Mammalian play: training for the unexpected.

PubMed

Spinka, M; Newberry, R C; Bekoff, M

2001-06-01

In this review, we present a new conceptual framework for the study of play behavior, a hitherto puzzling array of seemingly purposeless and unrelated behavioral elements that are recognizable as play throughout the mammalian lineage. Our major new functional hypothesis is that play enables animals to develop flexible kinematic and emotional responses to unexpected events in which they experience a sudden loss of control. Specifically, we propose that play functions to increase the versatility of movements used to recover from sudden shocks such as loss of balance and falling over, and to enhance the ability of animals to cope emotionally with unexpected stressful situations. To obtain this "training for the unexpected," we suggest that animals actively seek and create unexpected situations in play through self-handicapping; that is, deliberately relaxing control over their movements or actively putting themselves into disadvantageous positions and situations. Thus, play is comprised of sequences in which the players switch rapidly between well-controlled movements similar to those used in "serious" behavior and self-handicapping movements that result in temporary loss of control. We propose that this playful switching between in-control and out-of-control elements is cognitively demanding, setting phylogenetic and ontogenetic constraints on play, and is underlain by neuroendocrinological responses that produce a complex emotional state known as "having fun." Furthermore, we propose that play is often prompted by relatively novel or unpredictable stimuli, and is thus related to, although distinct from, exploration. We present 24 predictions that arise from our new theoretical framework, examining the extent to which they are supported by the existing empirical evidence and contrasting them with the predictions of four major alternative hypotheses about play. We argue that our "training for the unexpected" hypothesis can account for some previously puzzling kinematic, structural, motivational, emotional, cognitive, social, ontogenetic, and phylogenetic aspects of play. It may also account for a diversity of individual methods for coping with unexpected misfortunes.

[Triggering role of emotional stress and childbirth. Unexpected occurrence of Graves' disease compared to 96 cases of Hashimoto thyroiditis and 97 cases of thyroid nodules].

PubMed

Martin-du Pan, R C

1998-07-01

98 patients with Graves' disease have been compared to 95 patients with Hashimoto's thyroiditis and to 97 patients with benign thyroid nodules (control group) in order to evaluate the triggering role of major stressors and pregnancy in the occurrence of autoimmune thyroid diseases. A stress factor has been encountered in 11% cases of Graves' disease and in 6% of Hashimoto's and thyroid nodes (chi 2 test, not different). Graves' disease occurred after a pregnancy in 25% of the women in child bearing age versus 10% of the cases of Hashimoto's (p < 0.05) and 13% of the thyroid nodes. The role of stressors, if any, in triggering Graves' disease seems to be weak and dubious compared to the role of pregnancy and post-partum. It is assumed that the decrease of immunosuppressive hormones occurring after stress or delivery could induce a rebound autoimmune reaction responsible for the thyroid disease. In Hashimoto's thyroiditis, stress and pregnancies do not seem to have any triggering role.

The detection of faked identity using unexpected questions and mouse dynamics.

PubMed

Monaro, Merylin; Gamberini, Luciano; Sartori, Giuseppe

2017-01-01

The detection of faked identities is a major problem in security. Current memory-detection techniques cannot be used as they require prior knowledge of the respondent's true identity. Here, we report a novel technique for detecting faked identities based on the use of unexpected questions that may be used to check the respondent identity without any prior autobiographical information. While truth-tellers respond automatically to unexpected questions, liars have to "build" and verify their responses. This lack of automaticity is reflected in the mouse movements used to record the responses as well as in the number of errors. Responses to unexpected questions are compared to responses to expected and control questions (i.e., questions to which a liar also must respond truthfully). Parameters that encode mouse movement were analyzed using machine learning classifiers and the results indicate that the mouse trajectories and errors on unexpected questions efficiently distinguish liars from truth-tellers. Furthermore, we showed that liars may be identified also when they are responding truthfully. Unexpected questions combined with the analysis of mouse movement may efficiently spot participants with faked identities without the need for any prior information on the examinee.

The domestication and evolutionary ecology of apples.

PubMed

Cornille, Amandine; Giraud, Tatiana; Smulders, Marinus J M; Roldán-Ruiz, Isabel; Gladieux, Pierre

2014-02-01

The cultivated apple is a major fruit crop in temperate zones. Its wild relatives, distributed across temperate Eurasia and growing in diverse habitats, represent potentially useful sources of diversity for apple breeding. We review here the most recent findings on the genetics and ecology of apple domestication and its impact on wild apples. Genetic analyses have revealed a Central Asian origin for cultivated apple, together with an unexpectedly large secondary contribution from the European crabapple. Wild apple species display strong population structures and high levels of introgression from domesticated apple, and this may threaten their genetic integrity. Recent research has revealed a major role of hybridization in the domestication of the cultivated apple and has highlighted the value of apple as an ideal model for unraveling adaptive diversification processes in perennial fruit crops. We discuss the implications of this knowledge for apple breeding and for the conservation of wild apples. Copyright © 2013 Elsevier Ltd. All rights reserved.

The processing of unexpected positive response outcomes in the mediofrontal cortex.

PubMed

Ferdinand, Nicola K; Mecklinger, Axel; Kray, Jutta; Gehring, William J

2012-08-29

The human mediofrontal cortex, especially the anterior cingulate cortex, is commonly assumed to contribute to higher cognitive functions like performance monitoring. How exactly this is achieved is currently the subject of lively debate but there is evidence that an event's valence and its expectancy play important roles. One prominent theory, the reinforcement learning theory by Holroyd and colleagues (2002, 2008), assigns a special role to feedback valence, while the prediction of response-outcome (PRO) model by Alexander and Brown (2010, 2011) claims that the mediofrontal cortex is sensitive to unexpected events regardless of their valence. However, paradigms examining this issue have included confounds that fail to separate valence and expectancy. In the present study, we tested the two competing theories of performance monitoring by using an experimental task that separates valence and unexpectedness of performance feedback. The feedback-related negativity of the event-related potential, which is commonly assumed to be a reflection of mediofrontal cortex activity, was elicited not only by unexpected negative feedback, but also by unexpected positive feedback. This implies that the mediofrontal cortex is sensitive to the unexpectedness of events in general rather than their valence and by this supports the PRO model.

Acute Promyelocytic Leukemia: A Paradigm for Oncoprotein-Targeted Cure.

PubMed

de Thé, Hugues; Pandolfi, Pier Paolo; Chen, Zhu

2017-11-13

Recent clinical trials have demonstrated that the immense majority of acute promyelocytic leukemia (APL) patients can be definitively cured by the combination of two targeted therapies: retinoic acid (RA) and arsenic. Mouse models have provided unexpected insights into the mechanisms involved. Restoration of PML nuclear bodies upon RA- and/or arsenic-initiated PML/RARA degradation is essential, while RA-triggered transcriptional activation is dispensable for APL eradication. Mutations of the arsenic-binding site of PML/RARA, but also PML, have been detected in therapy-resistant patients, demonstrating the key role of PML in APL cure. PML nuclear bodies are druggable and could be harnessed in other conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell lymphoproliferations

PubMed Central

2011-01-01

Epstein-Barr virus (EBV) is a highly successful herpesvirus, colonizing more than 90% of the adult human population worldwide, although it is also associated with various malignant diseases. Primary infection is usually clinically silent, and subsequent establishment of latency in the memory B lymphocyte compartment allows persistence of the virus in the infected host for life. EBV is so markedly B-lymphotropic when exposed to human lymphocytes in vitro that the association of EBV with rare but distinct types of T and NK cell lymphoproliferations was quite unexpected. Whilst relatively rare, these EBV-associated T and NK lymphoproliferations can be therapeutically challenging and prognosis for the majority of patients is dismal. In this review, we summarize the current knowledge on the role of EBV in the pathogenesis of these tumours, and the implications for treatment. PMID:21899744

The Ecology, Biogeochemistry, and Optical Properties of Coccolithophores

NASA Astrophysics Data System (ADS)

Balch, William M.

2018-01-01

Coccolithophores are major contributors to phytoplankton communities and ocean biogeochemistry and are strong modulators of the optical field in the sea. New discoveries are changing paradigms about these calcifiers. A new role for silicon in coccolithophore calcification is coupling carbonate and silicon cycles. Phosphorus and iron play key roles in regulating coccolithophore growth. Comparing molecular phylogenies with coccolith morphometrics is forcing the reconciliation of biological and geological observations. Mixotrophy may be a possible life strategy for deep-dwelling species, which has ramifications for biological pump and alkalinity pump paradigms. Climate, ocean temperatures, and pH appear to be affecting coccolithophores in unexpected ways. Global calcification is approximately 1-3% of primary productivity and affects CO2 budgets. New measurements of the backscattering cross section of coccolithophores have improved satellite-based algorithms and their application in case I and case II optical waters. Remote sensing has allowed the detection of basin-scale coccolithophore features in the Southern Ocean.

Memory for musical tones: the impact of tonality and the creation of false memories.

PubMed

Vuvan, Dominique T; Podolak, Olivia M; Schmuckler, Mark A

2014-01-01

Although the relation between tonality and musical memory has been fairly well-studied, less is known regarding the contribution of tonal-schematic expectancies to this relation. Three experiments investigated the influence of tonal expectancies on memory for single tones in a tonal melodic context. In the first experiment, listener responses indicated superior recognition of both expected and unexpected targets in a major tonal context than for moderately expected targets. Importantly, and in support of previous work on false memories, listener responses also revealed a higher false alarm rate for expected than unexpected targets. These results indicate roles for tonal schematic congruency as well as distinctiveness in memory for melodic tones. The second experiment utilized minor melodies, which weakened tonal expectancies since the minor tonality can be represented in three forms simultaneously. Finally, tonal expectancies were abolished entirely in the third experiment through the use of atonal melodies. Accordingly, the expectancy-based results observed in the first experiment were disrupted in the second experiment, and disappeared in the third experiment. These results are discussed in light of schema theory, musical expectancy, and classic memory work on the availability and distinctiveness heuristics.

Memory for musical tones: the impact of tonality and the creation of false memories

PubMed Central

Vuvan, Dominique T.; Podolak, Olivia M.; Schmuckler, Mark A.

2014-01-01

Although the relation between tonality and musical memory has been fairly well-studied, less is known regarding the contribution of tonal-schematic expectancies to this relation. Three experiments investigated the influence of tonal expectancies on memory for single tones in a tonal melodic context. In the first experiment, listener responses indicated superior recognition of both expected and unexpected targets in a major tonal context than for moderately expected targets. Importantly, and in support of previous work on false memories, listener responses also revealed a higher false alarm rate for expected than unexpected targets. These results indicate roles for tonal schematic congruency as well as distinctiveness in memory for melodic tones. The second experiment utilized minor melodies, which weakened tonal expectancies since the minor tonality can be represented in three forms simultaneously. Finally, tonal expectancies were abolished entirely in the third experiment through the use of atonal melodies. Accordingly, the expectancy-based results observed in the first experiment were disrupted in the second experiment, and disappeared in the third experiment. These results are discussed in light of schema theory, musical expectancy, and classic memory work on the availability and distinctiveness heuristics. PMID:24971071

Influence of non-spatial working memory demands on reach-grasp responses to loss of balance: Effects of age and fall risk.

PubMed

Westlake, Kelly P; Johnson, Brian P; Creath, Robert A; Neff, Rachel M; Rogers, Mark W

2016-03-01

Reactive balance recovery strategies following an unexpected loss of balance are crucial to the prevention of falls, head trauma and other major injuries in older adults. While a longstanding focus has been on understanding lower limb recovery responses, the upper limbs also play a critical role. However, when a fall occurs, little is known about the role of memory and attention shifting on the reach to grasp recovery strategy and what factors determine the speed and precision of this response beyond simple reaction time. The objective of this study was to compare response time and accuracy of a stabilizing grasp following a balance perturbation in older adult fallers compared to non-fallers and younger adults while loading the processing demands of non-spatial, verbal working memory. Working memory was engaged with a progressively challenging verb-generation task that was interrupted by an unexpected sideways platform perturbation and a pre-instructed reach to grasp response. Results revealed that the older adults, particularly those at high fall risk, demonstrated significantly increased movement time to handrail contact and grasping errors during conditions in which non-spatial memory was actively engaged. These findings provide preliminary evidence of the cognitive deficit in attention shifting away from an ongoing working memory task that underlies delayed and inaccurate protective reach to grasp responses in older adult fallers. Copyright © 2016 Elsevier B.V. All rights reserved.

Striatal and midbrain connectivity with the hippocampus selectively boosts memory for contextual novelty

PubMed Central

Kafkas, Alexandros; Montaldi, Daniela

2015-01-01

The role of contextual expectation in processing familiar and novel stimuli was investigated in a series of experiments combining eye tracking, functional magnetic resonance imaging, and behavioral methods. An experimental paradigm emphasizing either familiarity or novelty detection at retrieval was used. The detection of unexpected familiar and novel stimuli, which were characterized by lower probability, engaged activity in midbrain and striatal structures. Specifically, detecting unexpected novel stimuli, relative to expected novel stimuli, produced greater activity in the substantia nigra/ventral tegmental area (SN/VTA), whereas the detection of unexpected familiar, relative to expected, familiar stimuli, elicited activity in the striatum/globus pallidus (GP). An effective connectivity analysis showed greater functional coupling between these two seed areas (GP and SN/VTA) and the hippocampus, for unexpected than for expected stimuli. Within this network of midbrain/striatal–hippocampal interactions two pathways are apparent; the direct SN–hippocampal pathway sensitive to unexpected novelty and the perirhinal–GP–hippocampal pathway sensitive to unexpected familiarity. In addition, increased eye fixations and pupil dilations also accompanied the detection of unexpected relative to expected familiar and novel stimuli, reflecting autonomic activity triggered by the functioning of these two pathways. Finally, subsequent memory for unexpected, relative to expected, familiar, and novel stimuli was characterized by enhanced recollection, but not familiarity, accuracy. Taken together, these findings suggest that a hippocampal–midbrain network, characterized by two distinct pathways, mediates encoding facilitation and most critically, that this facilitation is driven by contextual novelty, rather than by the absolute novelty of a stimulus. This contextually sensitive neural mechanism appears to elicit increased exploratory behavior, leading subsequently to greater recollection of the unexpected stimulus. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:25708843

Phylogenomic analysis of Copepoda (Arthropoda, Crustacea) reveals unexpected similarities with earlier proposed morphological phylogenies.

PubMed

Eyun, Seong-Il

2017-01-19

Copepods play a critical role in marine ecosystems but have been poorly investigated in phylogenetic studies. Morphological evidence supports the monophyly of copepods, whereas interordinal relationships continue to be debated. In particular, the phylogenetic position of the order Harpacticoida is still ambiguous and inconsistent among studies. Until now, a small number of molecular studies have been done using only a limited number or even partial genes and thus there is so far no consensus at the order-level. This study attempted to resolve phylogenetic relationships among and within four major copepod orders including Harpacticoida and the phylogenetic position of Copepoda among five other crustacean groups (Anostraca, Cladocera, Sessilia, Amphipoda, and Decapoda) using 24 nuclear protein-coding genes. Phylogenomics has confirmed the monophyly of Copepoda and Podoplea. However, this study reveals surprising differences with the majority of the copepod phylogenies and unexpected similarities with postembryonic characters and earlier proposed morphological phylogenies; More precisely, Cyclopoida is more closely related to Siphonostomatoida than to Harpacticoida which is likely the most basally-branching group of Podoplea. Divergence time estimation suggests that the origin of Harpacticoida can be traced back to the Devonian, corresponding well with recently discovered fossil evidence. Copepoda has a close affinity to the clade of Malacostraca and Thecostraca but not to Branchiopoda. This result supports the hypothesis of the newly proposed clades, Communostraca, Multicrustacea, and Allotriocarida but further challenges the validity of Hexanauplia and Vericrustacea. The first phylogenomic study of Copepoda provides new insights into taxonomic relationships and represents a valuable resource that improves our understanding of copepod evolution and their wide range of ecological adaptations.

Sudden Unexpected Death in Fetal Life Through Early Childhood

PubMed Central

Kinney, Hannah C.; Willinger, Marian

2016-01-01

In March 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop entitled “Sudden Unexpected Death in Fetal Life Through Early Childhood: New Opportunities.” Its objective was to advance efforts to understand and ultimately prevent sudden deaths in early life, by considering their pathogenesis as a potential continuum with some commonalities in biological origins or pathways. A second objective of this meeting was to highlight current issues surrounding the classification of sudden infant death syndrome (SIDS), and the implications of variations in the use of the term “SIDS” in forensic practice, and pediatric care and research. The proceedings reflected the most current knowledge and understanding of the origins and biology of vulnerability to sudden unexpected death, and its environmental triggers. Participants were encouraged to consider the application of new technologies and “omics” approaches to accelerate research. The major advances in delineating the intrinsic vulnerabilities to sudden death in early life have come from epidemiologic, neural, cardiac, metabolic, genetic, and physiologic research, with some commonalities among cases of unexplained stillbirth, SIDS, and sudden unexplained death in childhood observed. It was emphasized that investigations of sudden unexpected death are inconsistent, varying by jurisdiction, as are the education, certification practices, and experience of death certifiers. In addition, there is no practical consensus on the use of “SIDS” as a determination in cause of death. Major clinical, forensic, and scientific areas are identified for future research. PMID:27230764

The Burden of Loss: Unexpected death of a loved one and psychiatric disorders across the life course in a national study

PubMed Central

Keyes, Katherine M.; Pratt, Charissa; Galea, Sandro; McLaughlin, Katie A.; Koenen, Karestan C.; Shear, M. Katherine

2014-01-01

Background Unexpected death of a loved one is common and associated with subsequent elevations in symptoms of multiple forms of psychopathology. Determining whether this experience predicts novel onset of psychiatric disorders and whether these associations vary across the life course has important clinical implications. Aims To examine associations of a loved one’s unexpected death with first onset of common anxiety, mood, and substance disorders in a population-based sample. Methods Relation between unexpected death and first onset of lifetime DSM-IV disorders estimated using a structured interview of adults in the US general population (analytic sample size=27,534). Models controlled for prior occurrence of any disorder, other traumatic event experiences, and demographics. Results Unexpected death was the most common traumatic experience and most likely to be rated as the respondent’s worst, regardless of other traumatic experiences. Increased incidence after unexpected death was observed at every point across the life course for major depressive episodes, panic disorder, and post-traumatic stress disorder. Increased incidence was clustered in later adult age groups for manic episodes, phobias, alcohol disorders, and generalized anxiety disorder. Conclusions The bereavement period is associated with elevated risk for the onset of multiple psychiatric disorders, consistently across the life course and coincident with the experience of the loved one’s death. Novel associations between unexpected death and onset of several disorders, including mania, confirm multiple case reports and small studies, and suggest an important emerging area for clinical research and practice. PMID:24832609

Breaking Frame in a Role-Play Simulation: A Language Socialization Perspective

ERIC Educational Resources Information Center

Schick, Laurie

2008-01-01

This article uses key concepts developed in frame analysis and language socialization theories to reconceptualize role-play simulation as socialization practice. The reconceptualization includes (a) an effort to explain an unexpected response to a role-play simulation on the topic of bullying and (b) a discussion regarding how this explanation…

Trimodel Mammography with Perfect Coregistration

DTIC Science & Technology

2017-02-01

background, the major confounding factor in reading mammography; the imaging characteristics suggest that this contrast mechanism would be preferable...image with enhanced edges and reduced anatomical background, the major confounding factor in reading mammography; the imaging characteristics suggest...subjects, vertebrate animals , biohazards, and/or select agents Describe significant deviations, unexpected outcomes, or changes in approved protocols

Capping protein is essential for cell migration in vivo and for filopodial morphology and dynamics

PubMed Central

Sinnar, Shamim A.; Antoku, Susumu; Saffin, Jean-Michel; Cooper, Jon A.; Halpain, Shelley

2014-01-01

Capping protein (CP) binds to barbed ends of growing actin filaments and inhibits elongation. CP is essential for actin-based motility in cell-free systems and in Dictyostelium. Even though CP is believed to be critical for creating the lamellipodial actin structure necessary for protrusion and migration, CP's role in mammalian cell migration has not been directly tested. Moreover, recent studies have suggested that structures besides lamellipodia, including lamella and filopodia, may have unappreciated roles in cell migration. CP has been postulated to be absent from filopodia, and thus its role in filopodial activity has remained unexplored. We report that silencing CP in both cultured mammalian B16F10 cells and in neurons of developing neocortex impaired cell migration. Moreover, we unexpectedly observed that low levels of CP were detectable in the majority of filopodia. CP depletion decreased filopodial length, altered filopodial shape, and reduced filopodial dynamics. Our results support an expansion of the potential roles that CP plays in cell motility by implicating CP in filopodia as well as in lamellipodia, both of which are important for locomotion in many types of migrating cells. PMID:24829386

Unexpected inhibition of CO 2 gas hydrate formation in dilute TBAB solutions and the critical role of interfacial water structure

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

Nguyen, Ngoc N.; Nguyen, Anh V.; Nguyen, Khoi T.

Gas hydrates formed under moderated conditions open up novel approaches to tackling issues related to energy supply, gas separation, and CO 2 sequestration. Several additives like tetra-n-butylammonium bromide (TBAB) have been empirically developed and used to promote gas hydrate formation. Here we report unexpected experimental results which show that TBAB inhibits CO 2 gas hydrate formation when used at minuscule concentration. We also used spectroscopic techniques and molecular dynamics simulation to gain further insights and explain the experimental results. They have revealed the critical role of water alignment at the gas-water interface induced by surface adsorption of tetra-n-butylammonium cation (TBAmore » +) which gives rise to the unexpected inhibition of dilute TBAB solution. The water perturbation by TBA + in the bulk is attributed to the promotion effect of high TBAB concentration on gas hydrate formation. We explain our finding using the concept of activation energy of gas hydrate formation. Our results provide a step toward to mastering the control of gas hydrate formation.« less

Is anybody doing it? An experimental study of the effect of normative messages on intention to do physical activity.

PubMed

van Bavel, René; Esposito, Gabriele; Baranowski, Tom

2014-07-31

The study explores whether messages about the physical activity levels of the majority (i.e. normative messages) affect young adults' intention to engage in regular physical activity. An experimental survey among 16 to 24 year-olds in Bulgaria, Croatia and Romania (n = 1200) was conducted in March 2013. A control group received no message; one treatment group was told that the majority was physically active (positive message); and another treatment group was told that the majority was not physically active (negative message). Both the positive and (unexpectedly) the negative normative messages showed a significant and positive effect on intention to be physically active. There was no difference between the effects of the messages. Normative messages affect intention, which is encouraging for public health campaigns. The effect of the positive message confirms previous findings on conformity to the norm; the effect of the negative message is unexpected and requires further research to be understood.

The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis.

PubMed

Bielli, Pamela; Busà, Roberta; Di Stasi, Savino M; Munoz, Manuel J; Botti, Flavia; Kornblihtt, Alberto R; Sette, Claudio

2014-04-01

Alternative splicing (AS) is tightly coupled to transcription for the majority of human genes. However, how these two processes are linked is not well understood. Here, we unveil a direct role for the transcription factor FBI-1 in the regulation of AS. FBI-1 interacts with the splicing factor SAM68 and reduces its binding to BCL-X mRNA. This, in turn, results in the selection of the proximal 5' splice site in BCL-X exon 2, thereby favoring the anti-apoptotic BCL-XL variant and counteracting SAM68-mediated apoptosis. Conversely, depletion of FBI-1, or expression of a SAM68 mutant lacking the FBI-1 binding region, restores the ability of SAM68 to induce BCL-XS splicing and apoptosis. FBI-1's role in splicing requires the activity of histone deacetylases, whose pharmacological inhibition recapitulates the effects of FBI-1 knockdown. Our study reveals an unexpected function for FBI-1 in splicing modulation with a direct impact on cell survival.

The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis

PubMed Central

Bielli, Pamela; Busà, Roberta; Di Stasi, Savino M; Munoz, Manuel J; Botti, Flavia; Kornblihtt, Alberto R; Sette, Claudio

2014-01-01

Alternative splicing (AS) is tightly coupled to transcription for the majority of human genes. However, how these two processes are linked is not well understood. Here, we unveil a direct role for the transcription factor FBI-1 in the regulation of AS. FBI-1 interacts with the splicing factor SAM68 and reduces its binding to BCL-X mRNA. This, in turn, results in the selection of the proximal 5′ splice site in BCL-X exon 2, thereby favoring the anti-apoptotic BCL-XL variant and counteracting SAM68-mediated apoptosis. Conversely, depletion of FBI-1, or expression of a SAM68 mutant lacking the FBI-1 binding region, restores the ability of SAM68 to induce BCL-XS splicing and apoptosis. FBI-1's role in splicing requires the activity of histone deacetylases, whose pharmacological inhibition recapitulates the effects of FBI-1 knockdown. Our study reveals an unexpected function for FBI-1 in splicing modulation with a direct impact on cell survival. PMID:24514149

DNA Methylation in Embryo Development: Epigenetic Impact of ART (Assisted Reproductive Technologies).

PubMed

Canovas, Sebastian; Ross, Pablo J; Kelsey, Gavin; Coy, Pilar

2017-11-01

DNA methylation can be considered a component of epigenetic memory with a critical role during embryo development, and which undergoes dramatic reprogramming after fertilization. Though it has been a focus of research for many years, the reprogramming mechanism is still not fully understood. Recent results suggest that absence of maintenance at DNA replication is a major factor, and that there is an unexpected role for TET3-mediated oxidation of 5mC to 5hmC in guarding against de novo methylation. Base-resolution and genome-wide profiling methods are enabling more comprehensive assessments of the extent to which ART might impair DNA methylation reprogramming, and which sequence elements are most vulnerable. Indeed, as we also review here, studies showing the effect of culture media, ovarian stimulation or embryo transfer on the methylation pattern of embryos emphasize the need to face ART-associated defects and search for strategies to mitigate adverse effects on the health of ART-derived children. © 2017 WILEY Periodicals, Inc.

The hypothalamic-pituitary-thyroid axis and biological rhythms: The discovery of TSH's unexpected role using animal models.

PubMed

Ikegami, Keisuke; Yoshimura, Takashi

2017-10-01

Thyroid hormones (TH) are important for development, growth, and metabolism. It is also clear that the synthesis and secretion of TH are regulated by the hypothalamic-pituitary-thyroid (HPT) axis. Animal models have helped advance our understanding of the roles and regulatory mechanisms of TH. The animals' bodies develop through coordinated timing of cell division and differentiation. Studies of frog metamorphosis led to the discovery of TH and their role in development. However, to adapt to rhythmic environmental changes, animals also developed various endocrine rhythms. Studies of rodents clarified the neural and molecular mechanisms underlying the circadian regulation of the HPT axis. Moreover, birds have a sophisticated seasonal adaptation mechanism, and recent studies of quail revealed unexpected roles for thyroid-stimulating hormone (TSH) and TH in the seasonal regulation of reproduction. Interestingly, this mechanism is conserved in mammals. Thus, we review how animal studies have shaped our general understanding of the HPT axis in relation to biological rhythms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Control of fast elbow movement: a study of electromyographic patterns during movements against unexpectedly decreased inertial load.

PubMed

Latash, M L

1994-01-01

Predictions of three models of single-joint motor control were compared with experimental observations of the changes in electromyographic (EMG) patterns during fast voluntary movements against an unexpectedly reduced inertial load. The subjects performed elbow flexions over 40 degrees "as fast as possible" in two series. During the first series, an approximately 40% decrease in inertia, simulated by a torque-motor, might occur unpredictably on half of the trials (unloaded trials). During the second series, all the trials were unloaded. The major findings are: (1) no differences in the antagonist burst latency in unexpectedly unloaded and unperturbed trials; (2) a decrease in the antagonist latency during expected unloadings; (3) a small, statistically non significant decrease in the first agonist burst EMG integral; and (4) a larger, statistically significant increase in the antagonist burst EMG integral in unexpectedly unloaded trials as compared to unperturbed trials. The data are in good correspondence with a version of the equilibrium-point hypothesis that assumes central programming of the beginning of the antagonist burst and incorporates the possibility of reflex-induced changes in EMG amplitudes.

Sudden unexpected death related to enterovirus myocarditis: histopathology, immunohistochemistry and molecular pathology diagnosis at post-mortem

PubMed Central

2012-01-01

Background Viral myocarditis is a major cause of sudden unexpected death in children and young adults. Until recently, coxsackievirus B3 (CVB3) has been the most commonly implicated virus in myocarditis. At present, no standard diagnosis is generally accepted due to the insensitivity of traditional diagnostic tests. This has prompted health professionals to seek new diagnostic approaches, which resulted in the emergence of new molecular pathological tests and a more detailed immunohistochemical and histopathological analysis. When supplemented with immunohistochemistry and molecular pathology, conventional histopathology may provide important clues regarding myocarditis underlying etiology. Methods This study is based on post-mortem samples from sudden unexpected death victims and controls who were investigated prospectively. Immunohistochemical investigations for the detection of the enteroviral capsid protein VP1 and the characterization and quantification of myocardial inflammatory reactions as well as molecular pathological methods for enteroviral genome detection were performed. Results Overall, 48 sudden unexpected death victims were enrolled. As for controls, 37 cases of unnatural traffic accident victims were studied. Enterovirus was detected in 6 sudden unexpected death cases (12.5 %). The control samples were completely enterovirus negative. Furthermore, the enteroviral capsid protein VP1 in the myocardium was detected in enterovirus-positive cases revealed by means of reverse transcriptase-polymerase chain reaction (RT-PCR). Unlike control samples, immunohistochemical investigations showed a significant presence of T and B lymphocytes in sudden unexpected death victims. Conclusions Our findings demonstrate clearly a higher prevalence of viral myocarditis in cases of sudden unexpected death compared to control subjects, suggesting that coxsackie B enterovirus may contribute to myocarditis pathogenesis significantly. PMID:22966951

Structural imaging biomarkers of sudden unexpected death in epilepsy

PubMed Central

Wandschneider, Britta; Koepp, Matthias; Scott, Catherine; Micallef, Caroline; Balestrini, Simona; Sisodiya, Sanjay M.; Thom, Maria; Harper, Ronald M.; Sander, Josemir W.; Vos, Sjoerd B.; Duncan, John S.; Lhatoo, Samden

2015-01-01

Sudden unexpected death in epilepsy is a major cause of premature death in people with epilepsy. We aimed to assess whether structural changes potentially attributable to sudden death pathogenesis were present on magnetic resonance imaging in people who subsequently died of sudden unexpected death in epilepsy. In a retrospective, voxel-based analysis of T1 volume scans, we compared grey matter volumes in 12 cases of sudden unexpected death in epilepsy (two definite, 10 probable; eight males), acquired 2 years [median, interquartile range (IQR) 2.8] before death [median (IQR) age at scanning 33.5 (22) years], with 34 people at high risk [age 30.5 (12); 19 males], 19 at low risk [age 30 (7.5); 12 males] of sudden death, and 15 healthy controls [age 37 (16); seven males]. At-risk subjects were defined based on risk factors of sudden unexpected death in epilepsy identified in a recent combined risk factor analysis. We identified increased grey matter volume in the right anterior hippocampus/amygdala and parahippocampus in sudden death cases and people at high risk, when compared to those at low risk and controls. Compared to controls, posterior thalamic grey matter volume, an area mediating oxygen regulation, was reduced in cases of sudden unexpected death in epilepsy and subjects at high risk. The extent of reduction correlated with disease duration in all subjects with epilepsy. Increased amygdalo-hippocampal grey matter volume with right-sided changes is consistent with histo-pathological findings reported in sudden infant death syndrome. We speculate that the right-sided predominance reflects asymmetric central influences on autonomic outflow, contributing to cardiac arrhythmia. Pulvinar damage may impair hypoxia regulation. The imaging findings in sudden unexpected death in epilepsy and people at high risk may be useful as a biomarker for risk-stratification in future studies. PMID:26264515

Omnipresence of the polyproline II helix in fibrous and globular proteins.

PubMed

Esipova, Natalia G; Tumanyan, Vladimir G

2017-02-01

Left-handed helical conformation of a polypeptide chain (PPII) is the third type of the protein backbone structure. This conformation universally exists in fibrous, globular proteins, and biologically active peptides. It has unique physical and chemical properties determining a wide range of biological functions, from the protein folding to the tissue differentiation. New examples of the structure have been appearing in spite of difficulties in their detection and investigation. The annotation and prediction of the PPII was also a challenging task. Recently, many PPII motifs with new and/or unexpected functions are being accumulated in databases. In this review we describe the major structural and dynamic forms of PPII, the diversity of its functions, and the role in different biological processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spinal Endocannabinoids and CB1 Receptors Mediate C-Fiber-Induced Heterosynaptic Pain Plasticity

PubMed Central

Pernía-Andrade, Alejandro J.; Kato, Ako; Witschi, Robert; Nyilas, Rita; Katona, István; Freund, Tamás F.; Watanabe, Masahiko; Filitz, Jörg; Koppert, Wolfgang; Schüttler, Jürgen; Ji, Guangchen; Neugebauer, Volker; Marsicano, Giovanni; Lutz, Beat; Vanegas, Horacio; Zeilhofer, Hanns Ulrich

2010-01-01

Diminished synaptic inhibition in the spinal dorsal horn is a major contributor to chronic pain. Pathways, which reduce synaptic inhibition in inflammatory and neuropathic pain states, have been identified, but central hyperalgesia and diminished dorsal horn synaptic inhibition also occur in the absence of inflammation or neuropathy, solely triggered by intense nociceptive (C–fiber) input to the spinal dorsal horn. We found that endocannabinoids produced upon strong nociceptive stimulation activated CB1 receptors on inhibitory dorsal horn neurons to reduce the synaptic release of GABA and glycine and thus rendered nociceptive neurons excitable by non-painful stimuli. Spinal endocannabinoids and CB1 receptors on inhibitory dorsal horn interneurons act as mediators of heterosynaptic pain sensitization and play an unexpected role in dorsal horn pain controlling circuits. PMID:19661434

[Post-mortem microbiology analysis].

PubMed

Fernández-Rodríguez, Amparo; Alberola, Juan; Cohen, Marta Cecilia

2013-12-01

Post-mortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. Indeed, it is routinely applied to donor studies in the clinical setting, as well as in sudden and unexpected death in the forensic field. Implementation of specific sampling techniques in autopsy can minimize the possibility of contamination, making interpretation of the results easier. Specific interpretation criteria for post-mortem cultures, the use of molecular diagnosis, and its fusion with molecular biology and histopathology have led to post-mortem microbiology playing a major role in autopsy. Multidisciplinary work involving microbiologists, pathologists, and forensic physicians will help to improve the achievements of post-mortem microbiology, prevent infectious diseases, and contribute to a healthier population. Crown Copyright © 2012. Published by Elsevier Espana. All rights reserved.

Erythrocyte Alloimmunization and Autoimmunization among Blood Donors and Recipients visiting a Tertiary Care Hospital.

PubMed

Kaur, Daljit; Bains, Lovenish; Kandwal, Manoj; Parmar, Indu

2017-03-01

The ultimate aim of pretransfusion testing is the acceptable survival of donor red cells in recipient's body and antibody detection plays a critical role in achieving the same. The cornerstone of antibody detection method is detecting an unexpected antibody as against the expected antibodies of ABO blood group system. Autoantibodies can also interfere with the detection of clinically significant alloantibodies. To study the frequency of alloantibodies and autoantibodies in the healthy blood donors and patient population visiting our hospital. The Column Agglutination Technology (CAT) was used for ABO RhD blood grouping, Direct Antiglobulin Test (DAT), Autocontrol (AC), Indirect Antiglobulin Test (IAT) and red cell antibody screening and the unexpected reactions in any of these tests were recorded for further evaluation. Ethylene Diamine Tetra Acetic Acid (EDTA) blood samples were used for all these tests for both blood donors and admitted patients. The CAT was exercised for the blood grouping (using ABD-Reverse Diluent cassettes) and antibody screening (using 0.8% Surgiscreen, Ortho Clinical Diagnostics Limited, USA and Low Ionic Strength Saline Ortho BLISS with AHG cassettes) on the automated immunohaematology platform ORTHO AutoVue ® Innova system (Ortho Clinical Diagnostics Limited, USA). Among all blood donors (n=6350), seven (0.11%) donors had showed unexpected reaction. Of these, four had positive antibody screen (three having naturally occuring antibodies 2=anti-M, 1=anti-Le a and 1=inconclusive) and the other three had positive DAT. Of all the patient samples (n=6136) screened for irregular red cell antibodies, four (0.06%) patients were found to have unexpected reaction revealing one (0.02%) with anti-M antibody and the other three (0.05%) had autoantibodies in their serum. The combined prevalence for both blood donor and recipient population (n=12,486) was found to be 0.11% at our center. The alloimmunisation among patient population was found to be lower than many other studies worldwide as our hospital does not cater to multitransfused or transfusion dependant patients with haematological disorders and majorly elective surgery patients with no history of previous blood transfusions visit our hospital.

Erythrocyte Alloimmunization and Autoimmunization among Blood Donors and Recipients visiting a Tertiary Care Hospital

PubMed Central

Bains, Lovenish; Kandwal, Manoj; Parmar, Indu

2017-01-01

Introduction The ultimate aim of pretransfusion testing is the acceptable survival of donor red cells in recipient’s body and antibody detection plays a critical role in achieving the same. The cornerstone of antibody detection method is detecting an unexpected antibody as against the expected antibodies of ABO blood group system. Autoantibodies can also interfere with the detection of clinically significant alloantibodies. Aim To study the frequency of alloantibodies and autoantibodies in the healthy blood donors and patient population visiting our hospital. Materials and Methods The Column Agglutination Technology (CAT) was used for ABO RhD blood grouping, Direct Antiglobulin Test (DAT), Autocontrol (AC), Indirect Antiglobulin Test (IAT) and red cell antibody screening and the unexpected reactions in any of these tests were recorded for further evaluation. Ethylene Diamine Tetra Acetic Acid (EDTA) blood samples were used for all these tests for both blood donors and admitted patients. The CAT was exercised for the blood grouping (using ABD-Reverse Diluent cassettes) and antibody screening (using 0.8% Surgiscreen, Ortho Clinical Diagnostics Limited, USA and Low Ionic Strength Saline Ortho BLISS with AHG cassettes) on the automated immunohaematology platform ORTHO AutoVue® Innova system (Ortho Clinical Diagnostics Limited, USA). Results Among all blood donors (n=6350), seven (0.11%) donors had showed unexpected reaction. Of these, four had positive antibody screen (three having naturally occuring antibodies 2=anti-M, 1=anti-Lea and 1=inconclusive) and the other three had positive DAT. Of all the patient samples (n=6136) screened for irregular red cell antibodies, four (0.06%) patients were found to have unexpected reaction revealing one (0.02%) with anti-M antibody and the other three (0.05%) had autoantibodies in their serum. Conclusion The combined prevalence for both blood donor and recipient population (n=12,486) was found to be 0.11% at our center. The alloimmunisation among patient population was found to be lower than many other studies worldwide as our hospital does not cater to multitransfused or transfusion dependant patients with haematological disorders and majorly elective surgery patients with no history of previous blood transfusions visit our hospital. PMID:28511387

Cytotoxic T Lymphocyte Epitopes of HIV-1 Nef

PubMed Central

Lucchiari-Hartz, Maria; van Endert, Peter M.; Lauvau, Grégoire; Maier, Reinhard; Meyerhans, Andreas; Mann, Derek; Eichmann, Klaus; Niedermann, Gabriele

2000-01-01

Although a pivotal role of proteasomes in the proteolytic generation of epitopes for major histocompatibility complex (MHC) class I presentation is undisputed, their precise function is currently the subject of an active debate: do proteasomes generate many epitopes in definitive form, or do they merely generate the COOH termini, whereas the definitive NH2 termini are cleaved by aminopeptidases? We determined five naturally processed MHC class I ligands derived from HIV-1 Nef. Unexpectedly, the five ligands correspond to only three cytotoxic T lymphocyte (CTL) epitopes, two of which occur in two COOH-terminal length variants. Parallel analyses of proteasomal digests of a Nef fragment encompassing the epitopes revealed that all five ligands are direct products of proteasomes. Moreover, in four of the five ligands, the NH2 termini correspond to major proteasome cleavage sites, and putative NH2-terminally extended precursor fragments were detected for only one of the five ligands. All ligands are transported by the transporter associated with antigen processing (TAP). The combined results from these five ligands provide strong evidence that many definitive MHC class I ligands are precisely cleaved at both ends by proteasomes. Additional evidence supporting this conclusion is discussed, along with contrasting results of others who propose a strong role for NH2-terminal trimming with direct proteasomal epitope generation being a rare event. PMID:10637269

18 F-FDG PET/CT for planning external beam radiotherapy alters therapy in 11% of 581 patients.

PubMed

Birk Christensen, Charlotte; Loft-Jakobsen, Annika; Munck Af Rosenschöld, Per; Højgaard, Liselotte; Roed, Henrik; Berthelsen, Anne K

2018-03-01

18 F-FDG PET/CT (FDG PET/CT) used in radiotherapy planning for extra-cerebral malignancy may reveal metastases to distant sites that may affect the choice of therapy. To investigate the role of FDG PET/CT on treatment strategy changes induced by the use of PET/CT as part of the radiotherapy planning. 'A major change of treatment strategy' was defined as either including more lesions in the gross tumour volume (GTV) distant from the primary tumour or a change in treatment modalities. The study includes 581 consecutive patients who underwent an FDG PET/CT scan for radiotherapy planning in our institution in the year 2008. All PET/CT scans were performed with the patient in treatment position with the use of immobilization devices according to the intended radiotherapy treatment. All scans were evaluated by a nuclear medicine physician together with a radiologist to delineate PET-positive GTV (GTV-PET). For 63 of the patients (11%), the PET/CT simulation scans resulted in a major change in treatment strategy because of the additional diagnostic information. Changes were most frequently observed in patients with lung cancer (20%) or upper gastrointestinal cancer (12%). In 65% of the patients for whom the PET/CT simulation scan revealed unexpected dissemination, radiotherapy was given - changed (n = 38) or unchanged (n = 13) according to the findings on the FDG PET/CT. Unexpected dissemination on the FDG PET/CT scanning performed for radiotherapy planning caused a change in treatment strategy in 11% of 581 patients. © 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface

PubMed Central

Juranic Lisnic, Vanda; Babic Cac, Marina; Lisnic, Berislav; Trsan, Tihana; Mefferd, Adam; Das Mukhopadhyay, Chitrangada; Cook, Charles H.; Jonjic, Stipan; Trgovcich, Joanne

2013-01-01

Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases. PMID:24086132

Insulin-like growth factor binding protein-3 (IGFBP-3): Novel ligands mediate unexpected functions.

PubMed

Baxter, Robert C

2013-08-01

In addition to its important role in the regulation of somatic growth by acting as the major circulating transport protein for the insulin-like growth factors (IGFs), IGF binding protein-3 (IGFBP-3) has a variety of intracellular ligands that point to its function within major signaling pathways. The discovery of its interaction with the retinoid X receptor has led to the elucidation of roles in regulating the function of several nuclear hormone receptors including retinoic acid receptor-α, Nur77 and vitamin D receptor. Its interaction with the nuclear hormone receptor peroxisome proliferator-activated receptor-γ is believed to be involved in regulating adipocyte differentiation, which is also modulated by IGFBP-3 through an interaction with TGFβ/Smad signaling. IGFBP-3 can induce apoptosis alone or in conjunction with other agents, and in different systems can activate caspases -8 and -9. At least two unrelated proteins (LRP1 and TMEM219) have been designated as receptors for IGFBP-3, the latter with a demonstrated role in inducing caspase-8-dependent apoptosis. In contrast, IGFBP-3 also has demonstrated roles in survival-related functions, including the repair of DNA double-strand breaks through interaction with the epidermal growth factor receptor and DNA-dependent protein kinase, and the induction of autophagy through interaction with GRP78. The ability of IGFBP-3 to modulate the balance between pro-apoptotic and pro-survival sphingolipids by regulating sphingosine kinase 1 and sphingomyelinases may be integral to its role at the crossroads between cell death and survival in response to a variety of stimuli. The pleiotropic nature of IGFBP-3 activity supports the idea that IGFBP-3 itself, or pathways with which it interacts, should be investigated as targets of therapy for a variety of diseases.

Profound and Rapid Reduction in Body Temperature Induced by the Melanocortin Receptor Agonists

PubMed Central

Xu, Yuanzhong; Kim, Eun Ran; Fan, Shengjie; Xia, Yan; Xu, Yong; Huang, Cheng; Tong, Qingchun

2014-01-01

The melanocortin receptor 4 (MC4R) plays a major role in body weight regulation and its agonist MTII has been widely used to study the role of MC4Rs in energy expenditure promotion and feeding reduction. Unexpectedly, we observed that intraperitoneal (i.p.) administration of MTII induced a rapid reduction in both body temperature and energy expenditure, which was independent of its effect on feeding and followed by a prolonged increase in energy expenditure. The rapid reduction was at least partly mediated by brain neurons since intracerebroventricular (icv) administration of alpha melanocyte-stimulating hormone, an endogenous melanocortin receptor agonist, produced a similar response. In addition, the body temperature-lowering effect of MTII was independent of the presence of MC4Rs, but in a similar fashion to the previously shown effect on body temperature by 5′AMP. Moreover, β-adrenergic receptors (β-ARs) were required for the recovery from low body temperature induced by MTII and further pharmacological studies showed that the MTII’s effect on body temperature may be partially mediated by the vasopressin V1a receptors. Collectively, our results reveal a previously unappreciated role for the melanocortin pathway in rapidly lowering body temperature. PMID:25065745

Loss of Polycomb Group Protein Pcgf1 Severely Compromises Proper Differentiation of Embryonic Stem Cells

PubMed Central

Yan, Yun; Zhao, Wukui; Huang, Yikai; Tong, Huan; Xia, Yin; Jiang, Qing; Qin, Jinzhong

2017-01-01

The Polycomb repressive complex 1 (PRC1) is essential for fate decisions of embryonic stem (ES) cells. Emerging evidence suggests that six major variants of PRC1 complex, defined by the mutually exclusive presence of Pcgf subunit, regulate distinct biological processes, yet very little is known about the mechanism by which each version of PRC1 instructs and maintains cell fate. Here, we disrupted the Pcgf1, also known as Nspc1 and one of six Pcgf paralogs, in mouse ES cells by the CRISPR/Cas9 technology. We showed that although these mutant cells were viable and retained normal self-renewal, they displayed severe defects in differentiation in vitro. To gain a better understanding of the role of Pcgf1 in transcriptional control of differentiation, we analysed mRNA profiles from Pcgf1 deficient cells using RNA-seq. Interestingly, we found that Pcgf1 positively regulated expression of essential transcription factors involved in ectoderm and mesoderm differentiation, revealing an unexpected function of Pcgf1 in gene activation during ES cell lineage specification. Chromatin immunoprecipitation experiments demonstrated that Pcgf1 deletion caused a decrease in Ring1B and its associated H2AK119ub1 mark binding to target genes. Altogether, our results suggested an unexpected function of Pcgf1 in gene activation during ES cell maintenance. PMID:28393894

The Role of Facilitators in Project Action Learning Implementation

ERIC Educational Resources Information Center

Cao, Rui; Chuah, Kong Bieng; Chao, Yiu Chung; Kwong, Kar Fai; Law, Mo Yin

2012-01-01

Purpose: This paper addresses the importance of a more proactive role of organizational learning (OL) facilitators, learning motivation reinforcer, through a two-part longitudinal study in a case company. The first part of this study aims to investigate and analyze some unexpected challenges in the project action learning-driven (PAL) OL…

People and Plans: Training's Role in Homeland Security.

ERIC Educational Resources Information Center

Kaplan-Leiserson, Eva

2003-01-01

Describes how organizations and trainers are preparing for the unexpected in the wake of the September 11, 2001 terrorist attacks. Includes to-do lists, emergency procedures, and additional resources. (JOW)

[Headache case that responded to alendronate treatment in Paget's disease].

PubMed

Bozkurt, Dilek; Hiz, Fazilet; Çinar, Meral; Can, Meltem

2012-01-01

Paget's disease of the bone is a chronic, focal skeletal disease characterized by bone pain and deformity, pathological fractures and neurological symptoms such as headache, hearing loss and tinnitus, etc. The frequency of the disease increases in later ages. Viral and genetical factors play a role in the etiology. The majority of cases are asymptomatic. It is often diagnosed with an incidental finding on radiography or with an unexpected high serum alkaline phosphatase level. Bone fractures or neurological complications can negatively affect the quality of life. Early diagnosis and treatment are thus very important. Bisphosphonates are the most frequently used medication in the treatment. We present a case who sought medical help because of headache and was diagnosed as Paget's disease. Neurological complications and the diagnosis and treatment of Paget's disease are reviewed in the literature.

PEPCK Coordinates the Regulation of Central Carbon Metabolism to Promote Cancer Cell Growth.

PubMed

Montal, Emily D; Dewi, Ruby; Bhalla, Kavita; Ou, Lihui; Hwang, Bor Jang; Ropell, Ashley E; Gordon, Chris; Liu, Wan-Ju; DeBerardinis, Ralph J; Sudderth, Jessica; Twaddel, William; Boros, Laszlo G; Shroyer, Kenneth R; Duraisamy, Sekhar; Drapkin, Ronny; Powers, R Scott; Rohde, Jason M; Boxer, Matthew B; Wong, Kwok-Kin; Girnun, Geoffrey D

2015-11-19

Phosphoenolpyruvate carboxykinase (PEPCK) is well known for its role in gluconeogenesis. However, PEPCK is also a key regulator of TCA cycle flux. The TCA cycle integrates glucose, amino acid, and lipid metabolism depending on cellular needs. In addition, biosynthetic pathways crucial to tumor growth require the TCA cycle for the processing of glucose and glutamine derived carbons. We show here an unexpected role for PEPCK in promoting cancer cell proliferation in vitro and in vivo by increasing glucose and glutamine utilization toward anabolic metabolism. Unexpectedly, PEPCK also increased the synthesis of ribose from non-carbohydrate sources, such as glutamine, a phenomenon not previously described. Finally, we show that the effects of PEPCK on glucose metabolism and cell proliferation are in part mediated via activation of mTORC1. Taken together, these data demonstrate a role for PEPCK that links metabolic flux and anabolic pathways to cancer cell proliferation. Copyright © 2015 Elsevier Inc. All rights reserved.

Economic impact of traffic incidents on North Carolina's interstate facilities : final report, January 2008.

DOT National Transportation Integrated Search

2008-01-01

Unexpected delays due to traffic incidents represent a significant proportion of overall delay, especially in urban areas. The resulting uncertainty can represent major costs to businesses and travelers, as well as restrict employment opportunities. ...

Spatiotemporally regulated proteolysis to dissect the role of vegetative proteins during Bacillus subtilis sporulation: cell-specific requirement of σH and σA.

PubMed

Riley, Eammon P; Trinquier, Aude; Reilly, Madeline L; Durchon, Marine; Perera, Varahenage R; Pogliano, Kit; Lopez-Garrido, Javier

2018-04-01

Sporulation in Bacillus subtilis is a paradigm of bacterial development, which involves the interaction between a larger mother cell and a smaller forespore. The mother cell and the forespore activate different genetic programs, leading to the production of sporulation-specific proteins. A critical gap in our understanding of sporulation is how vegetative proteins, made before sporulation initiation, contribute to spore formation. Here we present a system, spatiotemporally regulated proteolysis (STRP), which enables the rapid, developmentally regulated degradation of target proteins, thereby providing a suitable method to dissect the cell- and developmental stage-specific role of vegetative proteins. STRP has been used to dissect the role of two major vegetative sigma factors, σ H and σ A , during sporulation. The results suggest that σ H is only required in predivisional cells, where it is essential for sporulation initiation, but that it is dispensable during subsequent steps of spore formation. However, evidence has been provided that σ A plays different roles in the mother cell, where it replenishes housekeeping functions, and in the forespore, where it plays an unexpected role in promoting spore germination and outgrowth. Altogether, the results demonstrate that STRP has the potential to provide a comprehensive molecular dissection of every stage of sporulation, germination and outgrowth. © 2018 John Wiley & Sons Ltd.

The role of high-frequency oscillatory activity in reward processing and learning.

PubMed

Marco-Pallarés, Josep; Münte, Thomas F; Rodríguez-Fornells, Antoni

2015-02-01

Oscillatory activity has been proposed as a key mechanism in the integration of brain activity of distant structures. Particularly, high frequency brain oscillatory activity in the beta and gamma range has received increasing interest in the domains of attention and memory. In addition, a number of recent studies have revealed an increase of beta-gamma activity (20-35 Hz) after unexpected or relevant positive reward outcomes. In the present manuscript we review the literature on this phenomenon and we propose that this activity is a brain signature elicited by unexpected positive outcomes in order to transmit a fast motivational value signal to the reward network. In addition, we hypothesize that beta-gamma oscillatory activity indexes the interaction between attentional and emotional systems, and that it directly reflects the appearance of unexpected positive rewards in learning-related contexts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of HIV-specific CD8+ T cells in pediatric HIV cure strategies after widespread early viral escape.

PubMed

Leitman, Ellen M; Thobakgale, Christina F; Adland, Emily; Ansari, M Azim; Raghwani, Jayna; Prendergast, Andrew J; Tudor-Williams, Gareth; Kiepiela, Photini; Hemelaar, Joris; Brener, Jacqui; Tsai, Ming-Han; Mori, Masahiko; Riddell, Lynn; Luzzi, Graz; Jooste, Pieter; Ndung'u, Thumbi; Walker, Bruce D; Pybus, Oliver G; Kellam, Paul; Naranbhai, Vivek; Matthews, Philippa C; Gall, Astrid; Goulder, Philip J R

2017-11-06

Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in "shock-and-kill" cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to "corner" the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection. © 2017 Leitman et al.

Immunosuppressive Environment in Basal Cell Carcinoma: The Role of Regulatory T Cells.

PubMed

Omland, Silje H; Nielsen, Patricia S; Gjerdrum, Lise M R; Gniadecki, Robert

2016-11-02

Interaction between tumour survival tactics and anti-tumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed by immunohistochemistry followed by automated image analysis in facial BCC, peritumoural skin and normal, buttock skin. Quantitative real-time PCR (qRT-PCR) was performed for FOXP3 and cytokines involved in T-reg attraction and T-cell activation. T-regs comprised 45% of CD4-cells surrounding BCC. FOXP3 was highly expressed in BCC, but absent in buttock skin. Unexpectedly, expression of FOXP3 was increased in peritumoural skin, with the FOXP3/CD3 fractions exceeding those of BCC (p?=?0.0065). Transforming growth factor (TGF)-? and T-reg chemokine expression was increased in BCC and peritumoural skin, but not in buttock skin, with expression levels correlating with FOXP3. T-regs are abundantly present both in BCC and in peritumoural skin, mediating an immunosuppressed microenvironment permissive for skin cancer.

TRPM8 inhibits endothelial cell migration via a non-channel function by trapping the small GTPase Rap1

PubMed Central

Grolez, Guillaume P.; Bernardini, Michela; Richard, Elodie; Scianna, Marco; Lemonnier, Loic; Munaron, Luca; Mattot, Virginie; Prevarskaya, Natalia; Gkika, Dimitra

2017-01-01

Endothelial cell adhesion and migration are critical steps of the angiogenic process, whose dysfunction is associated with tumor growth and metastasis. The TRPM8 channel has recently been proposed to play a protective role in prostate cancer by impairing cell motility. However, the mechanisms by which it could influence vascular behavior are unknown. Here, we reveal a novel non-channel function for TRPM8 that unexpectedly acts as a Rap1 GTPase inhibitor, thereby inhibiting endothelial cell motility, independently of pore function. TRPM8 retains Rap1 intracellularly through direct protein–protein interaction, thus preventing its cytoplasm–plasma membrane trafficking. In turn, this mechanism impairs the activation of a major inside-out signaling pathway that triggers the conformational activation of integrin and, consequently, cell adhesion, migration, in vitro endothelial tube formation, and spheroid sprouting. Our results bring to light a novel, pore-independent molecular mechanism by which endogenous TRPM8 expression inhibits Rap1 GTPase and thus plays a critical role in the behavior of vascular endothelial cells by inhibiting migration. PMID:28550110

Behavior of the Edible Seaweed Sargassum fusiforme to Copper Pollution: Short-Term Acclimation and Long-Term Adaptation

PubMed Central

Lin, Li-Dong; Zhang, Ai-Qin; Li, Nan; Lin, Yan-Qing; Li, Lu-Min; Wu, Qin-Qin; Yan, Xiu-Feng

2014-01-01

Aquatic agriculture in heavy-metal-polluted coastal areas faces major problems due to heavy metal transfer into aquatic organisms, leading to various unexpected changes in nutrition and primary and/or secondary metabolism. In the present study, the dual role of heavy metal copper (Cu) played in the metabolism of photosynthetic organism, the edible seaweed Sargassum fusiforme, was evaluated by characterization of biochemical and metabolic responses using both 1H NMR and GC-MS techniques under acute (47 µM, 1 day) and chronic stress (8 µM, 7 days). Consequently, photosynthesis may be seriously inhibited by acute Cu exposure, resulting in decreasing levels of carbohydrates, e.g., mannitol, the main products of photosynthesis. Ascorbate may play important roles in the antioxidant system, whose content was much more seriously decreased under acute than that under chronic Cu stress. Overall, these results showed differential toxicological responses on metabolite profiles of S. fusiforme subjected to acute and chronic Cu exposures that allowed assessment of impact of Cu on marine organisms. PMID:25025229

Replacing Nitrogen by Sulfur: From Structurally Disordered Eumelanins to Regioregular Thiomelanin Polymers

PubMed Central

Iacomino, Mariagrazia; Mancebo-Aracil, Juan; Guardingo, Mireia; Martín, Raquel; Perfetti, Marco; Manini, Paola; Crescenzi, Orlando; Busqué, Félix; Sedó, Josep; Ruiz-Molina, Daniel

2017-01-01

The oxidative polymerization of 5,6-dihydroxybenzothiophene (DHBT), the sulfur analog of the key eumelanin building block 5,6-dihydroxyindole (DHI), was investigated to probe the role of nitrogen in eumelanin build-up and properties. Unlike DHI, which gives a typical black insoluble eumelanin polymer on oxidation, DHBT is converted to a grayish amorphous solid (referred to as thiomelanin) with visible absorption and electron paramagnetic resonance properties different from those of DHI melanin. Mass spectrometry experiments revealed gradational mixtures of oligomers up to the decamer level. Quite unexpectedly, nuclear magnetic resonance (NMR) analysis of the early oligomer fractions indicated linear, 4-, and 7-linked structures in marked contrast with DHI, which gives highly complex mixtures of partially degraded oligomers. Density functional theory (DFT) calculations supported the tendency of DHBT to couple via the 4- and 7-positions. These results uncover the role of nitrogen as a major determinant of the structural diversity generated by the polymerization of DHI, and point to replacement by sulfur as a viable entry to regioregular eumelanin-type materials for potential applications for surface functionalization by dip coating. PMID:29039817

Fostering the Development and Implementation of Principles for Managing Ethics in Higher Education Institutions: An International Comparative Perspective

ERIC Educational Resources Information Center

Marmolejo, Francisco

2006-01-01

In today's world, higher education faces important opportunities and challenges, many of which are new and unexpected. The increased complexity of higher education institutions themselves is reflected in the expansion of their roles and responsibilities. These roles and responsibilities include: greater demands for regional engagement and other…

Enhance Learning on Software Project Management through a Role-Play Game in a Virtual World

ERIC Educational Resources Information Center

Maratou, Vicky; Chatzidaki, Eleni; Xenos, Michalis

2016-01-01

This article presents a role-play game for software project management (SPM) in a three-dimensional online multiuser virtual world. The Opensimulator platform is used for the creation of an immersive virtual environment that facilitates students' collaboration and realistic interaction, in order to manage unexpected events occurring during the…

A disulfide-stabilized conformer of methionine synthase reveals an unexpected role for the histidine ligand of the cobalamin cofactor

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

Datta, Supratim; Koutmos, Markos; Pattridge, Katherine A.

2008-07-08

B{sub 12}-dependent methionine synthase (MetH) from Escherichia coli is a large modular protein that is alternately methylated by methyltetrahydrofolate to form methylcobalamin and demethylated by homocysteine to form cob(I)alamin. Major domain rearrangements are required to allow cobalamin to react with three different substrates: homocysteine, methyltetrahydrofolate, and S-adenosyl-l-methionine (AdoMet). These same rearrangements appear to preclude crystallization of the wild-type enzyme. Disulfide cross-linking was used to lock a C-terminal fragment of the enzyme into a unique conformation. Cysteine point mutations were introduced at Ile-690 and Gly-743. These cysteine residues span the cap and the cobalamin-binding module and form a cross-link that reducesmore » the conformational space accessed by the enzyme, facilitating protein crystallization. Here, we describe an x-ray structure of the mutant fragment in the reactivation conformation; this conformation enables the transfer of a methyl group from AdoMet to the cobalamin cofactor. In the structure, the axial ligand to the cobalamin, His-759, dissociates from the cobalamin and forms intermodular contacts with residues in the AdoMet-binding module. This unanticipated intermodular interaction is expected to play a major role in controlling the distribution of conformers required for the catalytic and the reactivation cycles of the enzyme.« less

Plants and climate change: complexities and surprises

PubMed Central

Parmesan, Camille; Hanley, Mick E.

2015-01-01

Background Anthropogenic climate change (ACC) will influence all aspects of plant biology over coming decades. Many changes in wild species have already been well-documented as a result of increased atmospheric CO2 concentrations, warming climate and changing precipitation regimes. A wealth of available data has allowed the use of meta-analyses to examine plant–climate interactions on more sophisticated levels than before. These analyses have revealed major differences in plant response among groups, e.g. with respect to functional traits, taxonomy, life-history and provenance. Interestingly, these meta-analyses have also exposed unexpected mismatches between theory, experimental, and observational studies. Scope We reviewed the literature on species’ responses to ACC, finding ∼42 % of 4000 species studied globally are plants (primarily terrestrial). We review impacts on phenology, distributions, ecophysiology, regeneration biology, plant–plant and plant–herbivore interactions, and the roles of plasticity and evolution. We focused on apparent deviations from expectation, and highlighted cases where more sophisticated analyses revealed that unexpected changes were, in fact, responses to ACC. Conclusions We found that conventionally expected responses are generally well-understood, and that it is the aberrant responses that are now yielding greater insight into current and possible future impacts of ACC. We argue that inconclusive, unexpected, or counter-intuitive results should be embraced in order to understand apparent disconnects between theory, prediction, and observation. We highlight prime examples from the collection of papers in this Special Issue, as well as general literature. We found use of plant functional groupings/traits had mixed success, but that some underutilized approaches, such as Grime's C/S/R strategies, when incorporated, have improved understanding of observed responses. Despite inherent difficulties, we highlight the need for ecologists to conduct community-level experiments in systems that replicate multiple aspects of ACC. Specifically, we call for development of coordinating experiments across networks of field sites, both natural and man-made. PMID:26555281

Developing a NASA strategy for sampling a major Pinatubo-like volcanic eruption

NASA Astrophysics Data System (ADS)

Newman, P. A.; Jucks, K. W.; Maring, H. B.

2016-12-01

Based on history, it is reasonable to expect a major volcanic eruption in the foreseeable future. By "major volcanic eruption", we mean an eruption that injects a substantial amount of material, gases and particles, into the stratosphere as a result of one eruption event. Such a volcanic eruption can impact weather, climate, and atmospheric chemistry on regional, hemispheric and global scales over significant time periods. Further, such an eruption can be an unintended analog for a number of geo-engineering schemes for mitigating greenhouse warming of the Earth. In order to understand and project the consequences of a major eruption, it is necessary to make a number of observations from a variety of perspectives. Such an eruption will occur, in the immediate sense, unexpectedly. Therefore, it is wise to have a thoughtfully developed plan for executing a rapid response that makes useful observations. A workshop was held on 17-18 May 2016 at NASA GSFC to develop a NASA observation strategy that could be quickly implemented in response to a major volcanic eruption, and would characterize the changes to atmospheric (especially stratospheric) composition following a large volcanic eruption. In this presentation we will provide an overview of the elements of this strategy with respect to satellite, balloon, ground, and aircraft observations. In addition, models simulations and forecasts will play a key role in any response strategy. Results will also be shown from a spectrum of simulations of volcanic eruptions that support this NASA strategy.

Challenges in transformation of the "traditional block rotation" medical student clinical education into a longitudinal integrated clerkship model.

PubMed

Heddle, William; Roberton, Gayle; Mahoney, Sarah; Walters, Lucie; Strasser, Sarah; Worley, Paul

2014-01-01

Longitudinal integrated clerkships (LIC) in the first major clinical year in medical student training have been demonstrated to be at least equivalent to and in some areas superior to the "traditional block rotation" (TBR). Flinders University School of Medicine is starting a pilot changing the traditional teaching at the major Academic Medical Centre from TBR to LIC (50% of students in other locations in the medical school already have a partial or full LIC programme). This paper summarises the expected challenges presented at the "Rendez-Vous" Conference in October 2012: (a) creating urgency, (b) training to be a clinician rather than imparting knowledge, (c) resistance to change. We discuss the unexpected challenges that have evolved since then: (a) difficulty finalising the precise schedule, (b) underestimating time requirements, (c) managing the change process inclusively. Transformation of a "block rotation" to "LIC" medical student education in a tertiary academic teaching hospital has many challenges, many of which can be anticipated, but some are unexpected.

Unexpected biotic resilience on the Japanese seafloor caused by the 2011 Tōhoku-Oki tsunami

NASA Astrophysics Data System (ADS)

Toyofuku, Takashi; Duros, Pauline; Fontanier, Christophe; Mamo, Briony; Bichon, Sabrina; Buscail, Roselyne; Chabaud, Gérard; Deflandre, Bruno; Goubet, Sarah; Grémare, Antoine; Menniti, Christophe; Fujii, Minami; Kawamura, Kiichiro; Koho, Karoliina Annika; Noda, Atsushi; Namegaya, Yuichi; Oguri, Kazumasa; Radakovitch, Olivier; Murayama, Masafumi; de Nooijer, Lennart Jan; Kurasawa, Atushi; Ohkawara, Nina; Okutani, Takashi; Sakaguchi, Arito; Jorissen, Frans; Reichart, Gert-Jan; Kitazato, Hiroshi

2014-12-01

On March 11th, 2011 the Mw 9.0 2011 Tōhoku-Oki earthquake resulted in a tsunami which caused major devastation in coastal areas. Along the Japanese NE coast, tsunami waves reached maximum run-ups of 40 m, and travelled kilometers inland. Whereas devastation was clearly visible on land, underwater impact is much more difficult to assess. Here, we report unexpected results obtained during a research cruise targeting the seafloor off Shimokita (NE Japan), shortly (five months) after the disaster. The geography of the studied area is characterized by smooth coastline and a gradually descending shelf slope. Although high-energy tsunami waves caused major sediment reworking in shallow-water environments, investigated shelf ecosystems were characterized by surprisingly high benthic diversity and showed no evidence of mass mortality. Conversely, just beyond the shelf break, the benthic ecosystem was dominated by a low-diversity, opportunistic fauna indicating ongoing colonization of massive sand-bed deposits.

Unexpected biotic resilience on the Japanese seafloor caused by the 2011 Tōhoku-Oki tsunami

PubMed Central

Toyofuku, Takashi; Duros, Pauline; Fontanier, Christophe; Mamo, Briony; Bichon, Sabrina; Buscail, Roselyne; Chabaud, Gérard; Deflandre, Bruno; Goubet, Sarah; Grémare, Antoine; Menniti, Christophe; Fujii, Minami; Kawamura, Kiichiro; Koho, Karoliina Annika; Noda, Atsushi; Namegaya, Yuichi; Oguri, Kazumasa; Radakovitch, Olivier; Murayama, Masafumi; de Nooijer, Lennart Jan; Kurasawa, Atushi; Ohkawara, Nina; Okutani, Takashi; Sakaguchi, Arito; Jorissen, Frans; Reichart, Gert-Jan; Kitazato, Hiroshi

2014-01-01

On March 11th, 2011 the Mw 9.0 2011 Tōhoku-Oki earthquake resulted in a tsunami which caused major devastation in coastal areas. Along the Japanese NE coast, tsunami waves reached maximum run-ups of 40 m, and travelled kilometers inland. Whereas devastation was clearly visible on land, underwater impact is much more difficult to assess. Here, we report unexpected results obtained during a research cruise targeting the seafloor off Shimokita (NE Japan), shortly (five months) after the disaster. The geography of the studied area is characterized by smooth coastline and a gradually descending shelf slope. Although high-energy tsunami waves caused major sediment reworking in shallow-water environments, investigated shelf ecosystems were characterized by surprisingly high benthic diversity and showed no evidence of mass mortality. Conversely, just beyond the shelf break, the benthic ecosystem was dominated by a low-diversity, opportunistic fauna indicating ongoing colonization of massive sand-bed deposits. PMID:25515588

Unexpected biotic resilience on the Japanese seafloor caused by the 2011 Tōhoku-Oki tsunami.

