On Known Unknowns: Fluency and the Neural Mechanisms of Illusory Truth

PubMed Central

Wang, Wei-Chun; Brashier, Nadia M.; Wing, Erik A.; Marsh, Elizabeth J.; Cabeza, Roberto

2016-01-01

The “illusory truth” effect refers to the phenomenon whereby repetition of a statement increases its likelihood of being judged true. This phenomenon has important implications for how we come to believe oft-repeated information that may be misleading or unknown. Behavioral evidence indicates that fluency or the subjective ease experienced while processing a statement underlies this effect. This suggests that illusory truth should be mediated by brain regions previously linked to fluency, such as the perirhinal cortex (PRC). To investigate this possibility, we scanned participants with fMRI while they rated the truth of unknown statements, half of which were presented earlier (i.e., repeated). The only brain region that showed an interaction between repetition and ratings of perceived truth was PRC, where activity increased with truth ratings for repeated, but not for new, statements. This finding supports the hypothesis that illusory truth is mediated by a fluency mechanism and further strengthens the link between PRC and fluency. PMID:26765947

Personality and Longevity: Knowns, Unknowns, and Implications for Public Health and Personalized Medicine

PubMed Central

Chapman, Benjamin P.; Roberts, Brent; Duberstein, Paul

2011-01-01

We review evidence for links between personality traits and longevity. We provide an overview of personality for health scientists, using the primary organizing framework used in the study of personality and longevity. We then review data on various aspects of personality linked to longevity. In general, there is good evidence that higher level of conscientiousness and lower levels of hostility and Type D or “distressed” personality are associated with greater longevity. Limited evidence suggests that extraversion, openness, perceived control, and low levels of emotional suppression may be associated with longer lifespan. Findings regarding neuroticism are mixed, supporting the notion that many component(s) of neuroticism detract from life expectancy, but some components at some levels may be healthy or protective. Overall, evidence suggests various personality traits are significant predictors of longevity and points to several promising directions for further study. We conclude by discussing the implications of these links for epidemiologic research and personalized medicine and lay out a translational research agenda for integrating the psychology of individual differences into public health and medicine. PMID:21766032

Olfactory behavior and physiology are disrupted in prion protein knockout mice.

PubMed

Le Pichon, Claire E; Valley, Matthew T; Polymenidou, Magdalini; Chesler, Alexander T; Sagdullaev, Botir T; Aguzzi, Adriano; Firestein, Stuart

2009-01-01

The prion protein PrP(C) is infamous for its role in disease, but its normal physiological function remains unknown. Here we found a previously unknown behavioral phenotype of Prnp(-/-) mice in an odor-guided task. This phenotype was manifest in three Prnp knockout lines on different genetic backgrounds, which provides strong evidence that the phenotype is caused by a lack of PrP(C) rather than by other genetic factors. Prnp(-/-) mice also showed altered behavior in a second olfactory task, suggesting that the phenotype is olfactory specific. Furthermore, PrP(C) deficiency affected oscillatory activity in the deep layers of the main olfactory bulb, as well as dendrodendritic synaptic transmission between olfactory bulb granule and mitral cells. Notably, both the behavioral and electrophysiological alterations found in Prnp(-/-) mice were rescued by transgenic neuronal-specific expression of PrP(C). These data suggest that PrP(C) is important in the normal processing of sensory information by the olfactory system.

The first oviraptorosaur (Dinosauria: Theropoda) bonebed: evidence of gregarious behaviour in a maniraptoran theropod.

PubMed

Funston, Gregory F; Currie, Philip J; Eberth, David A; Ryan, Michael J; Chinzorig, Tsogtbaatar; Badamgarav, Demchig; Longrich, Nicholas R

2016-10-21

A monodominant bonebed of Avimimus from the Nemegt Formation of Mongolia is the first oviraptorosaur bonebed described and the only recorded maniraptoran bonebed from the Late Cretaceous. Cranial elements recovered from the bonebed provide insights on the anatomy of the facial region, which was formerly unknown in Avimimus. Both adult and subadult material was recovered from the bonebed, but small juveniles are underrepresented. The taphonomic and sedimentological evidence suggests that the Avimimus bonebed represents a perimortem gregarious assemblage. The near absence of juveniles in the bonebed may be evidence of a transient age-segregated herd or 'flock', but the behaviour responsible for this assemblage is unclear. Regardless, the Avimimus bonebed is the first evidence of gregarious behaviour in oviraptorosaurs, and highlights a potential trend of increasing gregariousness in dinosaurs towards the end of the Mesozoic.

Female genital mutilation: a urology focus.

PubMed

Clarke, Elinor

2016-10-13

Female genital mutilation (FGM) is a collective term for the deliberate alteration, removal and cutting of the female genitalia. It has no known health benefits and can have negative physical and psychological consequences. The number of women and girls in the UK that are affected by FGM is unknown. Recent NHS data suggested that FGM has been evident (declared or observed) in women who have accessed health care; however, there are gaps in knowledge and a limited evidence base on the health consequences of FGM. This article explores the urological complications experienced by women who have undergone this practice, and the effects this can have on their health and wellbeing.

Two processes support visual recognition memory in rhesus monkeys.

PubMed

Guderian, Sebastian; Brigham, Danielle; Mishkin, Mortimer

2011-11-29

A large body of evidence in humans suggests that recognition memory can be supported by both recollection and familiarity. Recollection-based recognition is characterized by the retrieval of contextual information about the episode in which an item was previously encountered, whereas familiarity-based recognition is characterized instead by knowledge only that the item had been encountered previously in the absence of any context. To date, it is unknown whether monkeys rely on similar mnemonic processes to perform recognition memory tasks. Here, we present evidence from the analysis of receiver operating characteristics, suggesting that visual recognition memory in rhesus monkeys also can be supported by two separate processes and that these processes have features considered to be characteristic of recollection and familiarity. Thus, the present study provides converging evidence across species for a dual process model of recognition memory and opens up the possibility of studying the neural mechanisms of recognition memory in nonhuman primates on tasks that are highly similar to the ones used in humans.

Two processes support visual recognition memory in rhesus monkeys

PubMed Central

Guderian, Sebastian; Brigham, Danielle; Mishkin, Mortimer

2011-01-01

A large body of evidence in humans suggests that recognition memory can be supported by both recollection and familiarity. Recollection-based recognition is characterized by the retrieval of contextual information about the episode in which an item was previously encountered, whereas familiarity-based recognition is characterized instead by knowledge only that the item had been encountered previously in the absence of any context. To date, it is unknown whether monkeys rely on similar mnemonic processes to perform recognition memory tasks. Here, we present evidence from the analysis of receiver operating characteristics, suggesting that visual recognition memory in rhesus monkeys also can be supported by two separate processes and that these processes have features considered to be characteristic of recollection and familiarity. Thus, the present study provides converging evidence across species for a dual process model of recognition memory and opens up the possibility of studying the neural mechanisms of recognition memory in nonhuman primates on tasks that are highly similar to the ones used in humans. PMID:22084079

Probing the influence of unconscious fear-conditioned visual stimuli on eye movements.

PubMed

Madipakkam, Apoorva Rajiv; Rothkirch, Marcus; Wilbertz, Gregor; Sterzer, Philipp

2016-11-01

Efficient threat detection from the environment is critical for survival. Accordingly, fear-conditioned stimuli receive prioritized processing and capture overt and covert attention. However, it is unknown whether eye movements are influenced by unconscious fear-conditioned stimuli. We performed a classical fear-conditioning procedure and subsequently recorded participants' eye movements while they were exposed to fear-conditioned stimuli that were rendered invisible using interocular suppression. Chance-level performance in a forced-choice-task demonstrated unawareness of the stimuli. Differential skin conductance responses and a change in participants' fearfulness ratings of the stimuli indicated the effectiveness of conditioning. However, eye movements were not biased towards the fear-conditioned stimulus. Preliminary evidence suggests a relation between the strength of conditioning and the saccadic bias to the fear-conditioned stimulus. Our findings provide no strong evidence for a saccadic bias towards unconscious fear-conditioned stimuli but tentative evidence suggests that such an effect may depend on the strength of the conditioned response. Copyright © 2016 Elsevier Inc. All rights reserved.

Plant hormones: a fungal point of view.

PubMed

Chanclud, Emilie; Morel, Jean-Benoit

2016-10-01

Most classical plant hormones are also produced by pathogenic and symbiotic fungi. The way in which these molecules favour the invasion of plant tissues and the development of fungi inside plant tissues is still largely unknown. In this review, we examine the different roles of such hormone production by pathogenic fungi. Converging evidence suggests that these fungal-derived molecules have potentially two modes of action: (i) they may perturb plant processes, either positively or negatively, to favour invasion and nutrient uptake; and (ii) they may also act as signals for the fungi themselves to engage appropriate developmental and physiological processes adapted to their environment. Indirect evidence suggests that abscisic acid, gibberellic acid and ethylene produced by fungi participate in pathogenicity. There is now evidence that auxin and cytokinins could be positive regulators required for virulence. Further research should establish whether or not fungal-derived hormones act like other fungal effectors. © 2016 The Authors. Molecular Plant Pathology Published by British Society for Plant Pathology and John Wiley & Sons Ltd.

Evidence Based Assessment of Public Health Planning: A Case Study of the 2014 Crisis in Ukraine

DTIC Science & Technology

2015-06-12

Unknowns, Unknown Unknowns and the Propagation of Scientific Enquiry,” Journal of Experimental Botany 60, no. 3 (March 2009): 712-714. Risk...David C. Logan, “Known Knowns, Known Unknowns, Unknown Unknowns and the Propagation of Scientific Enquiry,” Journal of Experimental Botany 60, no. 3...Experimental Botany 60, no. 3 (March 2009): 712-714. Markel, Howard. “Facing Tuberculosis,” When Germs Travel: Six Major Epidemics That Have Invaded America

What lysosomes actually tell us about Parkinson's disease?

PubMed

Bourdenx, Mathieu; Dehay, Benjamin

2016-12-01

Parkinson's disease is a common neurodegenerative disorder of unknown origin mainly characterized by the loss of neuromelanin-containing dopaminergic neurons in the substantia nigra pars compacta and the presence of intraneuronal proteinaceous inclusions called Lewy bodies. Lysosomes are dynamic organelles that degrade, in a controlled manner, cellular components delivered via the secretory, endocytic, autophagic and phagocytic membrane-trafficking pathways. Increasing amounts of evidence suggest a central role of lysosomal impairment in PD aetiology. This review provides an update on how genetic evidence support this connection and highlights how the neuropathologic and mechanistic evidence might relate to the disease process in sporadic forms of Parkinson's disease. Finally, we discuss the influence of ageing on lysosomal impairment and PD aetiology and therapeutic strategies targeting lysosomal function. Copyright © 2016 Elsevier B.V. All rights reserved.

The generalizability of working-memory capacity in the sport domain.

PubMed

Buszard, Tim; Masters, Rich Sw; Farrow, Damian

2017-08-01

Working-memory capacity has been implicated as an influential variable when performing and learning sport-related skills. In this review, we critically evaluate evidence linking working-memory capacity with performing under pressure, tactical decision making, motor skill acquisition, and sport expertise. Laboratory experiments link low working-memory capacity with poorer performance under pressure and poorer decision making when required to inhibit distractions or resolve conflict. However, the generalizability of these findings remains unknown. While working-memory capacity is associated with the acquisition of simple motor skills, there is no such evidence from the available data for complex motor skills. Likewise, currently there is no evidence to suggest that a larger working-memory capacity facilitates the attainment of sport expertise. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evidence-based practice in women's health: hormone therapy for women at menopause.

PubMed

Rousseau, M E

2001-01-01

Women's health providers, especially midwives, must take into account the known benefits and risks, as well as the "unknown," when recommending the use of hormone therapy for menopausal women, especially as it relates to heart disease, breast cancer, impaired cognition, and osteoporosis. The most recent evidence available from various studies about the benefits and risks of estrogen and hormone therapy at menopause suggests that, although hormone therapy may be protective in some women against heart disease and osteoporosis, evidence is less certain about the benefits of hormone protection against impaired cognition and the risks of breast cancer with use. The clinical approach used by midwives in which individualizing care based on each woman's health status history as well as preferences is highly appropriate for women in the perimenopausal and menopausal period.

Petrology of a nonindigenous microgranitic clast in polymict ureilite EET 87720: Evidence for formation of evolved melt on an unknown parent body

NASA Astrophysics Data System (ADS)

Beard, A. D.; Downes, H.; Chaussidon, M.

2015-09-01

EET 87720 is a polymict ureilite breccia known to contain numerous nonindigenous fragments. We have discovered a microgranitic clast in an interior chip of Elephant Moraine (EET) 87720. The clast consists of a granophyre-like intergrowth of a pure SiO2 phase (tridymite) and albite, mantling a zoned oligoclase phenocryst. In the intergrowth, the tridymite occurs as thin elongate vermicular blebs within larger albite crystals. The granophyre-like intergrowth and the oligoclase phenocryst share a common margin, suggesting that the clast was originally part of a larger fragment. An estimate of its bulk composition is equivalent to that of granite (77 wt% SiO2). Patches of high-Si K-bearing glass occur interstitially within the clast; they have high concentrations of SO3 (11-12 wt%) and contain Cl (0.6 wt%), suggesting that the clast formed on a volatile-rich parent body perhaps resembling early Mars. The mean oxygen isotope composition of the feldspar and tridymite in the clast is very different from the oxygen isotope compositions of ureilites, and is similar to those of silicate inclusions in IIE and IVA irons. Thus, the clast is not indigenous to the ureilite parent body, but it provides evidence for the formation of evolved melts on an unknown parent body in the early solar system.

Glucose-dependent insulinotropic polypeptide directly induces glucose transport in rat skeletal muscle

PubMed Central

Snook, Laelie A.; Nelson, Emery M.; Dyck, David J.; Wright, David C.

2015-01-01

Several gastrointestinal proteins have been identified to have insulinotropic effects, including glucose-dependent insulinotropic polypeptide (GIP); however, the direct effects of incretins on skeletal muscle glucose transport remain largely unknown. Therefore, the purpose of the current study was to examine the role of GIP on skeletal muscle glucose transport and insulin signaling in rats. Relative to a glucose challenge, a mixed glucose+lipid oral challenge increased circulating GIP concentrations, skeletal muscle Akt phosphorylation, and improved glucose clearance by ∼35% (P < 0.05). These responses occurred without alterations in serum insulin concentrations. In an incubated soleus muscle preparation, GIP directly stimulated glucose transport and increased GLUT4 accumulation on the plasma membrane in the absence of insulin. Moreover, the ability of GIP to stimulate glucose transport was mitigated by the addition of the PI 3-kinase (PI3K) inhibitor wortmannin, suggesting that signaling through PI3K is required for these responses. We also provide evidence that the combined stimulatory effects of GIP and insulin on soleus muscle glucose transport are additive. However, the specific GIP receptor antagonist (Pro3)GIP did not attenuate GIP-stimulated glucose transport, suggesting that GIP is not signaling through its classical receptor. Together, the current data provide evidence that GIP regulates skeletal muscle glucose transport; however, the exact signaling mechanism(s) remain unknown. PMID:26041107

Do not Bet on the Unknown Versus Try to Find Out More: Estimation Uncertainty and “Unexpected Uncertainty” Both Modulate Exploration

PubMed Central

Payzan-LeNestour, Élise; Bossaerts, Peter

2012-01-01

Little is known about how humans solve the exploitation/exploration trade-off. In particular, the evidence for uncertainty-driven exploration is mixed. The current study proposes a novel hypothesis of exploration that helps reconcile prior findings that may seem contradictory at first. According to this hypothesis, uncertainty-driven exploration involves a dilemma between two motives: (i) to speed up learning about the unknown, which may beget novel reward opportunities; (ii) to avoid the unknown because it is potentially dangerous. We provide evidence for our hypothesis using both behavioral and simulated data, and briefly point to recent evidence that the brain differentiates between these two motives. PMID:23087606

The first oviraptorosaur (Dinosauria: Theropoda) bonebed: evidence of gregarious behaviour in a maniraptoran theropod

PubMed Central

Funston, Gregory F.; Currie, Philip J.; Eberth, David A.; Ryan, Michael J.; Chinzorig, Tsogtbaatar; Badamgarav, Demchig; Longrich, Nicholas R.

2016-01-01

A monodominant bonebed of Avimimus from the Nemegt Formation of Mongolia is the first oviraptorosaur bonebed described and the only recorded maniraptoran bonebed from the Late Cretaceous. Cranial elements recovered from the bonebed provide insights on the anatomy of the facial region, which was formerly unknown in Avimimus. Both adult and subadult material was recovered from the bonebed, but small juveniles are underrepresented. The taphonomic and sedimentological evidence suggests that the Avimimus bonebed represents a perimortem gregarious assemblage. The near absence of juveniles in the bonebed may be evidence of a transient age-segregated herd or ‘flock’, but the behaviour responsible for this assemblage is unclear. Regardless, the Avimimus bonebed is the first evidence of gregarious behaviour in oviraptorosaurs, and highlights a potential trend of increasing gregariousness in dinosaurs towards the end of the Mesozoic. PMID:27767062

The lasting memory enhancements of retrospective attention.

PubMed

Reaves, Sarah; Strunk, Jonathan; Phillips, Shekinah; Verhaeghen, Paul; Duarte, Audrey

2016-07-01

Behavioral research has shown that spatial cues that orient attention toward task relevant items being maintained in visual short-term memory (VSTM) enhance item memory accuracy. However, it is unknown if these retrospective attentional cues ("retro-cues") enhance memory beyond typical short-term memory delays. It is also unknown whether retro-cues affect the spatial information associated with VSTM representations. Emerging evidence suggests that processes that affect short-term memory maintenance may also affect long-term memory (LTM) but little work has investigated the role of attention in LTM. In the current event-related potential (ERP) study, we investigated the duration of retrospective attention effects and the impact of retrospective attention manipulations on VSTM representations. Results revealed that retro-cueing improved both VSTM and LTM memory accuracy and that posterior maximal ERPs observed during VSTM maintenance predicted subsequent LTM performance. N2pc ERPs associated with attentional selection were attenuated by retro-cueing suggesting that retrospective attention may disrupt maintenance of spatial configural information in VSTM. Collectively, these findings suggest that retrospective attention can alter the structure of memory representations, which impacts memory performance beyond short-term memory delays. Copyright © 2016 Elsevier B.V. All rights reserved.

Families that fire together smile together: Resting state connectome similarity and daily emotional synchrony in parent-child dyads

PubMed Central

Lee, Tae-Ho; Miernicki, Michelle E.; Telzer, Eva H.

2017-01-01

Despite emerging evidence suggesting a biological basis to our social tiles, our understanding of the neural processes which link two minds is unknown. We implemented a novel approach, which included connectome similarity analysis using resting state intrinsic networks of parent-child dyads as well as daily diaries measured across 14 days. Intrinsic resting-state networks for both parents and their adolescent child were identified using independent component analysis (ICA). Results indicate that parents and children who had more similar RSN connectome also had more similar day-to-day emotional synchrony. Furthermore, dyadic RSN connectome similarity was associated with children’s emotional competence, suggesting that being neurally in-tune with their parents confers emotional benefits. We provide the first evidence that dyadic RSN similarity is associated with emotional synchrony in what is often our first and most essential social bond, the parent-child relationship. PMID:28254510

A sarcoidosis clinician's perspective of MHC functional elements outside the antigen binding site.

PubMed

Judson, Marc A

2018-05-30

Sarcoidosis is a multisystem granulomatous disease of unknown cause. Evidence supports an integral role for interactions at the MHC binding site in the development of sarcoidosis. However, despite this evidence, there are clinical data that suggest that additional mechanisms are involved in the immunopathogenesis of this disease. This manuscript provides a brief clinical description of sarcoidosis, and a clinician's perspective of the immunopathogenesis of sarcoidosis in terms of the MHC binding site, MHC functional elements beyond the binding site, and other possible alternative mechanisms. Input from clinicians will be essential in establishing the immunologic cause of sarcoidosis as a detailed phenotypic characterization of disease will be required. Copyright © 2018. Published by Elsevier Inc.

Carcinoma of Unknown Primary—Health Professional Version

Cancer.gov

Carcinoma of unknown primary (CUP) is a rare disease in which malignant cells are found in the body but the site of the primary cancer is not known. Most CUPs are adenocarcinomas, or undifferentiated tumors. Find evidence-based information on the treatment for carcinoma of unknown primary.

Molecular evidence for deep phylogenetic divergence in Mandrillus sphinx.

PubMed

Telfer, P T; Souquière, S; Clifford, S L; Abernethy, K A; Bruford, M W; Disotell, T R; Sterner, K N; Roques, P; Marx, P A; Wickings, E J

2003-07-01

Mandrills (Mandrillus sphinx) are forest primates indigenous to western central Africa. Phylogenetic analysis of 267 base pairs (bp) of the cytochrome b gene from 53 mandrills of known and 17 of unknown provenance revealed two phylogeographical groups, with haplotypes differentiated by 2.6% comprising seven synonymous transitions. The distribution of the haplotypes suggests that the Ogooué River, Gabon, which bisects their range, separates mandrill populations in Cameroon and northern Gabon from those in southern Gabon. The haplotype distribution is also concordant with that of two known mandrill simian immunodeficiency viruses, suggesting that these two mandrill phylogroups have followed different evolutionary trajectories since separation.

Harnessing the beneficial heterologous effects of vaccination

PubMed Central

Goodridge, Helen S.; Ahmed, S. Sohail; Curtis, Nigel; Kollmann, Tobias R.; Levy, Ofer; Netea, Mihai G.; Pollard, Andrew J.; van Crevel, Reinout; Wilson, Christopher B.

2016-01-01

Clinical evidence strongly suggests that certain live vaccines, in particular Bacille Calmette–Guérin (BCG) and measles vaccines, can reduce all-cause mortality, likely via protection against non-targeted pathogens in addition to the targeted pathogen. The underlying mechanisms are currently unknown. We discuss how heterologous lymphocyte activation and innate immune memory could promote protection beyond the intended target pathogen and consider how vaccinologists could leverage heterologous immunity to improve outcomes in vulnerable populations, in particular the very young and the elderly. PMID:27157064

A single footshock causes long-lasting hypoactivity in unknown environments that is dependent on the development of contextual fear conditioning.

PubMed

Daviu, Núria; Fuentes, Silvia; Nadal, Roser; Armario, Antonio

2010-09-01

Exposure to a single session of footshocks induces long-lasting inhibition of activity in unknown environments that markedly differ from the shock context. Interestingly, these effects are not necessarily associated to an enhanced anxiety and interpretation of this hypoactivity remains unclear. In the present experiment we further studied this phenomenon in male Sprague-Dawley rats. In a first experiment, a session of three shocks resulted in hypoactivity during exposure, 6-12days later, to three different unknown environments. This altered behaviour was not accompanied by a greater hypothalamic-pituitary-adrenal (HPA) activation, although greater HPA activation paralleling higher levels of freezing was observed in the shock context. In a second experiment we used a single shock and two procedures, one with pre-exposure to the context before the shock and another with immediate shock that did not induce contextual fear conditioning. Hypoactivity and a certain level of generalization of fear (freezing) to the unknown environments only appeared in the group that developed fear conditioning, but no evidence for enhanced anxiety in the elevated plus-maze was found in any group. The results suggest that if animals are able to associate an aversive experience with a distinct unknown environment, they would display more cautious behaviour in any unknown environment and such strategy persists despite repeated experience with different environments. This long-lasting cautious behaviour was not associated to greater HPA response to the unknown environment that was however observed in the shock context. The present findings raised some concerns about interpretation of long-lasting behavioural changes caused by brief stressors. Copyright 2010 Elsevier Inc. All rights reserved.

Diphthamide biosynthesis requires an organic radical generated by an iron-sulphur enzyme

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

Zhang, Yang; Zhu, Xuling; Torelli, Andrew T

2010-08-30

Archaeal and eukaryotic translation elongation factor 2 contain a unique post-translationally modified histidine residue called diphthamide, which is the target of diphtheria toxin. The biosynthesis of diphthamide was proposed to involve three steps, with the first being the formation of a C-C bond between the histidine residue and the 3-amino-3-carboxypropyl group of S-adenosyl-l-methionine (SAM). However, further details of the biosynthesis remain unknown. Here we present structural and biochemical evidence showing that the first step of diphthamide biosynthesis in the archaeon Pyrococcus horikoshii uses a novel iron-sulphur-cluster enzyme, Dph2. Dph2 is a homodimer and each of its monomers can bind amore » [4Fe-4S] cluster. Biochemical data suggest that unlike the enzymes in the radical SAM superfamily, Dph2 does not form the canonical 5'-deoxyadenosyl radical. Instead, it breaks the C γ,Met-S bond of SAM and generates a 3-amino-3-carboxypropyl radical. Our results suggest that P. horikoshii Dph2 represents a previously unknown, SAM-dependent, [4Fe-4S]-containing enzyme that catalyses unprecedented chemistry.« less

Nuclear and chloroplast DNA phylogeny reveals complex evolutionary history of Elymus pendulinus.

PubMed

Yan, Chi; Hu, Qianni; Sun, Genlou

2014-02-01

Evidence accumulated over the last decade has shown that allopolyploid genomes may undergo complex reticulate evolution. In this study, 13 accessions of tetraploid Elymus pendulinus were analyzed using two low-copy nuclear genes (RPB2 and PepC) and two regions of chloroplast genome (Rps16 and trnD-trnT). Previous studies suggested that Pseudoroegneria (St) and an unknown diploid (Y) were genome donors to E. pendulinus, and that Pseudoroegneria was the maternal donor. Our results revealed an extreme reticulate pattern, with at least four distinct gene lineages coexisting within this species that might be acquired through a possible combination of allotetraploidization and introgression from both within and outside the tribe Hordeeae. Chloroplast DNA data identified two potential maternal genome donors (Pseudoroegneria and an unknown species outside Hordeeae) to E. pendulinus. Nuclear gene data indicated that both Pseudoroegneria and an unknown Y diploid have contributed to the nuclear genome of E. pendulinus, in agreement with cytogenetic data. However, unexpected contributions from Hordeum and unknown aliens from within or outside Hordeeae to E. pendulinus without genome duplication were observed. Elymus pendulinus provides a remarkable instance of the previously unsuspected chimerical nature of some plant genomes and the resulting phylogenetic complexity produced by multiple historical reticulation events.

