalaw, Cecilia; Bottorff, Joan L

2007-01-01

The objective was to identify and describe elements of power and control evident in couple tobacco-related interaction patterns during pregnancy. Using a case study approach, elements of the Duluth Abuse Intervention Project Power and Control Wheel were used to examine women's experiences of tobacco reduction during pregnancy and post partum. Three cases were selected from a larger qualitative sample, using a maximum variation sampling approach. Although no direct evidence of partner abuse or violence accompanying partner efforts to influence women's smoking was described, most of the elements of power and control were present in the case study, and appeared to cause an emotional toll and a negative impact on women's ability to freely express their views about their own tobacco use. Elements of power and control, however subtle, are potentially important and unrecognized dimensions of women's tobacco reduction experiences. Additional care and attention should be taken in designing tobacco reduction interventions and policies directed at pregnant and post partum women and their partners to reduce the possibility that these interventions may contribute to the use of power and control.

Affective forecasting: an unrecognized challenge in making serious health decisions.

PubMed

Halpern, Jodi; Arnold, Robert M

2008-10-01

Patients facing medical decisions that will impact quality of life make assumptions about how they will adjust emotionally to living with health declines and disability. Despite abundant research on decision-making, we have no direct research on how accurately patients envision their future well-being and how this influences their decisions. Outside medicine, psychological research on "affective forecasting" consistently shows that people poorly predict their future ability to adapt to adversity. This finding is important for medicine, since many serious health decisions hinge on quality-of-life judgments. We describe three specific mechanisms for affective forecasting errors that may influence health decisions: focalism, in which people focus more on what will change than on what will stay the same; immune neglect, in which they fail to envision how their own coping skills will lessen their unhappiness; and failure to predict adaptation, in which people fail to envision shifts in what they value. We discuss emotional and social factors that interact with these cognitive biases. We describe how caregivers can recognize these biases in the clinical setting and suggest interventions to help patients recognize and address affective forecasting errors.

Patient engagement: four case studies that highlight the potential for improved health outcomes and reduced costs.

PubMed

Laurance, Jeremy; Henderson, Sarah; Howitt, Peter J; Matar, Mariam; Al Kuwari, Hanan; Edgman-Levitan, Susan; Darzi, Ara

2014-09-01

The energy of patients and members of the public worldwide who care about improving health is a huge, but still largely unrecognized and untapped, resource. The aim of patient engagement is to shift the clinical paradigm from determining "what is the matter?" to discovering "what matters to you?" This article presents four case studies from around the world that highlight the proven and potential abilities of increased patient engagement to improve health outcomes and reduce costs, while extending the reach of treatment and diagnostic programs into the community. The cases are an online mental health community in the United Kingdom, a genetic screening program in the United Arab Emirates, a World Health Organization checklist for new mothers, and a hospital-based patient engagement initiative in the United States. Evidence from these and similar endeavors suggests that closer collaboration on the part of patients, families, health care providers, health care systems, and policy makers at multiple levels could help diverse nations provide more effective and population-appropriate health care with fewer resources. Project HOPE—The People-to-People Health Foundation, Inc.

Some Neglected Economic Factors behind Recent Tax and Spending Limitation Movements.

ERIC Educational Resources Information Center

Boskin, Michael J.

1979-01-01

The demand for tax and spending limitations is caused primarily by the generally unrecognized complete lack of growth in real private income since 1973. Journal availability: see EA 511 898. (Author/IRT)

Hope: A Panacea Unrecognized

PubMed Central

Obayuwana, Alphonsus O.

1980-01-01

This paper identifies stress as a common and constant irritation to human homeostasis, evaluates the role of hope in the maintenance of health, and recommends a method of anticipatory care for securing optimum health for mankind. PMID:7373668

Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa

PubMed Central

Folarin, Onikepe A.; Grove, Jessica N.; Odia, Ikponmwonsa; Ehiane, Philomena E.; Omoniwa, Omowunmi; Omoregie, Omigie; Jiang, Pan-Pan; Yozwiak, Nathan L.; Matranga, Christian B.; Yang, Xiao; Gire, Stephen K.; Winnicki, Sarah; Tariyal, Ridhi; Schaffner, Stephen F.; Okokhere, Peter O.; Okogbenin, Sylvanus; Akpede, George O.; Asogun, Danny A.; Agbonlahor, Dennis E.; Walker, Peter J.; Tesh, Robert B.; Levin, Joshua Z.; Garry, Robert F.; Sabeti, Pardis C.; Happi, Christian T.

2015-01-01

Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance. PMID:25781465

Prevalence of unrecognized diabetes, prediabetes and metabolic syndrome in patients undergoing elective percutaneous coronary intervention.

PubMed

Balakrishnan, Revathi; Berger, Jeffrey S; Tully, Lisa; Vani, Anish; Shah, Binita; Burdowski, Joseph; Fisher, Edward; Schwartzbard, Arthur; Sedlis, Steven; Weintraub, Howard; Underberg, James A; Danoff, Ann; Slater, James A; Gianos, Eugenia

2015-09-01

Diabetes mellitus (DM) and metabolic syndrome are important targets for secondary prevention in cardiovascular disease. However, the prevalence in patients undergoing elective percutaneous coronary intervention is not well defined. We aimed to analyse the prevalence and characteristics of patients undergoing percutaneous coronary intervention with previously unrecognized prediabetes, diabetes and metabolic syndrome. Data were collected from 740 patients undergoing elective percutaneous coronary intervention between November 2010 and March 2013 at a tertiary referral center. Prevalence of DM and prediabetes was evaluated using Haemoglobin A1c (A1c ≥ 6.5% for DM, A1c 5.7-6.4% for prediabetes). A modified definition was used for metabolic syndrome [three or more of the following criteria: body mass index ≥30 kg/m2; triglycerides ≥ 150 mg/dL; high density lipoprotein <40 mg/dL in men and <50 mg/dL in women; systolic blood pressure ≥ 130 mmHg and/or diastolic ≥ 85 mmHg; and A1c ≥ 5.7% or on therapy]. Mean age was 67 years, median body mass index was 28.2 kg/m(2) and 39% had known DM. Of those without known DM, 8.3% and 58.5% met A1c criteria for DM and for prediabetes at time of percutaneous coronary intervention. Overall, 54.9% met criteria for metabolic syndrome (69.2% of patients with DM and 45.8% of patients without DM). Among patients undergoing elective percutaneous coronary intervention, a substantial number were identified with a new DM, prediabetes, and/or metabolic syndrome. Routine screening for an abnormal glucometabolic state at the time of revascularization may be useful for identifying patients who may benefit from additional targeting of modifiable risk factors. Copyright © 2015 John Wiley & Sons, Ltd.

Screening for autism identifies behavioral disorders in children functional defecation disorders.

PubMed

Kuizenga-Wessel, Sophie; Di Lorenzo, Carlo; Nicholson, Lisa M; Butter, Eric M; Ratliff-Schaub, Karen L; Benninga, Marc A; Williams, Kent C

2016-10-01

This study prospectively assessed whether positive screening surveys for autism spectrum disorders (ASDs) in children with functional defecation disorders (FDDs) accurately identify ASD. Parents of children (4-12 years) who met Rome III criteria for functional constipation (FC), FC with fecal incontinence (FI) and functional nonretentive FI (FNRFI) completed two ASD screening surveys. Children with positive screens were referred for psychological evaluation, and a year later, follow-up surveys were conducted. Of the 97 study participants, 30.9 % were diagnosed with FC, 62.9 % with FC with FI, and 6.2 % with FNRFI. ASD surveys were positive for 27 children (27.8 %). New DSM diagnoses were made in 10 out of the 15 children that completed further evaluation. Two (2.1 %) met criteria for ASD, and 12 (12.4 %) met criteria for other behavioral disorders. Average SRS and SCQ-L scores were higher in subjects with FC with FI as compared to FC alone and in those who reported no improvement versus those who reported improvement 1 year later. While positive ASD screening surveys did not correctly identify ASD in the majority, it did help to identify other unrecognized behavioral disorders in children with FDD. High screening scores were more common in children with FC with FI and in children with poorer responses to current medical treatments. •A prior study found that 29 % of children with FDD scored positive on ASD screening questionnaires. •Whether positive screens correctly identify ASD in children with FDD is unknown. What is New: •This study shows that positive ASD screens do not correctly identify ASD in children with FDD. However, the use of ASD screening questionnaires can identify previously unrecognized and untreated behavioral/developmental disorders in children with FDD. •High screening scores are more common in children with FC with FI and in children with poorer responses to current medical treatments.

Nuclear Shield: A Multi-Enzyme Task-Force for Nucleus Protection

PubMed Central

Pallottini, Valentina; Canuti, Lorena; De Canio, Michele; Urbani, Andrea; Marzano, Valeria; Cornetta, Tommaso; Stano, Pasquale; Giovanetti, Anna; Stella, Lorenzo; Canini, Antonella; Federici, Giorgio; Ricci, Giorgio

2010-01-01

Background In eukaryotic cells the nuclear envelope isolates and protects DNA from molecules that could damage its structure or interfere with its processing. Moreover, selected protection enzymes and vitamins act as efficient guardians against toxic compounds both in the nucleoplasm and in the cytosol. The observation that a cytosolic detoxifying and antioxidant enzyme i.e. glutathione transferase is accumulated in the perinuclear region of the rat hepatocytes suggests that other unrecognized modalities of nuclear protection may exist. Here we show evidence for the existence of a safeguard enzyme machinery formed by an hyper-crowding of cationic enzymes and proteins encompassing the nuclear membrane and promoted by electrostatic interactions. Methodology/Principal Findings Electron spectroscopic imaging, zeta potential measurements, isoelectrofocusing, comet assay and mass spectrometry have been used to characterize this surprising structure that is present in the cells of all rat tissues examined (liver, kidney, heart, lung and brain), and that behaves as a “nuclear shield”. In hepatocytes, this hyper-crowding structure is about 300 nm thick, it is mainly formed by cationic enzymes and the local concentration of key protection enzymes, such as glutathione transferase, catalase and glutathione peroxidase is up to seven times higher than in the cytosol. The catalytic activity of these enzymes, when packed in the shield, is not modified and their relative concentrations vary remarkably in different tissues. Removal of this protective shield renders chromosomes more sensitive to damage by oxidative stress. Specific nuclear proteins anchored to the outer nuclear envelope are likely involved in the shield formation and stabilization. Conclusions/Significance The characterization of this previously unrecognized nuclear shield in different tissues opens a new interesting scenario for physiological and protection processes in eukaryotic cells. Selection and accumulation of protection enzymes near sensitive targets represents a new safeguard modality which deeply differs from the adaptive response which is based on expression of specific enzymes. PMID:21170318

Revised history of the great Kanto earthquakes from the ages of Holocene marine terraces

NASA Astrophysics Data System (ADS)

Komori, J.; Shishikura, M.; Ando, R.; Yokoyama, Y.; Miyairi, Y.

2017-12-01

The Sagami Trough, where the Philippine Sea Plate subducts beneath the continental plate of the Japanese Archipelago, is considered to be a typical example where characteristic earthquakes repeat. Previous studies in some decades claimed that approximate M8 interplate earthquakes, called Genroku type earthquakes, occur with the interval of 2,000―2,700 years. In this study, we measured the emergence ages of the marine terraces in the Chikura lowland, which lies to the southeast of the Boso Peninsula, to reevaluate the history of the great earthquake over the past 10,000 years. The dates of the marine terraces are measured via radiocarbon dating of shell fossils obtained from the marine deposits. The sampling method employed in this study collects core samples using a dense and systematic drilling survey, which increased the reliability when correlating shell fossils with marine terraces. Moreover, we explored the surface profiles of the terraces with detailed digital elevation model (DEM) data obtained using LiDAR. The maximum emergence ages of the marine terraces were dated at 6300 cal yBP, 3000 cal yBP, and 2200 cal yBP from the top terrace excepting the lowest terrace (which was estimated at AD1703). In addition, another previously unrecognized terrace was detected between the highest and the second terrace in both the dating and the geomorphological analyses and was dated at 5800 cal yBP. The newly obtained ages are nearly a thousand of years younger than previously estimated ages; consequently, the intervals of the great earthquakes that occurred along the Sagami Trough are estimated to be much shorter and more varied than those of previous estimations. This result indicates that the temporal pattern of the large earthquakes occur along the Sagami Trough does not follow a characteristic pattern as previously considered.

Moment of Inertia: Psychophysical Study of an Overlooked Sensation.

ERIC Educational Resources Information Center

Science, 1979

1979-01-01

This article describes the distribution of mass in a hand-held object as a fundamental but unrecognized contributor to the sensation one receives from the object. Experiments producing fractions for human sensitivity are given. (SA)

Unrecognized Subclinical Infection with Tickborne Encephalitis Virus, Japan

PubMed Central

Yoshii, Kentaro; Kojima, Reiji

2017-01-01

During early 2017, we conducted a seroepidemiologic investigation for tickborne encephalitis virus among 291 Japan Self-Defense Forces members in Hokkaido. Two (0.7%) tested positive. Neither had clinically apparent symptoms after removing ticks. PMID:28930025

Unrecognized "AIDS" in Monkeys, 1969-1980: Explanations and Implications.