PubMed

Toyofuku, Takashi; Duros, Pauline; Fontanier, Christophe; Mamo, Briony; Bichon, Sabrina; Buscail, Roselyne; Chabaud, Gérard; Deflandre, Bruno; Goubet, Sarah; Grémare, Antoine; Menniti, Christophe; Fujii, Minami; Kawamura, Kiichiro; Koho, Karoliina Annika; Noda, Atsushi; Namegaya, Yuichi; Oguri, Kazumasa; Radakovitch, Olivier; Murayama, Masafumi; de Nooijer, Lennart Jan; Kurasawa, Atushi; Ohkawara, Nina; Okutani, Takashi; Sakaguchi, Arito; Jorissen, Frans; Reichart, Gert-Jan; Kitazato, Hiroshi

2014-12-17

On March 11(th), 2011 the Mw 9.0 2011 Tōhoku-Oki earthquake resulted in a tsunami which caused major devastation in coastal areas. Along the Japanese NE coast, tsunami waves reached maximum run-ups of 40 m, and travelled kilometers inland. Whereas devastation was clearly visible on land, underwater impact is much more difficult to assess. Here, we report unexpected results obtained during a research cruise targeting the seafloor off Shimokita (NE Japan), shortly (five months) after the disaster. The geography of the studied area is characterized by smooth coastline and a gradually descending shelf slope. Although high-energy tsunami waves caused major sediment reworking in shallow-water environments, investigated shelf ecosystems were characterized by surprisingly high benthic diversity and showed no evidence of mass mortality. Conversely, just beyond the shelf break, the benthic ecosystem was dominated by a low-diversity, opportunistic fauna indicating ongoing colonization of massive sand-bed deposits.

Regulative recovery in the sea urchin embryo and the stabilizing role of fail-safe gene network wiring

PubMed Central

Smith, Joel; Davidson, Eric H.

2009-01-01

Design features that ensure reproducible and invariant embryonic processes are major characteristics of current gene regulatory network models. New cis-regulatory studies on a gene regulatory network subcircuit activated early in the development of the sea urchin embryo reveal a sequence of encoded “fail-safe” regulatory devices. These ensure the maintenance of fate separation between skeletogenic and nonskeletogenic mesoderm lineages. An unexpected consequence of the network design revealed in the course of these experiments is that it enables the embryo to “recover” from regulatory interference that has catastrophic effects if this feature is disarmed. A reengineered regulatory system inserted into the embryo was used to prove how this system operates in vivo. Genomically encoded backup control circuitry thus provides the mechanism underlying a specific example of the regulative development for which the sea urchin embryo has long been famous. PMID:19822764

A potential target for organophosphate insecticides leading to spermatotoxicity.

PubMed

Suzuki, Himiko; Tomizawa, Motohiro; Ito, Yuki; Abe, Keisuke; Noro, Yuki; Kamijima, Michihiro

2013-10-16

Organophosphate (OP) insecticides as an anticholinesterase also act on the diverse serine hydrolase targets, thereby revealing secondary or unexpected toxic effects including male reproductive toxicity. The present investigation detects a possible target molecule(s) for OP-induced spermatotoxicity (sperm deformity, underdevelopment, and reduced motility) from a chemical standpoint. The activity-based protein profiling (ABPP) approach with a phosphonofluoridate fluorescent probe pinpointed the molecular target for fenitrothion (FNT, a major OP insecticide) oxon (bioactive metabolite of FNT) in the mouse testicular membrane proteome, i.e., FNT oxon phosphorylates the fatty acid amide hydrolase (FAAH), which plays pivotal roles in spermatogenesis and sperm motility acquirement. Subsequently, mice were treated orally with vehicle or FNT for 10 days, and FAAH activity in testis or epididymis cauda was markedly reduced by the subacute exposure. ABPP analysis revealed that FAAH was selectively inhibited among the FNT-treated testicular membrane proteome. Accordingly, FAAH is a potential target for OP-elicited spermatotoxicity.

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging.

PubMed

Cornils, Astrid; Maurya, Ashish K; Tereshko, Lauren; Kennedy, Julie; Brear, Andrea G; Prahlad, Veena; Blacque, Oliver E; Sengupta, Piali

2016-12-01

The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT. We demonstrate that while DAF-16/FOXO is dispensable, the age-dependent suppression of cilia phenotypes in IFT mutants requires cell-autonomous functions of the HSF1 heat shock factor and the Hsp90 chaperone. Our results describe an unexpected role of early aging and protein quality control mechanisms in suppressing ciliary phenotypes of IFT mutants, and suggest possible strategies for targeting subsets of ciliopathies.

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging

PubMed Central

Kennedy, Julie; Brear, Andrea G.; Prahlad, Veena; Blacque, Oliver E.; Sengupta, Piali

2016-01-01

The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT. We demonstrate that while DAF-16/FOXO is dispensable, the age-dependent suppression of cilia phenotypes in IFT mutants requires cell-autonomous functions of the HSF1 heat shock factor and the Hsp90 chaperone. Our results describe an unexpected role of early aging and protein quality control mechanisms in suppressing ciliary phenotypes of IFT mutants, and suggest possible strategies for targeting subsets of ciliopathies. PMID:27906968

[HIV in the lung from 1982 to 2013].

PubMed

Mayaud, C; Cadranel, J

2014-02-01

During the last 30 years pulmonary involvement has played a major role in the history of HIV infection. Initially, the unexplained occurrence of pneumocystis revealed the emergence of AIDS and the suspicion of its African origin. Before the era of triple therapy the natural history of AIDS was dominated by the occurrence of repeated lung infections and respiratory physicians were at the forefront of their diagnosis, treatment and prophylaxis. With the provision of antiretroviral therapy (ART), the natural history of AIDS has been transformed in those patients who benefit from it. In addition to paradoxical reactions observed following the introduction of ART, the pulmonologist is also facing a chronic stage of controlled HIV infection, and unexpected events, the incidence of which increases with time: pulmonary arterial hypertension and lung cancer certainly, COPD and fibrosis perhaps… but this story remains to be written. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Design and Evaluation of a Boron Dipyrrin Electrophore for Redox Flow Batteries.

PubMed

Heiland, Niklas; Cidarér, Clemens; Rohr, Camilla; Piescheck, Mathias; Ahrens, Johannes; Bröring, Martin; Schröder, Uwe

2017-08-29

A boron dipyrrin (BODIPY) dye was designed as a molecular single-component electrophore for redox flow batteries. All positions of the BODIPY core were assessed on the basis of literature data, in particular cyclic voltammetry and density functional calculations, and a minimum required substitution pattern was designed to provide solubility, aggregation, radical cation and anion stabilities, a large potential window, and synthetic accessibility. In-depth electrochemical and physical studies of this electrophore revealed suitable cathodic behavior and stability of the radical anion but rapid anodic decomposition of the radical cation. The three products that formed under the conditions of controlled oxidative electrolysis were isolated, and their structures were determined by spectroscopy and comparison with a synthetic model compound. From these structures, a benzylic radical reactivity, initiated by one-electron oxidation, was concluded to play the major role in this unexpected decomposition. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Unexpected Side-Effects of Dissonance

ERIC Educational Resources Information Center

Bodner, Ehud; Gilboa, Avi; Amir, Dorit

2007-01-01

The effects of dissonant and consonant music on cognitive performance were examined. Situational dissonance and consonance were also tested and determined as the state where one's opinion is contrasted or matched with the majority's opinion, respectively. Subjects performed several cognitive tasks while listening to a melody arranged dissonantly,…

School Crisis Response: Expecting the Unexpected.

ERIC Educational Resources Information Center

Lichtenstein, Robert; And Others

1994-01-01

The typical administrator certification program does not devote specific attention to shootings, suicide, terminal illness, and natural disasters. A crisis of major proportion calls for enlightened leadership: a take-charge manner, combined with effective teamwork and delegation of vital operations. Crisis teams should exist at regional, district,…

Crisis Management in the Community College

ERIC Educational Resources Information Center

Murray, John P.; Kishur, Joseph M., Jr.

2008-01-01

This study examined the decision-making processes of community college presidents when confronted with unexpected and major challenges. During the day-to-day operations of community colleges, presidents typically rely on their best judgment when making routine decisions. However, this decision-making process needs to change when the unexpected…

Negotiated risk and resident autonomy: Frontline care staff perspectives on culture change in long term care in Nova Scotia, Canada.

PubMed

Roberts, Emily

2016-08-12

Regulating risk, freedom of action, and autonomy in decision making are problems shared by both caregivers and residents in long term care settings, and may become the subject of tension and constant negotiation. This study focuses on long term care staff and management perceptions of day to day life in a care community which has gone through a culture change transition, where small residentially scaled households replace large instutional models of care. In each household, the setting is considered to be home for the 8-12 residents, creating a major shift of roles for the caregivers; they are, in essence, coming into a home rather than institutional environment as a place of work. This potentially changes the dynamics of both patterns of work for caregivers and patterns of daily living for residents. Participant observations and care staff interviews. Several key themes emrged which include: teamwork; the culture of care; regulating risk; the physical environment and care staff empowerment. An unexpected outcome was the consensus among care staff that it is they who feel at home while working in the care households, leading to empowerment in their work roles and a deeper understanding of the importance of their role in the lives of the residents.

Profound and rapid reduction in body temperature induced by the melanocortin receptor agonists.

PubMed

Xu, Yuanzhong; Kim, Eun Ran; Fan, Shengjie; Xia, Yan; Xu, Yong; Huang, Cheng; Tong, Qingchun

2014-08-22

The melanocortin receptor 4 (MC4R) plays a major role in body weight regulation and its agonist MTII has been widely used to study the role of MC4Rs in energy expenditure promotion and feeding reduction. Unexpectedly, we observed that intraperitoneal (i.p.) administration of MTII induced a rapid reduction in both body temperature and energy expenditure, which was independent of its effect on feeding and followed by a prolonged increase in energy expenditure. The rapid reduction was at least partly mediated by brain neurons since intracerebroventricular (icv) administration of alpha melanocyte-stimulating hormone, an endogenous melanocortin receptor agonist, produced a similar response. In addition, the body temperature-lowering effect of MTII was independent of the presence of MC4Rs, but in a similar fashion to the previously shown effect on body temperature by 5'AMP. Moreover, β-adrenergic receptors (β-ARs) were required for the recovery from low body temperature induced by MTII and further pharmacological studies showed that the MTII's effect on body temperature may be partially mediated by the vasopressin V1a receptors. Collectively, our results reveal a previously unappreciated role for the melanocortin pathway in rapidly lowering body temperature. Copyright © 2014 Elsevier Inc. All rights reserved.

Gene Expression Dynamics in Major Endocrine Regulatory Pathways along the Transition from Solitary to Social Life in a Bumblebee, Bombus terrestris.

PubMed

Jedlička, Pavel; Ernst, Ulrich R; Votavová, Alena; Hanus, Robert; Valterová, Irena

2016-01-01

Understanding the social evolution leading to insect eusociality requires, among other, a detailed insight into endocrine regulatory mechanisms that have been co-opted from solitary ancestors to play new roles in the complex life histories of eusocial species. Bumblebees represent well-suited models of a relatively primitive social organization standing on the mid-way to highly advanced eusociality and their queens undergo both, a solitary and a social phase, separated by winter diapause. In the present paper, we characterize the gene expression levels of major endocrine regulatory pathways across tissues, sexes, and life-stages of the buff-tailed bumblebee, Bombus terrestris , with special emphasis on critical stages of the queen's transition from solitary to social life. We focused on fundamental genes of three pathways: (1) Forkhead box protein O and insulin/insulin-like signaling, (2) Juvenile hormone (JH) signaling, and (3) Adipokinetic hormone signaling. Virgin queens were distinguished by higher expression of forkhead box protein O and downregulated insulin-like peptides and JH signaling, indicated by low expression of methyl farnesoate epoxidase ( MFE ) and transcription factor Krüppel homolog 1 ( Kr-h1 ). Diapausing queens showed the expected downregulation of JH signaling in terms of low MFE and vitellogenin ( Vg ) expressions, but an unexpectedly high expression of Kr-h1 . By contrast, reproducing queens revealed an upregulation of MFE and Vg together with insulin signaling. Surprisingly, the insulin growth factor 1 (IGF-1) turned out to be a queen-specific hormone. Workers exhibited an expression pattern of MFE and Vg similar to that of reproducing queens. Males were characterized by high Kr-h1 expression and low Vg level. The tissue comparison unveiled an unexpected resemblance between the fat body and hypopharyngeal glands across all investigated genes, sexes, and life stages.

The role of conversation in health care interventions: enabling sensemaking and learning.

PubMed

Jordan, Michelle E; Lanham, Holly J; Crabtree, Benjamin F; Nutting, Paul A; Miller, William L; Stange, Kurt C; McDaniel, Reuben R

2009-03-13

Those attempting to implement changes in health care settings often find that intervention efforts do not progress as expected. Unexpected outcomes are often attributed to variation and/or error in implementation processes. We argue that some unanticipated variation in intervention outcomes arises because unexpected conversations emerge during intervention attempts. The purpose of this paper is to discuss the role of conversation in shaping interventions and to explain why conversation is important in intervention efforts in health care organizations. We draw on literature from sociolinguistics and complex adaptive systems theory to create an interpretive framework and develop our theory. We use insights from a fourteen-year program of research, including both descriptive and intervention studies undertaken to understand and assist primary care practices in making sustainable changes. We enfold these literatures and these insights to articulate a common failure of overlooking the role of conversation in intervention success, and to develop a theoretical argument for the importance of paying attention to the role of conversation in health care interventions. Conversation between organizational members plays an important role in the success of interventions aimed at improving health care delivery. Conversation can facilitate intervention success because interventions often rely on new sensemaking and learning, and these are accomplished through conversation. Conversely, conversation can block the success of an intervention by inhibiting sensemaking and learning. Furthermore, the existing relationship contexts of an organization can influence these conversational possibilities. We argue that the likelihood of intervention success will increase if the role of conversation is considered in the intervention process. The generation of productive conversation should be considered as one of the foundations of intervention efforts. We suggest that intervention facilitators consider the following actions as strategies for reducing the barriers that conversation can present and for using conversation to leverage improvement change: evaluate existing conversation and relationship systems, look for and leverage unexpected conversation, create time and space where conversation can unfold, use conversation to help people manage uncertainty, use conversation to help reorganize relationships, and build social interaction competence.

The role of conversation in health care interventions: enabling sensemaking and learning

PubMed Central

Jordan, Michelle E; Lanham, Holly J; Crabtree, Benjamin F; Nutting, Paul A; Miller, William L; Stange, Kurt C; McDaniel, Reuben R

2009-01-01

Background Those attempting to implement changes in health care settings often find that intervention efforts do not progress as expected. Unexpected outcomes are often attributed to variation and/or error in implementation processes. We argue that some unanticipated variation in intervention outcomes arises because unexpected conversations emerge during intervention attempts. The purpose of this paper is to discuss the role of conversation in shaping interventions and to explain why conversation is important in intervention efforts in health care organizations. We draw on literature from sociolinguistics and complex adaptive systems theory to create an interpretive framework and develop our theory. We use insights from a fourteen-year program of research, including both descriptive and intervention studies undertaken to understand and assist primary care practices in making sustainable changes. We enfold these literatures and these insights to articulate a common failure of overlooking the role of conversation in intervention success, and to develop a theoretical argument for the importance of paying attention to the role of conversation in health care interventions. Discussion Conversation between organizational members plays an important role in the success of interventions aimed at improving health care delivery. Conversation can facilitate intervention success because interventions often rely on new sensemaking and learning, and these are accomplished through conversation. Conversely, conversation can block the success of an intervention by inhibiting sensemaking and learning. Furthermore, the existing relationship contexts of an organization can influence these conversational possibilities. We argue that the likelihood of intervention success will increase if the role of conversation is considered in the intervention process. Summary The generation of productive conversation should be considered as one of the foundations of intervention efforts. We suggest that intervention facilitators consider the following actions as strategies for reducing the barriers that conversation can present and for using conversation to leverage improvement change: evaluate existing conversation and relationship systems, look for and leverage unexpected conversation, create time and space where conversation can unfold, use conversation to help people manage uncertainty, use conversation to help reorganize relationships, and build social interaction competence. PMID:19284660

Progress in Understanding Autism: 2007-2010

ERIC Educational Resources Information Center

Rutter, Michael L.

2011-01-01

Scientific progress is discussed in relation to clinical issues; genetic issues; environmental issues; and the state of play on psychological treatments. It is concluded that substantial gains in knowledge have been achieved during the last 3 years, and there have been some unexpected findings, but major puzzles remain. We should be hopeful of…

Unexpected Attitudinal Growth in a Course Combining Reformed Curricula

ERIC Educational Resources Information Center

Hull, Michael M.; Lindsey, Beth A.; Archambault, Matthew; Davey, Kathleen; Liu, Amy Y.

2016-01-01

In this paper, we show data from the Colorado Learning Attitudes about Science Survey that suggests that Georgetown physics majors become increasingly expert in their attitudes towards physics learning and knowing after taking a course that combines two reformed curricula, Matter and Interactions (M&I) and Tutorials in Introductory Physics…

Demographic Trends Affecting the Future Labor Force.

ERIC Educational Resources Information Center

Taeuber, Karl E.

This report reviews recent population and manpower projections and examines how they take into account certain unexpected shifts in demographic, social, and economic behavior. It also assesses how well the particular circumstances, trends, and problems of the nation's major minority groups have been brought into the purview of the projection…

Improving the Textbook Adoption Process in Taiwan

ERIC Educational Resources Information Center

Ho, Hsuan-fu; Hsu, Ying-tsun

2011-01-01

Textbooks were centrally selected in Taiwan until 1996 when the government commissioned its Textbook Liberalization Reform. Although this policy received complements from scholars and the general public, it encounters many unexpected problems in its implementation. The aims of this research are thus to identify the major criteria used by…

Unexpected findings and promoting monocausal claims, a cautionary tale.

PubMed

Copeland, Samantha Marie

2017-10-01

Stories of serendipitous discoveries in medicine incorrectly imply that the path from an unexpected observation to major discovery is straightforward or guaranteed. In this paper, I examine a case from the field of research about chronic fatigue syndrome (CFS). In Norway, an unexpected positive result during clinical care has led to the development of a research programme into the potential for the immunosuppressant drug rituximab to relieve the symptoms of CFS. The media and public have taken up researchers' speculations that their research results indicate a causal mechanism for CFS - consequently, patients now have great hope that 'the cause' of CFS has been found, and thus, a cure is sure to follow. I argue that a monocausal claim cannot be correctly asserted, either on the basis of the single case of an unexpected, although positive, result or on the basis of the empirical research that has followed up on that result. Further, assertion and promotion of this claim will have specific harmful effects: it threatens to inappropriately narrow the scope of research on CFS, might misdirect research altogether, and could directly and indirectly harm patients. Therefore, the CFS case presents a cautionary tale, illustrating the risks involved in drawing a theoretical hypothesis from an unexpected observation. Further, I draw attention to the tendency in contemporary clinical research with CFS to promote new research directions on the basis of reductive causal models of that syndrome. Particularly, in the case of CFS research, underdetermination and causal complexity undermine the potential value of a monocausal claim. In sum, when an unexpected finding occurs in clinical practice or medical research, the value of following up on that finding is to be found not in the projected value of a singular causal relationship inferred from the finding but rather in the process of research that follows. © 2016 John Wiley & Sons, Ltd.

Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosa

PubMed Central

Ikeda, Hanako Ohashi; Sasaoka, Norio; Koike, Masaaki; Nakano, Noriko; Muraoka, Yuki; Toda, Yoshinobu; Fuchigami, Tomohiro; Shudo, Toshiyuki; Iwata, Ayana; Hori, Seiji; Yoshimura, Nagahisa; Kakizuka, Akira

2014-01-01

Neuroprotection may prevent or forestall the progression of incurable eye diseases, such as retinitis pigmentosa, one of the major causes of adult blindness. Decreased cellular ATP levels may contribute to the pathology of this eye disease and other neurodegenerative diseases. Here we describe small compounds (Kyoto University Substances, KUSs) that were developed to inhibit the ATPase activity of VCP (valosin-containing protein), the most abundant soluble ATPase in the cell. Surprisingly, KUSs did not significantly impair reported cellular functions of VCP but nonetheless suppressed the VCP-dependent decrease of cellular ATP levels. Moreover, KUSs, as well as exogenous ATP or ATP-producing compounds, e.g. methylpyruvate, suppressed endoplasmic reticulum stress, and demonstrably protected various types of cultured cells from death, including several types of retinal neuronal cells. We then examined their in vivo efficacies in rd10, a mouse model of retinitis pigmentosa. KUSs prevented photoreceptor cell death and preserved visual function. These results reveal an unexpected, crucial role of ATP consumption by VCP in determining cell fate in this pathological context, and point to a promising new neuroprotective strategy for currently incurable retinitis pigmentosa. PMID:25096051

High Frequency and Diversity of Antimicrobial Activities Produced by Nasal Staphylococcus Strains against Bacterial Competitors

PubMed Central

Janek, Daniela; Zipperer, Alexander; Kulik, Andreas; Krismer, Bernhard; Peschel, Andreas

2016-01-01

The human nasal microbiota is highly variable and dynamic often enclosing major pathogens such as Staphylococcus aureus. The potential roles of bacteriocins or other mechanisms allowing certain bacterial clones to prevail in this nutrient-poor habitat have hardly been studied. Of 89 nasal Staphylococcus isolates, unexpectedly, the vast majority (84%) was found to produce antimicrobial substances in particular under habitat-specific stress conditions, such as iron limitation or exposure to hydrogen peroxide. Activity spectra were generally narrow but highly variable with activities against certain nasal members of the Actinobacteria, Proteobacteria, Firmicutes, or several groups of bacteria. Staphylococcus species and many other Firmicutes were insusceptible to most of the compounds. A representative bacteriocin was identified as a nukacin-related peptide whose inactivation reduced the capacity of the producer Staphylococcus epidermidis IVK45 to limit growth of other nasal bacteria. Of note, the bacteriocin genes were found on mobile genetic elements exhibiting signs of extensive horizontal gene transfer and rearrangements. Thus, continuously evolving bacteriocins appear to govern bacterial competition in the human nose and specific bacteriocins may become important agents for eradication of notorious opportunistic pathogens from human microbiota. PMID:27490492

Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae.

PubMed

François, J; Parrou, J L

2001-01-01

Glycogen and trehalose are the two glucose stores of yeast cells. The large variations in the cell content of these two compounds in response to different environmental changes indicate that their metabolism is controlled by complex regulatory systems. In this review we present information on the regulation of the activity of the enzymes implicated in the pathways of synthesis and degradation of glycogen and trehalose as well as on the transcriptional control of the genes encoding them. cAMP and the protein kinases Snf1 and Pho85 appear as major actors in this regulation. From a metabolic point of view, glucose-6-phosphate seems the major effector in the net synthesis of glycogen and trehalose. We discuss also the implication of the recently elucidated TOR-dependent nutrient signalling pathway in the control of the yeast glucose stores and its integration in growth and cell division. The unexpected roles of glycogen and trehalose found in the control of glycolytic flux, stress responses and energy stores for the budding process, demonstrate that their presence confers survival and reproductive advantages to the cell. The findings discussed provide for the first time a teleonomic value for the presence of two different glucose stores in the yeast cell.

Unconventional binding sites and receptors for VIP and related peptides PACAP and PHI/PHM: an update.

PubMed

Muller, Jean-Marc; Debaigt, Colin; Goursaud, Stéphanie; Montoni, Alicia; Pineau, Nicolas; Meunier, Annie-Claire; Janet, Thierry

2007-09-01

The 28-amino-acid neuropeptide VIP and related peptides PACAP and PHI/PHM modulate virtually all of the vital functions in the body. These peptides are also commonly recognized as major regulators of cell growth and differentiation. Through their trophic and cytoprotective functions, they appear to play major roles in embryonic development, neurogenesis and the progression of a number of cancer types. These peptides bind to three well-characterized subtypes of G-protein coupled receptors: VPAC1 and VPAC2 share a common high affinity in the nanomolar range for VIP and PACAP; a third receptor type, PAC1, has been characterized for its high affinity for PACAP but its low affinity for VIP. Complex effects and pharmacological behaviors of these peptides suggest that multiple subtypes of binding sites may cooperate to mediate their function in target cells and tissues. In this complex response, some of these binding sites correspond to the definition of the conventional receptors cited above, while others display unexpected pharmacological and functional properties. Here we present potential clues that may lead investigators to further characterize the molecular nature and functions of these atypical binding species.

Nurses' Experiences With Patients Who Die From Failure to Rescue After Surgery.

PubMed

Bacon, Cynthia Thornton

2017-05-01

To describe the lived experiences of hospital nurses caring for surgical patients who died from failure to rescue (FTR). A qualitative phenomenologic approach was used. Methods to ensure rigor and trustworthiness were incorporated into the design. The investigator conducted one-on-one semistructured interviews with 14 nurses, and data were analyzed using Colaizzi's methods. Six themes were identified: (a) the environment surrounding the FTR was unexpected; (b) FTR was unexpected but not preventable; (c) nurses were emotionally ill-prepared for the FTR; (d) nurse outcomes are different in unexpected versus expected death; (e) nurses' roles as protectors are important; and (f) FTR effects future nursing practice. Nurses' reactions after an FTR surgical death may be different when there is no identified nursing error contributing to the event. There may be key differences between deaths that are simply unexpected and those that involve FTR. The importance of mentoring junior nurses in protective surveillance skills is vital. Developing an understanding of nurses' experiences with FTR can assist nurse leaders to better support nurses who experience FTR deaths. Insight into the environment surrounding FTR deaths provides a foundation for future research aimed at improving patient safety and quality through an improved working environment for nurses. © 2017 Sigma Theta Tau International.

More than just water channels: unexpected cellular roles of aquaporins.

PubMed

Verkman, A S

2005-08-01

Aquaporins (AQPs) are membrane proteins that transport water and, in some cases, also small solutes such as glycerol. AQPs are expressed in many fluid-transporting tissues, such as kidney tubules and glandular epithelia, as well as in non-fluid-transporting tissues, such as epidermis, adipose tissue and astroglia. Their classical role in facilitating trans-epithelial fluid transport is well understood, as in the urinary concentrating mechanism and gland fluid secretion. AQPs are also involved in swelling of tissues under stress, as in the injured cornea and the brain in stroke, tumor and infection. Recent analysis of AQP-knockout mice has revealed unexpected cellular roles of AQPs. AQPs facilitate cell migration, as manifested by reduced tumor angiogenesis in AQP1-knockout mice, by a mechanism that might involve facilitated water transport in lamellipodia of migrating cells. AQPs that transport both glycerol and water regulate glycerol content in epidermis and fat, and consequently skin hydration/biosynthesis and fat metabolism. AQPs might also be involved in neural signal transduction, cell volume regulation and organellar physiology. The many roles of AQPs could be exploited for clinical benefit; for example, treatments that modulate AQP expression/function could be used as diuretics, and in the treatment of brain swelling, glaucoma, epilepsy, obesity and cancer.

Causes and Characteristics of Death in Intensive Care Units: A Prospective Multicenter Study.

PubMed

Orban, Jean-Christophe; Walrave, Yannick; Mongardon, Nicolas; Allaouchiche, Bernard; Argaud, Laurent; Aubrun, Frédéric; Barjon, Geneviève; Constantin, Jean-Michel; Dhonneur, Gilles; Durand-Gasselin, Jacques; Dupont, Hervé; Genestal, Michèle; Goguey, Chloé; Goutorbe, Philippe; Guidet, Bertrand; Hyvernat, Hervé; Jaber, Samir; Lefrant, Jean-Yves; Mallédant, Yannick; Morel, Jerôme; Ouattara, Alexandre; Pichon, Nicolas; Guérin Robardey, Anne-Marie; Sirodot, Michel; Theissen, Alexandre; Wiramus, Sandrine; Zieleskiewicz, Laurent; Leone, Marc; Ichai, Carole

2017-05-01

Different modes of death are described in selected populations, but few data report the characteristics of death in a general intensive care unit population. This study analyzed the causes and characteristics of death of critically ill patients and compared anticipated death patients to unexpected death counterparts. An observational multicenter cohort study was performed in 96 intensive care units. During 1 yr, each intensive care unit was randomized to participate during a 1-month period. Demographic data, characteristics of organ failures (Sequential Organ Failure Assessment subscore greater than or equal to 3), and organ supports were collected on all patients who died in the intensive care unit. Modes of death were defined as anticipated (after withdrawal or withholding of treatment or brain death) or unexpected (despite engagement of full-level care or sudden refractory cardiac arrest). A total of 698 patients were included during the study period. At the time of death, 84% had one or more organ failures (mainly hemodynamic) and 89% required at least one organ support (mainly mechanical ventilation). Deaths were considered unexpected and anticipated in 225 and 473 cases, respectively. Compared to its anticipated counterpart, unexpected death occurred earlier (1 day vs. 5 days; P< 0.001) and had fewer organ failures (1 [1 to 2] vs. 1 [1 to 3]; P< 0.01) and more organ supports (2 [2 to 3] vs. 1 [1 to 2]; P< 0.01). Withdrawal or withholding of treatments accounted for half of the deaths. In a general intensive care unit population, the majority of patients present with at least one organ failure at the time of death. Anticipated and unexpected deaths represent two different modes of dying and exhibit profiles reflecting the different pathophysiologic underlying mechanisms.

Sudden and unexpected childhood deaths investigated at the Pretoria Medico-Legal Laboratory, South Africa, 2007 - 2011.

PubMed

Van Deventer, B S; Rossouw, S H; Du Toit-Prinsloo, L

2016-09-06

 Sudden and unexpected death is well known to occur in infants, and although sudden deaths are less frequent after the first birthday, they still account for a significant proportion of childhood deaths. In 2009, 1.9% of the total deaths in the USA were childhood deaths. In South Africa (SA) this proportion was much higher at 11.85%. According to the law, sudden and unexpected deaths are generally investigated as unnatural deaths. Establishing an exact underlying anatomical cause of death will depend on available resources and can be difficult in a substantial proportion of cases.  A retrospective descriptive case audit was conducted at the Pretoria Medico-Legal Laboratory (PMLL), SA, from 1 January 2007 through to 31 December 2011. All children aged 1 - 18 years who died suddenly and unexpectedly were included.  Ninety-eight cases were identified, which constituted nearly 1% of total admissions to the PMLL. The majority of the deaths were of children aged 1 - 5 years, and the male/female ratio was 1.04:1. In the largest proportion of cases (n=28, 28.6%), the medicolegal investigation, including autopsy and ancillary investigations, did not establish an underlying anatomical cause of death. In the cases where a cause of death was established, pneumonia was the most common diagnosis (n=22, 22.4%).  The fact that the cause of the largest proportion of deaths could not be ascertained emphasises the need for consideration of additional investigative techniques, such as molecular/genetic screening, which have provided an underlying cause of death in a significant number of cases in other countries. There is a lack of published research on the causes and incidence of sudden unexpected deaths in children in SA, and further research in this area is needed.

True Lies: The Double Life of the Nucleotide Excision Repair Factors in Transcription and DNA Repair

PubMed Central

Le May, Nicolas; Egly, Jean-Marc; Coin, Frédéric

2010-01-01

Nucleotide excision repair (NER) is a major DNA repair pathway in eukaryotic cells. NER removes structurally diverse lesions such as pyrimidine dimers, arising upon UV irradiation or bulky chemical adducts, arising upon exposure to carcinogens and some chemotherapeutic drugs. NER defects lead to three genetic disorders that result in predisposition to cancers, accelerated aging, neurological and developmental defects. During NER, more than 30 polypeptides cooperate to recognize, incise, and excise a damaged oligonucleotide from the genomic DNA. Recent papers reveal an additional and unexpected role for the NER factors. In the absence of a genotoxic attack, the promoters of RNA polymerases I- and II-dependent genes recruit XPA, XPC, XPG, and XPF to initiate gene expression. A model that includes the growth arrest and DNA damage 45α protein (Gadd45α) and the NER factors, in order to maintain the promoter of active genes under a hypomethylated state, has been proposed but remains controversial. This paper focuses on the double life of the NER factors in DNA repair and transcription and describes the possible roles of these factors in the RNA synthesis process. PMID:20725631

Role of healthcare apparel and other healthcare textiles in the transmission of pathogens: a review of the literature.

PubMed

Mitchell, A; Spencer, M; Edmiston, C

2015-08-01

Healthcare workers (HCWs) wear uniforms, such as scrubs and lab coats, for several reasons: (1) to identify themselves as hospital personnel to their patients and employers; (2) to display professionalism; and (3) to provide barrier protection for street clothes from unexpected exposures during the work shift. A growing body of evidence suggests that HCWs' apparel is often contaminated with micro-organisms or pathogens that can cause infections or illnesses. While the majority of scrubs and lab coats are still made of the same traditional textiles used to make street clothes, new evidence suggests that current innovative textiles function as an engineering control, minimizing the acquisition, retention and transmission of infectious pathogens by reducing the levels of bioburden and microbial sustainability. This paper summarizes recent literature on the role of apparel worn in healthcare settings in the acquisition and transmission of healthcare-associated pathogens. It proposes solutions or technological interventions that can reduce the risk of transmission of micro-organisms that are associated with the healthcare environment. Healthcare apparel is the emerging frontier in epidemiologically important environmental surfaces. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Chronic low-dose ultraviolet-induced mutagenesis in nucleotide excision repair-deficient cells.

PubMed

Haruta, Nami; Kubota, Yoshino; Hishida, Takashi

2012-09-01

UV radiation induces two major types of DNA lesions, cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidine photoproducts, which are both primarily repaired by nucleotide excision repair (NER). Here, we investigated how chronic low-dose UV (CLUV)-induced mutagenesis occurs in rad14Δ NER-deficient yeast cells, which lack the yeast orthologue of human xeroderma pigmentosum A (XPA). The results show that rad14Δ cells have a marked increase in CLUV-induced mutations, most of which are C→T transitions in the template strand for transcription. Unexpectedly, many of the CLUV-induced C→T mutations in rad14Δ cells are dependent on translesion synthesis (TLS) DNA polymerase η, encoded by RAD30, despite its previously established role in error-free TLS. Furthermore, we demonstrate that deamination of cytosine-containing CPDs contributes to CLUV-induced mutagenesis. Taken together, these results uncover a novel role for Polη in the induction of C→T transitions through deamination of cytosine-containing CPDs in CLUV-exposed NER deficient cells. More generally, our data suggest that Polη can act as both an error-free and a mutagenic DNA polymerase, depending on whether the NER pathway is available to efficiently repair damaged templates.

Analysis on an illusion unexpected occurred on a moving statue leaving in fact but approaching by environmental judgment

NASA Astrophysics Data System (ADS)

He, Youwu; Li, Zhifang; Qiu, Yishen; Li, Hui

2017-08-01

Earlier this year we visited Sanya, Hainan Province, China. There is a huge statue, the South Sea Avalokitesvara (南海观世音菩萨), at Sanya Nanshan Buddhism Cultural Tourism Resort. When we were gazing at the statue on a leaving car on gradually rising road, an unexpected visual illusion took place in which the statue seemed running after us. In this presentation, an optical model is developed to explain the illusion occurred on a moving object leaving in fact but approaching by environmental judgement. Such an interesting illusion analysis will play a significant role in having students understood the main principles in geometrical optics.

Invisible Transfer: An Unexpected Finding in the Pursuit of Transfer

ERIC Educational Resources Information Center

Schieber, Danica L.

2016-01-01

Much research shows that students do not transfer learning well from one class to the next. This study was designed to investigate if students were transferring rhetorical strategies from their disciplinary courses to advanced writing courses. The findings suggest that business majors not only transferred rhetorical knowledge from their other…

Women and Higher Education; Recommendations for Change.

ERIC Educational Resources Information Center

Cohen, Audrey C.

Society has traditionally discriminated against women in the educational and professional areas, and studies have shown that even talented and educated women are affected by what has been labeled "a climate of unexpectation." Colleges and universities, as part of their responsibility to build a new society, must play a major part in affecting…

The Intersections and Impact of Professional Development for Women Chief Student Affairs Officers

ERIC Educational Resources Information Center

Wegner, Jennifer

2017-01-01

Professional development is learner-centered, where the responsibility to engage in further educational experiences belongs to the individual and is a critical way to prepare for career advancement. In higher education, cisgender women do not hold the majority of chief student affairs officers (CSAO) positions, which is unexpected given their…

The Unexpected Connection: Serendipity and Human Mediation in Networked Learning

ERIC Educational Resources Information Center

Kop, Rita

2012-01-01

Major changes on the Web in recent years have contributed to an abundance of information for people to harness in their learning. Emerging technologies have instigated the need for critical literacies to support learners on open online networks in the mastering of critical information gathering during their learning journeys. This paper will argue…

Copy number variations of six and seven α-globin genes in a family with intermedia and major thalassemia phenotypes.

PubMed

Farashi, Samaneh; Vakili, Shadi; Faramarzi Garous, Negin; Ashki, Mehri; Imanian, Hashem; Azarkeivan, Azita; Najmabadi, Hossein

2015-10-01

Copy number variations in α-globin genes are results of unequal crossover between homologous segments in the α-globin gene cluster that misalign during the meiosis phase of the gametogenesis process. Reduction or augmentation of α-globin genes leads to imbalance of α/β chains in hemoglobin tetramer and consequently attenuate or worsen the β-thal clinical symptoms, respectively. Multiplications in α-globin genes have been found in some populations, justifying unexpected severe phenotype of β-thal carriers. Unexpected severe phenotype in the family members may result from coexistence of extra α-globin genes, which is an important factor in the causation of thalassemia intermedia and major in heterozygous β-thalassemia. We described different multiplications in α-globin locus in an Iranian family with one, two or three extra α-globin genes (ααα/αα, αααα/αα and αααα/ααα). The excess α-globin gene/genes cause increment in β/α chain imbalance and leads to worsening pathophysiology and clinical severity of β-thalassemia carriers.

Encouraging Civility as a Community College Leader

ERIC Educational Resources Information Center

Elsner, Paul A., Ed.; Boggs, George R., Ed.

2006-01-01

The contributors relate examples of situations in which leaders encountered unexpected and sometimes unprecedented incivility in their role as community college leaders. The chapters present their experiences, observations, lessons, and recommendations for handling crises that may befall leaders in an academic setting. This book contains the…

The methionine salvage pathway in Bacillus subtilis

PubMed Central

Sekowska, Agnieszka; Danchin, Antoine

2002-01-01

Background Polyamine synthesis produces methylthioadenosine, which has to be disposed of. The cell recycles it into methionine through methylthioribose (MTR). Very little was known about MTR recycling for methionine salvage in Bacillus subtilis. Results Using in silico genome analysis and transposon mutagenesis in B. subtilis we have experimentally uncovered the major steps of the dioxygen-dependent methionine salvage pathway, which, although similar to that found in Klebsiella pneumoniae, recruited for its implementation some entirely different proteins. The promoters of the genes have been identified by primer extension, and gene expression was analyzed by Northern blotting and lacZ reporter gene expression. Among the most remarkable discoveries in this pathway is the role of an analog of ribulose diphosphate carboxylase (Rubisco, the plant enzyme used in the Calvin cycle which recovers carbon dioxide from the atmosphere) as a major step in MTR recycling. Conclusions A complete methionine salvage pathway exists in B. subtilis. This pathway is chemically similar to that in K. pneumoniae, but recruited different proteins to this purpose. In particular, a paralogue or Rubisco, MtnW, is used at one of the steps in the pathway. A major observation is that in the absence of MtnW, MTR becomes extremely toxic to the cell, opening an unexpected target for new antimicrobial drugs. In addition to methionine salvage, this pathway protects B. subtilis against dioxygen produced by its natural biotope, the surface of leaves (phylloplane). PMID:12022921

Metatranscriptomic analysis of a high-sulfide aquatic spring reveals insights into sulfur cycling and unexpected aerobic metabolism

PubMed Central

Elshahed, Mostafa S.; Najar, Fares Z.; Krumholz, Lee R.

2015-01-01

Zodletone spring is a sulfide-rich spring in southwestern Oklahoma characterized by shallow, microoxic, light-exposed spring water overlaying anoxic sediments. Previously, culture-independent 16S rRNA gene based diversity surveys have revealed that Zodletone spring source sediments harbor a highly diverse microbial community, with multiple lineages putatively involved in various sulfur-cycling processes. Here, we conducted a metatranscriptomic survey of microbial populations in Zodletone spring source sediments to characterize the relative prevalence and importance of putative phototrophic, chemolithotrophic, and heterotrophic microorganisms in the sulfur cycle, the identity of lineages actively involved in various sulfur cycling processes, and the interaction between sulfur cycling and other geochemical processes at the spring source. Sediment samples at the spring’s source were taken at three different times within a 24-h period for geochemical analyses and RNA sequencing. In depth mining of datasets for sulfur cycling transcripts revealed major sulfur cycling pathways and taxa involved, including an unexpected potential role of Actinobacteria in sulfide oxidation and thiosulfate transformation. Surprisingly, transcripts coding for the cyanobacterial Photosystem II D1 protein, methane monooxygenase, and terminal cytochrome oxidases were encountered, indicating that genes for oxygen production and aerobic modes of metabolism are actively being transcribed, despite below-detectable levels (<1 µM) of oxygen in source sediment. Results highlight transcripts involved in sulfur, methane, and oxygen cycles, propose that oxygenic photosynthesis could support aerobic methane and sulfide oxidation in anoxic sediments exposed to sunlight, and provide a viewpoint of microbial metabolic lifestyles under conditions similar to those seen during late Archaean and Proterozoic eons. PMID:26417542

Attitudes toward clinical autopsy in unexpected patient deaths in Japan: a nation-wide survey of the general public and physicians.

PubMed

Kamishiraki, Etsuko; Maeda, Shoichi; Starkey, Jay; Ikeda, Noriaki

2012-12-01

Autopsy is a useful tool for understanding the cause and manner of unexpected patient death. However, the attitudes of the general public and physicians in Japan about clinical autopsy are limited. To describe the beliefs of the general public about whether autopsy should be performed and ascertain if they would actually request one given specific clinical situations where patient death occurred with the additional variable of medical error. To compare these attitudes with previously obtained attitudes of physicians practising at Japanese teaching hospitals. We conducted a cross-sectional study of the general public. We sent standardised questionnaires in 2010 to a randomly selected non-physician adult population using a survey company for participant selection. Respondents gave their opinions about the necessity of autopsy and how they might act given various clinical scenarios of patient death. We compared these results with those of a previous survey of Japanese physicians conducted in 2009. Of the 2300 eligible general adult population, 1575 (68.5%) responded. The majority of the general public indicated they believed an autopsy was necessary. However, in cases of unclear medical error or unclear cause and effect relationship of medical care and patient death, the general public were much less likely to indicate they would actually request an autopsy than were physicians (p<0.0001). Currently in Japan the debate about the role autopsy should play in the case of error related to death is underway. The results from this study will be important in informing related decisions.

Metatranscriptomic analysis of a high-sulfide aquatic spring reveals insights into sulfur cycling and unexpected aerobic metabolism.

PubMed

Spain, Anne M; Elshahed, Mostafa S; Najar, Fares Z; Krumholz, Lee R

2015-01-01

Zodletone spring is a sulfide-rich spring in southwestern Oklahoma characterized by shallow, microoxic, light-exposed spring water overlaying anoxic sediments. Previously, culture-independent 16S rRNA gene based diversity surveys have revealed that Zodletone spring source sediments harbor a highly diverse microbial community, with multiple lineages putatively involved in various sulfur-cycling processes. Here, we conducted a metatranscriptomic survey of microbial populations in Zodletone spring source sediments to characterize the relative prevalence and importance of putative phototrophic, chemolithotrophic, and heterotrophic microorganisms in the sulfur cycle, the identity of lineages actively involved in various sulfur cycling processes, and the interaction between sulfur cycling and other geochemical processes at the spring source. Sediment samples at the spring's source were taken at three different times within a 24-h period for geochemical analyses and RNA sequencing. In depth mining of datasets for sulfur cycling transcripts revealed major sulfur cycling pathways and taxa involved, including an unexpected potential role of Actinobacteria in sulfide oxidation and thiosulfate transformation. Surprisingly, transcripts coding for the cyanobacterial Photosystem II D1 protein, methane monooxygenase, and terminal cytochrome oxidases were encountered, indicating that genes for oxygen production and aerobic modes of metabolism are actively being transcribed, despite below-detectable levels (<1 µM) of oxygen in source sediment. Results highlight transcripts involved in sulfur, methane, and oxygen cycles, propose that oxygenic photosynthesis could support aerobic methane and sulfide oxidation in anoxic sediments exposed to sunlight, and provide a viewpoint of microbial metabolic lifestyles under conditions similar to those seen during late Archaean and Proterozoic eons.

An unexpected effect of TNF-α on F508del-CFTR maturation and function

PubMed Central

Bitam, Sara; Urbach, Valérie; Sermet-Gaudelus, Isabelle; Hinzpeter, Alexandre; Edelman, Aleksander

2015-01-01

Cystic fibrosis (CF) is a multifactorial disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene ( CFTR), which encodes a cAMP-dependent Cl - channel. The most frequent mutation, F508del, leads to the synthesis of a prematurely degraded, otherwise partially functional protein. CFTR is expressed in many epithelia, with major consequences in the airways of patients with CF, characterized by both fluid transport abnormalities and persistent inflammatory responses. The relationship between the acute phase of inflammation and the expression of wild type (WT) CFTR or F508del-CFTR is poorly understood. The aim of the present study was to investigate this effect. The results show that 10 min exposure to TNF-alpha (0.5-50ng/ml) of F508del-CFTR-transfected HeLa cells and human bronchial cells expressing F508del-CFTR in primary culture (HBE) leads to the maturation of F508del-CFTR and induces CFTR chloride currents. The enhanced CFTR expression and function upon TNFα is sustained, in HBE cells, for at least 24 h. The underlying mechanism of action involves a protein kinase C (PKC) signaling pathway, and occurs through insertion of vesicles containing F508del-CFTR to the plasma membrane, with TNFα behaving as a corrector molecule. In conclusion, a novel and unexpected action of TNFα has been discovered and points to the importance of systematic studies on the roles of inflammatory mediators in the maturation of abnormally folded proteins in general and in the context of CF in particular. PMID:26594334

Failing American Indian Languages

ERIC Educational Resources Information Center

Meek, Barbara A.

2011-01-01

This article critically examines the mediating role of scholarly expectations and the unexpected in the management--and transcendence--of failure/success as these concepts relate to language revitalization. Deloria remarks that, "expectations tend to assume a status quo defined around failure, the result of some innate limitation on the part of…

Serendipity and Scientific Discovery.

ERIC Educational Resources Information Center

Rosenman, Martin F.

1988-01-01

The discovery of penicillin is cited in a discussion of the role of serendipity as it relates to scientific discovery. The importance of sagacity as a personality trait is noted. Successful researchers have questioning minds, are willing to view data from several perspectives, and recognize and appreciate the unexpected. (JW)

Role of mp 17O Seprase in Breast Cancer.

DTIC Science & Technology

1998-07-01

identical subunits of MT 97 kDa. Recent evidence indicated that the Seprase subunit is identical to Fibroblast Activation Protein a ( FAPa ). To characterize...and define the role of this molecule in cancer, human Seprase/ FAPa cDNA was cloned and stable transfected in two human epithelial carcinoma cell lines...SW-13 and MCF-7. Unexpectedly, overexpression of Seprase/ FAPa has no apparent effect on the proliferation, matrix adhesion and matrigel invasion of

A pharmacy student's role as a teaching assistant in an undergraduate medicinal chemistry course - Implementation, evaluation, and unexpected opportunities for educational outreach.

PubMed

DellaVecchia, Matthew J; Claudio, Alyssa M; Fairclough, Jamie L

2017-11-01

To describe 1) a pharmacy student's teaching assistant (TA) role in an undergraduate medicinal chemistry course, 2) an active learning module co-developed by the TA and instructor, and 3) the unexpected opportunities for pharmacy educational outreach that resulted from this collaboration. Medicinal Chemistry (CHM3413) is an undergraduate course offered each fall at Palm Beach Atlantic University (PBA). As a TA for CHM3413, a pharmacy student from the Gregory School of Pharmacy (GSOP) at PBA co-developed and implemented an active learning module emphasizing foundational medicinal chemistry concepts as they pertain to performance enhancing drugs (PEDs). Surveys assessed undergraduate students' perceived knowledge of medicinal chemistry concepts, PEDs, and TA involvement. Students' (total n = 60, three fall semesters) perceived confidence in knowledge of medicinal chemistry concepts and PEDs increased significantly (p < 0.001) after the TA's module. Nearly 93% of students acknowledged this was their first interaction with a TA at PBA, ~ 82% "agreed/strongly agreed" that the TA provided effective instruction, and ~ 62% "agreed/strongly agreed" that TA availability raised overall confidence in CHM3413. Unexpected "side-effects" of this collaboration included opportunities for the TA and instructor to discuss health risks associated with PED usage with student-athletes and coaches at PBA. This collaboration developed the pharmacy student's teaching skills and reinforced knowledge of foundational pharmaceutical science concepts for both the TA and undergraduate students. Unexpected "side-effects" that resulted from this collaboration included opportunities for the TA and instructor to discuss health risks associated with PED usage with student-athletes in PBA's athletic department. Educational/interprofessional outreach opportunities resulted from a pharmacy student TA's involvement in an undergraduate medicinal chemistry course. An advanced pharmacy practice experience elective in sports pharmacy (based on Ambrose's model) begins Fall 2017. Copyright © 2017 Elsevier Inc. All rights reserved.

New Insights into Microglia-Neuron Interactions: A Neuron's Perspective.

PubMed

Pósfai, Balázs; Cserép, Csaba; Orsolits, Barbara; Dénes, Ádám

2018-05-19

Microglia are the primary immune cells of the central nervous system. However, recent data indicate that microglia also contribute to diverse physiological and pathophysiological processes that extend beyond immune-related functions and there is a growing interest to understand the mechanisms through which microglia interact with other cells in the brain. In particular, the molecular processes that contribute to microglia-neuron communication in the healthy brain and their role in common brain diseases have been intensively studied during the last decade. In line with this, fate-mapping studies, genetic models and novel pharmacological approaches have revealed the origin of microglial progenitors, demonstrated the role of self-maintaining microglial populations during brain development or in adulthood, and identified the unexpectedly long lifespan of microglia that may profoundly change our view about senescence and age-related human diseases. Despite the exponentially increasing knowledge about microglia, the role of these cells in health and disease is still extremely controversial and the precise molecular targets for intervention are not well defined. This is in part due to the lack of microglia-specific manipulation approaches until very recently and to the high level of complexity of the interactions between microglia and other cells in the brain that occur at different temporal and spatial scales. In this review, we briefly summarize the known physiological roles of microglia-neuron interactions in brain homeostasis and attempt to outline some major directions and challenges of future microglia research. Copyright © 2018. Published by Elsevier Ltd.

Plants and climate change: complexities and surprises.

PubMed

Parmesan, Camille; Hanley, Mick E

2015-11-01

Anthropogenic climate change (ACC) will influence all aspects of plant biology over coming decades. Many changes in wild species have already been well-documented as a result of increased atmospheric CO2 concentrations, warming climate and changing precipitation regimes. A wealth of available data has allowed the use of meta-analyses to examine plant-climate interactions on more sophisticated levels than before. These analyses have revealed major differences in plant response among groups, e.g. with respect to functional traits, taxonomy, life-history and provenance. Interestingly, these meta-analyses have also exposed unexpected mismatches between theory, experimental, and observational studies. We reviewed the literature on species' responses to ACC, finding ∼42 % of 4000 species studied globally are plants (primarily terrestrial). We review impacts on phenology, distributions, ecophysiology, regeneration biology, plant-plant and plant-herbivore interactions, and the roles of plasticity and evolution. We focused on apparent deviations from expectation, and highlighted cases where more sophisticated analyses revealed that unexpected changes were, in fact, responses to ACC. We found that conventionally expected responses are generally well-understood, and that it is the aberrant responses that are now yielding greater insight into current and possible future impacts of ACC. We argue that inconclusive, unexpected, or counter-intuitive results should be embraced in order to understand apparent disconnects between theory, prediction, and observation. We highlight prime examples from the collection of papers in this Special Issue, as well as general literature. We found use of plant functional groupings/traits had mixed success, but that some underutilized approaches, such as Grime's C/S/R strategies, when incorporated, have improved understanding of observed responses. Despite inherent difficulties, we highlight the need for ecologists to conduct community-level experiments in systems that replicate multiple aspects of ACC. Specifically, we call for development of coordinating experiments across networks of field sites, both natural and man-made. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Population of Projection Neurons that Inhibits the Lateral Horn but Excites the Antennal Lobe through Chemical Synapses in Drosophila

PubMed Central

Shimizu, Kazumichi; Stopfer, Mark

2017-01-01

In the insect olfactory system, odor information is transferred from the antennal lobe (AL) to higher brain areas by projection neurons (PNs) in multiple AL tracts (ALTs). In several species, one of the ALTs, the mediolateral ALT (mlALT), contains some GABAergic PNs; in the Drosophila brain, the great majority of ventral PNs (vPNs) are GABAergic and project through this tract to the lateral horn (LH). Most excitatory PNs (ePNs), project through the medial ALT (mALT) to the mushroom body (MB) and the LH. Recent studies have shown that GABAergic vPNs play inhibitory roles at their axon terminals in the LH. However, little is known about the properties and functions of vPNs at their dendritic branches in the AL. Here, we used optogenetic and patch clamp techniques to investigate the functional roles of vPNs in the AL. Surprisingly, our results show that specific activation of vPNs reliably elicits strong excitatory postsynaptic potentials (EPSPs) in ePNs. Moreover, the connections between vPNs and ePNs are mediated by direct chemical synapses. Neither pulses of GABA, nor pharmagological, or genetic blockade of GABAergic transmission gave results consistent with the involvement of GABA in vPN-ePN excitatory transmission. These unexpected results suggest new roles for the vPN population in olfactory information processing. PMID:28515683

A New Role for Browning as a Redox and Stress Adaptive Mechanism?

PubMed

Jeanson, Yannick; Carrière, Audrey; Casteilla, Louis

2015-01-01

The worldwide epidemic of obesity and metabolic disorders is focusing the attention of the scientific community on white adipose tissue (WAT) and its biology. This tissue is characterized not only by its capability to change in size and shape but also by its heterogeneity and versatility. WAT can be converted into brown fat-like tissue according to different physiological and pathophysiological situations. The expression of uncoupling protein-1 in brown-like adipocytes changes their function from energy storage to energy dissipation. This plasticity, named browning, was recently rediscovered and convergent recent accounts, including in humans, have revived the idea of using these oxidative cells to fight against metabolic diseases. Furthermore, recent reports suggest that, beside the increased energy dissipation and thermogenesis that may have adverse effects in situations such as cancer-associated cachexia and massive burns, browning could be also considered as an adaptive stress response to high redox pressure and to major stress that could help to maintain tissue homeostasis and integrity. The aim of this review is to summarize the current knowledge concerning brown adipocytes and the browning process and also to explore unexpected putative role(s) for these cells. While it is important to find new browning inducers to limit energy stores and metabolic diseases, it also appears crucial to develop new browning inhibitors to limit adverse energy dissipation in wasting-associated syndromes.

Evidence for glycosylation as a regulator of the pigmentary system: key roles of sialyl(α2-6)gal/GalNAc-terminated glycans in melanin synthesis and transfer.

PubMed

Diwakar, Ganesh; Klump, Vincent; Lazova, Rossitza; Pawelek, John

2015-08-01

The major regulators of melanogenesis are glycoproteins, however no role for glycosylation in the pathway has yet been described. We stained skin biopsies and melanocyte-keratinocyte co-cultures with a panel of 20 lectins as oligosaccharide markers. Notably, the Elderberry Bark Lectin (EBL/SNA) stained melanocytes in both systems. EBL binds the sequence Neu5Ac(α(2-6)Gal/GalNAc)- at the termini of some oligosaccharide antennae. We used inhibitors of synthesis and/or binding of this sequence to assess effects on pigmentation. Cell culture, lectin histochemistry, siRNA transfection, and assays for dopa oxidase and melanin were carried out by standard techniques. 6'-sialyllactose, a short homolog of the sequence in question, anti-sialyltransferase 6 (ST6) siRNA, and cytidine, a sialyltransferase (ST) inhibitor, each inhibited EBL binding, melanogenesis and melanosome transfer. Unexpectedly, 3'-sialyllactose and siRNA for ST3, chosen as a negative controls, also inhibited these processes. Though strong inhibitors of melanization, none of the agents affected tyrosinase/dopa oxidase activity, indicating previously unrecognized post-tyrosinase regulation of melanization. We report for the first time that Neu5Ac (α(2-6)Gal/GalNAc)- and possibly Neu5Ac(α(2-3)Gal/GalNAc)-terminated oligosaccharides play multiple roles in melanin synthesis and transfer.

A Population of Projection Neurons that Inhibits the Lateral Horn but Excites the Antennal Lobe through Chemical Synapses in Drosophila.

PubMed

Shimizu, Kazumichi; Stopfer, Mark

2017-01-01

In the insect olfactory system, odor information is transferred from the antennal lobe (AL) to higher brain areas by projection neurons (PNs) in multiple AL tracts (ALTs). In several species, one of the ALTs, the mediolateral ALT (mlALT), contains some GABAergic PNs; in the Drosophila brain, the great majority of ventral PNs (vPNs) are GABAergic and project through this tract to the lateral horn (LH). Most excitatory PNs (ePNs), project through the medial ALT (mALT) to the mushroom body (MB) and the LH. Recent studies have shown that GABAergic vPNs play inhibitory roles at their axon terminals in the LH. However, little is known about the properties and functions of vPNs at their dendritic branches in the AL. Here, we used optogenetic and patch clamp techniques to investigate the functional roles of vPNs in the AL. Surprisingly, our results show that specific activation of vPNs reliably elicits strong excitatory postsynaptic potentials (EPSPs) in ePNs. Moreover, the connections between vPNs and ePNs are mediated by direct chemical synapses. Neither pulses of GABA, nor pharmagological, or genetic blockade of GABAergic transmission gave results consistent with the involvement of GABA in vPN-ePN excitatory transmission. These unexpected results suggest new roles for the vPN population in olfactory information processing.

Simultaneous repair of abdominal aortic aneurysm and resection of unexpected, associated abdominal malignancies.

PubMed

Illuminati, Giulio; Calio', Francesco G; D'Urso, Antonio; Lorusso, Riccardo; Ceccanei, Gianluca; Vietri, Francesco

2004-12-15

The management of unexpected intra-abdominal malignancy, discovered at laparotomy for elective treatment of an abdominal aortic aneurysm (AAA), is controversial. It is still unclear whether both conditions should be treated simultaneously or a staged approach is to be preferred. To contribute in improving treatment guidelines, we retrospectively reviewed the records of patients undergoing laparotomy for elective AAA repair. From January 1994 to March 2003, 253 patients underwent elective, trans-peritoneal repair of an AAA. In four patients (1.6%), an associated, unexpected neoplasm was detected at abdominal exploration, consisting of one renal, one gastric, one ileal carcinoid, and one ascending colon tumor. All of them were treated at the same operation, after aortic repair and careful isolation of the prosthetic graft. The whole series' operative mortality was 3.6%. None of the patients simultaneously treated for AAA and tumor resection died in the postoperative period. No graft-related infections were observed. Simultaneous treatment of AAA and tumor did not prolong significantly the mean length of stay in the hospital, compared to standard treatment of AAA alone. Except for malignancies of organs requiring major surgical resections, simultaneous AAA repair and resection of an associated, unexpected abdominal neoplasm can be safely performed, in most of the patients, sparing the need for a second procedure. Endovascular grafting of the AAA can be a valuable tool in simplifying simultaneous treatment, or in staging the procedures with a very short delay.

False Belief Understanding: The Influence of Person, Grammatical Mood, Counterfactual Reasoning and Working Memory

ERIC Educational Resources Information Center

Muller, Ulrich; Miller, Michael R.; Michalczyk, Kurt; Karapinka, Aaron

2007-01-01

The present study had two major goals. The first goal was to assess the relative difficulty among different versions of the unexpected contents task by systematically varying the dimensions of grammatical mood (indicative vs. subjunctive) and person (self vs. other), and to examine the correlational pattern between these different versions of the…

Pseudospectra in non-Hermitian quantum mechanics

NASA Astrophysics Data System (ADS)

Krejčiřík, D.; Siegl, P.; Tater, M.; Viola, J.

2015-10-01

We propose giving the mathematical concept of the pseudospectrum a central role in quantum mechanics with non-Hermitian operators. We relate pseudospectral properties to quasi-Hermiticity, similarity to self-adjoint operators, and basis properties of eigenfunctions. The abstract results are illustrated by unexpected wild properties of operators familiar from PT -symmetric quantum mechanics.

Gene-targeted mice lacking the Trex1 (DNase III) 3'-->5' DNA exonuclease develop inflammatory myocarditis.

PubMed

Morita, Masashi; Stamp, Gordon; Robins, Peter; Dulic, Anna; Rosewell, Ian; Hrivnak, Geza; Daly, Graham; Lindahl, Tomas; Barnes, Deborah E

2004-08-01

TREX1, originally designated DNase III, was isolated as a major nuclear DNA-specific 3'-->5' exonuclease that is widely distributed in both proliferating and nonproliferating mammalian tissues. The cognate cDNA shows homology to the editing subunit of the Escherichia coli replicative DNA polymerase III holoenzyme and encodes an exonuclease which was able to serve a DNA-editing function in vitro, promoting rejoining of a 3' mismatched residue in a reconstituted DNA base excision repair system. Here we report the generation of gene-targeted Trex1(-/-) mice. The null mice are viable and do not show the increase in spontaneous mutation frequency or cancer incidence that would be predicted if Trex1 served an obligatory role of editing mismatched 3' termini generated during DNA repair or DNA replication in vivo. Unexpectedly, Trex1(-/-) mice exhibit a dramatically reduced survival and develop inflammatory myocarditis leading to progressive, often dilated, cardiomyopathy and circulatory failure.

Unexpected link between an antibiotic, pannexin channels and apoptosis.

PubMed

Poon, Ivan K H; Chiu, Yu-Hsin; Armstrong, Allison J; Kinchen, Jason M; Juncadella, Ignacio J; Bayliss, Douglas A; Ravichandran, Kodi S

2014-03-20

Plasma membrane pannexin 1 channels (PANX1) release nucleotide find-me signals from apoptotic cells to attract phagocytes. Here we show that the quinolone antibiotic trovafloxacin is a novel PANX1 inhibitor, by using a small-molecule screen. Although quinolones are widely used to treat bacterial infections, some quinolones have unexplained side effects, including deaths among children. PANX1 is a direct target of trovafloxacin at drug concentrations seen in human plasma, and its inhibition led to dysregulated fragmentation of apoptotic cells. Genetic loss of PANX1 phenocopied trovafloxacin effects, revealing a non-redundant role for pannexin channels in regulating cellular disassembly during apoptosis. Increase in drug-resistant bacteria worldwide and the dearth of new antibiotics is a major human health challenge. Comparing different quinolone antibiotics suggests that certain structural features may contribute to PANX1 blockade. These data identify a novel linkage between an antibiotic, pannexin channels and cellular integrity, and suggest that re-engineering certain quinolones might help develop newer antibacterials.

Implications of low mechanical impedance in upper limb reaching motion.

PubMed

Popescu, Florin C; Rymeri, W Zev

2003-10-01

The equilibrium point hypothesis (EPH), much discussed in recent years, is central in a class of theories that posits an important role for muscular mechanical and reflex properties in the control of voluntary movement. We review briefly the findings of our studies testing the idea of equifinality, a major tenet of the EPH, which predicts that terminal limb position will be achieved regardless of transient perturbations in initial position or during ongoing movement. Our observations do not support this prediction of equifinality. We also report our findings that joint viscosity and elastic stiffness estimated during ballistic motion are unexpectedly low, limiting their potential contributions to the regulation either of limb movement trajectory or of limb stability. Taken together, our results imply that neuromuscular mechanical properties are unlikely to be used for regulating voluntary motion, and that other control strategies, most notably the use of feedforward controllers in which muscles act as force generators acting primarily on inertial loads, are more consistent with our observations.

Exploring the role of music therapy in cardiac rehabilitation after cardiothoracic surgery: a qualitative study using the Bonny method of guided imagery and music.

PubMed

Short, Alison; Gibb, Heather; Fildes, Jennifer; Holmes, Colin

2013-01-01

Cardiac rehabilitation integrates physical, psychological, and vocational strategies to restore and sustain optimal health. An innovative study using music therapy (Bonny Method of Guided Imagery and Music [BMGIM]) explored the experiences of cardiac rehabilitation participants in an outpatient setting at 2 major metropolitan teaching hospitals. Commencing 6 to 15 weeks after cardiothoracic surgery, 6 study participants were recruited for 6 weekly music therapy (BMGIM) sessions. Qualitative analysis of the patient narrative within a semiotic framework demonstrated that patients used music therapy to spontaneously explore their recovery process. Five grand themes emerged: (1) looking through the frame, (2) feeling the impact, (3) spiralling into the unexpected, (4) sublime plateau, and (5) rehearsing new steps. The themes related to physical changes, adjustment after surgery, and anticipated lifestyle. This study demonstrates that music therapy (BMGIM) may be used to access and understand the internal recovery process of postcardiothoracic surgical patients, providing an additional clinical tool to augment the external rehabilitation process.

Effects of orthographic consistency on eye movement behavior: German and English children and adults process the same words differently.

PubMed

Rau, Anne K; Moll, Kristina; Snowling, Margaret J; Landerl, Karin

2015-02-01

The current study investigated the time course of cross-linguistic differences in word recognition. We recorded eye movements of German and English children and adults while reading closely matched sentences, each including a target word manipulated for length and frequency. Results showed differential word recognition processes for both developing and skilled readers. Children of the two orthographies did not differ in terms of total word processing time, but this equal outcome was achieved quite differently. Whereas German children relied on small-unit processing early in word recognition, English children applied small-unit decoding only upon rereading-possibly when experiencing difficulties in integrating an unfamiliar word into the sentence context. Rather unexpectedly, cross-linguistic differences were also found in adults in that English adults showed longer processing times than German adults for nonwords. Thus, although orthographic consistency does play a major role in reading development, cross-linguistic differences are detectable even in skilled adult readers. Copyright © 2014 Elsevier Inc. All rights reserved.

Pronounced Environmental Effects on Injection Currents in EGaIn Tunneling Junctions Comprising Self-Assembled Monolayers.

PubMed

Carlotti, Marco; Degen, Maarten; Zhang, Yanxi; Chiechi, Ryan C

2016-09-15

Large-area tunneling junctions using eutectic Ga-In (EGaIn) as a top contact have proven to be a robust, reproducible, and technologically relevant platform for molecular electronics. Thus far, the majority of studies have focused on saturated molecules with backbones consisting mainly of alkanes in which the frontier orbitals are either highly localized or energetically inaccessible. We show that self-assembled monolayers of wire-like oligophenyleneethynylenes (OPEs), which are fully conjugated, only exhibit length-dependent tunneling behavior in a low-O 2 environment. We attribute this unexpected behavior to the sensitivity of injection current on environment. We conclude that, contrary to previous reports, the self-limiting layer of Ga 2 O 3 strongly influences transport properties and that the effect is related to the wetting behavior of the electrode. This result sheds light on the nature of the electrode-molecule interface and suggests that adhesive forces play a significant role in tunneling charge-transport in large-area molecular junctions.

Human body epigenome maps reveal noncanonical DNA methylation variation.

PubMed

Schultz, Matthew D; He, Yupeng; Whitaker, John W; Hariharan, Manoj; Mukamel, Eran A; Leung, Danny; Rajagopal, Nisha; Nery, Joseph R; Urich, Mark A; Chen, Huaming; Lin, Shin; Lin, Yiing; Jung, Inkyung; Schmitt, Anthony D; Selvaraj, Siddarth; Ren, Bing; Sejnowski, Terrence J; Wang, Wei; Ecker, Joseph R

2015-07-09

Understanding the diversity of human tissues is fundamental to disease and requires linking genetic information, which is identical in most of an individual's cells, with epigenetic mechanisms that could have tissue-specific roles. Surveys of DNA methylation in human tissues have established a complex landscape including both tissue-specific and invariant methylation patterns. Here we report high coverage methylomes that catalogue cytosine methylation in all contexts for the major human organ systems, integrated with matched transcriptomes and genomic sequence. By combining these diverse data types with each individuals' phased genome, we identified widespread tissue-specific differential CG methylation (mCG), partially methylated domains, allele-specific methylation and transcription, and the unexpected presence of non-CG methylation (mCH) in almost all human tissues. mCH correlated with tissue-specific functions, and using this mark, we made novel predictions of genes that escape X-chromosome inactivation in specific tissues. Overall, DNA methylation in several genomic contexts varies substantially among human tissues.