Vitamin E in Sarcopenia: Current Evidences on Its Role in Prevention and Treatment

PubMed Central

Abdul Karim, Norwahidah; Wan Ngah, Wan Zurinah

2014-01-01

Sarcopenia is a geriatric syndrome that is characterized by gradual loss of muscle mass and strength with increasing age. Although the underlying mechanism is still unknown, the contribution of increased oxidative stress in advanced age has been recognized as one of the risk factors of sarcopenia. Thus, eliminating reactive oxygen species (ROS) can be a strategy to combat sarcopenia. In this review, we discuss the potential role of vitamin E in the prevention and treatment of sarcopenia. Vitamin E is a lipid soluble vitamin, with potent antioxidant properties and current evidence suggesting a role in the modulation of signaling pathways. Previous studies have shown its possible beneficial effects on aging and age-related diseases. Although there are evidences suggesting an association between vitamin E and muscle health, they are still inconclusive compared to other more extensively studied chronic diseases such as neurodegenerative diseases and cardiovascular diseases. Therefore, we reviewed the role of vitamin E and its potential protective mechanisms on muscle health based on previous and current in vitro and in vivo studies. PMID:25097722

New Multicentury Evidence for Dispersal Limitation during Primary Succession.

PubMed

Makoto, K; Wilson, Scott D

2016-06-01

Primary succession is limited by both ecosystem development and plant dispersal, but the extent to which dispersal constrains succession over the long-term is unknown. We compared primary succession along two co-occurring arctic chronosequences with contrasting spatial scales: sorted circles that span a few meters and may have few dispersal constraints and glacial forelands that span several kilometers and may have greater dispersal constraints. Dispersal constraints slowed primary succession by centuries: plots were dominated by cryptogams after 20 years on circles but after 270 years on forelands; plots supported deciduous plants after 100 years on circles but after >400 years on forelands. Our study provides century-scale evidence suggesting that dispersal limitations constrain the rate of primary succession in glacial forelands.

Phylogenetic system and zoogeography of the Plecoptera.

PubMed

Zwick, P

2000-01-01

Information about the phylogenetic relationships of Plecoptera is summarized. The few characters supporting monophyly of the order are outlined. Several characters of possible significance for the search for the closest relatives of the stoneflies are discussed, but the sister-group of the order remains unknown. Numerous characters supporting the presently recognized phylogenetic system of Plecoptera are presented, alternative classifications are discussed, and suggestions for future studies are made. Notes on zoogeography are appended. The order as such is old (Permian fossils), but phylogenetic relationships and global distribution patterns suggest that evolution of the extant suborders started with the breakup of Pangaea. There is evidence of extensive recent speciation in all parts of the world.

Resveratrol modulates ATPase activity of liposome-reconstituted ABCG1.

PubMed

de Athayde Moncorvo Collado, Alejandro; Corbalán, Natalia; Homolya, László; Morero, Roberto; Minahk, Carlos

2013-08-02

ABCG1 is a half-sized transporter with an unquestionable importance in cholesterol homeostasis. So far, its expression and thus its activity was suggested to be regulated at transcriptional level by LXR and PPAR agonists including polyphenols. However, it is unknown whether there are other mechanisms of up-regulation of ABCG1 activity. In the present work resveratrol was shown to induce a nearly twofold increase in ATPase activity of reconstituted ABCG1. Evidence is presented for the first time suggesting that resveratrol is able to activate ABCG1 activity by an alternative mechanism that involves an indirect interaction. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Systemic lupus erythematosus associated with acute Epstein-Barr virus infection.

PubMed

Dror, Y; Blachar, Y; Cohen, P; Livni, N; Rosenmann, E; Ashkenazi, A

1998-11-01

Systemic lupus erythematosus (SLE) is a multisystem disease of unknown origin, characterized by a variety of autoimmune phenomena. Viruses have long been postulated to play a role in its pathogenesis. Several observations suggested a link between Epstein-Barr virus (EBV) and SLE. We describe a 14-year-old girl who presented with acute onset of SLE concurrently with clinical and laboratory findings consistent with EBV-induced infectious mononucleosis (IM). Evidence for acute EBV infection was confirmed by serological studies and detection of specific EBV antigens on kidney biopsy. This close association between EBV and SLE suggests a possible role of the virus in the pathogenesis of SLE in this patient.

39 CFR 946.4 - Disposition of property of unknown owners.

Code of Federal Regulations, 2010 CFR

2010-07-01

... DISPOSITION OF STOLEN MAIL MATTER AND PROPERTY ACQUIRED BY THE POSTAL INSPECTION SERVICE FOR USE AS EVIDENCE § 946.4 Disposition of property of unknown owners. (a) Where no apparent owner of property subject to... 39 Postal Service 1 2010-07-01 2010-07-01 false Disposition of property of unknown owners. 946.4...

39 CFR 946.4 - Disposition of property of unknown owners.

Code of Federal Regulations, 2011 CFR

2011-07-01

... DISPOSITION OF STOLEN MAIL MATTER AND PROPERTY ACQUIRED BY THE POSTAL INSPECTION SERVICE FOR USE AS EVIDENCE § 946.4 Disposition of property of unknown owners. (a) Where no apparent owner of property subject to... 39 Postal Service 1 2011-07-01 2011-07-01 false Disposition of property of unknown owners. 946.4...

Public Health Considerations Associated with the Location and Operation of Off-Leash Dog Parks.

PubMed

Rahim, Tissa; Barrios, Pablo Romero; McKee, Geoffrey; McLaws, Melissa; Kosatsky, Tom

2018-04-01

Off-leash dog parks may enhance human health, but may also lead to health risk through infection or canine aggression. Published evidence was reviewed to examine positive and negative public health impacts of off-leash dog parks, as well as strategies for enhancing benefits and mitigating risks. Evidence suggests that off-leash dog parks can benefit physical and social health, as well as community connectedness. While studies have documented shedding of zoonotic agents in dog parks, the risk of transmission to humans is relatively unknown. Evidence on the risk of dog bites in off-leash dog parks is also limited. Case-examples from North American off-leash dog parks highlight the importance of park location/design, public adherence to safe and hygienic practices, and effective regulatory strategies for mitigating potential risks and maximizing the benefits of off-leash dog parks.

Evidence Accumulation and Choice Maintenance Are Dissociated in Human Perceptual Decision Making

PubMed Central

Pedersen, Mads Lund; Endestad, Tor; Biele, Guido

2015-01-01

Perceptual decision making in monkeys relies on decision neurons, which accumulate evidence and maintain choices until a response is given. In humans, several brain regions have been proposed to accumulate evidence, but it is unknown if these regions also maintain choices. To test if accumulator regions in humans also maintain decisions we compared delayed and self-paced responses during a face/house discrimination decision making task. Computational modeling and fMRI results revealed dissociated processes of evidence accumulation and decision maintenance, with potential accumulator activations found in the dorsomedial prefrontal cortex, right inferior frontal gyrus and bilateral insula. Potential maintenance activation spanned the frontal pole, temporal gyri, precuneus and the lateral occipital and frontal orbital cortices. Results of a quantitative reverse inference meta-analysis performed to differentiate the functions associated with the identified regions did not narrow down potential accumulation regions, but suggested that response-maintenance might rely on a verbalization of the response. PMID:26510176

Families that fire together smile together: Resting state connectome similarity and daily emotional synchrony in parent-child dyads.

PubMed

Lee, Tae-Ho; Miernicki, Michelle E; Telzer, Eva H

2017-05-15

Despite emerging evidence suggesting a biological basis to our social tiles, our understanding of the neural processes which link two minds is unknown. We implemented a novel approach, which included connectome similarity analysis using resting state intrinsic networks of parent-child dyads as well as daily diaries measured across 14 days. Intrinsic resting-state networks for both parents and their adolescent child were identified using independent component analysis (ICA). Results indicate that parents and children who had more similar RSN connectome also had more similar day-to-day emotional synchrony. Furthermore, dyadic RSN connectome similarity was associated with children's emotional competence, suggesting that being neurally in-tune with their parents confers emotional benefits. We provide the first evidence that dyadic RSN similarity is associated with emotional synchrony in what is often our first and most essential social bond, the parent-child relationship. Copyright © 2017 Elsevier Inc. All rights reserved.

Cdk5: one of the links between senile plaques and neurofibrillary tangles?

PubMed

Lee, Ming-Sum; Tsai, Li-Huei

2003-04-01

The relationship between amyloid plaques and neurofibrillary tangles, the two pathologic hallmarks of Alzheimer's disease (AD), is an unknown and controversial subject. However, emerging evidence from genetic and biochemical studies suggests that accumulation of amyloid beta peptides may play a causative role in AD pathogenesis. This led to the amyloid hypothesis, which proposes that amyloid beta peptides disrupt neuronal metabolic and ionic homeostasis and cause aberrant activation of kinases and/or inhibition of phosphatases. The resulting alteration in kinase and phosphatase activities ultimately leads to hyperphosphorylation of tau and formation of neurofibrillary tangles. Cyclin-dependent kinase 5 (Cdk5) is a tau kinase whose activity is induced by amyloid beta peptides. Its deregulation may represent one of the signal transduction pathways that connect amyloid beta toxicity to tau hyperphosphorylation. This article reviews the functions and regulation of Cdk5. Evidence that suggests deregulation of Cdk5 activity in AD by virtue of calpain cleavage of its activator p35 to p25 will be discussed.

The early Martian environment: Clues from the cratered highlands and the Precambrian Earth

NASA Technical Reports Server (NTRS)

Craddock, R. A.; Maxwell, T. A.

1993-01-01

There is abundant geomorphic evidence to suggest that Mars once had a much denser and warmer atmosphere than present today. Outflow channel, ancient valley networks, and degraded impact craters in the highlands all suggest that ancient Martian atmospheric conditions supported liquid water on the surface. The pressure, composition, and duration of this atmosphere is largely unknown. However, we have attempted to place some constraints on the nature of the early Martian atmosphere by analyzing morphologic variations of highland impact crater populations, synthesizing results of other investigators, and incorporating what is know about the geologic history of the early Earth. This is important for understanding the climatic evolution of Mars, the relative abundance of martian volatiles, and the nature of highland surface materials.

Believe it or not: on the possibility of suspending belief.

PubMed

Hasson, Uri; Simmons, Joseph P; Todorov, Alexander

2005-07-01

We present two experiments that cast doubt on existing evidence suggesting that it is impossible to suspend belief in a comprehended proposition. In Experiment 1, we found that interrupting the encoding of a statement's veracity decreased memory for the statement's falsity when the false version of the statement was uninformative, but not when the false version was informative. This suggests that statements that are informative when false are not represented as if they were true. In Experiment 2, participants made faster lexical decisions to words implied by preceding statements when they were told that the statements were true than when the veracity of the statements was unknown or when the statements were false. The findings suggest that comprehending a statement may not require believing it, and that it may be possible to suspend belief in comprehended propositions.

Pack hunting by a common soil amoeba on nematodes.

PubMed

Geisen, Stefan; Rosengarten, Jamila; Koller, Robert; Mulder, Christian; Urich, Tim; Bonkowski, Michael

2015-11-01

Soils host the most complex communities on Earth, including the most diverse and abundant eukaryotes, i.e. heterotrophic protists. Protists are generally considered as bacterivores, but evidence for negative interactions with nematodes both from laboratory and field studies exist. However, direct impacts of protists on nematodes remain unknown. We isolated the soil-borne testate amoeba Cryptodifflugia operculata and found a highly specialized and effective pack-hunting strategy to prey on bacterivorous nematodes. Enhanced reproduction in presence of prey nematodes suggests a beneficial predatory life history of these omnivorous soil amoebae. Cryptodifflugia operculata appears to selectively impact the nematode community composition as reductions of nematode numbers were species specific. Furthermore, we investigated 12 soil metatranscriptomes from five distinct locations throughout Europe for 18S ribosomal RNA transcripts of C. operculata. The presence of C. operculata transcripts in all samples, representing up to 4% of the active protist community, indicates a potential ecological importance of nematophagy performed by C. operculata in soil food webs. The unique pack-hunting strategy on nematodes that was previously unknown from protists, together with molecular evidence that these pack hunters are likely to be abundant and widespread in soils, imply a considerable importance of the hitherto neglected trophic link 'nematophagous protists' in soil food webs. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Chimpanzees (Pan troglodytes) Flexibly Use Introduced Species for Nesting and Bark Feeding in a Human-Dominated Habitat.

PubMed

McCarthy, Maureen S; Lester, Jack D; Stanford, Craig B

2017-01-01

As habitat loss and fragmentation place growing pressure on endangered nonhuman primate populations, researchers find increasing evidence for novel responses in behavior. In western Uganda between the Budongo and Bugoma Forests, chimpanzees ( Pan troglodytes schweinfurthii ) inhabit a mosaic landscape comprising forest fragments, human settlements, and agricultural land. We recorded nests and feeding evidence of unhabituated chimpanzees in this region over a 12-mo period. We found extensive evidence of nesting in introduced tree species, including eucalyptus ( Eucalyptus grandis ), guava ( Psidium guajava ), cocoa ( Theobroma cacao ), and Caribbean pine ( Pinus caribaea ). In addition, we found instances of ground nesting, nest reuse, and composite nests constructed from branches of multiple trees. This evidence may indicate a lack of suitable nesting trees or attempts by chimpanzees to nest in areas of riparian forest that allow them to avoid human detection. We also found new evidence for eucalyptus bark feeding by chimpanzees. Such evidence suggests chimpanzees respond flexibly to mitigate anthropogenic pressures in human-dominated landscapes. The limits of such flexibility remain unknown. Further research is needed to examine systematically the factors influencing the use of such resources and to understand better the extent to which chimpanzees can persist while relying on them.

Dissemination and use of a participatory ergonomics guide for workplaces.

PubMed

Van Eerd, Dwayne; King, Trevor; Keown, Kiera; Slack, Tesha; Cole, Donald C; Irvin, Emma; Amick, Benjamin C; Bigelow, Philip

2016-06-01

Musculoskeletal disorders (MSDs) result in lost-time injury claims and lost productivity worldwide, placing a substantial burden on workers and workplaces. Participatory ergonomics (PE) is a popular approach to reducing MSDs; however, there are challenges to implementing PE programmes. Using evidence to overcome challenges may be helpful but the impacts of doing so are unknown. We sought to disseminate an evidence-based PE tool and to describe its use. An easy-to-use, evidence-based PE Guide was disseminated to workplace parties, who were surveyed about using the tool. The greatest barrier to using the tool was a lack of time. Reported tool use included for training purposes, sharing and integrating the tool into existing programmes. New actions related to tool use included training, defining team responsibilities and suggesting programme implementation steps. Evidence-based tools could help ergonomists overcome some challenges involved in implementing injury reduction programmes such as PE. Practitioner Summary Practitioners experience challenges implementing programmes to reduce the burden of MSDs in workplaces. Implementing participatory interventions requires multiple workplace parties to be 'on-board'. Disseminating and using evidence-based guides may help to overcome these challenges. Using evidence-based tools may help ergonomics practitioners implement PE programmes.

The Arabidopsis COBRA Protein Facilitates Cellulose Crystallization at the Plasma Membrane*

PubMed Central

Sorek, Nadav; Sorek, Hagit; Kijac, Aleksandra; Szemenyei, Heidi J.; Bauer, Stefan; Hématy, Kian; Wemmer, David E.; Somerville, Chris R.

2014-01-01

Mutations in the Arabidopsis COBRA gene lead to defects in cellulose synthesis but the function of COBRA is unknown. Here we present evidence that COBRA localizes to discrete particles in the plasma membrane and is sensitive to inhibitors of cellulose synthesis, suggesting that COBRA and the cellulose synthase complex reside in close proximity on the plasma membrane. Live-cell imaging of cellulose synthesis indicated that, once initiated, cellulose synthesis appeared to proceed normally in the cobra mutant. Using isothermal calorimetry, COBRA was found to bind individual β1–4-linked glucan chains with a KD of 3.2 μm. Competition assays suggests that COBRA binds individual β1–4-linked glucan chains with higher affinity than crystalline cellulose. Solid-state nuclear magnetic resonance studies of the cell wall of the cobra mutant also indicated that, in addition to decreases in cellulose amount, the properties of the cellulose fibrils and other cell wall polymers differed from wild type by being less crystalline and having an increased number of reducing ends. We interpret the available evidence as suggesting that COBRA facilitates cellulose crystallization from the emerging β1–4-glucan chains by acting as a “polysaccharide chaperone.” PMID:25331944

Characterization of Glass-Like Fragments from the 3714 Building

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

Buck, Edgar C.

2010-02-23

This report describes characterization of a sample obtained from the 3714 building in the 300 Area. Characterization of this unknown material was required for the demonolition activities in the 300 Area. The object of the study was to dertermine the nature of the material, composition, possible structure, evidence for hazards components. The green material is a sodium alumino-silicate glass. This conclusion is based on the composition provided by SEM-EDS, and the images that suggest a glass-like morphology. Further analysis with Ramin and/or infrared could be used to determine the presence of any organics.

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

Keane, T.J.; Van Dyk, J.; Rider, W.D.

Interstitial pneumonia is a frequent and often fatal complication of allogenic bone marrow transplantation. Thirty to 40 percent of such cases are of unknown etiology and have been labelled as cases of idiopathic interstitial pneumonia. Idiopathic cases are more commonly associated with the use of total body irradiation; their occurrence appears to be independent of immunosupression or graft versus host disease. Evidence is presented from the literature suggesting that the development of idiopathic interstitial pneumonia is related to the absolute absorbed dose of radiation to lung. The similarity of idiopathic pneumonia to radiation pneumonitis seen in a different clinical settingmore » is described.« less

A case of incomplete atypical femoral fracture with histomorphometrical evidence of osteomalacia.

PubMed

Tsuchie, Hiroyuki; Miyakoshi, Naohisa; Nishi, Tomio; Abe, Hidekazu; Segawa, Toyohito; Shimada, Yoichi

2015-01-01

Roughly half of the femoral fracture patients diagnosed with AFF according to the criteria suggested by a task force of the American Society for Bone and Mineral Research (ASBMR) have not undergone bisphosphonate (BP) therapy. One suspected cause of such fractures is severe bone loss due to osteomalacia, but the pathogenesis remains unknown. We report a case of an 84-year-old woman with AFF not treated by BP therapy, in whom underlying osteomalacia was histologically diagnosed. The involvement of femoral curvature and spino-pelvic malaligment in the fracture in the present case was considered.

Ofuji disease: a rare dermatosis and its challenging therapeutic approach*

PubMed Central

de Brito, Fernanda Freitas; Martelli, Antonio Carlos Ceribelli; Cavalcante, Maria Lopes Lamenha Lins; Pinto, Ana Cecília Versiani Duarte; Itimura, Gabriela; Soares, Cleverson Teixeira

2016-01-01

Eosinophilic pustular folliculitis (EPF) or Ofuji disease is a rare dermatosis, prone to recurrence and chronicity. The peak incidence occurs in the third decade of life and its exact etiology remains unknown. Evidence suggests that the expression of adhesion molecules and the production of cytokines activate the follicular unit, but the stimulus that triggers these changes remains unclear. The three clinical variants reported in the literature include classic EPF, immunosuppression-associated EPF, and infancy-associated EPF. We report a case of eosinophilic pustular folliculitis with peculiar epidemiological characteristics, which represents a challenging therapeutic scenario. PMID:27828641

Gene-culture coevolution in the age of genomics

PubMed Central

Richerson, Peter J.; Boyd, Robert; Henrich, Joseph

2010-01-01

The use of socially learned information (culture) is central to human adaptations. We investigate the hypothesis that the process of cultural evolution has played an active, leading role in the evolution of genes. Culture normally evolves more rapidly than genes, creating novel environments that expose genes to new selective pressures. Many human genes that have been shown to be under recent or current selection are changing as a result of new environments created by cultural innovations. Some changed in response to the development of agricultural subsistence systems in the Early and Middle Holocene. Alleles coding for adaptations to diets rich in plant starch (e.g., amylase copy number) and to epidemic diseases evolved as human populations expanded (e.g., sickle cell and G6PD deficiency alleles that provide protection against malaria). Large-scale scans using patterns of linkage disequilibrium to detect recent selection suggest that many more genes evolved in response to agriculture. Genetic change in response to the novel social environment of contemporary modern societies is also likely to be occurring. The functional effects of most of the alleles under selection during the last 10,000 years are currently unknown. Also unknown is the role of paleoenvironmental change in regulating the tempo of hominin evolution. Although the full extent of culture-driven gene-culture coevolution is thus far unknown for the deeper history of the human lineage, theory and some evidence suggest that such effects were profound. Genomic methods promise to have a major impact on our understanding of gene-culture coevolution over the span of hominin evolutionary history. PMID:20445092

Resveratrol protects the loss of connexin 43 induced by ethanol exposure in neonatal mouse cardiomyocytes.

PubMed

Tu, Su; Cao, Fu-Tao; Fan, Xiao-Chun; Yang, Cheng-Jian

2017-06-01

Excessive alcohol consumption provides risk to cardiomyopathy with unknown mechanisms. Resveratrol, a plant polyphenol, is widely reported for its cardiovascular benefits, while its effect on alcohol-induced impairments in cardiomyocytes largely remains unknown. Effects of resveratrol on the cardiomyocytes under ethanol insult were studied in vitro. Ethanol exposure in mouse neonatal cardiomyocytes increased cell death and induced a specific loss of tight junction protein, connexin 43. In spite of adverse effects at higher concentrations, resveratrol at 10 μM improved cell viability of cardiomyocytes in the presence of a deleterious dose of ethanol. Importantly, the co-treatment of resveratrol with ethanol exhibited the restoration of connexin 43 protein. Further assays showed that these effects were likely associated with the antioxidative actions of resveratrol, and correlated with the alleviation of MAP kinase activation in cultured cardiomyocytes in response to ethanol. Our data suggests a novel mechanism of cardiomyocyte cell loss under ethanol exposure and provides new evidence of protective effects of resveratrol in the cardiomyocytes.

An integrative, translational approach to understanding rare and orphan genetically based diseases

PubMed Central

Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.

2013-01-01

PhenomeNet is an approach for integrating phenotypes across species and identifying candidate genes for genetic diseases based on the similarity between a disease and animal model phenotypes. In contrast to ‘guilt-by-association’ approaches, PhenomeNet relies exclusively on the comparison of phenotypes to suggest candidate genes, and can, therefore, be applied to study the molecular basis of rare and orphan diseases for which the molecular basis is unknown. In addition to disease phenotypes from the Online Mendelian Inheritance in Man (OMIM) database, we have now integrated the clinical signs from Orphanet into PhenomeNet. We demonstrate that our approach can efficiently identify known candidate genes for genetic diseases in Orphanet and OMIM. Furthermore, we find evidence that mutations in the HIP1 gene might cause Bassoe syndrome, a rare disorder with unknown genetic aetiology. Our results demonstrate that integration and computational analysis of human disease and animal model phenotypes using PhenomeNet has the potential to reveal novel insights into the pathobiology underlying genetic diseases. PMID:23853703

Role of metabolism in drug-induced idiosyncratic hepatotoxicity.

PubMed

Walgren, Jennie L; Mitchell, Michael D; Thompson, David C

2005-01-01

Rare adverse reactions to drugs that are of unknown etiology, or idiosyncratic reactions, can produce severe medical complications or even death in patients. Current hypotheses suggest that metabolic activation of a drug to a reactive intermediate is a necessary, yet insufficient, step in the generation of an idiosyncratic reaction. We review evidence for this hypothesis with drugs that are associated with hepatotoxicity, one of the most common types of idiosyncratic reactions in humans. We identified 21 drugs that have either been withdrawn from the U.S. market due to hepatotoxicity or have a black box warning for hepatotoxicity. Evidence for the formation of reactive metabolites was found for 5 out of 6 drugs that were withdrawn, and 8 out of 15 drugs that have black box warnings. For the other drugs, either evidence was not available or suitable studies have not been carried out. We also review evidence for reactive intermediate formation from a number of additional drugs that have been associated with idiosyncratic hepatotoxicity but do not have black box warnings. Finally, we consider the potential role that high dosages may play in these adverse reactions.

The Association of DRD2 with Insight Problem Solving.

PubMed

Zhang, Shun; Zhang, Jinghuan

2016-01-01

Although the insight phenomenon has attracted great attention from psychologists, it is still largely unknown whether its variation in well-functioning human adults has a genetic basis. Several lines of evidence suggest that genes involved in dopamine (DA) transmission might be potential candidates. The present study explored for the first time the association of dopamine D2 receptor gene ( DRD2 ) with insight problem solving. Fifteen single-nucleotide polymorphisms (SNPs) covering DRD2 were genotyped in 425 unrelated healthy Chinese undergraduates, and were further tested for association with insight problem solving. Both single SNP and haplotype analysis revealed several associations of DRD2 SNPs and haplotypes with insight problem solving. In conclusion, the present study provides the first evidence for the involvement of DRD2 in insight problem solving, future studies are necessary to validate these findings.

The Association of DRD2 with Insight Problem Solving

PubMed Central

Zhang, Shun; Zhang, Jinghuan

2016-01-01

Although the insight phenomenon has attracted great attention from psychologists, it is still largely unknown whether its variation in well-functioning human adults has a genetic basis. Several lines of evidence suggest that genes involved in dopamine (DA) transmission might be potential candidates. The present study explored for the first time the association of dopamine D2 receptor gene (DRD2) with insight problem solving. Fifteen single-nucleotide polymorphisms (SNPs) covering DRD2 were genotyped in 425 unrelated healthy Chinese undergraduates, and were further tested for association with insight problem solving. Both single SNP and haplotype analysis revealed several associations of DRD2 SNPs and haplotypes with insight problem solving. In conclusion, the present study provides the first evidence for the involvement of DRD2 in insight problem solving, future studies are necessary to validate these findings. PMID:27933030

Role for Telomerase in Listeria monocytogenes Infection

PubMed Central

Samba-Louaka, Ascel; Stavru, Fabrizia

2012-01-01

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the human telomerase complex. Growing evidence suggests that hTERT also contributes to the cell physiology independently of telomere elongation. However, its role in bacterial infection is unknown. Here we show that hTERT is critical for Listeria monocytogenes infection, as the depletion of hTERT impaired bacterial intracellular replication. In addition, we observed that L. monocytogenes caused a decrease in hTERT levels at early time points of the infectious process. This effect was mediated by the pore-forming toxin listeriolysin O (LLO) and did not require bacterial entry into host cells. Calcium influx through the LLO pores contributed to a proteasome-independent decrease in hTERT protein levels. Together, our data provide evidence that these bacteria trigger hTERT degradation, an event that is detrimental to bacterial replication. PMID:23006849

Altered brain-gut axis in autism: comorbidity or causative mechanisms?