PubMed

Hammett, Theodore M; Bronson, Roderick T

2016-06-01

AIDS was recognized in humans in 1981 and a simian form was described in the years 1983 to 1985. However, beginning in the late 1960s, outbreaks of opportunistic infections of AIDS were seen in monkeys in the United States. This apparent syndrome went unrecognized at the time. We have assembled those early cases in monkeys and offer reasons why they did not result in earlier recognition of simian or human AIDS, including weaknesses in understanding disease mechanisms, absence of evidence of human retroviruses, and a climate of opinion that devalued investigation of infectious disease and immunologic origins of disease. The "epistemological obstacle" explains important elements of this history in that misconceptions blocked understanding of the dependent relationship among viral infection, immunodeficiency, and opportunistic diseases. Had clearer understanding of the evidence from monkeys allowed human AIDS to be recognized earlier, life-saving prevention and treatment interventions might have been implemented sooner.

The pupil as an indicator of unconscious memory: Introducing the pupil priming effect.

PubMed

Gomes, Carlos Alexandre; Montaldi, Daniela; Mayes, Andrew

2015-06-01

We explored whether object behavioral priming and pupil changes occur in the absence of recognition memory. Experiment 1 found behavioral priming for unrecognized objects (Ms) regardless of whether they had been encoded perceptually or conceptually. Using the same perceptual encoding task, Experiment 2 showed greater pupil dilation for Ms than for correct rejections of unstudied objects (CRs) when reaction times were matched. In Experiment 3, there was relatively less pupil dilation for Ms than for similarly matched CRs when objects had been encoded conceptually. Mean/peak pupil dilation for CRs, but not Ms, increased in Experiment 3, in which novelty expectation was also reduced, and the pupillary time course for both Ms and CRs was distinct in the two experiments. These findings indicate that both behavioral and pupil memory occur for studied, but unrecognized stimuli, and suggest that encoding and novelty expectation modulate pupillary memory responses. © 2015 Society for Psychophysiological Research.

Tendon Disorders After Total Hip Arthroplasty: Evaluation and Management.

PubMed

Capogna, Brian M; Shenoy, Kartik; Youm, Thomas; Stuchin, Steven A

2017-10-01

Most patients who undergo total hip arthroplasty are very satisfied with their outcomes. However, there is a small subset of patients who have persistent pain after surgery. The etiology of pain after total hip arthroplasty varies widely; however, tendon disorders are a major cause of debilitating pain that often go unrecognized. We performed a literature review to identify the most common tendon pathologies after total hip arthroplasty which include iliopsoas tendinitis, greater trochanteric pain syndrome, snapping hip syndrome, and abductor tendinopathy. We present a simplified approach highlighting the presentation and management of patients with suspected tendinopathies after total hip arthroplasty. These tendinopathies are treatable, and management begins with nonoperative modalities; however, in cases not responsive to conservative management, operative intervention may be necessary. Tendinopathies after total hip arthroplasty sometimes go unrecognized but when treated can result in higher surgeon and patient satisfaction. Copyright © 2017 Elsevier Inc. All rights reserved.

[Biometric method for the description of the head of an unrecognized corpse for the purpose of personality individualization and identification].

PubMed

Zviagin, V N; Galitskaia, O I; Negasheva, M A

2012-01-01

We have determined absolute dimensions of the head and the relationship between the dimensions of its selected parts. The study enrolled adult subjects (mostly of Russian ethnicity) at the age from 17 to 22 years (1108 men and 1153 women). We calculated the normal values for the estimation of real dimensional characteristics and the frequency of their occurrence in the population. The proposed approach makes it possible to reliably identify the dimensional features of human appearance in terms of the quantitative verbal description (categories 1-5) and to reveal its most characteristic features. The results of this biometric study of the heads of unrecognized corpses obtained by the specially developed technology may be used in operational and search investigations, in the procedure of corpse identification, and forensic medical personality identification of a missing subject.

Unrecognized “AIDS” in Monkeys, 1969–1980: Explanations and Implications

PubMed Central

Bronson, Roderick T.

2016-01-01

AIDS was recognized in humans in 1981 and a simian form was described in the years 1983 to 1985. However, beginning in the late 1960s, outbreaks of opportunistic infections of AIDS were seen in monkeys in the United States. This apparent syndrome went unrecognized at the time. We have assembled those early cases in monkeys and offer reasons why they did not result in earlier recognition of simian or human AIDS, including weaknesses in understanding disease mechanisms, absence of evidence of human retroviruses, and a climate of opinion that devalued investigation of infectious disease and immunologic origins of disease. The “epistemological obstacle” explains important elements of this history in that misconceptions blocked understanding of the dependent relationship among viral infection, immunodeficiency, and opportunistic diseases. Had clearer understanding of the evidence from monkeys allowed human AIDS to be recognized earlier, life-saving prevention and treatment interventions might have been implemented sooner. PMID:27077355

Comorbidity of Asperger's syndrome and Bipolar disorder

PubMed Central

2008-01-01

Background and objective Asperger's Syndrome (AS) is a pervasive developmental disorder that is sometimes unrecognized, especially in the adult psychiatric setting. On the other hand, in patients with an AS diagnosis, comorbid psychiatric disorders may be unrecognized in the juvenile setting. The aim of the paper is to show and discuss some troublesome and complex problems of the management of patients with AS and comorbid Bipolar Disorder (BD). Methods The paper describes three patients affected by AS and bipolar spectrum disorders. Results and conclusion Mood stabilizers and 2nd generation antipsychotics were effective in the treatment of these AS patients with comorbid BD, while the use of antidepressants was associated with worsening of the mood disorder. It is of importance to recognize both the psychiatric diagnoses in order to arrange an exhaustive therapeutic program and to define specific and realistic goals of treatment. PMID:19014623

Environmental hazards of waste disposal patterns--a multimethod study in an unrecognized Bedouin village in the Negev area of Israel.

PubMed

Meallem, Ilana; Garb, Yaakov; Cwikel, Julie

2010-01-01

The Bedouin of the Negev region of Israel are a formerly nomadic, indigenous, ethnic minority, of which 40% currently live in unrecognized villages without organized, solid waste disposal. This study, using both quantitative and qualitative methods, explored the transition from traditional rubbish production and disposal to current uses, the current composition of rubbish, methods of waste disposal, and the extent of exposure to waste-related environmental hazards in the village of Um Batim. The modern, consumer lifestyle produced both residential and construction waste that was dumped very close to households. Waste was tended to by women who predominantly used backyard burning for disposal, exposing villagers to corrosive, poisonous, and dangerously flammable items at these burn sites. Village residents expressed a high level of concern over environmental hazards, yet no organized waste disposal or environmental hazards reduction was implemented.

Transcriptome Analysis of Scrippsiella trochoidea CCMP 3099 Reveals Physiological Changes Related to Nitrate Depletion

PubMed Central

Cooper, Joshua T.; Sinclair, Geoffrey A.; Wawrik, Boris

2016-01-01

Dinoflagellates are a major component of marine phytoplankton and many species are recognized for their ability to produce harmful algal blooms (HABs). Scrippsiella trochoidea is a non-toxic, marine dinoflagellate that can be found in both cold and tropic waters where it is known to produce “red tide” events. Little is known about the genomic makeup of S. trochoidea and a transcriptome study was conducted to shed light on the biochemical and physiological adaptations related to nutrient depletion. Cultures were grown under N and P limiting conditions and transcriptomes were generated via RNAseq technology. De novo assembly reconstructed 107,415 putative transcripts of which only 41% could be annotated. No significant transcriptomic response was observed in response to initial P depletion, however, a strong transcriptional response to N depletion was detected. Among the down-regulated pathways were those for glutamine/glutamate metabolism as well as urea and nitrate/nitrite transporters. Transcripts for ammonia transporters displayed both up- and down-regulation, perhaps related to a shift to higher affinity transporters. Genes for the utilization of DON compounds were up-regulated. These included transcripts for amino acids transporters, polyamine oxidase, and extracellular proteinase and peptidases. N depletion also triggered down regulation of transcripts related to the production of Photosystems I & II and related proteins. These data are consistent with a metabolic strategy that conserves N while maximizing sustained metabolism by emphasizing the relative contribution of organic N sources. Surprisingly, the transcriptome also contained transcripts potentially related to secondary metabolite production, including a homolog to the Short Isoform Saxitoxin gene (sxtA) from Alexandrium fundyense, which was significantly up-regulated under N-depletion. A total of 113 unique hits to Sxt genes, covering 17 of the 34 genes found in C. raciborskii were detected, indicating that S. trochoidea has previously unrecognized potential for the production of secondary metabolites with potential toxicity. PMID:27242681

Dopamine D3 Receptor Availability Is Associated with Inflexible Decision Making.

PubMed

Groman, Stephanie M; Smith, Nathaniel J; Petrullli, J Ryan; Massi, Bart; Chen, Lihui; Ropchan, Jim; Huang, Yiyun; Lee, Daeyeol; Morris, Evan D; Taylor, Jane R

2016-06-22

Dopamine D2/3 receptor signaling is critical for flexible adaptive behavior; however, it is unclear whether D2, D3, or both receptor subtypes modulate precise signals of feedback and reward history that underlie optimal decision making. Here, PET with the radioligand [(11)C]-(+)-PHNO was used to quantify individual differences in putative D3 receptor availability in rodents trained on a novel three-choice spatial acquisition and reversal-learning task with probabilistic reinforcement. Binding of [(11)C]-(+)-PHNO in the midbrain was negatively related to the ability of rats to adapt to changes in rewarded locations, but not to the initial learning. Computational modeling of choice behavior in the reversal phase indicated that [(11)C]-(+)-PHNO binding in the midbrain was related to the learning rate and sensitivity to positive, but not negative, feedback. Administration of a D3-preferring agonist likewise impaired reversal performance by reducing the learning rate and sensitivity to positive feedback. These results demonstrate a previously unrecognized role for D3 receptors in select aspects of reinforcement learning and suggest that individual variation in midbrain D3 receptors influences flexible behavior. Our combined neuroimaging, behavioral, pharmacological, and computational approach implicates the dopamine D3 receptor in decision-making processes that are altered in psychiatric disorders. Flexible decision-making behavior is dependent upon dopamine D2/3 signaling in corticostriatal brain regions. However, the role of D3 receptors in adaptive, goal-directed behavior has not been thoroughly investigated. By combining PET imaging with the D3-preferring radioligand [(11)C]-(+)-PHNO, pharmacology, a novel three-choice probabilistic discrimination and reversal task and computational modeling of behavior in rats, we report that naturally occurring variation in [(11)C]-(+)-PHNO receptor availability relates to specific aspects of flexible decision making. We confirm these relationships using a D3-preferring agonist, thus identifying a unique role of midbrain D3 receptors in decision-making processes. Copyright © 2016 the authors 0270-6474/16/366732-10$15.00/0.

Internationally educated nurses' reflections on nursing communication in Canada.

PubMed

Lum, L; Dowedoff, P; Englander, K

2016-09-01

The overall goal of this study was to explore internationally educated nurses' perceptions of the English language and nursing communication skill requirements in a Canadian bridging education program. The increased global mobility of nurses creates a need to address the educational needs of migrating nurses. A large percentage of these nurses require additional language and professional education. New research is needed that would represent an in-depth analysis of their educational experiences associated with learning academic English and Canadian nursing communication. Developing proficiency with a new language has been documented as posing challenges for new immigrants. Since language proficiency is a key requirement of Canadian nursing regulatory bodies, previously unrecognized barriers such as attitudes and beliefs about required English language and nursing communication competency which may hinder their ability to meet local practice standards need to be explored. Using a grounded theory study design, narratives from 22 participants from the Philippines, Nigeria and Europe enrolled in bridging education were collected and analysed. The participants identified the incongruence in professional norms between Canada and their home country as a major challenge. The major themes identified included cultural dissonance, academic literacy challenges and skepticism regarding unexpected communication competency requirements. The participants possessed varying degrees of comprehension and acceptance of new educational and professional regulatory requirements. A certain degree of culture shock, which may be associated with frustration and disillusionment, is a typical and anticipated aspect of the immigration process. Their perceptions need to be recognized and accommodated when assisting internationally educated nurses to integrate into the Canadian practice culture. Any generalizations to other host countries need to be made cautiously. Clear communication from regulators about English language and nursing communication requirements during the pre-arrival period is recommended. If bridging education is required, these programs need to be designed to address English language competency and nursing communication skills of non-native English speakers. © 2016 International Council of Nurses.

The investigation and differential diagnosis of Asperger syndrome in adults.