Highlighting the History of French Radio Astronomy. 7: The Genesis of the Institute of Astronomy at Millimeter Wavelengths (IRAM)

NASA Astrophysics Data System (ADS)

Encrenaz, Pierre; Gómez González, Jesús; Lequeux, James; Orchiston, Wayne

2011-07-01

Radio astronomy in France and in Germany started around 1950. France was then building interferometers and Germany large single dishes, so it was not unexpected that their first projects involving millimetre radio astronomy were respectively with an interferometer and a single dish. In this paper, we explain in detail how these two projects finally merged in 1979 with the formation of the Institute of Radio Astronomy at Millimetre Wavelengths (IRAM), after a long process with many ups and downs. We also describe how Spain started radio astronomy by joining IRAM. Presently, IRAM is the most powerful facility worldwide for millimetre radio astronomy. We wish to dedicate our paper to the memory of Émile-Jacques Blum (1923-2009), who played a major role in the construction of IRAM but died before he could participate in the writing of this paper. An interview made one month before his death was very useful in the preparation of this paper.

DNA Looping Facilitates Targeting of a Chromatin Remodeling Enzyme

PubMed Central

Yadon, Adam N; Singh, Badri Nath; Hampsey, Michael; Tsukiyama, Toshio

2013-01-01

Summary ATP-dependent chromatin remodeling enzymes are highly abundant and play pivotal roles regulating DNA-dependent processes. The mechanisms by which they are targeted to specific loci have not been well understood on a genome-wide scale. Here we present evidence that a major targeting mechanism for the Isw2 chromatin remodeling enzyme to specific genomic loci is through sequence-specific transcription factor (TF)-dependent recruitment. Unexpectedly, Isw2 is recruited in a TF-dependent fashion to a large number of loci without TF binding sites. Using the 3C assay, we show that Isw2 can be targeted by Ume6- and TFIIB-dependent DNA looping. These results identify DNA looping as a previously unknown mechanism for the recruitment of a chromatin remodeling enzyme and defines a novel function for DNA looping. We also present evidence suggesting that Ume6-dependent DNA looping is involved in chromatin remodeling and transcriptional repression, revealing a mechanism by which the three-dimensional folding of chromatin affects DNA-dependent processes. PMID:23478442

Ecto-F1-ATPase: A moonlighting protein complex and an unexpected apoA-I receptor

PubMed Central

Vantourout, Pierre; Radojkovic, Claudia; Lichtenstein, Laeticia; Pons, Véronique; Champagne, Eric; Martinez, Laurent O

2010-01-01

Mitochondrial ATP synthase has been recently detected at the surface of different cell types, where it is a high affinity receptor for apoA-I, the major protein component in high density lipoproteins (HDL). Cell surface ATP synthase (namely ecto-F1-ATPase) expression is related to different biological effects, such as regulation of HDL uptake by hepatocytes, endothelial cell proliferation or antitumor activity of Vγ9/Vδ2 T lymphocytes. This paper reviews the recently discovered functions and regulations of ecto-F1-ATPase. Particularly, the role of the F1-ATPase pathway(s) in HDL-cholesterol uptake and apoA-I-mediated endothelial protection suggests its potential importance in reverse cholesterol transport and its regulation might represent a potential therapeutic target for HDL-related therapy for cardiovascular diseases. Therefore, it is timely for us to better understand how this ecto-enzyme and downstream pathways are regulated and to develop pharmacologic interventions. PMID:21157968

Immune modulation by genetic modification of dendritic cells with lentiviral vectors.

PubMed

Liechtenstein, Therese; Perez-Janices, Noemi; Bricogne, Christopher; Lanna, Alessio; Dufait, Inès; Goyvaerts, Cleo; Laranga, Roberta; Padella, Antonella; Arce, Frederick; Baratchian, Mehdi; Ramirez, Natalia; Lopez, Natalia; Kochan, Grazyna; Blanco-Luquin, Idoia; Guerrero-Setas, David; Breckpot, Karine; Escors, David

2013-09-01

Our work over the past eight years has focused on the use of HIV-1 lentiviral vectors (lentivectors) for the genetic modification of dendritic cells (DCs) to control their functions in immune modulation. DCs are key professional antigen presenting cells which regulate the activity of most effector immune cells, including T, B and NK cells. Their genetic modification provides the means for the development of targeted therapies towards cancer and autoimmune disease. We have been modulating with lentivectors the activity of intracellular signalling pathways and co-stimulation during antigen presentation to T cells, to fine-tune the type and strength of the immune response. In the course of our research, we have found unexpected results such as the surprising immunosuppressive role of anti-viral signalling pathways, and the close link between negative co-stimulation in the immunological synapse and T cell receptor trafficking. Here we review our major findings and put them into context with other published work. Copyright © 2013 Elsevier B.V. All rights reserved.

Skylab

NASA Image and Video Library

1973-05-01

The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Intrnal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image shows astronaut Kerwin cutting the metal strap to free and deploy the Orbital Workshop solar array. Kerwin used special cutting tools developed by engineers at the Marshall Space Flight Center (MSFC). The MSFC had a major role in developing the procedures to repair the damaged Skylab.

Skylab

NASA Image and Video Library

1973-05-01

The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image, taken during a fly-around inspection by the Skylab-2 crew, shows the station's remaining solar panel jammed against its side. The Marshall Space Flight Center had a major role in developing the procedures to repair the damaged Skylab.

Pronounced Environmental Effects on Injection Currents in EGaIn Tunneling Junctions Comprising Self-Assembled Monolayers

PubMed Central

2016-01-01

Large-area tunneling junctions using eutectic Ga–In (EGaIn) as a top contact have proven to be a robust, reproducible, and technologically relevant platform for molecular electronics. Thus far, the majority of studies have focused on saturated molecules with backbones consisting mainly of alkanes in which the frontier orbitals are either highly localized or energetically inaccessible. We show that self-assembled monolayers of wire-like oligophenyleneethynylenes (OPEs), which are fully conjugated, only exhibit length-dependent tunneling behavior in a low-O2 environment. We attribute this unexpected behavior to the sensitivity of injection current on environment. We conclude that, contrary to previous reports, the self-limiting layer of Ga2O3 strongly influences transport properties and that the effect is related to the wetting behavior of the electrode. This result sheds light on the nature of the electrode–molecule interface and suggests that adhesive forces play a significant role in tunneling charge-transport in large-area molecular junctions. PMID:27738488

Computational Analysis Reveals a Key Regulator of Cryptococcal Virulence and Determinant of Host Response

PubMed Central

Gish, Stacey R.; Maier, Ezekiel J.; Haynes, Brian C.; Santiago-Tirado, Felipe H.; Srikanta, Deepa L.; Ma, Cynthia Z.; Li, Lucy X.; Williams, Matthew; Crouch, Erika C.; Khader, Shabaana A.

2016-01-01

ABSTRACT Cryptococcus neoformans is a ubiquitous, opportunistic fungal pathogen that kills over 600,000 people annually. Here, we report integrated computational and experimental investigations of the role and mechanisms of transcriptional regulation in cryptococcal infection. Major cryptococcal virulence traits include melanin production and the development of a large polysaccharide capsule upon host entry; shed capsule polysaccharides also impair host defenses. We found that both transcription and translation are required for capsule growth and that Usv101 is a master regulator of pathogenesis, regulating melanin production, capsule growth, and capsule shedding. It does this by directly regulating genes encoding glycoactive enzymes and genes encoding three other transcription factors that are essential for capsule growth: GAT201, RIM101, and SP1. Murine infection with cryptococci lacking Usv101 significantly alters the kinetics and pathogenesis of disease, with extended survival and, unexpectedly, death by pneumonia rather than meningitis. Our approaches and findings will inform studies of other pathogenic microbes. PMID:27094327

Memory Effects of Benzodiazepines: Memory Stages and Types Versus Binding-Site Subtypes

PubMed Central

Savić, Miroslav M.; Obradović, Dragan I.; Ugrešić, Nenad D.; Bokonjić, Dubravko R.

2005-01-01

Benzodiazepines are well established as inhibitory modulators of memory processing. This effect is especially prominent when applied before the acquisition phase of a memory task. This minireview concentrates on the putative subtype selectivity of the acquisition-impairing action of benzodiazepines. Namely, recent genetic studies and standard behavioral tests employing subtype-selective ligands pointed to the predominant involvement of two subtypes of benzodiazepine binding sites in memory modulation. Explicit memory learning seems to be affected through the GABAA receptors containing the α1 and α1 subunits, whereas the effects on procedural memory can be mainly mediated by the α1 subunit. The pervading involvement of the α1 subunit in memory modulation is not at all unexpected because this subunit is the major subtype, present in 60% of all GABAA receptors. On the other hand, the role of α5 subunits, mainly expressed in the hippocampus, in modulating distinct forms of memory gives promise of selective pharmacological coping with certain memory deficit states. PMID:16444900

Protein Kinase A Activity Is Necessary for Fission and Fusion of Golgi to Endoplasmic Reticulum Retrograde Tubules

PubMed Central

Tenorio, María J.; Luchsinger, Charlotte; Mardones, Gonzalo A.

2015-01-01

It is becoming increasingly accepted that together with vesicles, tubules play a major role in the transfer of cargo between different cellular compartments. In contrast to our understanding of the molecular mechanisms of vesicular transport, little is known about tubular transport. How signal transduction molecules regulate these two modes of membrane transport processes is also poorly understood. In this study we investigated whether protein kinase A (PKA) activity regulates the retrograde, tubular transport of Golgi matrix proteins from the Golgi to the endoplasmic reticulum (ER). We found that Golgi-to-ER retrograde transport of the Golgi matrix proteins giantin, GM130, GRASP55, GRASP65, and p115 was impaired in the presence of PKA inhibitors. In addition, we unexpectedly found accumulation of tubules containing both Golgi matrix proteins and resident Golgi transmembrane proteins. These tubules were still attached to the Golgi and were highly dynamic. Our data suggest that both fission and fusion of retrograde tubules are mechanisms regulated by PKA activity. PMID:26258546

Equalizer technology--Equal rights for disparate beads.

PubMed

Keidel, Eva-Maria; Ribitsch, Doris; Lottspeich, Friedrich

2010-06-01

One major limitation in proteomics is the detection and analysis of low-abundant proteins, i.e. in plasma. Several years ago, a technique to selectively enrich the relative concentration of low-abundant proteins was introduced by Boschetti and co-workers. It is based on a specific and saturable interaction of proteins to a high diversity of binding sites, realized by a hexapeptide library coupled to beads. This technology was commercialized as Equalizer beads or ProteoMiner. However, during application of ProteoMiner beads to plasma samples unexpected results questioned the proposed mode of action. Therefore, ProteoMiner beads were compared with chromatographic beads exhibiting completely different surface chemistry. Sepabeads FP-OD400 octadecyl, FP-DA400 diethylamine, FP-BU400 butyl, FP-HG400 hydroxyl and EXE056 epoxy were used. The results show that ProteoMiner or the different Sepabeads behave surprisingly similarly in the separation of complex protein mixtures. ProteoMiner beads interact with protein mixtures according to a general hydrophobic binding mechanism, where diversity in surface ligands plays only a negligible role.

Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain.

PubMed

Albuixech-Crespo, Beatriz; López-Blanch, Laura; Burguera, Demian; Maeso, Ignacio; Sánchez-Arrones, Luisa; Moreno-Bravo, Juan Antonio; Somorjai, Ildiko; Pascual-Anaya, Juan; Puelles, Eduardo; Bovolenta, Paola; Garcia-Fernàndez, Jordi; Puelles, Luis; Irimia, Manuel; Ferran, José Luis

2017-04-01

All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice.

Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain

PubMed Central

Albuixech-Crespo, Beatriz; Maeso, Ignacio; Sánchez-Arrones, Luisa; Moreno-Bravo, Juan Antonio; Somorjai, Ildiko; Pascual-Anaya, Juan; Puelles, Eduardo; Bovolenta, Paola; Garcia-Fernàndez, Jordi; Puelles, Luis; Ferran, José Luis

2017-01-01

All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice. PMID:28422959

Tyrosine kinase inhibitors and mesenchymal stromal cells: effects on self-renewal, commitment and functions

PubMed Central

Borriello, Adriana; Caldarelli, Ilaria; Bencivenga, Debora; Stampone, Emanuela; Perrotta, Silverio; Oliva, Adriana; Ragione, Fulvio Della

2017-01-01

The hope of selectively targeting cancer cells by therapy and eradicating definitively malignancies is based on the identification of pathways or metabolisms that clearly distinguish “normal” from “transformed” phenotypes. Some tyrosine kinase activities, specifically unregulated and potently activated in malignant cells, might represent important targets of therapy. Consequently, tyrosine kinase inhibitors (TKIs) might be thought as the “vanguard” of molecularly targeted therapy for human neoplasias. Imatinib and the successive generations of inhibitors of Bcr-Abl1 kinase, represent the major successful examples of TKI use in cancer treatment. Other tyrosine kinases have been selected as targets of therapy, but the efficacy of their inhibition, although evident, is less definite. Two major negative effects exist in this therapeutic strategy and are linked to the specificity of the drugs and to the role of the targeted kinase in non-malignant cells. In this review, we will discuss the data available on the TKIs effects on the metabolism and functions of mesenchymal stromal cells (MSCs). MSCs are widely distributed in human tissues and play key physiological roles; nevertheless, they might be responsible for important pathologies. At present, bone marrow (BM) MSCs have been studied in greater detail, for both embryological origins and functions. The available data are evocative of an unexpected degree of complexity and heterogeneity of BM-MSCs. It is conceivable that this grade of intricacy occurs also in MSCs of other organs. Therefore, in perspective, the negative effects of TKIs on MSCs might represent a critical problem in long-term cancer therapies based on such inhibitors. PMID:27750212

A WISE CENSUS OF YOUNG STELLAR OBJECTS IN CANIS MAJOR

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

Fischer, William J.; Padgett, Deborah L.; Sewiło, Marta

With the Wide-field Infrared Survey Explorer (WISE), we searched for young stellar objects (YSOs) in a 100 deg{sup 2} region centered on the lightly studied Canis Major star-forming region. Applying stringent magnitude cuts to exclude the majority of extragalactic contaminants, we find 144 Class I candidates and 335 Class II candidates. The sensitivity to Class II candidates is limited by their faintness at the distance to Canis Major (assumed as 1000 pc). More than half the candidates (53%) are found in 16 groups of more than four members, including four groups with more than 25 members each. The ratio ofmore » Class II to Class I objects, N {sub II}/ N {sub I}, varies from 0.4 to 8.3 in just the largest four groups. We compare our results to those obtainable with combined Two Micron All Sky Survey and post-cryogenic Spitzer Space Telescope data; the latter approach recovers missing Class II sources. Via a comparison to protostars characterized with the Herschel Space Observatory , we propose new WISE color criteria for flat-spectrum and Class 0 protostars, finding 80 and 7 of these, respectively. The distribution of YSOs in CMa OB1 is consistent with supernova-induced star formation, although the diverse N {sub II}/ N {sub I} ratios are unexpected if this parameter traces age and the YSOs are due to the same supernova. Less massive clouds feature larger N {sub II}/ N {sub I} ratios, suggesting that initial conditions play a role in determining this quantity.« less

Phenotypic and functional characterization of the major lymphocyte populations in the fruit-eating bat Pteropus alecto.

PubMed

Martínez Gómez, Julia María; Periasamy, Pravin; Dutertre, Charles-Antoine; Irving, Aaron Trent; Ng, Justin Han Jia; Crameri, Gary; Baker, Michelle L; Ginhoux, Florent; Wang, Lin-Fa; Alonso, Sylvie

2016-11-24

The unique ability of bats to act as reservoir for viruses that are highly pathogenic to humans suggests unique properties and functional characteristics of their immune system. However, the lack of bat specific reagents, in particular antibodies, has limited our knowledge of bat's immunity. Using cross-reactive antibodies, we report the phenotypic and functional characterization of T cell subsets, B and NK cells in the fruit-eating bat Pteropus alecto. Our findings indicate the predominance of CD8 + T cells in the spleen from wild-caught bats that may reflect either the presence of viruses in this organ or predominance of this cell subset at steady state. Instead majority of T cells in circulation, lymph nodes and bone marrow (BM) were CD4 + subsets. Interestingly, 40% of spleen T cells expressed constitutively IL-17, IL-22 and TGF-β mRNA, which may indicate a strong bias towards the Th17 and regulatory T cell subsets. Furthermore, the unexpected high number of T cells in bats BM could suggest an important role in T cell development. Finally, mitogenic stimulation induced proliferation and production of effector molecules by bats immune cells. This work contributes to a better understanding of bat's immunity, opening up new perspectives of therapeutic interventions for humans.

Phenotypic and functional characterization of the major lymphocyte populations in the fruit-eating bat Pteropus alecto

PubMed Central

Martínez Gómez, Julia María; Periasamy, Pravin; Dutertre, Charles-Antoine; Irving, Aaron Trent; Ng, Justin Han Jia; Crameri, Gary; Baker, Michelle L.; Ginhoux, Florent; Wang, Lin-Fa; Alonso, Sylvie

2016-01-01

The unique ability of bats to act as reservoir for viruses that are highly pathogenic to humans suggests unique properties and functional characteristics of their immune system. However, the lack of bat specific reagents, in particular antibodies, has limited our knowledge of bat’s immunity. Using cross-reactive antibodies, we report the phenotypic and functional characterization of T cell subsets, B and NK cells in the fruit-eating bat Pteropus alecto. Our findings indicate the predominance of CD8+ T cells in the spleen from wild-caught bats that may reflect either the presence of viruses in this organ or predominance of this cell subset at steady state. Instead majority of T cells in circulation, lymph nodes and bone marrow (BM) were CD4+ subsets. Interestingly, 40% of spleen T cells expressed constitutively IL-17, IL-22 and TGF-β mRNA, which may indicate a strong bias towards the Th17 and regulatory T cell subsets. Furthermore, the unexpected high number of T cells in bats BM could suggest an important role in T cell development. Finally, mitogenic stimulation induced proliferation and production of effector molecules by bats immune cells. This work contributes to a better understanding of bat’s immunity, opening up new perspectives of therapeutic interventions for humans. PMID:27883085

Major Cys protease activities are not essential for senescence in individually darkened Arabidopsis leaves.

PubMed

Pružinská, Adriana; Shindo, Takayuki; Niessen, Sherry; Kaschani, Farnusch; Tóth, Réka; Millar, A Harvey; van der Hoorn, Renier A L

2017-01-06

Papain-like Cys Proteases (PLCPs) and Vacuolar Processing Enzymes (VPEs) are amongst the most highly expressed proteases during leaf senescence in Arabidopsis. Using activity-based protein profiling (ABPP), a method that enables detection of active enzymes within a complex sample using chemical probes, the activities of PLCPs and VPEs were investigated in individually darkened leaves of Arabidopsis, and their role in senescence was tested in null mutants. ABPP and mass spectrometry revealed an increased activity of several PLCPs, particularly RD21A and AALP. By contrast, despite increased VPE transcript levels, active VPE decreased in individually darkened leaves. Eight protease knock-out lines and two protease over expressing lines were subjected to senescence phenotype analysis to determine the importance of individual protease activities to senescence. Unexpectedly, despite the absence of dominating PLCP activities in these plants, the rubisco and chlorophyll decline in individually darkened leaves and the onset of whole plant senescence were unaltered. However, a significant delay in progression of whole plant senescence was observed in aalp-1 and rd21A-1/aalp-1 mutants, visible in the reduced number of senescent leaves. Major Cys protease activities are not essential for dark-induced and developmental senescence and only a knock out line lacking AALP shows a slight but significant delay in plant senescence.

A Proteome Translocation Response to Complex Desert Stress Environments in Perennial Phragmites Sympatric Ecotypes with Contrasting Water Availability.

PubMed

Li, Li; Chen, Xiaodan; Shi, Lu; Wang, Chuanjing; Fu, Bing; Qiu, Tianhang; Cui, Suxia

2017-01-01

After a long-term adaptation to desert environment, the perennial aquatic plant Phragmites communis has evolved a desert-dune ecotype. The desert-dune ecotype (DR) of Phragmites communis showed significant differences in water activity and protein distribution compared to its sympatric swamp ecotype (SR). Many proteins that were located in the soluble fraction of SR translocated to the insoluble fraction of DR, suggesting that membrane-associated proteins were greatly reinforced in DR. The unknown phenomenon in plant stress physiology was defined as a proteome translocation response. Quantitative 2D-DIGE technology highlighted these 'bound' proteins in DR. Fifty-eight kinds of proteins were identified as candidates of the translocated proteome in Phragmites . The majority were chloroplast proteins. Unexpectedly, Rubisco was the most abundant protein sequestered by DR. Rubisco activase, various chaperons and 2-cysteine peroxiredoxin were major components in the translocation response. Conformational change was assumed to be the main reason for the Rubisco translocation due to no primary sequence difference between DR and SR. The addition of reductant in extraction process partially reversed the translocation response, implying that intracellular redox status plays a role in the translocation response of the proteome. The finding emphasizes the realistic significance of the membrane-association of biomolecule for plant long-term adaptation to complex stress conditions.

On-the-Spot Problem Solving of Airline Professionals: A Case Study of Sky Business School Personnel Training Program

ERIC Educational Resources Information Center

Nara, Jun

2010-01-01

This research explores how chief cabin crew members of major airlines made their decisions on-the-spot when they had unexpected problems. This research also presents some insights that may improve personnel training programs for future stewardesses and stewards based on the investigation of their decision-making styles. The theoretical framework…

Unexpected high intragenomic variation in two of three major pest thrips species does not affect ribosomal internal transcribed spacer 2 (ITS2)utility for thrips identification

USDA-ARS?s Scientific Manuscript database

The mitochondrial gene mtCO1 and the internal transcribed spacer (ITS) region of the ribosomal DNA are among the most widely used molecular markers for insect taxonomic characterization. Three economically important species of thrips, Scirtothrips dorsalis, Thrips palmi, and Frankliniella occidental...

Imagining Education: An Arendtian Response to an Inmate's Question

ERIC Educational Resources Information Center

Meyer, Karen Ann; Fels, Lynn

2013-01-01

This article responds to a "what-if" question regarding education, raised by a woman inmate. Emerging in the midst of a research project with women in prison, the unexpected question haunts the two authors, both educational researchers, who in turn reconsider education's role in difficult circumstances. For guidance, the authors turn to…

Transcriptomic and field evaluation of apple trees overexpressing a peach CBF gene

USDA-ARS?s Scientific Manuscript database

The role of CBF genes in cold response and acclimation has been well documented in both herbaceous and woody plants. Our initial research demonstrated that overexpression of a peach CBF gene (PpCBF1) in ‘M.26’ apple increases freezing tolerance of non-acclimated plants and unexpectedly also results...

Unexpected Rift Valley Fever Outbreak, Northern Mauritania

PubMed Central

El Mamy, Ahmed B. Ould; Baba, Mohamed Ould; Barry, Yahya; Isselmou, Katia; Dia, Mamadou L.; Hampate, Ba; Diallo, Mamadou Y.; El Kory, Mohamed Ould Brahim; Diop, Mariam; Lo, Modou Moustapha; Thiongane, Yaya; Bengoumi, Mohammed; Puech, Lilian; Plee, Ludovic; Claes, Filip; Doumbia, Baba

2011-01-01

During September–October 2010, an unprecedented outbreak of Rift Valley fever was reported in the northern Sahelian region of Mauritania after exceptionally heavy rainfall. Camels probably played a central role in the local amplification of the virus. We describe the main clinical signs (hemorrhagic fever, icterus, and nervous symptoms) observed during the outbreak. PMID:22000364

Regional Queensland Parents' Views of Science Education: Some Unexpected Perceptions

ERIC Educational Resources Information Center

Boon, Helen J.

2012-01-01

Low post-compulsory science enrolments for secondary students have been a growing concern across the Western world. Research has examined factors relating to science curricula and students' attitudes about science, but parental views of science education remain largely unexplored in Australia. Because parents have a strong role in shaping their…

Teaching Health and Safety: Preparing Staff for the Unexpected.

ERIC Educational Resources Information Center

Cronin, Greg

1999-01-01

Discusses methods for training camp counselors in safety standards. Safety awareness and camp wellness should be introduced during staff interviews. During precamp training, staff should complete a test in OSHA requirements, followed by role playing to expand staff's knowledge in each OSHA safety and health area. First aid training, fire safety,…

Distress, Stress and Solidarity in Palliative Care.

ERIC Educational Resources Information Center

deMontigny, Johanne

1993-01-01

Notes that role of psychologist on palliative care unit is to be there for terminally ill, their friends, and their families, both during the dying and the bereavement and for the caregiver team. Focuses on work of decoding ordinary words which for many patients hide painful past. Stresses necessity to remain open to unexpected. (Author/NB)

On the Role of Mathematics in Physics: A Constructivist Epistemic Perspective

ERIC Educational Resources Information Center

Quale, Andreas

2011-01-01

The association between the observable physical world and the mathematical models used in theoretical physics to describe this world is examined. Such models will frequently exhibit solutions that are "unexpected," in the sense that they describe physical situations which are different from that which the physicist may initially have had in mind…

University of Iowa Flooding: The Expected and Unexpected

ERIC Educational Resources Information Center

Bourbon, Julie

2008-01-01

This past June, the Iowa River overflowed its banks and deluged 20 buildings on the University of Iowa's Iowa City campus. As the floodwaters finally receded, regents and administrators on the Iowa campus began dealing with all the ramifications and lessons of the flooding--including the key roles of testing emergency plans, nonstop communication,…

Discovery of endocannabinoids and some random thoughts on their possible roles in neuroprotection and aggression.

PubMed

Mechoulam, R

2002-01-01

A short history of the discovery of the main plant cannabinoid, Delta(9)-tetrahydrocannabinol and of the endogenous cannabinoids anandamide, 2-arachidonoyl glycerol and 2-arachidonyl glyceryl ether (noladin ether) is presented. The role of the cannabinoids in neuroprotection, with emphasis on the endocannabinoids, is described. The unexpected production of aggression by Cannabis and cannabinoids under stressful conditions, published mainly in the past, is summarized. Copyright 2002 Elsevier Science Ltd. All rights reserved.

Dispensable, Redundant, Complementary, and Cooperative Roles of Dopamine, Octopamine, and Serotonin in Drosophila melanogaster

PubMed Central

Chen, Audrey; Ng, Fanny; Lebestky, Tim; Grygoruk, Anna; Djapri, Christine; Lawal, Hakeem O.; Zaveri, Harshul A.; Mehanzel, Filmon; Najibi, Rod; Seidman, Gabriel; Murphy, Niall P.; Kelly, Rachel L.; Ackerson, Larry C.; Maidment, Nigel T.; Jackson, F. Rob; Krantz, David E.

2013-01-01

To investigate the regulation of Drosophila melanogaster behavior by biogenic amines, we have exploited the broad requirement of the vesicular monoamine transporter (VMAT) for the vesicular storage and exocytotic release of all monoamine neurotransmitters. We used the Drosophila VMAT (dVMAT) null mutant to globally ablate exocytotic amine release and then restored DVMAT activity in either individual or multiple aminergic systems, using transgenic rescue techniques. We find that larval survival, larval locomotion, and female fertility rely predominantly on octopaminergic circuits with little apparent input from the vesicular release of serotonin or dopamine. In contrast, male courtship and fertility can be rescued by expressing DVMAT in octopaminergic or dopaminergic neurons, suggesting potentially redundant circuits. Rescue of major aspects of adult locomotion and startle behavior required octopamine, but a complementary role was observed for serotonin. Interestingly, adult circadian behavior could not be rescued by expression of DVMAT in a single subtype of aminergic neurons, but required at least two systems, suggesting the possibility of unexpected cooperative interactions. Further experiments using this model will help determine how multiple aminergic systems may contribute to the regulation of other behaviors. Our data also highlight potential differences between behaviors regulated by standard exocytotic release and those regulated by other mechanisms. PMID:23086220

Implicit and Explicit Associations with Erotic Stimuli in Sexually Functional and Dysfunctional Men.

PubMed

van Lankveld, Jacques; Odekerken, Ingrid; Kok-Verhoeven, Lydia; van Hooren, Susan; de Vries, Peter; van den Hout, Anja; Verboon, Peter

2015-08-01

Although conceptual models of sexual functioning have suggested a major role for implicit cognitive processing in sexual functioning, this has thus far, only been investigated in women. The aim of this study was to investigate the role of implicit cognition in sexual functioning in men. Men with (N = 29) and without sexual dysfunction (N = 31) were compared. Participants performed two single-target implicit association tests (ST-IAT), measuring the implicit association of visual erotic stimuli with attributes representing, respectively, valence ('liking') and motivation ('wanting'). Participants also rated the erotic pictures that were shown in the ST-IAT on the dimensions of valence, attractiveness, and sexual excitement to assess their explicit associations with these erotic stimuli. Participants completed the International Index of Erectile Functioning for a continuous measure of sexual functioning. Unexpectedly, compared with sexually functional men, sexually dysfunctional men were found to show stronger implicit associations of erotic stimuli with positive valence than with negative valence. Level of sexual functioning, however, was not predicted by explicit nor implicit associations. Level of sexual distress was predicted by explicit valence ratings, with positive ratings predicting higher levels of sexual distress. Men with and without sexual dysfunction differed significantly with regard to implicit liking. Research recommendations and implications are discussed. © 2015 International Society for Sexual Medicine.

Tryptophan 2,3-Dioxygenfase and Indoleamine 2,3-Dioxygenase 1 Make Separate, Tissue-Specific Contributions to Basal and Inflammation-Induced Kynurenine Pathway Metabolism in Mice

PubMed Central

Larkin, Paul B.; Sathyasaikumar, Korrapati V.; Notarangelo, Francesca M.; Funakoshi, Hiroshi; Nakamura, Toshikazu; Schwarcz, Robert; Muchowski, Paul J.

2018-01-01

In mammals, the majority of the essential amino acid tryptophan is degraded via the kynurenine pathway (KP). Several KP metabolites play distinct physiological roles, often linked to immune system functions, and may also be causally involved in human diseases including neurodegenerative disorders, schizophrenia and cancer. Pharmacological manipulation of the KP has therefore become an active area of drug development. To target the pathway effectively, it is important to understand how specific KP enzymes control levels of the bioactive metabolites in vivo. Here, we conducted a comprehensive biochemical characterization of mice with a targeted deletion of either tryptophan 2,3-dioxygenase (TDO) or indoleamine 2,3-dioxygenase (IDO), the two initial rate-limiting enzymes of the KP. These enzymes catalyze the same reaction, but differ in biochemical characteristics and expression patterns. We measured KP metabolite levels and enzyme activities and expression in several tissues in basal and immune-stimulated conditions. Although our study revealed several unexpected downstream effects on KP metabolism in both knockout mice, the results were essentially consistent with TDO-mediated control of basal KP metabolism and a role of IDO in phenomena involving stimulation of the immune system. PMID:27392942

[Study of stutter originating from the frustrated clinging instinct and its relation to anxiety and self-esteem].

PubMed

Nagy, Beáta Erika; Józsa, Tamás

2016-05-22

The analytic and family therapeutic theories connected to the topic of stutter have to be actualized. The aim of this work was to point out connections which originate from the instinct of frustrated clinging, however, these can be interpretated in new ways these days. Two questionnaires in 48 subjects suffering from stutter were used; Rosenberg's Self-Esteem Scale measured the children's self representation, while the Multidimensional Anxiety Scale for Children measured the degree of their anxiety. At first the subjects had to anwser the questions as themselves, for the second time they had to anwser as an ordinary person without a speech disorder. The hypothesis of the authors was verified: stutterers attributed a significant role to the speech disorder of the subjects in connection with their self-esteem. According to this a significant amount of their anxiety is based on their deficit. An unexpected result was that girls and boys estimated ordinary people's level of anxiety similarly. There was no significant difference between boys and girls regarding the level of other's self-esteem. Based on the thesis of evolutionary psychology, the adequate use of speech is more important to women who have a connecting role in the family. This results that they see stutter as a major problem.

Influence of gender constancy and social power on sex-linked modeling.

PubMed

Bussey, K; Bandura, A

1984-12-01

Competing predictions derived from cognitive-developmental theory and social learning theory concerning sex-linked modeling were tested. In cognitive-developmental theory, gender constancy is considered a necessary prerequisite for the emulation of same-sex models, whereas according to social learning theory, sex-role development is promoted through a vast system of social influences with modeling serving as a major conveyor of sex role information. In accord with social learning theory, even children at a lower level of gender conception emulated same-sex models in preference to opposite-sex ones. Level of gender constancy was associated with higher emulation of both male and female models rather than operating as a selective determinant of modeling. This finding corroborates modeling as a basic mechanism in the sex-typing process. In a second experiment we explored the limits of same-sex modeling by pitting social power against the force of collective modeling of different patterns of behavior by male and female models. Social power over activities and rewarding resources produced cross-sex modeling in boys, but not in girls. This unexpected pattern of cross-sex modeling is explained by the differential sex-typing pressures that exist for boys and girls and socialization experiences that heighten the attractiveness of social power for boys.

Promoter Targeting RNAs: Unexpected Contributors to the Control of HIV-1 Transcription.

PubMed

Suzuki, Kazuo; Ahlenstiel, Chantelle; Marks, Katherine; Kelleher, Anthony D

2015-01-27

In spite of prolonged and intensive treatment with combined antiretroviral therapy (cART), which efficiently suppresses plasma viremia, the integrated provirus of HIV-1 persists in resting memory CD4(+) T cells as latent infection. Treatment with cART does not substantially reduce the burden of latent infection. Once cART is ceased, HIV-1 replication recrudesces from these reservoirs in the overwhelming majority of patients. There is increasing evidence supporting a role for noncoding RNAs (ncRNA), including microRNAs (miRNAs), antisense (as)RNAs, and short interfering (si)RNA in the regulation of HIV-1 transcription. This appears to be mediated by interaction with the HIV-1 promoter region. Viral miRNAs have the potential to act as positive or negative regulators of HIV transcription. Moreover, inhibition of virally encoded long-asRNA can induce positive transcriptional regulation, while antisense strands of siRNA targeting the NF-κB region suppress viral transcription. An in-depth understanding of the interaction between ncRNAs and the HIV-1 U3 promoter region may lead to new approaches for the control of HIV reservoirs. This review focuses on promoter associated ncRNAs, with particular emphasis on their role in determining whether HIV-1 establishes active or latent infection.

Promoter Targeting RNAs: Unexpected Contributors to the Control of HIV-1 Transcription

PubMed Central

Suzuki, Kazuo; Ahlenstiel, Chantelle; Marks, Katherine; Kelleher, Anthony D

2015-01-01

In spite of prolonged and intensive treatment with combined antiretroviral therapy (cART), which efficiently suppresses plasma viremia, the integrated provirus of HIV-1 persists in resting memory CD4+ T cells as latent infection. Treatment with cART does not substantially reduce the burden of latent infection. Once cART is ceased, HIV-1 replication recrudesces from these reservoirs in the overwhelming majority of patients. There is increasing evidence supporting a role for noncoding RNAs (ncRNA), including microRNAs (miRNAs), antisense (as)RNAs, and short interfering (si)RNA in the regulation of HIV-1 transcription. This appears to be mediated by interaction with the HIV-1 promoter region. Viral miRNAs have the potential to act as positive or negative regulators of HIV transcription. Moreover, inhibition of virally encoded long-asRNA can induce positive transcriptional regulation, while antisense strands of siRNA targeting the NF-κB region suppress viral transcription. An in-depth understanding of the interaction between ncRNAs and the HIV-1 U3 promoter region may lead to new approaches for the control of HIV reservoirs. This review focuses on promoter associated ncRNAs, with particular emphasis on their role in determining whether HIV-1 establishes active or latent infection. PMID:25625613

Crisis management during anaesthesia: difficult intubation.

PubMed

Paix, A D; Williamson, J A; Runciman, W B

2005-06-01

Anaesthetists may experience difficulty with intubation unexpectedly which may be associated with difficulty in ventilating the patient. If not well managed, there may be serious consequences for the patient. A simple structured approach to this problem was developed to assist the anaesthetist in this difficult situation. To examine the role of a specific sub-algorithm for the management of difficult intubation. The potential performance of a structured approach developed by review of the literature and analysis of each of the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. There were 147 reports of difficult intubation capable of analysis among the first 4000 incidents reported to AIMS. The difficulty was unexpected in 52% of cases; major physiological changes occurred in 37% of these cases. Saturation fell below 90% in 22% of cases, oesophageal intubation was reported in 19%, and an emergency transtracheal airway was required in 4% of cases. Obesity and limited neck mobility and mouth opening were the most common anatomical contributing factors. The data confirm previously reported failures to predict difficult intubation with existing preoperative clinical tests and suggest an ongoing need to teach a pre-learned strategy to deal with difficult intubation and any associated problem with ventilation. An easy-to-follow structured approach to these problems is outlined. It is recommended that skilled assistance be obtained (preferably another anaesthetist) when difficulty is expected or the patient's cardiorespiratory reserve is low. Patients should be assessed postoperatively to exclude any sequelae and to inform them of the difficulties encountered. These should be clearly documented and appropriate steps taken to warn future anaesthetists.

Some See It, Some Don’t: Exploring the Relation between Inattentional Blindness and Personality Factors

PubMed Central

Kreitz, Carina; Schnuerch, Robert; Gibbons, Henning; Memmert, Daniel

2015-01-01

Human awareness is highly limited, which is vividly demonstrated by the phenomenon that unexpected objects go unnoticed when attention is focused elsewhere (inattentional blindness). Typically, some people fail to notice unexpected objects while others detect them instantaneously. Whether this pattern reflects stable individual differences is unclear to date. In particular, hardly anything is known about the influence of personality on the likelihood of inattentional blindness. To fill this empirical gap, we examined the role of multiple personality factors, namely the Big Five, BIS/BAS, absorption, achievement motivation, and schizotypy, in these failures of awareness. In a large-scale sample (N = 554), susceptibility to inattentional blindness was associated with a low level of openness to experience and marginally with a low level of achievement motivation. However, in a multiple regression analysis, only openness emerged as an independent, negative predictor. This suggests that the general tendency to be open to experience extends to the domain of perception. Our results complement earlier work on the possible link between inattentional blindness and personality by demonstrating, for the first time, that failures to consciously perceive unexpected objects reflect individual differences on a fundamental dimension of personality. PMID:26011567

Critical role for ERK1/2 in bone marrow and fetal liver–derived primary megakaryocyte differentiation, motility, and proplatelet formation

PubMed Central

Mazharian, Alexandra; Watson, Steve P.; Séverin, Sonia

2009-01-01

Objective Megakaryopoiesis and platelet formation is a multistep process through which hematopoietic progenitor cells develop into mature megakaryocytes (MKs) and form proplatelets. The present study investigates the regulation of different steps of megakaryopoiesis (i.e., differentiation, migration, and proplatelet formation) by extracellar signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) in two models of primary murine MKs derived from bone marrow (BM) cells and fetal liver (FL) cells. Materials and Methods A preparation of MKs was generated from BM obtained from femora and tibiae of C57BL6 mice. FL-derived MKs were obtained from the liver of mouse fetuses aged 13 to 15 days. Results For both cell populations, activation of MEK-ERK1/2 pathway by thrombopoietin was found to have a critical role in MK differentiation, regulating polyploidy and surface expression of CD34, GPIIb, and GPIb. The MEK-ERK1/2 pathway plays a major role in migration of BM-derived MKs toward a stromal-cell−derived factor 1α (SDF1α) gradient, whereas unexpectedly, FL-derived cells fail to migrate in response to the chemokine due to negligible expression of its receptor, CXCR4. The MEK-ERK1/2 pathway also plays a critical role in the generation of proplatelets. In contrast, p38MAPK pathway was not involved in any of these processes. Conclusion This report demonstrates a critical role of MEK-ERK1/2 pathway in MK differentiation, motility, and proplatelet formation. This study highlights several differences between BM- and FL-derived MKs, which are discussed. PMID:19619605

Fragile X Mental Retardation Protein Restricts Small Dye Iontophoresis Entry into Central Neurons

PubMed Central

2017-01-01

Fragile X mental retardation protein (FMRP) loss causes Fragile X syndrome (FXS), a major disorder characterized by autism, intellectual disability, hyperactivity, and seizures. FMRP is both an RNA- and channel-binding regulator, with critical roles in neural circuit formation and function. However, it remains unclear how these FMRP activities relate to each other and how dysfunction in their absence underlies FXS neurological symptoms. In testing circuit level defects in the Drosophila FXS model, we discovered a completely unexpected and highly robust neuronal dye iontophoresis phenotype in the well mapped giant fiber (GF) circuit. Controlled dye injection into the GF interneuron results in a dramatic increase in dye uptake in neurons lacking FMRP. Transgenic wild-type FMRP reintroduction rescues the mutant defect, demonstrating a specific FMRP requirement. This phenotype affects only small dyes, but is independent of dye charge polarity. Surprisingly, the elevated dye iontophoresis persists in shaking B mutants that eliminate gap junctions and dye coupling among GF circuit neurons. We therefore used a wide range of manipulations to investigate the dye uptake defect, including timed injection series, pharmacology and ion replacement, and optogenetic activity studies. The results show that FMRP strongly limits the rate of dye entry via a cytosolic mechanism. This study reveals an unexpected new phenotype in a physical property of central neurons lacking FMRP that could underlie aspects of FXS disruption of neural function. SIGNIFICANCE STATEMENT FXS is a leading heritable cause of intellectual disability and autism spectrum disorders. Although researchers established the causal link with FMRP loss >;25 years ago, studies continue to reveal diverse FMRP functions. The Drosophila FXS model is key to discovering new FMRP roles, because of its genetic malleability and individually identified neuron maps. Taking advantage of a well characterized Drosophila neural circuit, we discovered that neurons lacking FMRP take up dramatically more current-injected small dye. After examining many neuronal properties, we determined that this dye defect is cytoplasmic and occurs due to a highly elevated dye iontophoresis rate. We also report several new factors affecting neuron dye uptake. Understanding how FMRP regulates iontophoresis should reveal new molecular factors underpinning FXS dysfunction. PMID:28887386

Three-dimensional structure of Escherichia coli initiator tRNA/f//Met/

NASA Technical Reports Server (NTRS)

Woo, N. H.; Rich, A.; Roe, B. A.

1980-01-01

The crystal structure of Escherichia coli tRNA(f)(Met), an initiator transfer RNA, has been determined. While grossly similar to that of the chain-elongating yeast tRNA(Phe), there are three major differences. One involves the folding of the anticodon loop; in particular, the position of the constant uridine, U33. This difference was unexpected and may be of functional significance.

Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected.

PubMed

Marvel, Douglas; Gabrilovich, Dmitry I

2015-09-01

Our understanding of the role of myeloid-derived suppressor cells (MDSCs) in cancer is becoming increasingly complex. In addition to their eponymous role in suppressing immune responses, they directly support tumor growth, differentiation, and metastasis in a number of ways that are only now beginning to be appreciated. It is because of this increasingly complex role that these cells may become an important factor in the treatment of human cancer. In this Review, we discuss the most pertinent and controversial issues of MDSC biology and their role in promoting cancer progression and highlight how these cells may be used in the clinic, both as prognostic factors and as therapeutic targets.

The Expected but Well-Hidden EMF in the Jumping Wire Experiment and Its Unexpected Role

ERIC Educational Resources Information Center

Donoso, G.; Ladera, C. L.

2015-01-01

As presented in physics textbooks, as well as in a few papers, the typical example of an induced motional electromotive force e[subscript mot] = "Blv" consists of a conductive rod of length "l" frictionlessly sliding with speed v along parallel wires within an orthogonal and constant uniform magnetic field of magnitude…

Unexpected Discovery: A Guided-Inquiry Experiment on the Reaction Kinetics of Zinc with Sulfuric Acid

ERIC Educational Resources Information Center

Rusek, Martin; Beneš, Pavel; Carroll, John

2018-01-01

The role of practical work in the training of student teachers is central to the development of their future pedagogy and practice. However, not all laboratory based activities give sufficient challenge in the development of both cognitive and practical skills. The activity proposed in this paper helps reinforce an understanding of reaction…

Perceptions and Expectations at New York State's Centers for Advanced Technology: Some Implications for Research Management.

ERIC Educational Resources Information Center

Bitting, Robert K.

1989-01-01

An evaluation of the 10 Centers for Advanced Ceramic Technology in New York State's collaborative research and development program yielded unexpected perceptions held by center, government, and industry personnel. Implications for the research effort, including the role of basic research and the importance of the research center administrators,…

Weathering "A Climate of Unexpectation": Gender Equity and the Radcliffe Institute, 1960-1995.

ERIC Educational Resources Information Center

Eisenmann, Linda

1995-01-01

The evolution and role of the Radcliffe Institute for Independent Study, founded to provide year-long, part-time fellowships for women doctorates wishing to pursue independent scholarly or creative projects, are described. The program, which encourages applications from mothers whose intellectual work had been put on hold, is seen as one of the…

Esophageal Cancer Metastases to Unexpected Sites: A Systematic Review

PubMed Central

2017-01-01

The most common pattern of esophageal cancer metastases (ECM) is to the lymph nodes, lung, liver, bones, adrenal glands, and brain. On the other hand, unexpected metastasis (UM) spread to uncommon sites has increasingly reported and consequently affected the pathway of diagnosis, staging, and management. Using the PubMed database, a systematic search of the following headings “Esophageal” and “Metastasis” or “Metastases” was performed, 10049 articles were identified, and the articles were included if they demonstrated unexpected ECM. 84% of cases were men with an average age of 60.7 years. EC was located in the lower third in 65%. Two-thirds of the UM originated from the lower esophagus, and the two major histological types were adenocarcinoma 40% and squamous cell carcinoma 60%. Metastases were disseminated toward five main anatomical sites: the head and neck (42%), thoracic (17%), abdomen and pelvis (25%), extremities (9%), and multiple skin and muscle metastases (7%). The EC metastases were found to be synchronous 42% and metachronous 58%, isolated in 53.5% and multiple in 46.5%. The overall survival rate was 10.2 months. Since distant metastases are responsible for most EC-related deaths, understanding of ECM dissemination patterns needs more extensive studies. These critical data are the cornerstone of optimal cancer approach and treatment. PMID:28659974

Neurons in the Primate Medial Basal Forebrain Signal Combined Information about Reward Uncertainty, Value, and Punishment Anticipation

PubMed Central

Leopold, David A.; Hikosaka, Okihide

2015-01-01

It has been suggested that the basal forebrain (BF) exerts strong influences on the formation of memory and behavior. However, what information is used for the memory-behavior formation is unclear. We found that a population of neurons in the medial BF (medial septum and diagonal band of Broca) of macaque monkeys encodes a unique combination of information: reward uncertainty, expected reward value, anticipation of punishment, and unexpected reward and punishment. The results were obtained while the monkeys were expecting (often with uncertainty) a rewarding or punishing outcome during a Pavlovian procedure, or unexpectedly received an outcome outside the procedure. In vivo anterograde tracing using manganese-enhanced MRI suggested that the major recipient of these signals is the intermediate hippocampal formation. Based on these findings, we hypothesize that the medial BF identifies various contexts and outcomes that are critical for memory processing in the hippocampal formation. PMID:25972172

Unexpected fold in the circumsporozoite protein target of malaria vaccines

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

Doud, Michael B.; Koksal, Adem C.; Mi, Li-Zhi

Circumsporozoite (CS) protein is the major surface component of Plasmodium falciparum sporozoites and is essential for host cell invasion. A vaccine containing tandem repeats, region III, and thrombospondin type-I repeat (TSR) of CS is efficacious in phase III trials but gives only a 35% reduction in severe malaria in the first year postimmunization. We solved crystal structures showing that region III and TSR fold into a single unit, an '{alpha}TSR' domain. The {alpha}TSR domain possesses a hydrophobic pocket and core, missing in TSR domains. CS binds heparin, but {alpha}TSR does not. Interestingly, polymorphic T-cell epitopes map to specialized {alpha}TSR regions.more » The N and C termini are unexpectedly close, providing clues for sporozoite sheath organization. Elucidation of a unique structure of a domain within CS enables rational design of next-generation subunit vaccines and functional and medicinal chemical investigation of the conserved hydrophobic pocket.« less

Idiopathic infantile arterial calcification: a rare cause of sudden unexpected death in childhood.

PubMed

Guimarães, Susana; Lopes, José Manuel; Oliveira, José Bessa; Santos, Agostinho

2010-07-27

Unexpected child death investigation is a difficult area of forensic practice in view of the wide range of possible genetic, congenital, and acquired natural and nonnatural causes. Idiopathic infantile arterial calcification (IIAC) is a rare autosomic recessive disease usually diagnosed postmortem. Inactivating mutations of the ENPP1 gene were described in 80% of the cases with IIAC. We report a case of a 5-year-old girl submitted to a forensic autopsy due to sudden death and possible medical negligence/parents child abuse. Major alterations found (intimal proliferation and deposition of calcium hydroxyapatite around the internal elastic lamina and media of arteries; acute myocardial infarct, stenotic and calcified coronary artery; perivascular and interstitial myocardial fibrosis; and subendocardial fibroelastosis) were diagnostic of IIAC. We reviewed IIAC cases published in the English literature and highlight the importance of adequate autopsy evaluation in cases of sudden child death.

Idiopathic Infantile Arterial Calcification: A Rare Cause of Sudden Unexpected Death in Childhood

PubMed Central

Guimarães, Susana; Lopes, José Manuel; Oliveira, José Bessa; Santos, Agostinho

2010-01-01

Unexpected child death investigation is a difficult area of forensic practice in view of the wide range of possible genetic, congenital, and acquired natural and nonnatural causes. Idiopathic infantile arterial calcification (IIAC) is a rare autosomic recessive disease usually diagnosed postmortem. Inactivating mutations of the ENPP1 gene were described in 80% of the cases with IIAC. We report a case of a 5-year-old girl submitted to a forensic autopsy due to sudden death and possible medical negligence/parents child abuse. Major alterations found (intimal proliferation and deposition of calcium hydroxyapatite around the internal elastic lamina and media of arteries; acute myocardial infarct, stenotic and calcified coronary artery; perivascular and interstitial myocardial fibrosis; and subendocardial fibroelastosis) were diagnostic of IIAC. We reviewed IIAC cases published in the English literature and highlight the importance of adequate autopsy evaluation in cases of sudden child death. PMID:21151691

Ventral striatum response during reward and punishment reversal learning in unmedicated major depressive disorder.

PubMed

Robinson, Oliver J; Cools, Roshan; Carlisi, Christina O; Sahakian, Barbara J; Drevets, Wayne C

2012-02-01

Affective biases may underlie many of the key symptoms of major depressive disorder, from anhedonia to altered cognitive performance. Understanding the cause of these biases is therefore critical in the quest for improved treatments. Depression is associated, for example, with a negative affective bias in reversal learning. However, despite the fact that reversal learning is associated with striatal response in healthy individuals and depressed individuals exhibit attenuated striatal function on multiple tasks, studies to date have not demonstrated striatal involvement in the negative bias in reversal learning in depression. In this study, the authors sought to determine whether this may be because reversal learning tasks conventionally used to study behavior examine reversals only on the basis of unexpected punishment and therefore do not adequately separate reward- and punishment-based behavior. The authors used functional MRI to compare the hemodynamic response to a reversal learning task with mixed reward- and punishment-based reversal stages between individuals with unmedicated major depressive disorder (N=13) and healthy comparison subjects (N=14). Impaired reward (but not punishment) reversal accuracy was found alongside attenuated anteroventral striatal response to unexpected reward in depression. Attenuated neurophysiological response of the anteroventral striatum may reflect dysfunction in circuits involving afferent projections from the orbitofrontal, limbic, and/or mesostriatal dopaminergic pathways, which conceivably may, together with the ventral striatum, underlie anhedonia in depression. Learning to appreciate and enjoy positive life experiences is critical for recovery from depression. This study pinpoints a neural target for such recovery.

The adenovirus major core protein VII is dispensable for virion assembly but is essential for lytic infection

PubMed Central

Suomalainen, Maarit; Zheng, Yueting; Boucke, Karin

2017-01-01

The Adenovirus (Ad) genome within the capsid is tightly associated with a virus-encoded, histone-like core protein—protein VII. Two other Ad core proteins, V and X/μ, also are located within the virion and are loosely associated with viral DNA. Core protein VII remains associated with the Ad genome during the early phase of infection. It is not known if naked Ad DNA is packaged into the capsid, as with dsDNA bacteriophage and herpesviruses, followed by the encapsidation of viral core proteins, or if a unique packaging mechanism exists with Ad where a DNA-protein complex is simultaneously packaged into the virion. The latter model would require an entirely new molecular mechanism for packaging compared to known viral packaging motors. We characterized a virus with a conditional knockout of core protein VII. Remarkably, virus particles were assembled efficiently in the absence of protein VII. No changes in protein composition were evident with VII−virus particles, including the abundance of core protein V, but changes in the proteolytic processing of some capsid proteins were evident. Virus particles that lack protein VII enter the cell, but incoming virions did not escape efficiently from endosomes. This greatly diminished all subsequent aspects of the infectious cycle. These results reveal that the Ad major core protein VII is not required to condense viral DNA within the capsid, but rather plays an unexpected role during virus maturation and the early stages of infection. These results establish a new paradigm pertaining to the Ad assembly mechanism and reveal a new and important role of protein VII in early stages of infection. PMID:28628648

Subclinical hyperthyroidism and sudden unexpected death in epilepsy.

PubMed

Scorza, Fulvio A; Arida, Ricardo M; Cysneiros, Roberta M; Terra, Vera C; de Albuquerque, Marly; Machado, Hélio R; Cavalheiro, Esper A

2010-04-01

Epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but high seizure frequency is a potential risk factor. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role. In parallel, several studies have shown a link between hormones and epilepsy. However, exact knowledge regarding the association of thyroid hormones and epilepsy is lacking. As subclinical hyperthyroidism has been linked with increased risk of cardiovascular disease, we propose in this paper that SUDEP, at least in some cases, could be related with subclinical thyroid dysfunction. (c) 2009 Elsevier Ltd. All rights reserved.

Sudden unexpected nocturnal death in Chiari type 1 malformation and potential role of opioid analgesics

PubMed Central

Roohi, Fereydoon; Gropen, Toby; Kula, Roger W.

2014-01-01

Background: Chiari malformation type 1 (CM1) is a common congenital anomaly of the craniocervical junction. CM1 is reported to run a usually benign course and patients typically experience no symptoms or chronic, slowly progressive symptoms. However, recent reports indicate that a subset of patients with CM1 may present with acute deterioration and sudden unexpected death (SUD). We report a case of SUD during sleep in a young man with CM1, which we believe was related to the administration of common and therapeutic doses of narcotic analgesics for the management of pain. We will clarify the pathophysiology of acute deterioration and SUD in CM1 and the possibility that the adverse effects of opiate analgesics likely were the leading cause of death in our patient. Case Description: In this review, we present a 29-year-old male with worsening headache secondary to previously diagnosed CM1. The patient died suddenly and unexpectedly after administration of common and therapeutic doses of narcotic analgesics for the management of pain. Conclusion: The mechanism(s) of acute neurological deterioration and sudden death in patients with CM1 remains poorly understood. We believe the rapid fatal deterioration in our patient following administration of opioids suggests that this category of medication may cause sudden unexpected “neurogenic” cardiac death in CM1 patients by inducing sleep-related breathing difficulties and associated hypercapnia. Hypercapnia by further increasing intracranial pressure can result in a sudden pressure-induced decompensation of the cardiopulmonary control centers in the brain stem and cause instantaneous cardiorespiratory arrest. PMID:24778905

PRAS40 promotes NF-κB transcriptional activity through association with p65. | Office of Cancer Genomics

Cancer.gov

PRAS40 has been shown to have a crucial role in the repression of mammalian target of rapamycin (mTOR). Nonetheless, PRAS40 appears to have an oncogenic function in cancer cells. Whether PRAS40 mediates signaling independent of mTOR inhibition in cancer cells remains elusive. Here PRAS40 overexpression in lung adenocarcinoma and cutaneous melanoma was significantly correlated to worse prognosis. And we identified an unexpected role for PRAS40 in the regulation of nuclear factor (NF)-κB signaling.

Development of New Therapeutics Targeting Biofilm Formation by the Opportunistic Pulmonary Pathogens Pseudomonas aeruginosa and Aspergillus Fumigatus

DTIC Science & Technology

2017-10-01

antibacterial activity . The unexpected departure of PDF Perrin Baker in early June 2017 and the delay in recruiting his...characterize the ability of recombinant GH enzymes to enhance the activity of antimicrobial agents against PA and AF in vitro (2) Perform...major goals of the project as stated in the approved SOW. If the application listed milestones/target dates for important activities

Analysis of the Inhibition of Mammalian Carboxylesterases by Novel Fluorobenzoins and Fluorobenzils

PubMed Central

Hicks, Latorya D.; Hyatt, Janice L; Moak, Teri; Edwards, Carol C.; Tsurkan, Lyudmila; Wierdl, Monika; Ferreira, Antonio; Wadkins, Randy M.; Potter, Philip M.

2007-01-01

We have synthesized and assessed the ability of symmetrical fluorobenzoins and fluorobenzils to inhibit mammalian carboxylesterases (CE). The majority of the latter were excellent inhibitors of CEs however unexpectedly, the fluorobenzoins were very good enzyme inhibitors. Positive correlations were seen with the charge on the hydroxyl carbon atom, the carbonyl oxygen, and the Hammett constants for the derived Ki values with the fluorobenzoins. PMID:17399985

Towards a Cognitive Model of Distraction by Auditory Novelty: The Role of Involuntary Attention Capture and Semantic Processing

ERIC Educational Resources Information Center

Parmentier, Fabrice B. R.

2008-01-01

Unexpected auditory stimuli are potent distractors, able to break through selective attention and disrupt performance in an unrelated visual task. This study examined the processing fate of novel sounds by examining the extent to which their semantic content is analyzed and whether the outcome of this processing can impact on subsequent behavior.…

Double-Edged Innovations: Preventing the Misuse of Emerging Biological/Chemical Technologies

DTIC Science & Technology

2010-07-01

1953 paper describing the double-helical structure of the DNA molecule and suggesting a mechanism for its replication. In 1973, Stanley Cohen of...Virology in early 2001. The security implications of the paper , however, triggered a storm of...unexpected findings of the mousepox experiment could have been predicted because a paper describing the role of interleukin-4 in poxvirus virulence

Hope in the Unexpected: How Can Teachers Still Make a Difference in the World?

ERIC Educational Resources Information Center

Edgoose, Julian

2010-01-01

Background/Context: The central role of hope in teaching has long been acknowledged by authors such as Sonia Nieto and Larry Cuban, but hope has received little focused attention from scholars. While books such as David Halpin's Hope and Education and Stephen Fishman and Lucille McCarthy's John Dewey and the Philosophy and Practice of Hope each…

The Timing of Parental Income and Child Outcomes: The Role of Permanent and Transitory Shocks. CEE DP 120

ERIC Educational Resources Information Center

Tominey, Emma

2010-01-01

How do shocks to parental income drive adolescent human capital, such as university attendance, IQ and health? Unexpected changes to family income may have a predictable effect on child adolescent outcomes, by shifting the money parents spend on human capital investments in their children. The extent to which consumers insure themselves against…

Bis-guanylhydrazone diimidazo[1,2-a:1,2-c]pyrimidine as a novel and specific G-quadruplex binding motif.

PubMed

Sparapani, Silvia; Bellini, Stefania; Gunaratnam, Mekala; Haider, Shozeb M; Andreani, Aldo; Rambaldi, Mirella; Locatelli, Alessandra; Morigi, Rita; Granaiola, Massimiliano; Varoli, Lucilla; Burnelli, Silvia; Leoni, Alberto; Neidle, Stephen

2010-08-21

A bis-guanylhydrazone derivative of diimidazo[1,2-a:1,2-c]pyrimidine has unexpectedly been found to be a potent stabiliser of several quadruplex DNAs, whereas there is no significant interaction with duplex DNA. Molecular modeling suggests that the guanylhydrazone groups play an active role in quadruplex binding.

Vacuolar CAX1 and CAX3 influence auxin transport in guard cells via regulation of apoplastic pH

USDA-ARS?s Scientific Manuscript database

Cation exchangers CAX1 and CAX3 are vacuolar ion transporters involved in ion homeostasis in plants. Widely expressed in the plant, they mediate calcium transport from the cytosol to the vacuole lumen using the proton gradient across the tonoplast. Here, we report an unexpected role of CAX1 and CAX3...

Targeting IL-2: an unexpected effect in treating immunological diseases.

PubMed

Ye, Congxiu; Brand, David; Zheng, Song G

2018-01-01

Regulatory T cells (Treg) play a crucial role in maintaining immune homeostasis since Treg dysfunction in both animals and humans is associated with multi-organ autoimmune and inflammatory disease. While IL-2 is generally considered to promote T-cell proliferation and enhance effector T-cell function, recent studies have demonstrated that treatments that utilize low-dose IL-2 unexpectedly induce immune tolerance and promote Treg development resulting in the suppression of unwanted immune responses and eventually leading to treatment of some autoimmune disorders. In the present review, we discuss the biology of IL-2 and its signaling to help define the key role played by IL-2 in the development and function of Treg cells. We also summarize proof-of-concept clinical trials which have shown that low-dose IL-2 can control autoimmune diseases safely and effectively by specifically expanding and activating Treg. However, future studies will be needed to validate a better and safer dosing strategy for low-dose IL-2 treatments utilizing well-controlled clinical trials. More studies will also be needed to validate the appropriate dose of IL-2/anti-cytokine or IL-2/anti-IL-2 complex in the experimental animal models before moving to the clinic.

Microglia PACAP and glutamate: Friends or foes in seizure-induced autonomic dysfunction and SUDEP?

PubMed

Bhandare, Amol M; Kapoor, Komal; Farnham, Melissa M J; Pilowsky, Paul M

2016-06-01

Seizure-induced cardiorespiratory autonomic dysfunction is a major cause of sudden unexpected death in epilepsy (SUDEP), and the underlying mechanism is unclear. Seizures lead to increased synthesis, and release of glutamate, pituitary adenylate cyclase activating polypeptide (PACAP), and other neurotransmitters, and cause extensive activation of microglia at multiple regions in the brain including central autonomic cardiorespiratory brainstem nuclei. Glutamate contributes to neurodegeneration, and inflammation in epilepsy. PACAP has neuroprotective, and anti-inflammatory properties, whereas microglia are key players in inflammatory responses in CNS. Seizure-induced increase in PACAP is neuroprotective. PACAP produces neuroprotective effects acting on microglial PAC1 and VPAC1 receptors. Microglia also express glutamate transporters, and their expression can be increased by PACAP in response to harmful or stressful situations such as seizures. Here we discuss the mechanism of autonomic cardiorespiratory dysfunction in seizure, and the role of PACAP, glutamate and microglia in regulating cardiorespiratory brainstem neurons in their physiological state that could provide future therapeutic options for SUDEP. Copyright © 2016 Elsevier B.V. All rights reserved.

ERK1/2/MAPK pathway-dependent regulation of the telomeric factor TRF2

PubMed Central

Picco, Vincent; Coste, Isabelle; Giraud-Panis, Marie-Josèphe; Renno, Toufic; Gilson, Eric; Pagès, Gilles

2016-01-01

Telomere stability is a hallmark of immortalized cells, including cancer cells. While the telomere length is maintained in most cases by the telomerase, the activity of a protein complex called Shelterin is required to protect telomeres against unsuitable activation of the DNA damage response pathway. Within this complex, telomeric repeat binding factor 2 (TRF2) plays an essential role by blocking the ataxia telangiectasia-mutated protein (ATM) signaling pathway at telomeres and preventing chromosome end fusion. We showed that TRF2 was phosphorylated in vitro and in vivo on serine 323 by extracellular signal-regulated kinase (ERK1/2) in both normal and cancer cells. Moreover, TRF2 and activated ERK1/2 unexpectedly interacted in the cytoplasm of tumor cells and human tumor tissues. The expression of non-phosphorylatable forms of TRF2 in melanoma cells induced the DNA damage response, leading to growth arrest and tumor reversion. These findings revealed that the telomere stability is under direct control of one of the major pro-oncogenic signaling pathways (RAS/RAF/MEK/ERK) via TRF2 phosphorylation. PMID:27366950

Testing neoclassical competitive market theory in the field.

PubMed

List, John A

2002-11-26

This study presents results from a pilot field experiment that tests predictions of competitive market theory. A major advantage of this particular field experimental design is that my laboratory is the marketplace: subjects are engaged in buying, selling, and trading activities whether I run an exchange experiment or am a passive observer. In this sense, I am gathering data in a natural environment while still maintaining the necessary control to execute a clean comparison between treatments. The main results of the study fall into two categories. First, the competitive model predicts reasonably well in some market treatments: the expected price and quantity levels are approximated in many market rounds. Second, the data suggest that market composition is important: buyer and seller experience levels impact not only the distribution of rents but also the overall level of rents captured. An unexpected result in this regard is that average market efficiency is lowest in markets that match experienced buyers and experienced sellers and highest when experienced buyers engage in bargaining with inexperienced sellers. Together, these results suggest that both market experience and market composition play an important role in the equilibrium discovery process.

The Impact of Respite Programming on Caregiver Resilience in Dementia Care: A Qualitative Examination of Family Caregiver Perspectives

PubMed Central

Roberts, Emily; Struckmeyer, Kristopher M.

2018-01-01

Family members with a relative with dementia often experience what has been called the “unexpected career of caregiver” and face multifaceted, complex, and stressful life situations that can have important consequences. This exploratory study was designed to address this major public health challenge through the lens of caregiver resilience and caregiver respite programming. While many caregivers report that they derive significant emotional and spiritual rewards from their caregiving role, many also experience physical and emotional problems directly related to the stress and demands of daily care. One way to alleviate these demands is the growing respite care field, providing services in a variety of settings for caregiver. Through qualitative analysis from face-to-face interviews with 33 family caregivers of individuals with dementia, several themes emerged describing the path to caregiver resilience which include family dynamics, isolation, financial struggles, seeking respite, and acceptance. While much research focuses on a caregiving burden perspective, the innovation of the present study is applying the resilience framework to outcomes from respite programming. PMID:29424252

CD4+ T cells support establishment of RSV-specific IgG and IgA antibody secreting cells in the upper and lower murine respiratory tract following RSV infection.

PubMed

Sealy, Robert E; Surman, Sherri L; Hurwitz, Julia L

2017-05-09

The RSV vaccine field suffered a major set-back when children were vaccinated with a formalin-inactivated RSV vaccine (FI-RSV). Unexpectedly, the vaccinated children fared worse than unvaccinated children when they were naturally infected with RSV. Mouse models were then developed that implicated the CD4 + T helper cell population as a contributor to adverse events. Today, the T cell is viewed with much caution in the RSV field, and its induction by vaccination is sometimes discouraged. Here we re-emphasize the beneficial role of the CD4 + T cell. Experiments were performed with RSV-infected nude mice that received CD4 + T cells by adoptive transfer. Data demonstrated that CD4 + T cells were necessary for the induction of mucosal and systemic RSV-specific antibodies, for the establishment of RSV-specific IgG and IgA antibody secreting cells in the upper and lower respiratory tract, and for RSV clearance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stage- and subunit-specific functions of polycomb repressive complex 2 in bladder urothelial formation and regeneration

PubMed Central

Guo, Chunming; Balsara, Zarine R.

2017-01-01

ABSTRACT Urothelium is the protective lining of the urinary tract. The mechanisms underlying urothelial formation and maintenance are largely unknown. Here, we report the stage-specific roles of PRC2 epigenetic regulators in embryonic and adult urothelial progenitors. Without Eed, the obligatory subunit of PRC2, embryonic urothelial progenitors demonstrate reduced proliferation with concomitant dysregulation of genes including Cdkn2a (p16), Cdkn2b (p15) and Shh. These mutants display premature differentiation of keratin 5-positive (Krt5+) basal cells and ectopic expression of squamous-like differentiation markers. Deletion of Ezh2, the major enzymatic component of PRC2, causes upregulation of Upk3a+ superficial cells. Unexpectedly, Eed and Eed/Ezh2 double mutants exhibit delayed superficial cell differentiation. Furthermore, Eed regulates the proliferative and regenerative capacity of adult urothelial progenitors and prevents precocious differentiation. Collectively, these findings uncover the epigenetic mechanism by which PRC2 controls urothelial progenitor cell fate and the timing of differentiation, and further suggest an epigenetic basis of urothelial maintenance and regeneration. PMID:28049658

Phylogenetic Diversity of NTT Nucleotide Transport Proteins in Free-Living and Parasitic Bacteria and Eukaryotes

PubMed Central

Major, Peter; Embley, T. Martin

2017-01-01

Plasma membrane-located nucleotide transport proteins (NTTs) underpin the lifestyle of important obligate intracellular bacterial and eukaryotic pathogens by importing energy and nucleotides from infected host cells that the pathogens can no longer make for themselves. As such their presence is often seen as a hallmark of an intracellular lifestyle associated with reductive genome evolution and loss of primary biosynthetic pathways. Here, we investigate the phylogenetic distribution of NTT sequences across the domains of cellular life. Our analysis reveals an unexpectedly broad distribution of NTT genes in both host-associated and free-living prokaryotes and eukaryotes. We also identify cases of within-bacteria and bacteria-to-eukaryote horizontal NTT transfer, including into the base of the oomycetes, a major clade of parasitic eukaryotes. In addition to identifying sequences that retain the canonical NTT structure, we detected NTT gene fusions with HEAT-repeat and cyclic nucleotide binding domains in Cyanobacteria, pathogenic Chlamydiae and Oomycetes. Our results suggest that NTTs are versatile functional modules with a much wider distribution and a broader range of potential roles than has previously been appreciated. PMID:28164241

Regulation of Memory Formation by the Transcription Factor XBP1.