PubMed

Mayer, Emeran A; Padua, David; Tillisch, Kirsten

2014-10-01

The concept that alterated communications between the gut microbiome and the brain may play an important role in human brain disorders has recently received considerable attention. This is the result of provocative preclinical and some clinical evidence supporting early hypotheses about such communication in health and disease. Gastrointestinal symptoms are a common comorbidity in patients with autism spectrum disorders (ASD), even though the underlying mechanisms are largely unknown. In addition, alteration in the composition and metabolic products of the gut microbiome has long been implicated as a possible causative mechanism contributing to ASD pathophysiology, and this hypothesis has been supported by several recently published evidence from rodent models of autism induced by prenatal insults to the mother. Recent evidence in one such model involving maternal infection, that is characterized by alterations in behavior, gut physiology, microbial composition, and related metabolite profile, suggests a possible benefit of probiotic treatment on several of the observed abnormal behaviors. © 2014 WILEY Periodicals, Inc.

A systematic review of interventions to promote social support and parenting skills in parents with an intellectual disability.

PubMed

Wilson, S; McKenzie, K; Quayle, E; Murray, G

2014-01-01

The family support needs of parents with an intellectual disability (ID) are relatively unknown. This paper reviewed two types of intervention for parents with ID: those designed to strengthen social relationships and those teaching parenting skills. A literature search was conducted using electronic databases and a limited number of evaluative studies were found. The evidence for interventions aimed at strengthening social relationships was inconclusive; although positive changes were observed, there were limitations in study design which restricted the generalizability of the results. The evidence for parental skills teaching suggested that behavioural based interventions are more effective than less intensive forms such as lesson booklets and the provision of normal services, although these studies also had limitations. There is a need for further large scale controlled studies in this area to provide clearer evidence and to explore additional factors relating to child, parent and family which may impact on outcomes. © 2013 John Wiley & Sons Ltd.

Combining meteorites and missions to explore Mars.

PubMed

McCoy, Timothy J; Corrigan, Catherine M; Herd, Christopher D K

2011-11-29

Laboratory studies of meteorites and robotic exploration of Mars reveal scant atmosphere, no evidence of plate tectonics, past evidence for abundant water, and a protracted igneous evolution. Despite indirect hints, direct evidence of a martian origin came with the discovery of trapped atmospheric gases in one meteorite. Since then, the study of martian meteorites and findings from missions have been linked. Although the meteorite source locations are unknown, impact ejection modeling and spectral mapping of Mars suggest derivation from small craters in terrains of Amazonian to Hesperian age. Whereas most martian meteorites are young (< 1.3 Ga), the spread of whole rock isotopic compositions results from crystallization of a magma ocean > 4.5 Ga and formation of enriched and depleted reservoirs. However, the history inferred from martian meteorites conflicts with results from recent Mars missions, calling into doubt whether the igneous histor y inferred from the meteorites is applicable to Mars as a whole. Allan Hills 84001 dates to 4.09 Ga and contains fluid-deposited carbonates. Accompanying debate about the mechanism and temperature of origin of the carbonates came several features suggestive of past microbial life in the carbonates. Although highly disputed, the suggestion spurred interest in habitable extreme environments on Earth and throughout the Solar System. A flotilla of subsequent spacecraft has redefined Mars from a volcanic planet to a hydrologically active planet that may have harbored life. Understanding the history and habitability of Mars depends on understanding the coupling of the atmosphere, surface, and subsurface. Sample return that brings back direct evidence from these diverse reservoirs is essential.

Combining meteorites and missions to explore Mars

PubMed Central

McCoy, Timothy J.; Corrigan, Catherine M.; Herd, Christopher D. K.

2011-01-01

Laboratory studies of meteorites and robotic exploration of Mars reveal scant atmosphere, no evidence of plate tectonics, past evidence for abundant water, and a protracted igneous evolution. Despite indirect hints, direct evidence of a martian origin came with the discovery of trapped atmospheric gases in one meteorite. Since then, the study of martian meteorites and findings from missions have been linked. Although the meteorite source locations are unknown, impact ejection modeling and spectral mapping of Mars suggest derivation from small craters in terrains of Amazonian to Hesperian age. Whereas most martian meteorites are young (< 1.3 Ga), the spread of whole rock isotopic compositions results from crystallization of a magma ocean > 4.5 Ga and formation of enriched and depleted reservoirs. However, the history inferred from martian meteorites conflicts with results from recent Mars missions, calling into doubt whether the igneous histor y inferred from the meteorites is applicable to Mars as a whole. Allan Hills 84001 dates to 4.09 Ga and contains fluid-deposited carbonates. Accompanying debate about the mechanism and temperature of origin of the carbonates came several features suggestive of past microbial life in the carbonates. Although highly disputed, the suggestion spurred interest in habitable extreme environments on Earth and throughout the Solar System. A flotilla of subsequent spacecraft has redefined Mars from a volcanic planet to a hydrologically active planet that may have harbored life. Understanding the history and habitability of Mars depends on understanding the coupling of the atmosphere, surface, and subsurface. Sample return that brings back direct evidence from these diverse reservoirs is essential. PMID:21969535

In situ spectroscopic evidence for neptunium(V)-carbonate inner-sphere and outer-sphere ternary surface complexes on hematite surfaces.

PubMed

Arai, Yuji; Moran, P B; Honeyman, B D; Davis, J A

2007-06-01

Np(V) surface speciation on hematite surfaces at pH 7-9 under pC2 = 10(-3.45) atm was investigated using X-ray absorption spectroscopy (XAS). In situ XAS analyses suggest that bis-carbonato inner-sphere and tris-carbonato outer-sphere ternary surface species coexist at the hematite-water interface at pH 7-8.8, and the fraction of outer-sphere species gradually increases from 27 to 54% with increasing pH from 7 to 8.8. The results suggest that the heretofore unknown Np(V)-carbonato ternary surface species may be important in predicting the fate and transport of Np(V) in the subsurface environment down gradient of high-level nuclear waste respositories.

Interaction between telencephalic signals and respiratory dynamics in songbirds

PubMed Central

Méndez, Jorge M.; Mindlin, Gabriel B.

2012-01-01

The mechanisms by which telencephalic areas affect motor activities are largely unknown. They could either take over motor control from downstream motor circuits or interact with the intrinsic dynamics of these circuits. Both models have been proposed for telencephalic control of respiration during learned vocal behavior in birds. The interactive model postulates that simple signals from the telencephalic song control areas are sufficient to drive the nonlinear respiratory network into producing complex temporal sequences. We tested this basic assumption by electrically stimulating telencephalic song control areas and analyzing the resulting respiratory patterns in zebra finches and in canaries. We found strong evidence for interaction between the rhythm of stimulation and the intrinsic respiratory rhythm, including naturally emerging subharmonic behavior and integration of lateralized telencephalic input. The evidence for clear interaction in our experimental paradigm suggests that telencephalic vocal control also uses a similar mechanism. Furthermore, species differences in the response of the respiratory system to stimulation show parallels to differences in the respiratory patterns of song, suggesting that the interactive production of respiratory rhythms is manifested in species-specific specialization of the involved circuitry. PMID:22402649

The function of the sleep spindle: a physiological index of intelligence and a mechanism for sleep-dependent memory consolidation.

PubMed

Fogel, Stuart M; Smith, Carlyle T

2011-04-01

Until recently, the electrophysiological mechanisms involved in strengthening new memories into a more permanent form during sleep have been largely unknown. The sleep spindle is an event in the electroencephalogram (EEG) characterizing Stage 2 sleep. Sleep spindles may reflect, at the electrophysiological level, an ideal mechanism for inducing long-term synaptic changes in the neocortex. Recent evidence suggests the spindle is highly correlated with tests of intellectual ability (e.g.; IQ tests) and may serve as a physiological index of intelligence. Further, spindles increase in number and duration in sleep following new learning and are correlated with performance improvements. Spindle density and sigma (14-16Hz) spectral power have been found to be positively correlated with performance following a daytime nap, and animal studies suggest the spindle is involved in a hippocampal-neocortical dialogue necessary for memory consolidation. The findings reviewed here collectively provide a compelling body of evidence that the function of the sleep spindle is related to intellectual ability and memory consolidation. Copyright © 2010 Elsevier Ltd. All rights reserved.

An integrated mechanism of pediatric pseudotumor cerebri syndrome: evidence of bioenergetic and hormonal regulation of cerebrospinal fluid dynamics

PubMed Central

Sheldon, Claire A.; Kwon, Young Joon; Liu, Grant T.; McCormack, Shana E.

2015-01-01

Pseudotumor cerebri syndrome (PTCS) is defined by the presence of elevated intracranial pressure (ICP) in the setting of normal brain parenchyma and cerebrospinal fluid (CSF). Headache, vision changes, and papilledema are common presenting features. Up to 10% of appropriately treated patients may experience permanent visual loss. The mechanism(s) underlying PTCS is unknown. PTCS occurs in association with a variety of conditions, including kidney disease, obesity, and adrenal insufficiency, suggesting endocrine and/or metabolic derangements may occur. Recent studies suggest that fluid and electrolyte balance in renal epithelia is regulated by a complex interaction of metabolic and hormonal factors; these cells share many of the same features as the choroid plexus cells in the central nervous system (CNS) responsible for regulation of CSF dynamics. Thus, we posit that similar factors may influence CSF dynamics in both types of fluid-sensitive tissues. Specifically, we hypothesize that, in patients with PTCS, mitochondrial metabolites (glutamate, succinate) and steroid hormones (cortisol, aldosterone) regulate CSF production and/or absorption. In this integrated mechanism review, we consider the clinical and molecular evidence for each metabolite and hormone in turn. We illustrate how related intracellular signaling cascades may converge in the choroid plexus, drawing on evidence from functionally similar tissues. PMID:25420176

Molecular epidemiology of feline immunodeficiency virus in the domestic cat (Felis catus)

PubMed Central

Hayward, Jessica J; Rodrigo, Allen G

2009-01-01

Studying the evolutionary mechanisms of feline immunodeficiency virus in the domestic cat (Felis catus), FIVFca, provides a good comparison to other lentiviruses, such as HIV and FIVPco in the cougar (Puma concolor). We review the current epidemiological and evolutionary findings of FIVFca,. In addition to the five accepted FIVFca, subtypes, several recent phylogenetic studies have found strains that form separate clades, indicative of novel subtypes. In New Zealand cats, these strains of unknown subtype have been found to be involved in complex patterns of intergenic recombination, and whole genome sequences are required to resolve these. Evidence of recombination events has been documented with the highest levels in the env gene, the region involved in host cell receptor recognition. Several cases of FIVFca, multiple infection, both inter- and intra-subtype, have been reported. The findings of both unknown subtypes and relatively high levels of recombination suggest the need for further testing of the current vaccine. Limited studies on the evolutionary rate of FIVFca, document a value twice to three times that of FIV in the cougar, a result suggesting the different levels of co-adaptation between the viruses and their respective hosts. We studied the tissue distribution of FIVFca, in feral domestic cats, finding the first case of FIV compartmentalisation, a phenomenon well-documented in HIV-1 patients. PMID:19896220

Participant Diversity in Special Education Research: Parent-Implemented Behavior Interventions for Children with Autism

ERIC Educational Resources Information Center

Robertson, Rachel E.; Sobeck, Emily E.; Wynkoop, Kaylee; Schwartz, Rachel

2017-01-01

Evidence-based practices for children with disabilities have empirical support for their effectiveness; however, the demographics of participants making up the evidence base are generally unknown, leaving generalizability of the evidence unclear. This study presents a systematic literature review of participant racial and socioeconomic…

Theropod courtship: large scale physical evidence of display arenas and avian-like scrape ceremony behaviour by Cretaceous dinosaurs.

PubMed

Lockley, Martin G; McCrea, Richard T; Buckley, Lisa G; Lim, Jong Deock; Matthews, Neffra A; Breithaupt, Brent H; Houck, Karen J; Gierliński, Gerard D; Surmik, Dawid; Kim, Kyung Soo; Xing, Lida; Kong, Dal Yong; Cart, Ken; Martin, Jason; Hadden, Glade

2016-01-07

Relationships between non-avian theropod dinosaurs and extant and fossil birds are a major focus of current paleobiological research. Despite extensive phylogenetic and morphological support, behavioural evidence is mostly ambiguous and does not usually fossilize. Thus, inferences that dinosaurs, especially theropods displayed behaviour analogous to modern birds are intriguing but speculative. Here we present extensive and geographically widespread physical evidence of substrate scraping behavior by large theropods considered as compelling evidence of "display arenas" or leks, and consistent with "nest scrape display" behaviour among many extant ground-nesting birds. Large scrapes, up to 2 m in diameter, occur abundantly at several Cretaceous sites in Colorado. They constitute a previously unknown category of large dinosaurian trace fossil, inferred to fill gaps in our understanding of early phases in the breeding cycle of theropods. The trace makers were probably lekking species that were seasonally active at large display arena sites. Such scrapes indicate stereotypical avian behaviour hitherto unknown among Cretaceous theropods, and most likely associated with terrirorial activity in the breeding season. The scrapes most probably occur near nesting colonies, as yet unknown or no longer preserved in the immediate study areas. Thus, they provide clues to paleoenvironments where such nesting sites occurred.

Theropod courtship: large scale physical evidence of display arenas and avian-like scrape ceremony behaviour by Cretaceous dinosaurs

NASA Astrophysics Data System (ADS)

Lockley, Martin G.; McCrea, Richard T.; Buckley, Lisa G.; Deock Lim, Jong; Matthews, Neffra A.; Breithaupt, Brent H.; Houck, Karen J.; Gierliński, Gerard D.; Surmik, Dawid; Soo Kim, Kyung; Xing, Lida; Yong Kong, Dal; Cart, Ken; Martin, Jason; Hadden, Glade

2016-01-01

Relationships between non-avian theropod dinosaurs and extant and fossil birds are a major focus of current paleobiological research. Despite extensive phylogenetic and morphological support, behavioural evidence is mostly ambiguous and does not usually fossilize. Thus, inferences that dinosaurs, especially theropods displayed behaviour analogous to modern birds are intriguing but speculative. Here we present extensive and geographically widespread physical evidence of substrate scraping behavior by large theropods considered as compelling evidence of “display arenas” or leks, and consistent with “nest scrape display” behaviour among many extant ground-nesting birds. Large scrapes, up to 2 m in diameter, occur abundantly at several Cretaceous sites in Colorado. They constitute a previously unknown category of large dinosaurian trace fossil, inferred to fill gaps in our understanding of early phases in the breeding cycle of theropods. The trace makers were probably lekking species that were seasonally active at large display arena sites. Such scrapes indicate stereotypical avian behaviour hitherto unknown among Cretaceous theropods, and most likely associated with terrirorial activity in the breeding season. The scrapes most probably occur near nesting colonies, as yet unknown or no longer preserved in the immediate study areas. Thus, they provide clues to paleoenvironments where such nesting sites occurred.

Theropod courtship: large scale physical evidence of display arenas and avian-like scrape ceremony behaviour by Cretaceous dinosaurs

PubMed Central

Lockley, Martin G.; McCrea, Richard T.; Buckley, Lisa G.; Deock Lim, Jong; Matthews, Neffra A.; Breithaupt, Brent H.; Houck, Karen J.; Gierliński, Gerard D.; Surmik, Dawid; Soo Kim, Kyung; Xing, Lida; Yong Kong, Dal; Cart, Ken; Martin, Jason; Hadden, Glade

2016-01-01

Relationships between non-avian theropod dinosaurs and extant and fossil birds are a major focus of current paleobiological research. Despite extensive phylogenetic and morphological support, behavioural evidence is mostly ambiguous and does not usually fossilize. Thus, inferences that dinosaurs, especially theropods displayed behaviour analogous to modern birds are intriguing but speculative. Here we present extensive and geographically widespread physical evidence of substrate scraping behavior by large theropods considered as compelling evidence of “display arenas” or leks, and consistent with “nest scrape display” behaviour among many extant ground-nesting birds. Large scrapes, up to 2 m in diameter, occur abundantly at several Cretaceous sites in Colorado. They constitute a previously unknown category of large dinosaurian trace fossil, inferred to fill gaps in our understanding of early phases in the breeding cycle of theropods. The trace makers were probably lekking species that were seasonally active at large display arena sites. Such scrapes indicate stereotypical avian behaviour hitherto unknown among Cretaceous theropods, and most likely associated with terrirorial activity in the breeding season. The scrapes most probably occur near nesting colonies, as yet unknown or no longer preserved in the immediate study areas. Thus, they provide clues to paleoenvironments where such nesting sites occurred. PMID:26741567

Envisaging the use of evidence-based practice (EBP): how nurse academics facilitate EBP use in theory and practice across Australian undergraduate programmes.

PubMed

Malik, Gulzar; McKenna, Lisa; Griffiths, Debra

2017-09-01

This paper is drawn from a grounded theory study that aimed to investigate processes undertaken by academics when integrating evidence-based practice into undergraduate curricula. This paper focuses on how nurse academics facilitated students to apply evidence-based practice in theory and practice. Facilitating undergraduate nursing students to develop skills within an evidence-based practice framework is vital to achieving evidence-based care. Studies on evidence-based practice conducted globally suggests that there is a need to investigate approaches used by nurse academics in facilitating students' understanding and use of evidence-based practice during their nurse education. Employing constructivist grounded theory approach, 23 nurse academics across Australian universities were interviewed and nine observed during their teaching. Some study participants shared their unit guides to enrich analysis. Data analysis was performed by following Charmaz's approach of coding procedures; as a result, four categories were constructed. This paper focuses on the category conceptualised as Envisaging the use of evidence-based practice. Findings revealed that most academics-assisted students to use evidence in academic-related activities. Recognising the importance of evidence-based practice in practice, some also expected students to apply evidence-based practice during clinical experiences. However, the level of students' appreciation for evidence-based practice during clinical experiences was unknown to participants and was influenced by practice-related barriers. Acknowledging these challenges, academics were engaged in dialogue with students and suggested the need for academia-practice collaboration in combating the cited barriers. Ensuring academics are supported to emphasise clinical application of evidence-based practice requires strategies at school and practice levels. Faculty development, engagement of clinical nurses with evidence-based practice, supportive culture for nurses and students to apply evidence-based practice principles, and collaboration between academia and practice will make facilitation by academics practical and meaningful for students. Findings from this study point to a number of initiatives for clinical leadership to provide infrastructure and support for academics, practising nurses and undergraduate students to adopt evidence-based practice in practice settings, thereby influencing practice outcomes. © 2016 John Wiley & Sons Ltd.

Role of bevacizumab in uterine leiomyosarcoma.

PubMed

Bogani, Giorgio; Ditto, Antonino; Martineli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Fonatella, Caterina; Sanfilippo, Roberta; Leone Roberti Maggiore, Umberto; Ferrero, Simone; Lorusso, Domenica; Raspagliesi, Francesco

2018-06-01

In the recent years, angiogenetic inhibitors have emerged for the treatment of several malignancies. In particular, bevacizumab has proved to be effective in many types of cancers (including sarcoma), but the limitations of antiangiogenic therapy have been shown in practice. Here, we sought to review the current evidence on the role and efficacy of bevacizumab in patients affected by uterine leiomyosarcoma. On April 2017, Literature was searched in order to identify studies reporting outcomes of patients affected either by early stage or advanced/recurred uterine leiomyosarcoma undergoing treatment with bevacizumab, alone or in combination with other chemotherapeutic regimens. Searching the literature data of 69 patients affected by metastatic, unresectable uterine leiomyosarcoma were retrieved; on the contrary, no data regarding the use of bevacizumab in patients with early-stage uterine leiomyosarcoma was published. Current evidence suggested that the addiction of bevacizumab to standard treatment modality does not increase grade 3 or worse toxicity (assessed by CTCAE). Pooled data regarding response rate suggested that 35%, 28%, 26% and 11% of patients experienced objective cure (complete + partial response), stable disease, progressive disease and unknown response, respectively. Data from the only one randomized controlled trial suggested that objective cure rate does not differ from standard chemotherapy treatment, thus limiting the indication to add bevacizumab in patients affected by metastatic, unresectable uterine leiomyosarcoma. The current evidence does not justify the use of bevacizumab into clinical practice. Further randomized studies testing the role of bevacizumab are warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

Proteins required for lipopolysaccharide assembly in Escherichia coli form a transenvelope complex.

PubMed

Chng, Shu-Sin; Gronenberg, Luisa S; Kahne, Daniel

2010-06-08

The viability of Gram-negative organisms is dependent on the proper placement of lipopolysaccharide (LPS) in the outer leaflet of its outer membrane. LPS is synthesized inside the cell and transported to the surface by seven essential lipopolysaccharide transport (Lpt) proteins. How these proteins cooperate to transport LPS is unknown. We show that these Lpt proteins can be found in a membrane fraction that contains inner and outer membranes and that they copurify. This constitutes the first evidence that the Lpt proteins form a transenvelope complex. We suggest that this protein bridge provides a route for LPS transport across the cell envelope.

Proteins required for lipopolysaccharide assembly in Escherichia coli form a trans-envelope complex†

PubMed Central

Chng, Shu-Sin; Gronenberg, Luisa S.; Kahne, Daniel

2010-01-01

The viability of Gram-negative organisms is dependent on the proper placement of lipopolysaccharide (LPS) in the outer leaflet of its outer membrane. LPS is synthesized inside the cell and transported to the surface by seven essential Lpt proteins. How these proteins cooperate to transport LPS is unknown. We show that these Lpt proteins can be found in a membrane fraction that contains inner and outer membranes, and that they co-purify. This constitutes the first evidence that the Lpt proteins form a trans-envelope complex. We suggest that this protein bridge provides a route for LPS transport across the cell envelope. PMID:20446753

Environmental epigenetics in metal exposure

PubMed Central

Martinez-Zamudio, Ricardo

2011-01-01

Although it is widely accepted that chronic exposure to arsenite, nickel, chromium and cadmium increases cancer incidence in individuals, the molecular mechanisms underlying their ability to transform cells remain largely unknown. Carcinogenic metals are typically weak mutagens, suggesting that genetic-based mechanisms may not be primarily responsible for metal-induced carcinogenesis. Growing evidence shows that environmental metal exposure involves changes in epigenetic marks, which may lead to a possible link between heritable changes in gene expression and disease susceptibility and development. Here, we review recent advances in the understanding of metal exposure affecting epigenetic marks and discuss establishment of heritable gene expression in metal-induced carcinogenesis. PMID:21610324

The influence of spontaneous activity on stimulus processing in primary visual cortex.

PubMed

Schölvinck, M L; Friston, K J; Rees, G

2012-02-01

Spontaneous activity in the resting human brain has been studied extensively; however, how such activity affects the local processing of a sensory stimulus is relatively unknown. Here, we examined the impact of spontaneous activity in primary visual cortex on neuronal and behavioural responses to a simple visual stimulus, using functional MRI. Stimulus-evoked responses remained essentially unchanged by spontaneous fluctuations, combining with them in a largely linear fashion (i.e., with little evidence for an interaction). However, interactions between spontaneous fluctuations and stimulus-evoked responses were evident behaviourally; high levels of spontaneous activity tended to be associated with increased stimulus detection at perceptual threshold. Our results extend those found in studies of spontaneous fluctuations in motor cortex and higher order visual areas, and suggest a fundamental role for spontaneous activity in stimulus processing. Copyright © 2011. Published by Elsevier Inc.

The relative importance of noise level and number of events on human reactions to noise: Community survey findings and study methods

NASA Technical Reports Server (NTRS)

Fields, J. M.

1980-01-01

The data from seven surveys of community response to environmental noise are reanalyzed to assess the relative influence of peak noise levels and the numbers of noise events on human response. The surveys do not agree on the value of the tradeoff between the effects of noise level and numbers of events. The value of the tradeoff cannot be confidently specified in any survey because the tradeoff estimate may have a large standard error of estimate and because the tradeoff estimate may be seriously biased by unknown noise measurement errors. Some evidence suggests a decrease in annoyance with very high numbers of noise events but this evidence is not strong enough to lead to the rejection of the conventionally accepted assumption that annoyance is related to a log transformation of the number of noise events.

Pleistocene North African genomes link Near Eastern and sub-Saharan African human populations.

PubMed

van de Loosdrecht, Marieke; Bouzouggar, Abdeljalil; Humphrey, Louise; Posth, Cosimo; Barton, Nick; Aximu-Petri, Ayinuer; Nickel, Birgit; Nagel, Sarah; Talbi, El Hassan; El Hajraoui, Mohammed Abdeljalil; Amzazi, Saaïd; Hublin, Jean-Jacques; Pääbo, Svante; Schiffels, Stephan; Meyer, Matthias; Haak, Wolfgang; Jeong, Choongwon; Krause, Johannes

2018-05-04

North Africa is a key region for understanding human history, but the genetic history of its people is largely unknown. We present genomic data from seven 15,000-year-old modern humans, attributed to the Iberomaurusian culture, from Morocco. We find a genetic affinity with early Holocene Near Easterners, best represented by Levantine Natufians, suggesting a pre-agricultural connection between Africa and the Near East. We do not find evidence for gene flow from Paleolithic Europeans to Late Pleistocene North Africans. The Taforalt individuals derive one-third of their ancestry from sub-Saharan Africans, best approximated by a mixture of genetic components preserved in present-day West and East Africans. Thus, we provide direct evidence for genetic interactions between modern humans across Africa and Eurasia in the Pleistocene. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Pre-terrestrial origin of rust in the Nakhla meteorite

NASA Technical Reports Server (NTRS)

Wentworth, Susan J.; Gooding, James L.

1990-01-01

The authors present quantative elemental compositions and summarize textural evidence for the pre-terrestrial origin of rust on the Nakhla meteorite. The material in question is called 'rust' because its phase composition remains unknown. Compelling evidence for the pre-terrestrial origin of the rust is found in rust veins truncated by fusion crust and preserved as faults in sutured igneous crystals. Rust veins that approach the meteorite's fusion crust become discontinuous and exhibit vugs that suggest partial decrepitation; no veins that penetrate the fusion crust have been found. Because the rust probably contains volatile compounds, it is reasonable to expect that heating near the ablation surface (formed during atmospheric entry to Earth) would encourage devolatilization of the rust. Hence, the absence of rust veins in fusion crust and vugs in rust veins near fusion crust clearly imply that the rust existed in the meteorite before atmospheric entry.

Autoimmunity in narcolepsy.