PubMed

Lehnhardt, Fritz-Georg; Gawronski, Astrid; Pfeiffer, Kathleen; Kockler, Hanna; Schilbach, Leonhard; Vogeley, Kai

2013-11-08

As a result of the increased public interest in autism spectrum disorders (ASD), certain core manifestations of ASD--impaired social interaction and communication, bizarre interests--are now commonly recognized as being typical of autism, not only in children, but in adults as well. More often than before, general practitioners, neurologists, and psychiatrists find themselves being asked whether a patient is suffering from previously unrecognized Asperger syndrome (AS). The prevalence of ASD is estimated at 1%, and the ratio of diagnosed to undiagnosed cases at about 3:2. Little is known about the diagnostic evaluation of AS in adulthood. We selectively searched the Medline database for pertinent literature, paying special attention to diagnostic manuals and to the guideline of the United Kingdom's National Institute for Health and Care Excellence (NICE). Centrally important aspects of the diagnosis of AS include an assessment of the patient's ability to assume the emotional perspectives of others, non-verbal modes of expression, repetitive behavior patterns, and childhood social behavioral history. The autism quotient (AQ) is now established as a simple but nonspecific screening test. Up to 70% of all affected adults have comorbid disturbances, most often depression and anxiety disorders. The differential diagnosis includes personality disorders, anxiety disorders, obsessive-compulsive disorder, and attention deficit-hyperactivity disorder. The diagnostic assessment should proceed in stepwise fashion, starting from simple screening in primary care and then moving on to evaluation of the suspected diagnosis by a mental health care specialist, followed by extensive further investigation in an outpatient clinic specifically devoted to patients with autism spectrum disorders. The diagnostic assessment of autism in adults requires knowledge of the core and accompanying manifestations of autism and of their differential diagnoses. More research is needed for the development of further screening tests and the precise determination of diagnosis rates, differential diagnoses, nd comorbidities.

The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch

PubMed Central

Oberst, Andrew; Malatesta, Martina; Aqeilan, Rami I.; Rossi, Mario; Salomoni, Paolo; Murillas, Rodolfo; Sharma, Prashant; Kuehn, Michael R.; Oren, Moshe; Croce, Carlo M.; Bernassola, Francesca; Melino, Gerry

2007-01-01

Nedd4-binding partner-1 (N4BP1) has been identified as a protein interactor and a substrate of the homologous to E6AP C terminus (HECT) domain-containing E3 ubiquitin–protein ligase (E3), Nedd4. Here, we describe a previously unrecognized functional interaction between N4BP1 and Itch, a Nedd4 structurally related E3, which contains four WW domains, conferring substrate-binding activity. We show that N4BP1 association with the second WW domain (WW2) of Itch interferes with E3 binding to its substrates. In particular, we found that N4BP1 and p73α, a target of Itch-mediated ubiquitin/proteasome proteolysis, share the same binding site. By competing with p73α for binding to the WW2 domain, N4BP1 reduces the ability of Itch to recruit and ubiquitylate p73α and inhibits Itch autoubiquitylation activity both in in vitro and in vivo ubiquitylation assays. Similarly, both c-Jun and p63 polyubiquitylation by Itch are inhibited by N4BP1. As a consequence, genetic and RNAi knockdown of N4BP1 diminish the steady-state protein levels and significantly impair the transcriptional activity of Itch substrates. Notably, stress-induced induction of c-Jun was impaired in N4BP1−/− cells. These results demonstrate that N4BP1 functions as a negative regulator of Itch. In addition, because inhibition of Itch by N4BP1 results in the stabilization of crucial cell death regulators such as p73α and c-Jun, it is conceivable that N4BP1 may have a role in regulating tumor progression and the response of cancer cells to chemotherapy. PMID:17592138

Clinically unrecognized miliary tuberculosis: an autopsy study.

PubMed

Savic, Ivana; Trifunovic-Skodric, Vesna; Mitrovic, Dragan

2016-01-01

Miliary tuberculosis (TB) usually presents with atypical clinical manifestations; thus it is often recognized only at autopsy. Our objectives were to study the frequency of MT diagnosed at autopsy and determine clinical diagnoses that masked TB, as well as causes of death and comorbidities. Retrospective study of all autopsies performed between 2008 and 2014. Institute of Pathology, Belgrade, Serbia. in subjects where autopsy showed the presence of MT that was not recognized clinically, we recorded the clinical diagnoses (presumed causes of death) as reported in autopsy request forms, as well as actual cause of death and comorbidities as determined at autopsy. Clinically unrecognized MT. The total number of autopsies in this period was 6206. thirty-five individuals showed clinically unrecognized MT (0.56% of all autopsies, age: 62.2 [17.2] years, M:F=2:3). Common clinical diagnoses masking pulmonary MT were exacerbation of COPD (25%) and pulmonary thromboembolism (25%), with common radiological presentation of diffuse pulmonary infiltrates (56.3%). Dominant clinical diagnoses in patients with generalized MT were adult respiratory distress syndrome, sepsis, gastrointestinal bleeding and meningoencephalitis. Disseminated MT was often associated with secondary anemia or thrombocytopenia (15.8%) and recent surgery (15.8%). Frequent comorbidities included chronic renal failure and malignancies, whereas MT was a dominant cause of death. Greater awareness of MT is needed to improve recognition in clinical settings. In particular, MT should be considered in patients with atypical clinical presentation and diffuse pulmonary infiltrates on chest X-ray, particularly if they have chronic renal failure, malignancy, hematological disorders or a history of recent surgery. None.

Transient Asymptomatic Pulmonary Opacities Occurring during Osimertinib Treatment.

PubMed

Noonan, Sinead A; Sachs, Peter B; Camidge, D Ross

2016-12-01

Osimertinib is an EGFR inhibitor licensed for the treatment of EGFR-mutant, T790M-positive NSCLC. Previously unreported, frequent transient asymptomatic pulmonary opacities were noted in patients during osimertinib therapy at the University of Colorado. Computed tomography imaging and clinical notes on patients with NSCLC who had been treated with osimertinib at the University of Colorado were retrospectively reviewed. Transient asymptomatic pulmonary opacities developed in seven of 20 patients (35%) while they were receiving osimertinib. The radiological patterns seen included ground-glass opacities with or without nodular consolidation. The median time to development of the first lesion was 8.7 weeks (range 1.6-43 weeks), the median time to resolution during continued osimertinib was 6 weeks (range 1-11 weeks). Transient asymptomatic pulmonary opacities may be a previously unrecognized, benign feature associated with osimertinib therapy that may be mistaken for isolated pulmonary progression or the beginning of more severe pneumonitis. If new-onset pulmonary lesions, especially those associated with ground-glass appearances, are asymptomatic and localized and there is no evidence of disease progression elsewhere, it may be reasonable to continue treatment with osimertinib and monitor the lesions for resolution. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Spheroplastic phase of mycobacteria isolated from patients with Crohn's disease.

PubMed Central

Chiodini, R J; Van Kruiningen, H J; Thayer, W R; Coutu, J A

1986-01-01

Two strains of an unclassified Mycobacterium species were isolated after 18 and 30 months of incubation of media inoculated with resected intestinal tissues from patients with Crohn's disease. These strains represented the third and fourth isolates of this organism from Crohn's disease patients. Ultrastructural examination of this strain and two previously isolated strains revealed the presence of spheroplasts which eventually transformed into the bacillary form of a previously unrecognized Mycobacterium species. These cell wall-deficient forms did not stain with conventional dyes and failed to grow on hypertonic media. Restriction polymorphism of the ribosomal DNA genes was used to determine the relationship between the cell wall-deficient and bacillary forms. Identical restriction patterns of the ribosomal DNA genes were found between the spheroplasts and Mycobacterium sp. isolates with EcoRI, BamHI, and XhoI restriction endonucleases, thus providing definitive evidence of their origin. Unidentified spheroplasts were isolated from an additional 12 patients with Crohn's disease, of which 7 of 10 seroagglutinated with antiserum prepared against the Mycobacterium sp. Spheroplasts were isolated from 16 of 26 (61%) patients with Crohn's disease but not from tissues of 13 patients with ulcerative colitis or 13 patients with other diseases of the bowel. These findings support the role of mycobacteria as etiologic agents in some cases of Crohn's disease. Images PMID:3760132

Edge-Driven Block Rotations Interpreted From New GPS Results: Papua New Guinea

NASA Astrophysics Data System (ADS)

Wallace, L.

2001-12-01

An ongoing discussion in plate tectonics involves whether microplate motions are driven by plate edge forces or by flow at the base of the lithosphere. We present results from a GPS network of 40 sites spanning much of the mainland of Papua New Guinea (PNG). Most of the sites are concentrated in the region of the active Finisterre arc-continent collision and have been observed on multiple campaigns from 1993-2001. Significant portions of the Ramu-Markham fault are locked, which has implications for seismic hazard assessment in the Markham Valley region. Additionally, we find that out-of-sequence thrusting is important in emplacement of the Finisterre arc terrane onto the PNG mainland. Site velocities derived from these GPS data have helped to delineate the major tectonic blocks in the region. We model site velocities by simultaneously dealing with rigid block rotation and elastic strain. We find that the mainland of PNG consists of four distinct tectonic plates: the Australian, South Bismarck and Woodlark plates (in agreement with previous studies), and a previously unrecognized New Guinea Highlands plate. The relative rotation poles for at least two of these plate pairs plot on their respective boundaries, indicating that microplate motion in PNG may be dominantly edge-driven, as predicted for this region by Schouten and Benes (1993).

Sediment Carbon Accumulation in Southern Latitude Saltmarsh Communities of Tasmania, Australia.

PubMed

Ellison, Joanna C; Beasy, Kim M

2018-05-02

Carbon sequestration values of wetlands are greatest in their sediments. Northern hemisphere research dominates the earlier saltmarsh carbon sequestration literature, recently augmented by analyses across mainland Australia where species assemblages, catchment histories and environmental settings differ. No previous assessment has been made for Tasmania. Carbon stores and accumulation rates in saltmarsh sediments of the Rubicon estuary, Tasmania, were investigated. Carbon was determined from sediment cores by Elemental Analyser, combined with analysis of organic content and bulk density. Carbon accumulation was determined using short-term and long-term sediment accretion indicators. Results showed carbon densities to be lower than global averages, with variation found between carbon stores of native and introduced species zones. Cores from introduced Spartina anglica indicated a trend of higher sediment carbon percentages relative to cores from native saltmarsh Juncus kraussii and Sarcocornia quinqueflora , and in finer grain sizes. Sediment carbon stock of 30 cm depths was 49.5 Mg C ha −1 for native saltmarsh and 55.5 Mg C ha −1 for Spartina . Carbon percentages were low owing to high catchment inorganic sediment yields, however carbon accumulation rates were similar to global averages, particularly under Spartina . Covering 85% of saltmarsh area in the estuary, Spartina contributes the majority to carbon stores, potentially indicating a previously unrecognized value for this invasive species in Australia.

Comparative ultrastructure of CRM1-Nucleolar bodies (CNoBs), Intranucleolar bodies (INBs) and hybrid PML/p62 bodies uncovers new facets of nuclear body dynamic and diversity

PubMed Central

Souquere, Sylvie; Weil, Dominique; Pierron, Gérard

2015-01-01

In order to gain insights on the nuclear organization in mammalian cells, we characterized ultrastructurally nuclear bodies (NBs) previously described as fluorescent foci. Using high resolution immunoelectron microscopy (I-EM), we provide evidence that CNoBs (CRM1-Nucleolar bodies) and INBs (Intranucleolar bodies) are distinct genuine nucleolar structures in untreated HeLa cells. INBs are fibrillar and concentrate the post-translational modifiers SUMO1 and SUMO-2/3 as strongly as PML bodies. In contrast, the smallest CRM1-labeled CNoBs are vitreous, preferentially located at the periphery of the nucleolus and, intricately linked to the chromatin network. Upon blockage of the CRM1-dependent nuclear export by leptomycin B (LMB), CNoBs disappear while p62/SQSTM1-containing fibrillar nuclear bodies are induced. These p62 bodies are enriched in ubiquitinated proteins. They progressively associate with PML bodies to form hybrid bodies of which PML decorates the periphery while p62/SQSTM1 is centrally-located. Our study is expanding the repertoire of nuclear bodies; revealing a previously unrecognized composite nucleolar landscape and a new mode of interactions between ubiquitous (PML) and stress-induced (p62) nuclear bodies, resulting in the formation of hybrid bodies. PMID:26275159

Three cases of donor-derived pulmonary tuberculosis in lung transplant recipients and review of 12 previously reported cases: opportunities for early diagnosis and prevention.