PubMed

Martínez, Gabriela; Vidal, René L; Mardones, Pablo; Serrano, Felipe G; Ardiles, Alvaro O; Wirth, Craig; Valdés, Pamela; Thielen, Peter; Schneider, Bernard L; Kerr, Bredford; Valdés, Jose L; Palacios, Adrian G; Inestrosa, Nibaldo C; Glimcher, Laurie H; Hetz, Claudio

2016-02-16

Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer's disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR), mediating adaptation to endoplasmic reticulum (ER) stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP), whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF), a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Computational methods for analysis and inference of kinase/inhibitor relationships

PubMed Central

Ferrè, Fabrizio; Palmeri, Antonio; Helmer-Citterich, Manuela

2014-01-01

The central role of kinases in virtually all signal transduction networks is the driving motivation for the development of compounds modulating their activity. ATP-mimetic inhibitors are essential tools for elucidating signaling pathways and are emerging as promising therapeutic agents. However, off-target ligand binding and complex and sometimes unexpected kinase/inhibitor relationships can occur for seemingly unrelated kinases, stressing that computational approaches are needed for learning the interaction determinants and for the inference of the effect of small compounds on a given kinase. Recently published high-throughput profiling studies assessed the effects of thousands of small compound inhibitors, covering a substantial portion of the kinome. This wealth of data paved the road for computational resources and methods that can offer a major contribution in understanding the reasons of the inhibition, helping in the rational design of more specific molecules, in the in silico prediction of inhibition for those neglected kinases for which no systematic analysis has been carried yet, in the selection of novel inhibitors with desired selectivity, and offering novel avenues of personalized therapies. PMID:25071826

Perioperative Nurses' Work Experience With Robotic Surgery: A Focus Group Study.

PubMed

Kang, Min Jung; De Gagne, Jennie C; Kang, Hee Sun

2016-04-01

The aim of this study was to explore the work experience of perioperative nurses involved in robotic surgery. A qualitative descriptive study was conducted. Participants were 15 nurses who had been on a robotic surgery team at one of five major university hospitals in Seoul, South Korea. Participants were one male and 14 female nurses (mean age, 31.33 [SD, 4.19] years; range, 25-41 years). Their experience as robotic surgery nurses ranged from 8 months to 6 years. Nurses' experiences with robotic surgery were categorized within four main themes: (1) constant checking on patients' safety and the robot's functions; (2) unexpected robotic machine errors or malfunctions; (3) feelings of burden in a robotic surgical team; and (4) need and desire for more information and education. This study showed that there are common concerns about patient safety and the possibility of emergencies related to robot system failure among nurses. Offering more support for nurses involved in robotic surgery should be a priority to empower them to play an extended role in robotic surgery.

A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity.

PubMed

Rajasethupathy, Priyamvada; Antonov, Igor; Sheridan, Robert; Frey, Sebastian; Sander, Chris; Tuschl, Thomas; Kandel, Eric R

2012-04-27

Small RNA-mediated gene regulation during development causes long-lasting changes in cellular phenotypes. To determine whether small RNAs of the adult brain can regulate memory storage, a process that requires stable and long-lasting changes in the functional state of neurons, we generated small RNA libraries from the Aplysia CNS. In these libraries, we discovered an unexpectedly abundant expression of a 28 nucleotide sized class of piRNAs in brain, which had been thought to be germline specific. These piRNAs have unique biogenesis patterns, predominant nuclear localization, and robust sensitivity to serotonin, a modulatory transmitter that is important for memory. We find that the Piwi/piRNA complex facilitates serotonin-dependent methylation of a conserved CpG island in the promoter of CREB2, the major inhibitory constraint of memory in Aplysia, leading to enhanced long-term synaptic facilitation. These findings provide a small RNA-mediated gene regulatory mechanism for establishing stable long-term changes in neurons for the persistence of memory. Copyright © 2012 Elsevier Inc. All rights reserved.

University nurse graduates: perspectives on factors of retention and mobility.

PubMed

Gillis, Angela; Jackson, Winston; Beiswanger, Donna

2004-03-01

This descriptive study explored the perspectives of 51 university nurse graduates from the St. Francis Xavier University School of Nursing. Qualitative and quantitative data were collected using telephone interviews to study a range of variables including geographic mobility patterns, career satisfaction and attitudes towards recruitment and retention factors. Given the negative perceptions in the media about nursing, the results of the study were unexpected and offer a sense of hope to those considering nursing as a career. Results indicate that graduates remained enthusiastic about their career choice and would choose nursing again as a career given the opportunity to do so. Furthermore, they would recommend nursing to others as a desirable career. The majority of graduates entered nursing because of a desire to make a meaningful difference in people's lives, and they were strongly influenced by positive nurse role models. Participants remained committed to a career in nursing, enjoyed considerable geographic mobility with migration to other Canadian provinces and the USA, but the majority returned to Canada for employment in nursing. The study confirms that the supportive nature of the work environment in which care is practised, the presence of visible and empowering nurse leaders, adequate compensation and benefits, and appropriate investment in continuing education and professional development of staff are significant factors in retaining nurses. Additional recommendations for enhanced recruitment and retention strategies are provided.

Differing growth responses of major phylogenetic groups of marine bacteria to natural phytoplankton blooms in the western North Pacific Ocean.

PubMed

Tada, Yuya; Taniguchi, Akito; Nagao, Ippei; Miki, Takeshi; Uematsu, Mitsuo; Tsuda, Atsushi; Hamasaki, Koji

2011-06-01

Growth and productivity of phytoplankton substantially change organic matter characteristics, which affect bacterial abundance, productivity, and community structure in aquatic ecosystems. We analyzed bacterial community structures and measured activities inside and outside phytoplankton blooms in the western North Pacific Ocean by using bromodeoxyuridine immunocytochemistry and fluorescence in situ hybridization (BIC-FISH). Roseobacter/Rhodobacter, SAR11, Betaproteobacteria, Alteromonas, SAR86, and Bacteroidetes responded differently to changes in organic matter supply. Roseobacter/Rhodobacter bacteria remained widespread, active, and proliferating despite large fluctuations in organic matter and chlorophyll a (Chl-a) concentrations. The relative contribution of Bacteroidetes to total bacterial production was consistently high. Furthermore, we documented the unexpectedly large contribution of Alteromonas to total bacterial production in the bloom. Bacterial abundance, productivity, and growth potential (the proportion of growing cells in a population) were significantly correlated with Chl-a and particulate organic carbon concentrations. Canonical correspondence analysis showed that organic matter supply was critical for determining bacterial community structures. The growth potential of each bacterial group as a function of Chl-a concentration showed a bell-shaped distribution, indicating an optimal organic matter concentration to promote growth. The growth of Alteromonas and Betaproteobacteria was especially strongly correlated with organic matter supply. These data elucidate the distinctive ecological role of major bacterial taxa in organic matter cycling during open ocean phytoplankton blooms.

Differing Growth Responses of Major Phylogenetic Groups of Marine Bacteria to Natural Phytoplankton Blooms in the Western North Pacific Ocean ▿ †

PubMed Central

Tada, Yuya; Taniguchi, Akito; Nagao, Ippei; Miki, Takeshi; Uematsu, Mitsuo; Tsuda, Atsushi; Hamasaki, Koji

2011-01-01

Growth and productivity of phytoplankton substantially change organic matter characteristics, which affect bacterial abundance, productivity, and community structure in aquatic ecosystems. We analyzed bacterial community structures and measured activities inside and outside phytoplankton blooms in the western North Pacific Ocean by using bromodeoxyuridine immunocytochemistry and fluorescence in situ hybridization (BIC-FISH). Roseobacter/Rhodobacter, SAR11, Betaproteobacteria, Alteromonas, SAR86, and Bacteroidetes responded differently to changes in organic matter supply. Roseobacter/Rhodobacter bacteria remained widespread, active, and proliferating despite large fluctuations in organic matter and chlorophyll a (Chl-a) concentrations. The relative contribution of Bacteroidetes to total bacterial production was consistently high. Furthermore, we documented the unexpectedly large contribution of Alteromonas to total bacterial production in the bloom. Bacterial abundance, productivity, and growth potential (the proportion of growing cells in a population) were significantly correlated with Chl-a and particulate organic carbon concentrations. Canonical correspondence analysis showed that organic matter supply was critical for determining bacterial community structures. The growth potential of each bacterial group as a function of Chl-a concentration showed a bell-shaped distribution, indicating an optimal organic matter concentration to promote growth. The growth of Alteromonas and Betaproteobacteria was especially strongly correlated with organic matter supply. These data elucidate the distinctive ecological role of major bacterial taxa in organic matter cycling during open ocean phytoplankton blooms. PMID:21515719

A Proteome Translocation Response to Complex Desert Stress Environments in Perennial Phragmites Sympatric Ecotypes with Contrasting Water Availability

PubMed Central

Li, Li; Chen, Xiaodan; Shi, Lu; Wang, Chuanjing; Fu, Bing; Qiu, Tianhang; Cui, Suxia

2017-01-01

After a long-term adaptation to desert environment, the perennial aquatic plant Phragmites communis has evolved a desert-dune ecotype. The desert-dune ecotype (DR) of Phragmites communis showed significant differences in water activity and protein distribution compared to its sympatric swamp ecotype (SR). Many proteins that were located in the soluble fraction of SR translocated to the insoluble fraction of DR, suggesting that membrane-associated proteins were greatly reinforced in DR. The unknown phenomenon in plant stress physiology was defined as a proteome translocation response. Quantitative 2D-DIGE technology highlighted these ‘bound’ proteins in DR. Fifty-eight kinds of proteins were identified as candidates of the translocated proteome in Phragmites. The majority were chloroplast proteins. Unexpectedly, Rubisco was the most abundant protein sequestered by DR. Rubisco activase, various chaperons and 2-cysteine peroxiredoxin were major components in the translocation response. Conformational change was assumed to be the main reason for the Rubisco translocation due to no primary sequence difference between DR and SR. The addition of reductant in extraction process partially reversed the translocation response, implying that intracellular redox status plays a role in the translocation response of the proteome. The finding emphasizes the realistic significance of the membrane-association of biomolecule for plant long-term adaptation to complex stress conditions. PMID:28450873

CCC meets ICU: redefining the role of critical care of cancer patients.

PubMed

von Bergwelt-Baildon, Michael; Hallek, Michael J; Shimabukuro-Vornhagen, Alexander A; Kochanek, Matthias

2010-11-08

Currently the majority of cancer patients are considered ineligible for intensive care treatment and oncologists are struggling to get their patients admitted to intensive care units. Critical care and oncology are frequently two separate worlds that communicate rarely and thus do not share novel developments in their fields. However, cancer medicine is rapidly improving and cancer is eventually becoming a chronic disease. Oncology is therefore characterized by a growing number of older and medically unfit patients that receive numerous novel drug classes with unexpected side effects. All of these changes will generate more medically challenging patients in acute distress that need to be considered for intensive care. An intense exchange between intensivists, oncologists, psychologists and palliative care specialists is warranted to communicate the developments in each field in order to improve triage and patient treatment. Here, we argue that "critical care of cancer patients" needs to be recognized as a medical subspecialty and that there is an urgent need to develop it systematically. As prognosis of cancer improves, novel therapeutic concepts are being introduced and more and more older cancer patients receive full treatment the number of acutely ill patients is growing significantly. This development a major challenge to current concepts of intensive care and it needs to be redefined who of these patients should be treated, for how long and how intensively.

Subxiphoid complex uniportal video-assisted major pulmonary resections.

PubMed

Gonzalez-Rivas, Diego; Lirio, Francisco; Sesma, Julio; Abu Akar, Firas

2017-01-01

In recent years, the search for a less invasive and thus, less painful approach has driven technical innovation in modern thoracic surgery. In this context, subxiphoid uniportal approach has emerged as an alternative to avoid intercostal space manipulation and decrease postoperative pain and intercostal nerve chronic impairment. Subxiphoid uniportal major lung resections have been safe and effective procedures when performed by experienced surgeons even in complex cases or unexpected intraoperative situations. We present six of these surgical scenarios such as big tumors, incomplete or absent fissures, hilar calcified lymph nodes, active bleeding and massive adhesions to show the feasibility of subxiphoid approach to manage even these conditions.

Subxiphoid complex uniportal video-assisted major pulmonary resections

PubMed Central

Lirio, Francisco; Sesma, Julio; Abu Akar, Firas

2017-01-01

In recent years, the search for a less invasive and thus, less painful approach has driven technical innovation in modern thoracic surgery. In this context, subxiphoid uniportal approach has emerged as an alternative to avoid intercostal space manipulation and decrease postoperative pain and intercostal nerve chronic impairment. Subxiphoid uniportal major lung resections have been safe and effective procedures when performed by experienced surgeons even in complex cases or unexpected intraoperative situations. We present six of these surgical scenarios such as big tumors, incomplete or absent fissures, hilar calcified lymph nodes, active bleeding and massive adhesions to show the feasibility of subxiphoid approach to manage even these conditions. PMID:29078655

Resistant Bacterial Spore Coats and Their Breakdown During Germination

DTIC Science & Technology

2010-01-01

proteins are released into the outer layers of the spore (SspA, B) or released into the supernatant ( SspE ). 4. Two major proteases of broad...40 30 20 15 10 3.5 N o ve x Sh ar p cw lD ge rm in at io n e xu d at e N o ve x Sh ar p cw lD ge rm in at io n e xu d at e CotA CotQ SodA SspE ...Finally, and unexpectedly, SspE , the major gamma-type SASP (small acid soluble protein) present in the inner cellular compartment of dormant spores, and

Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming.

PubMed

Tian, Lin; Goldstein, Amit; Wang, Hai; Ching Lo, Hin; Sun Kim, Ik; Welte, Thomas; Sheng, Kuanwei; Dobrolecki, Lacey E; Zhang, Xiaomei; Putluri, Nagireddy; Phung, Thuy L; Mani, Sendurai A; Stossi, Fabio; Sreekumar, Arun; Mancini, Michael A; Decker, William K; Zong, Chenghang; Lewis, Michael T; Zhang, Xiang H-F

2017-04-13

Blockade of angiogenesis can retard tumour growth, but may also paradoxically increase metastasis. This paradox may be resolved by vessel normalization, which involves increased pericyte coverage, improved tumour vessel perfusion, reduced vascular permeability, and consequently mitigated hypoxia. Although these processes alter tumour progression, their regulation is poorly understood. Here we show that type 1 T helper (T H 1) cells play a crucial role in vessel normalization. Bioinformatic analyses revealed that gene expression features related to vessel normalization correlate with immunostimulatory pathways, especially T lymphocyte infiltration or activity. To delineate the causal relationship, we used various mouse models with vessel normalization or T lymphocyte deficiencies. Although disruption of vessel normalization reduced T lymphocyte infiltration as expected, reciprocal depletion or inactivation of CD4 + T lymphocytes decreased vessel normalization, indicating a mutually regulatory loop. In addition, activation of CD4 + T lymphocytes by immune checkpoint blockade increased vessel normalization. T H 1 cells that secrete interferon-γ are a major population of cells associated with vessel normalization. Patient-derived xenograft tumours growing in immunodeficient mice exhibited enhanced hypoxia compared to the original tumours in immunocompetent humans, and hypoxia was reduced by adoptive T H 1 transfer. Our findings elucidate an unexpected role of T H 1 cells in vasculature and immune reprogramming. T H 1 cells may be a marker and a determinant of both immune checkpoint blockade and anti-angiogenesis efficacy.

CD1a presentation of endogenous antigens by group 2 innate lymphoid cells.

PubMed

Hardman, Clare S; Chen, Yi-Ling; Salimi, Maryam; Jarrett, Rachael; Johnson, David; Järvinen, Valtteri J; Owens, Raymond J; Repapi, Emmanouela; Cousins, David J; Barlow, Jillian L; McKenzie, Andrew N J; Ogg, Graham

2017-12-22

Group 2 innate lymphoid cells (ILC2) are effectors of barrier immunity, with roles in infection, wound healing, and allergy. A proportion of ILC2 express MHCII (major histocompatibility complex II) and are capable of presenting peptide antigens to T cells and amplifying the subsequent adaptive immune response. Recent studies have highlighted the importance of CD1a-reactive T cells in allergy and infection, activated by the presentation of endogenous neolipid antigens and bacterial components. Using a human skin challenge model, we unexpectedly show that human skin-derived ILC2 can express CD1a and are capable of presenting endogenous antigens to T cells. CD1a expression is up-regulated by TSLP (thymic stromal lymphopoietin) at levels observed in the skin of patients with atopic dermatitis, and the response is dependent on PLA2G4A. Furthermore, this pathway is used to sense Staphylococcus aureus by promoting Toll-like receptor-dependent CD1a-reactive T cell responses to endogenous ligands. These findings define a previously unrecognized role for ILC2 in lipid surveillance and identify shared pathways of CD1a- and PLA2G4A-dependent ILC2 inflammation amenable to therapeutic intervention. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Systematic discovery of novel ciliary genes through functional genomics in the zebrafish

PubMed Central

Choksi, Semil P.; Babu, Deepak; Lau, Doreen; Yu, Xianwen; Roy, Sudipto

2014-01-01

Cilia are microtubule-based hair-like organelles that play many important roles in development and physiology, and are implicated in a rapidly expanding spectrum of human diseases, collectively termed ciliopathies. Primary ciliary dyskinesia (PCD), one of the most prevalent of ciliopathies, arises from abnormalities in the differentiation or motility of the motile cilia. Despite their biomedical importance, a methodical functional screen for ciliary genes has not been carried out in any vertebrate at the organismal level. We sought to systematically discover novel motile cilia genes by identifying the genes induced by Foxj1, a winged-helix transcription factor that has an evolutionarily conserved role as the master regulator of motile cilia biogenesis. Unexpectedly, we find that the majority of the Foxj1-induced genes have not been associated with cilia before. To characterize these novel putative ciliary genes, we subjected 50 randomly selected candidates to a systematic functional phenotypic screen in zebrafish embryos. Remarkably, we find that over 60% are required for ciliary differentiation or function, whereas 30% of the proteins encoded by these genes localize to motile cilia. We also show that these genes regulate the proper differentiation and beating of motile cilia. This collection of Foxj1-induced genes will be invaluable for furthering our understanding of ciliary biology, and in the identification of new mutations underlying ciliary disorders in humans. PMID:25139857

Understanding rare adverse sequelae of breast implants: anaplastic large-cell lymphoma, late seromas, and double capsules

PubMed Central

Nava, Maurizio Bruno; Rocco, Nicola

2017-01-01

Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a distinct type of T-cell lymphoma arising around breast implants. The United States FDA recently updated the 2011 safety communication, warning that women with breast implants may have a very low risk of developing ALCL adjacent to a breast implant. According to the World Health Organization, BI-LCL is not a breast cancer or cancer of the breast tissue; it is a lymphoma, a cancer of immune cells. BI-ALCL is highly curable in the majority of patients. Informed consent should include the risk of BI-ALCL with breast implant patients. Women with breast implants are encouraged to contact their plastic surgeon if they notice swelling, fluid collections, or unexpected changes in breast shape. Physicians are encouraged to send suspicious peri-prosthetic fluid for CD30 immunohistochemistry, cell block cytology, and culture in symptomatic patients. An observation from reported cases indicates a predominance of textured device involvement. More information is needed to fully understand risk factors and etiology. The association of bacteria and biofilm with ALCL is currently being investigated and one theory is that biofilm may play a role in this disease process stressing the importance of best practice techniques intraoperatively. Recent studies have reported clinical presentation, prognosis, and treatment outcomes with long term followup demonstrating the critical role for surgical management. PMID:28497021

Understanding rare adverse sequelae of breast implants: anaplastic large-cell lymphoma, late seromas, and double capsules.

PubMed

Clemens, Mark W; Nava, Maurizio Bruno; Rocco, Nicola; Miranda, Roberto N

2017-04-01

Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a distinct type of T-cell lymphoma arising around breast implants. The United States FDA recently updated the 2011 safety communication, warning that women with breast implants may have a very low risk of developing ALCL adjacent to a breast implant. According to the World Health Organization, BI-LCL is not a breast cancer or cancer of the breast tissue; it is a lymphoma, a cancer of immune cells. BI-ALCL is highly curable in the majority of patients. Informed consent should include the risk of BI-ALCL with breast implant patients. Women with breast implants are encouraged to contact their plastic surgeon if they notice swelling, fluid collections, or unexpected changes in breast shape. Physicians are encouraged to send suspicious peri-prosthetic fluid for CD30 immunohistochemistry, cell block cytology, and culture in symptomatic patients. An observation from reported cases indicates a predominance of textured device involvement. More information is needed to fully understand risk factors and etiology. The association of bacteria and biofilm with ALCL is currently being investigated and one theory is that biofilm may play a role in this disease process stressing the importance of best practice techniques intraoperatively. Recent studies have reported clinical presentation, prognosis, and treatment outcomes with long term followup demonstrating the critical role for surgical management.

Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4[S

PubMed Central

Lukic, Ana; Ji, Jie; Idborg, Helena; Samuelsson, Bengt; Palmberg, Lena

2016-01-01

Leukotrienes (LTs) play major roles in lung immune responses, and LTD4 is the most potent agonist for cysteinyl LT1, leading to bronchoconstriction and tissue remodeling. Here, we studied LT crosstalk between myeloid cells and pulmonary epithelial cells. Monocytic cells (Mono Mac 6 cell line, primary dendritic cells) and eosinophils produced primarily LTC4. In coincubations of these myeloid cells and epithelial cells, LTD4 became a prominent product. LTC4 released from the myeloid cells was further transformed by the epithelial cells in a transcellular manner. Formation of LTD4 was rapid when catalyzed by γ-glutamyl transpeptidase (GGT)1 in the A549 epithelial lung cancer cell line, but considerably slower when catalyzed by GGT5 in primary bronchial epithelial cells. When A549 cells were cultured in the presence of IL-1β, GGT1 expression increased about 2-fold. Also exosomes from A549 cells contained GGT1 and augmented LTD4 formation. Serine-borate complex (SBC), an inhibitor of GGT, inhibited conversion of LTC4 to LTD4. Unexpectedly, SBC also upregulated translocation of 5-lipoxygenase (LO) to the nucleus in Mono Mac 6 cells, and 5-LO activity. Our results demonstrate an active role for epithelial cells in biosynthesis of LTD4, which may be of particular relevance in the lung. PMID:27436590

Enigma Variations for Peptides and Their Transporters in Higher Plants

PubMed Central

WATERWORTH, WANDA M.; BRAY, CLIFFORD M.

2006-01-01

• Background. Two families of proteins that transport small peptides, the oligopeptide transporters (OPTs) and the peptide transporters (PTRs), have been recognized in eukaryotes. Higher plants contain a far greater number of genes for these transporters than do other eukaryotes. This may be indicative of the relative importance of (oligo)peptides and their transport to plant growth and metabolism. • Recent progress. Recent studies are now allowing us to assign functions to these transporters and are starting to identify their in-planta substrates, revealing unexpected and important contributions of the transporters to plant growth and developmental processes. This Botanical Briefing appraises recent findings that PTRs and OPTs have key roles to play in the control of plant cell growth and development. Evidence is presented that some of these transporters have functions outside that of nitrogen nutrition and that these carriers can also surprise us with their totally unexpected choice of substrates. PMID:16735405

Long-range DHPS mutations unexpectedly increase Mycobacterium chimaera susceptibility to sulfonamides.

PubMed

Gotthard, Guillaume; Muhammed Ameen, Sirwan; Drancourt, Michel; Chabriere, Eric

2013-12-01

The two closely related mycobacteria, Mycobacterium intracellulare and Mycobacterium chimaera, exhibit a more than two-fold difference in their in vitro susceptibility to sulfonamides. Sulfonamides are antibiotics targeting the 6-hydroxymethyl-7,8-dihydropteroate synthase (DHPS) enzyme involved in the folate synthesis pathway. Comparing the DHPS gene sequence in six M. intracellulare and M. chimaera types trains and clinical isolates yielded only four amino acid changes. In silico structural modelling surprisingly indicated that these amino acids are not located in the active site of DHPS and do not interact directly with sulfonamides. Unexpectedly, these amino acids in distal positions may play a key role in the increased sulfonamide susceptibility observed in M. chimaera compared with M. intracellulare. This example illustrates how three-dimensional models could help to identify distal mutations capable of modulating enzymatic activity. Copyright © 2013 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Left Ventricular Aneurysm: Sudden Unexpected Deaths in a 29-Year-Old Man.

PubMed

Srettabunjong, Supawon

2018-05-01

Left ventricular aneurysm (LVA) is an abnormal dilated heart structure, either congenital or acquired. LVA is a rare cardiac condition with no symptoms in most cases, thus occasionally diagnosed during investigations of other diseases. Its association with certain cardiac complications and sudden cardiac deaths has been reported. However, its role as a cause of sudden unexpected death is rare. The author reported a sudden cardiac death in a 29-year-old man with LVA. Without a significant coronary artery disease and known etiologies of LVA, such an abnormal heart structure in the present case was considered congenital LVA. As no other possible mechanisms of death could be identified other than LVA with its associated pathologic lesions, mural thrombi, and dilated cardiomegaly, his death was attributable to fatal cardiac arrhythmia (most commonly ventricular tachycardia) secondary to LVA. © 2017 American Academy of Forensic Sciences.

What Military Officers Need to Know About Civil-Military Relations

DTIC Science & Technology

2012-04-01

2012, Vol. 65, No. 2 Mackubin Thomas Owens ivil-military relations describe the interactions among the people of a state, the institutions of that...civilians for the unexpect- edly difficult occupation of Iraq,” one close observer—U.S. Army major Isaiah Wilson III, an official historian of the...U.S. Civil- Military Relations. 4. I have addressed these questions in depth in Mackubin Thomas Owens, US Civil-Military Relations after 9/11

Ventral Striatum Response During Reward and Punishment Reversal Learning in Unmedicated Major Depressive Disorder

PubMed Central

Robinson, Oliver J.; Cools, Roshan; Carlisi, Christina O.; Sahakian, Barbara J.; Drevets, Wayne C.

2017-01-01

Objective Affective biases may underlie many of the key symptoms of major depressive disorder, from anhedonia to altered cognitive performance. Understanding the cause of these biases is therefore critical in the quest for improved treatments. Depression is associated, for example, with a negative affective bias in reversal learning. However, despite the fact that reversal learning is associated with striatal response in healthy individuals and depressed individuals exhibit attenuated striatal function on multiple tasks, studies to date have not demonstrated striatal involvement in the negative bias in reversal learning in depression. In this study, the authors sought to determine whether this may be because reversal learning tasks conventionally used to study behavior examine reversals only on the basis of unexpected punishment and therefore do not adequately separate reward- and punishment-based behavior. Method The authors used functional MRI to com pare the hemodynamic response to a reversal learning task with mixed reward- and punishment-based reversal stages between individuals with unmedicated major depressive disorder (N=13) and healthy comparison subjects (N=14). Results Impaired reward (but not punishment) reversal accuracy was found alongside attenuated anteroventral striatal response to unexpected reward in depression. Conclusions Attenuated neurophysiological response of the anteroventral striatum may reflect dysfunction in circuits involving afferent projections from the orbitofrontal, limbic, and/or mesostriatal dopaminergic pathways, which conceivably may, together with the ventral striatum, underlie anhedonia in depression. Learning to appreciate and enjoy positive life experiences is critical for recovery from depression. This study pinpoints a neural target for such recovery. PMID:22420038

Complex role of HIF in cancer: the known, the unknown, and the unexpected

PubMed Central

Tiburcio, Patricia Denise; Choi, Hyunsung; Huang, L Eric

2014-01-01

Tumor hypoxia has long been recognized as a driving force of malignant progression and therapeutic resistance. The discovery of hypoxia-inducible transcription factors (HIFs) has greatly advanced our understanding of how cancer cells cope with hypoxic stress by maintaining bioenergetics through the stimulation of glycolysis. Until recently, however, it remained perplexing why proliferative cancer cells opt for aerobic glycolysis, an energy-inefficient process of glucose metabolism. Furthermore, the role of HIF in cancer has also become complex. In this review, we highlight recent groundbreaking findings in cancer metabolism, put forward plausible explanations to the complex role of HIF, and underscore remaining issues in cancer biology. PMID:27774467

"I Would Rather Be Size 10 Than Have Straight A's": A Focus Study Group of Adolescent Girls' Wish To Be Thinner.

ERIC Educational Resources Information Center

Tiggemann, Marika; Gardiner, Maria; Slater, Amy

2000-01-01

Investigates the body concerns of adolescent girls (N=67), together with the underlying motivations for wishes to be thinner. Results of focus group studies reveal that sociocultural influences exerted the strongest pressures to be thin. The girls displayed an unexpected sophistication in their conceptualization of the role of both media effects…

An Unsung Fashion Designer, Congo Square, Pinktoe Tarantulas, and Dead People: Expecting the Unexpected in Children's Literature

ERIC Educational Resources Information Center

McNair, Jonda C.

2017-01-01

Children's literature plays an essential role in the literacy development of children. This department column focuses on the teaching and use of children's literature and provides educators with information about a wide range of books across multiple genres that are representative of the diverse world in which we live. A strong emphasis is placed…

Controlled English for Effective Communication during Coalition Operations

DTIC Science & Technology

2013-06-01

Linguistic variations and cultural differences often create unexpected challenges for effective communication and thus for Command and Control (C2...CE), and CE-based tools to improve cross- linguistic /cross-cultural communication. We will discuss various types of linguistic variations and cultural...human-computer interaction, reasoning, and explanation CE and CE-based tools can play an important role in facilitating cross- linguistic and cross

40 years of neutrino physics

NASA Astrophysics Data System (ADS)

Reines, Frederick

Wolfgang Pauli and Enrico Fermi pioneered the hypothesis and characteristics of the weak interaction and the elementary particle called the neutrino. Since its discovery some forty years ago the neutrino has been shown to be a fundamental constituent of matter with a surprisingly rich, and in very many ways unexpected, set of characteristics ranging from basic roles in the generation of energy in the sun to supernovæ.

Why don't you like me? Midfrontal theta power in response to unexpected peer rejection feedback.

PubMed

van der Molen, M J W; Dekkers, L M S; Westenberg, P M; van der Veen, F M; van der Molen, M W

2017-02-01

Social connectedness theory posits that the brain processes social rejection as a threat to survival. Recent electrophysiological evidence suggests that midfrontal theta (4-8Hz) oscillations in the EEG provide a window on the processing of social rejection. Here we examined midfrontal theta dynamics (power and inter-trial phase synchrony) during the processing of social evaluative feedback. We employed the Social Judgment paradigm in which 56 undergraduate women (mean age=19.67 years) were asked to communicate their expectancies about being liked vs. disliked by unknown peers. Expectancies were followed by feedback indicating social acceptance vs. rejection. Results revealed a significant increase in EEG theta power to unexpected social rejection feedback. This EEG theta response could be source-localized to brain regions typically reported during activation of the saliency network (i.e., dorsal anterior cingulate cortex, insula, inferior frontal gyrus, frontal pole, and the supplementary motor area). Theta phase dynamics mimicked the behavior of the time-domain averaged feedback-related negativity (FRN) by showing stronger phase synchrony for feedback that was unexpected vs. expected. Theta phase, however, differed from the FRN by also displaying stronger phase synchrony in response to rejection vs. acceptance feedback. Together, this study highlights distinct roles for midfrontal theta power and phase synchrony in response to social evaluative feedback. Our findings contribute to the literature by showing that midfrontal theta oscillatory power is sensitive to social rejection but only when peer rejection is unexpected, and this theta response is governed by a widely distributed neural network implicated in saliency detection and conflict monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.

Glycoprotein A repetitions predominant (GARP) positively regulates transforming growth factor (TGF) β3 and is essential for mouse palatogenesis.

PubMed

Wu, Bill X; Li, Anqi; Lei, Liming; Kaneko, Satoshi; Wallace, Caroline; Li, Xue; Li, Zihai

2017-11-03

Glycoprotein A repetitions predominant (GARP) (encoded by the Lrrc32 gene) plays important roles in cell-surface docking and activation of TGFβ. However, GARP's role in organ development in mammalian systems is unclear. To determine the function of GARP in vivo , we generated a GARP KO mouse model. Unexpectedly, the GARP KO mice died within 24 h after birth and exhibited defective palatogenesis without apparent abnormalities in other major organs. Furthermore, we observed decreased apoptosis and SMAD2 phosphorylation in the medial edge epithelial cells of the palatal shelf of GARP KO embryos at embryonic day 14.5 (E14.5), indicating a defect in the TGFβ signaling pathway in the GARP-null developing palates. Of note, the failure to develop the secondary palate and concurrent reduction of SMAD phosphorylation without other defects in GARP KO mice phenocopied TGFβ3 KO mice, although GARP has not been suggested previously to interact with TGFβ3. We found that GARP and TGFβ3 co-localize in medial edge epithelial cells at E14.5. In vitro studies confirmed that GARP and TGFβ3 directly interact and that GARP is indispensable for the surface expression of membrane-associated latent TGFβ3. Our findings indicate that GARP is essential for normal morphogenesis of the palate and demonstrate that GARP plays a crucial role in regulating TGFβ3 signaling during embryogenesis. In conclusion, we have uncovered a novel function of GARP in positively regulating TGFβ3 activation and function. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Stimulus-Dependent, Promoter-Specific Binding of Transcription Factor WRKY1 to Its Native Promoter and the Defense-Related Gene PcPR1-1 in ParsleyW⃞

PubMed Central

Turck, Franziska; Zhou, Aifen; Somssich, Imre E.

2004-01-01

WRKY transcription factors form a large family that plays a role in plant responses to biotic stress and during senescence. Defining in vivo relevant WRKY/promoter relationships has been hampered by the factors' indiscriminate binding to known W box DNA elements and their possible genetic redundance. Employing chromatin immunoprecipitations (ChIP) of cultured cells, we show that parsley (Petroselinum crispum) WRKY1 protein binds to the W boxes of its native promoter as well as to that of PcWRKY3 and the defense-related PR10-class marker gene Pathogenesis-Related1-1 (PcPR1-1). Although present at low concentrations in resting cells, WRKY1 does not appear to play a role in the immediate early gene response upon elicitation because it does not bind to the promoter at this time. Paradoxically, in vivo binding at the PcWRKY1 promoter correlates more with downregulation of gene expression, whereas previous overexpression studies suggested an activating function of WRKY1 on PcWRKY1 expression. By contrast, PcPR1-1 expression remains strong when its promoter is occupied in vivo by WRKY1. Unexpectedly, ChIP revealed that W boxes at promoter sites are constitutively occupied by other WRKY transcription factors, indicating that site recruitment does not seem to play a major role in their regulation. Rather, WRKY proteins very likely act in a network of mutually competing participants with temporal displacement occurring at defined preoccupied sites by other family members in a stimulus-dependent manner. PMID:15367720

The role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases.

PubMed

Mack, Ines; Hector, Andreas; Ballbach, Marlene; Kohlhäufl, Julius; Fuchs, Katharina J; Weber, Alexander; Mall, Marcus A; Hartl, Dominik

2015-12-01

Chitin, after cellulose, the second most abundant biopolymer on earth, is a key component of insects, fungi, and house-dust mites. Lower life forms are endowed with chitinases to defend themselves against chitin-bearing pathogens. Unexpectedly, humans were also found to express chitinases as well as chitinase-like proteins that modulate immune responses. Particularly, increased levels of the chitinase-like protein YKL-40 have been associated with severe asthma, cystic fibrosis, and other inflammatory disease conditions. Here, we summarize and discuss the potential role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases.

Modeling infectious diseases dissemination through online role-playing games.

PubMed

Balicer, Ran D

2007-03-01

As mathematical modeling of infectious diseases becomes increasingly important for developing public health policies, a novel platform for such studies might be considered. Millions of people worldwide play interactive online role-playing games, forming complex and rich networks among their virtual characters. An unexpected outbreak of an infective communicable disease (unplanned by the game creators) recently occurred in this virtual world. This outbreak holds surprising similarities to real-world epidemics. It is possible that these virtual environments could serve as a platform for studying the dissemination of infectious diseases, and as a testing ground for novel interventions to control emerging communicable diseases.

The Intertwined Roles of Transcription and Repair Proteins

PubMed Central

Fong, Yick W.; Cattoglio, Claudia; Tjian, Robert

2014-01-01

Transcription is apparently risky business. Its intrinsic mutagenic potential must be kept in check by networks of DNA repair factors that monitor the transcription process to repair DNA lesions that could otherwise compromise transcriptional fidelity and genome integrity. Intriguingly, recent studies point to an even more direct function of DNA repair complexes as co-activators of transcription and the unexpected role of “scheduled” DNA damage/repair at gene promoters. Paradoxically, spontaneous DNA double-strand breaks also induce ectopic transcription that is essential for repair. Thus, transcription, DNA damage and repair may be more physically and functionally intertwined than previously appreciated. PMID:24207023

Strange bedfellows: A Russian prince, A Scottish Economist, and the role of empathy in early theories for the evolution of cooperation.

PubMed

Dugatkin, Lee Alan

2013-11-01

From 1888 to his death in 1921, Russian Prince Peter Kropotkin forced biologists to ask themselves whether natural selection inevitably led to a dog-eat-dog world, or whether pro-social behavior could also be a product of the evolutionary process. In this historical vignette, I focus on Kropotkin's theory of "mutual aid," with emphasis on the role that empathy played in that theory, and the unexpected source--economist Adam Smith's 1759 book, The Theory of Moral Sentiments--of Kropotkin's ideas on empathy in animals. © 2013 Wiley Periodicals, Inc.

On the globality of motor suppression: unexpected events and their influence on behavior and cognition

PubMed Central

Wessel, Jan R.; Aron, Adam R.

2016-01-01

SUMMARY Unexpected events are part of everyday experience. They come in several varieties – action errors, unexpected action outcomes, and unexpected perceptual events – and they lead to motor slowing and cognitive distraction. While different varieties of unexpected events have been studied largely independently, and many different mechanisms are thought to explain their effects on action and cognition, we suggest a unifying theory. We propose that unexpected events recruit a fronto-basal-ganglia network for stopping. This network includes specific prefrontal cortical nodes and is posited to project to the subthalamic nucleus, with a putative global suppressive effect on basal-ganglia output. We argue that unexpected events interrupt action and impact cognition, partly at least, by recruiting this global suppressive network. This provides a common mechanistic basis for different types of unexpected events, links the literatures on motor inhibition, performance-monitoring, attention, and working memory, and is relevant for understanding clinical symptoms of distractibility and mental inflexibility. PMID:28103476

On the Globality of Motor Suppression: Unexpected Events and Their Influence on Behavior and Cognition.

PubMed

Wessel, Jan R; Aron, Adam R

2017-01-18

Unexpected events are part of everyday experience. They come in several varieties-action errors, unexpected action outcomes, and unexpected perceptual events-and they lead to motor slowing and cognitive distraction. While different varieties of unexpected events have been studied largely independently, and many different mechanisms are thought to explain their effects on action and cognition, we suggest a unifying theory. We propose that unexpected events recruit a fronto-basal-ganglia network for stopping. This network includes specific prefrontal cortical nodes and is posited to project to the subthalamic nucleus, with a putative global suppressive effect on basal-ganglia output. We argue that unexpected events interrupt action and impact cognition, partly at least, by recruiting this global suppressive network. This provides a common mechanistic basis for different types of unexpected events; links the literatures on motor inhibition, performance monitoring, attention, and working memory; and is relevant for understanding clinical symptoms of distractibility and mental inflexibility. Copyright © 2017 Elsevier Inc. All rights reserved.

Islam, Assisted Reproduction, and the Bioethical Aftermath.

PubMed

Inhorn, Marcia C; Tremayne, Soraya

2016-04-01

Assisted reproductive technologies (ARTs), including in vitro fertilization to overcome infertility, are now widely available across the Middle East. Islamic fatwas emerging from the Sunni Islamic countries have permitted many ARTs, while prohibiting others. However, recent religious rulings emanating from Shia Muslim-dominant Iran have created unique avenues for infertile Muslim couples to obtain donor gametes through third-party reproductive assistance. The opening of Iran to gamete donation has had major impacts in Shia-dominant Lebanon and has led to so-called reproductive tourism of Sunni Muslim couples who are searching for donor gametes across national and international borders. This paper explores the "bioethical aftermath" of donor technologies in the Muslim Middle East. Other unexpected outcomes include new forms of sex selection and fetal "reduction." In general, assisted reproduction in the Muslim world has been a key site for understanding how emerging biomedical technologies are generating new Islamic bioethical discourses and local moral responses, as ARTs are used in novel and unexpected ways.

A dual contribution to the involuntary semantic processing of unexpected spoken words.

PubMed

Parmentier, Fabrice B R; Turner, Jacqueline; Perez, Laura

2014-02-01

Sounds are a major cause of distraction. Unexpected to-be-ignored auditory stimuli presented in the context of an otherwise repetitive acoustic background ineluctably break through selective attention and distract people from an unrelated visual task (deviance distraction). This involuntary capture of attention by deviant sounds has been hypothesized to trigger their semantic appraisal and, in some circumstances, interfere with ongoing performance, but it remains unclear how such processing compares with the automatic processing of distractors in classic interference tasks (e.g., Stroop, flanker, Simon tasks). Using a cross-modal oddball task, we assessed the involuntary semantic processing of deviant sounds in the presence and absence of deviance distraction. The results revealed that some involuntary semantic analysis of spoken distractors occurs in the absence of deviance distraction but that this processing is significantly greater in its presence. We conclude that the automatic processing of spoken distractors reflects 2 contributions, one that is contingent upon deviance distraction and one that is independent from it.

Large apparent electric size of solid-state nanopores due to spatially extended surface conduction.

PubMed

Lee, Choongyeop; Joly, Laurent; Siria, Alessandro; Biance, Anne-Laure; Fulcrand, Rémy; Bocquet, Lydéric

2012-08-08

Ion transport through nanopores drilled in thin membranes is central to numerous applications, including biosensing and ion selective membranes. This paper reports experiments, numerical calculations, and theoretical predictions demonstrating an unexpectedly large ionic conduction in solid-state nanopores, taking its origin in anomalous entrance effects. In contrast to naive expectations based on analogies with electric circuits, the surface conductance inside the nanopore is shown to perturb the three-dimensional electric current streamlines far outside the nanopore in order to meet charge conservation at the pore entrance. This unexpected contribution to the ionic conductance can be interpreted in terms of an apparent electric size of the solid-state nanopore, which is much larger than its geometric counterpart whenever the number of charges carried by the nanopore surface exceeds its bulk counterpart. This apparent electric size, which can reach hundreds of nanometers, can have a major impact on the electrical detection of translocation events through nanopores, as well as for ionic transport in biological nanopores.

Sudden unexpected death in epilepsy following resective epilepsy surgery in two patients withdrawn from anticonvulsants.

PubMed

Mansouri, Alireza; Alhadid, Kenda; Valiante, Taufik A

2015-09-01

We report sudden unexpected death in epilepsy (SUDEP) following resective epilepsy surgery in two patients who had been documented as seizure free. One patient had been weaned off of anticonvulsants and was leading a normal life. The other patient had discontinued only one anticonvulsant but had recently started working night shifts. Following resective epilepsy surgery, one of the major objectives among patients, caregivers, and the healthcare team is to safely wean patients off anticonvulsant medications. The main concern regarding anticonvulsant withdrawal is seizure recurrence. While SUDEP following surgical resection has been reported, to our knowledge, there have been no confirmed cases in patients who have been seizure free. Considering the patients reported here, and given that there are no concrete guidelines for the safe withdrawal of anticonvulsants following epilepsy surgery, the discontinuation of anticonvulsants should be considered carefully and must be accompanied by close monitoring and counseling of patients regarding activities that lower seizure threshold, even after successful epilepsy surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transcriptome-Wide Identification of RNA Targets of Arabidopsis SERINE/ARGININE-RICH45 Uncovers the Unexpected Roles of This RNA Binding Protein in RNA Processing[OPEN

PubMed Central

Wang, Yajun; Hamilton, Michael; Ben-Hur, Asa; Reddy, Anireddy S.N.

2015-01-01

Plant SR45 and its metazoan ortholog RNPS1 are serine/arginine-rich (SR)-like RNA binding proteins that function in splicing/postsplicing events and regulate diverse processes in eukaryotes. Interactions of SR45 with both RNAs and proteins are crucial for regulating RNA processing. However, in vivo RNA targets of SR45 are currently unclear. Using RNA immunoprecipitation followed by high-throughput sequencing, we identified over 4000 Arabidopsis thaliana RNAs that directly or indirectly associate with SR45, designated as SR45-associated RNAs (SARs). Comprehensive analyses of these SARs revealed several roles for SR45. First, SR45 associates with and regulates the expression of 30% of abscisic acid (ABA) signaling genes at the postsplicing level. Second, although most SARs are derived from intron-containing genes, surprisingly, 340 SARs are derived from intronless genes. Expression analysis of the SARs suggests that SR45 differentially regulates intronless and intron-containing SARs. Finally, we identified four overrepresented RNA motifs in SARs that likely mediate SR45’s recognition of its targets. Therefore, SR45 plays an unexpected role in mRNA processing of intronless genes, and numerous ABA signaling genes are targeted for regulation at the posttranscriptional level. The diverse molecular functions of SR45 uncovered in this study are likely applicable to other species in view of its conservation across eukaryotes. PMID:26603559

Leishmania major survival in selective Phlebotomus papatasi sand fly vector requires a specific SCG-encoded lipophosphoglycan galactosylation pattern.

PubMed

Dobson, Deborah E; Kamhawi, Shaden; Lawyer, Phillip; Turco, Salvatore J; Beverley, Stephen M; Sacks, David L

2010-11-11

Phlebotomine sand flies that transmit the protozoan parasite Leishmania differ greatly in their ability to support different parasite species or strains in the laboratory: while some show considerable selectivity, others are more permissive. In "selective" sand flies, Leishmania binding and survival in the fly midgut typically depends upon the abundant promastigote surface adhesin lipophosphoglycan (LPG), which exhibits species- and strain-specific modifications of the dominant phosphoglycan (PG) repeat units. For the "selective" fly Phlebotomus papatasi PpapJ, side chain galactosyl-modifications (scGal) of PG repeats play key roles in parasite binding. We probed the specificity and properties of this scGal-LPG PAMP (Pathogen Associated Molecular Pattern) through studies of natural isolates exhibiting a wide range of galactosylation patterns, and of a panel of isogenic L. major engineered to express similar scGal-LPG diversity by transfection of SCG-encoded β1,3-galactosyltransferases with different activities. Surprisingly, both 'poly-scGal' and 'null-scGal' lines survived poorly relative to PpapJ-sympatric L. major FV1 and other 'mono-scGal' lines. However, survival of all lines was equivalent in P. duboscqi, which naturally transmit L. major strains bearing 'null-scGal'-LPG PAMPs. We then asked whether scGal-LPG-mediated interactions were sufficient for PpapJ midgut survival by engineering Leishmania donovani, which normally express unsubstituted LPG, to express a 'PpapJ-optimal' scGal-LPG PAMP. Unexpectedly, these "L. major FV1-cloaked" L. donovani-SCG lines remained unable to survive within PpapJ flies. These studies establish that midgut survival of L. major in PpapJ flies is exquisitely sensitive to the scGal-LPG PAMP, requiring a specific 'mono-scGal' pattern. However, failure of 'mono-scGal' L. donovani-SCG lines to survive in selective PpapJ flies suggests a requirement for an additional, as yet unidentified L. major-specific parasite factor(s). The interplay of the LPG PAMP and additional factor(s) with sand fly midgut receptors may determine whether a given sand fly host is "selective" or "permissive", with important consequences to both disease transmission and the natural co-evolution of sand flies and Leishmania.

Selectively De-animating and Stabilizing Videos

DTIC Science & Technology

2014-12-11

unexpectedly engaging. They are now widely seen in major online newspapers, magazines, advertising and retail websites. Our cinemagraph examples can be seen...total, we seek a labeling that minimizes ∑ p1,p2 Φ(p1, p2, λ1, λ2) (3.11) CHAPTER 3. SELECTIVELY DE-ANIMATING VIDEOS 26 Model K Model S Beer Glass...Our next four examples are seamlessly looping cinemagraphs (Figure 3.6). Beer and Glass: We have generated two cinemagraphs that immobilize glassware

Irian Jaya earthquake and tsunami cause serious damage

NASA Astrophysics Data System (ADS)

Imamura, Fumihiko; Subandono, D.; Watson, G.; Moore, A.; Takahashi, T.; Matsutomi, H.; Hidayat, R.

On February 17,1996, at 0559 UT, a major earthquake with moment magnitude (Mw) 7.9 killed 107 people and caused major damage at Biak Island, 30-40 km southwest of the earthquake's epicenter (Figures 1 and 2). A devastating tsunami washed away all of the houses at Korim, a small village located in a narrow bay facing directly towards the incoming wave, and it left behind clear evidence of sand erosion and deposition that indicated how far the tsunami advanced. An unexpectedly large tsunami run-up of 7.7 m was measured at Wardo in western Biak, which faces away from the primary tsunami source. This high run-up may have been caused by a local submarine landslide.

Advances in Understanding the Fate and Effects of Oil from Accidental Spills in the United States Beginning with the Exxon Valdez.

PubMed

Short, Jeffrey W

2017-07-01

Scientific studies of the environmental effects of oil spills in the United States have produced a steady stream of unexpected discoveries countering prior and often simplistic assumptions. In this brief review, I present how major discoveries from scientific studies of oil spill effects on marine ecosystems and environments, beginning with the 1989 Exxon Valdez, have led to a more informed appreciation for the complexity and the severity of the damage that major spills can do to marine ecosystems and to an increasing recognition that our ability to evaluate those damages is very limited, resulting in a structural bias toward underestimation of adverse environmental effects.

The Role of the Counterfactually Satisfied Desire in the Lag between False-Belief and False-Emotion Attributions in Children Aged 4-7

ERIC Educational Resources Information Center

Bradmetz, Joel; Schneider, Roland

2004-01-01

A robust lag was evidenced between the attribution to an individual of a false belief about the world and the attribution of the false emotion associated with this false belief (Bradmetz & Schneider, 1999). This lag was unexpected in the frame of current theories of mind which consider that emotion has a rational cognitive basis. The present paper…

Dualities of fields and strings

NASA Astrophysics Data System (ADS)

Polchinski, Joseph

2017-08-01

Duality, the equivalence between seemingly distinct quantum systems, is a curious property that has been known for at least three quarters of a century. In the past two decades it has played a central role in mapping out the structure of theoretical physics. I discuss the unexpected connections that have been revealed among quantum field theories and string theories. Written for a special issue of Studies in History and Philosophy of Modern Physics.

Workplace mobbing and bystanders' helping behaviour towards victims: the role of gender, perceived responsibility and anticipated stigma by association.

PubMed

Mulder, Roelie; Pouwelse, Mieneke; Lodewijkx, Hein; Bolman, Catherine

2014-08-01

We examined victims' perceived responsibility and bystanders' anticipated risk of being victimized themselves when others associate them with the victim (stigma by association, SBA) as possible antecedents of bystanders' helping behaviour towards a victim of workplace mobbing, and explored the effects of gender. Guided by the attribution model of social conduct (Weiner, 2006), a 2 × 2 vignette experiment was conducted. Participants were Dutch regional government employees (N = 161). Path analyses generally supported the hypotheses, but showed different results for women and men. In the strong (Vs. weak) responsibility condition, women reported less sympathy and more anger and men only more anger, which resulted in lower helping intention. Additionally, for men the results showed an unexpected direct positive effect of responsibility on helping intention. Furthermore, in the strong SBA condition, women and men reported more fear and men, unexpectedly, more anger. Consequently, helping intention decreased. The findings on gender are discussed in the context of social role theory, gender and emotion. Our findings suggest that to prevent and tackle mobbing, organizations and professionals should be aware of the attributional and emotional processes and gender differences in bystanders' helping behaviour. © 2013 International Union of Psychological Science.

Effects of hydrostatic pressure on yeasts isolated from deep-sea hydrothermal vents.

PubMed

Burgaud, Gaëtan; Hué, Nguyen Thi Minh; Arzur, Danielle; Coton, Monika; Perrier-Cornet, Jean-Marie; Jebbar, Mohamed; Barbier, Georges

2015-11-01

Hydrostatic pressure plays a significant role in the distribution of life in the biosphere. Knowledge of deep-sea piezotolerant and (hyper)piezophilic bacteria and archaea diversity has been well documented, along with their specific adaptations to cope with high hydrostatic pressure (HHP). Recent investigations of deep-sea microbial community compositions have shown unexpected micro-eukaryotic communities, mainly dominated by fungi. Molecular methods such as next-generation sequencing have been used for SSU rRNA gene sequencing to reveal fungal taxa. Currently, a difficult but fascinating challenge for marine mycologists is to create deep-sea marine fungus culture collections and assess their ability to cope with pressure. Indeed, although there is no universal genetic marker for piezoresistance, physiological analyses provide concrete relevant data for estimating their adaptations and understanding the role of fungal communities in the abyss. The present study investigated morphological and physiological responses of fungi to HHP using a collection of deep-sea yeasts as a model. The aim was to determine whether deep-sea yeasts were able to tolerate different HHP and if they were metabolically active. Here we report an unexpected taxonomic-based dichotomic response to pressure with piezosensitve ascomycetes and piezotolerant basidiomycetes, and distinct morphological switches triggered by pressure for certain strains. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Simultaneous Downregulation of MTHFR and COMT in Switchgrass Affects Plant Performance and Induces Lesion-Mimic Cell Death.

PubMed

Liu, Sijia; Fu, Chunxiang; Gou, Jiqing; Sun, Liang; Huhman, David; Zhang, Yunwei; Wang, Zeng-Yu

2017-01-01

Switchgrass ( Panicum virgatum ) has been developed into a model lignocellulosic bioenergy crop. Downregulation of caffeic acid O -methyltransferase (COMT), a key enzyme in lignin biosynthesis, has been shown to alter lignification and increase biofuel yield in switchgrass. Methylenetetrahydrofolate reductase (MTHFR) mediates C1 metabolism and provides methyl units consumed by COMT. It was predicted that co-silencing of MTHFR and COMT would impact lignification even more than either of the single genes. However, our results showed that strong downregulation of MTHFR in a COMT -deficient background led to altered plant growth and development, but no significant change in lignin content or composition was found when compared with COMT plants. Another unexpected finding was that the double MTHFR/COMT downregulated plants showed a novel lesion-mimic leaf phenotype. Molecular analyses revealed that the lesion-mimic phenotype was caused by the synergistic effect of MTHFR and COMT genes, with MTHFR playing a predominant role. Microarray analysis showed significant induction of genes related to oxidative and defense responses. The results demonstrated the lack of additive effects of MTHFR and COMT on lignification. Furthermore, this research revealed an unexpected role of the two genes in the modulation of lesion-mimic cell death as well as their synergistic effects on agronomic performance.

Simultaneous Downregulation of MTHFR and COMT in Switchgrass Affects Plant Performance and Induces Lesion-Mimic Cell Death

PubMed Central

Liu, Sijia; Fu, Chunxiang; Gou, Jiqing; Sun, Liang; Huhman, David; Zhang, Yunwei; Wang, Zeng-Yu

2017-01-01

Switchgrass (Panicum virgatum) has been developed into a model lignocellulosic bioenergy crop. Downregulation of caffeic acid O-methyltransferase (COMT), a key enzyme in lignin biosynthesis, has been shown to alter lignification and increase biofuel yield in switchgrass. Methylenetetrahydrofolate reductase (MTHFR) mediates C1 metabolism and provides methyl units consumed by COMT. It was predicted that co-silencing of MTHFR and COMT would impact lignification even more than either of the single genes. However, our results showed that strong downregulation of MTHFR in a COMT-deficient background led to altered plant growth and development, but no significant change in lignin content or composition was found when compared with COMT plants. Another unexpected finding was that the double MTHFR/COMT downregulated plants showed a novel lesion-mimic leaf phenotype. Molecular analyses revealed that the lesion-mimic phenotype was caused by the synergistic effect of MTHFR and COMT genes, with MTHFR playing a predominant role. Microarray analysis showed significant induction of genes related to oxidative and defense responses. The results demonstrated the lack of additive effects of MTHFR and COMT on lignification. Furthermore, this research revealed an unexpected role of the two genes in the modulation of lesion-mimic cell death as well as their synergistic effects on agronomic performance. PMID:28676804

From unwitnessed fatality to witnessed rescue: Nonpharmacologic interventions in sudden unexpected death in epilepsy.

PubMed

Rugg-Gunn, Fergus; Duncan, John; Hjalgrim, Helle; Seyal, Masud; Bateman, Lisa

2016-01-01

Sudden unexpected death in epilepsy (SUDEP) risk reduction remains a critical aim in epilepsy care. To date, only aggressive medical and surgical efforts to control seizures have been demonstrated to be of benefit. Incomplete understanding of SUDEP mechanisms limits the development of more specific interventions. Periictal cardiorespiratory dysfunction is implicated in SUDEP; postictal electroencephalography (EEG) suppression, coma, and immobility may also play a role. Nocturnal supervision is protective against SUDEP, presumably by permitting intervention in the case of a life-threatening event. Resuscitative efforts were implemented promptly in near-SUDEP cases but delayed in SUDEP deaths in the Mortality in Epilepsy Monitoring Unit Study (MORTEMUS) study. Nursing interventions--including repositioning, oral suctioning, and oxygen administration--reduce seizure duration, respiratory dysfunction, and EEG suppression in the epilepsy monitoring unit (EMU), but have not been studied in outpatients. Cardiac pacemakers or cardioverter-defibrillator devices may be of benefit in a few select individuals. A role for implantable neurostimulators has not yet been established. Seizure detection devices, including those that monitor generalized tonic-clonic seizure-associated movements or cardiorespiratory parameters, may provide a means to permit timely periictal intervention. However, these and other devices, such as antisuffocation pillows, have not been adequately investigated with respect to SUDEP prevention. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Jazz musicians reveal role of expectancy in human creativity.

PubMed

Przysinda, Emily; Zeng, Tima; Maves, Kellyn; Arkin, Cameron; Loui, Psyche

2017-12-01

Creativity has been defined as the ability to produce work that is novel, high in quality, and appropriate to an audience. While the nature of the creative process is under debate, many believe that creativity relies on real-time combinations of known neural and cognitive processes. One useful model of creativity comes from musical improvisation, such as in jazz, in which musicians spontaneously create novel sound sequences. Here we use jazz musicians to test the hypothesis that individuals with training in musical improvisation, which entails creative generation of musical ideas, might process expectancy differently. We compare jazz improvisers, non-improvising musicians, and non-musicians in the domain-general task of divergent thinking, as well as the musical task of preference ratings for chord progressions that vary in expectation while EEGs were recorded. Behavioral results showed for the first time that jazz musicians preferred unexpected chord progressions. ERP results showed that unexpected stimuli elicited larger early and mid-latency ERP responses (ERAN and P3b), followed by smaller long-latency responses (Late Positivity Potential) in jazz musicians. The amplitudes of these ERP components were significantly correlated with behavioral measures of fluency and originality on the divergent thinking task. Together, results highlight the role of expectancy in creativity. Copyright © 2017 Elsevier Inc. All rights reserved.

Using Role-Playing Games to Teach Astronomy: An Evaluation

NASA Astrophysics Data System (ADS)

Francis, Paul

Since 1998, I've been experimenting with the use of role-playing games to teach astronomy. Students play the role of competing teams of researchers, racing to solve some astrophysical mystery. In this article, I review what has been learned from using these games around the world over the last eight years. The most common problem encountered is a tendency for students to become overly political. An unexpected benefit of these games is the boost that they give to student self- confidence. Overall, they seem to work well with a wide range of students, ranging from ninth grade to graduate school, and students exposed to this game comment repeatedly on how the games changed their attitudes toward the scientific process.

Chronic Toxic Metal Exposure and Cardiovascular Disease: Mechanisms of Risk and Emerging Role of Chelation Therapy.

PubMed

Aneni, Ehimen C; Escolar, Esteban; Lamas, Gervasio A

2016-12-01

Over the last few decades, there has been a growing body of epidemiologic evidence linking chronic toxic metal exposure to cardiovascular disease-related morbidity and mortality. The recent and unexpectedly positive findings from a randomized, double-blind, multicenter trial of metal chelation for the secondary prevention of atherosclerotic cardiovascular disease (Trial to Assess Chelation Therapy (TACT)) have focused the discussion on the role of chronic exposure to toxic metals in the development and propagation of cardiovascular disease and the role of toxic metal chelation therapy in the secondary prevention of cardiovascular disease. This review summarizes the most recent evidence linking chronic toxic metal exposure to cardiovascular disease and examines the findings of TACT.

The importance of working memory for school achievement in primary school children with intellectual or learning disabilities.

PubMed

Maehler, Claudia; Schuchardt, Kirsten

2016-11-01

Given the well-known relation between intelligence and school achievement we expect children with normal intelligence to perform well at school and those with intelligence deficits to meet learning problems. But, contrary to these expectations, some children do not perform according to these predictions: children with normal intelligence but sub-average school achievement and children with lower intelligence but average success at school. Yet, it is an open question how the unexpected failure or success can be explained. This study examined the role of working memory sensu Baddeley (1986) for school achievement, especially for unexpected failure or success. An extensive working memory battery with a total of 14 tasks for the phonological loop, the visual-spatial sketchpad and central executive skills was presented in individual sessions to four groups of children differing in IQ (normal vs. low) and school success (good vs. poor). Results reveal that children with sub-average school achievement showed deficits in working memory functioning, irrespective of intelligence. By contrast, children with regular school achievement did not show deficits in working memory, again irrespective of intelligence. Therefore working memory should be considered an important predictor of academic success that can lead both to unexpected overachievement and failure at school. Individual working memory competencies should be taken into account with regard to diagnosis and intervention for children with learning problems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fragile X Mental Retardation Protein Restricts Small Dye Iontophoresis Entry into Central Neurons.

PubMed

Kennedy, Tyler; Broadie, Kendal

2017-10-11

Fragile X mental retardation protein (FMRP) loss causes Fragile X syndrome (FXS), a major disorder characterized by autism, intellectual disability, hyperactivity, and seizures. FMRP is both an RNA- and channel-binding regulator, with critical roles in neural circuit formation and function. However, it remains unclear how these FMRP activities relate to each other and how dysfunction in their absence underlies FXS neurological symptoms. In testing circuit level defects in the Drosophila FXS model, we discovered a completely unexpected and highly robust neuronal dye iontophoresis phenotype in the well mapped giant fiber (GF) circuit. Controlled dye injection into the GF interneuron results in a dramatic increase in dye uptake in neurons lacking FMRP. Transgenic wild-type FMRP reintroduction rescues the mutant defect, demonstrating a specific FMRP requirement. This phenotype affects only small dyes, but is independent of dye charge polarity. Surprisingly, the elevated dye iontophoresis persists in shaking B mutants that eliminate gap junctions and dye coupling among GF circuit neurons. We therefore used a wide range of manipulations to investigate the dye uptake defect, including timed injection series, pharmacology and ion replacement, and optogenetic activity studies. The results show that FMRP strongly limits the rate of dye entry via a cytosolic mechanism. This study reveals an unexpected new phenotype in a physical property of central neurons lacking FMRP that could underlie aspects of FXS disruption of neural function. SIGNIFICANCE STATEMENT FXS is a leading heritable cause of intellectual disability and autism spectrum disorders. Although researchers established the causal link with FMRP loss >;25 years ago, studies continue to reveal diverse FMRP functions. The Drosophila FXS model is key to discovering new FMRP roles, because of its genetic malleability and individually identified neuron maps. Taking advantage of a well characterized Drosophila neural circuit, we discovered that neurons lacking FMRP take up dramatically more current-injected small dye. After examining many neuronal properties, we determined that this dye defect is cytoplasmic and occurs due to a highly elevated dye iontophoresis rate. We also report several new factors affecting neuron dye uptake. Understanding how FMRP regulates iontophoresis should reveal new molecular factors underpinning FXS dysfunction. Copyright © 2017 the authors 0270-6474/17/379844-15$15.00/0.

Fungal diversity in deep-sea sediments associated with asphalt seeps at the Sao Paulo Plateau

NASA Astrophysics Data System (ADS)

Nagano, Yuriko; Miura, Toshiko; Nishi, Shinro; Lima, Andre O.; Nakayama, Cristina; Pellizari, Vivian H.; Fujikura, Katsunori

2017-12-01

We investigated the fungal diversity in a total of 20 deep-sea sediment samples (of which 14 samples were associated with natural asphalt seeps and 6 samples were not associated) collected from two different sites at the Sao Paulo Plateau off Brazil by Ion Torrent PGM targeting ITS region of ribosomal RNA. Our results suggest that diverse fungi (113 operational taxonomic units (OTUs) based on clustering at 97% sequence similarity assigned into 9 classes and 31 genus) are present in deep-sea sediment samples collected at the Sao Paulo Plateau, dominated by Ascomycota (74.3%), followed by Basidiomycota (11.5%), unidentified fungi (7.1%), and sequences with no affiliation to any organisms in the public database (7.1%). However, it was revealed that only three species, namely Penicillium sp., Cadophora malorum and Rhodosporidium diobovatum, were dominant, with the majority of OTUs remaining a minor community. Unexpectedly, there was no significant difference in major fungal community structure between the asphalt seep and non-asphalt seep sites, despite the presence of mass hydrocarbon deposits and the high amount of macro organisms surrounding the asphalt seeps. However, there were some differences in the minor fungal communities, with possible asphalt degrading fungi present specifically in the asphalt seep sites. In contrast, some differences were found between the two different sampling sites. Classification of OTUs revealed that only 47 (41.6%) fungal OTUs exhibited >97% sequence similarity, in comparison with pre-existing ITS sequences in public databases, indicating that a majority of deep-sea inhabiting fungal taxa still remain undescribed. Although our knowledge on fungi and their role in deep-sea environments is still limited and scarce, this study increases our understanding of fungal diversity and community structure in deep-sea environments.