PubMed

Bonvalet, Melodie; Ollila, Hanna M; Ambati, Aditya; Mignot, Emmanuel

2017-11-01

Summarize the recent findings in narcolepsy focusing on the environmental and genetic risk factors in disease development. Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Recent studies suggest both humoral and cellular immune responses in the disease development. Narcolepsy is a severe sleep disorder, in which neurons producing orexin/hypocretin in the hypothalamus are destroyed. The core symptoms of narcolepsy are debilitating, extreme sleepiness, cataplexy, and abnormalities in the structure of sleep. Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Importantly, the highest environmental risk is seen with influenza-A infection and immunization. However, how the cells are destroyed is currently unknown. In this review we summarize the disease symptoms, and focus on the immunological findings in narcolepsy. We also discuss the environmental and genetic risk factors as well as propose a model for disease development.

Physical and Mental Health Trajectories of Cancer Patients and Caregivers Across the Year Post-Diagnosis: A Dyadic Investigation

PubMed Central

Shaffer, Kelly M.; Kim, Youngmee; Carver, Charles S.

2016-01-01

Objective Evidence suggests interdependence between cancer patients’ and their caregivers’ physical and mental health. However, the extent to which caregivers’ health relates to their patients’ recovery, or patients’ health affects their caregivers’ outcomes, is largely unknown. This dyadic investigation reports the relations between cancer patients’ and their caregivers’ physical and mental health trajectories during the year following diagnosis. Design Ninety-two colorectal cancer patient-caregiver dyads completed questionnaires at two, six, and twelve months post-diagnosis. Outcome Measures Self-reported physical and mental health using the Medical Outcomes Study Short Form Health Survey-12. Results Patients reported improved physical health over the year following their diagnosis, whereas caregivers reported declining physical health. Patients with lower mental health at diagnosis had stagnated physical health recovery. Caregivers’ physical health declined most noticeably among those reporting low mental health at diagnosis and whose patients reported low physical health at diagnosis. Conclusion Findings suggest targeting health interventions to cancer patients and caregivers reporting poor mental health at diagnosis may mitigate their long-term physical morbidity. Limited evidence of dyadic interdependence between patients’ and caregivers’ physical and mental health trajectories suggests future studies are warranted to identify psychosocial and medical characteristics moderating the relations between patients’ and caregivers’ health. PMID:26680247

Inhibitors of endocytosis prevent Wnt/Wingless signalling by reducing the level of basal β-catenin/Armadillo.

PubMed

Gagliardi, Maria; Hernandez, Ana; McGough, Ian J; Vincent, Jean-Paul

2014-11-15

A key step in the canonical Wnt signalling pathway is the inhibition of GSK3β, which results in the accumulation of nuclear β-catenin (also known as CTNNB1), and hence regulation of target genes. Evidence suggests that endocytosis is required for signalling, yet its role and the molecular understanding remains unclear. A recent and controversial model suggests that endocytosis contributes to Wnt signalling by causing the sequestration of the ligand-receptor complex, including LRP6 and GSK3 to multivesicular bodies (MVBs), thus preventing GSK3β from accessing β-catenin. Here, we use specific inhibitors (Dynasore and Dyngo-4a) to confirm the essential role of endocytosis in Wnt/Wingless signalling in human and Drosophila cells. However, we find no evidence that, in Drosophila cells or wing imaginal discs, LRP6/Arrow traffics to MVBs or that MVBs are required for Wnt/Wingless signalling. Moreover, we show that activation of signalling through chemical blockade of GSK3β is prevented by endocytosis inhibitors, suggesting that endocytosis impacts on Wnt/Wingless signalling downstream of the ligand-receptor complex. We propose that, through an unknown mechanism, endocytosis boosts the resting pool of β-catenin upon which GSK3β normally acts. © 2014. Published by The Company of Biologists Ltd.

Is counter-terrorism policy evidence-based? What works, what harms, and what is unknown.

PubMed

Lum, Cynthia; Kennedy, Leslie W; Sherley, Alison

2008-02-01

Is counter-terrorism policy evidence-based? What works, what harms, and what is unknown. One of the central concerns surrounding counter-terrorism interventions today, given the attention and money spent on them, is whether such interventions are effective. To explore this issue, we conducted a general review of terrorism literature as well as a Campbell systematic review on counter-terrorism strategies. In this article, we summarize some of our findings from these works. Overall, we found an almost complete absence of evaluation research on counter-terrorism strategies and conclude that counter-terrorism policy is not evidence-based. The findings of this review emphasise the need for government leaders, policy makers, researchers, and funding agencies to include and insist on evaluations of the effectiveness of these programs in their agendas.

Striving for evidence-based practice innovations through a hybrid model journal club: A pilot study.

PubMed

Wilson, Marian; Ice, Suzanna; Nakashima, Cathy Y; Cox, Lynn Annette; Morse, Elizabeth C; Philip, Ginu; Vuong, Ellen

2015-05-01

The purpose of this study was to pilot a "hybrid" style journal club and determine whether measurable effects could be detected over 8-weeks' time on evidence-based practice ability, desire, behaviors, use, and barriers. Journal clubs have been suggested as a method to increase nurses' confidence with using research evidence to guide practice. However, it is yet unknown how nurse educators can best implement effective programs for clinicians with varying schedules, education levels, and research skills. Thirty-six participants from one large urban United States hospital (72% registered nurses) were invited to access bi-weekly interdisciplinary journal club activities. Nurse educators created curriculum focused on clinical problem solving that was offered via in-person sessions or a social media site. A pretest-posttest no control group design was used to measure impacts of those engaged in journal club activities. Data were collected using a combination of validated evidence-based practice instruments and program participation records. A two-tailed paired t test showed significant increases over 8weeks' time in evidence-based practice use (p=.002) and behaviors (p=.007). Slight preference for in-person sessions was reported, although greater participation was reflected in online activities. Mean satisfaction ratings were high; however, attrition rates suggest that more is needed to maximize clinician engagement. A hybrid method using online and in-person sessions was feasible and adaptive for varying learning styles and work schedules. Positive changes in measurements were detected among journal club participants. Instruments were identified that may be useful for trialing similar programs intended to increase evidence-based practice self-efficacy, use, behaviors, and ability. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association of Lutzomyia columbiana (Diptera: Psychodidae) with a leishmaniasis focus in Colombia due to species of the Leishmania mexicana complex.

PubMed

Montoya-Lerma, J; Cadena, H; Segura, I; Travi, B L

1999-01-01

In Colombia, Leishmania mexicana has a scattered geographical distribution and no sand fly vectors have been associated with its transmission. During the present study, the anthropophilic sand fly Lutzomyia columbiana was found to be the only species collected using diverse methods, in a small focus of Le. mexicana in the municipality of Samaniego, SW Colombia. Ecological data indicate that this sand fly species is present in both peri and intradomestic habitats, where it readily bites man. Further evidence comes from experimental infections of wild-caught Lu. columbiana with Le. mexicana after feeding on infected hamsters. Based on these results, it is suggested that this sand fly is the most likely vector in the study area, suggesting the existence of a previously unknown sand fly-parasite association.

Real-time quantification of xeroderma pigmentosum mRNA from the mammalian cochlea

PubMed Central

Guthrie, O'neil W.; Carrero-Martínez, Franklin A.

2010-01-01

Short Summary Xeroderma pigmentosum (XP) is a genetic disease that results in poor genomic defense from endogenous and exogenous stressors. Patients with mutations in the XPC and XPA genes exhibit cochlear hearing loss and to date, the underlying molecular mechanism is unknown. However, recent evidence suggests that the cochlea experiences persistent oxidative stress under normal conditions. In the current study, XPC and XPA gene products were purified from the cochlea and quantitative polymerase chain reaction was used to study the kinetics and magnitude of their expression. Additionally, immunohistochemistry was used to locate their respective polypeptides in the cochlea. The results revealed a significant demand for XP genes in the mammalian cochlea, which suggest that XP genomic defenses contribute in counterbalancing endogenous stress in the peripheral end-organ under normal conditions. PMID:20539233

Prevalence of and Factors Associated with the Use of HIV Serosorting and Other Biomedical Prevention Strategies Among Men Who Have Sex with Men in a US Nationwide Survey.

PubMed

Grov, Christian; Jonathan Rendina, H; Patel, Viraj V; Kelvin, Elizabeth; Anastos, Kathryn; Parsons, Jeffrey T

2018-03-17

PrEP and treatment-as-prevention (TasP) are biomedical strategies to reduce HIV transmission. Some men who have sex with men (MSM) are combining biomedical strategies with HIV serosorting-termed "biomed matching" when both partners are either on PrEP or TasP, or "biomed sorting" when one partner is using PrEP and the other TasP. Nevertheless, there is limited data on the extent of biomed matching/sorting in large geographically diverse samples. In 2016-2017, 5021 MSM from across the US were surveyed about their HIV status and HIV viral load/PrEP use, as well as that of their recent casual male partners. For each participant, we calculated the proportion of his partners who were (1) HIV-positive and undetectable, (2) HIV-positive and detectable/unknown, (3) HIV unknown/undiscussed, (4) HIV-negative on PrEP, (5) HIV-negative, not on PrEP. In total, 66.6% (n = 3346) of participants were HIV-negative and not on PrEP, 11.9% (n = 599) on PrEP, 14.1% (n = 707) HIV-positive and undetectable, 1.1% (n = 55) HIV-positive and viral load detectable/unknown, and 6.2% (n = 313) HIV unsure/unknown. A participant's own HIV and PrEP status/was significantly associated with that of his partners (all p < 0.001), evincing evidence of both serosorting and biomed matching. Among men on PrEP and those who were HIV-undetectable, there was also some evidence to suggest these participants dually engaged in biomed matching as well as biomed sorting. We found evidence of biomed matching and sorting, which may compound its effectiveness for those using it (i.e., both partners bring biomedical protection). Unintended consequences of biomed matching/sorting include that men not using a biomedical strategy may be less likely to benefit from a partner's use of the strategy-potentially further driving disparities in HIV infections. Public health campaigns might be well served to highlight not only the benefits that biomedical HIV prevention strategies provide for their users (e.g., "being on PrEP protects me from getting HIV"), but also the benefits that a user brings to his partners (e.g., "my use of PrEP means my partners won't get HIV"), and the benefits of being with a partner who is using a biomedical strategy (e.g., "my partner's use of PrEP/TasP protects me from HIV").

Telling in-tune from out-of-tune: widespread evidence for implicit absolute intonation.

PubMed

Van Hedger, Stephen C; Heald, Shannon L M; Huang, Alex; Rutstein, Brooke; Nusbaum, Howard C

2017-04-01

Absolute pitch (AP) is the rare ability to name or produce an isolated musical note without the aid of a reference note. One skill thought to be unique to AP possessors is the ability to provide absolute intonation judgments (e.g., classifying an isolated note as "in-tune" or "out-of-tune"). Recent work has suggested that absolute intonation perception among AP possessors is not crystallized in a critical period of development, but is dynamically maintained by the listening environment, in which the vast majority of Western music is tuned to a specific cultural standard. Given that all listeners of Western music are constantly exposed to this specific cultural tuning standard, our experiments address whether absolute intonation perception extends beyond AP possessors. We demonstrate that non-AP listeners are able to accurately judge the intonation of completely isolated notes. Both musicians and nonmusicians showed evidence for absolute intonation recognition when listening to familiar timbres (piano and violin). When testing unfamiliar timbres (triangle and inverted sine waves), only musicians showed weak evidence of absolute intonation recognition (Experiment 2). Overall, these results highlight a previously unknown similarity between AP and non-AP possessors' long-term musical note representations, including evidence of sensitivity to frequency.

Should dairy be recommended as part of a healthy vegetarian diet? Point.

PubMed

Weaver, Connie M

2009-05-01

A benefit-risk evaluation of the evidence for including dairy foods in the diet is presented. For many persons dairy products provide a substantial portion of essential nutrients, but especially calcium, potassium, and magnesium. Dietary supplements and fortified foods can be alternative sources of these nutrients, although other components of dairy foods such as amino acid composition and conjugated linoleic acid may be instrumental in the benefits associated with dairy product consumption for bone health and reduced risk of stroke, metabolic syndrome, and some cancers. Newer evidence shows that protein-induced calciuria does not have a detrimental effect on net calcium retention, and the concentrations of hormones in milk are not outside of the range of endogenous concentrations. Increased dietary protein, including from milk, can elevate serum concentrations of insulin-like growth factor I, which has an unknown relation to cancer. The concern over consumption of milk leading to increased risk of prostate cancer through reduction of serum 1,25-dihydroxyvitamin D, a potent anti-prostate cancer hormone, has been resolved with new evidence that local production of this hormone is independent of diet. Overall, evidence suggests that being a lactovegetarian has greater health benefits and reduced health risks than being a vegan.

The contribution of LM to the neuroscience of movement vision

PubMed Central

Zihl, Josef; Heywood, Charles A.

2015-01-01

The significance of early and sporadic reports in the 19th century of impairments of motion vision following brain damage was largely unrecognized. In the absence of satisfactory post-mortem evidence, impairments were interpreted as the consequence of a more general disturbance resulting from brain damage, the location and extent of which was unknown. Moreover, evidence that movement constituted a special visual perception and may be selectively spared was similarly dismissed. Such skepticism derived from a reluctance to acknowledge that the neural substrates of visual perception may not be confined to primary visual cortex. This view did not persist. First, it was realized that visual movement perception does not depend simply on the analysis of spatial displacements and temporal intervals, but represents a specific visual movement sensation. Second persuasive evidence for functional specialization in extrastriate cortex, and notably the discovery of cortical area V5/MT, suggested a separate region specialized for motion processing. Shortly thereafter the remarkable case of patient LM was published, providing compelling evidence for a selective and specific loss of movement vision. The case is reviewed here, along with an assessment of its contribution to visual neuroscience. PMID:25741251

Mechanisms of action of brief alcohol interventions remain largely unknown - a narrative review.

PubMed

Gaume, Jacques; McCambridge, Jim; Bertholet, Nicolas; Daeppen, Jean-Bernard

2014-01-01

A growing body of evidence has shown the efficacy of brief intervention (BI) for hazardous and harmful alcohol use in primary health care settings. Evidence for efficacy in other settings and effectiveness when implemented at larger scale are disappointing. Indeed, BI comprises varying content; exploring BI content and mechanisms of action may be a promising way to enhance efficacy and effectiveness. Medline and PsychInfo, as well as references of retrieved publications were searched for original research or review on active ingredients (components or mechanisms) of face-to-face BIs [and its subtypes, including brief advice and brief motivational interviewing (BMI)] for alcohol. Overall, BI active ingredients have been scarcely investigated, almost only within BMI, and mostly among patients in the emergency room, young adults, and US college students. This body of research has shown that personalized feedback may be an effective component; specific MI techniques showed mixed findings; decisional balance findings tended to suggest a potential detrimental effect; while change plan exercises, advice to reduce or stop drinking, presenting alternative change options, and moderation strategies are promising but need further study. Client change talk is a potential mediator of BMI effects; change in norm perceptions and enhanced discrepancy between current behavior and broader life goals and values have received preliminary support; readiness to change was only partially supported as a mediator; while enhanced awareness of drinking, perceived risks/benefits of alcohol use, alcohol treatment seeking, and self-efficacy were seldom studied and have as yet found no significant support as such. Research is obviously limited and has provided no clear and consistent evidence on the mechanisms of alcohol BI. How BI achieves the effects seen in randomized trials remains mostly unknown and should be investigated to inform the development of more effective interventions.

Laterodorsal Nucleus of the Thalamus: A Processor of Somatosensory Inputs

PubMed Central

BEZDUDNAYA, TATIANA; KELLER, ASAF

2009-01-01

The laterodorsal (LD) nucleus of the thalamus has been considered a “higher order” nucleus that provides inputs to limbic cortical areas. Although its functions are largely unknown, it is often considered to be involved in spatial learning and memory. Here we provide evidence that LD is part of a hitherto unknown pathway for processing somatosensory information. Juxtacellular and extracellular recordings from LD neurons reveal that they respond to vibrissa stimulation with short latency (median = 7 ms) and large magnitude responses (median = 1.2 spikes/stimulus). Most neurons (62%) had large receptive fields, responding to six and more individual vibrissae. Electrical stimulation of the trigeminal nucleus interpolaris (SpVi) evoked short latency responses (median = 3.8 ms) in vibrissa-responsive LD neurons. Labeling produced by anterograde and retrograde neuroanatomical tracers confirmed that LD neurons receive direct inputs from SpVi. Electrophysiological and neuroanatomical analyses revealed also that LD projects upon the cingulate and retrosplenial cortex, but has only sparse projections to the barrel cortex. These findings suggest that LD is part of a novel processing stream involved in spatial orientation and learning related to somatosensory cues. PMID:18273888

Clinical implications of basic science discoveries: nociceptive neurons as targets to control immunity--potential relevance for transplantation.

PubMed

Larregina, A T; Divito, S J; Morelli, A E

2015-06-01

Increasing evidence indicates the existence of a complex cross-regulation between the most important biosensors of the human body: The immune and nervous systems. Cytokines control body temperature and trigger autoimmune disorders in the central nervous system, whereas neuropeptides released in peripheral tissues and lymphoid organs modulate inflammatory (innate) and adaptive immune responses. Surprisingly, the effects of nerve fibers and the antidromic release of its pro-inflammatory neuropeptides on the leukocytes of the immune system that mediate graft rejection are practically unknown. In the transplantation field, such area of research remains practically unexplored. A recent study by Riol-Blanco et al has revealed new details on how nociceptive nerves regulate the pro-inflammatory function of leukocytes in peripheral tissues. Although the mechanism(s) by which neuroinflammation affects the immune response against the allograft remains unknown, recent data suggest that this new area of research is worth exploring for potential development of novel complementary therapies for prevention/treatment of graft rejection. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Botulinum neurotoxin type A: Actions beyond SNAP-25?

PubMed

Matak, Ivica; Lacković, Zdravko

2015-09-01

Botulinum neurotoxin type A (BoNT/A), the most potent toxin known in nature which causes botulism, is a commonly used therapeutic protein. It prevents synaptic vesicle neuroexocytosis by proteolytic cleavage of synaptosomal-associated protein of 25 kDa (SNAP-25). It is widely believed that BoNT/A therapeutic or toxic actions are exclusively mediated by SNAP-25 cleavage. On the other hand, in vitro and in vivo findings suggest that several BoNT/A actions related to neuroexocytosis, cell cycle and apoptosis, neuritogenesis and gene expression are not necessarily mediated by this widely accepted mechanism of action. In present review we summarize the literature evidence which point to the existence of unknown BoNT/A molecular target(s) and modulation of unknown signaling pathways. The effects of BoNT/A apparently independent of SNAP-25 occur at similar doses/concentrations known to induce SNAP-25 cleavage and prevention of neurotransmitter release. Accordingly, these effects might be pharmacologically significant. Potentially the most interesting are observations of antimitotic and antitumor activity of BoNT/A. However, the exact mechanisms require further studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Early human symbolic behavior in the Late Pleistocene of Wallacea

PubMed Central

Brumm, Adam; Hakim, Budianto; Ramli, Muhammad; Sumantri, Iwan; Burhan, Basran; Saiful, Andi Muhammad; Siagian, Linda; Suryatman; Sardi, Ratno; Jusdi, Andi; Abdullah; Mubarak, Andi Pampang; Hasliana; Hasrianti; Oktaviana, Adhi Agus; Adhityatama, Shinatria; van den Bergh, Gerrit D.; Aubert, Maxime; Zhao, Jian-xin; Huntley, Jillian; Li, Bo; Roberts, Richard G.; Saptomo, E. Wahyu; Perston, Yinika; Grün, Rainer

2017-01-01

Wallacea, the zone of oceanic islands separating the continental regions of Southeast Asia and Australia, has yielded sparse evidence for the symbolic culture of early modern humans. Here we report evidence for symbolic activity 30,000–22,000 y ago at Leang Bulu Bettue, a cave and rock-shelter site on the Wallacean island of Sulawesi. We describe hitherto undocumented practices of personal ornamentation and portable art, alongside evidence for pigment processing and use in deposits that are the same age as dated rock art in the surrounding karst region. Previously, assemblages of multiple and diverse types of Pleistocene “symbolic” artifacts were entirely unknown from this region. The Leang Bulu Bettue assemblage provides insight into the complexity and diversification of modern human culture during a key period in the global dispersal of our species. It also shows that early inhabitants of Sulawesi fashioned ornaments from body parts of endemic animals, suggesting modern humans integrated exotic faunas and other novel resources into their symbolic world as they colonized the biogeographically unique regions southeast of continental Eurasia. PMID:28373568

Early human symbolic behavior in the Late Pleistocene of Wallacea.

PubMed

Brumm, Adam; Langley, Michelle C; Moore, Mark W; Hakim, Budianto; Ramli, Muhammad; Sumantri, Iwan; Burhan, Basran; Saiful, Andi Muhammad; Siagian, Linda; Suryatman; Sardi, Ratno; Jusdi, Andi; Abdullah; Mubarak, Andi Pampang; Hasliana; Hasrianti; Oktaviana, Adhi Agus; Adhityatama, Shinatria; van den Bergh, Gerrit D; Aubert, Maxime; Zhao, Jian-Xin; Huntley, Jillian; Li, Bo; Roberts, Richard G; Saptomo, E Wahyu; Perston, Yinika; Grün, Rainer

2017-04-18

Wallacea, the zone of oceanic islands separating the continental regions of Southeast Asia and Australia, has yielded sparse evidence for the symbolic culture of early modern humans. Here we report evidence for symbolic activity 30,000-22,000 y ago at Leang Bulu Bettue, a cave and rock-shelter site on the Wallacean island of Sulawesi. We describe hitherto undocumented practices of personal ornamentation and portable art, alongside evidence for pigment processing and use in deposits that are the same age as dated rock art in the surrounding karst region. Previously, assemblages of multiple and diverse types of Pleistocene "symbolic" artifacts were entirely unknown from this region. The Leang Bulu Bettue assemblage provides insight into the complexity and diversification of modern human culture during a key period in the global dispersal of our species. It also shows that early inhabitants of Sulawesi fashioned ornaments from body parts of endemic animals, suggesting modern humans integrated exotic faunas and other novel resources into their symbolic world as they colonized the biogeographically unique regions southeast of continental Eurasia.

fMRI evidence for a dual process account of the speed-accuracy tradeoff in decision-making.

PubMed

Ivanoff, Jason; Branning, Philip; Marois, René

2008-07-09

The speed and accuracy of decision-making have a well-known trading relationship: hasty decisions are more prone to errors while careful, accurate judgments take more time. Despite the pervasiveness of this speed-accuracy trade-off (SAT) in decision-making, its neural basis is still unknown. Using functional magnetic resonance imaging (fMRI) we show that emphasizing the speed of a perceptual decision at the expense of its accuracy lowers the amount of evidence-related activity in lateral prefrontal cortex. Moreover, this speed-accuracy difference in lateral prefrontal cortex activity correlates with the speed-accuracy difference in the decision criterion metric of signal detection theory. We also show that the same instructions increase baseline activity in a dorso-medial cortical area involved in the internal generation of actions. These findings suggest that the SAT is neurally implemented by modulating not only the amount of externally-derived sensory evidence used to make a decision, but also the internal urge to make a response. We propose that these processes combine to control the temporal dynamics of the speed-accuracy trade-off in decision-making.

Emotional Relationships between Mothers* and Infants: Knowns, Unknowns, and Unknown Unknowns

PubMed Central

Bornstein, Marc H.; Suwalsky, Joan T. D.; Breakstone, Dana A.

2012-01-01

An overview of the literature pertaining to the construct of emotional availability is presented, illustrated by a sampling of relevant studies. Methodological, statistical, and conceptual problems in the existing corpus of research are discussed, and suggestions for improving future investigations of this important construct are offered. PMID:22292998

Genomic Evidence of Widespread Admixture from Polar Bears into Brown Bears during the Last Ice Age.

PubMed

Cahill, James A; Heintzman, Peter D; Harris, Kelley; Teasdale, Matthew D; Kapp, Joshua; Soares, Andre E R; Stirling, Ian; Bradley, Daniel; Edwards, Ceiridwen J; Graim, Kiley; Kisleika, Aliaksandr A; Malev, Alexander V; Monaghan, Nigel; Green, Richard E; Shapiro, Beth

2018-05-01

Recent genomic analyses have provided substantial evidence for past periods of gene flow from polar bears (Ursus maritimus) into Alaskan brown bears (Ursus arctos), with some analyses suggesting a link between climate change and genomic introgression. However, because it has mainly been possible to sample bears from the present day, the timing, frequency, and evolutionary significance of this admixture remains unknown. Here, we analyze genomic DNA from three additional and geographically distinct brown bear populations, including two that lived temporally close to the peak of the last ice age. We find evidence of admixture in all three populations, suggesting that admixture between these species has been common in their recent evolutionary history. In addition, analyses of ten fossil bears from the now-extinct Irish population indicate that admixture peaked during the last ice age, whereas brown bear and polar bear ranges overlapped. Following this peak, the proportion of polar bear ancestry in Irish brown bears declined rapidly until their extinction. Our results support a model in which ice age climate change created geographically widespread conditions conducive to admixture between polar bears and brown bears, as is again occurring today. We postulate that this model will be informative for many admixing species pairs impacted by climate change. Our results highlight the power of paleogenomics to reveal patterns of evolutionary change that are otherwise masked in contemporary data.

Effective physical treatment for chronic low back pain.

PubMed

Maher, C G

2004-01-01

It is now feasible to adopt an evidence-based approach when providing physical treatment for patients with chronic LBP. A summary of the efficacy of a range of physical treatments is provided in Table 1. The evidence-based primary care options are exercise, laser, massage, and spinal manipulation; however, the latter three have small or transient effects that limit their value as therapies for chronic LBP. In contrast, exercise produces large reductions in pain and disability, a feature that suggests that exercise should play a major role in the management of chronic LBP. Physical treatments, such as acupuncture, backschool, hydrotherapy, lumbar supports, magnets, TENS, traction, ultrasound, Pilates therapy, Feldenkrais therapy, Alexander technique, and craniosacral therapy are either of unknown value or ineffective and so should not be considered. Outside of primary care, multidisciplinary treatment or functional restoration is effective; however, the high cost probably means that these programs should be reserved for patients who do not respond to cheaper treatment options for chronic LBP. Although there are now effective treatment options for chronic LBP, it needs to be acknowledged that the problem of chronic LBP is far from solved. Though treatments can provide marked improvements in the patient's condition, the available evidence suggests that the typical chronic LBP patient is left with some residual pain and disability. Developing new, more powerful treatments and refining the current group of known effective treatments is the challenge for the future.

Exogenous testosterone affects early threat processing in socially anxious and healthy women.