PubMed

Mortensen, E; Hellinger, W; Keller, C; Cowan, L S; Shaw, T; Hwang, S; Pegues, D; Ahmedov, S; Salfinger, M; Bower, W A

2014-02-01

Solid organ transplant recipients have a higher frequency of tuberculosis (TB) than the general population, with mortality rates of approximately 30%. Although donor-derived TB is reported to account for <5% of TB in solid organ transplants, the source of Mycobacterium tuberculosis infection is infrequently determined. We report 3 new cases of pulmonary TB in lung transplant recipients attributed to donor infection, and review the 12 previously reported cases to assess whether cases could have been prevented and whether any cases that might occur in the future could be detected and investigated more quickly. Specifically, we evaluate whether opportunities existed to determine TB risk on the basis of routine donor history, to expedite diagnosis through routine mycobacterial smears and cultures of respiratory specimens early post transplant, and to utilize molecular tools to investigate infection sources epidemiologically. On review, donor TB risk was present among 7 cases. Routine smears and cultures diagnosed 4 asymptomatic cases. Genotyping was used to support epidemiologic findings in 6 cases. Validated screening protocols, including microbiological testing and newer technologies (e.g., interferon-gamma release assays) to identify unrecognized M. tuberculosis infection in deceased donors, are warranted. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Previously unrecognized stages of species-specific colonization in the mutualism between Xenorhabdus bacteria and Steinernema nematodes

PubMed Central

Chaston, John M.; Murfin, Kristen E.; Heath-Heckman, Elizabeth A.; Goodrich-Blair, Heidi

2013-01-01

Summary The specificity of a horizontally transmitted microbial symbiosis is often defined by molecular communication between host and microbe during initial engagement, which can occur in discrete stages. In the symbiosis between Steinernema nematodes and Xenorhabdus bacteria, previous investigations focused on bacterial colonization of the intestinal lumen (receptacle) of the nematode infective juvenile (IJ), as this was the only known persistent, intimate, and species-specific contact between the two. Here we show that bacteria colonize the anterior intestinal cells of other nematode developmental stages in a species-specific manner. Also, we describe three processes that only occur in juveniles that are destined to become IJs. First, a few bacterial cells colonize the nematode pharyngeal-intestinal valve (PIV) anterior to the intestinal epithelium. Second, the nematode intestine constricts while bacteria initially remain in the PIV. Third, anterior intestinal constriction relaxes and colonizing bacteria occupy the receptacle. At each stage, colonization requires X. nematophila symbiosis region 1 (SR1) genes and is species-specific: X. szentirmaii, which naturally lacks SR1, does not colonize unless SR1 is ectopically expressed. These findings reveal new aspects of Xenorhabdus bacteria interactions with and transmission by their Steinernema nematode hosts, and demonstrate that bacterial SR1 genes aid in colonizing nematode epithelial surfaces. PMID:23480552

Fibroblast Growth Factor 23–Induced Hypophosphatemia in Acute Leukemia

PubMed Central

Reinert, Rachel B; Bixby, Dale; Koenig, Ronald J

2018-01-01

Abstract Fibroblast growth factor 23 (FGF23)–induced hypophosphatemia is a rare paraneoplastic syndrome of phosphate wasting that, if unrecognized, may cause tumor-induced osteomalacia. It is classically associated with benign mesenchymal tumors but occasionally has been found in patients with other malignancies. Hypophosphatemia has been associated with acute leukemia but has not previously been reported to be due to inappropriate FGF23 secretion. Here, we describe FGF23-induced severe hypophosphatemia and renal phosphate wasting associated with a mixed-phenotype Philadelphia chromosome-like acute leukemia in a previously healthy 22-year-old man. He was found to have low serum 1,25-dihydroxyvitamin D and extremely high FGF23 levels, as well as inappropriate urinary phosphorus excretion. The hypophosphatemia improved with calcitriol and oral phosphate treatment but normalized only during chemotherapy-induced ablation of the blasts. FGF23 levels declined with a reduction in peripheral blast counts. Using real-time reverse transcription polymerase chain reaction, we found that the leukemia cells were the source of FGF23. To our knowledge, this is the first description of FGF23-induced hypophosphatemia associated with acute leukemia. We recommend that the FGF23 paraneoplastic syndrome be considered as a possible etiology of hypophosphatemia in patients with acute leukemia. PMID:29696242

Nodal-chain metals.

PubMed

Bzdušek, Tomáš; Wu, QuanSheng; Rüegg, Andreas; Sigrist, Manfred; Soluyanov, Alexey A

2016-10-06

The band theory of solids is arguably the most successful theory of condensed-matter physics, providing a description of the electronic energy levels in various materials. Electronic wavefunctions obtained from the band theory enable a topological characterization of metals for which the electronic spectrum may host robust, topologically protected, fermionic quasiparticles. Many of these quasiparticles are analogues of the elementary particles of the Standard Model, but others do not have a counterpart in relativistic high-energy theories. A complete list of possible quasiparticles in solids is lacking, even in the non-interacting case. Here we describe the possible existence of a hitherto unrecognized type of fermionic excitation in metals. This excitation forms a nodal chain-a chain of connected loops in momentum space-along which conduction and valence bands touch. We prove that the nodal chain is topologically distinct from previously reported excitations. We discuss the symmetry requirements for the appearance of this excitation and predict that it is realized in an existing material, iridium tetrafluoride (IrF 4 ), as well as in other compounds of this class of materials. Using IrF 4 as an example, we provide a discussion of the topological surface states associated with the nodal chain. We argue that the presence of the nodal-chain fermions will result in anomalous magnetotransport properties, distinct from those of materials exhibiting previously known excitations.

Pirfenidone inhibits p38-mediated generation of procoagulant microparticles by human alveolar epithelial cells.

PubMed

Neri, Tommaso; Lombardi, Stefania; Faìta, Francesca; Petrini, Silvia; Balìa, Cristina; Scalise, Valentina; Pedrinelli, Roberto; Paggiaro, Pierluigi; Celi, Alessandro

2016-08-01

Pirfenidone is a drug recently approved for idiopathic pulmonary fibrosis but its mechanisms of action are partially unknown. We have previously demonstrated that the airways of patients with idiopathic pulmonary fibrosis contain procoagulant microparticles that activate coagulation factor X to its active form, Xa, a proteinase that signals fibroblast growth and differentiation, thus potentially contributing to the pathogenesis of the disease. We also reported that in vitro exposure of human alveolar cells to H2O2 causes microparticle generation. Since p38 activation is involved in microparticle generation in some cell models and p38 inhibition is one of the mechanisms of action of pirfenidone, we investigated the hypothesis that H2O2-induced generation of microparticles by alveolar cells is dependent on p38 phosphorylation and is inhibited by pirfenidone. H2O2 stimulation of alveolar cells caused p38 phosphorylation that was inhibited by pirfenidone. The drug also inhibited H2O2 induced microparticle generation as assessed by two independent methods (solid phase thrombin generation and flow cytometry). The shedding of microparticle-bound tissue factor activity was also inhibited by pirfenidone. Inhibition of p38-mediated generation of procoagulant microparticle is a previously unrecognized mechanism of action of the antifibrotic drug, pirfenidone. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rare association between cystic fibrosis, Chiari I malformation, and hydrocephalus in a baby: a case report and review of the literature

PubMed Central

2011-01-01

Introduction Cystic fibrosis, an epithelial cell transport disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator gene, is not generally associated with malformations of the central nervous system. We review eight previously published reports detailing an infrequent association between cystic fibrosis and Chiari I malformation. Case presentation To the best of our knowledge, our report describes only the ninth case of a baby presenting with a new diagnosis of cystic fibrosis and Chiari I malformation, in this case in a 10-month-old, full-term Caucasian baby boy from the United States of America. Neurosurgical consultation was obtained for associated developmental delay, macrocephaly, bulging anterior fontanel, and papilledema. An MRI scan demonstrated an extensive Chiari I malformation with effacement of the fourth ventricle, obliteration of the outlets of the fourth ventricle and triventricular hydrocephalus without aqueductal stenosis. Our patient was taken to the operating room for ventriculoperitoneal shunt placement. Conclusions It is possible that the cystic fibrosis transmembrane conductance regulator gene may play a previously unrecognized role in central nervous system development; alternatively, this central nervous system abnormality may have been acquired due to constant valsalva from recurrent coughing or wheezing or metabolic and electrolyte imbalances that occur characteristically in cystic fibrosis. PMID:21838874

Short Toxin-like Proteins Abound in Cnidaria Genomes

PubMed Central

Tirosh, Yitshak; Linial, Itai; Askenazi, Manor; Linial, Michal

2012-01-01

Cnidaria is a rich phylum that includes thousands of marine species. In this study, we focused on Anthozoa and Hydrozoa that are represented by the Nematostella vectensis (Sea anemone) and Hydra magnipapillata genomes. We present a method for ranking the toxin-like candidates from complete proteomes of Cnidaria. Toxin-like functions were revealed using ClanTox, a statistical machine-learning predictor trained on ion channel inhibitors from venomous animals. Fundamental features that were emphasized in training ClanTox include cysteines and their spacing along the sequences. Among the 83,000 proteins derived from Cnidaria representatives, we found 170 candidates that fulfill the properties of toxin-like-proteins, the vast majority of which were previously unrecognized as toxins. An additional 394 short proteins exhibit characteristics of toxin-like proteins at a moderate degree of confidence. Remarkably, only 11% of the predicted toxin-like proteins were previously classified as toxins. Based on our prediction methodology and manual annotation, we inferred functions for over 400 of these proteins. Such functions include protease inhibitors, membrane pore formation, ion channel blockers and metal binding proteins. Many of the proteins belong to small families of paralogs. We conclude that the evolutionary expansion of toxin-like proteins in Cnidaria contributes to their fitness in the complex environment of the aquatic ecosystem. PMID:23202321

Short toxin-like proteins abound in Cnidaria genomes.

PubMed

Tirosh, Yitshak; Linial, Itai; Askenazi, Manor; Linial, Michal

2012-11-16

Cnidaria is a rich phylum that includes thousands of marine species. In this study, we focused on Anthozoa and Hydrozoa that are represented by the Nematostella vectensis (Sea anemone) and Hydra magnipapillata genomes. We present a method for ranking the toxin-like candidates from complete proteomes of Cnidaria. Toxin-like functions were revealed using ClanTox, a statistical machine-learning predictor trained on ion channel inhibitors from venomous animals. Fundamental features that were emphasized in training ClanTox include cysteines and their spacing along the sequences. Among the 83,000 proteins derived from Cnidaria representatives, we found 170 candidates that fulfill the properties of toxin-like-proteins, the vast majority of which were previously unrecognized as toxins. An additional 394 short proteins exhibit characteristics of toxin-like proteins at a moderate degree of confidence. Remarkably, only 11% of the predicted toxin-like proteins were previously classified as toxins. Based on our prediction methodology and manual annotation, we inferred functions for over 400 of these proteins. Such functions include protease inhibitors, membrane pore formation, ion channel blockers and metal binding proteins. Many of the proteins belong to small families of paralogs. We conclude that the evolutionary expansion of toxin-like proteins in Cnidaria contributes to their fitness in the complex environment of the aquatic ecosystem.

Analysis of BmNPV orf101 disruption: orf101 is essential for mediating budded virus production.

PubMed

Chen, Huiqing; Li, Mei; Mai, Weijun; Tang, Qi; Li, Guohui; Chen, Keping; Zhou, Yajing

2014-12-01

In our previous study, Orf101 (Bm101) of Bombyx mori nucleopolyhedrovirus (BmNPV) was identified as a component of the budded virions important for viral late gene expression. In this study we demonstrate that Bm101 is actually a previously unrecognized core gene and that it is essential for mediating budded virus production. To determine the role of Bm101 in the baculovirus life cycle, a Bm101 knockout bacmid containing the BmNPV genome was generated through homologous recombination in Escherichia coli. Furthermore, a Bm101 repair bacmid was constructed by transposing the Bm101 open reading frame with its native promoter region into the polyhedrin locus of the Bm101 knockout bacmid. Bacmid DNA transfection assay revealed that the Bm101 knockout bacmid was unable to produce the infectious budded virus, while the Bm101 repair bacmid rescued this defect, allowing budded-virus titers to reach wild-type levels. Real time PCR analysis indicated that the viral DNA genome in the absence of Bm101 was unaffected in the first 24 h p.t. Thus, studies of a Bm101-null BACmid indicate that Bm101 is required for viral DNA replication during the infection cycle.