Unexpected Hospitalisations at a 23-Hour Observation Unit in a Paediatric Emergency Department of Northern India

PubMed Central

Mahajan, Vidushi; Arora, Sumant; Kaur, Tarundeep; Gupta, Sorab; Guglani, Vishal

2013-01-01

Background: The 23-hour Observation Unit (OU) is a novel and an effective means for tackling overcrowding in busy Paediatric Emergency Departments (PED) worldwide. However, unexpected hospitalisations in the OU involve transfer of care and they reduce the efficiency of the OU. Hence, we aimed to study the presenting diagnoses which were responsible for the unexpected hospitalisations in a 23-hour OU. Methods and Design: A prospective cohort study Setting: The PED at a tertiary care teaching hospital. Duration: 15th Feb-15th March 2011. Protocol: Consecutive children were triaged at presentation to the PED, according to the WHO paediatric emergency triage algorithm. Those who were transferred to the 23-hour OU, were further followed up for duration of the stay, the hospital course, and the outcome (discharge/hospitalisation). Results: Three hundred (228 males, 72 females) consecutive children who attended the PED over one month were enrolled. All the children, at presentation, were triaged by the medical intern/s who was/were posted in the PED, and they were crosschecked by a PED consultant. A majority (55%, n=165) of the children were triaged as non-urgent, 32% (n=97) as priority and 13% (n=38) as emergent. Out of the 300 children, 173(58%) were transferred to the 23-hour OU. Of these, 16 (9.1%) required unexpected hospitalisations. The children who required hospitalisations had the following diagnoses: bronchiolitis (4), bronchopneumonia (4), seizure (2), viral hepatitis (2), high fever (1), bronchial asthma (1), severe anaemia (1), and urticaria (1). The mean duration of the stay in the OU was 19 hours for those who needed hospitalisation, as against 13 hours for those who were discharged from the OU. Conclusion: The children with respiratory complaints (bronchiolitis and bronchopneumonia) need frequent monitoring in the 23-hour OU, as they have high hospitalisation rates in the OU. PMID:23998079

Remarkable effects of disorder on superconductivity of single atomic layers of lead on silicon

NASA Astrophysics Data System (ADS)

Brun, Christophe

2015-03-01

It is well known that conventional superconductivity is very robust against non-magnetic disorder. Nevertheless for thin and ultrathin films the structural properties play a major role in determining the superconducting properties, through a subtle interplay between disorder and Coulomb interactions. Unexpectedly, in 2010 superconductivity was discovered in single atomic layers of lead and indium grown on silicon substrate using scanning tunneling spectroscopy and confirmed later on by macroscopic transport measurements. Such well-controlled and tunable crystalline monolayers are ideal systems for studying the influence of various kinds of structural defects on the superconducting properties at the atomic and mesoscopic scale. In particular, Pb monolayers offer the opportunity of probing new effects of disorder because not only superconductivity is 2D but also the electronic wave functions are 2D. Our study of two Pb monolayers of different crystal structures by very-low temperature STM (300 mK) under magnetic field reveals unexpected results involving new spatial spectroscopic variations. Our results show that although the sheet resistance of the Pb monolayers is much below the resistance quantum, strong non-BCS corrections appear leading to peak heights fluctuations in the dI/dV tunneling spectra at a spatial scale much smaller than the superconducting coherence length. Furthermore, strong local evidence of the signature of Rashba effect on the superconductivity of the Pb/Si(111) monolayer is revealed through filling of in gap states and local spatial variations of this filling. Finally the nature of vortices in a monolayer is found to be very sensitive to the properties of step edges areas. This work was supported by University Pierre et Marie Curie UPMC `Emergence' project, French ANR Project `ElectroVortex,' ANR-QuDec and Templeton Foundation (40381), ARO (W911NF-13-1-0431) and CNRS PICS funds. Partial funding by US-DOE Grant DE-AC02-07CH1.

Influence of gait speed on stability: recovery from anterior slips and compensatory stepping.

PubMed

Bhatt, T; Wening, J D; Pai, Y-C

2005-02-01

Falls precipitated by slipping are a major health concern, with the majority of all slip-related falls occurring during gait. Recent evidence shows that a faster and/or more anteriorly positioned center of mass (COM) is more stable against backward balance loss, and that compensatory stepping is the key to recovering stability upon balance loss. The purposes of this paper were to determine whether walking speed affected gait stability for backward balance loss at slip onset and touchdown of compensatory stepping, and whether compensatory stepping response resembled the regular gait pattern. Forty-seven young subjects were slipped unexpectedly either at a self-selected fast, natural or slow speed. Speed-related differences in stability at slip onset and touchdown of the subsequent compensatory step were analyzed using the COM position-velocity state. The results indicate that gait speed highly correlated with stability against backward balance loss at slip onset. The low COM velocity of the slow group was not sufficiently compensated for by a more anteriorly positioned COM associated with a shorter step length at slip onset. At touchdown of the compensatory step, the speed-related differences in stability diminished, due to the continued advantage of anterior COM positioning from a short compensatory step retained by the slow group, coupled with an increase in COM velocity. Compensatory step length and relative COM position altered as a function of gait speed, indicating the motor program for gait regulation may play a role in modulating the compensatory step.

Inactivation of the Major Hemolysin Gene Influences Expression of the Nonribosomal Peptide Synthetase Gene swrA in the Insect Pathogen Serratia sp. Strain SCBI

PubMed Central

Petersen, Lauren M.; LaCourse, Kaitlyn; Schöner, Tim A.; Bode, Helge

2017-01-01

ABSTRACT Hemolysins are important virulence factors for many bacterial pathogens, including Serratia marcescens. The role of the major hemolysin gene in the insect pathogen Serratia sp. strain SCBI was investigated using both forward and reverse-genetics approaches. Introduction of the major hemolysin gene into Escherichia coli resulted in a gain of both virulence and hemolytic activity. Inactivation of this hemolysin in Serratia sp. SCBI resulted in a loss of hemolysis but did not attenuate insecticidal activity. Unexpectedly, inactivation of the hemolysin gene in Serratia sp. SCBI resulted in significantly increased motility and increased antimicrobial activity. Reverse transcription-quantitative PCR (qRT-PCR) analysis of mutants with a disrupted hemolysin gene showed a dramatic increase in mRNA levels of a nonribosomal peptide synthetase gene, swrA, which produces the surfactant serrawettin W2. Mutation of the swrA gene in Serratia sp. SCBI resulted in highly varied antibiotic activity, motility, virulence, and hemolysis phenotypes that were dependent on the site of disruption within this 17.75-kb gene. When introduced into E. coli, swrA increases rates of motility and confers antimicrobial activity. While it is unclear how inactivation of the major hemolysin gene influences the expression of swrA, these results suggest that swrA plays an important role in motility and antimicrobial activity in Serratia sp. SCBI. IMPORTANCE The opportunistic Gram-negative bacteria of the genus Serratia are widespread in the environment and can cause human illness. A comparative genomics analysis between Serratia marcescens and a new Serratia species from South Africa, termed Serratia sp. strain SCBI, shows that these two organisms are closely related but differ in pathogenesis. S. marcescens kills Caenorhabditis nematodes, while Serratia sp. SCBI is not harmful and forms a beneficial association with them. This distinction presented the opportunity to investigate potential differences in regulation of common virulence mechanisms between these two species. With the emergence of antibiotic-resistant microorganisms, there is a widespread need to understand the regulation of pathogenesis. The significance of this study is the presentation of evidence for cross-pathway regulation of virulence factors and how the elimination of one mechanism may be compensated for by the upregulation of others. PMID:28784817

Inactivation of the Major Hemolysin Gene Influences Expression of the Nonribosomal Peptide Synthetase Gene swrA in the Insect Pathogen Serratia sp. Strain SCBI.

PubMed

Petersen, Lauren M; LaCourse, Kaitlyn; Schöner, Tim A; Bode, Helge; Tisa, Louis S

2017-11-01

Hemolysins are important virulence factors for many bacterial pathogens, including Serratia marcescens The role of the major hemolysin gene in the insect pathogen Serratia sp. strain SCBI was investigated using both forward and reverse-genetics approaches. Introduction of the major hemolysin gene into Escherichia coli resulted in a gain of both virulence and hemolytic activity. Inactivation of this hemolysin in Serratia sp. SCBI resulted in a loss of hemolysis but did not attenuate insecticidal activity. Unexpectedly, inactivation of the hemolysin gene in Serratia sp. SCBI resulted in significantly increased motility and increased antimicrobial activity. Reverse transcription-quantitative PCR (qRT-PCR) analysis of mutants with a disrupted hemolysin gene showed a dramatic increase in mRNA levels of a nonribosomal peptide synthetase gene, swrA , which produces the surfactant serrawettin W2. Mutation of the swrA gene in Serratia sp. SCBI resulted in highly varied antibiotic activity, motility, virulence, and hemolysis phenotypes that were dependent on the site of disruption within this 17.75-kb gene. When introduced into E. coli , swrA increases rates of motility and confers antimicrobial activity. While it is unclear how inactivation of the major hemolysin gene influences the expression of swrA , these results suggest that swrA plays an important role in motility and antimicrobial activity in Serratia sp. SCBI. IMPORTANCE The opportunistic Gram-negative bacteria of the genus Serratia are widespread in the environment and can cause human illness. A comparative genomics analysis between Serratia marcescens and a new Serratia species from South Africa, termed Serratia sp. strain SCBI, shows that these two organisms are closely related but differ in pathogenesis. S. marcescens kills Caenorhabditis nematodes, while Serratia sp. SCBI is not harmful and forms a beneficial association with them. This distinction presented the opportunity to investigate potential differences in regulation of common virulence mechanisms between these two species. With the emergence of antibiotic-resistant microorganisms, there is a widespread need to understand the regulation of pathogenesis. The significance of this study is the presentation of evidence for cross-pathway regulation of virulence factors and how the elimination of one mechanism may be compensated for by the upregulation of others. Copyright © 2017 American Society for Microbiology.

Development of New Therapeutics Targeting Biofilm Formation by the Opportunistic Pulmonary Pathogens Pseudomonas aeruginosa and Aspergillus Fumigatus

DTIC Science & Technology

2017-10-01

antibacterial activity . The unexpected departure of PDF Perrin Baker Page 26 of 36 in early June 2017 and the delay in recruiting his replacement...characterize the ability of recombinant GH enzymes to enhance the activity of antimicrobial agents against PA and AF in vitro (2) Perform...FOR YEAR 1: Specific Aim 1: To characterize the ability of the hydrolases to enhance the activity of antimicrobial agents in vitro. Major Task 1

Exposure to sibutramine during pregnancy

PubMed Central

Garcia-Bournissen, Facundo; Shrim, Alon; Koren, Gideon

2007-01-01

QUESTION One of my patients who was taking sibutramine to lose weight found out that she had unexpectedly conceived. The medication was stopped as soon as she found out, about 5 weeks into the pregnancy. Is the baby at risk? Should the pregnancy be aborted? ANSWER No data to date suggest that involuntary exposure to sibutramine during pregnancy carries major risk of congenital malformations. Nevertheless, this medicationshould be avoided whenever possible during pregnancy, as there is little information on its effects. PMID:17872638

Avoiding (or fixing) problems with lawyers and courts.

PubMed

Reid, William H

2013-03-01

Clinicians who do work for attorneys and courts sometimes encounter problems in defining their roles, with access to records or litigants, with unexpected changes or additions to their tasks, or with being compensated for their work. Understanding the context of the forensic consultation and the processes commonly employed by lawyers and the judiciary can prevent many problems. Be cautious about "informal" requests from attorneys, particularly if they involve your own patients. Maintain solid business practices and make sure your role, relationship, and financial agreement with the person or entity retaining you are clear, ethical, and well documented before you begin work on a case.

[Health and disability in the elderly: old paradigms and future prospects].

PubMed

Liotta, Giuseppe; Mancinelli, Sandro; Scarcella, Paola; Pompei, Daniela; Mastromattei, Antonio; Cutini, Rita; Marazzi, Maria Cristina; Buonomo, Ersilia; Palombi, Leonardo; Gilardi, Francesco

2012-01-01

The projections regarding the ageing of the Italian population are cause for great concern; however, the ageing scenario may actually be interpreted in a more optimistic way. Theories formulated in the 80s envisaging a decline of mortality, morbidity and disability in the elderly are now confirmed and prefigure an unexpected decrease in disability rates in the elderly population. The aim of this review is to attempt to explain the reasons for this by analyzing the role played by the various determinants of health, in particular social isolation, which are likely to play an important role in the future as well.

A Conserved Asparagine Residue in Transmembrane Segment 1 (TM1) of Serotonin Transporter Dictates Chloride-coupled Neurotransmitter Transport*

PubMed Central

Henry, L. Keith; Iwamoto, Hideki; Field, Julie R.; Kaufmann, Kristian; Dawson, Eric S.; Jacobs, Miriam T.; Adams, Chelsea; Felts, Bruce; Zdravkovic, Igor; Armstrong, Vanessa; Combs, Steven; Solis, Ernesto; Rudnick, Gary; Noskov, Sergei Y.; DeFelice, Louis J.; Meiler, Jens; Blakely, Randy D.

2011-01-01

Na+- and Cl−-dependent uptake of neurotransmitters via transporters of the SLC6 family, including the human serotonin transporter (SLC6A4), is critical for efficient synaptic transmission. Although residues in the human serotonin transporter involved in direct Cl− coordination of human serotonin transport have been identified, the role of Cl− in the transport mechanism remains unclear. Through a combination of mutagenesis, chemical modification, substrate and charge flux measurements, and molecular modeling studies, we reveal an unexpected role for the highly conserved transmembrane segment 1 residue Asn-101 in coupling Cl− binding to concentrative neurotransmitter uptake. PMID:21730057

Unexpected Events Induce Motor Slowing via a Brain Mechanism for Action-Stopping with Global Suppressive Effects

PubMed Central

Aron, Adam R.

2013-01-01

When an unexpected event occurs in everyday life (e.g., a car honking), one experiences a slowing down of ongoing action (e.g., of walking into the street). Motor slowing following unexpected events is a ubiquitous phenomenon, both in laboratory experiments as well as such everyday situations, yet the underlying mechanism is unknown. We hypothesized that unexpected events recruit the same inhibition network in the brain as does complete cancellation of an action (i.e., action-stopping). Using electroencephalography and independent component analysis in humans, we show that a brain signature of successful outright action-stopping also exhibits activity following unexpected events, and more so in blocks with greater motor slowing. Further, using transcranial magnetic stimulation to measure corticospinal excitability, we show that an unexpected event has a global motor suppressive effect, just like outright action-stopping. Thus, unexpected events recruit a common mechanism with outright action-stopping, moreover with global suppressive effects. These findings imply that we can now leverage the considerable extant knowledge of the neural architecture and functional properties of the stopping system to better understand the processing of unexpected events, including perhaps how they induce distraction via global suppression. PMID:24259571

Robotic Exploration: The Role of Science Autonomy

NASA Technical Reports Server (NTRS)

Roush, Ted L.; DeVincenzi, D. (Technical Monitor)

2002-01-01

Historical mission operations have involved: (1) commands transmitted to the craft; (2) execution of commands; (3) return of scientific data; (4) evaluation of these data by scientists; and (5) recommendations for future mission activity by scientists. This cycle is repeated throughout the mission with command opportunities once or twice per day. For a rover, this historical cycle is not amenable to rapid long range traverses or rapid response to any novel or unexpected situations.

GABA regulates synaptic integration of newly generated neurons in the adult brain

NASA Astrophysics Data System (ADS)

Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

2006-02-01

Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

Live-cell Imaging Approaches for the Investigation of ...

EPA Pesticide Factsheets

BACKGROUND: Oxidant stress is arguably a universal feature in toxicology. Research studies on the role of oxidant stress induced by xenobiotic exposures have typically relied on the identification of damaged biomolecules using a variety of conventional biochemical and molecular techniques. However, there is increasing evidence that low-level exposure to a variety of toxicants dysregulates cellular physiology by interfering with redox-dependent processes.SCOPE OF REVIEW: The study of events involved in redox toxicology requires methodology capable of detecting transient modifications at relatively low signal strength. This article reviews the advantages of live-cell imaging for redox toxicology studies.MAJOR CONCLUSIONS: Toxicological studies with xenobiotics of supra-physiological reactivity require careful consideration when using fluorogenic sensors in order to avoid potential artifacts and false negatives. Fortunately, experiments conducted for the purpose of validating the use of these sensors in toxicological applications often yield unexpected insights into the mechanisms through which xenobiotic exposure induces oxidant stress.GENERAL SIGNIFICANCE: Live-cell imaging using a new generation of small molecule and genetically encoded fluorophores with excellent sensitivity and specificity affords unprecedented spatiotemporal resolution that is optimal for redox toxicology studies. This article is part of a Special Issue entitled Air Pollution, edited by Wenju

The strange case of a biofilm-forming strain of Pichia fermentans, which controls Monilinia brown rot on apple but is pathogenic on peach fruit.

PubMed

Giobbe, Sara; Marceddu, Salvatore; Scherm, Barbara; Zara, Giacomo; Mazzarello, Vittorio L; Budroni, Marilena; Migheli, Quirico

2007-12-01

A biofilm-forming strain of Pichia fermentans proved to be most effective in controlling brown rot on apple fruit when coinoculated into artificial wounds with a phytopathogenic isolate of Monilinia fructicola. Culture filtrates and autoclaved cells had no significant influence on the disease. When sprayed onto the apple fruit surface, this yeast formed a thin biofilm but failed to colonize the underlying tissues. When inoculated into wounds artificially inflicted to peach fruit or when sprayed onto the surface of peach fruit, the same strain showed an unexpected pathogenic behaviour, causing rapid decay of fruit tissues even in the absence of M. fructicola. Both optical and scanning electron microscopy were used to evaluate the pattern of fruit tissue colonization by P. fermentans. While on apple surface and within the apple wound the antagonist retained its yeast-like shape, colonization of peach fruit tissue was always characterized by a transition from budding growth to pseudohyphal growth. These results suggest that pseudohyphal growth plays a major role in governing the potential pathogenicity of P. fermentans, further emphasizing the importance of a thorough risk assessment for the safe use of any novel biocontrol agent.

Systematic Association of Genes to Phenotypes by Genome and Literature Mining

PubMed Central

Jensen, Lars J; Perez-Iratxeta, Carolina; Kaczanowski, Szymon; Hooper, Sean D; Andrade, Miguel A

2005-01-01

One of the major challenges of functional genomics is to unravel the connection between genotype and phenotype. So far no global analysis has attempted to explore those connections in the light of the large phenotypic variability seen in nature. Here, we use an unsupervised, systematic approach for associating genes and phenotypic characteristics that combines literature mining with comparative genome analysis. We first mine the MEDLINE literature database for terms that reflect phenotypic similarities of species. Subsequently we predict the likely genomic determinants: genes specifically present in the respective genomes. In a global analysis involving 92 prokaryotic genomes we retrieve 323 clusters containing a total of 2,700 significant gene–phenotype associations. Some clusters contain mostly known relationships, such as genes involved in motility or plant degradation, often with additional hypothetical proteins associated with those phenotypes. Other clusters comprise unexpected associations; for example, a group of terms related to food and spoilage is linked to genes predicted to be involved in bacterial food poisoning. Among the clusters, we observe an enrichment of pathogenicity-related associations, suggesting that the approach reveals many novel genes likely to play a role in infectious diseases. PMID:15799710

Applications of Fisher Information to the Management of Sustainable Environmental Systems

NASA Astrophysics Data System (ADS)

Mayer, Audrey L.; Pawlowski, Christopher; Fath, Brian D.; Cabezas, Heriberto

All organisms alter their surroundings, and humans now have the ability to affect environments at increasingly larger temporal and spatial scales. Indeed, mechanical and engineering advances of the twentieth century greatly enhanced the scale of human activities. Among these are the use and redistribution of natural resources. Unfortunately, these activities can have unexpected and unintended consequences. Environmental systems often respond to these activities with diminished or lost capacity of natural function. Fortunately, environmental management can play an important role in ameliorating these negative effects. The aim is to promote sustainable development, i.e., enrichment of the lives of the majority of people without seriously degrading the diversity and richness of the environment. However, the management tools themselves often fall prey to the same narrow levels of perspective that generated the negative conditions. The challenge is to develop a system-level index, one that indicates the organization and direction of ecological system dynamics. This index could detect when the system is changing its configuration to a new, perhaps less desirable, dynamic regime and may be incorporated into a sustainable management plan for the system. In this chapter, we demonstrate the use of Fisher information (FI) as such an environmental system index.

Testing neoclassical competitive market theory in the field

PubMed Central

List, John A.

2002-01-01

This study presents results from a pilot field experiment that tests predictions of competitive market theory. A major advantage of this particular field experimental design is that my laboratory is the marketplace: subjects are engaged in buying, selling, and trading activities whether I run an exchange experiment or am a passive observer. In this sense, I am gathering data in a natural environment while still maintaining the necessary control to execute a clean comparison between treatments. The main results of the study fall into two categories. First, the competitive model predicts reasonably well in some market treatments: the expected price and quantity levels are approximated in many market rounds. Second, the data suggest that market composition is important: buyer and seller experience levels impact not only the distribution of rents but also the overall level of rents captured. An unexpected result in this regard is that average market efficiency is lowest in markets that match experienced buyers and experienced sellers and highest when experienced buyers engage in bargaining with inexperienced sellers. Together, these results suggest that both market experience and market composition play an important role in the equilibrium discovery process. PMID:12432103

Hadron Collider Detectors

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

Incandela, J.R.

2000-03-07

Experiments are being prepared at the Fermilab Tevatron and the CERN Large Hadron Collider that promise to deliver extraordinary insights into the nature of spontaneous symmetry breaking, and the role of supersymmetry in the universe. This article reviews the goals, challenges, and designs of these experiments. The first hadron collider, the ISR at CERN, has to overcome two initial obstacles. The first was low luminosity, which steadily improved over time. The second was the broad angular spread of interesting events. In this regard Maurice Jacob noted (1): The answer is ... sophisticated detectors covering at least the whole central regionmore » (45{degree} {le} {theta} {le} 135{degree}) and full azimuth. This statement, while obvious today, reflects the major revelation of the ISR period that hadrons have partonic substructure. The result was an unexpectedly strong hadronic yield at large transverse momentum (p{sub T}). Partly because of this, the ISR missed the discovery of the J/{psi} and later missed the {Upsilon}. The ISR era was therefore somewhat less auspicious than it might have been. It did however make important contributions in areas such as jet production and charm excitation and it paved the way for the SPS collider, also at CERN.« less

Zinc sorption to three gram-negative bacteria: combined titration, modeling, and EXAFS study.

PubMed

Guiné, V; Spadini, L; Sarret, G; Muris, M; Delolme, C; Gaudet, J P; Martins, J M F

2006-03-15

The acid-base and Zn sorption properties of three bacteria, Cupriavidus metallidurans CH34, Pseudomonas putida ATCC12633, and Escherichia coli K12DH5alpha, were investigated through an original combination of extended X-ray absorption fine structure (EXAFS) spectroscopy and equilibrium titration studies. Acid-base titration curves of the three strains were fitted with a model accounting for three conceptual reactive sites: an acidic (carboxyl and/or phosphodiester), a neutral (phosphomonoester), and a basic (amine and/or hydroxyl) group. Calculated proton and Zn equilibrium constants and site densities compare with literature data. The nature of Zn binding sites was studied by EXAFS spectroscopy. Phosphoester, carboxyl, and unexpectedly sulfhydryl ligands were identified. Their proportions depended on Zn loading and bacterial strain and were consistent with the titration results. These findings were compared to the structure and site density of the major cell wall components. It appeared that the cumulated theoretical site density of these structures (<2 Zn nm(-2)) was much lower than the total site density of the investigated strains (16-56 Zn nm(-2)). These results suggest a dominant role of extracellular polymeric substances in Zn retention processes, although Zn binding to inner cell components cannot be excluded.

Heme exporter FLVCR is required for T cell development and peripheral survival.

PubMed

Philip, Mary; Funkhouser, Scott A; Chiu, Edison Y; Phelps, Susan R; Delrow, Jeffrey J; Cox, James; Fink, Pamela J; Abkowitz, Janis L

2015-02-15

All aerobic cells and organisms must synthesize heme from the amino acid glycine and the tricarboxylic acid cycle intermediate succinyl CoA for incorporation into hemoproteins, such as the cytochromes needed for oxidative phosphorylation. Most studies on heme regulation have been done in erythroid cells or hepatocytes; however, much less is known about heme metabolism in other cell types. The feline leukemia virus subgroup C receptor (FLVCR) is a 12-transmembrane domain surface protein that exports heme from cells, and it was shown to be required for erythroid development. In this article, we show that deletion of Flvcr in murine hematopoietic precursors caused a complete block in αβ T cell development at the CD4(+)CD8(+) double-positive stage, although other lymphoid lineages were not affected. Moreover, FLVCR was required for the proliferation and survival of peripheral CD4(+) and CD8(+) T cells. These studies identify a novel and unexpected role for FLVCR, a major facilitator superfamily metabolite transporter, in T cell development and suggest that heme metabolism is particularly important in the T lineage. Copyright © 2015 by The American Association of Immunologists, Inc.

Role of Clinical Endoscopy in Emphasizing Endoscope Disinfection

PubMed Central

Ryu, Ji Kon; Kim, Eun Young; Kwon, Kwang An; Choi, Il Ju

2015-01-01

Based on the unexpected Middle East respiratory syndrome (MERS) outbreak in Korea, it was established that the virus can spread easily, MERS exposure in hospitals carries an extreme risk for infection as well as mortality, and the sharing of information was essential for infection control. Although the incidence of exogenous infections related to contaminated endoscopes is very low, the majority of published outbreaks have been caused by various shortcomings in reprocessing procedures, including insufficient training or awareness. Ever since the inauguration of "Clinical Endoscopy" as an English-language journal of the Korean Society of Gastrointestinal Endoscopy in 2011, it has published several articles on disinfection of the endoscope and its accessories. Many Science Citation Index journals have also emphasized high-level disinfection of the gastrointestinal endoscope. Many papers have been produced specifically, since the outbreak of carbapenem-resistant Enterobacteriaceae in 2013. The recent review papers concluded that quality control is the most important issue among all the aspects of procedural care, including the efficiency of the gastrointestinal endoscopy unit and reprocessing room. Thorough reprocessing of endoscopes using high-level disinfection and sterilization methods may be essential for reducing the risk of infection. PMID:26473114

cGAS drives noncanonical-inflammasome activation in age-related macular degeneration.

PubMed

Kerur, Nagaraj; Fukuda, Shinichi; Banerjee, Daipayan; Kim, Younghee; Fu, Dongxu; Apicella, Ivana; Varshney, Akhil; Yasuma, Reo; Fowler, Benjamin J; Baghdasaryan, Elmira; Marion, Kenneth M; Huang, Xiwen; Yasuma, Tetsuhiro; Hirano, Yoshio; Serbulea, Vlad; Ambati, Meenakshi; Ambati, Vidya L; Kajiwara, Yuji; Ambati, Kameshwari; Hirahara, Shuichiro; Bastos-Carvalho, Ana; Ogura, Yuichiro; Terasaki, Hiroko; Oshika, Tetsuro; Kim, Kyung Bo; Hinton, David R; Leitinger, Norbert; Cambier, John C; Buxbaum, Joseph D; Kenney, M Cristina; Jazwinski, S Michal; Nagai, Hiroshi; Hara, Isao; West, A Phillip; Fitzgerald, Katherine A; Sadda, SriniVas R; Gelfand, Bradley D; Ambati, Jayakrishna

2018-01-01

Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, interferon-β, and cGAS levels were elevated in the RPE in human eyes with geographic atrophy. Collectively, these data highlight an unexpected role of cGAS in responding to mobile-element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial-damage-induced inflammasome activation, expand the immune-sensing repertoire of cGAS and caspase-4 to noninfectious human disease, and identify new potential targets for treatment of a major cause of blindness.

Small RNA-based feedforward loop with AND-gate logic regulates extrachromosomal DNA transfer in Salmonella.

PubMed

Papenfort, Kai; Espinosa, Elena; Casadesús, Josep; Vogel, Jörg

2015-08-25

Horizontal gene transfer via plasmid conjugation is a major driving force in microbial evolution but constitutes a complex process that requires synchronization with the physiological state of the host bacteria. Although several host transcription factors are known to regulate plasmid-borne transfer genes, RNA-based regulatory circuits for host-plasmid communication remain unknown. We describe a posttranscriptional mechanism whereby the Hfq-dependent small RNA, RprA, inhibits transfer of pSLT, the virulence plasmid of Salmonella enterica. RprA employs two separate seed-pairing domains to activate the mRNAs of both the sigma-factor σ(S) and the RicI protein, a previously uncharacterized membrane protein here shown to inhibit conjugation. Transcription of ricI requires σ(S) and, together, RprA and σ(S) orchestrate a coherent feedforward loop with AND-gate logic to tightly control the activation of RicI synthesis. RicI interacts with the conjugation apparatus protein TraV and limits plasmid transfer under membrane-damaging conditions. To our knowledge, this study reports the first small RNA-controlled feedforward loop relying on posttranscriptional activation of two independent targets and an unexpected role of the conserved RprA small RNA in controlling extrachromosomal DNA transfer.

Exploring learning content and knowledge transfer in baccalaureate nursing students using a hybrid mental health practice experience.

PubMed

Booth, Richard G; Scerbo, Christina Ko; Sinclair, Barbara; Hancock, Michele; Reid, David; Denomy, Eileen

2017-04-01

Little research has been completed exploring knowledge development and transfer from and between simulated and clinical practice settings in nurse education. This study sought to explore the content learned, and the knowledge transferred, in a hybrid mental health clinical course consisting of simulated and clinical setting experiences. A qualitative, interpretive descriptive study design. Clinical practice consisted of six 10-hour shifts in a clinical setting combined with six two-hour simulations. 12 baccalaureate nursing students enrolled in a compressed time frame program at a large, urban, Canadian university participated. Document analysis and a focus group were used to draw thematic representations of content and knowledge transfer between clinical environments (i.e., simulated and clinical settings) using the constant comparative data analysis technique. Four major themes arose: (a) professional nursing behaviors; (b) understanding of the mental health nursing role; (c) confidence gained in interview skills; and, (d) unexpected learning. Nurse educators should further explore the intermingling of simulation and clinical practice in terms of knowledge development and transfer with the goal of preparing students to function within the mental health nursing specialty. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel mouse model for sudden unexpected death in epilepsy (SUDEP): role of impaired adenosine clearance.

PubMed

Shen, Hai-Ying; Li, Tianfu; Boison, Detlev

2010-03-01

Sudden unexpected death in epilepsy (SUDEP) is a significant cause of mortality in people with epilepsy. Two postulated causes for SUDEP, cardiac and respiratory depression, can both be explained by overstimulation of adenosine receptors. We hypothesized that SUDEP is a consequence of a surge in adenosine as a result of prolonged seizures combined with deficient adenosine clearance; consequently, blockade of adenosine receptors should prevent SUDEP. Here we induced impaired adenosine clearance in adult mice by pharmacologic inhibition of the adenosine-removing enzymes, adenosine kinase and deaminase. Combination of impaired adenosine clearance with kainic acid-induced seizures triggered sudden death in all animals. Most importantly, the adenosine receptor antagonist caffeine, when given after seizure onset, increased survival from 23.75 +/- 1.35 min to 54.86 +/- 6.59 min (p < 0.01). Our data indicate that SUDEP is due to overactivation of adenosine receptors and that caffeine treatment after seizure onset might be beneficial.

Metal Cycling by Bacteria: Moving Electrons Around

ScienceCinema

Nealson, Ken

2017-12-09

About 20 years ago, Shewanella oneidensis MR-1 was isolated from a manganese-rich lack in upstate New York, and subsequently shown to utilize solid forms of oxidized manganese or iron as an electron acceptor. Recent studies of metal-reducing bacterial have unveiled a number of unexpected properties of microbes that have enlarged our view of microbes and their role(s) in natural ecosystems. For example, the processes of metal reduction themselves are fundamental to the carbon cycle in many lakes and sediments, where iron and manganese account for the major portion of organic carbon oxidation in many sediments. On more modest spatial scales, iron and manganese reduction can be linked to the oxidation of a wide variety of carbon compounds, many of them recalcitrant and/or toxic. One remarkable property of metal reducers is their ability to reduce solid, often highly crystalline substrates such as iron and manganese oxides and oxyhydroxides. It is now clear that this is done via the utilization of enzymes located on the outer wall of the bacteria - enzymes that apparently interact directly with these solid substrates. Molecular and genomic studies combined have revealed the genes and protoeins responsible for these activities, and many facets of the regulation. This talk focuses on the general features and properties of these remarkable organisms that seem to communicate via electron transfer across a wide variety of soluable, insoluable, and even "inert" substrates, and the way that these processes may be mechanistically linked.

A myogenic precursor cell that could contribute to regeneration in zebrafish and its similarity to the satellite cell.

PubMed

Siegel, Ashley L; Gurevich, David B; Currie, Peter D

2013-09-01

The cellular basis for mammalian muscle regeneration has been an area of intense investigation over recent decades. The consensus is that a specialized self-renewing stem cell, termed the satellite cell, plays a major role during the process of regeneration in amniotes. How broadly this mechanism is deployed within the vertebrate phylogeny remains an open question. A lack of information on the role of cells analogous to the satellite cell in other vertebrate systems is even more unexpected given the fact that satellite cells were first designated in frogs. An intriguing aspect of this debate is that a number of amphibia and many fish species exhibit epimorphic regenerative processes in specific tissues, whereby regeneration occurs by the dedifferentiation of the damaged tissue, without deploying specialized stem cell populations analogous to satellite cells. Hence, it is feasible that a cellular process completely distinct from that deployed during mammalian muscle regeneration could operate in species capable of epimorphic regeneration. In this minireview, we examine the evidence for the broad phylogenetic distribution of satellite cells. We conclude that, in the vertebrates examined so far, epimorphosis does not appear to be deployed during muscle regeneration, and that analogous cells expressing similar marker genes to satellite cells appear to be deployed during the regenerative process. However, the functional definition of these cells as self-renewing muscle stem cells remains a final hurdle to the definition of the satellite cell as a generic vertebrate cell type. © 2013 FEBS.

Involvement of T6 pili in biofilm formation by serotype M6 Streptococcus pyogenes.

PubMed

Kimura, Keiji Richard; Nakata, Masanobu; Sumitomo, Tomoko; Kreikemeyer, Bernd; Podbielski, Andreas; Terao, Yutaka; Kawabata, Shigetada

2012-02-01

The group A streptococcus (GAS) Streptococcus pyogenes is known to cause self-limiting purulent infections in humans. The role of GAS pili in host cell adhesion and biofilm formation is likely fundamental in early colonization. Pilus genes are found in the FCT (fibronectin-binding protein, collagen-binding protein, and trypsin-resistant antigen) genomic region, which has been classified into nine subtypes based on the diversity of gene content and nucleotide sequence. Several epidemiological studies have indicated that FCT type 1 strains, including serotype M6, produce large amounts of monospecies biofilm in vitro. We examined the direct involvement of pili in biofilm formation by serotype M6 clinical isolates. In the majority of tested strains, deletion of the tee6 gene encoding pilus shaft protein T6 compromised the ability to form biofilm on an abiotic surface. Deletion of the fctX and srtB genes, which encode pilus ancillary protein and class C pilus-associated sortase, respectively, also decreased biofilm formation by a representative strain. Unexpectedly, these mutant strains showed increased bacterial aggregation compared with that of the wild-type strain. When the entire FCT type 1 pilus region was ectopically expressed in serotype M1 strain SF370, biofilm formation was promoted and autoaggregation was inhibited. These findings indicate that assembled FCT type 1 pili contribute to biofilm formation and also function as attenuators of bacterial aggregation. Taken together, our results show the potential role of FCT type 1 pili in the pathogenesis of GAS infections.

Astylus atromaculatus (Coleoptera: Melyridae): abundance and role in pollen dispersal in Bt and non-Bt cotton in South Africa.

PubMed

Pierre, Jacqueline; Hofs, Jean-Luc

2010-10-01

In South Africa, modified Bt (Cry1 Ac) cotton cultivars and organic ones coexist. This raises the question of the risk of dissemination of genetically modified (GM) pollen to non-GM crops by visiting insects. We inventoried the flower-visiting insects in Bt and non-Bt cotton fields of the South African Highveld region and investigated their role in pollen dispersal. Their diversity and abundance varied slightly among sites, with Astylus atromaculatus as the predominant insect on both Bt and non-Bt cotton flowers. The other major flower-visiting species were Apis mellifera and solitary Apidae. No differences were found in the abundance of each taxum between Bt and non-Bt cotton except for Scoliidae and Nitidulidae, which were scarce overall (<0.5%) but more abundant on the non-Bt flowers in the central area of the field at one site. The pollen load on A. atromaculatus was as high as on Apis mellifera. Cage tests showed that A. atromaculatus can pollinate female cotton plants by transferring pollen from male donor plants. In the field, the flight range of this insect was generally short (25 m), but it can occasionally reach up to 200 m or even more. This study therefore highlights that A. atromaculatus, commonly regarded as a pest, could be an unexpected but efficient pollinator. Because its population density can be high, this species could mediate unwanted cotton pollen flow when distances between coexiting fields are not sufficient.

Lack of MyD88 protects the immunodeficient host against fatal lung inflammation triggered by the opportunistic bacteria Burkholderia cenocepacia.

PubMed

Ventura, Grasiella M de C; Balloy, Viviane; Ramphal, Reuben; Khun, Huot; Huerre, Michel; Ryffel, Bernhard; Plotkowski, Maria-Cristina M; Chignard, Michel; Si-Tahar, Mustapha

2009-07-01

Burkholderia cenocepacia is an opportunistic pathogen of major concern for cystic fibrosis patients as well as immunocompromised cancer patients and transplant recipients. The mechanisms by which B. cenocepacia triggers a rapid health deterioration of the susceptible host have yet to be characterized. TLR and their key signaling intermediate MyD88 play a central role in the detection of microbial molecular patterns and in the initiation of an effective immune response. We performed a study to better understand the role of TLR-MyD88 signaling in B. cenocepacia-induced pathogenesis in the immunocompromised host, using an experimental murine model. The time-course of several dynamic parameters, including animal survival, bacterial load, and secretion of critical inflammatory mediators, was compared in infected and immunosuppressed wild-type and MyD88(-/-) mice. Notably, when compared with wild-type mice, infected MyD88(-/-) animals displayed significantly reduced levels of inflammatory mediators (including KC, TNF-alpha, IL-6, MIP-2, and G-CSF) in blood and lung airspaces. Moreover, despite a higher transient bacterial load in the lungs, immunosuppressed mice deficient in MyD88 had an unexpected survival advantage. Finally, we showed that this B. cenocepacia-induced life-threatening infection of wild-type mice involved the proinflammatory cytokine TNF-alpha and could be prevented by corticosteroids. Altogether, our findings demonstrate that a MyD88-dependent pathway can critically contribute to a detrimental host inflammatory response that leads to fatal pneumonia.

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

Vasuri, Francesco; Capizzi, Elisa; Bellavista, Elena

Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive ({alpha}4 and {beta}1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28{alpha}{beta} regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical datamore » have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28{alpha}{beta}. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.« less

Interacting Physical and Biological Processes Affecting Nutrient Transport Through Human Dominated Landscapes

NASA Astrophysics Data System (ADS)

Finlay, J. C.

2015-12-01

Human activities increasingly dominate biogeochemical cycles of limiting nutrients on Earth. Urban and agricultural landscapes represent the largest sources of excess nutrients that drive water quality degradation. The physical structure of both urban and agricultural watersheds has been extensively modified, and these changes have large impacts on water and nutrient transport. Despite strong physical controls over nutrient transport in human dominated landscapes, biological processes play important roles in determining the fates of both nitrogen and phosphorus. This talk uses examples from research in urban and agricultural watersheds in the Midwestern USA to illustrate interactions of physical and biological controls over nutrient cycles that have shifted nitrogen (N) and phosphorus (P) sources and cycling in unexpected ways in response to management changes. In urban watersheds, efforts to improve water quality have been hindered by legacy sources of phosphorus added to storm water through transport to drainage systems by vegetation. Similarly, reductions in field erosion in agricultural watersheds have not led to major reductions in phosphorus transport, because of continued release of biological sources of P. Where management of phosphorus has been most effective in reducing eutrophication of lakes, decreases in N removal processes have led to long term increases in N concentration and transport. Together, these examples show important roles for biological processes affecting nutrient movement in highly modified landscapes. Consideration of the downstream physical and biological responses of management changes are thus critical toward identification of actions that will most effectively reduce excess nutrients watersheds and coastal zones.

Erythropoietin-mediated tissue protection: reducing collateral damage from the primary injury response.

PubMed

Brines, M; Cerami, A

2008-11-01

In its classic hormonal role, erythropoietin (EPO) is produced by the kidney and regulates the number of erythrocytes within the circulation to provide adequate tissue oxygenation. EPO also mediates other effects directed towards optimizing oxygen delivery to tissues, e.g. modulating regional blood flow and reducing blood loss by promoting thrombosis within damaged vessels. Over the past 15 years, many unexpected nonhaematopoietic functions of EPO have been identified. In these more recently appreciated nonhormonal roles, locally-produced EPO signals through a different receptor isoform and is a major molecular component of the injury response, in which it counteracts the effects of pro-inflammatory cytokines. Acutely, EPO prevents programmed cell death and reduces the development of secondary, pro-inflammatory cytokine-induced injury. Within a longer time frame, EPO provides trophic support to enable regeneration and healing. As the region immediately surrounding damage is typically relatively deficient in endogenous EPO, administration of recombinant EPO can provide increased tissue protection. However, effective use of EPO as therapy for tissue injury requires higher doses than for haematopoiesis, potentially triggering serious adverse effects. The identification of a tissue-protective receptor isoform has facilitated the engineering of nonhaematopoietic, tissue-protective EPO derivatives, e.g. carbamyl EPO, that avoid these complications. Recently, regions within the EPO molecule mediating tissue protection have been identified and this has enabled the development of potent tissue-protective peptides, including some mimicking EPO's tertiary structure but unrelated in primary sequence.

The effects of captivity survival training on mood, dissociation, PTSD symptoms, cognitive performance and stress hormones.

PubMed

Suurd Ralph, Cindy; Vartanian, Oshin; Lieberman, Harris R; Morgan, Charles A; Cheung, Bob

2017-07-01

In the Canadian Armed Forces (CAF), Conduct After Capture (CAC) training is a 4-day captivity survival course during which soldiers are exposed to increasing stress, and evaluated on their ability to accomplish military objectives. We hypothesized that: (a) compared to baseline, CAC training would cause significant, reversible perturbations in measures of psychological functioning and serum and salivary stress hormone levels relevant to models of stress hardiness and vulnerability; and (b) deviations from baseline would be maximal at the time point of most intense stress during training. CAF personnel were assessed at baseline, twice during training (immediately prior to a less challenging interrogation role-play scenario and again following another much more intense interrogation role-play scenario), and after completion of training. At each occasion, mood, fatigue, dissociation, PTSD symptoms, short-term and working memory, and salivary cortisol and dehydroepiandrosterone (DHEA) were assessed. As predicted, scores on all measures were degraded during CAC but recovered after completion of training, and almost all measures were most degraded at the more intense interrogation role-play scenario. Unexpectedly, memory performance was unaffected by training, suggesting that a short duration of intense stress might be insufficient for degrading it. Another unexpected finding was that mood assessed prior to training predicted successful completion of training, which bears important practical implications for increasing the success rate of training in similar environments. These results demonstrate that despite its relative brevity, CAC training nevertheless induces significant but reversible effects on psychological and physiological function-necessary preconditions for stress inoculation training. Copyright © 2017. Published by Elsevier B.V.

Systematic CRISPR-Cas9-Mediated Modifications of Plasmodium yoelii ApiAP2 Genes Reveal Functional Insights into Parasite Development

PubMed Central

Zhang, Cui; Li, Zhenkui; Cui, Huiting; Jiang, Yuanyuan; Yang, Zhenke; Wang, Xu; Gao, Han; Liu, Cong; Zhang, Shujia

2017-01-01

ABSTRACT Malaria parasites have a complex life cycle with multiple developmental stages in mosquito and vertebrate hosts, and different developmental stages express unique sets of genes. Unexpectedly, many transcription factors (TFs) commonly found in eukaryotic organisms are absent in malaria parasites; instead, a family of genes encoding proteins similar to the plant Apetala2 (ApiAP2) transcription factors is expanded in the parasites. Several malaria ApiAP2 genes have been shown to play a critical role in parasite development; however, the functions of the majority of the ApiAP2 genes remain to be elucidated. In particular, no study on the Plasmodium yoelii ApiAP2 (PyApiAP2) gene family has been reported so far. This study systematically investigated the functional roles of PyApiAP2 genes in parasite development. Twenty-four of the 26 PyApiAP2 genes were selected for disruption, and 12 were successfully knocked out using the clustered regularly interspaced short palindromic repeat–CRISPR-associated protein 9 (CRISPR-Cas9) method. The effects of gene knockout (KO) on parasite development in mouse and mosquito stages were evaluated. Ten of 12 successfully disrupted genes, including two genes that have not been functionally characterized in any Plasmodium species previously, were shown to be critical for P. yoelii development of sexual and mosquito stages. Additionally, seven of the genes were labeled for protein expression analysis, revealing important information supporting their functions. This study represents the first systematic functional characterization of the P. yoelii ApiAP2 gene family and discovers important insights on the roles of the ApiAP2 genes in parasite development. PMID:29233900

Complex Evolutionary Dynamics of Massively Expanded Chemosensory Receptor Families in an Extreme Generalist Chelicerate Herbivore.

PubMed

Ngoc, Phuong Cao Thi; Greenhalgh, Robert; Dermauw, Wannes; Rombauts, Stephane; Bajda, Sabina; Zhurov, Vladimir; Grbić, Miodrag; Van de Peer, Yves; Van Leeuwen, Thomas; Rouzé, Pierre; Clark, Richard M

2016-12-14

While mechanisms to detoxify plant produced, anti-herbivore compounds have been associated with plant host use by herbivores, less is known about the role of chemosensory perception in their life histories. This is especially true for generalists, including chelicerate herbivores that evolved herbivory independently from the more studied insect lineages. To shed light on chemosensory perception in a generalist herbivore, we characterized the chemosensory receptors (CRs) of the chelicerate two-spotted spider mite, Tetranychus urticae, an extreme generalist. Strikingly, T. urticae has more CRs than reported in any other arthropod to date. Including pseudogenes, 689 gustatory receptors were identified, as were 136 degenerin/Epithelial Na+ Channels (ENaCs) that have also been implicated as CRs in insects. The genomic distribution of T. urticae gustatory receptors indicates recurring bursts of lineage-specific proliferations, with the extent of receptor clusters reminiscent of those observed in the CR-rich genomes of vertebrates or C. elegans Although pseudogenization of many gustatory receptors within clusters suggests relaxed selection, a subset of receptors is expressed. Consistent with functions as CRs, the genomic distribution and expression of ENaCs in lineage-specific T. urticae expansions mirrors that observed for gustatory receptors. The expansion of ENaCs in T. urticae to > 3-fold that reported in other animals was unexpected, raising the possibility that ENaCs in T. urticae have been co-opted to fulfill a major role performed by unrelated CRs in other animals. More broadly, our findings suggest an elaborate role for chemosensory perception in generalist herbivores that are of key ecological and agricultural importance. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Centrally Administered Ghrelin Acutely Influences Food Choice in Rodents

PubMed Central

Schéle, Erik; Bake, Tina; Rabasa, Cristina; Dickson, Suzanne L.

2016-01-01

We sought to determine whether the orexigenic hormone, ghrelin, is involved in the intrinsic regulation of food choice in rats. Ghrelin would seem suited to serve such a role given that it signals hunger information from the stomach to brain areas important for feeding control, including the hypothalamus and reward system (e.g. ventral tegmental area, VTA). Thus, in rats offered a choice of palatable foods (sucrose pellets and lard) superimposed on regular chow for 2 weeks, we explored whether acute central delivery of ghrelin (intracerebroventricular (ICV) or intra-VTA) is able to redirect their dietary choice. The major unexpected finding is that, in rats with high baseline lard intake, acute ICV ghrelin injection increased their chow intake over 3-fold, relative to vehicle-injected controls, measured at both 3 hr and 6 hr after injection. Similar effects were observed when ghrelin was delivered to the VTA, thereby identifying the VTA as a likely contributing neurobiological substrate for these effects. We also explored food choice after an overnight fast, when endogenous ghrelin levels are elevated, and found similar effects of dietary choice to those described for ghrelin. These effects of fasting on food choice were suppressed in models of suppressed ghrelin signaling (i.e. peripheral injection of a ghrelin receptor antagonist to rats and ghrelin receptor (GHSR) knock-out mice), implicating a role for endogenous ghrelin in the changes in food choice that occur after an overnight fast. Thus, in line with its role as a gut-brain hunger hormone, ghrelin appears to be able to acutely alter food choice, with notable effects to promote “healthy” chow intake, and identify the VTA as a likely contributing neurobiological substrate for these effects. PMID:26925974

RNA polymerases IV and V influence the 3' boundaries of Polymerase II transcription units in Arabidopsis.

PubMed

McKinlay, Anastasia; Podicheti, Ram; Wendte, Jered M; Cocklin, Ross; Rusch, Douglas B

2018-02-01

Nuclear multisubunit RNA polymerases IV and V (Pol IV and Pol V) evolved in plants as specialized forms of Pol II. Their functions are best understood in the context of RNA-directed DNA methylation (RdDM), a process in which Pol IV-dependent 24 nt siRNAs direct the de novo cytosine methylation of regions transcribed by Pol V. Pol V has additional functions, independent of Pol IV and 24 nt siRNA biogenesis, in maintaining the repression of transposons and genomic repeats whose silencing depends on maintenance cytosine methylation. Here we report that Pol IV and Pol V play unexpected roles in defining the 3' boundaries of Pol II transcription units. Nuclear run-on assays reveal that in the absence of Pol IV or Pol V, Pol II occupancy downstream of poly A sites increases for approximately 12% of protein-coding genes. This effect is most pronounced for convergently transcribed gene pairs. Although Pols IV and V are detected near transcript ends of the affected Pol II - transcribed genes, their role in limiting Pol II read-through is independent of siRNA biogenesis or cytosine methylation for the majority of these genes. Interestingly, we observed that splicing was less efficient in pol IV or pol V mutant plants, compared to wild-type plants, suggesting that Pol IV or Pol V might affect pre-mRNA processing. We speculate that Pols IV and V (and/or their associated factors) play roles in Pol II transcription termination and pre-mRNA splicing by influencing polymerase elongation rates and/or release at collision sites for convergent genes.

Induction of Phosphoenolpyruvate Carboxykinase (PEPCK) during Acute Acidosis and Its Role in Acid Secretion by V-ATPase-Expressing Ionocytes.

PubMed

Furukawa, Fumiya; Tseng, Yung-Che; Liu, Sian-Tai; Chou, Yi-Ling; Lin, Ching-Chun; Sung, Po-Hsuan; Uchida, Katsuhisa; Lin, Li-Yih; Hwang, Pung-Pung

2015-01-01

Vacuolar-Type H(+)-ATPase (V-ATPase) takes the central role in pumping H(+) through cell membranes of diverse organisms, which is essential for surviving acid-base fluctuating lifestyles or environments. In mammals, although glucose is believed to be an important energy source to drive V-ATPase, and phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme for gluconeogenesis, is known to be activated in response to acidosis, the link between acid secretion and PEPCK activation remains unclear. In the present study, we used zebrafish larva as an in vivo model to show the role of acid-inducible PEPCK activity in glucose production to support higher rate of H(+) secretion via V-ATPase, by utilizing gene knockdown, glucose supplementation, and non-invasive scanning ion-selective electrode technique (SIET). Zebrafish larvae increased V-ATPase-mediated acid secretion and transiently expression of Pck1, a zebrafish homolog of PEPCK, in response to acid stress. When pck1 gene was knocked down by specific morpholino, the H(+) secretion via V-ATPase decreased, but this effect was rescued by supplementation of glucose into the yolk. By assessing changes in amino acid content and gene expression of respective enzymes, glutamine and glutamate appeared to be the major source for replenishment of Krebs cycle intermediates, which are subtracted by Pck1 activity. Unexpectedly, pck1 knockdown did not affect glutamine/glutamate catalysis, which implies that Pck1 does not necessarily drive this process. The present study provides the first in vivo evidence that acid-induced PEPCK provides glucose for acid-base homeostasis at an individual level, which is supported by rapid pumping of H(+) via V-ATPase at the cellular level.

The Role of Bacillithiol in Gram-Positive Firmicutes

PubMed Central

Chandrangsu, Pete; Loi, Vu Van

2018-01-01

Abstract Significance: Since the discovery and structural characterization of bacillithiol (BSH), the biochemical functions of BSH-biosynthesis enzymes (BshA/B/C) and BSH-dependent detoxification enzymes (FosB, Bst, GlxA/B) have been explored in Bacillus and Staphylococcus species. It was shown that BSH plays an important role in detoxification of reactive oxygen and electrophilic species, alkylating agents, toxins, and antibiotics. Recent Advances: More recently, new functions of BSH were discovered in metal homeostasis (Zn buffering, Fe-sulfur cluster, and copper homeostasis) and virulence control in Staphylococcus aureus. Unexpectedly, strains of the S. aureus NCTC8325 lineage were identified as natural BSH-deficient mutants. Modern mass spectrometry-based approaches have revealed the global reach of protein S-bacillithiolation in Firmicutes as an important regulatory redox modification under hypochlorite stress. S-bacillithiolation of OhrR, MetE, and glyceraldehyde-3-phosphate dehydrogenase (Gap) functions, analogous to S-glutathionylation, as both a redox-regulatory device and in thiol protection under oxidative stress. Critical Issues: Although the functions of the bacilliredoxin (Brx) pathways in the reversal of S-bacillithiolations have been recently addressed, significantly more work is needed to establish the complete Brx reduction pathway, including the major enzyme(s), for reduction of oxidized BSH (BSSB) and the targets of Brx action in vivo. Future Directions: Despite the large number of identified S-bacillithiolated proteins, the physiological relevance of this redox modification was shown for only selected targets and should be a subject of future studies. In addition, many more BSH-dependent detoxification enzymes are evident from previous studies, although their roles and biochemical mechanisms require further study. This review of BSH research also pin-points these missing gaps for future research. Antioxid. Redox Signal. 28, 445–462. PMID:28301954

Stimulating Fracture Healing in Ischemic Environments: Does Oxygen Direct Stem Cell Fate during Fracture Healing?

PubMed Central

Miclau, Katherine R.; Brazina, Sloane A.; Bahney, Chelsea S.; Hankenson, Kurt D.; Hunt, Thomas K.; Marcucio, Ralph S.; Miclau, Theodore

2017-01-01

Bone fractures represent an enormous societal and economic burden as one of the most prevalent causes of disability worldwide. Each year, nearly 15 million people are affected by fractures in the United States alone. Data indicate that the blood supply is critical for fracture healing; as data indicate that concomitant bone and vascular injury are major risk factors for non-union. However, the various role(s) that the vasculature plays remains speculative. Fracture stabilization dictates stem cell fate choices during repair. In stabilized fractures stem cells differentiate directly into osteoblasts and heal the injury by intramembranous ossification. In contrast, in non-stable fractures stem cells differentiate into chondrocytes and the bone heals through endochondral ossification, where a cartilage template transforms into bone as the chondrocytes transform into osteoblasts. One suggested role of the vasculature has been to participate in the stem cell fate decisions due to delivery of oxygen. In stable fractures, the blood vessels are thought to remain intact and promote osteogenesis, while in non-stable fractures, continual disruption of the vasculature creates hypoxia that favors formation of cartilage, which is avascular. However, recent data suggests that non-stable fractures are more vascularized than stable fractures, that oxygen does not appear associated with differentiation of stem cells into chondrocytes and osteoblasts, that cartilage is not hypoxic, and that oxygen, not sustained hypoxia, is required for angiogenesis. These unexpected results, which contrast other published studies, are indicative of the need to better understand the complex, spatio-temporal regulation of vascularization and oxygenation in fracture healing. This work has also revealed that oxygen, along with the promotion of angiogenesis, may be novel adjuvants that can stimulate healing in select patient populations. PMID:28523266

Incompletely treated malignancies of the major salivary gland: Toward evidence-based care.

PubMed

Tam, Samantha; Sandulache, Vlad C; Metwalli, Kareem A; Rock, Crosby D; Eraj, Salman A; Sheu, Tommy; El-Naggar, Adel K; Fuller, Clifton D; Weber, Randal S; Lai, Stephen Y

2018-05-07

Unexpected malignancy is common in major salivary gland tumors due to variability of workup, creating challenging treatment decisions. The purpose of this study was to define treatment-related outcomes for patients with incompletely treated major salivary gland tumors. A retrospective cohort study was completed of patients with incompletely treated major salivary gland tumors. Tumor burden at presentation was established and treatment categorized. The Cox Proportional Hazards model was used to determine predictors of survival and failure. Of the 440 included patients, patients with gross residual or metastatic disease had a worse overall survival (OS; P < .001). Presentation status was an independent predictor of OS on multivariate analysis (gross residual disease adjusted hazard ratio [HR adjusted ] 2.55; 95% confidence interval [CI] 1.20-5.30; metastatic disease HR adjusted 9.53; 95% CI 3.04-27.06). Failure to achieve gross total resection during initial surgery resulted in worse OS. Adequate preoperative planning is required for initial surgical management to optimize tumor control and survival. © 2018 Wiley Periodicals, Inc.

High ploidy diversity and distinct patterns of cytotype distribution in a widespread species of Oxalis in the Greater Cape Floristic Region

PubMed Central

Krejčíková, Jana; Sudová, Radka; Lučanová, Magdalena; Trávníček, Pavel; Urfus, Tomáš; Vít, Petr; Weiss-Schneeweiss, Hanna; Kolano, Bożena; Oberlander, Kenneth; Dreyer, Leanne L.; Suda, Jan

2013-01-01

Background and Aims Genome duplication is widely acknowledged as a major force in the evolution of angiosperms, although the incidence of polyploidy in different floras may differ dramatically. The Greater Cape Floristic Region of southern Africa is one of the world's biodiversity hotspots and is considered depauperate in polyploids. To test this assumption, ploidy variation was assessed in a widespread member of the largest geophytic genus in the Cape flora: Oxalis obtusa. Methods DNA flow cytometry complemented by confirmatory chromosome counts was used to determine ploidy levels in 355 populations of O. obtusa (1014 individuals) across its entire distribution range. Ecological differentiation among cytotypes was tested by comparing sets of vegetation and climatic variables extracted for each locality. Key Results Three majority (2x, 4x, 6x) and three minority (3x, 5x, 8x) cytotypes were detected in situ, in addition to a heptaploid individual originating from a botanical garden. While single-cytotype populations predominate, 12 mixed-ploidy populations were also found. The overall pattern of ploidy level distribution is quite complex, but some ecological segregation was observed. Hexaploids are the most common cytotype and prevail in the Fynbos biome. In contrast, tetraploids dominate in the Succulent Karoo biome. Precipitation parameters were identified as the most important climatic variables associated with cytotype distribution. Conclusions Although it would be premature to make generalizations regarding the role of genome duplication in the genesis of hyperdiversity of the Cape flora, the substantial and unexpected ploidy diversity in Oxalis obtusa is unparalleled in comparison with any other cytologically known native Cape plant species. The results suggest that ploidy variation in the Greater Cape Floristic Region may be much greater than currently assumed, which, given the documented role of polyploidy in speciation, has direct implications for radiation hypotheses in this biodiversity hotspot. PMID:23425783

The experience of being a traditional midwife: relationships with skilled birth attendants.

PubMed

Dietsch, Elaine

2010-01-01

This article focuses on an unexpected finding of a research project which explored the experience of being a traditional midwife. The unexpected finding was that traditional midwives often perceive skilled (professional) birth attendants to be abusive of both them and the women who are transferred to hospital for emergency obstetric care. Eighty-four traditional midwives in the Western Province of Kenya were interviewed individually or in groups with a Bukusu/Kiswahili/English-speaking interpreter. Interviews were audiotaped and the English components were transcribed verbatim. Interview transcripts and observations were thematically analysed. A minority of relationships between traditional midwives and skilled birth attendants were based on mutual respect and collaborative practice. However, the majority of encounters with skilled birth attendants were perceived by the traditional midwives to be abusive for them and the women requiring emergency obstetric care. In the interests of improving health outcomes for women and their newborns, interpersonal skills, including maintaining respectful communication and relationships must be a core competency for all caregivers. Providing opportunities for reciprocal learning and strategies to enhance relationships between traditional midwives and skilled birth attendants are recommended. Current global strategies to reduce maternal and newborn mortality by increasing the number of women birthing with a skilled (professional) birth attendant in an enabling environment may be limited while the reasons for traditional midwives being the caregiver of choice for the majority of women living in areas such as Western Kenya remain unaddressed.

Higher organ donation consent rates by relatives of potential uncontrolled donors versus potential controlled donors after death.

PubMed

Wind, Jentina; van Mook, Walther N K A; Willems, Monique E C; van Heurn, L W Ernest

2012-11-01

Refusal to consent to organ donation is an important cause of the persisting gap between the number of potential organ donors and effectuated donors. In the Netherlands, organ donors include both uncontrolled donors: donors who die unexpectedly after cardiac death (DCD), after failed resuscitation and donors in whom death can be expected and donors after brain death, and controlled DCD donors: those who die after the withdrawal of treatment. Different donor type implies a different setting in which relatives are requested to consent to organ donation. It is unknown whether the setting influences the eventual decision for donation or not. Therefore, we compared the consent rate in potential donors who died unexpectedly (UD group) and in whom death was expected. A total of 523 potential organ donors between 2003 and 2011 in the 715-bed Maastricht University Medical Centre, the Netherlands were included. Both the patients' registration in the national donor register (DR) and the relatives' refusal rate in the two groups were retrospectively assessed using data from the donation application database. There were 109 unexpected and 414 expected potential donors The potential donors in the UD group were younger (mean age 52 versus 55 years, P = 0.032) and more often male (68 versus 52%, P = 0.003). There were no significant differences in registration in the DR between the groups. The relatives' consent rate in non-registered potential donors, or those who mandated the relatives for that decision, was higher in the UD group (53 versus 29%, P < 0.001). Less than 50% of the potential donors were registered in the national DR. Therefore, the relatives have an important role in the choice for organ donation. The relatives of potential donors who died unexpectedly consented more often to donation than those in whom death was expected.

Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

DTIC Science & Technology

2016-01-01

temperatures and whole-animal oxygen consumption after exercise. Am J Physiol 221: 427-431, 1971. 33. Brouns I, De Proost I, Pintelon I, Timmermans JP...lactic acid production (Fig. 8). The lack of effect is not unexpected because the increase in arterial O2 content by oxygen ventilation is limited to the...triggering the bronchospasm; 2) whether this effect is heightened by acute airway inflammation; and 3) the temperature thresholds of thermal stress in

The N400 and the P300 are not all that independent.

PubMed

Arbel, Yael; Spencer, Kevin M; Donchin, Emanuel

2011-06-01

This study assessed whether two ERP components that are elicited by unexpected events interact. The conditions that are known to elicit the N400 and the P300 ERP components were applied separately and in combination to terminal-words in sentences. Each sentence ended with a terminal-word that was highly expected, semantically unexpected, physically deviant, or both semantically unexpected and physically deviant. In addition, we varied the level of semantic relatedness between the unexpected terminal-words and the expected exemplars. Physically deviant words elicited a P300, whereas semantically unexpected words elicited an N400, whose amplitude was sensitive to the level of semantic relatedness. Words that were both semantically unexpected and physically deviant elicited both an N400 with enhanced amplitude, and a P300 with reduced amplitude. These results suggest an interaction between the processes manifested by the two components. Copyright © 2010 Society for Psychophysiological Research.

The growing story of (ARABIDOPSIS) CRINKLY 4.

PubMed

Czyzewicz, Nathan; Nikonorova, Natalia; Meyer, Matthew R; Sandal, Priyanka; Shah, Shweta; Vu, Lam Dai; Gevaert, Kris; Rao, A Gururaj; De Smet, Ive

2016-08-01

Receptor kinases play important roles in plant growth and development, but only few of them have been functionally characterized in depth. Over the past decade CRINKLY 4 (CR4)-related research has peaked as a result of a newly discovered role of ARABIDOPSIS CR4 (ACR4) in the root. Here, we comprehensively review the available (A)CR4 literature and describe its role in embryo, seed, shoot, and root development, but we also flag an unexpected role in plant defence. In addition, we discuss ACR4 domains and protein structure, describe known ACR4-interacting proteins and substrates, and elaborate on the transcriptional regulation of ACR4 Finally, we address the missing knowledge in our understanding of ACR4 signalling. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Disambiguating ventral striatum fMRI-related bold signal during reward prediction in schizophrenia

PubMed Central

Morris, R W; Vercammen, A; Lenroot, R; Moore, L; Langton, J M; Short, B; Kulkarni, J; Curtis, J; O'Donnell, M; Weickert, C S; Weickert, T W

2012-01-01

Reward detection, surprise detection and prediction-error signaling have all been proposed as roles for the ventral striatum (vStr). Previous neuroimaging studies of striatal function in schizophrenia have found attenuated neural responses to reward-related prediction errors; however, as prediction errors represent a discrepancy in mesolimbic neural activity between expected and actual events, it is critical to examine responses to both expected and unexpected rewards (URs) in conjunction with expected and UR omissions in order to clarify the nature of ventral striatal dysfunction in schizophrenia. In the present study, healthy adults and people with schizophrenia were tested with a reward-related prediction-error task during functional magnetic resonance imaging to determine whether schizophrenia is associated with altered neural responses in the vStr to rewards, surprise prediction errors or all three factors. In healthy adults, we found neural responses in the vStr were correlated more specifically with prediction errors than to surprising events or reward stimuli alone. People with schizophrenia did not display the normal differential activation between expected and URs, which was partially due to exaggerated ventral striatal responses to expected rewards (right vStr) but also included blunted responses to unexpected outcomes (left vStr). This finding shows that neural responses, which typically are elicited by surprise, can also occur to well-predicted events in schizophrenia and identifies aberrant activity in the vStr as a key node of dysfunction in the neural circuitry used to differentiate expected and unexpected feedback in schizophrenia. PMID:21709684

Unexpected Solubility Enhancement of Drug Bases in the Presence of a Dimethylaminoethyl Methacrylate Copolymer.

PubMed

Saal, Wiebke; Ross, Alfred; Wyttenbach, Nicole; Alsenz, Jochem; Kuentz, Martin

2018-01-02

The methacrylate copolymer Eudragit EPO (EPO) has previously shown to greatly enhance solubilization of acidic drugs via ionic interactions and by multiple hydrophobic contacts with polymeric side chains. The latter type of interaction could also play a role for solubilization of other compounds than acids. The aim of this study was therefore to investigate the solubility of six poorly soluble bases in presence and absence of EPO by quantitative ultrapressure liquid chromatography with concomitant X-ray powder diffraction analysis of the solid state. For a better mechanistic understanding, spectra and diffusion data were obtained by 1 H nuclear magnetic resonance (NMR) spectroscopy. Unexpected high solubility enhancement (up to 360-fold) was evidenced in the presence of EPO despite the fact that bases and polymer were both carrying positive charges. This exceptional and unexpected solubilization was not due to a change in the crystalline solid state. NMR spectra and measured diffusion coefficients indicated both strong drug-polymer interactions in the bulk solution, and diffusion data suggested conformational changes of the polymer in solution. Such conformational changes may have increased the accessibility and extent of hydrophobic contacts thereby leading to increased overall molecular interactions. These initially surprising solubilization results demonstrate that excipient selection should not be based solely on simple considerations of, for example, opposite charges of drug and excipient, but it requires a more refined molecular view. Different solution NMR techniques are especially promising tools to gain such mechanistic insights.

Predictive teratology: teratogenic risk-hazard identification partnered in the discovery process.

PubMed

Augustine-Rauch, K A

2008-11-01

Unexpected teratogenicity is ranked as one of the most prevalent causes for toxicity-related attrition of drug candidates. Without proactive assessment, the liability tends to be identified relatively late in drug development, following significant investment in compound and engagement in pre clinical and clinical studies. When unexpected teratogenicity occurs in pre-clinical development, three principle questions arise: Can clinical trials that include women of child bearing populations be initiated? Will all compounds in this pharmacological class produce the same liability? Could this effect be related to the chemical structure resulting in undesirable off-target adverse effects? The first question is typically addressed at the time of the unexpected finding and involves considering the nature of the teratogenicity, whether or not maternal toxicity could have had a role in onset, human exposure margins and therapeutic indication. The latter two questions can be addressed proactively, earlier in the discovery process as drug target profiling and lead compound optimization is taking place. Such proactive approaches include thorough assessment of the literature for identification of potential liabilities and follow-up work that can be conducted on the level of target expression and functional characterization using molecular biology and developmental model systems. Developmental model systems can also be applied in the form of in vitro teratogenicity screens, and show potential for effective hazard identification or issue resolution on the level of characterizing teratogenic mechanism. This review discusses approaches that can be applied for proactive assessment of compounds for teratogenic liability.

Large-scale synchronized activity during vocal deviance detection in the zebra finch auditory forebrain.

PubMed

Beckers, Gabriël J L; Gahr, Manfred

2012-08-01

Auditory systems bias responses to sounds that are unexpected on the basis of recent stimulus history, a phenomenon that has been widely studied using sequences of unmodulated tones (mismatch negativity; stimulus-specific adaptation). Such a paradigm, however, does not directly reflect problems that neural systems normally solve for adaptive behavior. We recorded multiunit responses in the caudomedial auditory forebrain of anesthetized zebra finches (Taeniopygia guttata) at 32 sites simultaneously, to contact calls that recur probabilistically at a rate that is used in communication. Neurons in secondary, but not primary, auditory areas respond preferentially to calls when they are unexpected (deviant) compared with the same calls when they are expected (standard). This response bias is predominantly due to sites more often not responding to standard events than to deviant events. When two call stimuli alternate between standard and deviant roles, most sites exhibit a response bias to deviant events of both stimuli. This suggests that biases are not based on a use-dependent decrease in response strength but involve a more complex mechanism that is sensitive to auditory deviance per se. Furthermore, between many secondary sites, responses are tightly synchronized, a phenomenon that is driven by internal neuronal interactions rather than by the timing of stimulus acoustic features. We hypothesize that this deviance-sensitive, internally synchronized network of neurons is involved in the involuntary capturing of attention by unexpected and behaviorally potentially relevant events in natural auditory scenes.