PubMed

van Peer, Jacobien M; Enter, Dorien; van Steenbergen, Henk; Spinhoven, Philip; Roelofs, Karin

2017-10-01

Testosterone plays an important role in social threat processing. Recent evidence suggests that testosterone administration has socially anxiolytic effects, but it remains unknown whether this involves early vigilance or later, more sustained, processing-stages. We investigated the acute effects of testosterone administration on social threat processing in 19 female patients with Social Anxiety Disorder (SAD) and 19 healthy controls. Event-related potentials (ERPs) were recorded during an emotional Stroop task with subliminally presented faces. Testosterone induced qualitative changes in early ERPs (<200ms after stimulus onset) in both groups. An initial testosterone-induced spatial shift reflected a change in the basic processing (N170/VPP) of neutral faces, which was followed by a shift for angry faces suggesting a decrease in early threat bias. These findings suggest that testosterone specifically affects early automatic social information processing. The decreased attentional bias for angry faces explains how testosterone can decrease threat avoidance, which is particularly relevant for SAD. Copyright © 2017 Elsevier B.V. All rights reserved.

Na+/K+ ATPase regulates the expression and localization of acetylcholine receptors in a pump activity-independent manner

PubMed Central

Doi, Motomichi; Iwasaki, Kouichi

2008-01-01

Na+/K+ ATPase is a plasma membrane-localized sodium pump that maintains the ion gradients between the extracellular and intracellular environments, which in turn controls the cellular resting membrane potential. Recent evidence suggests that the pump is also localized at synapses and regulates synaptic efficacy. However, its precise function at the synapse is unknown. Here we show that two mutations in the α subunit of the eat-6 Na+/K+ ATPase in Caenorhabditis elegans dramatically increase the sensitivity to acetylcholine (Ach) agonists and alter the localization of nicotinic Ach receptors at the neuromuscular junction (NMJ). These defects can be rescued by mutated EAT-6 proteins which lack its pump activity, suggesting the presence of a novel function for Ach signaling. The Na+/K+ ATPase accumulates at postsynaptic sites and appears to surround Ach receptors to maintain rigid clusters at the NMJ. Our findings suggest a critical pump activity-independent, allele –specific role for Na+/K+ ATPase on postsynaptic organization and synaptic efficacy. PMID:18599311

Meta-analysis suggests choosy females get sexy sons more than "good genes".

PubMed

Prokop, Zofia M; Michalczyk, Łukasz; Drobniak, Szymon M; Herdegen, Magdalena; Radwan, Jacek

2012-09-01

Female preferences for specific male phenotypes have been documented across a wide range of animal taxa, including numerous species where males contribute only gametes to offspring production. Yet, selective pressures maintaining such preferences are among the major unknowns of evolutionary biology. Theoretical studies suggest that preferences can evolve if they confer genetic benefits in terms of increased attractiveness of sons ("Fisherian" models) or overall fitness of offspring ("good genes" models). These two types of models predict, respectively, that male attractiveness is heritable and genetically correlated with fitness. In this meta-analysis, we draw general conclusions from over two decades worth of empirical studies testing these predictions (90 studies on 55 species in total). We found evidence for heritability of male attractiveness. However, attractiveness showed no association with traits directly associated with fitness (life-history traits). Interestingly, it did show a positive correlation with physiological traits, which include immunocompetence and condition. In conclusion, our results support "Fisherian" models of preference evolution, while providing equivocal evidence for "good genes." We pinpoint research directions that should stimulate progress in our understanding of the evolution of female choice. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

The physics, biology, and environmental ethics of making mars habitable.

PubMed

McKay, C P; Marinova, M M

2001-01-01

The considerable evidence that Mars once had a wetter, more clement, environment motivates the search for past or present life on that planet. This evidence also suggests the possibility of restoring habitable conditions on Mars. While the total amounts of the key molecules--carbon dioxide, water, and nitrogen--needed for creating a biosphere on Mars are unknown, estimates suggest that there may be enough in the subsurface. Super greenhouse gases, in particular, perfluorocarbons, are currently the most effective and practical way to warm Mars and thicken its atmosphere so that liquid water is stable on the surface. This process could take approximately 100 years. If enough carbon dioxide is frozen in the South Polar Cap and absorbed in the regolith, the resulting thick and warm carbon dioxide atmosphere could support many types of microorganisms, plants, and invertebrates. If a planet-wide martian biosphere converted carbon dioxide into oxygen with an average efficiency equal to that for Earth's biosphere, it would take > 100,000 years to create Earth-like oxygen levels. Ethical issues associated with bringing life to Mars center on the possibility of indigenous martian life and the relative value of a planet with or without a global biosphere.

The physics, biology, and environmental ethics of making mars habitable

NASA Technical Reports Server (NTRS)

McKay, C. P.; Marinova, M. M.

2001-01-01

The considerable evidence that Mars once had a wetter, more clement, environment motivates the search for past or present life on that planet. This evidence also suggests the possibility of restoring habitable conditions on Mars. While the total amounts of the key molecules--carbon dioxide, water, and nitrogen--needed for creating a biosphere on Mars are unknown, estimates suggest that there may be enough in the subsurface. Super greenhouse gases, in particular, perfluorocarbons, are currently the most effective and practical way to warm Mars and thicken its atmosphere so that liquid water is stable on the surface. This process could take approximately 100 years. If enough carbon dioxide is frozen in the South Polar Cap and absorbed in the regolith, the resulting thick and warm carbon dioxide atmosphere could support many types of microorganisms, plants, and invertebrates. If a planet-wide martian biosphere converted carbon dioxide into oxygen with an average efficiency equal to that for Earth's biosphere, it would take > 100,000 years to create Earth-like oxygen levels. Ethical issues associated with bringing life to Mars center on the possibility of indigenous martian life and the relative value of a planet with or without a global biosphere.

Mammalian FMRP S499 Is Phosphorylated by CK2 and Promotes Secondary Phosphorylation of FMRP.

PubMed

Bartley, Christopher M; O'Keefe, Rachel A; Blice-Baum, Anna; Mihailescu, Mihaela-Rita; Gong, Xuan; Miyares, Laura; Karaca, Esra; Bordey, Angélique

2016-01-01

The fragile X mental retardation protein (FMRP) is an mRNA-binding regulator of protein translation that associates with 4-6% of brain transcripts and is central to neurodevelopment. Autism risk genes' transcripts are overrepresented among FMRP-binding mRNAs, and FMRP loss-of-function mutations are responsible for fragile X syndrome, the most common cause of monogenetic autism. It is thought that FMRP-dependent translational repression is governed by the phosphorylation of serine residue 499 (S499). However, recent evidence suggests that S499 phosphorylation is not modulated by metabotropic glutamate receptor class I (mGluR-I) or protein phosphatase 2A (PP2A), two molecules shown to regulate FMRP translational repression. Moreover, the mammalian FMRP S499 kinase remains unknown. We found that casein kinase II (CK2) phosphorylates murine FMRP S499. Further, we show that phosphorylation of FMRP S499 permits phosphorylation of additional, nearby residues. Evidence suggests that these nearby residues are modulated by mGluR-I and PP2A pathways. These data support an alternative phosphodynamic model of FMRP that is harmonious with prior studies and serves as a framework for further investigation.

Driver Cellphone and Texting Bans in the United States: Evidence of Effectiveness

PubMed Central

McCartt, Anne T.; Kidd, David G.; Teoh, Eric R.

2014-01-01

Almost all U.S. states have laws limiting drivers’ cellphone use. The evidence suggests that all-driver bans on hand-held phone conversations have resulted in long-term reductions in hand-held phone use, and drivers in ban states reported higher rates of hands-free phone use and lower overall phone use compared with drivers in non-ban states. Bans on all phone use by teenage drivers have not been shown to reduce their phone use. The effects of texting bans on the rates of drivers’ texting are unknown. With regard to the effects of bans on crashes, 11 peer-reviewed papers or technical reports of all-driver hand-held phone bans and texting bans were reviewed. Some were single-state studies examining crash measures before and after a state ban; other national or multi-state studies compared crashes in states with and without bans over time. The results varied widely. The lack of appropriate controls and other challenges in conducting strong evaluations limited the findings of some studies. Thus, despite the proliferation of laws limiting drivers’ cellphone use, it is unclear whether they are having the desired effects on safety. Priorities for future research are suggested. PMID:24776230

Evidence for the Initial Steps of DHA Biohydrogenation by Mixed Ruminal Microorganisms from Sheep Involves Formation of Conjugated Fatty Acids.

PubMed

Aldai, Noelia; Delmonte, Pierluigi; Alves, Susana P; Bessa, Rui J B; Kramer, John K G

2018-01-31

Incubation of DHA with sheep rumen fluid resulted in 80% disappearance in 6 h. The products were analyzed as their fatty acid (FA) methyl esters by GC-FID on SP-2560 and SLB-IL111 columns. The GC-online reduction × GC and GC-MS techniques demonstrated that all DHA metabolites retained the C22 structure (no evidence of chain-shortening). Two new transient DHA products were identified: mono-trans methylene interrupted-DHA and monoconjugated DHA (MC-DHA) isomers. Identification of MC-DHA was confirmed by their predicted elution using equivalent chain length differences from C18 FA, their molecular ions, and the 22:5 products formed which were the most abundant at 6 h. The 22:5 structures were established by fragmentation of their 4,4-dimethyloxazoline derivatives, and all 22:5 products contained an isolated double bond, suggesting formation via MC-DHA. The most abundant c4,c7,c10,t14,c19-22:5 appeared to be formed by unknown isomerases. Results suggest that the initial biohydrogenation of DHA was analogous to that of C18 FA.

Calcium transient prevalence across the dendritic arbour predicts place field properties.

PubMed

Sheffield, Mark E J; Dombeck, Daniel A

2015-01-08

Establishing the hippocampal cellular ensemble that represents an animal's environment involves the emergence and disappearance of place fields in specific CA1 pyramidal neurons, and the acquisition of different spatial firing properties across the active population. While such firing flexibility and diversity have been linked to spatial memory, attention and task performance, the cellular and network origin of these place cell features is unknown. Basic integrate-and-fire models of place firing propose that such features result solely from varying inputs to place cells, but recent studies suggest instead that place cells themselves may play an active role through regenerative dendritic events. However, owing to the difficulty of performing functional recordings from place cell dendrites, no direct evidence of regenerative dendritic events exists, leaving any possible connection to place coding unknown. Using multi-plane two-photon calcium imaging of CA1 place cell somata, axons and dendrites in mice navigating a virtual environment, here we show that regenerative dendritic events do exist in place cells of behaving mice, and, surprisingly, their prevalence throughout the arbour is highly spatiotemporally variable. Furthermore, we show that the prevalence of such events predicts the spatial precision and persistence or disappearance of place fields. This suggests that the dynamics of spiking throughout the dendritic arbour may play a key role in forming the hippocampal representation of space.

Electronic Nicotine Delivery Systems (“E-Cigarettes”): Review of Safety and Smoking Cessation Efficacy

PubMed Central

Harrell, Paul Truman; Simmons, Vani Nath; Correa, John Bernard; Padhya, Tapan Ashvin; Brandon, Thomas Henry

2015-01-01

Background and Objectives Cigarette smoking is common among cancer patients and is associated with negative outcomes. Electronic nicotine delivery systems (“e-cigarettes”) are rapidly growing in popularity and use, but there is limited information on their safety or effectiveness in helping individuals quit smoking. Data Sources The authors searched PubMed, Web of Science, and additional sources for published empirical data on safety and use of electronic cigarettes as an aid to quit smoking. Review Methods We conducted a structured search of the current literature up to and including November 2013. Results E-cigarettes currently vary widely in their contents and are sometimes inconsistent with labeling. Compared to tobacco cigarettes, available evidence suggests that e-cigarettes are often substantially lower in toxic content, cytotoxicity, associated adverse effects, and secondhand toxicity exposure. Data on the use of e-cigarettes for quitting smoking is suggestive, but ultimately inconclusive. Conclusions Clinicians are advised to be aware that the use of e-cigarettes, especially among cigarette smokers, is growing rapidly. These devices are unregulated, of unknown safety, and of uncertain benefit in quitting smoking. Implications for Practice In the absence of further data or regulation, oncologists are advised to discuss the known and unknown safety and efficacy information on e-cigarettes with interested patients, and to encourage patients to first try FDA-approved pharmacotherapies for smoking cessation. PMID:24898072

Electronic nicotine delivery systems ("e-cigarettes"): review of safety and smoking cessation efficacy.

PubMed

Harrell, Paul Truman; Simmons, Vani Nath; Correa, John Bernard; Padhya, Tapan Ashvin; Brandon, Thomas Henry

2014-09-01

Cigarette smoking is common among cancer patients and is associated with negative outcomes. Electronic nicotine delivery systems ("e-cigarettes") are rapidly growing in popularity and use, but there is limited information on their safety or effectiveness in helping individuals quit smoking. The authors searched PubMed, Web of Science, and additional sources for published empirical data on safety and use of electronic cigarettes as an aid to quit smoking. We conducted a structured search of the current literature up to and including November 2013. E-cigarettes currently vary widely in their contents and are sometimes inconsistent with labeling. Compared to tobacco cigarettes, available evidence suggests that e-cigarettes are often substantially lower in toxic content, cytotoxicity, associated adverse effects, and secondhand toxicity exposure. Data on the use of e-cigarettes for quitting smoking are suggestive but ultimately inconclusive. Clinicians are advised to be aware that the use of e-cigarettes, especially among cigarette smokers, is growing rapidly. These devices are unregulated, of unknown safety, and of uncertain benefit in quitting smoking. In the absence of further data or regulation, oncologists are advised to discuss the known and unknown safety and efficacy information on e-cigarettes with interested patients and to encourage patients to first try FDA-approved pharmacotherapies for smoking cessation. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Calcium transient prevalence across the dendritic arbor predicts place field properties

PubMed Central

Sheffield, Mark E. J.; Dombeck, Daniel A.

2014-01-01

Establishing the hippocampal cellular ensemble that represents an animal’s environment involves the emergence and disappearance of place fields in specific CA1 pyramidal neurons1–4, and the acquisition of different spatial firing properties across the active population5. While such firing flexibility and diversity have been linked to spatial memory, attention and task performance6,7, the cellular and network origin of these place cell features is unknown. Basic integrate-and-fire models of place firing propose that such features result solely from varying inputs to place cells8,9, but recent studies3,10 instead suggest that place cells themselves may play an active role through regenerative dendritic events. However, due to the difficulty of performing functional recordings from place cell dendrites, no direct evidence of regenerative dendritic events exists, leaving any possible connection to place coding unknown. Using multi-plane two-photon calcium imaging of CA1 place cell somata, axons, and dendrites in mice navigating a virtual environment, we show that regenerative dendritic events do exist in place cells of behaving mice and, surprisingly, their prevalence throughout the arbor is highly spatiotemporally variable. Further, we show that the prevalence of such events predicts the spatial precision and persistence or disappearance of place fields. This suggests that the dynamics of spiking throughout the dendritic arbor may play a key role in forming the hippocampal representation of space. PMID:25363782

Previously unknown and highly divergent ssDNA viruses populate the oceans.

PubMed

Labonté, Jessica M; Suttle, Curtis A

2013-11-01

Single-stranded DNA (ssDNA) viruses are economically important pathogens of plants and animals, and are widespread in oceans; yet, the diversity and evolutionary relationships among marine ssDNA viruses remain largely unknown. Here we present the results from a metagenomic study of composite samples from temperate (Saanich Inlet, 11 samples; Strait of Georgia, 85 samples) and subtropical (46 samples, Gulf of Mexico) seawater. Most sequences (84%) had no evident similarity to sequenced viruses. In total, 608 putative complete genomes of ssDNA viruses were assembled, almost doubling the number of ssDNA viral genomes in databases. These comprised 129 genetically distinct groups, each represented by at least one complete genome that had no recognizable similarity to each other or to other virus sequences. Given that the seven recognized families of ssDNA viruses have considerable sequence homology within them, this suggests that many of these genetic groups may represent new viral families. Moreover, nearly 70% of the sequences were similar to one of these genomes, indicating that most of the sequences could be assigned to a genetically distinct group. Most sequences fell within 11 well-defined gene groups, each sharing a common gene. Some of these encoded putative replication and coat proteins that had similarity to sequences from viruses infecting eukaryotes, suggesting that these were likely from viruses infecting eukaryotic phytoplankton and zooplankton.

Photocopy of photograph. Photographer unknown. Typical suggestion award photograph from ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photocopy of photograph. Photographer unknown. Typical suggestion award photograph from the World War II period. Useful suggestions were awarded a $ 50 bond and usually a photo in the shipyard newspaper, the beacon. This photo shows an improved bilge block template layout table left to right: Stuart S. Sanders, Rosalie Moschella, Eddie Ormond, Lt. CDR. J.M. Ballinger, and A.A. Goldman. - Naval Base Philadelphia-Philadelphia Naval Shipyard, League Island, Philadelphia, Philadelphia County, PA

Evaluation of the Green Dot Bystander Intervention to Reduce Interpersonal Violence Among College Students Across Three Campuses.

PubMed

Coker, Ann L; Fisher, Bonnie S; Bush, Heather M; Swan, Suzanne C; Williams, Corrine M; Clear, Emily R; DeGue, Sarah

2015-12-01

Evidence suggests that interventions to engage bystanders in violence prevention increase bystander intentions and efficacy to intervene, yet the impact of such programs on violence remains unknown. This study compared rates of violence by type among undergraduate students attending a college campus with the Green Dot bystander intervention (n = 2,768) with students at two colleges without bystander programs (n = 4,258). Violent victimization rates were significantly (p < .01) lower among students attending the campus with Green Dot relative to the two comparison campuses. Violence perpetration rates were lower among males attending the intervention campus. Implications of these results for research and practice are discussed. © The Author(s) 2014.

Bacterial avirulence genes.

PubMed

Leach, J E; White, F F

1996-01-01

Although more than 30 bacterial avirulence genes have been cloned and characterized, the function of the gene products in the elictitation of resistance is unknown in all cases but one. The product of avrD from Pseudomonas syringae pv. glycinea likely functions indirectly to elicit resistance in soybean, that is, evidence suggests the gene product is an enzyme involved in elicitor production. In most if not all cases, bacterial avirulence gene function is dependent on interactions with the hypersensitive response and pathogenicity (hrp) genes. Many hrp genes are similar to genes involved in delivery of pathogenicity factors in mammalian bacterial pathogens. Thus, analogies between mammalian and plant pathogens may provide needed clues to elucidate how virulence gene products control induction of resistance.

Evaluation of the Green Dot Bystander Intervention to Reduce Interpersonal Violence Among College Students Across Three Campuses

PubMed Central

Coker, Ann L.; Fisher, Bonnie S.; Bush, Heather M.; Swan, Suzanne C.; Williams, Corrine M.; Clear, Emily R.; DeGue, Sarah

2018-01-01

Evidence suggests that interventions to engage bystanders in violence prevention increase bystander intentions and efficacy to intervene, yet the impact of such programs on violence remains unknown. This study compared rates of violence by type among undergraduate students attending a college campus with the Green Dot bystander intervention (n = 2,768) with students at two colleges without bystander programs (n = 4,258). Violent victimization rates were significantly (p < .01) lower among students attending the campus with Green Dot relative to the two comparison campuses. Violence perpetration rates were lower among males attending the intervention campus. Implications of these results for research and practice are discussed. PMID:25125493

Efficacy of high-dose intravenous immunoglobulins in two patients with idiopathic recurrent pericarditis refractory to previous immunosuppressive treatment.

PubMed

Tona, Francesco; Bellotto, Fabio; Laveder, Francesco; Meneghin, Alessia; Sinagra, Gianfranco; Marcolongo, Renzo

2003-01-01

Although idiopathic acute pericarditis is usually a self-limiting disease, in many patients it may recur over a period of months or years. Even if some evidence seems to suggest the possible role of a deranged immune reactivity in the pathogenesis of idiopathic recurrent pericarditis, the etiology of the disease is still unknown. Furthermore, while some trial data confirm the usefulness of colchicine, its medical treatment is not yet clearly established. We here report the clinical history of 2 patients with idiopathic recurrent pericarditis resistant to prednisone, colchicine and other immunosuppressive drugs, who have been successfully treated with high-dose intravenous immunoglobulins.

Kinematic diversity suggests expanded roles for fly halteres

PubMed Central

Hall, Joshua M.; McLoughlin, Dane P.; Kathman, Nicholas D.; Yarger, Alexandra M.; Mureli, Shwetha; Fox, Jessica L.

2015-01-01

The halteres of flies are mechanosensory organs that provide information about body rotations during flight. We measured haltere movements in a range of fly taxa during free walking and tethered flight. We find a diversity of wing–haltere phase relationships in flight, with higher variability in more ancient families and less in more derived families. Diverse haltere movements were observed during free walking and were correlated with phylogeny. We predicted that haltere removal might decrease behavioural performance in those flies that move them during walking and provide evidence that this is the case. Our comparative approach reveals previously unknown diversity in haltere movements and opens the possibility of multiple functional roles for halteres in different fly behaviours. PMID:26601682

Prosecutors' Perspectives on Biological Evidence and Injury Evidence in Sexual Assault Cases.

PubMed

Alderden, Megan; Cross, Theodore P; Vlajnic, Maja; Siller, Laura

2018-06-01

Little prior research has explored how prosecutors perceive and utilize biological and injury evidences in sexual assault cases. In this qualitative study, semistructured interviews were conducted with assistant district attorneys (ADAs) working in an urban district attorney's office in the northeastern United States. ADAs were asked to describe how biological and injury evidences could be probative and their strategies for using this evidence. The interviews suggest that prosecutors perceive the probative value of biological and injury evidences on a continuum, varying based on case characteristics. Prosecutors felt that undergoing a forensic medical examination in itself supported victims' credibility. Biological evidence bolstered victims' credibility if it matched the victim's account better than the defendant's. They perceived DNA evidence as helpful when it identified unknown suspects, confirmed identification of suspects by other means, or rebutted defendants' denial of sexual contact. DNA evidence was also helpful when victims were incapacitated, too traumatized to recall or talk about the assault, or too young to identify assailants, and when police used the information in interrogating suspects. The biggest limitation to biological evidence prosecutors cited was overcoming the consent defense. The ADAs reported they used DNA evidence even when it was not particularly probative, because it confirms the correct person is being prosecuted, it communicates the victim's and prosecution's seriousness, and it meets jury expectations in trials. Prosecutors found injury evidence useful because it corroborated victims' accounts and helped refute defendant claims of consensual sex. The findings may assist in educating others about biological and injury evidences in these cases, and could inspire professionals and advocates to work to develop and support a broad range of investigative methods.

Natural Tendency towards Beauty in Humans: Evidence from Binocular Rivalry.

PubMed

Mo, Ce; Xia, Tiansheng; Qin, Kaixin; Mo, Lei

2016-01-01

Although human preference for beauty is common and compelling in daily life, it remains unknown whether such preference is essentially subserved by social cognitive demands or natural tendency towards beauty encoded in the human mind intrinsically. Here we demonstrate experimentally that humans automatically exhibit preference for visual and moral beauty without explicit cognitive efforts. Using a binocular rivalry paradigm, we identified enhanced gender-independent perceptual dominance for physically attractive persons, and the results suggested universal preference for visual beauty based on perceivable forms. Moreover, we also identified perceptual dominance enhancement for characters associated with virtuous descriptions after controlling for facial attractiveness and vigilance-related attention effects, which suggested a similar implicit preference for moral beauty conveyed in prosocial behaviours. Our findings show that behavioural preference for beauty is driven by an inherent natural tendency towards beauty in humans rather than explicit social cognitive processes.

Natural Tendency towards Beauty in Humans: Evidence from Binocular Rivalry

PubMed Central

Mo, Lei

2016-01-01

Although human preference for beauty is common and compelling in daily life, it remains unknown whether such preference is essentially subserved by social cognitive demands or natural tendency towards beauty encoded in the human mind intrinsically. Here we demonstrate experimentally that humans automatically exhibit preference for visual and moral beauty without explicit cognitive efforts. Using a binocular rivalry paradigm, we identified enhanced gender-independent perceptual dominance for physically attractive persons, and the results suggested universal preference for visual beauty based on perceivable forms. Moreover, we also identified perceptual dominance enhancement for characters associated with virtuous descriptions after controlling for facial attractiveness and vigilance-related attention effects, which suggested a similar implicit preference for moral beauty conveyed in prosocial behaviours. Our findings show that behavioural preference for beauty is driven by an inherent natural tendency towards beauty in humans rather than explicit social cognitive processes. PMID:26930202

Chemically cued suppression of coral reef resilience: Where is the tipping point?

NASA Astrophysics Data System (ADS)

Brooker, Rohan M.; Hay, Mark E.; Dixson, Danielle L.

2016-12-01

Coral reefs worldwide are shifting from high-diversity, coral-dominated communities to low-diversity systems dominated by seaweeds. This shift can impact essential recovery processes such as larval recruitment and ecosystem resilience. Recent evidence suggests that chemical cues from certain corals attract, and from certain seaweeds suppress, recruitment of juvenile fishes, with loss of coral cover and increases in seaweed cover creating negative feedbacks that prevent reef recovery and sustain seaweed dominance. Unfortunately, the level of seaweed increase and coral decline that creates this chemically cued tipping point remains unknown, depriving managers of data-based targets to prevent damaging feedbacks. We conducted flume and field assays that suggest juvenile fishes sense and respond to cues produced by low levels of seaweed cover. However, the herbivore species we tested was more tolerant of degraded reef cues than non-herbivores, possibly providing some degree of resilience if these fishes recruit, consume macroalgae, and diminish negative cues.

Foraging reactivation in the honeybee Apis mellifera L.: factors affecting the return to known nectar sources

NASA Astrophysics Data System (ADS)

Gil, Mariana; Farina, Walter Marcelo

2002-05-01

This paper addresses, what determines that experienced forager honeybees return to places where they have previously exploited nectar. Although there was already some evidence that dance and trophallaxis can cause bees to return to feed, the fraction of unemployed foragers that follow dance or receive food from employed foragers before revisiting the feeder was unknown. We found that 27% of the experienced foragers had no contact with the returning foragers inside the hive. The most common interactions were dance following (64%) and trophallaxis (21%). The great variability found in the amount of interactions suggests that individual bees require different stimulation before changing to the foraging mode. This broad disparity negatively correlated with the number of days after marking at the feeder, a variable that is closely related to the foraging experience, suggesting that a temporal variable might affect the decision-making in reactivated foragers.

Direct PCR amplification of forensic touch and other challenging DNA samples: A review.