Scaling and memory in volatility return intervals in financial markets

PubMed Central

Yamasaki, Kazuko; Muchnik, Lev; Havlin, Shlomo; Bunde, Armin; Stanley, H. Eugene

2005-01-01

For both stock and currency markets, we study the return intervals τ between the daily volatilities of the price changes that are above a certain threshold q. We find that the distribution function Pq(τ) scales with the mean return interval \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}{\\bar {{\\tau}}}\\end{equation*}\\end{document} as \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}P_{q}({\\tau})={\\bar {{\\tau}}}^{-1}f({\\tau}/{\\bar {{\\tau}}})\\end{equation*}\\end{document}. The scaling function f(x) is similar in form for all seven stocks and for all seven currency databases analyzed, and f(x) is consistent with a power-law form, f(x) ∼ x-γ with γ ≈ 2. We also quantify how the conditional distribution Pq(τ|τ0) depends on the previous return interval τ0 and find that small (or large) return intervals are more likely to be followed by small (or large) return intervals. This “clustering” of the volatility return intervals is a previously unrecognized phenomenon that we relate to the long-term correlations known to be present in the volatility. PMID:15980152

Scaling and memory in volatility return intervals in financial markets

NASA Astrophysics Data System (ADS)

Yamasaki, Kazuko; Muchnik, Lev; Havlin, Shlomo; Bunde, Armin; Stanley, H. Eugene

2005-06-01

For both stock and currency markets, we study the return intervals τ between the daily volatilities of the price changes that are above a certain threshold q. We find that the distribution function Pq(τ) scales with the mean return interval [Formula] as [Formula]. The scaling function f(x) is similar in form for all seven stocks and for all seven currency databases analyzed, and f(x) is consistent with a power-law form, f(x) ˜ x-γ with γ ≈ 2. We also quantify how the conditional distribution Pq(τ|τ0) depends on the previous return interval τ0 and find that small (or large) return intervals are more likely to be followed by small (or large) return intervals. This “clustering” of the volatility return intervals is a previously unrecognized phenomenon that we relate to the long-term correlations known to be present in the volatility. Author contributions: S.H. and H.E.S. designed research; K.Y., L.M., S.H., and H.E.S. performed research; A.B. contributed new reagents/analytic tools; A.B. analyzed data; and S.H. wrote the paper.Abbreviations: pdf, probability density function; S&P 500, Standard and Poor's 500 Index; USD, U.S. dollar; JPY, Japanese yen; SEK, Swedish krona.

Dicer uses distinct modules for recognizing dsRNA termini.

PubMed

Sinha, Niladri K; Iwasa, Janet; Shen, Peter S; Bass, Brenda L

2018-01-19

Invertebrates rely on Dicer to cleave viral double-stranded RNA (dsRNA), and Drosophila Dicer-2 distinguishes dsRNA substrates by their termini. Blunt termini promote processive cleavage, while 3' overhanging termini are cleaved distributively. To understand this discrimination, we used cryo-electron microscopy to solve structures of Drosophila Dicer-2 alone and in complex with blunt dsRNA. Whereas the Platform-PAZ domains have been considered the only Dicer domains that bind dsRNA termini, unexpectedly, we found that the helicase domain is required for binding blunt, but not 3' overhanging, termini. We further showed that blunt dsRNA is locally unwound and threaded through the helicase domain in an adenosine triphosphate-dependent manner. Our studies reveal a previously unrecognized mechanism for optimizing antiviral defense and set the stage for the discovery of helicase-dependent functions in other Dicers. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

PubMed

Lotta, Luca A; Gulati, Pawan; Day, Felix R; Payne, Felicity; Ongen, Halit; van de Bunt, Martijn; Gaulton, Kyle J; Eicher, John D; Sharp, Stephen J; Luan, Jian'an; De Lucia Rolfe, Emanuella; Stewart, Isobel D; Wheeler, Eleanor; Willems, Sara M; Adams, Claire; Yaghootkar, Hanieh; Forouhi, Nita G; Khaw, Kay-Tee; Johnson, Andrew D; Semple, Robert K; Frayling, Timothy; Perry, John R B; Dermitzakis, Emmanouil; McCarthy, Mark I; Barroso, Inês; Wareham, Nicholas J; Savage, David B; Langenberg, Claudia; O'Rahilly, Stephen; Scott, Robert A

2017-01-01

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage

PubMed Central

Wang, Jian; Doré, Sylvain

2008-01-01

Because heme oxygenase (HO) is the rate limiting enzyme in the degradation of the pro-oxidant hemin/heme from blood, here we investigated the contribution of the inducible HO-1 to early brain injury produced by intracerebral haemorrhage (ICH). We found that after induction of ICH, HO-1 proteins were highly detectable in the peri-ICH region predominantly in microglia/macrophages and endothelial cells. Remarkably, the injury volume was significantly smaller in HO-1 knockout (HO-1−/−) mice than in wild-type controls 24 and 72 h after ICH. Although the brain water content did not appear to be significantly different, the protection in HO-1−/− mice was associated with a marked reduction in ICH-induced leucocyte infiltration, microglia/macrophage activation and free radical levels. These data reveal a previously unrecognized role of HO-1 in early brain injury after ICH. Thus, modulation of HO-1 signalling should be assessed further in clinical settings, especially for haemorrhagic states. PMID:17525142

High-resolution Myogenic Lineage Mapping by Single-Cell Mass Cytometry

PubMed Central

Porpiglia, Ermelinda; Samusik, Nikolay; Ho, Andrew Tri Van; Cosgrove, Benjamin D.; Mai, Thach; Davis, Kara L.; Jager, Astraea; Nolan, Garry P.; Bendall, Sean C.; Fantl, Wendy J.; Blau, Helen M.

2017-01-01

Muscle regeneration is a dynamic process during which cell state and identity change over time. A major roadblock has been a lack of tools to resolve a myogenic progression in vivo. Here we capitalize on a transformative technology, single-cell mass cytometry (CyTOF), to identify in vivo skeletal muscle stem cell and previously unrecognized progenitor populations that precede differentiation. We discovered two cell surface markers, CD9 and CD104, whose combined expression enabled in vivo identification and prospective isolation of stem and progenitor cells. Data analysis using the X-shift algorithm paired with single-cell force directed layout visualization, defined a molecular signature of the activated stem cell state (CD44+/CD98+/MyoD+) and delineated a myogenic trajectory during recovery from acute muscle injury. Our studies uncover the dynamics of skeletal muscle regeneration in vivo and pave the way for the elucidation of the regulatory networks that underlie cell-state transitions in muscle diseases and aging. PMID:28414312

Comparative promoter analysis allows de novo identification of specialized cell junction-associated proteins.

PubMed

Cohen, Clemens D; Klingenhoff, Andreas; Boucherot, Anissa; Nitsche, Almut; Henger, Anna; Brunner, Bodo; Schmid, Holger; Merkle, Monika; Saleem, Moin A; Koller, Klaus-Peter; Werner, Thomas; Gröne, Hermann-Josef; Nelson, Peter J; Kretzler, Matthias

2006-04-11

Shared transcription factor binding sites that are conserved in distance and orientation help control the expression of gene products that act together in the same biological context. New bioinformatics approaches allow the rapid characterization of shared promoter structures and can be used to find novel interacting molecules. Here, these principles are demonstrated by using molecules linked to the unique functional unit of the glomerular slit diaphragm. An evolutionarily conserved promoter model was generated by comparative genomics in the proximal promoter regions of the slit diaphragm-associated molecule nephrin. Phylogenetic promoter fingerprints of known elements of the slit diaphragm complex identified the nephrin model in the promoter region of zonula occludens-1 (ZO-1). Genome-wide scans using this promoter model effectively predicted a previously unrecognized slit diaphragm molecule, cadherin-5. Nephrin, ZO-1, and cadherin-5 mRNA showed stringent coexpression across a diverse set of human glomerular diseases. Comparative promoter analysis can identify regulatory pathways at work in tissue homeostasis and disease processes.

A family of metal-dependent phosphatases implicated in metabolite damage-control

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

Huang, Lili; Khusnutdinova, Anna; Nocek, Boguslaw

DUF89 family proteins occur widely in both prokaryotes and eukaryotes, but their functions are unknown. Here we define three DUF89 subfamilies (I, II, and III), with subfamily II being split into stand-alone proteins and proteins fused to pantothenate kinase (PanK). We demonstrated that DUF89 proteins have metal-dependent phosphatase activity against reactive phosphoesters or their damaged forms, notably sugar phosphates (subfamilies II and III), phosphopantetheine and its S-sulfonate or sulfonate (subfamily II-PanK fusions), and nucleotides (subfamily I). Genetic and comparative genomic data strongly associated DUF89 genes with phosphoester metabolism. The crystal structure of the yeast (Saccharomyces cerevisiae) subfamily III protein YMR027Wmore » revealed a novel phosphatase active site with fructose 6-phosphate and Mg2+ bound near conserved signature residues Asp254 and Asn255 that are critical for activity. These findings indicate that DUF89 proteins are previously unrecognized hydrolases whose characteristic in vivo function is to limit potentially harmful buildups of normal or damaged phosphometabolites.« less

Integrated metatranscriptomics and metaproteomics for the characterization of bacterial microbiota in unfed Ixodes ricinus.

PubMed

Hernández-Jarguín, Angélica; Díaz-Sánchez, Sandra; Villar, Margarita; de la Fuente, José

2018-05-05

An innovative metaomics approach integrating metatranscriptomics and metaproteomics was used to characterize bacterial communities in the microbiota of the Lyme borreliosis spirochete vector, Ixodes ricinus (Acari: Ixodidae). Whole internal tissues and salivary glands from unfed larvae and female ticks, respectively were used. Reused I. ricinus RNA-sequencing data for metranscriptomics analysis together with metaproteomics provided a better characterization of tick bacterial microbiota by increasing bacteria identification and support for identified bacteria with putative functional implications. The results showed the presence of symbiotic, commensal, soil, environmental, and pathogenic bacteria in the I. ricinus microbiota, including previously unrecognized commensal and soil microorganisms. The results of the metaomics approach may have implications in the characterization of putative mechanisms by which pathogen infection manipulates tick microbiota to facilitate infection. Metaomics approaches integrating different omics datasets would provide a better description of tick microbiota compositions, and insights into tick interactions with microbiota, pathogens and hosts. Copyright © 2018 Elsevier GmbH. All rights reserved.

The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii.

PubMed

Beiting, Daniel P; Hidano, Shinya; Baggs, Julie E; Geskes, Jeanne M; Fang, Qun; Wherry, E John; Hunter, Christopher A; Roos, David S; Cherry, Sara

2015-07-01

The protozoan parasite, Toxoplasma, like many intracellular pathogens, suppresses interferon gamma (IFN-γ)-induced signal transducer and activator of transcription 1 (STAT1) activity. We exploited this well-defined host-pathogen interaction as the basis for a high-throughput screen, identifying nine transcription factors that enhance STAT1 function in the nucleus, including the orphan nuclear hormone receptor TLX. Expression profiling revealed that upon IFN-γ treatment TLX enhances the output of a subset of IFN-γ target genes, which we found is dependent on TLX binding at those loci. Moreover, infection of TLX deficient mice with the intracellular parasite Toxoplasma results in impaired production of the STAT1-dependent cytokine interleukin-12 by dendritic cells and increased parasite burden in the brain during chronic infection. These results demonstrate a previously unrecognized role for this orphan nuclear hormone receptor in regulating STAT1 signaling and host defense and reveal that STAT1 activity can be modulated in a context-specific manner by such "modifiers."

Reactive oxygen-mediated damage to a human DNA replication and repair protein.

PubMed

Montaner, Beatriz; O'Donovan, Peter; Reelfs, Olivier; Perrett, Conal M; Zhang, Xiaohong; Xu, Yao-Zhong; Ren, Xiaolin; Macpherson, Peter; Frith, David; Karran, Peter

2007-11-01

Ultraviolet A (UVA) makes up more than 90% of incident terrestrial ultraviolet radiation. Unlike shorter wavelength UVB, which damages DNA directly, UVA is absorbed poorly by DNA and is therefore considered to be less hazardous. Organ transplant patients treated with the immunosuppressant azathioprine frequently develop skin cancer. Their DNA contains 6-thioguanine-a base analogue that generates DNA-damaging singlet oxygen ((1)O(2)) when exposed to UVA. Here, we show that this (1)O(2) damages proliferating cell nuclear antigen (PCNA), the homotrimeric DNA polymerase sliding clamp. It causes covalent oxidative crosslinking between the PCNA subunits through a histidine residue in the intersubunit domain. Crosslinking also occurs after treatment with higher-although still moderate-doses of UVA alone or with chemical oxidants. Chronic accumulation of oxidized proteins is linked to neurodegenerative disorders and ageing. Our findings identify oxidative damage to an important DNA replication and repair protein as a previously unrecognized hazard of acute oxidative stress.