Unexpected angular or rotational deformity after corrective osteotomy

PubMed Central

2014-01-01

Background Codman’s paradox reveals a misunderstanding of geometry in orthopedic practice. Physicians often encounter situations that cannot be understood intuitively during orthopedic interventions such as corrective osteotomy. Occasionally, unexpected angular or rotational deformity occurs during surgery. This study aimed to draw the attention of orthopedic surgeons toward the concepts of orientation and rotation and demonstrate the potential for unexpected deformity after orthopedic interventions. This study focused on three situations: shoulder arthrodesis, femoral varization derotational osteotomy, and femoral derotation osteotomy. Methods First, a shoulder model was generated to calculate unexpected rotational deformity to demonstrate Codman’s paradox. Second, femoral varization derotational osteotomy was simulated using a cylinder model. Third, a reconstructed femoral model was used to calculate unexpected angular or rotational deformity during femoral derotation osteotomy. Results Unexpected external rotation was found after forward elevation and abduction of the shoulder joint. In the varization and derotation model, closed-wedge osteotomy and additional derotation resulted in an unexpected extension and valgus deformity, namely, under-correction of coxa valga. After femoral derotational osteotomy, varization and extension of the distal fragment occurred, although the extension was negligible. Conclusions Surgeons should be aware of unexpected angular deformity after surgical procedure involving bony areas. The degree of deformity differs depending on the context of the surgical procedure. However, this study reveals that notable deformities can be expected during orthopedic procedures such as femoral varization derotational osteotomy. PMID:24886469

New product trial, use of edibles, and unexpected highs among marijuana and hashish users in Colorado.

PubMed

Allen, Jane A; Davis, Kevin C; Duke, Jennifer C; Nonnemaker, James M; Bradfield, Brian R; Farrelly, Matthew C

2017-07-01

This study examines the relationships between trial of new marijuana or hashish products and unexpected highs, and use of edible products and unexpected highs. We conducted an online survey of 634 adult, past-year marijuana users in Colorado. We used logistic regression models to examine the relationship between new product trial or edible use and unexpected highs. In the first year that recreational marijuana was legal in Colorado, 71.4% of respondents tried a new marijuana or hashish product, and 53.6% used an edible product. Trial of new products was associated with greater odds of experiencing an unexpected high after controlling for age, gender, education, mental health status, current marijuana or hashish use, and mean amount of marijuana or hashish consumed in the past month (OR=2.13, p<0.001). Individuals who reported having used edibles had greater odds of experiencing an unexpected high, after controlling for the same set of variables (OR=1.56, p<0.05). People who try new marijuana or hashish products, or use edible marijuana or hashish products, are at greater risk for an unexpected high. It is possible that some negative outcomes associated with marijuana use and unexpected highs may be averted through a better understanding of how to use product packaging to communicate with consumers. Copyright © 2017 Elsevier B.V. All rights reserved.

Planarians as a Model to Assess In Vivo the Role of Matrix Metalloproteinase Genes during Homeostasis and Regeneration

PubMed Central

Isolani, Maria Emilia; Abril, Josep F.; Saló, Emili; Deri, Paolo; Bianucci, Anna Maria; Batistoni, Renata

2013-01-01

Matrix metalloproteinases (MMPs) are major executors of extracellular matrix remodeling and, consequently, play key roles in the response of cells to their microenvironment. The experimentally accessible stem cell population and the robust regenerative capabilities of planarians offer an ideal model to study how modulation of the proteolytic system in the extracellular environment affects cell behavior in vivo. Genome-wide identification of Schmidtea mediterranea MMPs reveals that planarians possess four mmp-like genes. Two of them (mmp1 and mmp2) are strongly expressed in a subset of secretory cells and encode putative matrilysins. The other genes (mt-mmpA and mt-mmpB) are widely expressed in postmitotic cells and appear structurally related to membrane-type MMPs. These genes are conserved in the planarian Dugesia japonica. Here we explore the role of the planarian mmp genes by RNA interference (RNAi) during tissue homeostasis and regeneration. Our analyses identify essential functions for two of them. Following inhibition of mmp1 planarians display dramatic disruption of tissues architecture and significant decrease in cell death. These results suggest that mmp1 controls tissue turnover, modulating survival of postmitotic cells. Unexpectedly, the ability to regenerate is unaffected by mmp1(RNAi). Silencing of mt-mmpA alters tissue integrity and delays blastema growth, without affecting proliferation of stem cells. Our data support the possibility that the activity of this protease modulates cell migration and regulates anoikis, with a consequent pivotal role in tissue homeostasis and regeneration. Our data provide evidence of the involvement of specific MMPs in tissue homeostasis and regeneration and demonstrate that the behavior of planarian stem cells is critically dependent on the microenvironment surrounding these cells. Studying MMPs function in the planarian model provides evidence on how individual proteases work in vivo in adult tissues. These results have high potential to generate significant information for development of regenerative and anti cancer therapies. PMID:23405188

Planarians as a model to assess in vivo the role of matrix metalloproteinase genes during homeostasis and regeneration.

PubMed

Isolani, Maria Emilia; Abril, Josep F; Saló, Emili; Deri, Paolo; Bianucci, Anna Maria; Batistoni, Renata

2013-01-01

Matrix metalloproteinases (MMPs) are major executors of extracellular matrix remodeling and, consequently, play key roles in the response of cells to their microenvironment. The experimentally accessible stem cell population and the robust regenerative capabilities of planarians offer an ideal model to study how modulation of the proteolytic system in the extracellular environment affects cell behavior in vivo. Genome-wide identification of Schmidtea mediterranea MMPs reveals that planarians possess four mmp-like genes. Two of them (mmp1 and mmp2) are strongly expressed in a subset of secretory cells and encode putative matrilysins. The other genes (mt-mmpA and mt-mmpB) are widely expressed in postmitotic cells and appear structurally related to membrane-type MMPs. These genes are conserved in the planarian Dugesia japonica. Here we explore the role of the planarian mmp genes by RNA interference (RNAi) during tissue homeostasis and regeneration. Our analyses identify essential functions for two of them. Following inhibition of mmp1 planarians display dramatic disruption of tissues architecture and significant decrease in cell death. These results suggest that mmp1 controls tissue turnover, modulating survival of postmitotic cells. Unexpectedly, the ability to regenerate is unaffected by mmp1(RNAi). Silencing of mt-mmpA alters tissue integrity and delays blastema growth, without affecting proliferation of stem cells. Our data support the possibility that the activity of this protease modulates cell migration and regulates anoikis, with a consequent pivotal role in tissue homeostasis and regeneration. Our data provide evidence of the involvement of specific MMPs in tissue homeostasis and regeneration and demonstrate that the behavior of planarian stem cells is critically dependent on the microenvironment surrounding these cells. Studying MMPs function in the planarian model provides evidence on how individual proteases work in vivo in adult tissues. These results have high potential to generate significant information for development of regenerative and anti cancer therapies.

484 Allergen Standardisation in Allergens and Allergoids—Challenges and Considerations

PubMed Central

Skinner, Murray; Bullimore, Alan; Hewings, Simon; Swan, Nicola

2012-01-01

Background The range of therapeutics and dosing schedules for allergen preparations and allergoids produced and used clinically are considerable. Standardisation of allergy immunotherapies is considered a positive step; however there are difficulties in identifying universal metrics for standardisation. Many advocate the use of major allergen content whilst others advocate total allergenicity. Additionally as a compounding argument, where major allergen is used, many disagree on what the major allergen is for certain species. Methods Major allergen content measurement allows a consistent recognised measure, and IgE responses of a serum pool are often dominated by IgE against major allergens. However issues such as specificity of different assays toward isoforms and other variants of single allergens often results in diverging allergen contents that can cause unexpected and misleading disparity. Other aspects that increase complication are the relevance to modified allergens, use of adjuvants and differing dosing regimes. Results The major allergen content of key products in different therapeutic formats has been measured. Conclusions This has been performed in conjunction with techniques such as total allergenicity, as allergy treatments and therapeutics require careful characterisation to allow supply of consistent, safe and efficacious products.

[Analysis of an ophthalmic pathology cohort of human fetal eyes with regard to interesting findings].

PubMed

Herwig, M C; Müller, A M; Holz, F G; Loeffler, K U

2010-11-01

Information on the evaluation of prenatal ocular findings is sparse. This article provides an overview of the morphology in a cohort of human fetal eyes, with particular emphasis on interesting findings. The study investigated 216 eyes from 115 human fetuses. The majority of fetal eyes presented with a regular phenotype. Rarely, unexpected findings were discovered in fetuses with or without systemic malformations. Routine evaluation of fetal eyes reveals-albeit rarely-new aspects providing further knowledge and occasionally enabling the exact classification of syndromes.

Earth observations taken during STS-83 mission

NASA Image and Video Library

2016-08-12

STS083-747-088 (4-8 April 1997)--- Mayon Volcano with a Plume, Luzon, the Philippines Mayon has the classic conical shape of a strato volcano. It is the most active volcano in the Philippines and continues to be active as demonstrated by the plume in the photo. Since 1616, Mayon has erupted 47 times. The most recent major eruption, in 1993, began unexpectedly with an explosion. The initial eruption lasted only 30 minutes but it generated pyroclastic flows that killed 68 people and prompted the evacuation of 60,000 others.

Reducing Bat Fatalities From Interactions with Operating Wind Turbines (Fact Sheet)

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

Lawson, M.

One of the biggest advantages of wind energy is that, overall, it has fewer negative impacts on the environment than fossil fuel-generated energy. Most professionals in the wind industry would like to reduce the impact of energy generation on plants, animals, and their habitats. This is why the industry is highly motivated to find out why migrating bats have unexpectedly high fatality rates near operating wind farms. New research has provided quantitative data that indicates barotrauma is not a major cause of bat deaths around operating turbines.

Teacher ratings of resilience and peer relationships of preschoolers whose fathers died unexpectedly.

PubMed

Gülay Ogelman, Hülya; Gündoğan, Aysun; Erten Sarıkaya, Hatice; Erol, Ahmet

2016-08-01

This study endeavors to compare resilience and peer relationships of children who lost their fathers in a major mining accident in Soma with those who did not. Teachers rated 51 preschoolers whose fathers died, and 53 preschoolers whose fathers were alive. On the negative side, bereaved children had lower resilience and higher exclusion; on the positive side, bereaved children had lower peer victimization and higher prosocial behavior. Death of fathers is associated with lower resilience and more exclusion among young children, but others treat them better as well.

Confronting the unexpected: temporal, situational, and attributive dimensions of distressing symptom experience for breast cancer survivors.

PubMed

Rosedale, Mary; Fu, Mei R

2010-01-01

To describe women's unexpected and distressing symptom experiences after breast cancer treatment. Qualitative and descriptive. Depending upon their preference, participants were interviewed in their homes or in a private office space in a nearby library. Purposive sample of 13 women 1-18 years after breast cancer treatment. Secondary analysis of phenomenologic data (constant comparative method). Breast cancer symptom distress, ongoing symptoms, and unexpected experiences. Women described experiences of unexpected and distressing symptoms in the years following breast cancer treatment. Symptoms included pain, loss of energy, impaired limb movement, cognitive disturbance, changed sexual experience, and lymphedema. Four central themes were derived: living with lingering symptoms, confronting unexpected situations, losing precancer being, and feeling like a has-been. Distress intensified when women expected symptoms to disappear but symptoms persisted instead. Increased distress also was associated with sudden and unexpected situations or when symptoms elicited feelings of loss about precancer being and feelings of being a has been. Findings suggest that symptom distress has temporal, situational, and attributive dimensions. Breast cancer survivors' perceptions of ongoing and unexpected symptoms have important influences on quality of life. Understanding temporal, situational, and attributive dimensions of symptom distress empowers nurses and healthcare professionals to help breast cancer survivors prepare for subsequent ongoing or unexpected experiences in the years after breast cancer treatment. Follow-up care for breast cancer survivors should foster dialogue about ways that symptoms might emerge and that unexpected situations might occur. Prospective studies are needed to examine symptom distress in terms of temporal, situational, and attributive dimensions and explore the relationship between symptom distress and psychological distress after breast cancer treatment.

Leishmania major Survival in Selective Phlebotomus papatasi Sand Fly Vector Requires a Specific SCG-Encoded Lipophosphoglycan Galactosylation Pattern

PubMed Central

Dobson, Deborah E.; Kamhawi, Shaden; Lawyer, Phillip; Turco, Salvatore J.; Beverley, Stephen M.; Sacks, David L.

2010-01-01

Phlebotomine sand flies that transmit the protozoan parasite Leishmania differ greatly in their ability to support different parasite species or strains in the laboratory: while some show considerable selectivity, others are more permissive. In “selective” sand flies, Leishmania binding and survival in the fly midgut typically depends upon the abundant promastigote surface adhesin lipophosphoglycan (LPG), which exhibits species- and strain-specific modifications of the dominant phosphoglycan (PG) repeat units. For the “selective” fly Phlebotomus papatasi PpapJ, side chain galactosyl-modifications (scGal) of PG repeats play key roles in parasite binding. We probed the specificity and properties of this scGal-LPG PAMP (Pathogen Associated Molecular Pattern) through studies of natural isolates exhibiting a wide range of galactosylation patterns, and of a panel of isogenic L. major engineered to express similar scGal-LPG diversity by transfection of SCG-encoded β1,3-galactosyltransferases with different activities. Surprisingly, both ‘poly-scGal’ and ‘null-scGal’ lines survived poorly relative to PpapJ-sympatric L. major FV1 and other ‘mono-scGal’ lines. However, survival of all lines was equivalent in P. duboscqi, which naturally transmit L. major strains bearing ‘null-scGal’-LPG PAMPs. We then asked whether scGal-LPG-mediated interactions were sufficient for PpapJ midgut survival by engineering Leishmania donovani, which normally express unsubstituted LPG, to express a ‘PpapJ-optimal’ scGal-LPG PAMP. Unexpectedly, these “L. major FV1-cloaked” L. donovani-SCG lines remained unable to survive within PpapJ flies. These studies establish that midgut survival of L. major in PpapJ flies is exquisitely sensitive to the scGal-LPG PAMP, requiring a specific ‘mono-scGal’ pattern. However, failure of ‘mono-scGal’ L. donovani-SCG lines to survive in selective PpapJ flies suggests a requirement for an additional, as yet unidentified L. major-specific parasite factor(s). The interplay of the LPG PAMP and additional factor(s) with sand fly midgut receptors may determine whether a given sand fly host is “selective” or “permissive”, with important consequences to both disease transmission and the natural co-evolution of sand flies and Leishmania. PMID:21085609

Molybdenum Trafficking for Nitrogen Fixation†

PubMed Central

Hernandez, Jose A.; George, Simon J.; Rubio, Luis M.

2009-01-01

The molybdenum nitrogenase is responsible for most biological nitrogen fixation, a prokaryotic metabolic process that determines the global biogeochemical cycles of nitrogen and carbon. Here we describe the trafficking of molybdenum for nitrogen fixation in the model diazotrophic bacterium Azotobacter vinelandii. The genes and proteins involved in molybdenum uptake, homeostasis, storage, regulation, and nitrogenase cofactor biosynthesis are reviewed. Molybdenum biochemistry in A. vinelandii reveals unexpected mechanisms and a new role for iron-sulfur clusters in the sequestration and delivery of molybdenum. PMID:19772354

Benefits to the nation from astronomy and astrophysics

NASA Technical Reports Server (NTRS)

Trimble, Virginia; Bahcall, John N.; Chaisson, Eric; Code, Arthur; Conklin, Edward K.; Cowan, John; Dalgarno, Alexander; Drake, Frank; Elson, Rebecca; Field, George

1991-01-01

It is argued that astronomy makes unexpectantly large contributions to formal and informal science education, given the small number of research astronomers. Technology transfer and spin-offs from astronomy have important applications in medicine, industry, defence, environmental monitoring, and consumer products. Astronomy provides unusually promising opportunities for international cooperation. Other sciences benefit from synergistic interactions with astronomy. A review is given of astronomy education and teacher training. The role of astronomy in medicine, industry, defence, energy technology, the environment, and everyday life is reviewed.

m6A and eIF2α-ⓟ Team Up to Tackle ATF4 Translation during Stress.

PubMed

Powers, Emily Nicole; Brar, Gloria Ann

2018-02-15

While m 6 A modification of mRNAs is now known to be widespread, the cellular roles of this modification remain largely mysterious. In this issue of Molecular Cell, Zhou et al. (2018) show that m 6 A modification unexpectedly contributes to the established uORF- and eIF2α-ⓟ-dependent mechanism of ATF4 translational regulation in response to stress. Copyright © 2018 Elsevier Inc. All rights reserved.

Requirements and Architecture Specification of the Joint Multi-Role (JMR) Joint Common Architecture (JCA) Demonstration System

DTIC Science & Technology

2015-12-01

response time re- quirements and in additional calibration requirements for DCFM that may create unexpected la - tency and latency jitter that can...manage the flight path of the aircraft. For more information about sensor correlation and fusion processes, the Air University New World Vistas ...request/reply actions. We specify its la - tency as a minimum and maximum of 300 ms.  SADataServiceProtocol: an abstraction of the SA data service as a

An unexpected cause of vaginal bleeding: the role of pelvic radiography.

PubMed

Kyrgios, Ioannis; Emmanouilidou, Eleftheria; Theodoridis, Theodoros; Galli-Tsinopoulou, Assimina

2014-02-14

Vaginal bleeding and/or discharge in young girls may result from infection, urological problems, endocrine causes, bleeding disorders, dermatological conditions, trauma, sexual abuse, masses or foreign bodies. We report a case of excessive vaginal bleeding caused by a foreign body in a prepubertal girl with emphasis on the diagnostic challenges and pitfalls regarding imaging techniques. In our patient, although invasive and expensive investigations had been initially made, the foreign body was last detected only when a plain pelvic radiography was performed.

Propfan noise propagation

NASA Technical Reports Server (NTRS)

George, Albert R.; Sim, Ben WEL-C.

1993-01-01

The unconventional supersonic tip speed of advanced propellers has led to uncertainties about Propfan's noise acceptability and compliance with Federal Aviation Noise Regulation (FAR 36). Overhead flight testing of the Propfan with an SR-7L blade during 1989's Propfan Test Assessment (PTA) Program have shown unexpectedly high far-field sound pressure levels. This study here attempts to provide insights into the acoustics of a single-rotating propeller (SRP) with supersonic tip speed. At the same time, the role of the atmosphere in shaping the far-field noise characteristics is investigated.

Wybutosine biosynthesis: Structural and mechanistic overview

PubMed Central

Perche-Letuvée, Phanélie; Molle, Thibaut; Forouhar, Farhad; Mulliez, Etienne; Atta, Mohamed

2014-01-01

Over the last 10 years, significant progress has been made in understanding the genetics, enzymology and structural components of the wybutosine (yW) biosynthetic pathway. These studies have played a key role in expanding our understanding of yW biosynthesis and have revealed unexpected evolutionary ties, which are presently being unraveled. The enzymes catalyzing the 5 steps of this pathway, from genetically encoded guanosine to wybutosine base, provide an ensemble of amazing reaction mechanisms that are to be discussed in this review article. PMID:25629788

Associations between sociocultural home environmental factors and vegetable consumption among Norwegian 3-5-year olds: BRA-study.

PubMed

Kristiansen, Anne Lene; Bjelland, Mona; Himberg-Sundet, Anne; Lien, Nanna; Frost Andersen, Lene

2017-10-01

The home environment is the first environment to shape childhood dietary habits and food preferences, hence greater understanding of home environmental factors associated with vegetable consumption among young children is needed. The objective has been to examine questionnaire items developed to measure the sociocultural home environment of children focusing on vegetables and to assess the psychometric properties of the resulting factors. Further, to explore associations between the environmental factors and vegetable consumption among Norwegian 3-5 year olds. Parents (n 633) were invited to participate and filled in a questionnaire assessing the child's vegetable intake and factors potentially influencing this, along with a 24-h recall of their child's fruit and vegetable intake. Children's fruit and vegetable intakes at two meals in one day in the kindergarten were observed by researchers. Principal components analysis was used to examine items assessing the sociocultural home environment. Encouragement items resulted in factors labelled "reactive encouragement", "child involvement" and "reward". Modelling items resulted in the factors labelled "active role model" and "practical role model". Items assessing negative parental attitudes resulted in the factor labelled "negative parental attitudes" and items assessing family pressure/demand resulted in the factor labelled "family demand". The psychometric properties of the factors were for most satisfactory. Linear regression of the associations between vegetable intake and the factors showed, as expected, generally positive associations with "child involvement", "practical role model" and "family demand", and negative associations with "negative parental attitudes" and "reward". Unexpectedly, "reactive encouragement" was negatively associated with vegetable consumption. In conclusion, associations between sociocultural home environmental factors and children's vegetable consumption showed both expected and unexpected associations some of which differed by maternal education - pointing to a need for further comparable studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

The unique and cooperative roles of the Grainy head-like transcription factors in epidermal development reflect unexpected target gene specificity.

PubMed

Boglev, Yeliz; Wilanowski, Tomasz; Caddy, Jacinta; Parekh, Vishwas; Auden, Alana; Darido, Charbel; Hislop, Nikki R; Cangkrama, Michael; Ting, Stephen B; Jane, Stephen M

2011-01-15

The Grainy head-like 3 (Grhl3) gene encodes a transcription factor that plays essential roles in epidermal morphogenesis during embryonic development, with deficient mice exhibiting failed skin barrier formation, defective wound repair, and loss of eyelid fusion. Despite sharing significant sequence homology, overlapping expression patterns, and an identical core consensus DNA binding site, the other members of the Grhl family (Grhl1 and -2) fail to compensate for the loss of Grhl3 in these processes. Here, we have employed diverse genetic models, coupled with biochemical studies, to define the inter-relationships of the Grhl factors in epidermal development. We show that Grhl1 and Grhl3 have evolved complete functional independence, as evidenced by a lack of genetic interactions in embryos carrying combinations of targeted alleles of these genes. In contrast, compound heterozygous Grhl2/Grhl3 embryos displayed failed wound repair, and loss of a single Grhl2 allele in Grhl3-null embryos results in fully penetrant eyes open at birth. Expression of Grhl2 from the Grhl3 locus in homozygous knock-in mice corrects the wound repair defect, but these embryos still display a complete failure of skin barrier formation. This functional dissociation is due to unexpected differences in target gene specificity, as both GRHL2 and GRHL3 bind to and regulate expression of the wound repair gene Rho GEF 19, but regulation of the barrier forming gene, Transglutaminase 1 (TGase1), is unique to GRHL3. Our findings define the mechanisms underpinning the unique and cooperative roles of the Grhl genes in epidermal development. Copyright © 2010 Elsevier Inc. All rights reserved.

Differential Responses of Anopheles stephensi (Diptera: Culicidae) to Skin Emanations of a Man, a Cow, and a Guinea Pig in the Olfactometer

PubMed Central

Omrani, S -M; Vatandoost, H; Oshaghi, MA; Shokri, F; Yaghoobi-Ershadi, MR; Rassi, Y; Tirgari, S

2010-01-01

Background: Biting habit of mosquitoes plays an important role in the epidemiology of mosquito-borne diseases. Mosquitoes use a set of elaborate sensory modalities to find their preferred hosts by exploiting cues emanating from a nearby host. It has been suggested that the chemical profile of skin can provide further support for anthropophilic mosquito species to find their suitable hosts. This study aimed at revealing the value of skin emanation for a zoophilic species like Anopheles stephensi as a model. Methods: Skin emanations of a man, a cow and a Guinea pig were collected by ethanol soaked cottons. Upwind responses of mosquitoes to 100 and 200 μl of filtered skin materials were non-competitively explored in a dual-choice olfactometer. L-lactic acid and other chemical content of the skin samples were identified by an enzymatic kit and GC-MS, respectively. Results: Unexpectedly, only human skin emanation was resulted in the statistically significant activation and attraction responses of An. stephensi in the wind tunnel. L-lactic acid content of this skin sample was 10 and 29 times more than the cow and the Guinea pig, respectively. The possible role of lactic acid and a few other identified compounds have been discussed here. Conclusion: Anopheles stephensi showed higher and more specific upwind responses to human skin emanation in the olfactometer. Undoubtedly, the thorough explanation of this unexpected finding needs further investigation. But, if new data verify this result, then, it may be necessary to reconsider the role of skin emanation and thence the human blood index and vectorial capacity of this zoophilic mosquito. PMID:22808383

The role of the concentration camps in the Nazi repression of prostitutes, 1933-9.

PubMed

Harris, Victoria

2010-01-01

This article uses prostitutes as a case study in order to investigate the role of the early concentration camps as centres of detention for social deviants. In contrasting the intensification of repressive policies towards prostitutes against narratives which demonstrate the unexpectedly lax treatment of these women, it explores what the reasons behind these contradictions might have been, and what this demonstrates about the development of these institutions. It asks the following questions. How and why were prostitutes interned? Which bureaucrats were responsible for incarcerating these women and what did they view the role of the camp to be? Were such policies centrally directed or the product of local decision-making? Through asking these questions, the article explores to what extent these camps were unique as mechanisms for the repression and marginalization of prostitutes.

Robust passive dynamics of the musculoskeletal system compensate for unexpected surface changes during human hopping

PubMed Central

van der Krogt, Marjolein M.; de Graaf, Wendy W.; Farley, Claire T.; Moritz, Chet T.; Richard Casius, L. J.; Bobbert, Maarten F.

2009-01-01

When human hoppers are surprised by a change in surface stiffness, they adapt almost instantly by changing leg stiffness, implying that neural feedback is not necessary. The goal of this simulation study was first to investigate whether leg stiffness can change without neural control adjustment when landing on an unexpected hard or unexpected compliant (soft) surface, and second to determine what underlying mechanisms are responsible for this change in leg stiffness. The muscle stimulation pattern of a forward dynamic musculoskeletal model was optimized to make the model match experimental hopping kinematics on hard and soft surfaces. Next, only surface stiffness was changed to determine how the mechanical interaction of the musculoskeletal model with the unexpected surface affected leg stiffness. It was found that leg stiffness adapted passively to both unexpected surfaces. On the unexpected hard surface, leg stiffness was lower than on the soft surface, resulting in close-to-normal center of mass displacement. This reduction in leg stiffness was a result of reduced joint stiffness caused by lower effective muscle stiffness. Faster flexion of the joints due to the interaction with the hard surface led to larger changes in muscle length, while the prescribed increase in active state and resulting muscle force remained nearly constant in time. Opposite effects were found on the unexpected soft surface, demonstrating the bidirectional stabilizing properties of passive dynamics. These passive adaptations to unexpected surfaces may be critical when negotiating disturbances during locomotion across variable terrain. PMID:19589956

RNAi-mediated silencing of vitellogenin gene function turns honeybee ( Apis mellifera) workers into extremely precocious foragers

NASA Astrophysics Data System (ADS)

Marco Antonio, David Santos; Guidugli-Lazzarini, Karina Rosa; Do Nascimento, Adriana Mendes; Simões, Zilá Luz Paulino; Hartfelder, Klaus

2008-10-01

The switch from within-hive activities to foraging behavior is a major transition in the life cycle of a honeybee ( Apis mellifera) worker. A prominent regulatory role in this switch has long been attributed to juvenile hormone (JH), but recent evidence also points to the yolk precursor protein vitellogenin as a major player in behavioral development. In the present study, we injected vitellogenin double-stranded RNA (dsVg) into newly emerged worker bees of Africanized genetic origin and introduced them together with controls into observation hives to record flight behavior. RNA interference-mediated silencing of vitellogenin gene function shifted the onset of long-duration flights (>10 min) to earlier in life (by 3 4 days) when compared with sham and untreated control bees. In fact, dsVg bees were observed conducting such flights extremely precociously, when only 3 days old. Short-duration flights (<10 min), which bees usually perform for orientation and cleaning, were not affected. Additionally, we found that the JH titer in dsVg bees collected after 7 days was not significantly different from the controls. The finding that depletion of the vitellogenin titer can drive young bees to become extremely precocious foragers could imply that vitellogenin is the primary switch signal. At this young age, downregulation of vitellogenin gene activity apparently had little effect on the JH titer. As this unexpected finding stands in contrast with previous results on the vitellogenin/JH interaction at a later age, when bees normally become foragers, we propose a three-step sequence in the constellation of physiological parameters underlying behavioral development.

Continual renewal and replication of persistent Leishmania major parasites in concomitantly immune hosts

PubMed Central

Mandell, Michael A.

2017-01-01

In most natural infections or after recovery, small numbers of Leishmania parasites remain indefinitely in the host. Persistent parasites play a vital role in protective immunity against disease pathology upon reinfection through the process of concomitant immunity, as well as in transmission and reactivation, yet are poorly understood. A key question is whether persistent parasites undergo replication, and we devised several approaches to probe the small numbers in persistent infections. We find two populations of persistent Leishmania major: one rapidly replicating, similar to parasites in acute infections, and another showing little evidence of replication. Persistent Leishmania were not found in “safe” immunoprivileged cell types, instead residing in macrophages and DCs, ∼60% of which expressed inducible nitric oxide synthase (iNOS). Remarkably, parasites within iNOS+ cells showed normal morphology and genome integrity and labeled comparably with BrdU to parasites within iNOS− cells, suggesting that these parasites may be unexpectedly resistant to NO. Nonetheless, because persistent parasite numbers remain roughly constant over time, their replication implies that ongoing destruction likewise occurs. Similar results were obtained with the attenuated lpg2− mutant, a convenient model that rapidly enters a persistent state without inducing pathology due to loss of the Golgi GDP mannose transporter. These data shed light on Leishmania persistence and concomitant immunity, suggesting a model wherein a parasite reservoir repopulates itself indefinitely, whereas some progeny are terminated in antigen-presenting cells, thereby stimulating immunity. This model may be relevant to understanding immunity to other persistent pathogen infections. PMID:28096392

Elevated striatal γ-aminobutyric acid in youth with major depressive disorder.

PubMed

Bradley, Kailyn A; Alonso, Carmen M; Mehra, Lushna M; Xu, Junqian; Gabbay, Vilma

2018-06-08

Alterations in γ-aminobutyric acid (GABA) have been hypothesized to play a role in the pathogenesis of psychiatric illness. Our previous work has specifically linked anterior cingulate cortex (ACC) GABA deficits with anhedonia in youth with major depressive disorder (MDD). As anhedonia reflects alterations within the reward circuitry, we sought to extend this investigation and examine GABA levels in another key reward-related region, the striatum, in the same adolescent population. Thirty-six youth [20 with MDD and 16 healthy controls; (HC)], ages 12 to 21 years old, underwent J-edited proton magnetic resonance spectroscopy ( 1 H MRS) whereby GABA levels were measured in striatal and ACC voxels. GABA levels were compared between groups and between voxel positions and were examined in relation to clinical symptomatology, such as depression severity, anhedonia, anxiety, and suicidality. Depressed youth had unexpectedly higher GABA levels in the striatum compared to HC. In both depressed and healthy youth, GABA levels were higher in the striatum than in the ACC, while the differences in depressed youth were greater. Moreover, in depressed youth, higher striatal GABA above the mean of HCs was correlated with lower ACC GABA below the mean of HCs. Striatal GABA was not correlated with clinical symptomatology in this small sample. Together, these findings suggest that higher striatal GABA levels may serve some compensatory function as a result of lower ACC GABA in depressed adolescents. It is also possible that, like lower ACC GABA, higher striatal GABA might simply be another pathological feature of adolescent depression. Copyright © 2018 Elsevier Inc. All rights reserved.

Emerging Paradigms in Cardiomyopathies Associated with Cancer Therapies

PubMed Central

Ky, Bonnie; Vejpongsa, Pimprapa; Yeh, Edward T.H.; Force, Thomas; Moslehi, Javid

2014-01-01

The cardiovascular care of cancer patients (“Cardio-Oncology”) has emerged as a new discipline in clinical medicine given recent advances in cancer therapy, and is driven by the cardiovascular complications that occur as a direct result of cancer therapy. Traditional therapies, such as anthracyclines and radiation, have been recognized for years to have cardiovascular complications. Less expected were the cardiovascular effects of “targeted” cancer therapies, which were initially felt to be specific to cancer cells and would spare any adverse effects on the heart. Cancers are typically driven by mutations, translocations, and/or over-expression of protein kinases. The majority of these mutated kinases are tyrosine kinases, though serine/threonine kinases also play key roles in some malignancies. Several agents were developed to target these kinases, but many more are in development. Major successes have been largely restricted to agents targeting Her2 (mutated or over-expressed in breast cancer), BCR-ABL (CML and some cases of ALL),and c-Kit (gastrointestinal stromal tumor).Other agents targeting more complex malignancies such as advanced solid tumors have had successes, but have not extended life to the degree seen with CML. Years before the first targeted therapeutic, Judah Folkman correctly proposed that to address solid tumors, one had to target the inherent neo-angiogenesis. Unfortunately, emerging evidence confirms that angiogenesis inhibitors cause cardiac complications, including hypertension, thrombosis, and heart failure. And therein lies the Catch 22. On the other hand, cardiomyopathies that arise unexpectedly from such targeted therapies can provide key insights into the normal function of the heart. PMID:23989717

Unexpected diversity of basidiomycetous endophytes in sapwood and leaves of Hevea.

PubMed

Martin, Rachael; Gazis, Romina; Skaltsas, Demetra; Chaverri, Priscila; Hibbett, David

2015-01-01

Research on fungal endophytes has expanded dramatically in recent years, but little is known about the diversity and ecological roles of endophytic basidiomycetes. Here we report the analysis of 310 basidiomycetous endophytes isolated from wild and planted populations of the rubber tree genus, Hevea. Species accumulation curves were nonasymptotic, as in the majority of endophyte surveys, indicating that more sampling is needed to recover the true diversity of the community. One hundred eighteen OTUs were delimited, representing nine orders of Basidiomycota (Agaricales, Atheliales, Auriculariales, Cantharellales, Hymenochaetales, Polyporales, Russulales, Septobasidiales, Tremellales). The diversity of basidiomycetous endophytes found inhabiting wild populations of Hevea was comparable to that present in plantations. However, when samples were segregated by tissue type, sapwood of wild populations was found to contain a higher number of species than sapwood of planted trees. Seventy-five percent of isolates were members of the Polyporales, the majority in the phlebioid clade. Most of the species belong to clades known to cause a white-rot type of wood decay. Two species in the insect-associated genus Septobasidium were isolated. The most frequently isolated genera included Bjerkandera, Ceriporia, Phanerochaete, Phlebia, Rigidoporus, Tinctoporellus, Trametes (Polyporales), Peniophora, Stereum (Russulales) and Coprinellus (Agaricales), all of which have been reported as endophytes from a variety of hosts, across wide geographic locations. Literature records on the geographic distribution and host association of these genera revealed that their distribution and substrate affinity could be extended if the endophytic niche was investigated as part of fungal biodiversity surveys. © 2015 by The Mycological Society of America.

Willingness and ability to pay for unexpected dental expenses by Finnish adults

PubMed Central

2012-01-01

Background Since 2002, adults have been able to choose oral health care services in the public sector or in the private sector in Finland. Though various subsidies for care exist in both sectors, the Public Dental Service (PDS) is a cheaper option for the patient but, on the other hand, there are no waiting lists for private care. The aim of this study was to assess middle-aged adults' use of dental services, willingness to pay (WTP) and ability to pay (ATP) for unexpected, urgent dental treatment. Methods Postal questionnaires on use of dental services were sent to a random sample of 1500 47-59 year old adults living in three large municipalities in the Helsinki region. The initial response rate was 65.8%. Two hypothetical scenarios were presented: "What would be the highest price you would be prepared to pay to have a lost filling replaced immediately, or, at the latest, the day after losing the filling?" and " How much could you pay for unexpected dental expenses at two weeks notice, if you suddenly needed more comprehensive treatment?" Logistic regression analysis was used to analyse factors related to WTP and ATP. Results Most respondents (89.6%) had visited a dentist recently and a majority (76.1%) had used private services. For immediate replacement of a lost filling, almost all respondents (93.2%) were willing to pay the lower price charged in the PDS and 46.2% were willing to pay the private fee. High income and no subjective need for dental treatment were positively associated with the probability of paying a higher price. Most respondents (93.0%) were able to pay a low fee, EUR 50 and almost half (41.6%) at least EUR 300 for unexpected treatment at short notice. High income and male sex were associated with high ATP. Conclusion There was a strong and statistically significant relationship between income and WTP and ATP for urgent dental care, indicating that access to publicly provided services improved equity for persons with low income. PMID:22935077

Genomic and Physiological Characterization of the Chromate-Reducing, Aquifer-Derived Firmicute Pelosinus sp. Strain HCF1

NASA Astrophysics Data System (ADS)

Beller, H. R.; Han, R.; Karaoz, U.; Lim, H.; Brodie, E. L.

2012-12-01

Pelosinus species are fermentative firmicutes that were recently reported to be prominent members of microbial communities at contaminated subsurface sites in multiple locations. Here we report metabolic characteristics and their putative genetic basis in Pelosinus sp. strain HCF1, an isolate that predominated anaerobic, Cr(VI)-reducing columns constructed with Hanford 100H aquifer sediment (constituting 80% of the total bacterial population in the columns). Strain HCF1 ferments lactate to propionate and acetate (a complete fermentation pathway was identified in the genome) and its genome encodes both [NiFe]- and [FeFe]-hydrogenases for H2 cycling. This bacterium has unexpected capabilities and gene content associated with reduction of nitrogen oxides. In this strain, either H2 or lactate can act as a sole electron donor for nitrate, Cr(VI), and Fe(III) reduction. Transcriptional studies demonstrated differential expression of nitrate reductases and hydrogenases. Overall, the unexpected metabolic capabilities and gene content reported here broaden our perspective on what biogeochemical and ecological roles this species might play as a prominent member of microbial communities in subsurface environments.

Transcriptome map of plant mitochondria reveals islands of unexpected transcribed regions.

PubMed

Fujii, Sota; Toda, Takushi; Kikuchi, Shunsuke; Suzuki, Ryutaro; Yokoyama, Koji; Tsuchida, Hiroko; Yano, Kentaro; Toriyama, Kinya

2011-06-01

Plant mitochondria contain a relatively large amount of genetic information, suggesting that their functional regulation may not be as straightforward as that of metazoans. We used a genomic tiling array to draw a transcriptomic atlas of Oryza sativa japonica (rice) mitochondria, which was predicted to be approximately 490-kb long. Whereas statistical analysis verified the transcription of all previously known functional genes such as the ones related to oxidative phosphorylation, a similar extent of RNA expression was frequently observed in the inter-genic regions where none of the previously annotated genes are located. The newly identified open reading frames (ORFs) predicted in these transcribed inter-genic regions were generally not conserved among flowering plant species, suggesting that these ORFs did not play a role in mitochondrial principal functions. We also identified two partial fragments of retrotransposon sequences as being transcribed in rice mitochondria. The present study indicated the previously unexpected complexity of plant mitochondrial RNA metabolism. Our transcriptomic data (Oryza sativa Mitochondrial rna Expression Server: OsMES) is publicly accessible at [http://bioinf.mind.meiji.ac.jp/cgi-bin/gbrowse/OsMes/#search].

Out of Mind, Out of Sight: Unexpected Scene Elements Frequently Go Unnoticed Until Primed.

PubMed

Slavich, George M; Zimbardo, Philip G

2013-12-01

The human visual system employs a sophisticated set of strategies for scanning the environment and directing attention to stimuli that can be expected given the context and a person's past experience. Although these strategies enable us to navigate a very complex physical and social environment, they can also cause highly salient, but unexpected stimuli to go completely unnoticed. To examine the generality of this phenomenon, we conducted eight studies that included 15 different experimental conditions and 1,577 participants in all. These studies revealed that a large majority of participants do not report having seen a woman in the center of an urban scene who was photographed in midair as she was committing suicide. Despite seeing the scene repeatedly, 46 % of all participants failed to report seeing a central figure and only 4.8 % reported seeing a falling person. Frequency of noticing the suicidal woman was highest for participants who read a narrative priming story that increased the extent to which she was schematically congruent with the scene. In contrast to this robust effect of inattentional blindness , a majority of participants reported seeing other peripheral objects in the visual scene that were equally difficult to detect, yet more consistent with the scene. Follow-up qualitative analyses revealed that participants reported seeing many elements that were not actually present, but which could have been expected given the overall context of the scene. Together, these findings demonstrate the robustness of inattentional blindness and highlight the specificity with which different visual primes may increase noticing behavior.

Novel Proinflammatory Function of Renal Intercalated Cells.

PubMed

Breton, Sylvie; Brown, Dennis

2018-01-01

Serious and often fatal acute kidney injury (AKI) is frequently seen after major surgery, local and remote organ damage, and sepsis. It is associated with uncontrolled inflammation, and is usually diagnosed only after the kidneys have gone through significant and often irreversible damage. During our work involving another type of kidney disease that leads to acid-base disorders of the blood, we unexpectedly found high levels of a protein called the P2Y14 "purinergic" receptor, in specialized kidney epithelial cells called intercalated cells (ICs). These cells are responsible for maintaining whole body acid-base balance by regulating the secretion of excess protons into the urine, which normalizes blood pH. However, it turns out that the P2Y14 receptor in these cells responds to a molecule called uridine diphosphate (UDP)-glucose, which is a danger signal released by damaged cells anywhere in the body. When UDP-glucose reaches the kidney, it stimulates ICs to produce chemoattractant cytokines; this results in renal inflammation and contributes to the onset of AKI. Key Message: Thus, our work now points to ICs as key mediators of renal inflammation and AKI, following surgery and/or damage to remote organs, sepsis, and also local insults to the kidney itself. The link between the proton secreting ICs of the kidney and AKI is an example of how a fundamental research project with a defined aim, in this case understanding acid-base homeostasis, can lead to a novel observation that has unexpected but major implications in another area of human health. © 2018 The Author(s) Published by S. Karger AG, Basel.

Conservation of Transcription Start Sites within Genes across a Bacterial Genus

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

Shao, Wenjun; Price, Morgan N.; Deutschbauer, Adam M.

Transcription start sites (TSSs) lying inside annotated genes, on the same or opposite strand, have been observed in diverse bacteria, but the function of these unexpected transcripts is unclear. Here, we use the metal-reducing bacterium Shewanella oneidensis MR-1 and its relatives to study the evolutionary conservation of unexpected TSSs. Using high-resolution tiling microarrays and 5'-end RNA sequencing, we identified 2,531 TSSs in S. oneidensis MR-1, of which 18% were located inside coding sequences (CDSs). Comparative transcriptome analysis with seven additional Shewanella species revealed that the majority (76%) of the TSSs within the upstream regions of annotated genes (gTSSs) were conserved.more » Thirty percent of the TSSs that were inside genes and on the sense strand (iTSSs) were also conserved. Sequence analysis around these iTSSs showed conserved promoter motifs, suggesting that many iTSS are under purifying selection. Furthermore, conserved iTSSs are enriched for regulatory motifs, suggesting that they are regulated, and they tend to eliminate polar effects, which confirms that they are functional. In contrast, the transcription of antisense TSSs located inside CDSs (aTSSs) was significantly less likely to be conserved (22%). However, aTSSs whose transcription was conserved often have conserved promoter motifs and drive the expression of nearby genes. Overall, our findings demonstrate that some internal TSSs are conserved and drive protein expression despite their unusual locations, but the majority are not conserved and may reflect noisy initiation of transcription rather than a biological function.« less

Patients' intentions to inform relatives about Type 2 diabetes risk: the role of worry in the process of family risk disclosure.

PubMed

van Esch, S C M; Nijkamp, M D; Cornel, M C; Snoek, F J

2012-12-01

Patients with Type 2 diabetes may play a role as intermediary between medical professionals and at-risk relatives to promote diabetes prevention in their family. This study aimed to further our understanding of factors that influence the decisional process of familial risk disclosure in patients with diabetes. In a cross-sectional study, patients with Type 2 diabetes (n = 546) filled in a questionnaire assessing family risk perception, worry, personal beliefs regarding diabetes prevention, diabetes-related family communication, intention and perceived ability to inform relatives about familial risk of diabetes. Data were analysed using hierarchical logistic regression and multiple mediation analyses. Sixty per cent of the patients were willing to inform their relatives about familial diabetes risk; 61% reported high family risk perception and 41% had positive control beliefs with regard to preventive options in relatives. A majority (69%) did not express serious concern about relatives developing diabetes. Worry about relatives, knowing what to tell, whom to notify, and communication about diabetes in general appeared to facilitate family risk disclosure. Unexpectedly, high family risk perception in itself did not significantly increase patients' intentions to inform relatives; rather, risk perception appeared to exert an indirect effect through worry and beliefs about diabetes prevention. Worry in patients with diabetes appears to be a key factor in the process of family risk disclosure. When professionals guide their patients in this process, they should not only provide risk information, but also address worries and emphasize opportunities for diabetes prevention. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health.

PubMed

Laurans, Ludivine; Venteclef, Nicolas; Haddad, Yacine; Chajadine, Mouna; Alzaid, Fawaz; Metghalchi, Sarvenaz; Sovran, Bruno; Denis, Raphael G P; Dairou, Julien; Cardellini, Marina; Moreno-Navarrete, Jose-Maria; Straub, Marjolene; Jegou, Sarah; McQuitty, Claire; Viel, Thomas; Esposito, Bruno; Tavitian, Bertrand; Callebert, Jacques; Luquet, Serge H; Federici, Massimo; Fernandez-Real, José Manuel; Burcelin, Remy; Launay, Jean-Marie; Tedgui, Alain; Mallat, Ziad; Sokol, Harry; Taleb, Soraya

2018-06-25

The association between altered gut microbiota, intestinal permeability, inflammation and cardiometabolic diseases is becoming increasingly clear but remains poorly understood 1,2 . Indoleamine 2,3-dioxygenase is an enzyme induced in many types of immune cells, including macrophages in response to inflammatory stimuli, and catalyzes the degradation of tryptophan along the kynurenine pathway. Indoleamine 2,3-dioxygenase activity is better known for its suppression of effector T cell immunity and its activation of regulatory T cells 3,4 . However, high indoleamine 2,3-dioxygenase activity predicts worse cardiovascular outcome 5-9 and may promote atherosclerosis and vascular inflammation 6 , suggesting a more complex role in chronic inflammatory settings. Indoleamine 2,3-dioxygenase activity is also increased in obesity 10-13 , yet its role in metabolic disease is still unexplored. Here, we show that obesity is associated with an increase of intestinal indoleamine 2,3-dioxygenase activity, which shifts tryptophan metabolism from indole derivative and interleukin-22 production toward kynurenine production. Indoleamine 2,3-dioxygenase deletion or inhibition improves insulin sensitivity, preserves the gut mucosal barrier, decreases endotoxemia and chronic inflammation, and regulates lipid metabolism in liver and adipose tissues. These beneficial effects are due to rewiring of tryptophan metabolism toward a microbiota-dependent production of interleukin-22 and are abrogated after treatment with a neutralizing anti-interleukin-22 antibody. In summary, we identify an unexpected function of indoleamine 2,3-dioxygenase in the fine tuning of intestinal tryptophan metabolism with major consequences on microbiota-dependent control of metabolic disease, which suggests indoleamine 2,3-dioxygenase as a potential therapeutic target.

Decision-making in a death investigation: Emotion, families and the coroner.

PubMed

Tait, Gordon; Carpenter, Belinda; Quadrelli, Carol; Barnes, Michael

2016-03-01

The role of the coroner in common law countries such as Australia, England, Canada and New Zealand is to preside over death investigations where there is uncertainty as to the manner of death, a need to identify the deceased, a death of unknown cause, or a violent or unnatural death. The vast majority of these deaths are not suspicious and thus require coroners to engage with grieving families who have been thrust into a legal process through the misfortune of a loved one's sudden or unexpected death. In this research, 10 experienced coroners discussed how they negotiated the grief and trauma evident in a death investigation. In doing so, they articulated two distinct ways in which legal officers engaged with emotions, which are also evident in the literature. The first engages the script of judicial dispassion, articulating a hierarchical relationship between reason and emotion, while the second introduces an ethic of care via the principles of therapeutic jurisprudence, and thus offers a challenge to the role of emotion in the personae of the professional judicial officer. By using Hochschild's work on the sociology of emotions, this article discusses the various ways in which coroners manage the emotion of a death investigation through emotion work. While emotional distance may be an understandable response by coroners to the grief and trauma experienced by families and directed at cleaner coronial decision-making, the article concludes that coroners may be better served by offering emotions such as sympathy, consideration and compassion directly to the family in those situations where families are struggling to accept, or are resistant to, coroners' decisions.

The future of continuing medical education: the roles of medical professional societies and the health care industry: Position paper prepared with contributions from the European Society of Cardiology Committees for Advocacy, Education and Industry Relations, Endorsed by the Board of the European Society of Cardiology.

PubMed

2018-02-28

In recent years, wide ranging biomedical innovation has provided powerful new approaches for prevention, diagnosis and management of diseases. In order to translate such innovation into effective practice, physicians must frequently update their knowledge base and skills through continuing medical education and training. Medical Professional Societies, run as not-for-profit organizations led by peers, are uniquely placed to deliver balanced, disease oriented and patient centred education. The medical industry has a major role in the development of new, improved technology, devices and medication. In fact, the best innovations have been achieved through collaboration with scientists, clinical academics and practicing physicians. Industry has for many years been committed to ensure the optimal and safe application of its products by providing unrestricted support of medical education developed and delivered by international and national learned societies. Recently adopted Codes of Practice for the Pharmaceutical and Device industry were intended to enhance public trust in the relationship between biomedical industry and physicians. Unexpectedly, changes resulting from adoption of the Codes have limited the opportunity for unconditional industry support of balanced medical education in favour of a more direct involvement of industry in informing physicians about their products. We describe the need for continuing medical education in Cardiovascular Medicine in Europe, interaction between the medical profession and medical industry, and propose measures to safeguard the provision of high quality, balanced medical education.

The Crystal Structure of Cancer Osaka Thyroid Kinase Reveals an Unexpected Kinase Domain Fold*

PubMed Central

Gutmann, Sascha; Hinniger, Alexandra; Fendrich, Gabriele; Drückes, Peter; Antz, Sylvie; Mattes, Henri; Möbitz, Henrik; Ofner, Silvio; Schmiedeberg, Niko; Stojanovic, Aleksandar; Rieffel, Sebastien; Strauss, André; Troxler, Thomas; Glatthar, Ralf; Sparrer, Helmut

2015-01-01

Macrophages are important cellular effectors in innate immune responses and play a major role in autoimmune diseases such as rheumatoid arthritis. Cancer Osaka thyroid (COT) kinase, also known as mitogen-activated protein kinase kinase kinase 8 (MAP3K8) and tumor progression locus 2 (Tpl-2), is a serine-threonine (ST) kinase and is a key regulator in the production of pro-inflammatory cytokines in macrophages. Due to its pivotal role in immune biology, COT kinase has been identified as an attractive target for pharmaceutical research that is directed at the discovery of orally available, selective, and potent inhibitors for the treatment of autoimmune disorders and cancer. The production of monomeric, recombinant COT kinase has proven to be very difficult, and issues with solubility and stability of the enzyme have hampered the discovery and optimization of potent and selective inhibitors. We developed a protocol for the production of recombinant human COT kinase that yields pure and highly active enzyme in sufficient yields for biochemical and structural studies. The quality of the enzyme allowed us to establish a robust in vitro phosphorylation assay for the efficient biochemical characterization of COT kinase inhibitors and to determine the x-ray co-crystal structures of the COT kinase domain in complex with two ATP-binding site inhibitors. The structures presented in this study reveal two distinct ligand binding modes and a unique kinase domain architecture that has not been observed previously. The structurally versatile active site significantly impacts the design of potent, low molecular weight COT kinase inhibitors. PMID:25918157

Involvement of T6 Pili in Biofilm Formation by Serotype M6 Streptococcus pyogenes

PubMed Central

Kimura, Keiji Richard; Nakata, Masanobu; Sumitomo, Tomoko; Kreikemeyer, Bernd; Podbielski, Andreas; Terao, Yutaka

2012-01-01

The group A streptococcus (GAS) Streptococcus pyogenes is known to cause self-limiting purulent infections in humans. The role of GAS pili in host cell adhesion and biofilm formation is likely fundamental in early colonization. Pilus genes are found in the FCT (fibronectin-binding protein, collagen-binding protein, and trypsin-resistant antigen) genomic region, which has been classified into nine subtypes based on the diversity of gene content and nucleotide sequence. Several epidemiological studies have indicated that FCT type 1 strains, including serotype M6, produce large amounts of monospecies biofilm in vitro. We examined the direct involvement of pili in biofilm formation by serotype M6 clinical isolates. In the majority of tested strains, deletion of the tee6 gene encoding pilus shaft protein T6 compromised the ability to form biofilm on an abiotic surface. Deletion of the fctX and srtB genes, which encode pilus ancillary protein and class C pilus-associated sortase, respectively, also decreased biofilm formation by a representative strain. Unexpectedly, these mutant strains showed increased bacterial aggregation compared with that of the wild-type strain. When the entire FCT type 1 pilus region was ectopically expressed in serotype M1 strain SF370, biofilm formation was promoted and autoaggregation was inhibited. These findings indicate that assembled FCT type 1 pili contribute to biofilm formation and also function as attenuators of bacterial aggregation. Taken together, our results show the potential role of FCT type 1 pili in the pathogenesis of GAS infections. PMID:22155780

Effect of c-myc on the ultrastructural structure of cochleae in guinea pigs with noise induced hearing loss

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

Han, Yu; Zhong, Cuiping; Hong, Liu

2009-12-18

Noise over-stimulation may induce hair cells loss and hearing deficit. The c-myc oncogene is a major regulator for cell proliferation, growth, and apoptosis. However, the role of this gene in the mammalian cochlea is still unclear. The study was designed to firstly investigate its function under noise condition, from the aspect of cochlear ultrastructural changes. We had established the adenoviral vector of c-myc gene and delivered the adenovirus suspension into the scala tympani of guinea pigs 4 days before noise exposure. The empty adenoviral vectors were injected as control. Then, all subjects were exposed to 4-kHz octave-band noise at 110more » dB SPL for 8 h/day, 3 days consecutively. Auditory thresholds were assessed by auditory brainstem response, prior to and 7 days following noise exposure. On the seventh days after noise exposure, the cochlear sensory epithelia surface was observed microscopically and the cochleae were taken to study the ultrastructural changes. The results indicated that auditory threshold shift after noise exposure was higher in the ears treated with Ad.EGFP than that treated with Ad.c-myc-EGFP. Stereocilia loss and the disarrangement of outer hair cells were observed, with greater changes found in the Ad.EGFP group. Also, the ultrastructure changes were severe in the Ad.EGFP group, but not obvious in the Ad.c-myc-EGFP group. Therefore, c-myc gene might play an unexpected role in hearing functional and morphological protection from acoustic trauma.« less

Anxiety sensitivity and expectation of arousal differentially affect the respiratory response to caffeine.

PubMed

Pané-Farré, Christiane A; Alius, Manuela G; Modeß, Christiane; Methling, Karen; Blumenthal, Terry; Hamm, Alfons O

2015-06-01

This study aimed to test how expectations and anxiety sensitivity influence respiratory and autonomic responses to caffeine. The current study investigated the effects of expected vs. unexpected caffeine ingestion in a group of persons prone to the anxiety-provoking effect of caffeine (high anxiety sensitive persons, that is, persons scoring at least one SD above the mean on the Anxiety Sensitivity Index (Peterson and Reiss 1992)) as compared to low-anxious controls. Autonomic arousal (heart rate, skin conductance level), respiratory responding (expired CO2, minute ventilation), and subjective report were assessed in high and low anxiety sensitive participants immediately after beverage consumption and at absorption peak (30 min post-consumption) in four separate sessions during which either coffee (expectation of caffeine) or bitter lemon soda (no expectation of caffeine) was crossed with 4 mg/kg caffeine vs. no drug. High and low anxiety sensitive persons showed comparable autonomic arousal and symptom reports to caffeine which was modulated by expectation, i.e., greater for coffee. Respiratory responding (CO2 decrease, minute ventilation increase) was more accentuated when caffeine was both expected and administered in the low anxiety sensitive group but more accentuated when caffeine was unexpectedly administered in the high anxiety sensitive group. Autonomic arousal and respiratory effects were observable within a few minutes after caffeine administration and were most pronounced at maximum absorption. The results highlight the modulating role of expectancies in respiratory responding to caffeine in low vs. high anxiety sensitive persons and might have important implications for the better understanding of unexpected panic attacks.

The role of post-mortem investigations in determining the cause of sudden unexpected death in infancy.

PubMed

Weber, M A; Ashworth, M T; Risdon, R A; Hartley, J C; Malone, M; Sebire, N J

2008-12-01

Several autopsy protocols have been suggested for investigating sudden unexpected deaths in infancy (SUDI). The aim of this study is to provide data on the utility of such post-mortem investigations from a large paediatric autopsy series to inform future policy. Retrospective analysis of >1500 consecutive post-mortem examinations carried out by specialist paediatric pathologists at a single centre during a 10-year period according to a common autopsy protocol that included the use of detailed ancillary investigations. SUDI was defined as the sudden unexpected death of an infant aged from 7 to 365 days. All data capture and cause of death classification were carried out according to defined criteria. Of 1516 paediatric post-mortem examinations, 546 presented as SUDI. In 202 infants (37%), death was explained by the autopsy findings. The other 344 cases (63%) remained unexplained. Of the explained deaths, over half (58%) were infective, most commonly due to pneumonia (22%). The component of the post-mortem examination that primarily determined the final cause of death was histological examination in 92 infants (46%), macroscopic examination in 61 (30%), microbiological investigations in 38 (19%) and clinical history in 10 (5%). This constitutes the largest single-institution autopsy study of SUDI. Ten years on from the Confidential Enquiry into Stillbirths and Deaths in Infancy (CESDI) SUDI studies, the ascertainment of a cause of death at autopsy has improved. However, with almost two thirds of SUDI remaining unexplained, alternative and/or additional diagnostic techniques are required to improve detection rates of identifiable causes of death at autopsy.

3 CFR - Unexpected Urgent Refugee and Migration Needs

Code of Federal Regulations, 2013 CFR

2013-01-01

... 3 The President 1 2013-01-01 2013-01-01 false Unexpected Urgent Refugee and Migration Needs... Unexpected Urgent Refugee and Migration Needs Memorandum for the Secretary of State By the authority vested...) of the Migration and Refugee Assistance Act of 1962 (the “Act”), as amended, (22 U.S.C. 2601(c)(1...

Orthographic Processing and Visual Sequential Memory in Unexpectedly Poor Spellers

ERIC Educational Resources Information Center

Holmes, Virginia M.; Malone, Aisling M.; Redenbach, Holly

2008-01-01

Does unexpectedly poor spelling in adults result from inferior visual sequential memory? In one experiment, unexpectedly poor spellers performed significantly worse than better spellers in the immediate reproduction of sequences of visual symbols, but in a second experiment, the effect was not replicated. Poor spellers were also no worse at the…

3 CFR - Unexpected Urgent Refugee and Migration Needs

Code of Federal Regulations, 2013 CFR

2013-01-01

... 3 The President 1 2013-01-01 2013-01-01 false Unexpected Urgent Refugee and Migration Needs Presidential Documents Other Presidential Documents Presidential Determination No. 2012-6 of April 3, 2012 Unexpected Urgent Refugee and Migration Needs Memorandum for the Secretary of State By the authority vested in me as President by the Constitution...

77 FR 21389 - Unexpected Urgent Refugee and Migration Needs

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

... April 3, 2012 Unexpected Urgent Refugee and Migration Needs Memorandum for the Secretary of State By the... 2(c)(1) of the Migration and Refugee Assistance Act of 1962 (the ``Act''), as amended, (22 U.S.C... United States Emergency Refugee and Migration Assistance Fund, for the purpose of meeting unexpected and...

Molecular dynamics correctly models the unusual major conformation of the GAGU RNA internal loop and with NMR reveals an unusual minor conformation.

PubMed

Spasic, Aleksandar; Kennedy, Scott D; Needham, Laura; Manoharan, Muthiah; Kierzek, Ryszard; Turner, Douglas H; Mathews, David H

2018-05-01

The RNA "GAGU" duplex, (5'GAC GAGU GUCA) 2 , contains the internal loop (5'-GAGU-3') 2 , which has two conformations in solution as determined by NMR spectroscopy. The major conformation has a loop structure consisting of trans -Watson-Crick/Hoogsteen GG pairs, A residues stacked on each other, U residues bulged outside the helix, and all sugars with a C2'- endo conformation. This differs markedly from the internal loops, (5'-G AG C-3') 2 , (5'-A AG U-3') 2 , and (5'-UAGG-3') 2 , which all have cis -Watson-Crick/Watson-Crick AG "imino" pairs flanked by cis -Watson-Crick/Watson-Crick canonical pairs resulting in maximal hydrogen bonding. Here, molecular dynamics was used to test whether the Amber force field (ff99 + bsc0 + OL3) approximates molecular interactions well enough to keep stable the unexpected conformation of the GAGU major duplex structure and the NMR structures of the duplexes containing (5'-G AG C-3') 2 , (5'-A AG U-3') 2 , and (5'-U AG G-3') 2 internal loops. One-microsecond simulations were repeated four times for each of the duplexes starting in their NMR conformations. With the exception of (5'-UAGG-3') 2 , equivalent simulations were also run starting with alternative conformations. Results indicate that the Amber force field keeps the NMR conformations of the duplexes stable for at least 1 µsec. They also demonstrate an unexpected minor conformation for the (5'-GAGU-3') 2 loop that is consistent with newly measured NMR spectra of duplexes with natural and modified nucleotides. Thus, unrestrained simulations led to the determination of the previously unknown minor conformation. The stability of the native (5'-GAGU-3') 2 internal loop as compared to other loops can be explained by changes in hydrogen bonding and stacking as the flanking bases are changed. © 2018 Spasic et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Paradoxical Role of DNA Methylation in Activation of FoxA2 Gene Expression during Endoderm Development*

PubMed Central

Bahar Halpern, Keren; Vana, Tal; Walker, Michael D.

2014-01-01

The transcription factor FoxA2 is a master regulator of endoderm development and pancreatic beta cell gene expression. To elucidate the mechanisms underlying the activation of the FoxA2 gene during differentiation, we have compared the epigenetic status of undifferentiated human embryonic stem cells (hESCs), hESC-derived early endoderm stage cells (CXCR4+ cells), and pancreatic islet cells. Unexpectedly, a CpG island in the promoter region of the FoxA2 gene displayed paradoxically high levels of DNA methylation in expressing tissues (CXCR4+, islets) and low levels in nonexpressing tissues. This CpG island region was found to repress reporter gene expression and bind the Polycomb group protein SUZ12 and the DNA methyltransferase (DNMT)3b preferentially in undifferentiated hESCs as compared with CXCR4+ or islets cells. Consistent with this, activation of FoxA2 gene expression, but not CXCR4 or SOX17, was strongly inhibited by 5-aza-2′-deoxycytidine and by knockdown of DNMT3b. We hypothesize that in nonexpressing tissues, the lack of DNA methylation allows the binding of DNA methyltransferases and repressing proteins, such as Polycomb group proteins; upon differentiation, DNMT activation leads to CpG island methylation, causing loss of repressor protein binding. These results suggest a novel and unexpected role for DNA methylation in the activation of FoxA2 gene expression during differentiation. PMID:25016019

Massive glutamine cyclization to pyroglutamic acid in human serum discovered using NMR spectroscopy.

PubMed

Nagana Gowda, G A; Gowda, Yashas N; Raftery, Daniel

2015-04-07

Glutamine is one of the most abundant metabolites in blood and is a precursor as well as end product central to numerous important metabolic pathways. A number of surprising and unexpected roles for glutamine, including cancer cell glutamine addiction discovered recently, stress the importance of accurate analysis of glutamine concentrations for understanding its role in health and numerous diseases. Utilizing a recently developed NMR approach that offers access to an unprecedented number of quantifiable blood metabolites, we have identified a surprising glutamine cyclization to pyroglutamic acid that occurs during protein removal. Intact, ultrafiltered and protein precipitated samples from the same pool of human serum were comprehensively investigated using (1)H NMR spectroscopy at 800 MHz to detect and quantitatively evaluate the phenomenon. Interestingly, although glutamine cyclization occurs in both ultrafiltered and protein precipitated serum, the cyclization was not detected in intact serum. Strikingly, due to cyclization, the apparent serum glutamine level drops by up to 75% and, concomitantly, the pyroglutamic acid level increases proportionately. Further, virtually under identical conditions, the magnitude of cyclization is vastly different for different portions of samples from the same pool of human serum. However, the sum of glutamine and pyroglutamic acid concentrations in each sample remains the same for all portions. These unexpected findings indicate the importance of considering the sum of apparent glutamine and pyroglutamic acid levels, obtained from the contemporary analytical methods, as the actual blood glutamine level for biomarker discovery and biological interpretations.

Inactivation of Msx1 and Msx2 in neural crest reveals an unexpected role in suppressing heterotopic bone formation in the head

PubMed Central

Roybal, Paul G.; Wu, Nancy L.; Sun, Jingjing; Ting, Man-chun; Schaefer, Christopher; Maxson, Robert E.

2011-01-01

In an effort to understand the morphogenetic forces that shape the bones of the skull, we inactivated Msx1 and Msx2 conditionally in neural crest. We show that Wnt1-Cre inactivation of up to three Msx1/2 alleles results in a progressively larger defect in the neural crest-derived frontal bone. Unexpectedly, in embryos lacking all four Msx1/2 alleles, the large defect is filled in with mispatterned bone consisting of ectopic islands of bone between the reduced frontal bones, just anterior to the parietal bones. The bone is derived from neural crest, not mesoderm, and, from DiI cell marking experiments, originates in a normally non-osteogenic layer of cells through which the rudiment elongates apically. Associated with the heterotopic osteogeneis is an upregulation of Bmp signaling in this cell layer. Prevention of this upregulation by implantation of noggin-soaked beads in head explants also prevented heterotopic bone formation. These results suggest that Msx genes have a dual role in calvarial development: They are required for the differentiation and proliferation of osteogenic cells within rudiments, and they are also required to suppress an osteogenic program in a cell layer within which the rudiments grow. We suggest that the inactivation of this repressive activity may be one cause of Wormian bones, ectopic bones that are a feature of a variety of pathological conditions in which calvarial bone development is compromised. PMID:20398647

Essential and Unexpected Role of YY1 to Promote Mesodermal Cardiac Differentiation

PubMed Central

Gregoire, Serge; Karra, Ravi; Passer, Derek; Deutsch, Marcus-Andre; Krane, Markus; Feistritzer, Rebecca; Sturzu, Anthony; Domian, Ibrahim; Saga, Yumiko; Wu, Sean M.

2013-01-01

Rational Cardiogenesis is regulated by a complex interplay between transcription factors. However, little is known about how these interactions regulate the transition from mesodermal precursors to cardiac progenitor cells (CPCs). Objective To identify novel regulators of mesodermal cardiac lineage commitment. Methods and Results We performed a bioinformatic-based transcription factor binding site analysis on upstream promoter regions of genes that are enriched in embryonic stem cell (ESC)-derived CPCs. From 32 candidate transcription factors screened, we found that YY1, a repressor of sarcomeric gene expression, is present in CPCs in vivo. Interestingly, we uncovered the ability of YY1 to transcriptionally activate Nkx2.5, a key marker of early cardiogenic commitment. YY1 regulates Nkx2.5 expression via a 2.1 kb cardiac-specific enhancer as demonstrated by in vitro luciferase-based assays and in vivo chromatin immunoprecipitation (ChIP) and genome-wide sequencing analysis. Furthermore, the ability of YY1 to activate Nkx2.5 expression depends on its cooperative interaction with Gata4 at a nearby chromatin. Cardiac mesoderm-specific loss-of-function of YY1 resulted in early embryonic lethality. This was corroborated in vitro by ESC-based assays where we show that the overexpression of YY1 enhanced the cardiogenic differentiation of ESCs into CPCs. Conclusion These results demonstrate an essential and unexpected role for YY1 to promote cardiogenesis as a transcriptional activator of Nkx2.5 and other CPC-enriched genes. PMID:23307821

A Comparison of the Pharmacokinetics and Pulmonary Lymphatic Exposure of a Generation 4 PEGylated Dendrimer Following Intravenous and Aerosol Administration to Rats and Sheep.