PubMed

Cavanaugh, Sarah E; Bathrick, Abigail S

2018-01-01

DNA evidence sample processing typically involves DNA extraction, quantification, and STR amplification; however, DNA loss can occur at both the DNA extraction and quantification steps, which is not ideal for forensic evidence containing low levels of DNA. Direct PCR amplification of forensic unknown samples has been suggested as a means to circumvent extraction and quantification, thereby retaining the DNA typically lost during those procedures. Direct PCR amplification is a method in which a sample is added directly to an amplification reaction without being subjected to prior DNA extraction, purification, or quantification. It allows for maximum quantities of DNA to be targeted, minimizes opportunities for error and contamination, and reduces the time and monetary resources required to process samples, although data analysis may take longer as the increased DNA detection sensitivity of direct PCR may lead to more instances of complex mixtures. ISO 17025 accredited laboratories have successfully implemented direct PCR for limited purposes (e.g., high-throughput databanking analysis), and recent studies indicate that direct PCR can be an effective method for processing low-yield evidence samples. Despite its benefits, direct PCR has yet to be widely implemented across laboratories for the processing of evidentiary items. While forensic DNA laboratories are always interested in new methods that will maximize the quantity and quality of genetic information obtained from evidentiary items, there is often a lag between the advent of useful methodologies and their integration into laboratories. Delayed implementation of direct PCR of evidentiary items can be attributed to a variety of factors, including regulatory guidelines that prevent laboratories from omitting the quantification step when processing forensic unknown samples, as is the case in the United States, and, more broadly, a reluctance to validate a technique that is not widely used for evidence samples. The advantages of direct PCR of forensic evidentiary samples justify a re-examination of the factors that have delayed widespread implementation of this method and of the evidence supporting its use. In this review, the current and potential future uses of direct PCR in forensic DNA laboratories are summarized. Copyright © 2017 Elsevier B.V. All rights reserved.

Egg shape mimicry in parasitic cuckoos.

PubMed

Attard, M R G; Medina, I; Langmore, N E; Sherratt, E

2017-11-01

Parasitic cuckoos lay their eggs in nests of host species. Rejection of cuckoo eggs by hosts has led to the evolution of egg mimicry by cuckoos, whereby their eggs mimic the colour and pattern of their host eggs to avoid egg recognition and rejection. There is also evidence of mimicry in egg size in some cuckoo-host systems, but currently it is unknown whether cuckoos can also mimic the egg shape of their hosts. In this study, we test whether there is evidence of mimicry in egg form (shape and size) in three species of Australian cuckoos: the fan-tailed cuckoo Cacomantis flabelliformis, which exploits dome nesting hosts, the brush cuckoo Cacomantis variolosus, which exploits both dome and cup nesting hosts, and the pallid cuckoo Cuculus pallidus, which exploits cup nesting hosts. We found evidence of size mimicry and, for the first time, evidence of egg shape mimicry in two Australian cuckoo species (pallid cuckoo and brush cuckoo). Moreover, cuckoo-host egg similarity was higher for hosts with open nests than for hosts with closed nests. This finding fits well with theory, as it has been suggested that hosts with closed nests have more difficulty recognizing parasitic eggs than open nests, have lower rejection rates and thus exert lower selection for mimicry in cuckoos. This is the first evidence of mimicry in egg shape in a cuckoo-host system, suggesting that mimicry at different levels (size, shape, colour pattern) is evolving in concert. We also confirm the existence of egg size mimicry in cuckoo-host systems. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

A Review on Attachment and Adolescent Substance Abuse: Empirical Evidence and Implications for Prevention and Treatment.

PubMed

Schindler, Andreas; Bröning, Sonja

2015-01-01

This paper reviews research on the relation of attachment and substance use disorders (SUD) in adolescence. Based on a theoretical introduction, we review evidence for a possible general link between SUD and insecure attachment, for links between specific forms of SUD and specific patterns of attachment, and for studies on family patterns of attachment in adolescence. Using medical and psychological databases, we identified 10 studies on adolescent SUD and another 13 studies on adult SUD. Empirical evidence strongly supports the assumption of insecure attachment in SUD samples. With regard to specific patterns of attachment, results mainly point towards fearful and dismissing-avoidance, whereas single studies report preoccupied and unresolved patterns. Results indicate different patterns of attachment in different groups of substance abusers, that is, fearful-avoidant attachment in heroin addicts and more heterogeneous results in abusers of other substances. Explorative data suggest different types of insecure family attachment patterns, which might imply different functions of substance abuse and lead to different treatment recommendations. Methodological problems such as poor assessment of SUD and the use of different measures of attachment limit comparability. Although a lot of research is still needed to address the unknowns in the relation between attachment and SUD, there is strong evidence for a general link between SUD and insecure attachment. Data on connections between different patterns of attachment and different pathways towards SUD are less conclusive but mainly point to disorganized and externalizing pathways. Evidence suggests that fostering attachment security might improve the outcome of state-of-the-art approaches in both early interventional treatment and prevention. Implications for individual and family approaches are outlined.

Magnetic resonance appearance of monoclonal gammopathies of unknown significance and multiple myeloma. The GRI Study Group.

PubMed

Bellaïche, L; Laredo, J D; Lioté, F; Koeger, A C; Hamze, B; Ziza, J M; Pertuiset, E; Bardin, T; Tubiana, J M

1997-11-01

A prospective multicenter study. To evaluate the use of magnetic resonance imaging, in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. Although multiple myeloma has been studied extensively with magnetic resonance imaging, to the authors' knowledge, no study has evaluated the clinical interest of magnetic resonance imaging in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. The magnetic resonance examinations of the thoracolumbar spine in 24 patients with newly diagnosed monoclonal gammopathies of unknown significance were compared with those performed in 44 patients with newly diagnosed nontreated multiple myeloma. All findings on magnetic resonance examination performed in patients with monoclonal gammopathies of unknown significance were normal, whereas findings on 38 (86%) of the 44 magnetic resonance examinations performed in patients with multiple myeloma were abnormal. Magnetic resonance imaging can be considered as an additional diagnostic tool in differentiating between monoclonal gammopathies of unknown significance and multiple myeloma, which may be helpful when routine criteria are not sufficient. An abnormal finding on magnetic resonance examination in a patient with monoclonal gammopathies of unknown significance should suggest the diagnosis of multiple myeloma after other causes of marrow signal abnormalities are excluded. Magnetic resonance imaging also may be proposed in the long-term follow-up of monoclonal gammopathies of unknown significance when a new biologic or clinical event suggests the diagnosis of malignant monoclonal gammopathy.

Evidence-Based Practices Project for Suicide Prevention

ERIC Educational Resources Information Center

Rodgers, Philip L.; Sudak, Howard S.; Silverman, Morton M.; Litts, David A.

2007-01-01

Suicide continues to be a serious public health problem. In response to this problem, a myriad of suicide prevention programs have been developed and employed across the United States. Unfortunately, the effectiveness of many of these programs is unknown because they have not been evaluated using rigorous methods. The Evidence-Based Practices…

Molecular toolbox for the identification of unknown genetically modified organisms.

PubMed

Ruttink, Tom; Demeyer, Rolinde; Van Gulck, Elke; Van Droogenbroeck, Bart; Querci, Maddalena; Taverniers, Isabel; De Loose, Marc

2010-03-01

Competent laboratories monitor genetically modified organisms (GMOs) and products derived thereof in the food and feed chain in the framework of labeling and traceability legislation. In addition, screening is performed to detect the unauthorized presence of GMOs including asynchronously authorized GMOs or GMOs that are not officially registered for commercialization (unknown GMOs). Currently, unauthorized or unknown events are detected by screening blind samples for commonly used transgenic elements, such as p35S or t-nos. If (1) positive detection of such screening elements shows the presence of transgenic material and (2) all known GMOs are tested by event-specific methods but are not detected, then the presence of an unknown GMO is inferred. However, such evidence is indirect because it is based on negative observations and inconclusive because the procedure does not identify the causative event per se. In addition, detection of unknown events is hampered in products that also contain known authorized events. Here, we outline alternative approaches for analytical detection and GMO identification and develop new methods to complement the existing routine screening procedure. We developed a fluorescent anchor-polymerase chain reaction (PCR) method for the identification of the sequences flanking the p35S and t-nos screening elements. Thus, anchor-PCR fingerprinting allows the detection of unique discriminative signals per event. In addition, we established a collection of in silico calculated fingerprints of known events to support interpretation of experimentally generated anchor-PCR GM fingerprints of blind samples. Here, we first describe the molecular characterization of a novel GMO, which expresses recombinant human intrinsic factor in Arabidopsis thaliana. Next, we purposefully treated the novel GMO as a blind sample to simulate how the new methods lead to the molecular identification of a novel unknown event without prior knowledge of its transgene sequence. The results demonstrate that the new methods complement routine screening procedures by providing direct conclusive evidence and may also be useful to resolve masking of unknown events by known events.

Teaching letter sounds to kindergarten English language learners using incremental rehearsal.

PubMed

Peterson, Meredith; Brandes, Dana; Kunkel, Amy; Wilson, Jennifer; Rahn, Naomi L; Egan, Andrea; McComas, Jennifer

2014-02-01

Proficiency in letter-sound correspondence is important for decoding connected text. This study examined the effects of an evidence-based intervention, incremental rehearsal (IR), on the letter-sound expression of three kindergarten English language learners (ELLs) performing below the district benchmark for letter-sound fluency. Participants were native speakers of Hmong, Spanish, and Polish. A multiple-baseline design across sets of unknown letter sounds was used to evaluate the effects of IR on letter-sound expression. Visual analysis of the data showed an increase in level and trend when IR was introduced in each phase. Percentage of all non-overlapping data (PAND) ranged from 95% to 100%. All participants exceeded expected growth and reached the spring district benchmark for letter-sound fluency. Results suggest that IR is a promising intervention for increasing letter-sound expression for ELLs who evidence delays in acquiring letter sounds. Copyright © 2013 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Severe Outbreak of Sorbitol-Fermenting Escherichia coli O157 via Unpasteurized Milk and Farm Visits, Finland 2012.

PubMed

Jaakkonen, A; Salmenlinna, S; Rimhanen-Finne, R; Lundström, H; Heinikainen, S; Hakkinen, M; Hallanvuo, S

2017-09-01

Shiga toxin-producing, sorbitol-fermenting Escherichia coli O157 (SF O157) has emerged as a cause of severe human illness. Despite frequent human findings, its transmission routes and reservoirs remain largely unknown. Foodborne transmission and reservoir in cattle have been suspected, but with limited supporting evidence. This study describes the outbreak of SF O157 that occurred in Finland in 2012. The outbreak originated from a recreational farm selling unpasteurized milk, as revealed by epidemiologic and microbiological investigations, and involved six hospitalized children and two asymptomatic adults with culture-confirmed infection. An identical strain of SF O157 was isolated from patients, cattle and the farm environment, and epidemiologic analysis suggested unpasteurized milk as the vehicle of transmission. This study reports the first milkborne outbreak of SF O157, provides supporting evidence of cattle as a reservoir and highlights the health risks related to the consumption of unpasteurized milk. © 2017 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.

Hippocampal and posterior parietal contributions to developmental increases in visual short-term memory capacity.

PubMed

von Allmen, David Yoh; Wurmitzer, Karoline; Klaver, Peter

2014-10-01

Developmental increases in visual short-term memory (VSTM) capacity have been associated with changes in attention processing limitations and changes in neural activity within neural networks including the posterior parietal cortex (PPC). A growing body of evidence suggests that the hippocampus plays a role in VSTM, but it is unknown whether the hippocampus contributes to the capacity increase across development. We investigated the functional development of the hippocampus and PPC in 57 children, adolescents and adults (age 8-27 years) who performed a visuo-spatial change detection task. A negative relationship between age and VSTM related activity was found in the right posterior hippocampus that was paralleled by a positive age-activity relationship in the right PPC. In the posterior hippocampus, VSTM related activity predicted individual capacity in children, whereas neural activity in the right anterior hippocampus predicted individual capacity in adults. The findings provide first evidence that VSTM development is supported by an integrated neural network that involves hippocampal and posterior parietal regions.

First bone-cracking dog coprolites provide new insight into bone consumption in Borophagus and their unique ecological niche

PubMed Central

White, Stuart C; Balisi, Mairin; Biewer, Jacob; Sankey, Julia; Garber, Dennis; Tseng, Z Jack

2018-01-01

Borophagine canids have long been hypothesized to be North American ecological ‘avatars’ of living hyenas in Africa and Asia, but direct fossil evidence of hyena-like bone consumption is hitherto unknown. We report rare coprolites (fossilized feces) of Borophagus parvus from the late Miocene of California and, for the first time, describe unambiguous evidence that these predatory canids ingested large amounts of bone. Surface morphology, micro-CT analyses, and contextual information reveal (1) droppings in concentrations signifying scent-marking behavior, similar to latrines used by living social carnivorans; (2) routine consumption of skeletons; (3) undissolved bones inside coprolites indicating gastrointestinal similarity to modern striped and brown hyenas; (4) B. parvus body weight of ~24 kg, reaching sizes of obligatory large-prey hunters; and (5) prey size ranging ~35–100 kg. This combination of traits suggests that bone-crushing Borophagus potentially hunted in collaborative social groups and occupied a niche no longer present in North American ecosystems. PMID:29785931

Inositol Treatment and ART Outcomes in Women with PCOS.

PubMed

Garg, Deepika; Tal, Reshef

2016-01-01

Polycystic ovary syndrome (PCOS) affects 5-10% of women in reproductive age and is characterized by oligo/amenorrhea, androgen excess, insulin resistance, and typical polycystic ovarian morphology. It is the most common cause of infertility secondary to ovulatory dysfunction. The underlying etiology is still unknown but is believed to be multifactorial. Insulin-sensitizing compounds such as inositol, a B-complex vitamin, and its stereoisomers (myo-inositol and D-chiro-inositol) have been studied as an effective treatment of PCOS. Administration of inositol in PCOS has been shown to improve not only the metabolic and hormonal parameters but also ovarian function and the response to assisted-reproductive technology (ART). Accumulating evidence suggests that it is also capable of improving folliculogenesis and embryo quality and increasing the mature oocyte yield following ovarian stimulation for ART in women with PCOS. In the current review, we collate the evidence and summarize our current knowledge on ovarian stimulation and ART outcomes following inositol treatment in women with PCOS undergoing in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI).

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

Rapid Nipah virus entry into the central nervous system of hamsters via the olfactory route

PubMed Central

Munster, Vincent J.; Prescott, Joseph B.; Bushmaker, Trenton; Long, Dan; Rosenke, Rebecca; Thomas, Tina; Scott, Dana; Fischer, Elizabeth R.; Feldmann, Heinz; de Wit, Emmie

2012-01-01

Encephalitis is a hallmark of Nipah virus (NiV) infection in humans. The exact route of entry of NiV into the central nervous system (CNS) is unknown. Here, we performed a spatio-temporal analysis of NiV entry into the CNS of hamsters. NiV initially predominantly targeted the olfactory epithelium in the nasal turbinates. From there, NiV infected neurons were visible extending through the cribriform plate into the olfactory bulb, providing direct evidence of rapid CNS entry. Subsequently, NiV disseminated to the olfactory tubercle and throughout the ventral cortex. Transmission electron microscopy on brain tissue showed extravasation of plasma cells, neuronal degeneration and nucleocapsid inclusions in affected tissue and axons, providing further evidence for axonal transport of NiV. NiV entry into the CNS coincided with the occurrence of respiratory disease, suggesting that the initial entry of NiV into the CNS occurs simultaneously with, rather than as a result of, systemic virus replication. PMID:23071900

Effects of short-term interventions to reduce mental health-related stigma in university or college students: a systematic review.

PubMed

Yamaguchi, Sosei; Wu, Shu-I; Biswas, Milly; Yate, Madinah; Aoki, Yuta; Barley, Elizabeth A; Thornicroft, Graham

2013-06-01

Although there are many interventions to reduce mental health-related stigma in university or college students, their overall effect is unknown. This article systematically reviews intervention studies and aims to identify the effective approaches. We searched 11 bibliographic databases, Google, Web sites of relevant associations, and reference lists and contacted specialists. A total of 35 studies (N = 4257) of a wide range of interventions met the inclusion criteria. Social contact or video-based social contact interventions seemed to be the most effective in improving attitudes and reducing desire for social distance. Evidence from one study suggests that a lecture that provided treatment information may enhance students' attitudes toward the use of services. However, methodological weaknesses in many studies were also found. There was a lack of evidence for interventions in medical students, for long-term effects of interventions, or for having a positive impact on actual behaviors. Further research having more rigorous methods is needed to confirm this.

Aberrant Classopollis pollen reveals evidence for unreduced (2n) pollen in the conifer family Cheirolepidiaceae during the Triassic-Jurassic transition.

PubMed

Kürschner, Wolfram M; Batenburg, Sietske J; Mander, Luke

2013-10-07

Polyploidy (or whole-genome doubling) is a key mechanism for plant speciation leading to new evolutionary lineages. Several lines of evidence show that most species among flowering plants had polyploidy ancestry, but it is virtually unknown for conifers. Here, we study variability in pollen tetrad morphology and the size of the conifer pollen type Classopollis extracted from sediments of the Triassic-Jurassic transition, 200 Ma. Classopollis producing Cheirolepidiaceae were one of the most dominant and diverse groups of conifers during the Mesozoic. We show that aberrant pollen Classopollis tetrads, triads and dyads, and the large variation in pollen size indicates the presence of unreduced (2n) pollen, which is one of the main mechanisms in modern polyploid formation. Polyploid speciation may explain the high variability of growth forms and adaptation of these conifers to different environments and their resistance to extreme growth conditions. We suggest that polyploidy may have also reduced the extinction risk of these conifers during the End-Triassic biotic crisis.

Critically endangered western gray whales migrate to the eastern North Pacific.

PubMed

Mate, Bruce R; Ilyashenko, Valentin Yu; Bradford, Amanda L; Vertyankin, Vladimir V; Tsidulko, Grigory A; Rozhnov, Vyacheslav V; Irvine, Ladd M

2015-04-01

Western North Pacific gray whales (WGWs), once considered extinct, are critically endangered with unknown migratory routes and reproductive areas. We attached satellite-monitored tags to seven WGWs on their primary feeding ground off Sakhalin Island, Russia, three of which subsequently migrated to regions occupied by non-endangered eastern gray whales (EGWs). A female with the longest-lasting tag visited all three major EGW reproductive areas off Baja California, Mexico, before returning to Sakhalin Island the following spring. Her 22 511 km round-trip is the longest documented mammal migration and strongly suggests that some presumed WGWs are actually EGWs foraging in areas historically attributed to WGWs. The observed migration routes provide evidence of navigational skills across open water that break the near-shore north-south migratory paradigm of EGWs. Despite evidence of genetic differentiation, these tagging data indicate that the population identity of whales off Sakhalin Island needs further evaluation. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

A grass molecular identification system for forensic botany: a critical evaluation of the strengths and limitations.

PubMed

Ward, Jodie; Gilmore, Simon R; Robertson, James; Peakall, Rod

2009-11-01

Plant material is frequently encountered in criminal investigations but often overlooked as potential evidence. We designed a DNA-based molecular identification system for 100 Australian grasses that consisted of a series of polymerase chain reaction assays that enabled the progressive identification of grasses to different taxonomic levels. The identification system was based on DNA sequence variation at four chloroplast and two mitochondrial loci. Seventeen informative indels and 68 single-nucleotide polymorphisms were utilized as molecular markers for subfamily to species-level identification. To identify an unknown sample to subfamily level required a minimum of four markers or nine markers for species identification. The accuracy of the system was confirmed by blind tests. We have demonstrated "proof of concept" of a molecular identification system for trace botanical samples. Our evaluation suggests that the adoption of a system that combines this approach with DNA sequencing could assist the morphological identification of grasses found as forensic evidence.

Integrative and distinctive coding of visual and conceptual object features in the ventral visual stream

PubMed Central

Douglas, Danielle; Newsome, Rachel N; Man, Louisa LY

2018-01-01

A significant body of research in cognitive neuroscience is aimed at understanding how object concepts are represented in the human brain. However, it remains unknown whether and where the visual and abstract conceptual features that define an object concept are integrated. We addressed this issue by comparing the neural pattern similarities among object-evoked fMRI responses with behavior-based models that independently captured the visual and conceptual similarities among these stimuli. Our results revealed evidence for distinctive coding of visual features in lateral occipital cortex, and conceptual features in the temporal pole and parahippocampal cortex. By contrast, we found evidence for integrative coding of visual and conceptual object features in perirhinal cortex. The neuroanatomical specificity of this effect was highlighted by results from a searchlight analysis. Taken together, our findings suggest that perirhinal cortex uniquely supports the representation of fully specified object concepts through the integration of their visual and conceptual features. PMID:29393853

Exercise, Appetite and Weight Control: Are There Differences between Men and Women?

PubMed Central

Thackray, Alice E.; Deighton, Kevin; King, James A.; Stensel, David J.

2016-01-01

Recent years have witnessed significant research interest surrounding the interaction among exercise, appetite and energy balance, which has important implications for health. The majority of exercise and appetite regulation studies have been conducted in males. Consequently, opportunities to examine sex-based differences have been limited, but represent an interesting avenue of inquiry considering postulations that men experience greater weight loss after exercise interventions than women. This article reviews the scientific literature relating to the acute and chronic effects of exercise on appetite control in men and women. The consensus of evidence demonstrates that appetite, appetite-regulatory hormone and energy intake responses to acute exercise do not differ between the sexes, and there is little evidence indicating compensatory changes occur after acute exercise in either sex. Limited evidence suggests women respond to the initiation of exercise training with more robust compensatory alterations in appetite-regulatory hormones than men, but whether this translates to long-term differences is unknown. Current exercise training investigations do not support sex-based differences in appetite or objectively assessed energy intake, and increasing exercise energy expenditure elicits at most a partial energy intake compensation in both sexes. Future well-controlled acute and chronic exercise studies directly comparing men and women are required to expand this evidence base. PMID:27657127

Influence of multiple categories on the prediction of unknown properties

PubMed Central

Verde, Michael F.; Murphy, Gregory L.; Ross, Brian H.

2006-01-01

Knowing an item's category helps us predict its unknown properties. Previous studies suggest that when asked to evaluate the probability of an unknown property, people tend to consider only an item's most likely category, ignoring alternative categories. In the present study, property prediction took the form of either a probability rating or a speeded, binary-choice judgment. Consistent with past findings, subjects ignored alternative categories in their probability ratings. However, their binary-choice judgments were influenced by alternative categories. This novel finding suggests that the way category knowledge is used in prediction depends critically on the form of the prediction. PMID:16156183

A multi-level examination of how the organizational context relates to readiness to implement prevention and evidence-based programming in community settings.

PubMed

Chilenski, Sarah M; Olson, Jonathan R; Schulte, Jill A; Perkins, Daniel F; Spoth, Richard

2015-02-01

Prior theoretical and empirical research suggests that multiple aspects of an organization's context are likely related to a number of factors, from their interest and ability to adopt new programming, to client outcomes. A limited amount of the prior research has taken a more community-wide perspective by examining factors that associate with community readiness for change, leaving how these findings generalize to community organizations that conduct prevention or positive youth development programs unknown. Thus for the current study, we examined how the organizational context of the Cooperative Extension System (CES) associates with current attitudes and practices regarding prevention and evidence-based programming. Attitudes and practices have been found in the empirical literature to be key indicators of an organization's readiness to adopt prevention and evidence-based programming. Based on multi-level mixed models, results indicate that organizational management practices distinct from program delivery may affect an organization's readiness to adopt and implement new prevention and evidence-based youth programs, thereby limiting the potential public health impact of evidence-based programs. Openness to change, openness of leadership, and communication were the strongest predictors identified within this study. An organization's morale was also found to be a strong predictor of an organization's readiness. The findings of the current study are discussed in terms of implications for prevention and intervention.

A Multi-level Examination of how the Organizational Context Relates to Readiness to Implement Prevention and Evidence-Based Programming in Community Settings

PubMed Central

Chilenski, Sarah M.; Olson, Jonathan R.; Schulte, Jill A.; Perkins, Daniel F.; Spoth, Richard

2015-01-01

Prior theoretical and empirical research suggests that multiple aspects of an organization’s context are likely related to a number of factors, from their interest and ability to adopt new programming, to client outcomes. A limited amount of the prior research has taken a more community-wide perspective by examining factors that associate with community readiness for change, leaving how these findings generalize to community organizations that conduct prevention or positive youth development programs unknown. Thus for the current study, we examined how the organizational context of the Cooperative Extension System (CES) associates with current attitudes and practices regarding prevention and evidence-based programming. Attitudes and practices have been found in the empirical literature to be key indicators of an organization’s readiness to adopt prevention and evidence-based programming. Based on multi-level mixed models, results indicate that organizational management practices distinct from program delivery may affect an organization’s readiness to adopt and implement new prevention and evidence-based youth programs, thereby limiting the potential public health impact of evidence-based programs. Openness to change, openness of leadership, and communication were the strongest predictors identified within this study. An organization’s morale was also found to be a strong predictor of an organization’s readiness. The findings of the current study are discussed in terms of implications for prevention and intervention. PMID:25463014

Traditional Chinese medicine for knee osteoarthritis: An overview of systematic review.

PubMed

Yang, Min; Jiang, Li; Wang, Qing; Chen, Hao; Xu, Guihua

2017-01-01

Traditional Chinese medicine (TCM) has been accepted as a complementary therapy for knee osteoarthritis. However, the efficacy and safety of the intervention were still conflicting and uncertain. Meanwhile, the quality of methodology and evidence in the field was unknown. To summarize the characteristics and critically evaluate the quality of methodology, as well as the evidence of systematic reviews (SRs) on TCM for knee osteoarthritis. Five electronic databases were searched from inception to April 2016. The methodological quality of the included studies was assessed by AMSTAR and ROBIS. The quality of the evidence was determined using the GRADE approach. Ten SRs were included. The conclusions suggest that TCM provides potential benefits for patients with knee osteoarthritis. These benefits include pain relief, functional improvement, and presence of few adverse events. Limitations of the methodological quality mainly included the lack of a-priori protocol or protocol registration and incomprehensive literature search. A list of excluded studies was also not provided. The overall quality of evidence in the SRs was poor, ranging from "very low" to "low," mainly because of the serious risk of bias of original trials, inconsistencies, and imprecision in the outcomes. TCM generally appears to be effective for knee osteoarthritis treatment. However, the evidence is not robust enough because of the methodological flaws in SRs. Hence, these conclusions on available SRs should be treated with caution for clinical practice.

Athletic Trainers' Current Knowledge and Envisioned Use of Foundational Evidence-Based Practice Concepts

ERIC Educational Resources Information Center

Manspeaker, Sarah A.; Hankemeier, Dorice A.