Pathway connectivity and signaling coordination in the yeast stress-activated signaling network

PubMed Central

Chasman, Deborah; Ho, Yi-Hsuan; Berry, David B; Nemec, Corey M; MacGilvray, Matthew E; Hose, James; Merrill, Anna E; Lee, M Violet; Will, Jessica L; Coon, Joshua J; Ansari, Aseem Z; Craven, Mark; Gasch, Audrey P

2014-01-01

Stressed cells coordinate a multi-faceted response spanning many levels of physiology. Yet knowledge of the complete stress-activated regulatory network as well as design principles for signal integration remains incomplete. We developed an experimental and computational approach to integrate available protein interaction data with gene fitness contributions, mutant transcriptome profiles, and phospho-proteome changes in cells responding to salt stress, to infer the salt-responsive signaling network in yeast. The inferred subnetwork presented many novel predictions by implicating new regulators, uncovering unrecognized crosstalk between known pathways, and pointing to previously unknown ‘hubs’ of signal integration. We exploited these predictions to show that Cdc14 phosphatase is a central hub in the network and that modification of RNA polymerase II coordinates induction of stress-defense genes with reduction of growth-related transcripts. We find that the orthologous human network is enriched for cancer-causing genes, underscoring the importance of the subnetwork's predictions in understanding stress biology. PMID:25411400

HLA-F and MHC-I Open Conformers Cooperate in a MHC-I Antigen Cross-Presentation Pathway

PubMed Central

Goodridge, Jodie P.; Lee, Ni; Burian, Aura; Pyo, Chul-Woo; Tykodi, Scott S.; Warren, Edus H.; Yee, Cassian; Riddell, Stanley R.

2013-01-01

Peptides that are presented by MHC class I (MHC-I) are processed from two potential sources, as follows: newly synthesized endogenous proteins for direct presentation on the surface of most nucleated cells and exogenous proteins for cross-presentation typically by professional APCs. In this study, we present data that implicate the nonclassical HLA-F and open conformers of MHC-I expressed on activated cells in a pathway for the presentation of exogenous proteins by MHC-I. This pathway is distinguished from the conventional endogenous pathway by its independence from TAP and tapasin and its sensitivity to inhibitors of lysosomal enzymes, and further distinguished by its dependence on MHC-I allotype-specific epitope recognition for Ag uptake. Thus, our data from in vitro experiments collectively support a previously unrecognized model of Ag cross-presentation mediated by HLA-F and MHC-I open conformers on activated lymphocytes and monocytes, which may significantly contribute to the regulation of immune system functions and the immune defense. PMID:23851683

A family of metal-dependent phosphatases implicated in metabolite damage-control

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

Huang, Lili; Shanklin, John; Khusnutdinova, Anna

DUF89 family proteins occur widely in pro- and eukaryotes but their functions are unknown. Here we define three DUF89 subfamilies (I, II, and III), subfamily II being split into standalone proteins and proteins fused to pantothenate kinase (PanK). We demonstrated that DUF89 proteins have metaldependent phosphatase activity against reactive phosphoesters or their damaged forms, notably sugar phosphates (subfamilies II and III), phosphopantetheine and its S-sulfonate or sulfonate (subfamily II-PanK fusions), and nucleotides (subfamily I). Genetic and comparative genomic data strongly associated DUF89 genes with phosphoester metabolism. The crystal structure of the yeast (Saccharomyces cerevisiae) subfamily III protein YMR027W revealed amore » novel phosphatase active site with fructose 6-phosphate and Mg 2+ bound near conserved signature residues Asp254 and Asn255 that are critical for activity. These findings indicate that DUF89 proteins are previously unrecognized hydrolases whose characteristic in vivo function is to limit potentially harmful buildups of normal or damaged phosphometabolites.« less

Reductive dechlorination of trichloroethene mediated by humic-metal complexes

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

O`Loughlin, E.J.; Burris, D.R.; Delcomyn, C.A.

1999-04-01

Experiments were conducted to determine if transition metal-humic acid complexes can act as e{sup {minus}} transfer mediators in the reductive dechlorination of trichloroethene (TCE) using Ti(III) citrate as the bulk reductant. In the presence of Ni-Aldrich humic acid (AHA) complexes, TCE reduction was rapid, with complete removal of TCE in less than 23 h. Cu-AHA complexes were less effective as e{sup {minus}} mediators than Ni-AHA complexes; only 60% of TCE was reduced after 150 h. Partially dechlorinated intermediates were observed during TCE reduction; however, they were transitory, and at no time accounted for more than 2% of the initial TCEmore » mass on a mole C basis. Ethane and ethene were the primary end products of TCE reduction; however, a suite of other non-chlorinated hydrocarbons consisting of methane and C{sub 3} to C{sub 6} alkanes and alkenes were also observed. The results suggest that humic-metal complexes may represent a previously unrecognized class of electron mediators in natural environments.« less

XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus.

PubMed

Li, Feng-Yen; Chaigne-Delalande, Benjamin; Su, Helen; Uzel, Gulbu; Matthews, Helen; Lenardo, Michael J

2014-04-03

Epstein-Barr virus (EBV) is an oncogenic gammaherpesvirus that infects and persists in 95% of adults worldwide and has the potential to cause fatal disease, especially lymphoma, in immunocompromised hosts. Primary immunodeficiencies (PIDs) that predispose to EBV-associated malignancies have provided novel insights into the molecular mechanisms of immune defense against EBV. We have recently characterized a novel PID now named "X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia" (XMEN) disease characterized by loss-of-function mutations in the gene encoding magnesium transporter 1 (MAGT1), chronic high-level EBV with increased EBV-infected B cells, and heightened susceptibility to EBV-associated lymphomas. The genetic etiology of XMEN disease has revealed an unexpected quantitative role for intracellular free magnesium in immune functions and has led to novel diagnostic and therapeutic strategies. Here, we review the clinical presentation, genetic mutation spectrum, molecular mechanisms of pathogenesis, and diagnostic and therapeutic considerations for this previously unrecognized disease.

Nanotubes mediate niche-stem cell signaling in the Drosophila testis

PubMed Central

Inaba, Mayu; Buszczak, Michael; Yamashita, Yukiko M.

2015-01-01

Stem cell niches provide resident stem cells with signals that specify their identity. Niche signals act over a short-range such that only stem cells but not their differentiating progeny receive the self-renewing signals1. However, the cellular mechanisms that limit niche signaling to stem cells remain poorly understood. Here we show that the Drosophila male germline stem cells (GSCs) form previously unrecognized structures, microtubule-based (MT)-nanotubes, which extend into the hub, a major niche component. MT-nanotubes are observed specifically within GSC populations, and require IFT (intraflagellar transport) proteins for their formation. The BMP receptor Tkv localizes to MT-nanotubes. Perturbation of MT-nanotubes compromises activation of Dpp signaling within GSCs, leading to GSC loss. Moreover, Dpp ligand and Tkv receptor interaction is necessary and sufficient for MT-nanotube formation. We propose that MT-nanotubes provide a novel mechanism for selective receptor-ligand interaction, contributing to the short-range nature of niche-stem cell signaling. PMID:26131929

Isolation of an Amoeba Naturally Harboring a Distinctive Legionella Species

PubMed Central

Newsome, Anthony L.; Scott, Tammy M.; Benson, Robert F.; Fields, Barry S.

1998-01-01

There are numerous in vitro studies documenting the multiplication of Legionella species in free-living amoebae and other protozoa. It is believed that protozoa serve as host cells for the intracellular replication of certain Legionella species in a variety of environmental settings. This study describes the isolation and characterization of a bacterium initially observed within an amoeba taken from a soil sample. In the laboratory, the bacterium multiplied within and was highly pathogenic for Acanthamoeba polyphaga. Extracellular multiplication was observed on buffered charcoal yeast extract agar but not on a variety of conventional laboratory media. A 16S rRNA gene analysis placed the bacterium within the genus Legionella. Serological studies indicate that it is distinct from previously described species of the genus. This report also describes methods that should prove useful for the isolation and characterization of additional Legionella-like bacteria from free-living amoebae. In addition, the characterization of bacterial pathogens of amoebae has significant implications for understanding the ecology and identification of other unrecognized bacterial pathogens. PMID:9572937

Stratigraphic relations and U-Pb geochronology of the Upper Cretaceous upper McCoy Mountains Formation, southwestern Arizona

USGS Publications Warehouse

Tosdal, R.M.; Stone, P.

1994-01-01

A previously unrecognized angular unconformity divides the Jurassic and Cretaceous McCoy Mountains Formation into a lower and an upper unit in the Dome Rock Mountains and Livingston Hills of western Arizona. The intraformation unconformity in the McCoy Mountains Formation developed where rocks of the lower unit were deformed adjacent to the southern margin of the Maria fold and thrust belt. The upper unit of the formation is interpreted as a foreland-basin deposit that was shed southward from the actively rising and deforming fold and thrust belt. The apparent absence of an equivalent unconformity in the McCoy Mountains Formation in adjacent California is presumably a consequence of the observed westward divergence of the outcrop belt from the fold and thrust belt. Tectonic burial beneath the north-vergent Mule Mountains thrust system in the latest Late Cretaceous (~70 Ma) marked the end of Mesozoic contractile deformation in the area. -from Authors

Development of a plastic surgical teaching service in a women's correctional institution.

PubMed

Fisher, J C; Powers, W E; Tuerk, D B; Edgerton, M T

1975-03-01

A plastic surgical teaching service has been organized at a women's correctional institution to provide a previously unrecognized medical need and to serve a valuable educational function for our residents in training. A total of 177 surgical candidates demonstrating a wide range of reconstructive problems including tattoos, scars, keloids, neoplasms of the skin and hands, deformities of the face and breasts, and numerous disabilities of the hands were identified among 241 inmates requesting examination. Thus far, 116 operative procedures have been performed on 101 patients. Patient acceptance has been high, and the support of prison authorities has been enthusiastic. Persistent efforts to convince legislators of the wisdom of supporting this program financially have only been partially successful and will require further accumulation of sociologic data bearing on the rehabilitative potential of the detained patient with a correctable deformity. Meanwhile, residents in training gain maturity as they provide a very "private" type of service for what has traditionally been considered a very "public" population of patients.

Open the gates: vascular neurocrine signaling mobilizes hematopoietic stem and progenitor cells.

PubMed

Itkin, Tomer; Gómez-Salinero, Jesús María; Rafii, Shahin

2017-12-01

Mobilization of hematopoietic stem and progenitor cells (HSPCs) from the bone marrow (BM) into the peripheral blood is a complex process that is enhanced dramatically under stress-induced conditions. A better understanding of how the mobilization process is regulated will likely facilitate the development of improved clinical protocols for stem cell harvesting and transplantation. In this issue of the JCI, Singh et al. (1) showed that the truncated cleaved form of neurotransmitter neuropeptide Y (NPY) actively promotes a breach of BM vascular sinusoidal portals, thereby augmenting HSPC trafficking to the circulation. The authors report a previously unrecognized axis, in which expression of the enzyme dipeptidylpeptidase-4 (DPP4)/CD26 by endothelial cells activates NPY-mediated signaling by increasing the bioavailability of the truncated form of NPY. These findings underscore the importance of and urgency to develop pharmacological therapies that target the vasculature and regulate diverse aspects of hematopoiesis, such as HSPC trafficking, in steady-state and stress-induced conditions.

Decoding the regulatory landscape of melanoma reveals TEADS as regulators of the invasive cell state

PubMed Central

Verfaillie, Annelien; Imrichova, Hana; Atak, Zeynep Kalender; Dewaele, Michael; Rambow, Florian; Hulselmans, Gert; Christiaens, Valerie; Svetlichnyy, Dmitry; Luciani, Flavie; Van den Mooter, Laura; Claerhout, Sofie; Fiers, Mark; Journe, Fabrice; Ghanem, Ghanem-Elias; Herrmann, Carl; Halder, Georg; Marine, Jean-Christophe; Aerts, Stein

2015-01-01

Transcriptional reprogramming of proliferative melanoma cells into a phenotypically distinct invasive cell subpopulation is a critical event at the origin of metastatic spreading. Here we generate transcriptome, open chromatin and histone modification maps of melanoma cultures; and integrate this data with existing transcriptome and DNA methylation profiles from tumour biopsies to gain insight into the mechanisms underlying this key reprogramming event. This shows thousands of genomic regulatory regions underlying the proliferative and invasive states, identifying SOX10/MITF and AP-1/TEAD as regulators, respectively. Knockdown of TEADs shows a previously unrecognized role in the invasive gene network and establishes a causative link between these transcription factors, cell invasion and sensitivity to MAPK inhibitors. Using regulatory landscapes and in silico analysis, we show that transcriptional reprogramming underlies the distinct cellular states present in melanoma. Furthermore, it reveals an essential role for the TEADs, linking it to clinically relevant mechanisms such as invasion and resistance. PMID:25865119

Analysis of a hyperdeformed band of 152(66)Dy86 on the basis of a structure with two revolving clusters, each with a previously unrecognized two-tiered structure.

PubMed

Pauling, L

1994-02-01

Analysis on the basis of the two-revolving-cluster model has been made of a cascade of 11 gamma-rays constituting a hyperdeformed band of 152(66)Dy86 (or possibly 153Dy) reported by Galindo-Uribarri et al. [Galindo-Uribarri, A., et al. (1993) Phys. Rev. Lett. 73, 231-234], leading to the conclusions that the band extends from values K approximately 82-104 for the angular-momentum quantum number, that the moment of inertia is approximately 5650 Da.fm2, that the composition of the central sphere is p40n50 and that of each of the clusters is p13n18, that each of the clusters consists of two tiers of spherons, and that the radii of revolution of the inner and outer tiers have values of about 8.00 and 11.20 fm, respectively.