PubMed

Ryan, Gemma M; Bischof, Robert J; Enkhbaatar, Perenlei; McLeod, Victoria M; Chan, Linda J; Jones, Seth A; Owen, David J; Porter, Christopher J H; Kaminskas, Lisa M

2016-02-01

Cancer metastasis to pulmonary lymph nodes dictates the need to deliver chemotherapeutic and diagnostic agents to the lung and associated lymph nodes. Drug conjugation to dendrimer-based delivery systems has the potential to reduce toxicity, enhance lung retention and promote lymphatic distribution in rats. The current study therefore evaluated the pharmacokinetics and lung lymphatic exposure of a PEGylated dendrimer following inhaled administration. Plasma pharmacokinetics and disposition of a 22 kDa PEGylated dendrimer were compared after aerosol administration to rats and sheep. Lung-derived lymph could not be sampled in rats and so lymphatic transport of the dendrimer from the lung was assessed in sheep. Higher plasma concentrations were achieved when dendrimer was administered to the lungs of rats as a liquid instillation when compared to an aerosol. Plasma pharmacokinetics were similar between sheep and rats, although some differences in disposition patterns were evident. Unexpectedly, less than 0.5% of the aerosol dose was recovered in pulmonary lymph. The data suggest that rats provide a relevant model for assessing the pharmacokinetics of inhaled macromolecules prior to evaluation in larger animals, but that the pulmonary lymphatics are unlikely to play a major role in the absorption of nanocarriers from the lungs.

Live-cell imaging approaches for the investigation of xenobiotic-induced oxidant stress☆,☆☆

PubMed Central

Wages, Phillip A.; Cheng, Wan-Yun; Gibbs-Flournoy, Eugene; Samet, James M.

2017-01-01

Background Oxidant stress is arguably a universal feature in toxicology. Research studies on the role of oxidant stress induced by xenobiotic exposures have typically relied on the identification of damaged biomolecules using a variety of conventional biochemical and molecular techniques. However, there is increasing evidence that low-level exposure to a variety of toxicants dysregulates cellular physiology by interfering with redox-dependent processes. Scope of review The study of events involved in redox toxicology requires methodology capable of detecting transient modifications at relatively low signal strength. This article reviews the advantages of live-cell imaging for redox toxicology studies. Major conclusions Toxicological studies with xenobiotics of supra-physiological reactivity require careful consideration when using fluorogenic sensors in order to avoid potential artifacts and false negatives. Fortunately, experiments conducted for the purpose of validating the use of these sensors in toxicological applications often yield unexpected insights into the mechanisms through which xenobiotic exposure induces oxidant stress. General significance Live-cell imaging using a new generation of small molecule and genetically encoded fluorophores with excellent sensitivity and specificity affords unprecedented spatiotemporal resolution that is optimal for redox toxicology studies. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. PMID:27208426

Very High Cycle Fatigue Failure Analysis and Life Prediction of Cr-Ni-W Gear Steel Based on Crack Initiation and Growth Behaviors.

PubMed

Deng, Hailong; Li, Wei; Sakai, Tatsuo; Sun, Zhenduo

2015-12-02

The unexpected failures of structural materials in very high cycle fatigue (VHCF) regime have been a critical issue in modern engineering design. In this study, the VHCF property of a Cr-Ni-W gear steel was experimentally investigated under axial loading with the stress ratio of R = -1, and a life prediction model associated with crack initiation and growth behaviors was proposed. Results show that the Cr-Ni-W gear steel exhibits the constantly decreasing S-N property without traditional fatigue limit, and the fatigue strength corresponding to 10⁸ cycles is around 485 MPa. The inclusion-fine granular area (FGA)-fisheye induced failure becomes the main failure mechanism in the VHCF regime, and the local stress around the inclusion play a key role. By using the finite element analysis of representative volume element, the local stress tends to increase with the increase of elastic modulus difference between inclusion and matrix. The predicted crack initiation life occupies the majority of total fatigue life, while the predicted crack growth life is only accounts for a tiny fraction. In view of the good agreement between the predicted and experimental results, the proposed VHCF life prediction model involving crack initiation and growth can be acceptable for inclusion-FGA-fisheye induced failure.

Plastic debris ingestion by marine catfish: an unexpected fisheries impact.

PubMed

Possatto, Fernanda E; Barletta, Mário; Costa, Monica F; do Sul, Juliana A Ivar; Dantas, David V

2011-05-01

Plastic marine debris is a pervasive type of pollution. River basins and estuaries are a source of plastics pollution for coastal waters and oceans. Estuarine fauna is therefore exposed to chronic plastic pollution. Three important catfish species [Cathorops spixii (N=60), Cathorops agassizii (N=60) and Sciades herzbergii (N=62)] from South Western Atlantic estuaries were investigated in a tropical estuary of the Brazilian Northeast in relation to their accidental ingestion of plastic marine debris. Individuals from all three species had ingested plastics. In C. spixii and C. agassizii, 18% and 33% of individuals had plastic debris in their stomachs, respectively. S. herzbergii showed 18% of individuals were contaminated. All ontogenetic phases (juveniles, sub-adults and adults) were contaminated. Nylon fragments from cables used in fishery activities (subsistence, artisanal and commercial) played a major role in this contamination. These catfish spend their entire life cycles within the estuary and are an important feeding resource for larger, economically important, species. It is not yet possible to quantify the scale and depth of the consequences of this type of pollution. However, plastics are well known threat to living resources in this and other estuaries. Conservation actions will need to from now onto take plastics pollution into consideration. Copyright © 2011 Elsevier Ltd. All rights reserved.

Microbial eukaryotic diversity and distribution in a river plume and cyclonic eddy-influenced ecosystem in the South China Sea

PubMed Central

Wu, Wenxue; Wang, Lei; Liao, Yu; Huang, Bangqin

2015-01-01

To evaluate microbial eukaryotic diversity and distribution in mesoscale processes, we investigated 18S rDNA diversity in a river plume and cyclonic eddy-influenced ecosystem in the southwestern South China Sea (SCS). Restriction fragment length polymorphism analysis was carried out using multiple primer sets. Relative to a wide range of previous similar studies, we observed a significantly higher proportion of sequences of pigmented taxa. Among the photosynthetic groups, Haptophyta accounted for 27.7% of the sequenced clones, which belonged primarily to Prymnesiophyceae. Unexpectedly, five operational taxonomic units of Cryptophyta were closely related to freshwater species. The Chlorophyta mostly fell within the Prasinophyceae, which was comprised of six clades, including Clade III, which is detected in the SCS for the first time in this study. Among the photosynthetic stramenopiles, Chrysophyceae was the most diverse taxon, which included seven clades. The majority of 18S rDNA sequences affiliated with the Dictyochophyceae, Eustigmatophyceae, and Pelagophyceae were closely related to those of pure cultures. The results of redundancy analysis and the permutation Mantel test based on unweighted UniFrac distances, conducted for spatial analyses of the Haptophyta subclades suggested that the Mekong River plume and cyclonic eddy play important roles in regulating microbial eukaryotic diversity and distribution in the southwestern SCS. PMID:26268071

Abnormal tau phosphorylation in the thorny excrescences of CA3 hippocampal neurons in patients with Alzheimer's disease.

PubMed

Blazquez-Llorca, Lidia; Garcia-Marin, Virginia; Merino-Serrais, Paula; Ávila, Jesús; DeFelipe, Javier

2011-01-01

A key symptom in the early stages of Alzheimer's disease (AD) is the loss of declarative memory. The anatomical substrate that supports this kind of memory involves the neural circuits of the medial temporal lobe, and in particular, of the hippocampal formation and adjacent cortex. A main feature of AD is the abnormal phosphorylation of the tau protein and the presence of tangles. The sequence of cellular changes related to tau phosphorylation and tangle formation has been studied with an antibody that binds to diffuse phosphotau (AT8). Moreover, another tau antibody (PHF-1) has been used to follow the pathway of neurofibrillary (tau aggregation) degeneration in AD. We have used a variety of quantitative immunocytochemical techniques and confocal microscopy to visualize and characterize neurons labeled with AT8 and PHF-1 antibodies. We present here the rather unexpected discovery that in AD, there is conspicuous abnormal phosphorylation of the tau protein in a selective subset of dendritic spines. We identified these spines as the typical thorny excrescences of hippocampal CA3 neurons in a pre-tangle state. Since thorny excrescences represent a major synaptic target of granule cell axons (mossy fibers), such aberrant phosphorylation may play an essential role in the memory impairment typical of AD patients.

Skylab

NASA Image and Video Library

1973-05-01

The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the the station uninhabitable, threatening foods, medicines, films, and experiments. This image shows the sun-ravaged skin of the Orbital Workshop, bared by the missing heat shield, with blister scars and tarnish from temperatures that reached 300 degrees F. The rectangular opening at the upper center is the scientific airlock through which the parasol to protect the workshop from sun's rays was later deployed. This view was taken during a fly-around inspection by the Skylab-2 crew. The Marshall Space Flight Center had a major role in developing the procedures to repair the damaged Skylab.

Rapid evolution of RNA editing sites in a small non-essential plastid gene

PubMed Central

Fiebig, Andreas; Stegemann, Sandra; Bock, Ralph

2004-01-01

Chloroplast RNA editing proceeds by C-to-U transitions at highly specific sites. Here, we provide a phylogenetic analysis of RNA editing in a small plastid gene, petL, encoding subunit VI of the cytochrome b6f complex. Analyzing representatives from most major groups of seed plants, we find an unexpectedly high frequency and dynamics of RNA editing. High-frequency editing has previously been observed in plastid ndh genes, which are remarkable in that their mutational inactivation does not produce an obvious mutant phenotype. In order to test the idea that reduced functional constraints allow for more flexible evolution of RNA editing sites, we have created petL knockout plants by tobacco chloroplast transformation. We find that, in the higher plant tobacco, targeted inactivation of petL does not impair plant growth under a variety of conditions markedly contrasting the important role of petL in photosynthesis in the green alga Chlamydomonas reinhardtii. Together with a low number of editing sites in plastid genes that are essential to gene expression and photosynthetic activity, these data suggest that RNA editing sites may evolve more readily in those genes whose transitory loss of function can be tolerated. Accumulated evidence for this ‘relative neutrality hypothesis for the evolution of plastid editing sites’ is discussed. PMID:15240834

JMJD5 (Jumonji Domain-containing 5) Associates with Spindle Microtubules and Is Required for Proper Mitosis.

PubMed

He, Zhimin; Wu, Junyu; Su, Xiaonan; Zhang, Ye; Pan, Lixia; Wei, Huimin; Fang, Qiang; Li, Haitao; Wang, Da-Liang; Sun, Fang-Lin

2016-02-26

Precise mitotic spindle assembly is a guarantee of proper chromosome segregation during mitosis. Chromosome instability caused by disturbed mitosis is one of the major features of various types of cancer. JMJD5 has been reported to be involved in epigenetic regulation of gene expression in the nucleus, but little is known about its function in mitotic process. Here we report the unexpected localization and function of JMJD5 in mitotic progression. JMJD5 partially accumulates on mitotic spindles during mitosis, and depletion of JMJD5 results in significant mitotic arrest, spindle assembly defects, and sustained activation of the spindle assembly checkpoint (SAC). Inactivating SAC can efficiently reverse the mitotic arrest caused by JMJD5 depletion. Moreover, JMJD5 is found to interact with tubulin proteins and associate with microtubules during mitosis. JMJD5-depleted cells show a significant reduction of α-tubulin acetylation level on mitotic spindles and fail to generate enough interkinetochore tension to satisfy the SAC. Further, JMJD5 depletion also increases the susceptibility of HeLa cells to the antimicrotubule agent. Taken together, these results suggest that JMJD5 plays an important role in regulating mitotic progression, probably by modulating the stability of spindle microtubules. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Calcium Currents Are Enhanced by α2δ-1 Lacking Its Membrane Anchor*

PubMed Central

Kadurin, Ivan; Alvarez-Laviada, Anita; Ng, Shu Fun Josephine; Walker-Gray, Ryan; D'Arco, Marianna; Fadel, Michael G.; Pratt, Wendy S.; Dolphin, Annette C.

2012-01-01

The accessory α2δ subunits of voltage-gated calcium channels are membrane-anchored proteins, which are highly glycosylated, possess multiple disulfide bonds, and are post-translationally cleaved into α2 and δ. All α2δ subunits have a C-terminal hydrophobic, potentially trans-membrane domain and were described as type I transmembrane proteins, but we found evidence that they can be glycosylphosphatidylinositol-anchored. To probe further the function of membrane anchoring in α2δ subunits, we have now examined the properties of α2δ-1 constructs truncated at their putative glycosylphosphatidylinositol anchor site, located before the C-terminal hydrophobic domain (α2δ-1ΔC-term). We find that the majority of α2δ-1ΔC-term is soluble and secreted into the medium, but unexpectedly, some of the protein remains associated with detergent-resistant membranes, also termed lipid rafts, and is extrinsically bound to the plasma membrane. Furthermore, heterologous co-expression of α2δ-1ΔC-term with CaV2.1/β1b results in a substantial enhancement of the calcium channel currents, albeit less than that produced by wild-type α2δ-1. These results call into question the role of membrane anchoring of α2δ subunits for calcium current enhancement. PMID:22869375

cGAS drives non-canonical inflammasome activation in age-related macular degeneration

PubMed Central

Kerur, Nagaraj; Fukuda, Shinichi; Banerjee, Daipayan; Kim, Younghee; Fu, Dongxu; Apicella, Ivana; Varshney, Akhil; Yasuma, Reo; Fowler, Benjamin J.; Baghdasaryan, Elmira; Marion, Kenneth M.; Huang, Xiwen; Yasuma, Tetsuhiro; Hirano, Yoshio; Serbulea, Vlad; Ambati, Meenakshi; Ambati, Vidya L.; Kajiwara, Yuji; Ambati, Kameshwari; Bastos-Carvalho, Ana; Ogura, Yuichiro; Terasaki, Hiroko; Oshika, Tetsuro; Kim, Kyung Bo; Hinton, David R.; Leitinger, Norbert; Cambier, John C.; Buxbaum, Joseph D.; Kenney, M. Cristina; Jazwinski, S. Michal; Nagai, Hiroshi; Hara, Isao; West, A. Phillip; Fitzgerald, Katherine A.; Sadda, SriniVas R.; Gelfand, Bradley D.; Ambati, Jayakrishna

2017-01-01

Geographic atrophy is a blinding form of age-related macular degeneration characterized by death of the retinal pigmented epithelium (RPE). In this disease, the RPE displays evidence of DICER1 deficiency, resultant accumulation of endogenous Alu retroelement RNA, and NLRP3 inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human cell culture and in mouse models is driven by a non-canonical inflammasome pathway that results in activation of caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β (IFN-β) production and gasdermin D-dependent interleukin-18 (IL-18) secretion. Reduction of DICER1 levelsor accumulation of Alu RNA triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, IFN-β, and cGAS levels are elevated in the RPE of human eyes with geographic atrophy. Collectively, these data highlight an unexpected role for cGAS in responding to mobile element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial damage-induced inflammasome activation, expand the immune sensing repertoire of cGAS and caspase-4 to non-infectious human disease, and identify new potential targets for treatment of a major cause of blindness. PMID:29176737

Casein Kinase 1 Promotes Synchrony of the Circadian Clock Network

PubMed Central

Zheng, Xiangzhong; Sowcik, Mallory; Chen, Dechun

2014-01-01

Casein kinase 1, known as DOUBLETIME (DBT) in Drosophila melanogaster, is a critical component of the circadian clock that phosphorylates and promotes degradation of the PERIOD (PER) protein. However, other functions of DBT in circadian regulation are not clear, in part because severe reduction of dbt causes preadult lethality. Here we report the molecular and behavioral phenotype of a viable dbtEY02910 loss-of-function mutant. We found that DBT protein levels are dramatically reduced in adult dbtEY02910 flies, and the majority of mutant flies display arrhythmic behavior, with a few showing weak, long-period (∼32 h) rhythms. Peak phosphorylation of PER is delayed, and both hyper- and hypophosphorylated forms of the PER and CLOCK proteins are present throughout the day. In addition, molecular oscillations of the circadian clock are dampened. In the central brain, PER and TIM expression is heterogeneous and decoupled in the canonical clock neurons of the dbtEY02910 mutants. We also report an interaction between dbt and the signaling pathway involving pigment dispersing factor (PDF), a synchronizing peptide in the clock network. These data thus demonstrate that overall reduction of DBT causes long and arrhythmic behavior, and they reveal an unexpected role of DBT in promoting synchrony of the circadian clock network. PMID:24820422

Genetic architecture of conspecific sperm precedence in Allonemobius fasciatus and A. socius.

PubMed

Britch, Seth C; Swartout, Emma J; Hampton, Daniel D; Draney, Michael L; Chu, Jiming; Marshall, Jeremy L; Howard, Daniel J

2007-06-01

The evolution of barriers to gene exchange is centrally important to speciation. We used the crickets Allonemobius fasciatus and A. socius to investigate the genetic architecture of conspecific sperm precedence (CSP), a postinsemination prezygotic reproductive barrier. With amplified fragment-length polymorphism (AFLP) markers and controlled crosses we constructed linkage maps and estimated positions of QTL associated with CSP. The majority of QTL have low to moderate effects, although a few QTL exist in A. socius with large effects, and the numbers of QTL are comparable to numbers of genes accounting for species differences in other studies. The QTL are spread across many unlinked markers, yet QTL placed with linked markers are on a small number of linkage groups that could reflect the role of the large Allonemobius sex chromosome in prezygotic isolation. Although many QTL had positive effects on conspecific sperm utilization several QTL also exerted negative effects, which could be explained by intraspecific sexual conflict, sperm competition, or epistasis of introgressed genes on novel backgrounds. One unexpected outcome was that A. socius CSP alleles have a stronger effect than those from A. fasciatus in hybrid females, causing hybrids to behave like A. socius with regard to sperm utilization. Implications of this asymmetry in the Allonemobius hybrid zone are discussed.

Conflicts in the operating theatre.

PubMed

Booij, Leo H D J

2007-04-01

Quality and safety of healthcare depend on team performance. Conflicts decrease team performance. A number of studied factors involved in the development and solution of conflicts are discussed. An operating team consists of individuals, with specific roles requiring specific expertise and skills, performing interdependent tasks with patient treatment as a common goal. Teams are prone to conflicts: a dispute, disagreement or difference of opinion related to patient management, requiring some decision or action. Many factors determine the character of the conflicts, and these vary between different countries, hospitals and teams. Factors include culture, professional social status, personality of members, etc. Conflicts can induce innovation, but can also result in job dissatisfaction. They even can affect the functioning of the hospital. On average, four conflicts can be observed per operation, which are mostly solved immediately. Communication in an open atmosphere is a major issue in dealing with conflicts. If conflicts are unresolved they grow into relationship conflicts, which are difficult to handle. Understanding the factors that contribute to the conflict is important for mediators. Most conflicts arise about theatre management, case acceptation, unexpected changes in the team or incapability of one of its members. There are many possible inductors of conflicts. Conflicts should be immediately resolved by open communication and respectful discussion.

Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone.

PubMed

López-Causapé, Carla; Sommer, Lea Mette; Cabot, Gabriel; Rubio, Rosa; Ocampo-Sosa, Alain A; Johansen, Helle Krogh; Figuerola, Joan; Cantón, Rafael; Kidd, Timothy J; Molin, Soeren; Oliver, Antonio

2017-07-17

Emergence of epidemic clones and antibiotic resistance development compromises the management of Pseudomonas aeruginosa cystic fibrosis (CF) chronic respiratory infections. Whole genome sequencing (WGS) was used to decipher the phylogeny, interpatient dissemination, WGS mutator genotypes (mutome) and resistome of a widespread clone (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. The coexistence of two divergent CC274 clonal lineages was revealed, but without evident geographical barrier; phylogenetic reconstructions and mutational resistome demonstrated the interpatient transmission of mutators. The extraordinary capacity of P. aeruginosa to develop resistance was evidenced by the emergence of mutations in >100 genes related to antibiotic resistance during the evolution of CC274, catalyzed by mutator phenotypes. While the presence of classical mutational resistance mechanisms was confirmed and correlated with resistance phenotypes, results also showed a major role of unexpected mutations. Among them, PBP3 mutations, shaping up β-lactam resistance, were noteworthy. A high selective pressure for mexZ mutations was evidenced, but we showed for the first time that high-level aminoglycoside resistance in CF is likely driven by mutations in fusA1/fusA2, coding for elongation factor G. Altogether, our results provide valuable information for understanding the evolution of the mutational resistome of CF P. aeruginosa.

Gene switching in Amoeba proteus caused by endosymbiotic bacteria.

PubMed

Jeon, Taeck J; Jeon, Kwang W

2004-02-01

The expression of genes for S-adenosylmethionine synthetase (SAMS), which catalyzes the synthesis of S-adenosylmethionine (AdoMet), a major methyl donor in cells, was studied in symbiont-free (D) and symbiont-bearing (xD) amoeba strains to determine the effect of bacterial endosymbionts. The symbionts suppressed the expression of the gene in host xD amoebae, but amoebae still exhibited about half the enzyme activity found in symbiont-free D amoebae. The study was aimed at elucidating mechanisms of the suppression of the amoeba's gene and determining the alternative source for the gene product. Unexpectedly, we found a second sams (sams2) gene in amoebae, which encoded 390 amino acids. Results of experiments measuring SAMS activities and amounts of AdoMet in D and xD amoebae showed that the half SAMS activity found in xD amoebae came from the amoeba's SAMS2 and not from their endosymbionts. The expression of amoeba sams genes was switched from sams1 to sams2 as a result of infection with X-bacteria, raising the possibility that the switch in the expression of sams genes by bacteria plays a role in the development of symbiosis and the host-pathogen interactions. This is the first report showing such a switch in the expression of host sams genes by infecting bacteria.

Metallocene-based antimalarials: an exploration into the influence of the ferrocenyl moiety on in vitro antimalarial activity in chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum.

PubMed

Blackie, Margaret A L; Beagley, Paul; Croft, Simon L; Kendrick, Howard; Moss, John R; Chibale, Kelly

2007-10-15

To establish the role of the ferrocenyl moiety in the antiplasmodial activity of ferroquine, compounds in which this moiety is replaced by the corresponding ruthenium-based moieties were synthesized and evaluated. In both the sensitive (D10) and resistant (K1) strains of Plasmodium falciparum, ruthenoquine analogues showed comparable potency to ferroquine. This suggests that a probable role of the ferrocenyl fragment is to serve simply as a hydrophobic spacer group. In addition, ferroquine analogues with different aromatic substituents were synthesized and evaluated. Unexpectedly high activity for quinoline compounds lacking the 7-chloro substituent suggests the ferrocenyl moiety may have an additive and/or synergistic effect.

From neural development to cognition: unexpected roles for chromatin

PubMed Central

Ronan, Jehnna L.; Wu, Wei

2014-01-01

Recent genome-sequencing studies in human neurodevelopmental and psychiatric disorders have uncovered mutations in many chromatin regulators. These human genetic studies, along with studies in model organisms, are providing insight into chromatin regulatory mechanisms in neural development and how alterations to these mechanisms can cause cognitive deficits, such as intellectual disability. We discuss several implicated chromatin regulators, including BAF (also known as SWI/SNF) and CHD8 chromatin remodellers, HDAC4 and the Polycomb component EZH2. Interestingly, mutations in EZH2 and certain BAF complex components have roles in both neurodevelopmental disorders and cancer, and overlapping point mutations are suggesting functionally important residues and domains. We speculate on the contribution of these similar mutations to disparate disorders. PMID:23568486

Unexpected Role for IL-17 in Protective Immunity against Hypervirulent Mycobacterium tuberculosis HN878 Infection

PubMed Central

Gopal, Radha; Monin, Leticia; Slight, Samantha; Uche, Uzodinma; Blanchard, Emmeline; A. Fallert Junecko, Beth; Ramos-Payan, Rosalio; Stallings, Christina L.; Reinhart, Todd A.; Kolls, Jay K.; Kaushal, Deepak; Nagarajan, Uma; Rangel-Moreno, Javier; Khader, Shabaana A.

2014-01-01

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), infects one third of the world's population. Among these infections, clinical isolates belonging to the W-Beijing appear to be emerging, representing about 50% of Mtb isolates in East Asia, and about 13% of all Mtb isolates worldwide. In animal models, infection with W-Beijing strain, Mtb HN878, is considered “hypervirulent” as it results in increased mortality and causes exacerbated immunopathology in infected animals. We had previously shown the Interleukin (IL) -17 pathway is dispensable for primary immunity against infection with the lab adapted Mtb H37Rv strain. However, it is not known whether IL-17 has any role to play in protective immunity against infection with clinical Mtb isolates. We report here that lab adapted Mtb strains, such as H37Rv, or less virulent Mtb clinical isolates, such as Mtb CDC1551, do not require IL-17 for protective immunity against infection while infection with Mtb HN878 requires IL-17 for early protective immunity. Unexpectedly, Mtb HN878 induces robust production of IL-1β through a TLR-2-dependent mechanism, which supports potent IL-17 responses. We also show that the role for IL-17 in mediating protective immunity against Mtb HN878 is through IL-17 Receptor signaling in non-hematopoietic cells, mediating the induction of the chemokine, CXCL-13, which is required for localization of T cells within lung lymphoid follicles. Correct T cell localization within lymphoid follicles in the lung is required for maximal macrophage activation and Mtb control. Since IL-17 has a critical role in vaccine-induced immunity against TB, our results have far reaching implications for the design of vaccines and therapies to prevent and treat emerging Mtb strains. In addition, our data changes the existing paradigm that IL-17 is dispensable for primary immunity against Mtb infection, and instead suggests a differential role for IL-17 in early protective immunity against emerging Mtb strains. PMID:24831696

Drones of the dwarf honey bee Apis florea are attracted to (2E)-9-oxodecenoic acid and (2E)-10-hydroxydecenoic acid.

PubMed

Nagaraja, Narayanappa; Brockmann, Axel

2009-06-01

The queen mandibular gland component (2E)-9-oxodecenoic acid (9-ODA) has been suggested to function as the major sex pheromone component in all honey bee species. In contrast to this hypothesis, chemical analyses showed that in the Asian dwarf honey bee species, Apis florea, a different decenoic acid, (2E)-10-hydroxydecenoic acid (10-HDA), is the major component in the mandibular gland secretion. We show here that A. florea drones are attracted to 9-ODA as well as to 10-HDA. However, 10-HDA attracted higher numbers of drones at lower dosages than 9-ODA, and also was more attractive when directly compared to 9-ODA in a dual attraction experiment. We conclude that 10-HDA has to be viewed as the major sex pheromone in A. florea. The result that both pheromone components are capable of attracting drones when presented alone was unexpected with regard to existing sex pheromone attraction experiments in honey bees.

Evaluating the Brazilian zero tolerance drinking and driving law: Time series analyses of traffic-related mortality in three major cities.

PubMed

Volpe, Fernando Madalena; Ladeira, Roberto Marini; Fantoni, Rosely

2017-05-19

A zero tolerance alcohol restriction law was adopted in Brazil in 2008. In order to assess the effectiveness of this intervention, the present study compares specific mortality in 2 time series: 1980-2007 and 2008-2013. Data on mortality and population were gathered from official Brazilian Ministry of Health information systems. Segmented regression analyses were carried out separately for 3 major Brazilian capitals: Belo Horizonte, Rio de Janeiro, and São Paulo. In 2 cities (Belo Horizonte and Rio de Janeiro) there were no significant changes in mortality rate trends in 2 periods, 1980 to 2007 and 2008 to 2013, where the observed rates did not differ significantly from predicted rates. In São Paulo, a decreasing trend until 2007 unexpectedly assumed higher levels after implementation of the law. There is no evidence of reduced traffic-related mortality in the 3 major Brazilian capitals 5.5 years after the zero tolerance drinking and driving law was adopted.

Global and Country-Level Fragility to Major Disruptions in Crop Production

NASA Astrophysics Data System (ADS)

Puma, M. J.; Wada, Y.; Chon, S. Y.; Cook, B. I.; Nordbotten, J. M.

2016-12-01

New food polices are needed to mitigate vulnerabilities in the global food system to unexpected and severe production losses. The starting point for developing such policies is the ability to quantify the potential range of food and economic losses associated with major food-production shocks. Although individual major shock events are unpredictable, it is possible to quantify the relative vulnerabilities of the global food system as a whole and of individual countries within the system to production shocks. Here we combine a scale for food disruptions, which links the magnitude for a production shock with the corresponding short-term food and economic losses for that event (analogous to the well-known Richter magnitude scale for earthquakes), with country-level food system metrics. We demonstrate the value of our approach using the recent El Niño event of 2015-2016. Ultimately, these metrics can be used as part of efforts to develop national and global level food policies to prepare for and mitigate possible food-supply disruptions.

Evidence for surface rupture in 1868 on the Hayward Fault in North Oakland and major rupturing in prehistoric earthquakes

NASA Astrophysics Data System (ADS)

Lienkaemper, James J.; Williams, Patrick L.

1999-07-01

WGCEP90 estimated the Hayward fault to have a high probability (0.45 in 30 yr) of producing a future M7 Bay Area earthquake. This was based on a generic recurrence time and an unverified segmentation model, because there were few direct observations for the southern fault and none for the northern Hayward fault. To better constrain recurrence and segmentation of the northern Hayward fault, we trenched in north Oakland. Unexpectedly, we observed evidence of surface rupture probably from the M7 1868 earthquake. This extends the limit of that surface rupture 13 km north of the segmentation boundary used in the WGCEP90 model and forces serious re-evaluation of the current two-segment paradigm. Although we found that major prehistoric ruptures have occurred here, we could not radiocarbon date them. However, the last major prehistoric event appears correlative with a recently recognized event 13 km to the north dated AD 1640-1776.

Evidence for surface rupture in 1868 on the Hayward fault in north Oakland and major rupturing in prehistoric earthquakes

USGS Publications Warehouse

Lienkaemper, J.J.; Williams, P.L.

1999-01-01

WGCEP90 estimated the Hayward fault to have a high probability (0.45 in 30 yr) of producing a future M7 Bay Area earthquake. This was based on a generic recurrence time and an unverified segmentation model, because there were few direct observations for the southern fault and none for the northern Hayward fault. To better constrain recurrence and segmentation of the northern Hayward fault, we trenched in north Oakland. Unexpectedly, we observed evidence of surface rupture probably from the M7 1868 earthquake. This extends the limit of that surface rupture 13 km north of the segmentation boundary used in the WGCEP90 model and forces serious re-evaluation of the current two-segment paradigm. Although we found that major prehistoric ruptures have occurred here, we could not radiocarbon date them. However, the last major prehistoric event appears correlative with a recently recognized event 13 km to the north dated AD 1640-1776. Copyright 1999 by the American Geophysical Union.

How insights from cardiovascular developmental biology have impacted the care of infants and children with congenital heart disease

PubMed Central

Chin, Alvin J.; Saint-Jeannet, Jean-Pierre; Lo, Cecilia W.

2012-01-01

To illustrate the impact developmental biology and genetics have already had on the clinical management of the million infants born worldwide each year with CHD, we have chosen three stories which have had particular relevance for pediatric cardiologists, cardiothoracic surgeons, cardiac anesthesiologists, and cardiac nurses. First, we show how Margaret Kirby’s finding of the unexpected contribution of an ectodermal cell population – the cranial neural crest – to the aortic arch arteries and arterial pole of the embryonic avian heart provided a key impetus to the field of cardiovascular patterning. Recognition that a majority of patients affected by the neurocristopathy DiGeorge syndrome have a chromosome 22q11 deletion, have also spurred tremendous efforts to characterize the molecular mechanisms contributing to this pathology, assigning a major role to the transcription factor Tbx1. Second, synthesizing the work of the last two decades by many laboratories on a wide gamut of metazoans (invertebrates, tunicates, agnathans, teleosts, lungfish, amphibians, and amniotes), we review the >20 major modifications and additions to the ancient circulatory arrangement composed solely of a unicameral (one-chambered), contractile myocardial tube and a short proximal aorta. Two changes will be discussed in detail – the interposition of a second cardiac chamber in the circulation and the septation of the cardiac ventricle. By comparing the developmental genetic data of several model organisms, we can better understand the origin of the various components of the multicameral (multi-chambered) heart seen in humans. Third, Martina Brueckner’s discovery that a faulty axonemal dynein was responsible for the phenotype of the iv/iv mouse (the first mammalian model of human heterotaxy) focused attention on the biology of cilia. We discuss how even the care of the complex cardiac and non-cardiac anomalies seen in heterotaxy syndrome, which have long seemed impervious to advancements in surgical and medical intensive care (Jacobs et al., 2011), may yet yield to strategies grounded in a better understanding of the cilium. The fact that all cardiac defects seen in patients with full-blown heterotaxy can also be seen in patients without obvious laterality defects hints at important roles for ciliary function not only in left-right axis specification but also in cardiovascular morphogenesis. These three developmental biology stories illustrate how the remaining unexplained mortality and morbidity of congenital heart disease can be solved. PMID:22640994

A case of a power failure in the operating room.

PubMed

Yasny, Jeffrey; Soffer, Robert

2005-01-01

In the operating room, safely administering anesthesia amidst a major power failure can instantly present one with a formidable challenge. A case is presented involving a 23-year-old healthy woman who underwent a complex oral and maxillofacial surgery to correct a dentofacial deformity. Three hours into the case and with the patient's maxilla downfractured, the overhead surgical lights blacked out, and there was an apparent loss of the anesthesia machine's ability to function. Providing adequate oxygenation, ventilation, anesthesia levels, monitoring of vital signs, and transportation of the patient were some of the challenges faced, and the response to this unexpected event is recounted. The importance of one's familiarity with an anesthesia machine's backup battery supply, routinely checking machinery, ensuring that appropriate and sufficient supplies are readily available, exercising calm leadership with clear communication, and formulating a clear plan with backup alternatives are discussed. Various recommendations are proposed with respect to the preparation for and the prevention of a power failure in the operating room. This report's account of events is aimed to "shed some light" on this topic, serve as a check of one's own preparedness, and facilitate the optimal management of a similarly unexpected incident.

3 CFR - Unexpected Urgent Refugee and Migration Needs Relating to Syria

Code of Federal Regulations, 2014 CFR

2014-01-01

... 3 The President 1 2014-01-01 2014-01-01 false Unexpected Urgent Refugee and Migration Needs Relating to Syria Presidential Documents Other Presidential Documents Presidential Determination No. 2013-4 of January 29, 2013 Unexpected Urgent Refugee and Migration Needs Relating to Syria Memorandum for the Secretary of State By the authority vested i...

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Libya

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to Libya Presidential Documents Other Presidential Documents Presidential Determination No. 2011-8 of March 7, 2011 Unexpected Urgent Refugee and Migration Needs Related to Libya Memorandum for the Secretary of State By the authority vested in me...

3 CFR - Unexpected Urgent Refugee and Migration Needs Resulting from Flooding in Pakistan

Code of Federal Regulations, 2011 CFR

2011-01-01

... 3 The President 1 2011-01-01 2011-01-01 false Unexpected Urgent Refugee and Migration Needs... Determination No. 2010-14 of September 3, 2010 Unexpected Urgent Refugee and Migration Needs Resulting from... the Constitution and the laws of the United States, including section 2(c)(1) of the Migration and...

3 CFR - Unexpected Urgent Refugee and Migration Needs Resulting from Violence in Kyrgyzstan

Code of Federal Regulations, 2011 CFR

2011-01-01

... 3 The President 1 2011-01-01 2011-01-01 false Unexpected Urgent Refugee and Migration Needs... Determination No. 2010-12 of August 26, 2010 Unexpected Urgent Refugee and Migration Needs Resulting from... the Constitution and the laws of the United States, including section 2(c)(1) of the Migration and...

Impact of Repeated Questioning on Interviewers: Learning From a Forensic Interview Training Project.

PubMed

Duron, Jacquelynn F; Cheung, Monit

2016-01-01

Forensic interviewers have a difficult job with high risk for career burnout and secondary trauma. Few studies have addressed how new forensic interviewers or trainees experience repeated questioning and multiple interviews. This study simulated the process of training new forensic interviewers through the creation of two interview videos in which social work graduate students participated as actors portraying the roles of interviewer and child. These films served as instructional aids preparing graduate social work students for professional child welfare roles while promoting research-based approaches to interviewing children about sexual abuse allegations. Qualitative data from two cohorts of student actors were collected to analyze interviewers' perspectives on repeated questioning and interviews in child sexual abuse cases. Two themes were extracted from the subjects' experiences: "It is emotionally taxing" and "Navigating the interviewer role is unexpectedly complex." Exposure to repeated questions and multiple interviews affected the performance and confidence of the interviewers.

What does a physics undergraduate education give you? A perspective from Australian physics

NASA Astrophysics Data System (ADS)

Sharma, Manjula; Pollard, Judith; Mendez, Alberto; Mills, David; O'Byrne, John; Scott, Dale; Hagon, Sue; Gribble, Joan; Kirkup, Les; Livett, Michelle; Low, David; Merchant, Alex; Rayner, Anton; Swan, Geoff; Zadnik, Marjan; Zealey, Willam

2008-01-01

In a study to assess how effectively undergraduate physics studies have prepared students for the workplace, we attempted to locate and interview traditional 3-year or 4-year physics students who had graduated in the past five years (2000 to 2004), and the employers of these graduates. The study was limited to recent graduates who have majored in physics and not obtained further or concurrent degrees. Overseas studies of the destinations of physics graduates referred to in this paper have not isolated the group we interviewed as a distinct group. A major finding was that the number of these graduates was unexpectedly low. Indeed, most physics graduates have two degrees. Interviews with graduates and employers suggest that physics graduates have particular strengths in problem solving and are good at applying their skills at the workplace.

Tangential migration of corridor guidepost neurons contributes to anxiety circuits.

PubMed

Tinterri, Andrea; Deck, Marie; Keita, Maryama; Mailhes, Caroline; Rubin, Anna Noren; Kessaris, Nicoletta; Lokmane, Ludmilla; Bielle, Franck; Garel, Sonia

2018-02-15

In mammals, thalamic axons are guided internally toward their neocortical target by corridor (Co) neurons that act as axonal guideposts. The existence of Co-like neurons in non-mammalian species, in which thalamic axons do not grow internally, raised the possibility that Co cells might have an ancestral role. Here, we investigated the contribution of corridor (Co) cells to mature brain circuits using a combination of genetic fate-mapping and assays in mice. We unexpectedly found that Co neurons contribute to striatal-like projection neurons in the central extended amygdala. In particular, Co-like neurons participate in specific nuclei of the bed nucleus of the stria terminalis, which plays essential roles in anxiety circuits. Our study shows that Co neurons possess an evolutionary conserved role in anxiety circuits independently from an acquired guidepost function. It furthermore highlights that neurons can have multiple sequential functions during brain wiring and supports a general role of tangential migration in the building of subpallial circuits. © 2017 Wiley Periodicals, Inc.

Genetic screen in Drosophila muscle identifies autophagy-mediated T-tubule remodeling and a Rab2 role in autophagy.

PubMed

Fujita, Naonobu; Huang, Wilson; Lin, Tzu-Han; Groulx, Jean-Francois; Jean, Steve; Nguyen, Jen; Kuchitsu, Yoshihiko; Koyama-Honda, Ikuko; Mizushima, Noboru; Fukuda, Mitsunori; Kiger, Amy A

2017-01-07

Transverse (T)-tubules make-up a specialized network of tubulated muscle cell membranes involved in excitation-contraction coupling for power of contraction. Little is known about how T-tubules maintain highly organized structures and contacts throughout the contractile system despite the ongoing muscle remodeling that occurs with muscle atrophy, damage and aging. We uncovered an essential role for autophagy in T-tubule remodeling with genetic screens of a developmentally regulated remodeling program in Drosophila abdominal muscles. Here, we show that autophagy is both upregulated with and required for progression through T-tubule disassembly stages. Along with known mediators of autophagosome-lysosome fusion, our screens uncovered an unexpected shared role for Rab2 with a broadly conserved function in autophagic clearance. Rab2 localizes to autophagosomes and binds to HOPS complex members, suggesting a direct role in autophagosome tethering/fusion. Together, the high membrane flux with muscle remodeling permits unprecedented analysis both of T-tubule dynamics and fundamental trafficking mechanisms.

NOVEL ROLES FOR INSULIN RECEPTOR (IR) IN ADIPOCYTES AND SKELETAL MUSCLE CELLS VIA NEW AND UNEXPECTED SUBSTRATES

PubMed Central

Ramalingam, Latha; Oh, Eunjin; Thurmond, Debbie C.

2012-01-01

The insulin signaling pathway regulates whole-body glucose homeostasis by transducing extracellular signals from the insulin receptor (IR) to downstream intracellular targets, thus coordinating a multitude of biological functions. Dysregulation of IR or its signal transduction is associated with insulin resistance, which may culminate in type 2 diabetes (T2D). Following initial stimulation of IR, insulin signaling diverges into different pathways, activating multiple substrates which have roles in various metabolic and cellular processes. The integration of multiple pathways arising from IR activation continues to expand as new IR substrates are identified and characterized. Accordingly, our review will focus on roles for IR substrates as they pertain to three primary areas: Metabolism/glucose uptake, Mitogenesis/growth, and Aging/Longevity. While IR functions in a seemingly pleotropic manner in many cell types, through these three main roles in fat and skeletal muscle cells, IR multi-tasks to regulate whole-body glucose homeostasis to impact healthspan and lifespan. PMID:23052216

CBX7 gene expression plays a negative role in adipocyte cell growth and differentiation

PubMed Central

Forzati, Floriana; Federico, Antonella; Pallante, Pierlorenzo; Colamaio, Marianna; Esposito, Francesco; Sepe, Romina; Gargiulo, Sara; Luciano, Antonio; Arra, Claudio; Palma, Giuseppe; Bon, Giulia; Bucher, Stefania; Falcioni, Rita; Brunetti, Arturo; Battista, Sabrina; Fedele, Monica; Fusco, Alfredo

2014-01-01

ABSTRACT We have recently generated knockout mice for the Cbx7 gene, coding for a polycomb group protein that is downregulated in human malignant neoplasias. These mice develop liver and lung adenomas and carcinomas, which confirms a tumour suppressor role for CBX7. The CBX7 ability to downregulate CCNE1 expression likely accounts for the phenotype of the Cbx7-null mice. Unexpectedly, Cbx7-knockout mice had a higher fat tissue mass than wild-type, suggesting a role of CBX7 in adipogenesis. Consistently, we demonstrate that Cbx7-null mouse embryonic fibroblasts go towards adipocyte differentiation more efficiently than their wild-type counterparts, and this effect is Cbx7 dose-dependent. Similar results were obtained when Cbx7-null embryonic stem cells were induced to differentiate into adipocytes. Conversely, mouse embryonic fibroblasts and human adipose-derived stem cells overexpressing CBX7 show an opposite behaviour. These findings support a negative role of CBX7 in the control of adipocyte cell growth and differentiation. PMID:25190058

Specific subcortical structures are activated during seizure-induced death in a model of sudden unexpected death in epilepsy (SUDEP): A manganese-enhanced magnetic resonance imaging study.

PubMed

Kommajosyula, Srinivasa P; Randall, Marcus E; Brozoski, Thomas J; Odintsov, Boris M; Faingold, Carl L

2017-09-01

Sudden unexpected death in epilepsy (SUDEP) is a major concern for patients with epilepsy. In most witnessed cases of SUDEP generalized seizures and respiratory failure preceded death, and pre-mortem neuroimaging studies in SUDEP patients observed changes in specific subcortical structures. Our study examined the role of subcortical structures in the DBA/1 mouse model of SUDEP using manganese-enhanced magnetic resonance imaging (MEMRI). These mice exhibit acoustically-evoked generalized seizures leading to seizure-induced respiratory arrest (S-IRA) that results in sudden death unless resuscitation is rapidly instituted. MEMRI data in the DBA/1 mouse brain immediately after acoustically-induced S-IRA were compared to data in C57 (control) mice that were exposed to the same acoustic stimulus that did not trigger seizures. The animals were anesthetized and decapitated immediately after seizure in DBA/1 mice and after an equivalent time in control mice. Comparative T1 weighted MEMRI images were evaluated using a 14T MRI scanner and quantified. We observed significant increases in activity in DBA/1 mice as compared to controls at previously-implicated auditory (superior olivary complex) and sensorimotor-limbic [periaqueductal gray (PAG) and amygdala] networks and also in structures in the respiratory network. The activity at certain raphe nuclei was also increased, suggesting activation of serotonergic mechanisms. These data are consistent with previous findings that enhancing the action of serotonin prevents S-IRA in this SUDEP model. Increased activity in the PAG and the respiratory and raphe nuclei suggest that compensatory mechanisms for apnea may have been activated by S-IRA, but they were not sufficient to prevent death. The present findings indicate that changes induced by S-IRA in specific subcortical structures in DBA/1 mice are consistent with human SUDEP findings. Understanding the changes in brain activity during seizure-induced death in animals may lead to improved approaches directed at prevention of human SUDEP. Copyright © 2017 Elsevier B.V. All rights reserved.

Inattentional blindness is influenced by exposure time not motion speed.

PubMed

Kreitz, Carina; Furley, Philip; Memmert, Daniel

2016-01-01

Inattentional blindness is a striking phenomenon in which a salient object within the visual field goes unnoticed because it is unexpected, and attention is focused elsewhere. Several attributes of the unexpected object, such as size and animacy, have been shown to influence the probability of inattentional blindness. At present it is unclear whether or how the speed of a moving unexpected object influences inattentional blindness. We demonstrated that inattentional blindness rates are considerably lower if the unexpected object moves more slowly, suggesting that it is the mere exposure time of the object rather than a higher saliency potentially induced by higher speed that determines the likelihood of its detection. Alternative explanations could be ruled out: The effect is not based on a pop-out effect arising from different motion speeds in relation to the primary-task stimuli (Experiment 2), nor is it based on a higher saliency of slow-moving unexpected objects (Experiment 3).

Should I stay or should I go? Attentional disengagement from visually unique and unexpected items at fixation.

PubMed

Brockmole, James R; Boot, Walter R

2009-06-01

Distinctive aspects of a scene can capture attention even when they are irrelevant to one's goals. The authors address whether visually unique, unexpected, but task-irrelevant features also tend to hold attention. Observers searched through displays in which the color of each item was irrelevant. At the start of search, all objects changed color. Critically, the foveated item changed to an unexpected color (it was novel), became a color singleton (it was unique), or both. Saccade latency revealed the time required to disengage overt attention from this object. Singletons resulted in longer latencies, but only if they were unexpected. Conversely, unexpected items only delayed disengagement if they were singletons. Thus, the time spent overtly attending to an object is determined, at least in part, by task-irrelevant stimulus properties, but this depends on the confluence of expectation and visual salience. (c) 2009 APA, all rights reserved.

Expecting the Unexpected: Radiation Hardened Software

NASA Technical Reports Server (NTRS)

Penix, John; Mehlitz, Peter C.

2005-01-01

Radiation induced Single Event Effects (SEEs) are a serious problem for spacecraft flight software, potentially leading to a complete loss of mission. Conventional risk mitigation has been focused on hardware, leading to slow, expensive and outdated on-board computing devices, increased power consumption and launch mass. Our approach is to look at SEEs from a software perspective, and to explicitly design flight software so that it can detect and correct the majority of SEES. Radiation hardened flight software will reduce the significant residual residual risk for critical missions and flight phases, and enable more use of inexpensive and fast COTS hardware.

High Rates of Nonsusceptibility to Ceftazidime-avibactam and Identification of New Delhi Metallo-β-lactamase Production in Enterobacteriaceae Bloodstream Infections at a Major Cancer Center.

PubMed

Aitken, Samuel L; Tarrand, Jeffrey J; Deshpande, Lalitagauri M; Tverdek, Frank P; Jones, Anne L; Shelburne, Samuel A; Prince, Randall A; Bhatti, Micah M; Rolston, Kenneth V I; Jones, Ronald N; Castanheira, Mariana; Chemaly, Roy F

2016-10-01

Resistance to the novel β-lactam/β-lactamase inhibitor combination ceftazidime-avibactam (CAZ-AVI) among carbapenem-resistant Enterobacteriaceae (CRE) has infrequently been reported in the United States. We report unexpectedly high rates of resistance to CAZ-AVI in CRE bloodstream isolates at our institution associated with the nonoutbreak spread of New Delhi metallo-β-lactamase in diverse Enterobacteriaceae species. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

INCREASED UNDERSTANDING OF BEAM LOSSES FROM THE SNS LINAC PROTON EXPERIMENT

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

Aleksandrov, Alexander V; Shishlo, Andrei P; Plum, Michael A

Beam loss is a major concern for high power hadron accelerators such as the Spallation Neutron Source (SNS). An unexpected beam loss in the SNS superconducting linac (SCL) was observed during the power ramp up and early operation. Intra-beam-stripping (IBS) loss, in which interactions between H- particles within the accelerated bunch strip the outermost electron, was recently identified as a possible cause of the beam loss. A set of experiments using proton beam acceleration in the SNS linac was conducted, which supports IBS as the primary beam loss mechanism in the SNS SCL.

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Cote d'Ivoire

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to Cote d'Ivoire Presidential Documents Other Presidential Documents Presidential Determination No. 2011-7 of March 7, 2011 Unexpected Urgent Refugee and Migration Needs Related to Cote d'Ivoire Memorandum for the Secretary of State By the...

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa Presidential Documents Other Presidential Documents Presidential Determination No. 2011-12 of August 8, 2011 Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa Memorandum for the Secretary of State By...

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Somalia and Food Pipeline Breaks for...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 3 The President 1 2011-01-01 2011-01-01 false Unexpected Urgent Refugee and Migration Needs... 8, 2010 Unexpected Urgent Refugee and Migration Needs Related to Somalia and Food Pipeline Breaks... section 2(c)(1) of the Migration and Refugee Assistance Act of 1962 (the “Act”), as amended, (22 U.S.C...

Investigating Teachers' Appraisal of Unexpected Moments and Underlying Values: An Exploratory Case in the Context of Changing Mathematics Classroom Discourse

ERIC Educational Resources Information Center

Cavanna, Jillian M.; Herbel-Eisenmann, Beth; Seah, Wee Tiong

2015-01-01

This article provides an exploratory case study that examines what one teacher indicated as unexpected as she worked to become more purposeful about her classroom discourse practices. We found that she highlighted three areas as being unexpected: (1) aspects of lesson enactment; (2) characteristics of student learning and (3) her own…

The Influence of Attention Set, Working Memory Capacity, and Expectations on Inattentional Blindness.

PubMed

Kreitz, Carina; Furley, Philip; Memmert, Daniel; Simons, Daniel J

2016-04-01

The probability of inattentional blindness, the failure to notice an unexpected object when attention is engaged on some primary task, is influenced by contextual factors like task demands, features of the unexpected object, and the observer's attention set. However, predicting who will notice an unexpected object and who will remain inattentionally blind has proven difficult, and the evidence that individual differences in cognition affect noticing remains ambiguous. We hypothesized that greater working memory capacity might modulate the effect of attention sets on noticing because working memory is associated with the ability to focus attention selectively. People with greater working memory capacity might be better able to attend selectively to target items, thereby increasing the chances of noticing unexpected objects that were similar to the attended items while decreasing the odds of noticing unexpected objects that differed from the attended items. Our study (N = 120 participants) replicated evidence that task-induced attention sets modulate noticing but found no link between noticing and working memory capacity. Our results are largely consistent with the idea that individual differences in working memory capacity do not predict noticing of unexpected objects in an inattentional blindness task. © The Author(s) 2015.

An Overview of Lipid Droplets in Cancer and Cancer Stem Cells

PubMed Central

Seco, J.

2017-01-01

For decades, lipid droplets have been considered as the main cellular organelles involved in the fat storage, because of their lipid composition. However, in recent years, some new and totally unexpected roles have been discovered for them: (i) they are active sites for synthesis and storage of inflammatory mediators, and (ii) they are key players in cancer cells and tissues, especially in cancer stem cells. In this review, we summarize the main concepts related to the lipid droplet structure and function and their involvement in inflammatory and cancer processes. PMID:28883835

Zirconium nitride precipitation in nominally pure yttria-stabilized zirconia

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

Gomez-Garcia, D.; Martinez-Fernandez, J.; Dominguez-Rodriguez, A.

Nominally pure yttria-stabilized zirconia alloys are shown to contain unexpectedly large amounts of dissolved nitrogen. Its presence in the lattice was detected through the observation of large precipitates in alloys with three different concentrations of yttria deformed in compression in argon in the temperature range 1,600--1,800 C. Electron diffraction, EDS and PEELS analyses, and Moire imaging were used to identify the precipitates as ZrN. The possible origin of the nitrogen, its likely effects on properties, and the role of annealing atmosphere are briefly discussed.

Spin Order and Phase Transitions in Chains of Polariton Condensates.

PubMed

Ohadi, H; Ramsay, A J; Sigurdsson, H; Del Valle-Inclan Redondo, Y; Tsintzos, S I; Hatzopoulos, Z; Liew, T C H; Shelykh, I A; Rubo, Y G; Savvidis, P G; Baumberg, J J

2017-08-11

We demonstrate that multiply coupled spinor polariton condensates can be optically tuned through a sequence of spin-ordered phases by changing the coupling strength between nearest neighbors. For closed four-condensate chains these phases span from ferromagnetic (FM) to antiferromagnetic (AFM), separated by an unexpected crossover phase. This crossover phase is composed of alternating FM-AFM bonds. For larger eight-condensate chains, we show the critical role of spatial inhomogeneities and demonstrate a scheme to overcome them and prepare any desired spin state. Our observations thus demonstrate a fully controllable nonequilibrium spin lattice.

Dramatic dilatation of the upper airway secondary to a Valsalva manoeuvre in a lateral cephalometric teleradiograph of a child

PubMed Central

Varela, M; Quiñones, D; Martínez-Pérez, D

2010-01-01

Radiographs are routinely used by orthodontists for the planning of treatment for their patients and they can, in some cases, play a decisive role in the early diagnosis of some unexpected medical or surgical disorders. This report presents the case of a substantial dilatation of the upper airway in a 10-year-old girl, which was attributed to a forced Valsalva manoeuvre. The diagnosis was confirmed upon repetition of the teleradiograph with the mouth open. PMID:21062946

Nitric Oxide--Some Old and New Perspectives

NASA Astrophysics Data System (ADS)

Ainscough, Eric W.; Brodie, Andrew M.

1995-08-01

The discovery and early use of NO is recalled followed by some of its chemical reactions to give useful products such as nitric acid and fertilizers. However NO produced from the internal combustion engine results in photochemical smog production and ozone depletion. A rebirth of interest in NO has occurred because of its unexpected roles in physiology and neurobiology. Its production can lead to biological responses such as vasodilation, cell adhesion, neurotransmission and immune regulation. Finally the ways denitrifying bacteria convert NO and other oxides of nitrogen to dinitrogen are discussed.

Silver-Catalyzed Cyclopropanation of Alkenes Using N-Nosylhydrazones as Diazo Surrogates.

PubMed

Liu, Zhaohong; Zhang, Xinyu; Zanoni, Giuseppe; Bi, Xihe

2017-12-15

An efficient silver-catalyzed [2 + 1] cyclopropanation of sterically hindered internal alkenes with diazo compounds in which room-temperature-decomposable N-nosylhydrazones are used as diazo surrogates is reported. The unexpected unique catalytic activity of silver was ascribed to its dual role as a Lewis acid activating alkene substrates and as a transition metal forming silver carbenoids. A wide range of internal alkenes, including challenging diarylethenes, were suitable for this protocol, thereby affording a variety of cyclopropanes with high efficiency in a stereoselective manner under mild conditions.

Shape diagram of vesicles in Poiseuille flow.

PubMed

Coupier, Gwennou; Farutin, Alexander; Minetti, Christophe; Podgorski, Thomas; Misbah, Chaouqi

2012-04-27

Soft bodies flowing in a channel often exhibit parachutelike shapes usually attributed to an increase of hydrodynamic constraint (viscous stress and/or confinement). We show that the presence of a fluid membrane leads to the reverse phenomenon and build a phase diagram of shapes-which are classified as bullet, croissant, and parachute-in channels of varying aspect ratio. Unexpectedly, shapes are relatively wider in the narrowest direction of the channel. We highlight the role of flow patterns on the membrane in this response to the asymmetry of stress distribution.

Aromatase in the brain: not just for reproduction anymore.

PubMed

Garcia-Segura, L M

2008-06-01

Aromatase, the enzyme that synthesises oestrogens from androgen precursors, is expressed in the brain, where it has been classically associated with the regulation of neuroendocrine events and behaviours linked with reproduction. Recent findings, however, have revealed new unexpected roles for brain aromatase, indicating that the enzyme regulates synaptic activity, synaptic plasticity, neurogenesis and the response of neural tissue to injury, and may contribute to control nonreproductive behaviours, mood and cognition. Therefore, the function of brain aromatase is not restricted to the regulation of reproduction as previously thought.

"She's woke": The paradoxical effects of the 2016 election on an individual client.

PubMed

Raskin, Patricia M

2018-05-01

The purpose of this article is to present a case history of an individual client deeply affected by the 2016 election of Donald Trump: an unexpected key to her self-empowerment. Raised in poverty and with a history of being sexually abused, the client's anger and frustration at Hillary Clinton's loss in the election led to an examination in therapy of the role of gender in her life and enabled her to strengthen her sense of agency in her world. © 2018 Wiley Periodicals, Inc.

Experimental study of supersonic viscous leeside flow over a slender delta wing

NASA Technical Reports Server (NTRS)

Szodruch, J.

1980-01-01

An investigation was conducted to study in detail the vortical flow over the leeward side of a 70 deg swept delta wing having subsonic and supersonic leading edges. Two types of flow were encountered and studied, namely leading edge separation and separation with a shock. Especially for the latter type, Reynolds number plays an important role and unexpected strong streamwise vortices were observed. An optical method is described to obtain a first aproximation of shear stress values in the streamwise direction across the wing span.

Learning from the unexpected in life and DNA self-assembly

PubMed Central

2015-01-01

Summary The greatest lessons in life and science often arise from the unexpected. Thus, rather than viewing these experiences as hindering our progress, they should be embraced and appreciated for their ability to lead to new discoveries. In this perspective, I will discuss the unexpected events that have shaped my career path and the early stages of my independent research program. PMID:26877793

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Libya and Côte d'Ivoire

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to Libya and Côte d'Ivoire Presidential Documents Other Presidential Documents Presidential Determination No. 2011-11 of June 8, 2011 Unexpected Urgent Refugee and Migration Needs Related to Libya and Côte d'Ivoire Memorandum for the Secretary of...

The moderating effects of coping strategies on major depression in the general population.

PubMed

Wang, JianLi; Patten, Scott B

2002-03-01

To evaluate the moderating effects of various coping strategies on the association between stressors and the prevalence of major depression in the general population. Subjects from the Alberta buy-in component of the 1994-1995 National Population Health Survey (NPHS) were included in the analysis (n = 1039). Each subject was asked 8 questions about coping strategies that dealt with unexpected stress from family problems and personal crises. Major depression was measured using the World Health Organization's (WHO) Composite International Diagnostic Interview-Short Form (CIDI-SF) for major depression. The impacts of coping strategies in relation to psychological stressors on the prevalence of major depression were determined by examining interactions between coping and life stress on major depression using logistic regression modelling. No robust impact of coping strategies in relation to various categories of stress evaluated in the NPHS was observed. There was evidence that the use of "pray and seek religious help" and "talks to others about the situations" as coping strategies by women moderated the risk of major depression in the presence of financial stress and relationship stress (with a partner). Using emotional expression as a coping strategy by women might decrease the risk of major depression in the presence of 1 or more recent life events, personal stress, relationship stress (with a partner), and environmental stress. Different coping strategies may have a differential impact on the prevalence of major depression in specific circumstances. These findings may be important both to prevent and to treat depressive disorders.

Did news reporters get it right? Translation of the 2002 hormone study findings.

PubMed

Canales, Mary K; Breslau, Erica S; Nelson, David E; Ballard-Barbash, Rachel R

2008-01-01

The news media play a critical role in communicating health information to the public. The unexpected findings in July 2002 about increased health risks associated with hormone therapy provided an opportunity to examine the process of translating scientific findings to reporters through communication intermediaries and appraise subsequent reporting in newspapers in the United States. Using qualitative research software, a qualitative analysis was conducted in 2006 to consider four types of messages: (1) hormone therapy health risks outweighed benefits (balance); (2) adverse hormone therapy health outcomes (health risk); (3) positive hormone therapy health outcomes (benefit); and (4) risk level (magnitude). The print materials analyzed included the original 2002 Journal of American Medical Association (JAMA) article and editorial; JAMA and National Institutes of Health (NIH) press releases; the NIH press conference transcript; and 198 articles about hormone therapy in 22 U.S. newspapers published from July to September 2002. The major study finding that hormone therapy risks outweighed benefits was reported consistently and accurately. Analyses of language and numbers on risk magnitude, and its interpretation revealed some variability, both within the translation materials and news stories. When risk numbers were included in newspaper stories, absolute risk was used more often than relative risk. Despite much criticism of journalists' coverage of health issues, U.S. newspaper reporting about hormone therapy in 2002 was generally consistent. Several translational and communication strategies used with hormone therapy may be applicable to other efforts that involve working with reporters on major health stories or events. An important process oversight was the absence of hormone therapy communication efforts and guidance directed specifically to medical practitioners.

Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases.

PubMed

Zha, Weibin

2018-04-01

The growing use of natural products in cardiovascular (CV) patients has been greatly raising the concerns about potential natural product-CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product-CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product-drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins) have been identified to be substrates and inhibitors of the solute carrier (SLC) transporters and the ATP-binding cassette (ABC) transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients) are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product-CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product-CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product-CV drug interactions and help public and physicians understand these type of interactions. Copyright © 2017. Published by Elsevier B.V.

OnGuard, a Computational Platform for Quantitative Kinetic Modeling of Guard Cell Physiology1[W][OA

PubMed Central

Hills, Adrian; Chen, Zhong-Hua; Amtmann, Anna; Blatt, Michael R.; Lew, Virgilio L.

2012-01-01

Stomatal guard cells play a key role in gas exchange for photosynthesis while minimizing transpirational water loss from plants by opening and closing the stomatal pore. Foliar gas exchange has long been incorporated into mathematical models, several of which are robust enough to recapitulate transpirational characteristics at the whole-plant and community levels. Few models of stomata have been developed from the bottom up, however, and none are sufficiently generalized to be widely applicable in predicting stomatal behavior at a cellular level. We describe here the construction of computational models for the guard cell, building on the wealth of biophysical and kinetic knowledge available for guard cell transport, signaling, and homeostasis. The OnGuard software was constructed with the HoTSig library to incorporate explicitly all of the fundamental properties for transporters at the plasma membrane and tonoplast, the salient features of osmolite metabolism, and the major controls of cytosolic-free Ca2+ concentration and pH. The library engenders a structured approach to tier and interrelate computational elements, and the OnGuard software allows ready access to parameters and equations ‘on the fly’ while enabling the network of components within each model to interact computationally. We show that an OnGuard model readily achieves stability in a set of physiologically sensible baseline or Reference States; we also show the robustness of these Reference States in adjusting to changes in environmental parameters and the activities of major groups of transporters both at the tonoplast and plasma membrane. The following article addresses the predictive power of the OnGuard model to generate unexpected and counterintuitive outputs. PMID:22635116

Plurality of Leptospira strains on slaughtered animals suggest a broader concept of adaptability of leptospires to cattle.

PubMed

Pinto, Priscila S; Pestana, Cristiane; Medeiros, Marco A; Lilenbaum, Walter

2017-08-01

Leptospirosis in bovines is in majority determined by the host-adapted serovars, mainly Hardjo (types Hardjoprajitno and Hardjobovis), that belong to the serogroup Sejroe. Members of other serogroups as Pomona and Tarassovi have been eventually reported, mainly when outbreaks occurs. Nevertheless, the real role of other strains (non-Hardjo) on determining disease or being transmitted by cattle free of apparent clinical signs of acute infection remains to be elucidated. In that context, the aim of the present study was to investigate the hypothesis that strains of serovars/serogroups other than Hardjo may also be maintained and shed by cattle free of clinical signs. Samples of urine and/or vaginal fluid were collected from 697 bovines from a slaughterhouse located close to Rio de Janeiro, Brazil. Culturing yielded 19 isolates what represents the largest number ever obtained in Brazil on similar studies. These strains were serogrouped and genetically characterized. Fifteen of those were described in other papers and four are first described on the present study. Isolates belong to three different species (Leptospira santarosai, L. alstonii and L. interrogans) and five serogroups (Sarmin, Tarassovi, Shermani, Grippotyphosa and Sejroe). The majority (84.2%) of the isolates belongs to the species L. santarosai, the most prevalent species on cattle in the studied region. Non-Hardjo (non-Sejroe) strains represent 57.9% of the isolates, what indicates an unexpected high diversity of serogroups obtained from these cattle. This suggest that non-Hardjo (non-Sejroe) strains may also be maintained and shed by cattle and that finding must be considered in the epidemiology and control of the disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Heveochlorella (Trebouxiophyceae): a little-known genus of unicellular green algae outside the Trebouxiales emerges unexpectedly as a major clade of lichen photobionts in foliicolous communities.

PubMed

Sanders, William B; Pérez-Ortega, Sergio; Nelsen, Matthew P; Lücking, Robert; de Los Ríos, Asunción

2016-10-01

Foliicolous lichens are formed by diverse, highly specialized fungi that establish themselves and complete their life cycle within the brief duration of their leaf substratum. Over half of these lichen-forming fungi are members of either the Gomphillaceae or Pilocarpaceae, and associate with Trebouxia-like green algae whose identities have never been positively determined. We investigated the phylogenetic affinities of these photobionts to better understand their role in lichen establishment on an ephemeral surface. Thallus samples of Gomphillaceae and Pilocarpaceae were collected from foliicolous communities in southwest Florida and processed for sequencing of photobiont marker genes, algal cultivation and/or TEM. Additional specimens from these families and also from Aspidothelium (Thelenellaceae) were collected from a variety of substrates globally. Sequences from rbcL and nuSSU regions were obtained and subjected to Maximum Likelihood and Bayesian analyses. Analysis of 37 rbcL and 7 nuSSU algal sequences placed all photobionts studied within the provisional trebouxiophycean assemblage known as the Watanabea clade. All but three of the sequences showed affinities within Heveochlorella, a genus recently described from tree trunks in East Asia. The photobiont chloroplast showed multiple thylakoid stacks penetrating the pyrenoid centripetally as tubules lined with pyrenoglobuli, similar to the two described species of Heveochlorella. We conclude that Heveochlorella includes algae of potentially major importance as lichen photobionts, particularly within (but not limited to) foliicolous communities in tropical and subtropical regions worldwide. The ease with which they may be cultivated on minimal media suggests their potential to thrive free-living as well as in lichen symbiosis. © 2016 Phycological Society of America.

A systematic review exploring the relationship between infection and sudden unexpected death between 2000 and 2016: A forensic perspective.

PubMed

Kruger, Mia M; Martin, Lorna J; Maistry, Sairita; Heathfield, Laura J

2018-05-21

Death due to infectious diseases is a major health concern worldwide. This is of particular concern in developing countries where poor-socio economic status and a lack of healthcare resources contribute to the high burden of disease. In some cases death due to infection can be acute and aggressive, and death may occur without a diagnosis whilst the person is still alive. These deaths may ultimately lead to a medico-legal autopsy being performed. There are various mechanisms by which sudden death due to infection may occur. In addition, there are many risk factors associated with sudden death due to infection, which differ between infants and older individuals. However, it is unclear which pathogens and risk factors are most frequently associated with sudden death due to infection. Therefore a systematic review of articles and case reports published between 1 January 2000 and 30 June 2016 was undertaken in order to (1) explore the relationship between pathogens and their causative role and (2) identify the relationship between predisposing and/or risk factors associated with sudden death due to infection. Major databases were searched and after critical appraisal 143 articles were identified. It was found that respiratory infections and deaths involving bacterial pathogens were most commonly associated with these deaths. In addition the most common risk factors in infants were exposure to tobacco smoke and co-sleeping. In adults the most common risk factors were co-morbid conditions and illnesses. This information aids in a better understanding of these deaths and highlights the need for more research in this field, particularly in developing countries. Copyright © 2018 Elsevier B.V. All rights reserved.