2017-01-01

Context: The Board of Certification (BOC) requires 10 continuing education units (CEUs) in evidence-based practice (EBP) each reporting period. It is unknown whether participation in programming in the Foundations category for CEUs results in improved knowledge of and confidence in EBP. Objective: To examine a continuing professional education…

Catecholaminergic Regulation of Learning Rate in a Dynamic Environment.

PubMed

Jepma, Marieke; Murphy, Peter R; Nassar, Matthew R; Rangel-Gomez, Mauricio; Meeter, Martijn; Nieuwenhuis, Sander

2016-10-01

Adaptive behavior in a changing world requires flexibly adapting one's rate of learning to the rate of environmental change. Recent studies have examined the computational mechanisms by which various environmental factors determine the impact of new outcomes on existing beliefs (i.e., the 'learning rate'). However, the brain mechanisms, and in particular the neuromodulators, involved in this process are still largely unknown. The brain-wide neurophysiological effects of the catecholamines norepinephrine and dopamine on stimulus-evoked cortical responses suggest that the catecholamine systems are well positioned to regulate learning about environmental change, but more direct evidence for a role of this system is scant. Here, we report evidence from a study employing pharmacology, scalp electrophysiology and computational modeling (N = 32) that suggests an important role for catecholamines in learning rate regulation. We found that the P3 component of the EEG-an electrophysiological index of outcome-evoked phasic catecholamine release in the cortex-predicted learning rate, and formally mediated the effect of prediction-error magnitude on learning rate. P3 amplitude also mediated the effects of two computational variables-capturing the unexpectedness of an outcome and the uncertainty of a preexisting belief-on learning rate. Furthermore, a pharmacological manipulation of catecholamine activity affected learning rate following unanticipated task changes, in a way that depended on participants' baseline learning rate. Our findings provide converging evidence for a causal role of the human catecholamine systems in learning-rate regulation as a function of environmental change.

Economic Value Biases Uncertain Perceptual Choices in the Parietal and Prefrontal Cortices

PubMed Central

Summerfield, Christopher; Koechlin, Etienne

2010-01-01

An observer detecting a noisy sensory signal is biased by the costs and benefits associated with its presence or absence. When these costs and benefits are asymmetric, sensory, and economic information must be integrated to inform the final choice. However, it remains unknown how this information is combined at the neural or computational levels. To address this question, we asked healthy human observers to judge the presence or absence of a noisy sensory signal under economic conditions that favored yes responses (liberal blocks), no responses (conservative blocks), or neither response (neutral blocks). Economic information biased fast choices more than slow choices, suggesting that value and sensory information are integrated early in the decision epoch. More formal simulation analyses using an Ornstein–Uhlenbeck process demonstrated that the influence of economic information was best captured by shifting the origin of evidence accumulation toward the more valuable bound. We then used the computational model to generate trial-by-trial estimates of decision-related evidence that were based on combined sensory and economic information (the decision variable or DV), and regressed these against fMRI activity recorded whilst participants performed the task. Extrastriate visual regions responded to the level of sensory input (momentary evidence), but fMRI signals in the parietal and prefrontal cortices responded to the decision variable. These findings support recent single-neuron data suggesting that economic information biases decision-related signals in higher cortical regions. PMID:21267421

No Evidence of Sex-Related Survival Disparities among Head and Neck Cancer Patients Receiving Similar Multidisciplinary Care: A Matched-Pair Analysis

PubMed Central

Roberts, Jess C.; Li, Guojun; Reitzel, Lorraine R.; Wei, Qingyi; Sturgis, Erich M.

2010-01-01

Purpose It is unknown whether there are survival disparities between men and women with squamous cell carcinoma of the head and neck (SCCHN), though some data suggest that men have worse outcomes. We conducted a matched-pair study that controlled for several potentially confounding prognostic variables to assess whether a survival advantage exists for female compared with male SCCHN patients receiving similar care. Experimental Design We selected 286 female patients and 286 matched male patients from within a prospective epidemiologic study of 1654 patients with incident SCCHN evaluated and treated at a single large multidisciplinary cancer center. Matching variables included age (± 10 years), race/ethnicity, smoking status (never versus ever), tumor site (oral cavity versus oropharynx versus larynx versus hypopharynx), tumor classification (T1–2 versus T3–4), nodal status (negative versus positive), and treatment (surgery, radiation therapy, surgery and radiation therapy, surgery and chemotherapy, chemoradiotherapy, or surgery and chemoradiotherapy). Results Matched-pair and log-rank analyses showed no significant differences between women and men in recurrence-free, disease-specific, or overall survival. When the analysis was restricted to individual sites (oral cavity, oropharynx, or larynx/hypopharynx), there was also no evidence of a disparity in survival associated with sex. Conclusions We conclude that there is no evidence to suggest that a survival advantage exists for women as compared to men with SCCHN receiving similar multidisciplinary directed care at a tertiary cancer center. PMID:20943762

Catecholaminergic Regulation of Learning Rate in a Dynamic Environment

PubMed Central

Jepma, Marieke; Nassar, Matthew R.; Rangel-Gomez, Mauricio; Meeter, Martijn; Nieuwenhuis, Sander

2016-01-01

Adaptive behavior in a changing world requires flexibly adapting one’s rate of learning to the rate of environmental change. Recent studies have examined the computational mechanisms by which various environmental factors determine the impact of new outcomes on existing beliefs (i.e., the ‘learning rate’). However, the brain mechanisms, and in particular the neuromodulators, involved in this process are still largely unknown. The brain-wide neurophysiological effects of the catecholamines norepinephrine and dopamine on stimulus-evoked cortical responses suggest that the catecholamine systems are well positioned to regulate learning about environmental change, but more direct evidence for a role of this system is scant. Here, we report evidence from a study employing pharmacology, scalp electrophysiology and computational modeling (N = 32) that suggests an important role for catecholamines in learning rate regulation. We found that the P3 component of the EEG—an electrophysiological index of outcome-evoked phasic catecholamine release in the cortex—predicted learning rate, and formally mediated the effect of prediction-error magnitude on learning rate. P3 amplitude also mediated the effects of two computational variables—capturing the unexpectedness of an outcome and the uncertainty of a preexisting belief—on learning rate. Furthermore, a pharmacological manipulation of catecholamine activity affected learning rate following unanticipated task changes, in a way that depended on participants’ baseline learning rate. Our findings provide converging evidence for a causal role of the human catecholamine systems in learning-rate regulation as a function of environmental change. PMID:27792728

Memory Accumulation Mechanisms in Human Cortex Are Independent of Motor Intentions

PubMed Central

Tosoni, Annalisa; Mignogna, Valeria; McAvoy, Mark P.; Shulman, Gordon L.; Corbetta, Maurizio; Romani, Gian Luca

2014-01-01

Previous studies on perceptual decision-making have often emphasized a tight link between decisions and motor intentions. Human decisions, however, also depend on memories or experiences that are not closely tied to specific motor responses. Recent neuroimaging findings have suggested that, during episodic retrieval, parietal activity reflects the accumulation of evidence for memory decisions. It is currently unknown, however, whether these evidence accumulation signals are functionally linked to signals for motor intentions coded in frontoparietal regions and whether activity in the putative memory accumulator tracks the amount of evidence for only previous experience, as reflected in “old” reports, or for both old and new decisions, as reflected in the accuracy of memory judgments. Here, human participants used saccadic-eye and hand-pointing movements to report recognition judgments on pictures defined by different degrees of evidence for old or new decisions. A set of cortical regions, including the middle intraparietal sulcus, showed a monotonic variation of the fMRI BOLD signal that scaled with perceived memory strength (older > newer), compatible with an asymmetrical memory accumulator. Another set, including the hippocampus and the angular gyrus, showed a nonmonotonic response profile tracking memory accuracy (higher > lower evidence), compatible with a symmetrical accumulator. In contrast, eye and hand effector-specific regions in frontoparietal cortex tracked motor intentions but were not modulated by the amount of evidence for the effector outcome. We conclude that item recognition decisions are supported by a combination of symmetrical and asymmetrical accumulation signals largely segregated from motor intentions. PMID:24828652

LANP mediates neuritic pathology in Spinocerebellar ataxia type 1

PubMed Central

Cvetanovic, Marija; Kular, Rupinder K.; Opal, Puneet

2014-01-01

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease that results from a pathogenic glutamine-repeat expansion in the protein ataxin-1 (ATXN1). Although the functions of ATXN1 are still largely unknown, there is evidence to suggest that ATXN1 plays a role in regulating gene expression, the earliest process known to go awry in SCA1 mouse models. In this study, we show that ATXN1 reduces histone acetylation, a post-translational modification of histones associated with enhanced transcription, and represses histone acetyl transferase-mediated transcription. In addition, we find that depleting the Leucine-rich Acidic Nuclear Protein (LANP)—an ATXN1 binding inhibitor of histone acetylation—reverses aspects of SCA1 neuritic pathology. PMID:22884877

Aztec arithmetic revisited: land-area algorithms and Acolhua congruence arithmetic.

PubMed

Williams, Barbara J; Jorge y Jorge, María del Carmen

2008-04-04

Acolhua-Aztec land records depicting areas and side dimensions of agricultural fields provide insight into Aztec arithmetic. Hypothesizing that recorded areas resulted from indigenous calculation, in a study of sample quadrilateral fields we found that 60% of the area values could be reproduced exactly by computation. In remaining cases, discrepancies between computed and recorded areas were consistently small, suggesting use of an unknown indigenous arithmetic. In revisiting the research, we discovered evidence for the use of congruence principles, based on proportions between the standard linear Acolhua measure and their units of shorter length. This procedure substitutes for computation with fractions and is labeled "Acolhua congruence arithmetic." The findings also clarify variance between Acolhua and Tenochca linear units, long an issue in understanding Aztec metrology.

Kinematic diversity suggests expanded roles for fly halteres.

PubMed

Hall, Joshua M; McLoughlin, Dane P; Kathman, Nicholas D; Yarger, Alexandra M; Mureli, Shwetha; Fox, Jessica L

2015-11-01

The halteres of flies are mechanosensory organs that provide information about body rotations during flight. We measured haltere movements in a range of fly taxa during free walking and tethered flight. We find a diversity of wing-haltere phase relationships in flight, with higher variability in more ancient families and less in more derived families. Diverse haltere movements were observed during free walking and were correlated with phylogeny. We predicted that haltere removal might decrease behavioural performance in those flies that move them during walking and provide evidence that this is the case. Our comparative approach reveals previously unknown diversity in haltere movements and opens the possibility of multiple functional roles for halteres in different fly behaviours. © 2015 The Author(s).

Correlating low-similarity peptide sequences and allergenic epitopes.

PubMed

Kanduc, D

2008-01-01

Although a high number of allergenic peptide epitopes has been experimentally identified and defined, the molecular basis and the precise mechanisms underlying peptide allergenicity are unknown. This issue was analyzed exploring the relationship between peptide allergenicity and sequence similarity to the human proteome. The structured analysis of the data reported in literature put into evidence that the most part of IgE-binding epitopes are (or harbor) pentapeptide unit(s) with no/low similarity to the human proteome, this way suggesting that no or low sequence similarity to the host proteome might represent a minimum common denominator identifying allergenic peptides. The present literature analysis might be of relevance in devising and designing short amino acid modules to be used for blocking pathogenic IgE.

Lack of Privileged Access to Awareness for Rewarding Social Scenes in Autism Spectrum Disorder.

PubMed

Gray, Katie L H; Haffey, Anthony; Mihaylova, Hristina L; Chakrabarti, Bhismadev

2018-05-04

Reduced social motivation is hypothesised to underlie social behavioural symptoms of Autism Spectrum Disorder (ASD). The extent to which rewarding social stimuli are granted privileged access to awareness in ASD is currently unknown. We use continuous flash suppression to investigate whether individuals with and without ASD show privileged access to awareness for social over nonsocial rewarding scenes that are closely matched for stimulus features. Strong evidence for a privileged access to awareness for rewarding social over nonsocial scenes was observed in neurotypical adults. No such privileged access was seen in ASD individuals, and moderate support for the null model was noted. These results suggest that the purported deficits in social motivation in ASD may extend to early processing mechanisms.

Adaptive neural coding: from biological to behavioral decision-making

PubMed Central

Louie, Kenway; Glimcher, Paul W.; Webb, Ryan

2015-01-01

Empirical decision-making in diverse species deviates from the predictions of normative choice theory, but why such suboptimal behavior occurs is unknown. Here, we propose that deviations from optimality arise from biological decision mechanisms that have evolved to maximize choice performance within intrinsic biophysical constraints. Sensory processing utilizes specific computations such as divisive normalization to maximize information coding in constrained neural circuits, and recent evidence suggests that analogous computations operate in decision-related brain areas. These adaptive computations implement a relative value code that may explain the characteristic context-dependent nature of behavioral violations of classical normative theory. Examining decision-making at the computational level thus provides a crucial link between the architecture of biological decision circuits and the form of empirical choice behavior. PMID:26722666

A Mechanism for Land-Atmosphere Feedback Involving Planetary Wave Structures

NASA Technical Reports Server (NTRS)

Koster, Randal D.; Chang, Yehui; Schubert, Siegfried D.

2014-01-01

While the ability of land surface conditions to influence the atmosphere has been demonstrated in various modeling and observational studies, the precise mechanisms by which land-atmosphere feedback occurs are still largely unknown particularly the mechanisms that allow land moisture state in one region to affect atmospheric conditions in another. Such remote impacts are examined here in the context of atmospheric general circulation model (AGCM) simulations, leading to the identification of one potential mechanism: the phase-locking and amplification of a planetary wave through the imposition of a spatial pattern of soil moisture at the land surface. This mechanism, shown here to be relevant in the AGCM, apparently also operates in nature, as suggested by supporting evidence found in reanalysis data.

Spaceflight-induced Bone Loss: Is there a Risk for Accelerated Osteoporosis after Return?

NASA Technical Reports Server (NTRS)

Sibonga, Jean

2008-01-01

The evidence-to to-date suggests that the rapid rate of site-specific bone loss in space, due to the unbalanced stimulation of bone resorption, may predispose crew members to irreversible changes in bone structure and microarchitecture. No analyses conducted in the postflight period to assess microarchitectural changes. There is no complete analysis of skeletal recovery in the postflight period to evaluate the structural changes that accompany increases in DXA aBMD. Postflight analyses based upon QCT scans performed on limited crew members indicate reductions in hip bone strength and incomplete recovery at 1 year. No recovery of trabecular vBMD after 1 year return (HRP IWG). Time course of bone loss in space unknown.

The biology and function of exosomes in cancer.

PubMed

Kalluri, Raghu

2016-04-01

Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40-150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients.

Laterodorsal nucleus of the thalamus: A processor of somatosensory inputs.

PubMed

Bezdudnaya, Tatiana; Keller, Asaf

2008-04-20

The laterodorsal (LD) nucleus of the thalamus has been considered a "higher order" nucleus that provides inputs to limbic cortical areas. Although its functions are largely unknown, it is often considered to be involved in spatial learning and memory. Here we provide evidence that LD is part of a hitherto unknown pathway for processing somatosensory information. Juxtacellular and extracellular recordings from LD neurons reveal that they respond to vibrissa stimulation with short latency (median = 7 ms) and large magnitude responses (median = 1.2 spikes/stimulus). Most neurons (62%) had large receptive fields, responding to six and more individual vibrissae. Electrical stimulation of the trigeminal nucleus interpolaris (SpVi) evoked short latency responses (median = 3.8 ms) in vibrissa-responsive LD neurons. Labeling produced by anterograde and retrograde neuroanatomical tracers confirmed that LD neurons receive direct inputs from SpVi. Electrophysiological and neuroanatomical analyses revealed also that LD projects upon the cingulate and retrosplenial cortex, but has only sparse projections to the barrel cortex. These findings suggest that LD is part of a novel processing stream involved in spatial orientation and learning related to somatosensory cues. (c) 2008 Wiley-Liss, Inc.

Evidence that KARRIKIN-INSENSITIVE2 (KAI2) Receptors may Perceive an Unknown Signal that is not Karrikin or Strigolactone.

PubMed

Conn, Caitlin E; Nelson, David C

2015-01-01

The α/β-hydrolases KAI2 and D14 are paralogous receptors for karrikins and strigolactones, two classes of plant growth regulators with butenolide moieties. KAI2 and D14 act in parallel signaling pathways that share a requirement for the F-box protein MAX2, but produce distinct growth responses by regulating different members of the SMAX1-LIKE/D53 family. kai2 and max2 mutants share seed germination, seedling growth, leaf shape, and petiole orientation phenotypes that are not found in d14 or SL-deficient mutants. This implies that KAI2 recognizes an unknown, endogenous signal, herein termed KAI2 ligand (KL). Recent studies of ligand-specificity among KAI2 paralogs in basal land plants and root parasitic plants suggest that karrikin and strigolactone perception may be evolutionary adaptations of KL receptors. Here we demonstrate that evolutionarily conserved KAI2c genes from two parasite species rescue multiple phenotypes of the Arabidopsis kai2 mutant, unlike karrikin-, and strigolactone-specific KAI2 paralogs. We hypothesize that KAI2c proteins recognize KL, which could be an undiscovered hormone.

Evidence that KARRIKIN-INSENSITIVE2 (KAI2) Receptors may Perceive an Unknown Signal that is not Karrikin or Strigolactone

PubMed Central

Conn, Caitlin E.; Nelson, David C.

2016-01-01

The α/β-hydrolases KAI2 and D14 are paralogous receptors for karrikins and strigolactones, two classes of plant growth regulators with butenolide moieties. KAI2 and D14 act in parallel signaling pathways that share a requirement for the F-box protein MAX2, but produce distinct growth responses by regulating different members of the SMAX1-LIKE/D53 family. kai2 and max2 mutants share seed germination, seedling growth, leaf shape, and petiole orientation phenotypes that are not found in d14 or SL-deficient mutants. This implies that KAI2 recognizes an unknown, endogenous signal, herein termed KAI2 ligand (KL). Recent studies of ligand-specificity among KAI2 paralogs in basal land plants and root parasitic plants suggest that karrikin and strigolactone perception may be evolutionary adaptations of KL receptors. Here we demonstrate that evolutionarily conserved KAI2c genes from two parasite species rescue multiple phenotypes of the Arabidopsis kai2 mutant, unlike karrikin-, and strigolactone-specific KAI2 paralogs. We hypothesize that KAI2c proteins recognize KL, which could be an undiscovered hormone. PMID:26779242

Waking up is the hardest thing I do all day: Sleep inertia and sleep drunkenness.

PubMed

Trotti, Lynn M

2017-10-01

The transition from sleep to wake is marked by sleep inertia, a distinct state that is measurably different from wakefulness and manifests as performance impairments and sleepiness. Although the precise substrate of sleep inertia is unknown, electroencephalographic, evoked potential, and neuroimaging studies suggest the persistence of some features of sleep beyond the point of awakening. Forced desynchrony studies have demonstrated that sleep inertia impacts cognition differently than do homeostatic and circadian drives and that sleep inertia is most intense during awakenings from the biological night. Recovery sleep after sleep deprivation also amplifies sleep inertia, although the effects of deep sleep vary based on task and timing. In patients with hypersomnolence disorders, especially but not exclusively idiopathic hypersomnia, a more pronounced period of confusion and sleepiness upon awakening, known as "sleep drunkenness", is common and problematic. Optimal treatment of sleep drunkenness is unknown, although several medications have been used with benefit in small case series. Difficulty with awakening is also commonly endorsed by individuals with mood disorders, disproportionately to the general population. This may represent an important treatment target, but evidence-based treatment guidance is not yet available. Copyright © 2016 Elsevier Ltd. All rights reserved.

Place, health, and community attachment: Is community capacity associated with self-rated health at the individual level?

PubMed

Lovell, Sarah A; Gray, Andrew R; Boucher, Sara E

2017-12-01

Community-level interventions dominate contemporary public health responses to health inequalities as a lack of political will has discouraged action at a structural level. Health promoters commonly leverage community capacity to achieve programme goals, yet the health implications of low community capacity are unknown. In this study, we analyse perceptions of community capacity at the individual-level to explore how place-based understandings of identity and connectedness are associated with self-rated health. We examine associations between individual community capacity, self-rated health and income using a cross-sectional survey that was disseminated to 303 residents of four small (populations 1500-2000) New Zealand towns. Evidence indicating a relationship between individual community capacity and self-reported health was unconvincing once the effects of income were incorporated. That is, people who rated their community's capacity higher did not have better self-rated health. Much stronger evidence supported the relationship between income and both higher individual community capacity and higher self-rated health. We conclude that individual community capacity may mediate the positive association between income and health, however, overall we find no evidence suggesting that intervening to enhance individual community capacity is likely to improve health outcomes.

Oxytocin promotes social bonding in dogs.

PubMed

Romero, Teresa; Nagasawa, Miho; Mogi, Kazutaka; Hasegawa, Toshikazu; Kikusui, Takefumi

2014-06-24

Recent evidence suggests that enduring social bonds have fitness benefits. However, very little is known about the neural circuitry and neurochemistry underlying the formation and maintenance of stable social bonds outside reproductive contexts. Oxytocin (OT), a neuropeptide synthetized by the hypothalamus in mammals, regulates many complex forms of social behavior and cognition in both human and nonhuman animals. Animal research, however, has concentrated on monogamous mammals, and it remains unknown whether OT also modulates social bonds in nonreproductive contexts. In this study we provide behavioral evidence that exogenous OT promotes positive social behaviors in the domestic dog toward not only conspecifics but also human partners. Specifically, when sprayed with OT, dogs showed higher social orientation and affiliation toward their owners and higher affiliation and approach behaviors toward dog partners than when sprayed with placebo. Additionally, the exchange of socio-positive behaviors with dog partners triggered the release of endogenous OT, highlighting the involvement of OT in the development of social relationships in the domestic dog. These data provide new insight into the mechanisms that facilitate the maintenance of close social bonds beyond immediate reproductive interest or genetic ties and complement a growing body of evidence that identifies OT as one of the neurochemical foundations of sociality in mammalian species.

Necroptosis in Acute Kidney Injury.

PubMed

Anders, Hans-Joachim

2018-05-31

Regulated necrosis is an expanding research field with important implications for acute kidney injury (AKI). A focused review of the evolving evidence for necroptosis in AKI, one of several forms of regulated necrosis defines the known and unknown. A literature search was performed in PUBMED and ScienceDirect between January 1957 and April 2018 using the following keywords: "acute kidney injury," "necrosis," "necroptosis," "necroinflammation." The necroptosis signaling cascade involves a number of proteins including receptor-interacting protein-1 (RIPK1), RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) as well as the MLKL regulator RGMb. The existing experimental evidence in AKI based on mice with genetic deletions of these proteins, more or less specific inhibitory compounds, and diverse experimental AKI models is reviewed. There is broad consistency suggesting a role for necroptosis in AKI, but some studies report divergent evidence potentially relating to the specific model used and the time point of analysis. Mlkl-deficient mice are currently the most specific and reliable experimental tool to study necroptosis in vivo (in kidney disease). The clinical potential of necroptosis inhibition in AKI is to be evaluated, but conceptual problems in AKI definitions and in complex clinical scenarios remain a concern. © 2018 S. Karger AG, Basel.

Roles of Inflammation, Oxidative Stress, and Vascular Dysfunction in Hypertension

PubMed Central

Dinh, Quynh N.; Drummond, Grant R.; Sobey, Christopher G.

2014-01-01

Hypertension is a complex condition and is the most common cardiovascular risk factor, contributing to widespread morbidity and mortality. Approximately 90% of hypertension cases are classified as essential hypertension, where the precise cause is unknown. Hypertension is associated with inflammation; however, whether inflammation is a cause or effect of hypertension is not well understood. The purpose of this review is to describe evidence from human and animal studies that inflammation leads to the development of hypertension, as well as the evidence for involvement of oxidative stress and endothelial dysfunction—both thought to be key steps in the development of hypertension. Other potential proinflammatory conditions that contribute to hypertension—such as activation of the sympathetic nervous system, aging, and elevated aldosterone—are also discussed. Finally, we consider the potential benefit of anti-inflammatory drugs and statins for antihypertensive therapy. The evidence reviewed suggests that inflammation can lead to the development of hypertension and that oxidative stress and endothelial dysfunction are involved in the inflammatory cascade. Aging and aldosterone may also both be involved in inflammation and hypertension. Hence, in the absence of serious side effects, anti-inflammatory drugs could potentially be used to treat hypertension in the future. PMID:25136585

ARC-1979-AC79-0164-1

NASA Image and Video Library

1979-02-13

Voyager 1 Image of Jupiter and two of its satellites (Io, left, and Europa). Io is about 350,000 kilometers (220,000 miles) above Jupiter's Great Red Spot; Europa is about 600,000 kilometers (375,000 miles) above Jupiter's clouds. Although both satellites have about the same brightness, Io's color is very different from Europa's. Io's equatorial region show two types of material -- dark orange, broken by several bright spots -- producing a mottled appearance. The poles are darker and reddish. Preliminary evidence suggests color variations within and between the polar regions. Io's surface composition is unknown, but scientists believe it may be a mixture of salts and sulfur. Erupoa is less strongly colored, although still relatively dark at short wavelengths. Markings on Eruopa are less evident that on the other satellites, although this picture shows darker regions toward the trailing half of the visible disk. Jupiter at this point is about 20 million kilometers (12.4 million miles) from the spacecraft. At this resolution (about 400 kimometers or 250 miles) there is evidence of circular motion in Jupiter's atmosphere. While the dominant large-scale motions are west-to-east, small-scale movement includes eddy-like circulation within and between the bands. (JPL ref: P-21082)

ARC-1979-A79-0164-1

NASA Image and Video Library

1979-02-13

Voyager 1 Image of Jupiter and two of its satellites (Io, left, and Europa). Io is about 350,000 kilometers (220,000 miles) above Jupiter's Great Red Spot; Europa is about 600,000 kilometers (375,000 miles) above Jupiter's clouds. Although both satellites have about the same brightness, Io's color is very different from Europa's. Io's equatorial region show two types of material -- dark orange, broken by several bright spots -- producing a mottled appearance. The poles are darker and reddish. Preliminary evidence suggests color variations within and between the polar regions. Io's surface composition is unknown, but scientists believe it may be a mixture of salts and sulfur. Erupoa is less strongly colored, although still relatively dark at short wavelengths. Markings on Eruopa are less evident that on the other satellites, although this picture shows darker regions toward the trailing half of the visible disk. Jupiter at this point is about 20 million kilometers (12.4 million miles) from the spacecraft. At this resolution (about 400 kimometers or 250 miles) there is evidence of circular motion in Jupiter's atmosphere. While the dominant large-scale motions are west-to-east, small-scale movement includes eddy-like circulation within and between the bands. (JPL ref: P-21082)

SLC26A9-mediated chloride secretion prevents mucus obstruction in airway inflammation

PubMed Central

Anagnostopoulou, Pinelopi; Riederer, Brigitte; Duerr, Julia; Michel, Sven; Binia, Aristea; Agrawal, Raman; Liu, Xuemei; Kalitzki, Katrin; Xiao, Fang; Chen, Mingmin; Schatterny, Jolanthe; Hartmann, Dorothee; Thum, Thomas; Kabesch, Michael; Soleimani, Manoocher; Seidler, Ursula; Mall, Marcus A.