Regulation of error-prone translesion synthesis by Spartan/C1orf124

PubMed Central

Kim, Myoung Shin; Machida, Yuka; Vashisht, Ajay A.; Wohlschlegel, James A.; Pang, Yuan-Ping; Machida, Yuichi J.

2013-01-01

Translesion synthesis (TLS) employs low fidelity polymerases to replicate past damaged DNA in a potentially error-prone process. Regulatory mechanisms that prevent TLS-associated mutagenesis are unknown; however, our recent studies suggest that the PCNA-binding protein Spartan plays a role in suppression of damage-induced mutagenesis. Here, we show that Spartan negatively regulates error-prone TLS that is dependent on POLD3, the accessory subunit of the replicative DNA polymerase Pol δ. We demonstrate that the putative zinc metalloprotease domain SprT in Spartan directly interacts with POLD3 and contributes to suppression of damage-induced mutagenesis. Depletion of Spartan induces complex formation of POLD3 with Rev1 and the error-prone TLS polymerase Pol ζ, and elevates mutagenesis that relies on POLD3, Rev1 and Pol ζ. These results suggest that Spartan negatively regulates POLD3 function in Rev1/Pol ζ-dependent TLS, revealing a previously unrecognized regulatory step in error-prone TLS. PMID:23254330

Broad Integration of Expression Maps and Co-Expression Networks Compassing Novel Gene Functions in the Brain

PubMed Central

Okamura-Oho, Yuko; Shimokawa, Kazuro; Nishimura, Masaomi; Takemoto, Satoko; Sato, Akira; Furuichi, Teiichi; Yokota, Hideo

2014-01-01

Using a recently invented technique for gene expression mapping in the whole-anatomy context, termed transcriptome tomography, we have generated a dataset of 36,000 maps of overall gene expression in the adult-mouse brain. Here, using an informatics approach, we identified a broad co-expression network that follows an inverse power law and is rich in functional interaction and gene-ontology terms. Our framework for the integrated analysis of expression maps and graphs of co-expression networks revealed that groups of combinatorially expressed genes, which regulate cell differentiation during development, were present in the adult brain and each of these groups was associated with a discrete cell types. These groups included non-coding genes of unknown function. We found that these genes specifically linked developmentally conserved groups in the network. A previously unrecognized robust expression pattern covering the whole brain was related to the molecular anatomy of key biological processes occurring in particular areas. PMID:25382412

Limitations to photosynthesis by proton motive force-induced photosystem II photodamage

PubMed Central

Davis, Geoffry A; Kanazawa, Atsuko; Schöttler, Mark Aurel; Kohzuma, Kaori; Froehlich, John E; Rutherford, A William; Satoh-Cruz, Mio; Minhas, Deepika; Tietz, Stefanie; Dhingra, Amit; Kramer, David M

2016-01-01

The thylakoid proton motive force (pmf) generated during photosynthesis is the essential driving force for ATP production; it is also a central regulator of light capture and electron transfer. We investigated the effects of elevated pmf on photosynthesis in a library of Arabidopsis thaliana mutants with altered rates of thylakoid lumen proton efflux, leading to a range of steady-state pmf extents. We observed the expected pmf-dependent alterations in photosynthetic regulation, but also strong effects on the rate of photosystem II (PSII) photodamage. Detailed analyses indicate this effect is related to an elevated electric field (Δψ) component of the pmf, rather than lumen acidification, which in vivo increased PSII charge recombination rates, producing singlet oxygen and subsequent photodamage. The effects are seen even in wild type plants, especially under fluctuating illumination, suggesting that Δψ-induced photodamage represents a previously unrecognized limiting factor for plant productivity under dynamic environmental conditions seen in the field. DOI: http://dx.doi.org/10.7554/eLife.16921.001 PMID:27697149

Wnt-Lrp5 Signaling Regulates Fatty Acid Metabolism in the Osteoblast

PubMed Central

Frey, Julie L.; Li, Zhu; Ellis, Jessica M.; Zhang, Qian; Farber, Charles R.; Aja, Susan; Wolfgang, Michael J.; Clemens, Thomas L.

2015-01-01

The Wnt coreceptors Lrp5 and Lrp6 are essential for normal postnatal bone accrual and osteoblast function. In this study, we identify a previously unrecognized skeletal function unique to Lrp5 that enables osteoblasts to oxidize fatty acids. Mice lacking the Lrp5 coreceptor specifically in osteoblasts and osteocytes exhibit the expected reductions in postnatal bone mass but also exhibit an increase in body fat with corresponding reductions in energy expenditure. Conversely, mice expressing a high bone mass mutant Lrp5 allele are leaner with reduced plasma triglyceride and free fatty acid levels. In this context, Wnt-initiated signals downstream of Lrp5, but not the closely related Lrp6 coreceptor, regulate the activation of β-catenin and thereby induce the expression of key enzymes required for fatty acid β-oxidation. These results suggest that Wnt-Lrp5 signaling regulates basic cellular activities beyond those associated with fate specification and differentiation in bone and that the skeleton influences global energy homeostasis via mechanisms independent of osteocalcin and glucose metabolism. PMID:25802278

Predictors of disease severity in patients admitted to a cholera treatment center in urban Haiti.

PubMed

Valcin, Claude-Lyne; Severe, Karine; Riche, Claudia T; Anglade, Benedict S; Moise, Colette Guiteau; Woodworth, Michael; Charles, Macarthur; Li, Zhongze; Joseph, Patrice; Pape, Jean W; Wright, Peter F

2013-10-01

Cholera, previously unrecognized in Haiti, spread through the country in the fall of 2010. An analysis was performed to understand the epidemiological characteristics, clinical management, and risk factors for disease severity in a population seen at the GHESKIO Cholera Treatment Center in Port-au-Prince. A comprehensive review of the medical records of patients admitted during the period of October 28, 2010-July 10, 2011 was conducted. Disease severity on admission was directly correlated with older age, more prolonged length of stay, and presentation during the two epidemic waves seen in the observation period. Although there was a high seroprevalence of human immunodeficiency virus (HIV), severity of cholera was not greater with HIV infection. This study documents the correlation of cholera waves with rainfall and its reduction in settings with improved sanitary conditions and potable water when newly introduced cholera affects all ages equally so that interventions must be directed throughout the population.

γδ T cells exhibit multifunctional and protective memory in intestinal tissues

PubMed Central

Sheridan, Brian S.; Romagnoli, Pablo A.; Pham, Quynh-Mai; Fu, Han-Hsuan; Alonzo, Francis; Schubert, Wolf-Dieter; Freitag, Nancy E.; Lefrançois, Leo

2013-01-01

Summary The study of T cell memory and the target of vaccine design has focused on memory subsumed by T cells bearing the αβ T cell receptor. Alternatively, γδ T cells are thought to provide rapid immunity particularly at mucosal borders. Here we have shown that a distinct subset of mucosal γδ T cells mounts an immune response to oral Listeria monocytogenes (Lm) infection leading to the development of multifunctional memory T cells in the murine intestinal mucosa that is capable of simultaneously producing interferon-γ and interleukin-17A. Challenge infection with oral Lm, but not oral Salmonella or intravenous Lm, induced rapid expansion of memory γδ T cells suggesting contextual specificity to the priming pathogen. Importantly, memory γδ T cells were able to provide enhanced protection against infection. These findings illustrate a previously unrecognized role for γδ T cells with hallmarks of adaptive immunity in the intestinal mucosa. PMID:23890071

Direct nitration and azidation of aliphatic carbons by an iron-dependent halogenase

PubMed Central

Chang, Wei-chen; Layne, Andrew P; Miles, Linde A; Krebs, Carsten

2014-01-01

Iron-dependent halogenases employ cis-halo-Fe(IV)-oxo (haloferryl) complexes to functionalize unactivated aliphatic carbon centers, a capability elusive to synthetic chemists. Halogenation requires (1) coordination of a halide anion (Cl− or Br−) to the enzyme's Fe(II) cofactor; (2) coupled activation of O2 and decarboxylation of α-ketoglutarate to generate the haloferryl intermediate; (3) abstraction of hydrogen (H•) from the substrate by the ferryl oxo group; and (4) transfer of the cis halogen as Cl• or Br• to the substrate radical. This enzymatic solution to an unsolved chemical challenge is potentially generalizable to installation of other functional groups, provided that the corresponding anions can support the four requisite steps. We show here that the wild-type halogenase SyrB2 can indeed direct aliphatic nitration and azidation reactions by the same chemical logic. The discovery and enhancement by mutagenesis of these previously unknown reaction types suggests unrecognized or untapped versatility in ferryl-mediated enzymatic C–H-bond activation. PMID:24463698

Global Analysis of Palmitoylated Proteins in Toxoplasma gondii.

PubMed

Foe, Ian T; Child, Matthew A; Majmudar, Jaimeen D; Krishnamurthy, Shruthi; van der Linden, Wouter A; Ward, Gary E; Martin, Brent R; Bogyo, Matthew

2015-10-14

Post-translational modifications (PTMs) such as palmitoylation are critical for the lytic cycle of the protozoan parasite Toxoplasma gondii. While palmitoylation is involved in invasion, motility, and cell morphology, the proteins that utilize this PTM remain largely unknown. Using a chemical proteomic approach, we report a comprehensive analysis of palmitoylated proteins in T. gondii, identifying a total of 282 proteins, including cytosolic, membrane-associated, and transmembrane proteins. From this large set of palmitoylated targets, we validate palmitoylation of proteins involved in motility (myosin light chain 1, myosin A), cell morphology (PhIL1), and host cell invasion (apical membrane antigen 1, AMA1). Further studies reveal that blocking AMA1 palmitoylation enhances the release of AMA1 and other invasion-related proteins from apical secretory organelles, suggesting a previously unrecognized role for AMA1. These findings suggest that palmitoylation is ubiquitous throughout the T. gondii proteome and reveal insights into the biology of this important human pathogen. Copyright © 2015 Elsevier Inc. All rights reserved.

A frontal cortex event-related potential driven by the basal forebrain

PubMed Central

Nguyen, David P; Lin, Shih-Chieh

2014-01-01

Event-related potentials (ERPs) are widely used in both healthy and neuropsychiatric conditions as physiological indices of cognitive functions. Contrary to the common belief that cognitive ERPs are generated by local activity within the cerebral cortex, here we show that an attention-related ERP in the frontal cortex is correlated with, and likely generated by, subcortical inputs from the basal forebrain (BF). In rats performing an auditory oddball task, both the amplitude and timing of the frontal ERP were coupled with BF neuronal activity in single trials. The local field potentials (LFPs) associated with the frontal ERP, concentrated in deep cortical layers corresponding to the zone of BF input, were similarly coupled with BF activity and consistently triggered by BF electrical stimulation within 5–10 msec. These results highlight the important and previously unrecognized role of long-range subcortical inputs from the BF in the generation of cognitive ERPs. DOI: http://dx.doi.org/10.7554/eLife.02148.001 PMID:24714497

Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

PubMed Central

Lerner, Thomas R.; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R.G.; Borel, Sophie; Diedrich, Collin R.; Rohde, Manfred; Wainwright, Helen; Collinson, Lucy M.; Wilkinson, Robert J.; Griffiths, Gareth; Gutierrez, Maximiliano G.

2016-01-01

In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. PMID:26901813

Responses of male sperm whales (Physeter macrocephalus) to killer whale sounds: implications for anti-predator strategies

PubMed Central

Curé, Charlotte; Antunes, Ricardo; Alves, Ana Catarina; Visser, Fleur; Kvadsheim, Petter H.; Miller, Patrick J. O.

2013-01-01

Interactions between individuals of different cetacean species are often observed in the wild. Killer whales (Orcinus orca) can be potential predators of many other cetaceans, and the interception of their vocalizations by unintended cetacean receivers may trigger anti-predator behavior that could mediate predator-prey interactions. We explored the anti-predator behaviour of five typically-solitary male sperm whales (Physeter macrocephalus) in the Norwegian Sea by playing sounds of mammal-feeding killer whales and monitoring behavioural responses using multi-sensor tags. Our results suggest that, rather than taking advantage of their large aerobic capacities to dive away from the perceived predator, sperm whales responded to killer whale playbacks by interrupting their foraging or resting dives and returning to the surface, changing their vocal production, and initiating a surprising degree of social behaviour in these mostly solitary animals. Thus, the interception of predator vocalizations by male sperm whales disrupted functional behaviours and mediated previously unrecognized anti-predator responses. PMID:23545484

Cut flowers: a potential pesticide hazard.