Biopersistence and Brain Translocation of Aluminum Adjuvants of Vaccines

PubMed Central

Gherardi, Romain Kroum; Eidi, Housam; Crépeaux, Guillemette; Authier, François Jerome; Cadusseau, Josette

2015-01-01

Aluminum oxyhydroxide (alum) is a crystalline compound widely used as an immunological adjuvant of vaccines. Concerns linked to the use of alum particles emerged following recognition of their causative role in the so-called macrophagic myofasciitis (MMF) lesion detected in patients with myalgic encephalomyelitis/chronic fatigue/syndrome. MMF revealed an unexpectedly long-lasting biopersistence of alum within immune cells in presumably susceptible individuals, stressing the previous fundamental misconception of its biodisposition. We previously showed that poorly biodegradable aluminum-coated particles injected into muscle are promptly phagocytosed in muscle and the draining lymph nodes, and can disseminate within phagocytic cells throughout the body and slowly accumulate in brain. This strongly suggests that long-term adjuvant biopersistence within phagocytic cells is a prerequisite for slow brain translocation and delayed neurotoxicity. The understanding of basic mechanisms of particle biopersistence and brain translocation represents a major health challenge, since it could help to define susceptibility factors to develop chronic neurotoxic damage. Biopersistence of alum may be linked to its lysosome-destabilizing effect, which is likely due to direct crystal-induced rupture of phagolysosomal membranes. Macrophages that continuously perceive foreign particles in their cytosol will likely reiterate, with variable interindividual efficiency, a dedicated form of autophagy (xenophagy) until they dispose of alien materials. Successful compartmentalization of particles within double membrane autophagosomes and subsequent fusion with repaired and re-acidified lysosomes will expose alum to lysosomal acidic pH, the sole factor that can solubilize alum particles. Brain translocation of alum particles is linked to a Trojan horse mechanism previously described for infectious particles (HIV, HCV), that obeys to CCL2, signaling the major inflammatory monocyte chemoattractant. PMID:25699008

Apoptosis-related proteins and proliferation markers in the orbitofrontal cortex in major depressive disorder

PubMed Central

Miguel-Hidalgo, Jose J.; Whittom, Angela; Villarreal, Ashley; Soni, Madhav; Meshram, Ashish; Pickett, Jason C.; Rajkowska, Grazyna; Stockmeier, Craig A.

2014-01-01

Background: In major depressive disorder (MDD), lowered neural activity and significant reductions of markers of cell resiliency to degeneration occur in the prefrontal cortex (PFC). It is still unclear whether changes in other relevant markers of cell vulnerability to degeneration and markers of cell proliferation are associated with MDD. Methods: Levels of caspase 8 (C8), X-linked inhibitor of apoptosis protein (XIAP), direct IAP binding protein with low pI (DIABLO), proliferating cell nuclear antigen (PCNA) and density of cells immunoreactive (-IR) for proliferation marker Ki-67 were measured in postmortem samples of the left orbitofrontal cortex (OFC) of subjects with MDD, and psychiatrically-normal comparison subjects. Results: There was significant increase in C8, a higher ratio of DIABLO to XIAP, lower packing density of Ki-67-IR cells, and an unexpected age-dependent increase in PCNA in subjects with MDD vs. controls. PCNA levels were significantly higher in MDD subjects unresponsive to antidepressants or untreated with antidepressants. The DIABLO/XIAP ratio was higher in MDD subjects without antidepressants than in comparison subjects. Limitations: Qualitative nature of responsiveness assessments; Definition of resistance to antidepressant treatment is still controversial; Unclear role of PCNA. Conclusions: Markers of cell vulnerability to degeneration are increased and density of Ki67-positive cells is low MDD, but accompanied by normal XIAP levels. The results suggest increased vulnerability to cell pathology in depression that is insufficient to cause morphologically conspicuous cell death. Persistent but low-grade vulnerability to cell degeneration coexisting with reduced proliferation readiness may explain age-dependent reductions in neuronal densities in the OFC of depressed subjects. PMID:24655767

First detection of Leishmania major DNA in Sergentomyia (Sintonius) clydei (Sinton, 1928, Psychodidae: Phlebotominae), from an outbreak area of cutaneous leishmaniasis in Tunisia.

PubMed

Ayari, Chiraz; Ben Othman, Souad; Chemkhi, Jomaa; Tabbabi, Ahmed; Fisa, Roser; Ben Salah, Afif; BenAbderrazak, Souha

2016-04-01

In recent years there has been growing interest in Sergentomyia species. Their role in the spread of mammalian leishmaniasis appears repeatedly in the literature and the possibility of its implication in Leishmania transmission to humans remains controversial. Sergentomyia (Sintonius) clydei is one of several cryptic species sharing therefore common morphologic criteria with others species of the subgenera Sintonius. Little is known about this specie in Tunisia. We sampled and identified different specimens including four specimens of S. clydei collected from Sidi Bouzid and Kairouan areas (center of Tunisia) using morphological tools. Male Sergentomyia clydei and Sergentomyia christophersi are known to share several morphological characters and can be mistaken for. Consequently we took advantage of 5 male S. christophersi available in our collection (Tataouin, South of Tunisia). In our study morphological tools were completed by molecular study of cytochrome b gene to identify S. clydei. For the detection of Leishmania spp. that might infect our specimens, Leishmania DNA was analyzed by amplification of kinetoplast minicircle DNA using real-time PCR and nested-PCR. Obtained result was confirmed by restriction analysis of the amplified ribosomal internal transcribed spacer 1 (ITS1). We provide in our study, the first molecular identification of S. clydei, in Tunisia. Our Neighbor Joining tree based on mitochondrial cytochrome b gene shows two different clusters. The first includes the Tunisians S. clydei and other specimens from Africa, Middle East and the Arabic peninsula, and the second cluster containing the specimens from Seychelle. Unexpectedly, we also demonstrate the infection of one anthropophilic female S. clydei by Leishmania major DNA. This finding shows that more attention should be paid when identifying parasites by molecular tools within sandfly vector. Copyright © 2015. Published by Elsevier B.V.

Near-Universal Prevalence of Pneumocystis and Associated Increase in Mucus in the Lungs of Infants With Sudden Unexpected Death

PubMed Central

Vargas, Sergio L.; Ponce, Carolina A.; Gallo, Miriam; Pérez, Francisco; Astorga, J.-Felipe; Bustamante, Rebeca; Chabé, Magali; Durand-Joly, Isabelle; Iturra, Pablo; Miller, Robert F.; Aliouat, El Moukthar; Dei-Cas, Eduardo

2013-01-01

Background. Pneumocystis without obvious accompanying pathology is occasionally reported in autopsied infant lungs. Its prevalence and significance are unknown. Interestingly, this mild infection induces a strong activation of mucus secretion–related genes in young immunocompetent rodents that has not been explored in infants. Excess mucus is induced by multiple airway offenders through nonspecific pathways and would explain a cofactor role of Pneumocystis in respiratory disease. We undertook characterization of the prevalence of Pneumocystis and associated mucus in infant lungs. Methods. Samples from 128 infants (mean age, 101 days) who died suddenly and unexpectedly in Santiago during 1999–2004 were examined for Pneumocystis using nested polymerase chain reaction (nPCR) amplification of the P. jirovecii mtLSU ribosomal RNA gene and immunofluorescence microscopy (IF). Pneumocystis-negative infants 28 days and older and their age-closest positives were studied for MUC5AC expression and Pneumocystis burden by Western blot and quantitative PCR, respectively. Results. Pneumocystis DNA was detected by nPCR in 105 of the 128 infants (82.0%) and Pneumocystis organisms were visualized by IF in 99 (94.3%) of the DNA-positive infants. The infection was commonest at 3–4 months with 40 of 41 (97.6%) infants of that age testing positive. MUC5AC was significantly increased in Pneumocystis-positive tissue specimens (P = .013). Death was unexplained in 113 (88.3%) infants; Pneumocystis was detected in 95 (84.0%) of them vs 10 of 15 (66.7%) with explained death (P = .28). Conclusions. A highly focal Pneumocystis infection associated to increased mucus expression is almost universally present in the lungs of infants dying unexpectedly in the community regardless of autopsy diagnosis. PMID:23074306

Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions.

PubMed

Cory, Seth A; Van Vranken, Jonathan G; Brignole, Edward J; Patra, Shachin; Winge, Dennis R; Drennan, Catherine L; Rutter, Jared; Barondeau, David P

2017-07-03

In eukaryotes, sulfur is mobilized for incorporation into multiple biosynthetic pathways by a cysteine desulfurase complex that consists of a catalytic subunit (NFS1), LYR protein (ISD11), and acyl carrier protein (ACP). This NFS1-ISD11-ACP (SDA) complex forms the core of the iron-sulfur (Fe-S) assembly complex and associates with assembly proteins ISCU2, frataxin (FXN), and ferredoxin to synthesize Fe-S clusters. Here we present crystallographic and electron microscopic structures of the SDA complex coupled to enzyme kinetic and cell-based studies to provide structure-function properties of a mitochondrial cysteine desulfurase. Unlike prokaryotic cysteine desulfurases, the SDA structure adopts an unexpected architecture in which a pair of ISD11 subunits form the dimeric core of the SDA complex, which clarifies the critical role of ISD11 in eukaryotic assemblies. The different quaternary structure results in an incompletely formed substrate channel and solvent-exposed pyridoxal 5'-phosphate cofactor and provides a rationale for the allosteric activator function of FXN in eukaryotic systems. The structure also reveals the 4'-phosphopantetheine-conjugated acyl-group of ACP occupies the hydrophobic core of ISD11, explaining the basis of ACP stabilization. The unexpected architecture for the SDA complex provides a framework for understanding interactions with acceptor proteins for sulfur-containing biosynthetic pathways, elucidating mechanistic details of eukaryotic Fe-S cluster biosynthesis, and clarifying how defects in Fe-S cluster assembly lead to diseases such as Friedreich's ataxia. Moreover, our results support a lock-and-key model in which LYR proteins associate with acyl-ACP as a mechanism for fatty acid biosynthesis to coordinate the expression, Fe-S cofactor maturation, and activity of the respiratory complexes.

Injury patterns and preventability in prehospital motor vehicle crash fatalities in Victoria.

PubMed

Ryan, Matt; Stella, Julian; Chiu, Herman; Ragg, Michael

2004-08-01

To examine the pattern of anatomical injury in victims of motor vehicle crashes who die prior to reaching hospital. Cases were identified where death was an unexpected outcome. A retrospective review of autopsy case records including police reports, of all persons who died in motor vehicle crashes between 1 January 1998 and 31 December 1999 and underwent full autopsy at the Victorian Institute of Forensic Medicine (VIFM). Those cases where the victim died in the prehospital phase were examined. Abbreviate Injury Scores and Injury Severity Scores were calculated in each case. Bull's probit analysis was used to identify unexpected deaths. There were 352 motor road crash fatalities identified that underwent autopsy at the VIFM in the study period. Two hundred and six of these were prehospital deaths involving motor vehicles, which satisfied specified criteria. 82% (95% CI: 77.7-86.3%) of cases had Abbreviated Injury Scores of 5 (critical) or 6 (incompatible with life). 80.1% (95% CI: 75.7-84.5%) had an Injury Severity Score greater than 40. 36.9% (95% CI: 34.5-39.3%) of cases had the maximum Injury Severity score of 75. 88.8% (95% CI: 85-92.7%) of cases sustained a head injury and 83.9% (95% CI: 79.8-88.2%) a chest injury. Possibly preventable fatality was identified in 30 (14.6% 95% CI: 13.9-15.3%) cases. In motor vehicle crash fatalities, most victims who die before reaching hospital do so because of major injury, with the head and chest the commonest regions involved. A large proportion of these injuries could be considered unsurvivable regardless of treatment. Earlier intervention or retrieval of such patients is unlikely to influence outcome in the majority of cases.

The Role of Magnetic Resonance Imaging in Athletic Pubalgia and Core Muscle Injury.

PubMed

Coker, Dana J; Zoga, Adam C

2015-08-01

Magnetic resonance imaging (MRI) has become the standard of care imaging modality for a difficult, often misunderstood spectrum of musculoskeletal injury termed athletic pubalgia or core muscle injury. Armed with a dedicated noncontrast athletic pubalgia protocol and a late model phased array receiver coil, the musculoskeletal imager can play a great role in effective diagnosis and treatment planning for lesions, including osteitis pubis, midline pubic plate lesions, and rectus abdominis/adductor aponeurosis injury. Beyond these established patterns of MRI findings, there are many confounders and contributing pathologies about the pelvis in patients with activity related groin pain, including internal and periarticular derangements of the hip. The MRI is ideally suited to delineate the extent of expected injury and to identify the unexpected visceral and musculoskeletal lesions.

Quantitative functional characterization of conserved molecular interactions in the active site of mannitol 2-dehydrogenase

PubMed Central

Lucas, James E; Siegel, Justin B

2015-01-01

Enzyme active site residues are often highly conserved, indicating a significant role in function. In this study we quantitate the functional contribution for all conserved molecular interactions occurring within a Michaelis complex for mannitol 2-dehydrogenase derived from Pseudomonas fluorescens (pfMDH). Through systematic mutagenesis of active site residues, we reveal that the molecular interactions in pfMDH mediated by highly conserved residues not directly involved in reaction chemistry can be as important to catalysis as those directly involved in the reaction chemistry. This quantitative analysis of the molecular interactions within the pfMDH active site provides direct insight into the functional role of each molecular interaction, several of which were unexpected based on canonical sequence conservation and structural analyses. PMID:25752240

The costs (or benefits) associated with attended objects do little to influence inattentional blindness.

PubMed

Stothart, Cary R; Wright, Timothy J; Simons, Daniel J; Boot, Walter R

2017-02-01

We sometimes fail to notice unexpected objects or events when our attention is directed elsewhere, a phenomenon called inattentional blindness. We explored whether unexpected objects that shared the color of consequential objects would be noticed more often. In three pre-registered experiments, participants played a custom video game in which they avoided both low- and high-cost missiles (Experiment 1 and 2) or tried to hit rewarding missiles while avoiding costly ones (Experiment 3). After participants had played the game for about 8min, an unexpected object moved across the screen. Although participants selectively avoided more costly missiles when playing, they were no more likely to notice an unexpected object when its color was associated with greater costs. Apparently, people are no more likely to notice unexpected objects that are associated with negative consequences. Future research should examine whether objects that are themselves consequential are noticed more frequently. Copyright © 2016 Elsevier B.V. All rights reserved.

Mutations in Four Glycosyl Hydrolases Reveal a Highly Coordinated Pathway for Rhodopsin Biosynthesis and N-Glycan Trimming in Drosophila melanogaster

PubMed Central

Rosenbaum, Erica E.; Vasiljevic, Eva; Brehm, Kimberley S.; Colley, Nansi Jo

2014-01-01

As newly synthesized glycoproteins move through the secretory pathway, the asparagine-linked glycan (N-glycan) undergoes extensive modifications involving the sequential removal and addition of sugar residues. These modifications are critical for the proper assembly, quality control and transport of glycoproteins during biosynthesis. The importance of N-glycosylation is illustrated by a growing list of diseases that result from defects in the biosynthesis and processing of N-linked glycans. The major rhodopsin in Drosophila melanogaster photoreceptors, Rh1, is highly unique among glycoproteins, as the N-glycan appears to be completely removed during Rh1 biosynthesis and maturation. However, much of the deglycosylation pathway for Rh1 remains unknown. To elucidate the key steps in Rh1 deglycosylation in vivo, we characterized mutant alleles of four Drosophila glycosyl hydrolases, namely α-mannosidase-II (α-Man-II), α-mannosidase-IIb (α-Man-IIb), a β-N-acetylglucosaminidase called fused lobes (Fdl), and hexosaminidase 1 (Hexo1). We have demonstrated that these four enzymes play essential and unique roles in a highly coordinated pathway for oligosaccharide trimming during Rh1 biosynthesis. Our results reveal that α-Man-II and α-Man-IIb are not isozymes like their mammalian counterparts, but rather function at distinct stages in Rh1 maturation. Also of significance, our results indicate that Hexo1 has a biosynthetic role in N-glycan processing during Rh1 maturation. This is unexpected given that in humans, the hexosaminidases are typically lysosomal enzymes involved in N-glycan catabolism with no known roles in protein biosynthesis. Here, we present a genetic dissection of glycoprotein processing in Drosophila and unveil key steps in N-glycan trimming during Rh1 biosynthesis. Taken together, our results provide fundamental advances towards understanding the complex and highly regulated pathway of N-glycosylation in vivo and reveal novel insights into the functions of glycosyl hydrolases in the secretory pathway. PMID:24785692

Characterization of C-type lectins reveals an unexpectedly limited interaction between Cryptococcus neoformans spores and Dectin-1

PubMed Central

Walsh, Naomi M.; Wuthrich, Marcel; Wang, Huafeng; Klein, Bruce; Hull, Christina M.

2017-01-01

Phagocytosis by innate immune cells is an important process for protection against multiple pathologies and is particularly important for resistance to infection. However, phagocytosis has also been implicated in the progression of some diseases, including the dissemination of the human fungal pathogen, Cryptococcus neoformans. Previously, we identified Dectin-1 as a likely phagocytic receptor for C. neoformans spores through the use of soluble components in receptor-ligand blocking experiments. In this study, we used gain-of-function and loss-of-function assays with intact cells to evaluate the in vivo role of Dectin-1 and other C-type lectins in interactions with C. neoformans spores and discovered stark differences in outcome when compared with previous assays. First, we found that non-phagocytic cells expressing Dectin-1 were unable to bind spores and that highly sensitive reporter cells expressing Dectin-1 were not stimulated by spores. Second, we determined that some phagocytes from Dectin-1-/- mice interacted with spores differently than wild type (WT) cells, but the effects varied among assays and were modest overall. Third, while we detected small but statistically significant reductions in phagocytosis by primary alveolar macrophages from Dectin-1-/- mice compared to WT, we found no differences in survival between WT and Dectin-1-/- mice challenged with spores. Further analyses to assess the roles of other C-type lectins and their adapters revealed very weak stimulation of Dectin-2 reporter cells by spores and modest differences in binding and phagocytosis by Dectin-2-/- bone marrow-derived phagocytes. There were no discernable defects in binding or phagocytosis by phagocytes lacking Mannose Receptor, Mincle, Card-9, or FcRγ. Taken together, these results lead to the conclusion that Dectin-1 and other C-type lectins do not individually play a major roles in phagocytosis and innate defense by phagocytes against C. neoformans spores and highlight challenges in using soluble receptor/ligand blocking experiments to recapitulate biologically relevant interactions. PMID:28282442

Activation-induced cytidine deaminase (AID)-dependent somatic hypermutation requires a splice isoform of the serine/arginine-rich (SR) protein SRSF1

PubMed Central

Kanehiro, Yuichi; Todo, Kagefumi; Negishi, Misaki; Fukuoka, Junji; Gan, Wenjian; Hikasa, Takuya; Kaga, Yoshiaki; Takemoto, Masayuki; Magari, Masaki; Li, Xialu; Manley, James L.; Ohmori, Hitoshi; Kanayama, Naoki

2012-01-01

Somatic hypermutation (SHM) of Ig variable region (IgV) genes requires both IgV transcription and the enzyme activation-induced cytidine deaminase (AID). Identification of a cofactor responsible for the fact that IgV genes are much more sensitive to AID-induced mutagenesis than other genes is a key question in immunology. Here, we describe an essential role for a splice isoform of the prototypical serine/arginine-rich (SR) protein SRSF1, termed SRSF1-3, in AID-induced SHM in a DT40 chicken B-cell line. Unexpectedly, we found that SHM does not occur in a DT40 line lacking SRSF1-3 (DT40-ASF), although it is readily detectable in parental DT40 cells. Strikingly, overexpression of AID in DT40-ASF cells led to a large increase in nonspecific (off-target) mutations. In contrast, introduction of SRSF1-3, but not SRSF1, into these cells specifically restored SHM without increasing off-target mutations. Furthermore, we found that SRSF1-3 binds preferentially to the IgV gene and inhibits processing of the Ig transcript, providing a mechanism by which SRSF1-3 makes the IgV gene available for AID-dependent SHM. SRSF1 not only acts as an essential splicing factor but also regulates diverse aspects of mRNA metabolism and maintains genome stability. Our findings, thus, define an unexpected and important role for SRSF1, particularly for its splice variant, in enabling AID to function specifically on its natural substrate during SHM. PMID:22232677

Activation-induced cytidine deaminase (AID)-dependent somatic hypermutation requires a splice isoform of the serine/arginine-rich (SR) protein SRSF1.

PubMed

Kanehiro, Yuichi; Todo, Kagefumi; Negishi, Misaki; Fukuoka, Junji; Gan, Wenjian; Hikasa, Takuya; Kaga, Yoshiaki; Takemoto, Masayuki; Magari, Masaki; Li, Xialu; Manley, James L; Ohmori, Hitoshi; Kanayama, Naoki

2012-01-24

Somatic hypermutation (SHM) of Ig variable region (IgV) genes requires both IgV transcription and the enzyme activation-induced cytidine deaminase (AID). Identification of a cofactor responsible for the fact that IgV genes are much more sensitive to AID-induced mutagenesis than other genes is a key question in immunology. Here, we describe an essential role for a splice isoform of the prototypical serine/arginine-rich (SR) protein SRSF1, termed SRSF1-3, in AID-induced SHM in a DT40 chicken B-cell line. Unexpectedly, we found that SHM does not occur in a DT40 line lacking SRSF1-3 (DT40-ASF), although it is readily detectable in parental DT40 cells. Strikingly, overexpression of AID in DT40-ASF cells led to a large increase in nonspecific (off-target) mutations. In contrast, introduction of SRSF1-3, but not SRSF1, into these cells specifically restored SHM without increasing off-target mutations. Furthermore, we found that SRSF1-3 binds preferentially to the IgV gene and inhibits processing of the Ig transcript, providing a mechanism by which SRSF1-3 makes the IgV gene available for AID-dependent SHM. SRSF1 not only acts as an essential splicing factor but also regulates diverse aspects of mRNA metabolism and maintains genome stability. Our findings, thus, define an unexpected and important role for SRSF1, particularly for its splice variant, in enabling AID to function specifically on its natural substrate during SHM.

Feedback-related negativity codes outcome valence, but not outcome expectancy, during reversal learning.

PubMed

von Borries, A K L; Verkes, R J; Bulten, B H; Cools, R; de Bruijn, E R A

2013-12-01

Optimal behavior depends on the ability to assess the predictive value of events and to adjust behavior accordingly. Outcome processing can be studied by using its electrophysiological signatures--that is, the feedback-related negativity (FRN) and the P300. A prominent reinforcement-learning model predicts an FRN on negative prediction errors, as well as implying a role for the FRN in learning and the adaptation of behavior. However, these predictions have recently been challenged. Notably, studies so far have used tasks in which the outcomes have been contingent on the response. In these paradigms, the need to adapt behavioral responses is present only for negative, not for positive feedback. The goal of the present study was to investigate the effects of positive as well as negative violations of expectancy on FRN amplitudes, without the usual confound of behavioral adjustments. A reversal-learning task was employed in which outcome value and outcome expectancy were orthogonalized; that is, both positive and negative outcomes were equally unexpected. The results revealed a double dissociation, with effects of valence but not expectancy on the FRN and, conversely, effects of expectancy but not valence on the P300. While FRN amplitudes were largest for negative-outcome trials, irrespective of outcome expectancy, P300 amplitudes were largest for unexpected-outcome trials, irrespective of outcome valence. These FRN effects were interpreted to reflect an evaluation along a good-bad dimension, rather than reflecting a negative prediction error or a role in behavioral adaptation. By contrast, the P300 reflects the updating of information relevant for behavior in a changing context.

Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation.

PubMed

Reddy, Jay P; Peddibhotla, Sirisha; Bu, Wen; Zhao, Jing; Haricharan, Svasti; Du, Yi-Chieh Nancy; Podsypanina, Katrina; Rosen, Jeffrey M; Donehower, Larry A; Li, Yi

2010-02-23

p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention.

Toxins and tradition: the impact of food-chain contamination on the Inuit of northern Quebec.

PubMed Central

Wormworth, J

1995-01-01

The dependence of Quebec Inuit on their traditional diet, known as "country food," is complicated by the presence of toxins in the northern food chain. Dr. Eric Dewailly's unexpected finding of high levels of polychlorinated biphenyls (PCBs) in Inuit women's breast milk prompted years of research into this troubling public health issue. In his recent study of heavy-metal contaminants Dewailly found that mercury and organic chlorine compounds such as PCBs were the major toxins in Inuit blood samples. Although not present at levels high enough to endanger adults, these contaminants may have adverse developmental effects on fetuses and breast-fed infants. Although country food is a major source of contaminants, it contains important nutrients that counter some of the toxic effects. Dewailly's research indicates that the nutritional, economic and cultural benefits of country food far outweigh the risks. Images p1238-a PMID:7736374

Gold, currencies and market efficiency

NASA Astrophysics Data System (ADS)

Kristoufek, Ladislav; Vosvrda, Miloslav

2016-05-01

Gold and currency markets form a unique pair with specific interactions and dynamics. We focus on the efficiency ranking of gold markets with respect to the currency of purchase. By utilizing the Efficiency Index (EI) based on fractal dimension, approximate entropy and long-term memory on a wide portfolio of 142 gold price series for different currencies, we construct the efficiency ranking based on the extended EI methodology we provide. Rather unexpected results are uncovered as the gold prices in major currencies lay among the least efficient ones whereas very minor currencies are among the most efficient ones. We argue that such counterintuitive results can be partly attributed to a unique period of examination (2011-2014) characteristic by quantitative easing and rather unorthodox monetary policies together with the investigated illegal collusion of major foreign exchange market participants, as well as some other factors discussed in some detail.

Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations.

PubMed

Varon, R; Seemanova, E; Chrzanowska, K; Hnateyko, O; Piekutowska-Abramczuk, D; Krajewska-Walasek, M; Sykut-Cegielska, J; Sperling, K; Reis, A

2000-11-01

Nijmegen breakage syndrome (NBS) is a chromosomal instability disorder, clinically characterised by microcephaly, immunodeficiency, radiosensitivity and a very high predisposition to lymphoid malignancy. Recently, it was demonstrated that mutations in the NBS1 gene are responsible for NBS. Most of the NBS patients known so far are of Slav origin and carry a major founder mutation 657del5 in exon 6 of the NBS1 gene. In this study we estimated the prevalence of the 657del5 mutation in the Czech Republic, Poland and the Ukraine. We found an unexpectedly high carrier frequency of the 657del5 mutation (1/177) in the three Slav populations, a factor that may contribute to cancer frequency in those countries. In addition, we show that NBS patients are often diagnosed late and therefore receive inappropriate therapy.

Personal efficacy, the information environment, and attitudes toward global warming and climate change in the United States.

PubMed

Kellstedt, Paul M; Zahran, Sammy; Vedlitz, Arnold

2008-02-01

Despite the growing scientific consensus about the risks of global warming and climate change, the mass media frequently portray the subject as one of great scientific controversy and debate. And yet previous studies of the mass public's subjective assessments of the risks of global warming and climate change have not sufficiently examined public informedness, public confidence in climate scientists, and the role of personal efficacy in affecting global warming outcomes. By examining the results of a survey on an original and representative sample of Americans, we find that these three forces-informedness, confidence in scientists, and personal efficacy-are related in interesting and unexpected ways, and exert significant influence on risk assessments of global warming and climate change. In particular, more informed respondents both feel less personally responsible for global warming, and also show less concern for global warming. We also find that confidence in scientists has unexpected effects: respondents with high confidence in scientists feel less responsible for global warming, and also show less concern for global warming. These results have substantial implications for the interaction between scientists and the public in general, and for the public discussion of global warming and climate change in particular.

Transcranial magnetic stimulation: language function.

PubMed

Epstein, C M

1998-07-01

Studies of language using transcranial magnetic stimulation (TMS) have focused both on identification of language areas and on elucidation of function. TMS may result in either inhibition or facilitation of language processes and may operate directly at a presumptive site of language cortex or indirectly through intracortical networks. TMS has been used to create reversible "temporary lesions," similar to those produced by Wada tests and direct cortical electrical stimulation, in cerebral cortical areas subserving language function. Rapid-rate TMS over the left inferior frontal region blocks speech output in most subjects. However, the results are not those predicted from classic models of language organization. Speech arrest is obtained most easily over facial motor cortex, and true aphasia is rare, whereas right hemisphere or bilateral lateralization is unexpectedly prominent. A clinical role for these techniques is not yet fully established. Interfering with language comprehension and verbal memory is currently more difficult than blocking speech output, but numerous TMS studies have demonstrated facilitation of language-related tasks, including oral word association, story recall, digit span, and picture naming. Conversely, speech output also facilitates motor responses to TMS in the dominant hemisphere. Such new and often-unexpected findings may provide important insights into the organization of language.

An unexpected role for the yeast nucleotide exchange factor Sil1 as a reductant acting on the molecular chaperone BiP

PubMed Central

Siegenthaler, Kevin D; Pareja, Kristeen A; Wang, Jie; Sevier, Carolyn S

2017-01-01

Unfavorable redox conditions in the endoplasmic reticulum (ER) can decrease the capacity for protein secretion, altering vital cell functions. While systems to manage reductive stress are well-established, how cells cope with an overly oxidizing ER remains largely undefined. In previous work (Wang et al., 2014), we demonstrated that the chaperone BiP is a sensor of overly oxidizing ER conditions. We showed that modification of a conserved BiP cysteine during stress beneficially alters BiP chaperone activity to cope with suboptimal folding conditions. How this cysteine is reduced to reestablish 'normal' BiP activity post-oxidative stress has remained unknown. Here we demonstrate that BiP's nucleotide exchange factor – Sil1 – can reverse BiP cysteine oxidation. This previously unexpected reductant capacity for yeast Sil1 has potential implications for the human ataxia Marinesco-Sjögren syndrome, where it is interesting to speculate that a disruption in ER redox-signaling (due to genetic defects in SIL1) may influence disease pathology. DOI: http://dx.doi.org/10.7554/eLife.24141.001 PMID:28257000

Inactivation of the spxA1 or spxA2 gene of Streptococcus mutans decreases virulence in the rat caries model.

PubMed

Galvão, L C C; Rosalen, P L; Rivera-Ramos, I; Franco, G C N; Kajfasz, J K; Abranches, J; Bueno-Silva, B; Koo, H; Lemos, J A

2017-04-01

In oral biofilms, the major environmental challenges encountered by Streptococcus mutans are acid and oxidative stresses. Previously, we showed that the transcriptional regulators SpxA1 and SpxA2 are involved in general stress survival of S. mutans with SpxA1 playing a primary role in activation of antioxidant and detoxification strategies whereas SpxA2 serves as a back up activator of oxidative stress genes. We have also found that spxA1 mutant strains (∆spxA1 and ∆spxA1∆spxA2) are outcompeted by peroxigenic oral streptococci in vitro and have impaired abilities to colonize the teeth of rats fed a highly cariogenic diet. Here, we show that the Spx proteins can also exert regulatory roles in the expression of additional virulence attributes of S. mutans. Competence activation is significantly impaired in Δspx strains and the production of mutacin IV and V is virtually abolished in ΔspxA1 strains. Unexpectedly, the ∆spxA2 strain showed increased production of glucans from sucrose, without affecting the total amount of bacteria within biofilms when compared with the parent strain. By using the rat caries model, we showed that the capacity of the ΔspxA1 and ΔspxA2 strains to cause caries on smooth tooth surfaces is significantly impaired. The ∆spxA2 strain also formed fewer lesions on sulcal surfaces. This report reveals that global regulation via Spx contributes to the cariogenic potential of S. mutans and highlights that animal models are essential in the characterization of bacterial traits implicated in virulence. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Structural characterization of a mixed-linkage glucan deficient mutant reveals alteration in cellulose microfibril orientation in rice coleoptile mesophyll cell walls

PubMed Central

Smith-Moritz, Andreia M.; Hao, Zhao; Fernández-Niño, Susana G.; Fangel, Jonatan U.; Verhertbruggen, Yves; Holman, Hoi-Ying N.; Willats, William G. T.; Ronald, Pamela C.; Scheller, Henrik V.; Heazlewood, Joshua L.; Vega-Sánchez, Miguel E.

2015-01-01

The CELLULOSE SYNTHASE-LIKE F6 (CslF6) gene was previously shown to mediate the biosynthesis of mixed-linkage glucan (MLG), a cell wall polysaccharide that is hypothesized to be tightly associated with cellulose and also have a role in cell expansion in the primary cell wall of young seedlings in grass species. We have recently shown that loss-of-function cslf6 rice mutants do not accumulate MLG in most vegetative tissues. Despite the absence of a structurally important polymer, MLG, these mutants are unexpectedly viable and only show a moderate growth compromise compared to wild type. Therefore these mutants are ideal biological systems to test the current grass cell wall model. In order to gain a better understanding of the role of MLG in the primary wall, we performed in-depth compositional and structural analyses of the cell walls of 3 day-old rice seedlings using various biochemical and novel microspectroscopic approaches. We found that cellulose content as well as matrix polysaccharide composition was not significantly altered in the MLG deficient mutant. However, we observed a significant change in cellulose microfibril bundle organization in mesophyll cell walls of the cslf6 mutant. Using synchrotron source Fourier Transform Mid-Infrared (FTM-IR) Spectromicroscopy for high-resolution imaging, we determined that the bonds associated with cellulose and arabinoxylan, another major component of the primary cell walls of grasses, were in a lower energy configuration compared to wild type, suggesting a slightly weaker primary wall in MLG deficient mesophyll cells. Taken together, these results suggest that MLG may influence cellulose deposition in mesophyll cell walls without significantly affecting anisotropic growth thus challenging MLG importance in cell wall expansion. PMID:26347754

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

Smith-Moritz, Andreia M.; Hao, Zhao; Fernández-Nino, Susana G.

The CELLULOSE SYNTHASE-LIKE F6 (CslF6) gene was previously shown to mediate the biosynthesis of mixed-linkage glucan (MLG), a cell wall polysaccharide that is hypothesized to be tightly associated with cellulose and also have a role in cell expansion in the primary cell wall of young seedlings in grass species. We have recently shown that loss-of-function cslf6 rice mutants do not accumulate MLG in most vegetative tissues. Despite the absence of a structurally important polymer, MLG, these mutants are unexpectedly viable and only show a moderate growth compromise compared to wild type. Therefore these mutants are ideal biological systems to testmore » the current grass cell wall model. In order to gain a better understanding of the role of MLG in the primary wall, we performed in-depth compositional and structural analyses of the cell walls of 3 day-old rice seedlings using various biochemical and novel microspectroscopic approaches. We found that cellulose content as well as matrix polysaccharide composition was not significantly altered in the MLG deficient mutant. However, we observed a significant change in cellulose microfibril bundle organization in mesophyll cell walls of the cslf6 mutant. Using synchrotron source Fourier Transform Mid-Infrared (FTM-IR) Spectromicroscopy for high-resolution imaging, we determined that the bonds associated with cellulose and arabinoxylan, another major component of the primary cell walls of grasses, were in a lower energy configuration compared to wild type, suggesting a slightly weaker primary wall in MLG deficient mesophyll cells. Finally, taken together, these results suggest that MLG may influence cellulose deposition in mesophyll cell walls without significantly affecting anisotropic growth thus challenging MLG importance in cell wall expansion.« less

Structural characterization of a mixed-linkage glucan deficient mutant reveals alteration in cellulose microfibril orientation in rice coleoptile mesophyll cell walls

DOE PAGES

Smith-Moritz, Andreia M.; Hao, Zhao; Fernández-Nino, Susana G.; ...

2015-08-18

The CELLULOSE SYNTHASE-LIKE F6 (CslF6) gene was previously shown to mediate the biosynthesis of mixed-linkage glucan (MLG), a cell wall polysaccharide that is hypothesized to be tightly associated with cellulose and also have a role in cell expansion in the primary cell wall of young seedlings in grass species. We have recently shown that loss-of-function cslf6 rice mutants do not accumulate MLG in most vegetative tissues. Despite the absence of a structurally important polymer, MLG, these mutants are unexpectedly viable and only show a moderate growth compromise compared to wild type. Therefore these mutants are ideal biological systems to testmore » the current grass cell wall model. In order to gain a better understanding of the role of MLG in the primary wall, we performed in-depth compositional and structural analyses of the cell walls of 3 day-old rice seedlings using various biochemical and novel microspectroscopic approaches. We found that cellulose content as well as matrix polysaccharide composition was not significantly altered in the MLG deficient mutant. However, we observed a significant change in cellulose microfibril bundle organization in mesophyll cell walls of the cslf6 mutant. Using synchrotron source Fourier Transform Mid-Infrared (FTM-IR) Spectromicroscopy for high-resolution imaging, we determined that the bonds associated with cellulose and arabinoxylan, another major component of the primary cell walls of grasses, were in a lower energy configuration compared to wild type, suggesting a slightly weaker primary wall in MLG deficient mesophyll cells. Finally, taken together, these results suggest that MLG may influence cellulose deposition in mesophyll cell walls without significantly affecting anisotropic growth thus challenging MLG importance in cell wall expansion.« less

Levels of palmitic acid ester of hydroxystearic acid (PAHSA) are reduced in the breast milk of obese mothers.

PubMed

Brezinova, Marie; Kuda, Ondrej; Hansikova, Jana; Rombaldova, Martina; Balas, Laurence; Bardova, Kristina; Durand, Thierry; Rossmeisl, Martin; Cerna, Marcela; Stranak, Zbynek; Kopecky, Jan

2018-02-01

To achieve optimal development of a newborn, breastfeeding is extensively recommended, but little is known about the role of non-nutritive bioactive milk components. We aimed to characterize the fatty acid esters of hydroxy fatty acids (FAHFAs), namely palmitic acid hydroxystearic acids (PAHSAs)-endogenous lipids with anti-inflammatory and anti-diabetic properties, in human breast milk. Breast milk samples from 30 lean (BMI=19-23) and 23 obese (BMI>30) women were collected 72h postpartum. Adipose tissue and milk samples were harvested from C57BL/6J mice. FAHFA lipid profiles were measured using reverse phase and chiral liquid chromatography-mass spectrometry method. PAHSA regioisomers as well as other FAHFAs were present in both human and murine milk. Unexpectedly, the levels of 5-PAHSA were higher relative to other regioisomers. The separation of both regioisomers and enantiomers of PAHSAs revealed that both R- and S-enantiomers were present in the biological samples, and that the majority of the 5-PAHSA signal is of R configuration. Total PAHSA levels were positively associated with weight gain during pregnancy, and 5-PAHSA as well as total PAHSA levels were significantly lower in the milk of the obese compared to the lean mothers. Our results document for the first time the presence of lipid mediators from the FAHFA family in breast milk, while giving an insight into the stereochemistry of PAHSAs. They also indicate the negative effect of obesity on 5-PAHSA levels. Future studies will be needed to explore the role and mechanism of action of FAHFAs in breast milk. Copyright © 2017 Elsevier B.V. All rights reserved.

Inactivation of the spxA1 or spxA2 gene of Streptococcus mutans decreases virulence in the rat caries model

PubMed Central

Galvão, Lívia C.C.; Rosalen, Pedro L.; Rivera-Ramos, Isamar; Franco, Gilson C.N.; Kajfasz, Jessica K; Abranches, Jacqueline; Bueno-Silva, Bruno; Koo, Hyun; Lemos, José A.

2016-01-01

SUMMARY In oral biofilms, the major environmental challenges encountered by Streptococcus mutans are acid and oxidative stresses. Previously, we showed that the transcriptional regulators SpxA1 and SpxA2 are involved in general stress survival of S. mutans with SpxA1 playing a primary role in activation of antioxidant and detoxification strategies whereas SpxA2 serves as a back up activator of oxidative stress genes. We have also found that spxA1 mutant strains (ΔspxA1 and ΔspxA1ΔspxA2) are outcompeted by peroxigenic oral streptococci in vitro and have impaired abilities to colonize the teeth of rats fed a highly cariogenic diet. Here, we show that the Spx proteins can also exert regulatory roles in the expression of additional virulence attributes of S. mutans. Competence activation is significantly impaired in Δspx strains and the production of mutacin IV and V is virtually abolished in ΔspxA1 strains. Unexpectedly, the ΔspxA2 strain showed increased production of glucans from sucrose, without affecting the total amount of bacteria within biofilms when compared to the parent strain. By using the rat caries model, we showed that the capacity of the ΔspxA1 and ΔspxA2 strains to cause caries on smooth tooth surfaces is significantly impaired. The ΔspxA2 strain also formed fewer lesions on sulcal surfaces. This report reveals that global regulation via Spx contributes to the cariogenic potential of S. mutans and highlights the essentiality of animal models in the characterization of bacterial traits implicated in virulence. PMID:27037617

What are reasonable expectations? Healthcare student perceptions of their programmes in the North West of England.

PubMed

Hamshire, Claire; Willgoss, Thomas G; Wibberley, Christopher

2013-02-01

Concerns about current levels of attrition from some healthcare programmes have emphasised the need to gain a greater insight into students' expectations and experiences. The aim of this study was to determine how students in the North West of England perceived their studies and to identify the factors that could contribute to students' dissatisfaction. A mixed methods sequential exploratory study. Nine universities in the North West of England. Phase one used narrative interviews with a purposive sample of 24 students to investigate their expectations and experiences. Data from these interviews were analysed using a thematic framework and direct quotes from key themes were incorporated into online survey for phase 2. Survey respondents were asked to rate their agreement to statements on a four-point Likert-type response format. There was also an opportunity to leave comments through open questions relating to each theme. A total of 1080 respondents completed the online survey in phase 2. The majority of students reported positive experiences of their course. There was strong agreement in the importance of the role of the personal tutor and of a supportive placement mentor. Some students indicated that the workload and academic level were a shock at first. Students identified difficulties around the cost of placement travel and the impact of placements on family life. Financial hardship was a frequently cited issue that students attributed to thoughts of discontinuation. Most students had positive learning experiences which meet their expectations. Students who have unmet expectations report poor placement experiences, lack of support, unexpectedly high workloads and financial difficulties. Clear guidance on the role of personal tutor and placement mentor is recommended. Copyright © 2012 Elsevier Ltd. All rights reserved.

Role of a membrane-bound aldehyde dehydrogenase complex AldFGH in acetic acid fermentation with Acetobacter pasteurianus SKU1108.

PubMed

Yakushi, Toshiharu; Fukunari, Seiya; Kodama, Tomohiro; Matsutani, Minenosuke; Nina, Shun; Kataoka, Naoya; Theeragool, Gunjana; Matsushita, Kazunobu

2018-05-01

Acetic acid fermentation is widely considered a consequence of ethanol oxidation by two membrane-bound enzymes-alcohol dehydrogenase and aldehyde dehydrogenase (ALDH)-of acetic acid bacteria. Here, we used a markerless gene disruption method to construct a mutant of the Acetobacter pasteurianus strain SKU1108 with a deletion in the aldH gene, which encodes the large catalytic subunit of a heterotrimeric ALDH complex (AldFGH), to examine the role of AldFGH in acetic acid fermentation. The ΔaldH strain grew less on ethanol-containing medium, i.e., acetic acid fermentation conditions, than the wild-type strain and significantly accumulated acetaldehyde in the culture medium. Unexpectedly, acetaldehyde oxidase activity levels of the intact ΔaldH cells and the ΔaldH cell membranes were similar to those of the wild-type strain, which might be attributed to an additional ALDH isozyme (AldSLC). The apparent K M values of the wild-type and ΔaldH membranes for acetaldehyde were similar to each other, when the cells were cultured in nonfermentation conditions, where ΔaldH cells grow as well as the wild-type cells. However, the membranes of the wild-type cells grown under fermentation conditions showed a 10-fold lower apparent K M value than those of the cells grown under nonfermentation conditions. Under fermentation conditions, transcriptional levels of a gene for AldSLC were 10-fold lower than those under nonfermentation conditions, whereas aldH transcript levels were not dramatically changed under the two conditions. We suggest that A. pasteurianus SKU1108 has two ALDHs, and the AldFGH complex is indispensable for acetic acid fermentation and is the major enzyme under fermentation conditions.

Identification of mRNAs that move over long distances using an RNA-Seq analysis of Arabidopsis/Nicotiana benthamiana heterografts.

PubMed

Notaguchi, Michitaka; Higashiyama, Tetsuya; Suzuki, Takamasa

2015-02-01

Phloem is a conductive tissue that allocates nutrients from mature source leaves to sinks such as young developing tissues. Phloem also delivers proteins and RNA species, such as small RNAs and mRNAs. Intensive studies on plant systemic signaling revealed the essential roles of proteins and RNA species. However, many of their functions are still largely unknown, with the roles of transported mRNAs being particularly poorly understood. A major difficulty is the absence of an accurate and comprehensive list of mobile transcripts. In this study, we used a hetero-graft system with Nicotiana benthamiana as the recipient scion and Arabidopsis as the donor stock, to identify transcripts that moved long distances across the graft union. We identified 138 Arabidopsis transcripts as mobile mRNAs, which we collectively termed the mRNA mobilome. Reverse transcription-PCR, quantitative real-time PCR and droplet digital PCR analyses confirmed the mobility. The transcripts included potential signaling factors and, unexpectedly, more general factors. In our investigations, we found no preferred transcript length, no previously known sequence motifs in promoter or transcript sequences and no similarities between the level of the transcripts and that in the source leaves. Grafting experiments regarding the function of ERECTA, an identified transcript, showed that no function of the transcript mobilized. To our knowledge, this is the first report identifying transcripts that move over long distances using a hetero-graft system between different plant taxa. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Glycosphingolipid-facilitated membrane insertion and internalization of cobra cardiotoxin. The sulfatide.cardiotoxin complex structure in a membrane-like environment suggests a lipid-dependent cell-penetrating mechanism for membrane binding polypeptides.

PubMed

Wang, Chia-Hui; Liu, Jyung-Hurng; Lee, Shao-Chen; Hsiao, Chwan-Deng; Wu, Wen-Guey

2006-01-06

Cobra cardiotoxins, a family of basic polypeptides having lipid- and heparin-binding capacities similar to the cell-penetrating peptides, induce severe tissue necrosis and systolic heart arrest in snakebite victims. Whereas cardiotoxins are specifically retained on the cell surface via heparan sulfate-mediated processes, their lipid binding ability appears to be responsible, at least in part, for cardiotoxin-induced membrane leakage and cell death. Although the exact role of lipids involved in toxin-mediated cytotoxicity remains largely unknown, monoclonal anti-sulfatide antibody O4 has recently been shown to inhibit the action of CTX A3, the major cardiotoxin from Taiwan cobra venom, on cardiomyocytes by preventing cardiotoxin-induced membrane leakage and CTX A3 internalization into mitochondria. Here, we show that anti-sulfatide acts by blocking the binding of CTX A3 to the sulfatides in the plasma membrane to prevent sulfatide-dependent CTX A3 membrane pore formation and internalization. We also describe the crystal structure of a CTX A3-sulfatide complex in a membrane-like environment at 2.3 angstroms resolution. The unexpected orientation of the sulfatide fatty chains in the structure allows prediction of the mode of toxin insertion into the plasma membrane. CTX A3 recognizes both the headgroup and the ceramide interfacial region of sulfatide to induce a lipid conformational change that may play a key role in CTX A3 oligomerization and cellular internalization. This proposed lipid-mediated toxin translocation mechanism may also shed light on the cellular uptake mechanism of the amphiphilic cell-penetrating peptides known to involve multiple internalization pathways.

Managing the Unexpected: Complexity as Distributed Sensemaking

NASA Astrophysics Data System (ADS)

Weick, Karl E.

In 1998 the Centers for Disease Control (CDC) published a statement of their strategy entitled "Preventing Emerging Infectious Diseases: A Strategy for the 21st Century." They described their central challenge this way: "because we do not know what new diseases will arise, we must always be prepared for the unexpected" (p. vii). Soon after they published that statement CDC was confronted with an unexpected emerging disease, the West Nile Virus, which they misdiagnosed initially.

Misbheaving Faults: The Expanding Role of Geodetic Imaging in Unraveling Unexpected Fault Slip Behavior

NASA Astrophysics Data System (ADS)

Barnhart, W. D.; Briggs, R.

2015-12-01

Geodetic imaging techniques enable researchers to "see" details of fault rupture that cannot be captured by complementary tools such as seismology and field studies, thus providing increasingly detailed information about surface strain, slip kinematics, and how an earthquake may be transcribed into the geological record. For example, the recent Haiti, Sierra El Mayor, and Nepal earthquakes illustrate the fundamental role of geodetic observations in recording blind ruptures where purely geological and seismological studies provided incomplete views of rupture kinematics. Traditional earthquake hazard analyses typically rely on sparse paleoseismic observations and incomplete mapping, simple assumptions of slip kinematics from Andersonian faulting, and earthquake analogs to characterize the probabilities of forthcoming ruptures and the severity of ground accelerations. Spatially dense geodetic observations in turn help to identify where these prevailing assumptions regarding fault behavior break down and highlight new and unexpected kinematic slip behavior. Here, we focus on three key contributions of space geodetic observations to the analysis of co-seismic deformation: identifying near-surface co-seismic slip where no easily recognized fault rupture exists; discerning non-Andersonian faulting styles; and quantifying distributed, off-fault deformation. The 2013 Balochistan strike slip earthquake in Pakistan illuminates how space geodesy precisely images non-Andersonian behavior and off-fault deformation. Through analysis of high-resolution optical imagery and DEMs, evidence emerges that a single fault map slip as both a strike slip and dip slip fault across multiple seismic cycles. These observations likewise enable us to quantify on-fault deformation, which account for ~72% of the displacements in this earthquake. Nonetheless, the spatial distribution of on- and off-fault deformation in this event is highly spatially variable- a complicating factor for comparisons of geologic and geodetic slip rates. As such, detailed studies such as this will play a continuing vital role in the accurate assessment of short- and long-term fault slip kinematics.

Electrodynamics of the middle atmosphere: Superpressure balloon program

NASA Technical Reports Server (NTRS)

Holzworth, Robert H.

1987-01-01

In this experiment a comprehensive set of electrical parameters were measured during eight long duration flights in the southern hemisphere stratosphere. These flight resulted in the largest data set ever collected from the stratosphere. The stratosphere has never been electrodynamically sampled in the systematic manner before. New discoveries include short term variability in the planetary scale electric current system, the unexpected observation of stratospheric conductivity variations over thunderstorms and the observation of direct stratospheric conductivity variations following a relatively small solar flare. Major statistical studies were conducted of the large scale current systems, the stratospheric conductivity and the neutral gravity waves (from pressure and temperature data) using the entire data set.

Design, development, mechanistic elucidation, and rational optimization of a tandem Ireland Claisen/Cope rearrangement reaction for rapid access to the (iso)cyclocitrinol core.

PubMed

Plummer, Christopher W; Wei, Carolyn S; Yozwiak, Carrie E; Soheili, Arash; Smithback, Sara O; Leighton, James L

2014-07-16

An approach to the synthesis of the (iso)cyclocitrinol core structure is described. The key step is a tandem Ireland Claisen/Cope rearrangement sequence, wherein the Ireland Claisen rearrangement effects ring contraction to a strained 10-membered ring, and that strain in turn drives the Cope rearrangement under unusually mild thermal conditions. A major side product was identified as resulting from an unexpected and remarkably facile [1,3]-sigmatropic rearrangement, and a tactic to disfavor the [1,3] pathway and increase the efficiency of the tandem reaction was rationally devised.

Life after Loss: Parent Bereavement and Coping Experiences after Infant Death in the Neonatal Intensive Care Unit.

PubMed

Currie, Erin R; Christian, Becky J; Hinds, Pamela S; Perna, Samuel J; Robinson, Cheryl; Day, Sara; Bakitas, Marie; Meneses, Karen

2018-05-14

The death of an infant in the neonatal intensive care unit (NICU) is a profound and unexpected loss for parents that results in a complex process of coping with bereavement. A descriptive qualitative approach was used to explore parent bereavement and coping experiences after infant death in the NICU. The Dual Process Model of Coping with Bereavement was used as a conceptual framework to help understand how parents cope with grief after infant death. Living with infant death was a process that resulted in major life changes and a process of oscillating among various coping strategies.

Aromatic fluorine compounds. VI. Displacement of aryl fluorine in diazonium salts

USGS Publications Warehouse

Finger, G.C.; Oesterling, R.E.

1956-01-01

Several chlorofluorobenzenes have been isolated from the Schiemann synthesis of fluorobenzenes. These have been shown to be the products of two side reactions occurring during thermal decomposition of the dry benzenediazonium fluoborate salt containing coprecipitated sodium chloride, an unavoidable contaminant in large preparations involving the use of hydrochloric acid and sodium fluoborate. The major side reaction and its chloro product were unexpected; a unique displacement of fluorine ortho to the diazonium group was observed. Replacement of the diazo group with chlorine was the predicted side reaction which proved to be minor. Conditions causing the side reactions and the isolation and identification of the products are described.

Retention and application of Skylab experiment experiences to future programs

NASA Technical Reports Server (NTRS)

Milly, N.; Gillespie, V. G.

1974-01-01

Problems encountered on Skylab Experiments are listed in order that these experiences and associated recommendations might help to prevent similar problems on future programs. The criteria for selection of the data to be utilized was to identify the problem areas within the Skylab Program which would be of major significance with respect to future programs. Also, the problem had to be unique in that it would help identify to a designer/manufacturer an unforeseen or unanticipated occurrence which could cause failures, delays, or additional cost. Only those unexpected problems that may occur due to the nature of aerospace experiment environmental and operational requirements are included.

Discovery of unexpected pain in intubated and sedated patients.

PubMed

Clukey, Lory; Weyant, Ruth A; Roberts, Melanie; Henderson, Ann

2014-05-01

The perceptions of patients who are restrained and sedated while being treated with mechanical ventilation in the intensive care unit are not well understood. The effectiveness of sedation used to aid in recovery and enhance comfort during intubation is unknown. To explore the perceptions of patients who were intubated and receiving pain medication while sedated and restrained in the intensive care unit, in particular, their experience and their memories of the experience. In a phenomenological study, 14 patients who were intubated and receiving pain medication while sedated and restrained were interviewed at the bedside. A semistructured interview guide was used. Data were analyzed by using an inductive method consistent with qualitative research. Three major themes were identified from the data: lack of memory of being restrained; a perception of being intubated as horrific; nursing behaviors that were helpful and comforting. An unexpected discovery was that sedation may be interfering with pain assessment and management. Being intubated can be painful and traumatic despite administration of sedatives and analgesics. Sedation may mask uncontrolled pain for intubated patients and prevent them from communicating this condition to a nurse. Nurses may need to evaluate current interventions in order to provide maximum comfort and promote optimal positive outcomes for intensive care patients who are intubated.

When Field Experiments Yield Unexpected Results: Lessons Learned from Measuring Selection in White Sands Lizards

PubMed Central

Hardwick, Kayla M.; Harmon, Luke J.; Hardwick, Scott D.; Rosenblum, Erica Bree

2015-01-01

Determining the adaptive significance of phenotypic traits is key for understanding evolution and diversification in natural populations. However, evolutionary biologists have an incomplete understanding of how specific traits affect fitness in most populations. The White Sands system provides an opportunity to study the adaptive significance of traits in an experimental context. Blanched color evolved recently in three species of lizards inhabiting the gypsum dunes of White Sands and is likely an adaptation to avoid predation. To determine whether there is a relationship between color and susceptibility to predation in White Sands lizards, we conducted enclosure experiments, quantifying survivorship of Holbrookia maculate exhibiting substrate-matched and substrate-mismatched phenotypes. Lizards in our study experienced strong predation. Color did not have a significant effect on survival, but we found several unexpected relationships including variation in predation over small spatial and temporal scales. In addition, we detected a marginally significant interaction between sex and color, suggesting selection for substrate matching may be stronger for males than females. We use our results as a case study to examine six major challenges frequently encountered in field-based studies of natural selection, and suggest that insight into the complexities of selection often results when experiments turn out differently than expected. PMID:25714838

Characteristics of unexpected protein bands in multiple myeloma patients after autologous stem cell transplantation.

PubMed

Kim, Soo-Kyung; Jeong, Tae-Dong; Kim, So Young; Lee, Woochang; Chun, Sail; Suh, Cheol Won; Min, Won-Ki

2014-05-01

The aim of this study is to investigate the characteristics of unexpected protein bands (UPBs) in patients with multiple myeloma (MM). Individuals diagnosed with MM (n=193) were enrolled. Their medical records and IFE patterns were reviewed. Of the patients that underwent ASCT, 54% developed UPBs. The median time for UPB appearance and duration was 1.8 and 5.7months, respectively. IFE revealed 74.1% of UPBs to be of the immunoglobulin G type and 72.2% to be of the κ-type. At UPB appearance, 42.6% of patients were defined as sCR or CR, and 50.0% of the patients satisfying the CR criteria had an abnormal FLC ratio. Of the patients who developed UPBs, five relapsed. Among these, four patients showed disappearance of the previous IFE oligoclonality and reappearance of the original paraprotein at relapse. Close follow-up of UPBs is critical for evaluating MM therapeutic response and disease progression. The presence of monoclonal bands may indicate relapse of disease, but in the vast majority of cases with UPBs, it does not; instead, it most likely represents a transient phenomenon caused by the immune response. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

The value of 'binder-off' imaging to identify occult and unexpected pelvic ring injuries.

PubMed

Fagg, James A C; Acharya, Mehool R; Chesser, Tim J S; Ward, Anthony J

2018-02-01

To determine the effectiveness of 'binder-off' plain pelvic radiographs in the assessment of pelvic ring injuries. All patients requiring operative intervention at our tertiary referral pelvic unit/major trauma centre for high-energy pelvic injuries between April 2012 and December 2014 were retrospectively identified. Pre-operative pelvic imaging with and without pelvic binder was reviewed with respect to fracture pattern and pelvic stability. The frequency with which the imaging without pelvic binder changed the opinion of the pelvic stability and need for operative intervention, when compared with the computed tomography (CT) scans and anteroposterior (AP) radiographs with the binder on, was assessed. Seventy-three percent (71 of 97) of patients had initial imaging with a pelvic binder in situ. Of these, 76% (54 of 71) went on to have 'binder-off' imaging. Seven percent (4 of 54) of patients had unexpected unstable pelvic ring injuries identified on 'binder-off' imaging that were not identified on CT imaging in binder. Trauma CT imaging of the pelvis with a pelvic binder in place is inadequate at excluding unstable pelvic ring injuries, and, based on the original findings in this paper, we recommend additional plain film 'binder-off' radiographs, when there is any clinical concern. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of the DAVROS (Development And Validation of Risk-adjusted Outcomes for Systems of emergency care) risk-adjustment model as a quality indicator for healthcare

PubMed Central

Wilson, Richard; Goodacre, Steve W; Klingbajl, Marcin; Kelly, Anne-Maree; Rainer, Tim; Coats, Tim; Holloway, Vikki; Townend, Will; Crane, Steve

2014-01-01

Background and objective Risk-adjusted mortality rates can be used as a quality indicator if it is assumed that the discrepancy between predicted and actual mortality can be attributed to the quality of healthcare (ie, the model has attributional validity). The Development And Validation of Risk-adjusted Outcomes for Systems of emergency care (DAVROS) model predicts 7-day mortality in emergency medical admissions. We aimed to test this assumption by evaluating the attributional validity of the DAVROS risk-adjustment model. Methods We selected cases that had the greatest discrepancy between observed mortality and predicted probability of mortality from seven hospitals involved in validation of the DAVROS risk-adjustment model. Reviewers at each hospital assessed hospital records to determine whether the discrepancy between predicted and actual mortality could be explained by the healthcare provided. Results We received 232/280 (83%) completed review forms relating to 179 unexpected deaths and 53 unexpected survivors. The healthcare system was judged to have potentially contributed to 10/179 (8%) of the unexpected deaths and 26/53 (49%) of the unexpected survivors. Failure of the model to appropriately predict risk was judged to be responsible for 135/179 (75%) of the unexpected deaths and 2/53 (4%) of the unexpected survivors. Some 10/53 (19%) of the unexpected survivors died within a few months of the 7-day period of model prediction. Conclusions We found little evidence that deaths occurring in patients with a low predicted mortality from risk-adjustment could be attributed to the quality of healthcare provided. PMID:23605036

77 FR 42947 - Unexpected Urgent Refugee and Migration Needs

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-20

... unexpected and urgent refugee and migration needs, including by contributions to international, governmental, and nongovernmental organizations and payment of administrative expenses of the Bureau of Population...

Does semantic preactivation reduce inattentional blindness?

PubMed

Kreitz, Carina; Schnuerch, Robert; Furley, Philip A; Gibbons, Henning; Memmert, Daniel

2015-04-01

We are susceptible to failures of awareness if a stimulus occurs unexpectedly and our attention is focused elsewhere. Such inattentional blindness is modulated by various parameters, including stimulus attributes, the observer's cognitive resources, and the observer's attentional set regarding the primary task. In three behavioral experiments with a total of 360 participants, we investigated whether mere semantic preactivation of the color of an unexpected object can reduce inattentional blindness. Neither explicitly mentioning the color several times before the occurrence of the unexpected stimulus nor priming the color more implicitly via color-related concepts could significantly reduce the susceptibility to inattentional blindness. Even putting the specific color concept in the main focus of the primary task did not lead to reduced inattentional blindness. Thus, we have shown that the failure to consciously perceive unexpected objects was not moderated by semantic preactivation of the objects' most prominent feature: its color. We suggest that this finding reflects the rather general principle that preactivations that are not motivationally relevant for one's current selection goals do not suffice to make an unexpected object overcome the threshold of awareness.

TNF{alpha} induced FOXP3-NF{kappa}B interaction dampens the tumor suppressor role of FOXP3 in gastric cancer cells

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

Hao, Qiang; Li, Weina; Zhang, Cun

2013-01-04

Highlights: Black-Right-Pointing-Pointer FOXP3 inhibition of cell proliferation is p21-dependent under basal conditions. Black-Right-Pointing-Pointer Inflammation induced by TNF{alpha} inhibits the tumor suppressor role of FOXP3. Black-Right-Pointing-Pointer Interaction between p65 and FOXP3 inhibits p21 transcription activation. -- Abstract: Controversial roles of FOXP3 in different cancers have been reported previously, while its role in gastric cancer is largely unknown. Here we found that FOXP3 is unexpectedly upregulated in some gastric cancer cells. To test whether increased FOXP3 remains the tumor suppressor role in gastric cancer as seen in other cancers, we test its function in cell proliferation both at basal and TNF{alpha} mimickedmore » inflammatory condition. Compared with the proliferation inhibitory role observed in basal condition, FOXP3 is insufficient to inhibit the cell proliferation under TNF{alpha} treatment. Molecularly, we found that TNF{alpha} induced an interaction between FOXP3 and p65, which in turn drive the FOXP3 away from the promoter of the well known target p21. Our data here suggest that although FOXP3 is upregulated in gastric cancer, its tumor suppressor role has been dampened due to the inflammation environment.« less

What do unicellular organisms teach us about DNA methylation?

PubMed

Harony, Hala; Ankri, Serge

2008-05-01

DNA methylation is an epigenetic hallmark that has been studied intensively in mammals and plants. However, knowledge of this phenomenon in unicellular organisms is scanty. Examining epigenetic regulation, and more specifically DNA methylation, in these organisms represents a unique opportunity to better understand their biology. The determination of their methylation status is often complicated by the presence of several differentiation stages in their life cycle. This article focuses on some recent advances that have revealed the unexpected nature of the epigenetic determinants present in protozoa. The role of the enigmatic DNA methyltransferase Dnmt2 in unicellular organisms is discussed.

Monophyly and extensive extinction of advanced eusocial bees: insights from an unexpected Eocene diversity.

PubMed

Engel, M S

2001-02-13

Advanced eusociality sometimes is given credit for the ecological success of termites, ants, some wasps, and some bees. Comprehensive study of bees fossilized in Baltic amber has revealed an unsuspected middle Eocene (ca. 45 million years ago) diversity of eusocial bee lineages. Advanced eusociality arose once in the bees with significant post-Eocene losses in diversity, leaving today only two advanced eusocial tribes comprising less than 2% of the total bee diversity, a trend analogous to that of hominid evolution. This pattern of changing diversity contradicts notions concerning the role of eusociality for evolutionary success in insects.

It's No Secret: Fifty-eight Years of National Security Programs at BNL (463rd Brookhaven Lecture)

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

Indusi, Joseph

2010-11-17

Prepare for a true tale of suspense and international intrigue. A tale that began in 1952, continued through the Cold War, and is not yet complete today. A tale of unexpected allies. Hear the true tale of one Laboratory’s efforts to keep nuclear materials out of the hands of evildoers. Freidlander. Higinbotham. Dodson. Kouts. And many more! See some of BNL’s all-star cast in the defining roles that shaped their careers as they worked toward keeping the nation and the world safe from the proliferation of nuclear weapons.

Nobel Lecture: Topological quantum matter*

NASA Astrophysics Data System (ADS)

Haldane, F. Duncan M.

2017-10-01

Nobel Lecture, presented December 8, 2016, Aula Magna, Stockholm University. I will describe the history and background of three discoveries cited in this Nobel Prize: The "TKNN" topological formula for the integer quantum Hall effect found by David Thouless and collaborators, the Chern insulator or quantum anomalous Hall effect, and its role in the later discovery of time-reversal-invariant topological insulators, and the unexpected topological spin-liquid state of the spin-1 quantum antiferromagnetic chain, which provided an initial example of topological quantum matter. I will summarize how these early beginnings have led to the exciting, and currently extremely active, field of "topological matter."

Syntheses of strychnine, norfluorocurarine, dehydrodesacetylretuline, and valparicine enabled by intramolecular cycloadditions of Zincke aldehydes.

PubMed

Martin, David B C; Nguyen, Lucas Q; Vanderwal, Christopher D

2012-01-06

A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions of tryptamine-derived Zincke aldehydes is described. This important complexity-generating transformation provides the tetracyclic core of many indole monoterpene alkaloids in only three steps from commercially available starting materials and played a key role in short syntheses of norfluorocurarine (five steps), dehydrodesacetylretuline (six steps), valparicine (seven steps), and strychnine (six steps). Reasonable mechanistic possibilities for this reaction, a surprisingly facile dimerization of the products, and an unexpected cycloreversion to regenerate Zincke aldehydes under specific conditions are also discussed.

Stochastic Growth of Ion Cyclotron And Mirror Waves In Earth's Magnetosheath

NASA Technical Reports Server (NTRS)

Cairns, Iver H.; Grubits, K. A.

2001-01-01

Electromagnetic ion cyclotron and mirror waves in Earth's magnetosheath are bursty, have widely variable fields, and are unexpectedly persistent, properties difficult to reconcile with uniform secular growth. Here it is shown for specific periods that stochastic growth theory (SGT) quantitatively accounts for the functional form of the wave statistics and qualitatively explains the wave properties. The wave statistics are inconsistent with uniform secular growth or self-organized criticality, but nonlinear processes sometimes play a role at high fields. The results show SGT's relevance near marginal stability and suggest that it is widely relevant to space and astrophysical plasmas.

Selfish DNA in protein-coding genes of Rickettsia.

PubMed

Ogata, H; Audic, S; Barbe, V; Artiguenave, F; Fournier, P E; Raoult, D; Claverie, J M

2000-10-13

Rickettsia conorii, the aetiological agent of Mediterranean spotted fever, is an intracellular bacterium transmitted by ticks. Preliminary analyses of the nearly complete genome sequence of R. conorii have revealed 44 occurrences of a previously undescribed palindromic repeat (150 base pairs long) throughout the genome. Unexpectedly, this repeat was found inserted in-frame within 19 different R. conorii open reading frames likely to encode functional proteins. We found the same repeat in proteins of other Rickettsia species. The finding of a mobile element inserted in many unrelated genes suggests the potential role of selfish DNA in the creation of new protein sequences.

Vision sensing techniques in aeronautics and astronautics

NASA Technical Reports Server (NTRS)

Hall, E. L.

1988-01-01

The close relationship between sensing and other tasks in orbital space, and the integral role of vision sensing in practical aerospace applications, are illustrated. Typical space mission-vision tasks encompass the docking of space vehicles, the detection of unexpected objects, the diagnosis of spacecraft damage, and the inspection of critical spacecraft components. Attention is presently given to image functions, the 'windowing' of a view, the number of cameras required for inspection tasks, the choice of incoherent or coherent (laser) illumination, three-dimensional-to-two-dimensional model-matching, edge- and region-segmentation techniques, and motion analysis for tracking.

Piezo Proteins: Regulators of Mechanosensation and Other Cellular Processes*

PubMed Central

Bagriantsev, Sviatoslav N.; Gracheva, Elena O.; Gallagher, Patrick G.

2014-01-01

Piezo proteins have recently been identified as ion channels mediating mechanosensory transduction in mammalian cells. Characterization of these channels has yielded important insights into mechanisms of somatosensation, as well as other mechano-associated biologic processes such as sensing of shear stress, particularly in the vasculature, and regulation of urine flow and bladder distention. Other roles for Piezo proteins have emerged, some unexpected, including participation in cellular development, volume regulation, cellular migration, proliferation, and elongation. Mutations in human Piezo proteins have been associated with a variety of disorders including hereditary xerocytosis and several syndromes with muscular contracture as a prominent feature. PMID:25305018

The Role of Simulation in Planning Intraoperative Magnetic Resonance Imaging-Guided Neurosurgical Procedures: A Case Report.

PubMed

Chowdhury, Tumul; Bergese, Sergio D; Soghomonyan, Suren; Cappellani, Ronald B

2017-04-01

Simulation of the actual procedure is a simple and yet effective method of increasing patient safety and reducing the rate of unexpected adverse effects. We present our experience with 2 cases of preprocedural simulation on healthy volunteers that were performed in the intraoperative magnetic resonance imaging suite. During one of the cases, we also simulated a scenario of sudden cardiac arrest. Such an approach helped us to refine the procedures and coordinate the work of different teams within the intraoperative magnetic resonance imaging suite as well as improve the quality of patient management.