PubMed Central

Morse, D L; Baker, E L; Landrigan, P J

1979-01-01

Following reports of ten cases of possible organophosphate pesticide poisoning in florists exposed to pesticide residues on cut flowers, we conducted a prospective random-sample survey to determine residual pesticide levels on flowers imported into the United States via Miami, Florida. A sample of all flowers imported into Miami on three days in January 1977 showed that 18 (17.7 per cent) of 105 lots contained pesticide residue levels greater than 5 ppm, and that three lots had levels greater than 400 ppm. Azodrin (monocrotophos) was the most important contaminant with levels of 7.7--4,750 ppm detected in nine lots. We examined 20 quarantine workers in Miami and 12 commercial florists exposed to contaminated flowers. Occasional nonspecific symptoms compatible with possible organophosphate exposure were noted, but we found no abnormalities in plasma or red blood cell cholinesterase levels. This study documents a previously unrecognized potential source of occupational pesticide exposure and suggests that safety standards should be set for residue levels on cut flowers. PMID:420356

Sympatric speciation as a consequence of male pregnancy in seahorses

PubMed Central

Jones, Adam G.; Moore, Glenn I.; Kvarnemo, Charlotta; Walker, DeEtte; Avise, John C.

2003-01-01

The phenomenon of male pregnancy in the family Syngnathidae (seahorses, pipefishes, and sea dragons) undeniably has sculpted the course of behavioral evolution in these fishes. Here we explore another potentially important but previously unrecognized consequence of male pregnancy: a predisposition for sympatric speciation. We present microsatellite data on genetic parentage that show that seahorses mate size-assortatively in nature. We then develop a quantitative genetic model based on these empirical findings to demonstrate that sympatric speciation indeed can occur under this mating regime in response to weak disruptive selection on body size. We also evaluate phylogenetic evidence bearing on sympatric speciation by asking whether tiny seahorse species are sister taxa to large sympatric relatives. Overall, our results indicate that sympatric speciation is a plausible mechanism for the diversification of seahorses, and that assortative mating (in this case as a result of male parental care) may warrant broader attention in the speciation process for some other taxonomic groups as well. PMID:12732712

Prospective evaluation of the clinical utility of laryngeal electromyography.

PubMed

Ingle, John W; Young, VyVy N; Smith, Libby J; Munin, Micheal C; Rosen, Clark A

2014-12-01

To prospectively evaluate the clinical utility of laryngeal electromyography (LEMG) STUDY DESIGN: Prospective observational study. The study involved 50 consecutive patients referred for LEMG. Laryngologists initially indicated diagnoses and treatment plans under the assumption of no access to LEMG. Patients then underwent LEMG by blinded examiners. LEMG results were reviewed by each patient's laryngologist. Diagnoses and treatment plans were either maintained or altered based on the LEMG results. The diagnosis changed 10% (5/50) of the time and treatment plans were altered 36% (18/50) of the time based on information provided by LEMG. Observational periods were eliminated in 13/50 patients based on LEMG, moving them to permanent treatment. LEMG allowed the differentiation between joint fixation and bilateral paralysis in three patients. Previously unrecognized superior laryngeal neuropathies were identified in three patients. Laryngeal electromyography often provides clinically useful information that typically leads to a more accurate diagnosis and a more appropriate, expedited treatment plan. 2b. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Major earthquakes recorded by Speleothems in Midwestern U.S. caves

USGS Publications Warehouse

Panno, S.V.; Lundstrom, C.C.; Hackley, Keith C.; Curry, B. Brandon; Fouke, B.W.; Zhang, Z.

2009-01-01

Historic earthquakes generated by the New Madrid seismic zone represent some of the largest recorded in the United States, yet prehistoric events are recognized only through deformation in late-Wisconsin to Holocene-age, near surface sediments (liquefaction, monoclinal folding, and changes in river meanders). In this article, we show that speleothems in caves of southwestern Illinois and southeastern Missouri may constitute a previously unrecognized recorder of large earthquakes in the U.S. midcontinent region. The timing of the initiation and regrowth of stalagmites in southwestern Illinois and southeastern Missouri caves is consistent with the historic and prehistoric record of several known seismic events in the U.S. midcontinent region. We conclude that dating the initiation of original stalagmite growth and later postearthquake rejuvenation constitutes a new paleoseismic method that has the potential for being applied to any region around the world in the vicinity of major seismic zones where caves exist. Use of this technique could expand the geographical distribution of paleoseimic data, document prehistoric earthquakes, and help improve interpretations of paleoearthquakes.

A lateral signalling pathway coordinates shape volatility during cell migration

PubMed Central

Zhang, Liang; Luga, Valbona; Armitage, Sarah K.; Musiol, Martin; Won, Amy; Yip, Christopher M.; Plotnikov, Sergey V.; Wrana, Jeffrey L.

2016-01-01

Cell migration is fundamental for both physiological and pathological processes. Migrating cells usually display high dynamics in morphology, which is orchestrated by an integrative array of signalling pathways. Here we identify a novel pathway, we term lateral signalling, comprised of the planar cell polarity (PCP) protein Pk1 and the RhoGAPs, Arhgap21/23. We show that the Pk1–Arhgap21/23 complex inhibits RhoA, is localized on the non-protrusive lateral membrane cortex and its disruption leads to the disorganization of the actomyosin network and altered focal adhesion dynamics. Pk1-mediated lateral signalling confines protrusive activity and is regulated by Smurf2, an E3 ubiquitin ligase in the PCP pathway. Furthermore, we demonstrate that dynamic interplay between lateral and protrusive signalling generates cyclical fluctuations in cell shape that we quantify here as shape volatility, which strongly correlates with migration speed. These studies uncover a previously unrecognized lateral signalling pathway that coordinates shape volatility during productive cell migration. PMID:27226243

Ventromedial prefrontal cortex mediates visual attention during facial emotion recognition.

PubMed

Wolf, Richard C; Philippi, Carissa L; Motzkin, Julian C; Baskaya, Mustafa K; Koenigs, Michael

2014-06-01

The ventromedial prefrontal cortex is known to play a crucial role in regulating human social and emotional behaviour, yet the precise mechanisms by which it subserves this broad function remain unclear. Whereas previous neuropsychological studies have largely focused on the role of the ventromedial prefrontal cortex in higher-order deliberative processes related to valuation and decision-making, here we test whether ventromedial prefrontal cortex may also be critical for more basic aspects of orienting attention to socially and emotionally meaningful stimuli. Using eye tracking during a test of facial emotion recognition in a sample of lesion patients, we show that bilateral ventromedial prefrontal cortex damage impairs visual attention to the eye regions of faces, particularly for fearful faces. This finding demonstrates a heretofore unrecognized function of the ventromedial prefrontal cortex-the basic attentional process of controlling eye movements to faces expressing emotion. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

NF-κB inhibitors that prevent foam cell formation and atherosclerotic plaque accumulation.

PubMed

Plotkin, Jesse D; Elias, Michael G; Dellinger, Anthony L; Kepley, Christopher L

2017-08-01

The transformation of monocyte-derived macrophages into lipid-laden foam cells is one inflammatory process underlying atherosclerotic disease. Previous studies have demonstrated that fullerene derivatives (FDs) have inflammation-blunting properties. Thus, it was hypothesized that FD could inhibit the transformation process underlying foam cell formation. Fullerene derivatives inhibited the phorbol myristic acid/oxidized low-density lipoprotein-induced differentiation of macrophages into foam cells as determined by lipid staining and morphology.Lipoprotein-induced generation of TNF-α, C5a-induced MC activation, ICAM-1 driven adhesion, and CD36 expression were significantly inhibited in FD treated cells compared to non-treated cells. Inhibition appeared to be mediated through the NF-κB pathway as FD reduced expression of NF-κB and atherosclerosis-associated genes. Compared to controls, FD dramatically inhibited plaque formation in arteries of apolipoprotein E null mice. Thus, FD may be an unrecognized therapy to prevent atherosclerotic lesions via inhibition of foam cell formation and MC stabilization. Copyright © 2017 Elsevier Inc. All rights reserved.

Multidrug transport protein norM from vibrio cholerae simultaneously couples to sodium- and proton-motive force.

PubMed

Jin, Yoonhee; Nair, Asha; van Veen, Hendrik W

2014-05-23

Membrane transporters belonging to the multidrug and toxic compound extrusion family mediate the efflux of unrelated pharmaceuticals from the interior of the cell in organisms ranging from bacteria to human. These proteins are thought to fall into two classes that couple substrate efflux to the influx of either Na(+) or H(+). We studied the energetics of drug extrusion by NorM from Vibrio cholerae in proteoliposomes in which purified NorM protein was functionally reconstituted in an inside-out orientation. We establish that NorM simultaneously couples to the sodium-motive force and proton-motive force, and biochemically identify protein regions and residues that play important roles in Na(+) or H(+) binding. As the positions of protons are not available in current medium and high-resolution crystal structures of multidrug and toxic compound extrusion transporters, our findings add a previously unrecognized parameter to mechanistic models based of these structures. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Neuronal Control of Metabolism through Nutrient-Dependent Modulation of Tracheal Branching

PubMed Central

Linneweber, Gerit A.; Jacobson, Jake; Busch, Karl Emanuel; Hudry, Bruno; Christov, Christo P.; Dormann, Dirk; Yuan, Michaela; Otani, Tomoki; Knust, Elisabeth; de Bono, Mario; Miguel-Aliaga, Irene

2014-01-01

Summary During adaptive angiogenesis, a key process in the etiology and treatment of cancer and obesity, the vasculature changes to meet the metabolic needs of its target tissues. Although the cues governing vascular remodeling are not fully understood, target-derived signals are generally believed to underlie this process. Here, we identify an alternative mechanism by characterizing the previously unrecognized nutrient-dependent plasticity of the Drosophila tracheal system: a network of oxygen-delivering tubules developmentally akin to mammalian blood vessels. We find that this plasticity, particularly prominent in the intestine, drives—rather than responds to—metabolic change. Mechanistically, it is regulated by distinct populations of nutrient- and oxygen-responsive neurons that, through delivery of both local and systemic insulin- and VIP-like neuropeptides, sculpt the growth of specific tracheal subsets. Thus, we describe a novel mechanism by which nutritional cues modulate neuronal activity to give rise to organ-specific, long-lasting changes in vascular architecture. PMID:24439370

Analysis of a hyperdeformed band of 152(66)Dy86 on the basis of a structure with two revolving clusters, each with a previously unrecognized two-tiered structure.

PubMed Central

Pauling, L

1994-01-01

Analysis on the basis of the two-revolving-cluster model has been made of a cascade of 11 gamma-rays constituting a hyperdeformed band of 152(66)Dy86 (or possibly 153Dy) reported by Galindo-Uribarri et al. [Galindo-Uribarri, A., et al. (1993) Phys. Rev. Lett. 73, 231-234], leading to the conclusions that the band extends from values K approximately 82-104 for the angular-momentum quantum number, that the moment of inertia is approximately 5650 Da.fm2, that the composition of the central sphere is p40n50 and that of each of the clusters is p13n18, that each of the clusters consists of two tiers of spherons, and that the radii of revolution of the inner and outer tiers have values of about 8.00 and 11.20 fm, respectively. PMID:11607453

Iron-absorption band analysis for the discrimination of iron-rich zones

NASA Technical Reports Server (NTRS)

Rowan, L. C. (Principal Investigator)

1973-01-01

The author has identified the following significant results. Study has concentrated on the two primary aspects of the project, structural analysis through evaluation of lineaments and circular features and spectral analyses through digital computer-processing techniques. Several previously unrecognized lineaments are mapped which may be the surface manifestations of major fault or fracture zones. Two of these, the Walker Lane and the Midas Trench lineament system, transect the predominantly NNE-NNW-trending moutain ranges for more than 500 km. Correlation of major lineaments with productive mining districts implies a genetic relationship, the 50 circular or elliptical features delineated suggest a related role for Tertiary volcanism. Color-ratio composites have been used to identify limonitic zones and to discriminate mafic and felsic rock by combing diazo color transparencies of three different ratios. EROS Data Center scene identification number for color composite in this report is ER 1 CC 500. Refinement of enhancement procedures for the ratio images is progressing. Fieldwork in coordination with both spectral and structural analyses is underway.

Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit

PubMed Central

Hatzold, Julia; Beleggia, Filippo; Herzig, Hannah; Altmüller, Janine; Nürnberg, Peter; Bloch, Wilhelm; Wollnik, Bernd; Hammerschmidt, Matthias

2016-01-01

The molecular pathways underlying tumor suppression are incompletely understood. Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress). Blockade of the ensuing PI3K-AKT-mTORC1-NFκB-MMP9 pathway activation in basal cells, as well as systemic isotonicity, prevents malignant transformation. Our results identify hypotonic stress as a (previously unrecognized) contributor to tumor development and establish a novel paradigm of tumor suppression. DOI: http://dx.doi.org/10.7554/eLife.14277.001 PMID:27240166