2012-01-01

Asthma is a chronic condition with unknown pathogenesis, and recent evidence suggests that enhanced airway epithelial chloride (Cl–) secretion plays a role in the disease. However, the molecular mechanism underlying Cl– secretion and its relevance in asthma pathophysiology remain unknown. To determine the role of the solute carrier family 26, member 9 (SLC26A9) Cl– channel in asthma, we induced Th2-mediated inflammation via IL-13 treatment in wild-type and Slc26a9-deficient mice and compared the effects on airway ion transport, morphology, and mucus content. We found that IL-13 treatment increased Cl– secretion in the airways of wild-type but not Slc26a9-deficient mice. While IL-13–induced mucus overproduction was similar in both strains, treated Slc26a9-deficient mice exhibited airway mucus obstruction, which did not occur in wild-type controls. In a study involving healthy children and asthmatics, a polymorphism in the 3′ UTR of SLC26A9 that reduced protein expression in vitro was associated with asthma. Our data demonstrate that the SLC26A9 Cl– channel is activated in airway inflammation and suggest that SLC26A9-mediated Cl– secretion is essential for preventing airway obstruction in allergic airway disease. These results indicate that SLC26A9 may serve as a therapeutic target for airway diseases associated with mucus plugging. PMID:22945630

Transient microbiota exposures activate dormant Escherichia coli infection in the bladder and drive severe outcomes of recurrent disease

PubMed Central

2017-01-01

Pathogens often inhabit the body asymptomatically, emerging to cause disease in response to unknown triggers. In the bladder, latent intracellular Escherichia coli reservoirs are regarded as likely origins of recurrent urinary tract infection (rUTI), a problem affecting millions of women worldwide. However, clinically plausible triggers that activate these reservoirs are unknown. Clinical studies suggest that the composition of a woman’s vaginal microbiota influences her susceptibility to rUTI, but the mechanisms behind these associations are unclear. Several lines of evidence suggest that the urinary tract is routinely exposed to vaginal bacteria, including Gardnerella vaginalis, a dominant member of the vaginal microbiota in some women. Using a mouse model, we show that bladder exposure to G. vaginalis triggers E. coli egress from latent bladder reservoirs and enhances the potential for life-threatening outcomes of the resulting E. coli rUTI. Transient G. vaginalis exposures were sufficient to cause bladder epithelial apoptosis and exfoliation and interleukin-1-receptor-mediated kidney injury, which persisted after G. vaginalis clearance from the urinary tract. These results support a broader view of UTI pathogenesis in which disease can be driven by short-lived but powerful urinary tract exposures to vaginal bacteria that are themselves not “uropathogenic” in the classic sense. This “covert pathogenesis” paradigm may apply to other latent infections, (e.g., tuberculosis), or for diseases currently defined as noninfectious because routine culture fails to detect microbes of recognized significance. PMID:28358889

Defining the Geographical Range of the Plasmodium knowlesi Reservoir

PubMed Central

Moyes, Catherine L.; Henry, Andrew J.; Golding, Nick; Huang, Zhi; Singh, Balbir; Baird, J. Kevin; Newton, Paul N.; Huffman, Michael; Duda, Kirsten A.; Drakeley, Chris J.; Elyazar, Iqbal R. F.; Anstey, Nicholas M.; Chen, Qijun; Zommers, Zinta; Bhatt, Samir; Gething, Peter W.; Hay, Simon I.

2014-01-01

Background The simian malaria parasite, Plasmodium knowlesi, can cause severe and fatal disease in humans yet it is rarely included in routine public health reporting systems for malaria and its geographical range is largely unknown. Because malaria caused by P. knowlesi is a truly neglected tropical disease, there are substantial obstacles to defining the geographical extent and risk of this disease. Information is required on the occurrence of human cases in different locations, on which non-human primates host this parasite and on which vectors are able to transmit it to humans. We undertook a systematic review and ranked the existing evidence, at a subnational spatial scale, to investigate the potential geographical range of the parasite reservoir capable of infecting humans. Methodology/Principal Findings After reviewing the published literature we identified potential host and vector species and ranked these based on how informative they are for the presence of an infectious parasite reservoir, based on current evidence. We collated spatial data on parasite occurrence and the ranges of the identified host and vector species. The ranked spatial data allowed us to assign an evidence score to 475 subnational areas in 19 countries and we present the results on a map of the Southeast and South Asia region. Conclusions/Significance We have ranked subnational areas within the potential disease range according to evidence for presence of a disease risk to humans, providing geographical evidence to support decisions on prevention, management and prophylaxis. This work also highlights the unknown risk status of large parts of the region. Within this unknown category, our map identifies which areas have most evidence for the potential to support an infectious reservoir and are therefore a priority for further investigation. Furthermore we identify geographical areas where further investigation of putative host and vector species would be highly informative for the region-wide assessment. PMID:24676231

High-Intensity Interval Training After Stroke: An Opportunity to Promote Functional Recovery, Cardiovascular Health, and Neuroplasticity.

PubMed

Crozier, Jennifer; Roig, Marc; Eng, Janice J; MacKay-Lyons, Marilyn; Fung, Joyce; Ploughman, Michelle; Bailey, Damian M; Sweet, Shane N; Giacomantonio, Nicholas; Thiel, Alexander; Trivino, Michael; Tang, Ada

2018-04-01

Stroke is the leading cause of adult disability. Individuals poststroke possess less than half of the cardiorespiratory fitness (CRF) as their nonstroke counterparts, leading to inactivity, deconditioning, and an increased risk of cardiovascular events. Preserving cardiovascular health is critical to lower stroke risk; however, stroke rehabilitation typically provides limited opportunity for cardiovascular exercise. Optimal cardiovascular training parameters to maximize recovery in stroke survivors also remains unknown. While stroke rehabilitation recommendations suggest the use of moderate-intensity continuous exercise (MICE) to improve CRF, neither is it routinely implemented in clinical practice, nor is the intensity always sufficient to elicit a training effect. High-intensity interval training (HIIT) has emerged as a potentially effective alternative that encompasses brief high-intensity bursts of exercise interspersed with bouts of recovery, aiming to maximize cardiovascular exercise intensity in a time-efficient manner. HIIT may provide an alternative exercise intervention and invoke more pronounced benefits poststroke. To provide an updated review of HIIT poststroke through ( a) synthesizing current evidence; ( b) proposing preliminary considerations of HIIT parameters to optimize benefit; ( c) discussing potential mechanisms underlying changes in function, cardiovascular health, and neuroplasticity following HIIT; and ( d) discussing clinical implications and directions for future research. Preliminary evidence from 10 studies report HIIT-associated improvements in functional, cardiovascular, and neuroplastic outcomes poststroke; however, optimal HIIT parameters remain unknown. Larger randomized controlled trials are necessary to establish ( a) effectiveness, safety, and optimal training parameters within more heterogeneous poststroke populations; (b) potential mechanisms of HIIT-associated improvements; and ( c) adherence and psychosocial outcomes.

ExprAlign - the identification of ESTs in non-model species by alignment of cDNA microarray expression profiles

PubMed Central

2009-01-01

Background Sequence identification of ESTs from non-model species offers distinct challenges particularly when these species have duplicated genomes and when they are phylogenetically distant from sequenced model organisms. For the common carp, an environmental model of aquacultural interest, large numbers of ESTs remained unidentified using BLAST sequence alignment. We have used the expression profiles from large-scale microarray experiments to suggest gene identities. Results Expression profiles from ~700 cDNA microarrays describing responses of 7 major tissues to multiple environmental stressors were used to define a co-expression landscape. This was based on the Pearsons correlation coefficient relating each gene with all other genes, from which a network description provided clusters of highly correlated genes as 'mountains'. We show that these contain genes with known identities and genes with unknown identities, and that the correlation constitutes evidence of identity in the latter. This procedure has suggested identities to 522 of 2701 unknown carp ESTs sequences. We also discriminate several common carp genes and gene isoforms that were not discriminated by BLAST sequence alignment alone. Precision in identification was substantially improved by use of data from multiple tissues and treatments. Conclusion The detailed analysis of co-expression landscapes is a sensitive technique for suggesting an identity for the large number of BLAST unidentified cDNAs generated in EST projects. It is capable of detecting even subtle changes in expression profiles, and thereby of distinguishing genes with a common BLAST identity into different identities. It benefits from the use of multiple treatments or contrasts, and from the large-scale microarray data. PMID:19939286

Behçet syndrome: is it one condition?

PubMed

Yazici, H; Ugurlu, S; Seyahi, E

2012-12-01

Behçet's syndrome (BS) is a disease of unknown etiology, and as such, there have been efforts to classify BS within the popular nosological identities of the times such as seronegative spondarthritides, autoimmune, and more recently autoinflammatory diseases. Current evidence suggests that BS does not easily fit into any one of these lumps, while on occasion, it might be impossible to tell BS from Crohn's disease, especially when the main clinical presentation is intestinal ulceration. There are distinct regional differences in disease expression of BS with fewer cases of intestinal disease in the Mediterranean basin and less severe eye disease and less frequent skin pathergy among patients reported from northern Europe or America. The clustering of symptoms, especially with the recently described increased frequency of the acne/arthritis cluster in familial cases, suggests that more than one pathological pathway is involved in what we call BS today. Supportive evidence for this contention also comes from the observations that (a) the genetic component is very complex with perhaps different genetic modes of inheritance in the adult and in the pediatric patients; and (b) there are differing organ responses to one same drug. For example, the anti-TNF agents successfully control the oral ulcers while they have no effect on the pathergy reaction.

Epidemiologic evidence for different roles of ultraviolet A and B radiation in melanoma mortality rates.

PubMed

Garland, Cedric F; Garland, Frank C; Gorham, Edward D

2003-07-01

The action spectrum of ultraviolet radiation mainly responsible for melanoma induction is unknown, but evidence suggests it could be ultraviolet A (UVA), which has a different geographic distribution than ultraviolet B (UVB). This study assessed whether melanoma mortality rates are more closely related to the global distribution of UVA or UVB. UVA and UVB radiation and age-adjusted melanoma mortality rates were obtained for all 45 countries reporting cancer data to the World Health Organization. Stratospheric ozone data were obtained from NASA satellites. Average population skin pigmentation was obtained from skin reflectometry measurements. Paradoxically, melanoma mortality rates decreased with increasing UVB in men (r = -0.48, p < 0.001), and women (r = -0.57, p < 0.001), and with increasing UVA in both sexes. By contrast, rates were positively associated with increasing UVA/UVB ratio in men (r = + 0.49, p < 0.001) and women (r = + 0.55, p < 0.001). After multiple adjustment that included controlling for skin pigmentation, only UVA was associated with melanoma mortality rates in men (p < 0.02) with a suggestive but non-significant trend present in women (p = 0.12). UVA radiation was associated with melanoma mortality rates after controlling for UVB and average pigmentation. The results require confirmation in observational studies.

Conserved G-matrices of morphological and life-history traits among continental and island blue tit populations.

PubMed

Delahaie, B; Charmantier, A; Chantepie, S; Garant, D; Porlier, M; Teplitsky, C

2017-08-01

The genetic variance-covariance matrix (G-matrix) summarizes the genetic architecture of multiple traits. It has a central role in the understanding of phenotypic divergence and the quantification of the evolutionary potential of populations. Laboratory experiments have shown that G-matrices can vary rapidly under divergent selective pressures. However, because of the demanding nature of G-matrix estimation and comparison in wild populations, the extent of its spatial variability remains largely unknown. In this study, we investigate spatial variation in G-matrices for morphological and life-history traits using long-term data sets from one continental and three island populations of blue tit (Cyanistes caeruleus) that have experienced contrasting population history and selective environment. We found no evidence for differences in G-matrices among populations. Interestingly, the phenotypic variance-covariance matrices (P) were divergent across populations, suggesting that using P as a substitute for G may be inadequate. These analyses also provide the first evidence in wild populations for additive genetic variation in the incubation period (that is, the period between last egg laid and hatching) in all four populations. Altogether, our results suggest that G-matrices may be stable across populations inhabiting contrasted environments, therefore challenging the results of previous simulation studies and laboratory experiments.

Removal of foreign bodies in the upper gastrointestinal tract in adults: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

PubMed

Birk, Michael; Bauerfeind, Peter; Deprez, Pierre H; Häfner, Michael; Hartmann, Dirk; Hassan, Cesare; Hucl, Tomas; Lesur, Gilles; Aabakken, Lars; Meining, Alexander

2016-05-01

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the removal of foreign bodies in the upper gastrointestinal tract in adults. Recommendations Nonendoscopic measures 1 ESGE recommends diagnostic evaluation based on the patient's history and symptoms. ESGE recommends a physical examination focused on the patient's general condition and to assess signs of any complications (strong recommendation, low quality evidence). 2 ESGE does not recommend radiological evaluation for patients with nonbony food bolus impaction without complications. We recommend plain radiography to assess the presence, location, size, configuration, and number of ingested foreign bodies if ingestion of radiopaque objects is suspected or type of object is unknown (strong recommendation, low quality evidence). 3 ESGE recommends computed tomography (CT) scan in all patients with suspected perforation or other complication that may require surgery (strong recommendation, low quality evidence). 4 ESGE does not recommend barium swallow, because of the risk of aspiration and worsening of the endoscopic visualization (strong recommendation, low quality evidence). 5 ESGE recommends clinical observation without the need for endoscopic removal for management of asymptomatic patients with ingestion of blunt and small objects (except batteries and magnets). If feasible, outpatient management is appropriate (strong recommendation, low quality evidence). 6 ESGE recommends close observation in asymptomatic individuals who have concealed packets of drugs by swallowing ("body packing"). We recommend against endoscopic retrieval. We recommend surgical referral in cases of suspected packet rupture, failure of packets to progress, or intestinal obstruction (strong recommendation, low quality evidence). Endoscopic measures 7 ESGE recommends emergent (preferably within 2 hours, but at the latest within 6 hours) therapeutic esophagogastroduodenoscopy for foreign bodies inducing complete esophageal obstruction, and for sharp-pointed objects or batteries in the esophagus. We recommend urgent (within 24 hours) therapeutic esophagogastroduodenoscopy for other esophageal foreign bodies without complete obstruction (strong recommendation, low quality evidence). 8 ESGE suggests treatment of food bolus impaction in the esophagus by gently pushing the bolus into the stomach. If this procedure is not successful, retrieval should be considered (weak recommendation, low quality evidence). The effectiveness of medical treatment of esophageal food bolus impaction is debated. It is therefore recommended, that medical treatment should not delay endoscopy (strong recommendation, low quality evidence). 9 In cases of food bolus impaction, ESGE recommends a diagnostic work-up for potential underlying disease, including histological evaluation, in addition to therapeutic endoscopy (strong recommendation, low quality evidence). 10 ESGE recommends urgent (within 24 hours) therapeutic esophagogastroduodenoscopy for foreign bodies in the stomach such as sharp-pointed objects, magnets, batteries and large/long objects. We suggest nonurgent (within 72 hours) therapeutic esophagogastroduodenoscopy for medium-sized blunt foreign bodies in the stomach (strong recommendation, low quality evidence). 11 ESGE recommends the use of a protective device in order to avoid esophagogastric/pharyngeal damage and aspiration during endoscopic extraction of sharp-pointed foreign bodies. Endotracheal intubation should be considered in the case of high risk of aspiration (strong recommendation, low quality evidence). 12 ESGE suggests the use of suitable extraction devices according to the type and location of the ingested foreign body (weak recommendation, low quality evidence). 13 After successful and uncomplicated endoscopic removal of ingested foreign bodies, ESGE suggests that the patient may be discharged. If foreign bodies are not or cannot be removed, a case-by-case approach depending on the size and type of the foreign body is suggested (weak recommendation, low quality evidence). © Georg Thieme Verlag KG Stuttgart · New York.

Transcriptional profiling of human breast cancer cells cultured under microgravity conditions revealed the key role of genetic gravity sensors previously detected in Drosophila melanogaster

NASA Astrophysics Data System (ADS)

Valdivia-Silva, Julio E.; Lavan, David; Diego Orihuela-Tacuri, M.; Sanabria, Gabriela

2016-07-01

Currently, studies in Drosophila melanogaster has shown emerging evidence that microgravity stimuli can be detected at the genetic level. Analysis of the transcriptome in the pupal stage of the fruit flies under microgravity conditions versus ground controls has suggested the presence of a few candidate genes as "gravity sensors" which are experimentally validated. Additionally, several studies have shown that microgravity causes inhibitory effects in different types of cancer cells, although the genes involved and responsible for these effects are still unknown. Here, we demonstrate that the genes suggested as the sensors of gravitational waves in Drosophila melanogaster and their human counterpart (orthologous genes) are highly involved in carcinogenesis, proliferation, anti-apoptotic signals, invasiveness, and metastatic potential of breast cancer cell tumors. The transcriptome analyses suggested that the observed inhibitory effect in cancer cells could be due to changes in the genetic expression of these candidates. These results encourage the possibility of new therapeutic targets managed together and not in isolation.

Paleomagnetic Evidence for Partial Differentiation of the Silicate-Bearing IIE Iron Meteorite Parent Body

NASA Astrophysics Data System (ADS)

Maurel, C.; Bryson, J. F. J.; Weiss, B. P.; Scholl, A.

2016-12-01

The identification of dozens of petrologically diverse chondritic and achondritic meteoritic groups indicates that a diversity of planetesimals formed in the early solar system. It is commonly thought that planetesimals formed as either unmelted or else fully differentiated bodies, implying that chondrites and achondrites cannot have originated on a single body. However, it has been suggested that partially melted bodies with chondritic crusts and achondritic interiors may also have formed. This alternative proposal is supported by the recent identification of post-accretional remanent magnetization in CV, H chondrites, and also possibly in CM chondrites, which has been interpreted as possible evidence for a core dynamo on their parent bodies. Other piece of evidence suggesting the existence of partially differentiated bodies is the existence of the silicate-bearing IIE iron meteorites. The IIEs are composed of a Fe-Ni alloy matrix containing a mixture of chondritic, primitive achondritic, and chondritic silicate inclusions that likely formed on a single parent body. Therefore, IIEs may sample all three putative layers of a layered, partially differentiated body. On the other hand, the siderophile element compositions of the matrix metal demonstrate that it is not the product of fractional crystallization of a molten core. This suggests that the matrix metal is derived from isolated reservoirs of metal in the mantle and/or crust. It is unknown whether a large-scale metallic core, not represented by known meteorite samples, also formed on the same parent planetesimal. We can search for evidence of a molten, advecting core by assessing whether IIE irons contain remanent magnetization produced by a core dynamo. With this goal, we studied the paleomagnetism of a cloudy zone (CZ) interface in the Fe-Ni matrix of the IIE iron Colomera using X-ray photoelectron emission microscopy (XPEEM). Our initial results suggest that a steady, intense magnetic field was present during the gradual formation of the CZ. This may indicate the existence of an advecting core on the IIE parent body, which would support the hypothesis of a partially differentiated structure. We are continuing to test this conclusion with further XPEEM measurements on Colomera and other IIE irons.

Paleomagnetic Evidence for Partial Differentiation of the Silicate-Bearing IIE Iron Meteorite Parent Body

NASA Astrophysics Data System (ADS)

Maurel, C.; Bryson, J. F. J.; Weiss, B. P.; Scholl, A.

2017-12-01

The identification of dozens of petrologically diverse chondritic and achondritic meteoritic groups indicates that a diversity of planetesimals formed in the early solar system. It is commonly thought that planetesimals formed as either unmelted or else fully differentiated bodies, implying that chondrites and achondrites cannot have originated on a single body. However, it has been suggested that partially melted bodies with chondritic crusts and achondritic interiors may also have formed. This alternative proposal is supported by the recent identification of post-accretional remanent magnetization in CV, H chondrites, and also possibly in CM chondrites, which has been interpreted as possible evidence for a core dynamo on their parent bodies. Other piece of evidence suggesting the existence of partially differentiated bodies is the existence of the silicate-bearing IIE iron meteorites. The IIEs are composed of a Fe-Ni alloy matrix containing a mixture of chondritic, primitive achondritic, and chondritic silicate inclusions that likely formed on a single parent body. Therefore, IIEs may sample all three putative layers of a layered, partially differentiated body. On the other hand, the siderophile element compositions of the matrix metal demonstrate that it is not the product of fractional crystallization of a molten core. This suggests that the matrix metal is derived from isolated reservoirs of metal in the mantle and/or crust. It is unknown whether a large-scale metallic core, not represented by known meteorite samples, also formed on the same parent planetesimal. We can search for evidence of a molten, advecting core by assessing whether IIE irons contain remanent magnetization produced by a core dynamo. With this goal, we studied the paleomagnetism of a cloudy zone (CZ) interface in the Fe-Ni matrix of the IIE iron Colomera using X-ray photoelectron emission microscopy (XPEEM). Our initial results suggest that a steady, intense magnetic field was present during the gradual formation of the CZ. This may indicate the existence of an advecting core on the IIE parent body, which would support the hypothesis of a partially differentiated structure. We are continuing to test this conclusion with further XPEEM measurements on Colomera and other IIE irons.

A Previously Unknown Path to Corpuscularism in the Seventeenth Century: Santorio’s Marginalia to the Commentaria in Primam Fen Primi Libri Canonis Avicennae (1625)

PubMed Central

Bigotti, Fabrizio

2017-01-01

This paper presents some of Santorio's marginalia to his Commentaria in primam fen primi libri Canonis Avicennae (Venice, 1625), which I identified in the Sloane Collection of the British Library in 2016, as well as the evidence for their authorship. The name of the Venetian physician Santorio Santori (1561–1636) is linked with the introduction of quantification in medicine and with the invention of precision instruments that, displayed for the first time in this work, laid down the foundations for what we today understand as evidence-based medicine. But Santorio's monumentale opus also contains evidence of many quantified experiments and displays his ideas on mixtures, structure of matter and corpuscles, which are in many cases clarified and completed by the new marginalia. These ideas testify to an early interest in chemistry within the Medical School of Padua which predates both Galileo and Sennert and which has hitherto been unknown. PMID:28350287

Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data.

PubMed

Bigham, Abigail; Bauchet, Marc; Pinto, Dalila; Mao, Xianyun; Akey, Joshua M; Mei, Rui; Scherer, Stephen W; Julian, Colleen G; Wilson, Megan J; López Herráez, David; Brutsaert, Tom; Parra, Esteban J; Moore, Lorna G; Shriver, Mark D

2010-09-09

High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude.

Identifying Signatures of Natural Selection in Tibetan and Andean Populations Using Dense Genome Scan Data

PubMed Central

Bigham, Abigail; Bauchet, Marc; Pinto, Dalila; Mao, Xianyun; Akey, Joshua M.; Mei, Rui; Scherer, Stephen W.; Julian, Colleen G.; Wilson, Megan J.; López Herráez, David; Brutsaert, Tom; Parra, Esteban J.; Moore, Lorna G.; Shriver, Mark D.

2010-01-01

High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude. PMID:20838600

LEAping to conclusions: a computational reanalysis of late embryogenesis abundant proteins and their possible roles.

PubMed

Wise, Michael J

2003-10-29

The late embryogenesis abundant (LEA) proteins cover a number of loosely related groups of proteins, originally found in plants but now being found in non-plant species. Their precise function is unknown, though considerable evidence suggests that LEA proteins are involved in desiccation resistance. Using a number of statistically-based bioinformatics tools the classification of a large set of LEA proteins, covering all Groups, is reexamined together with some previous findings. Searches based on peptide composition return proteins with similar composition to different LEA Groups; keyword clustering is then applied to reveal keywords and phrases suggestive of the Groups' properties. Previous research has suggested that glycine is characteristic of LEA proteins, but it is only highly over-represented in Groups 1 and 2, while alanine, thought characteristic of Group 2, is over-represented in Group 3, 4 and 6 but under-represented in Groups 1 and 2. However, for LEA Groups 1 2 and 3 it is shown that glutamine is very significantly over-represented, while cysteine, phenylalanine, isoleucine, leucine and tryptophan are significantly under-represented. There is also evidence that the Group 4 LEA proteins are more appropriately redistributed to Group 2 and Group 3. Similarly, Group 5 is better found among the Group 3 LEA proteins. There is evidence that Group 2 and Group 3 LEA proteins, though distinct, might be related. This relationship is also evident in the overlapping sets of keywords for the two Groups, emphasising alpha-helical structure and, at a larger scale, filaments, all of which fits well with experimental evidence that proteins from both Groups are natively unstructured, but become structured under stress conditions. The keywords support localisation of LEA proteins both in the nucleus and associated with the cytoskeleton, and a mode of action similar to chaperones, perhaps the cold shock chaperones, via a role in DNA-binding. In general, non-globular and low-complexity proteins, such as the LEA proteins, pose particular challenges in determining their functions and modes of action. Rather than masking off and ignoring low-complexity domains, novel tools and tool combinations are needed which are capable of analysing such proteins in their entirety.

Task-selective memory effects for successfully implemented encoding strategies.

PubMed

Leshikar, Eric D; Duarte, Audrey; Hertzog, Christopher

2012-01-01

Previous behavioral evidence suggests that instructed strategy use benefits associative memory formation in paired associate tasks. Two such effective encoding strategies--visual imagery and sentence generation--facilitate memory through the production of different types of mediators (e.g., mental images and sentences). Neuroimaging evidence suggests that regions of the brain support memory reflecting the mental operations engaged at the time of study. That work, however, has not taken into account self-reported encoding task success (i.e., whether participants successfully generated a mediator). It is unknown, therefore, whether task-selective memory effects specific to each strategy might be found when encoding strategies are successfully implemented. In this experiment, participants studied pairs of abstract nouns under either visual imagery or sentence generation encoding instructions. At the time of study, participants reported their success at generating a mediator. Outside of the scanner, participants further reported the quality of the generated mediator (e.g., images, sentences) for each word pair. We observed task-selective memory effects for visual imagery in the left middle occipital gyrus, the left precuneus, and the lingual gyrus. No such task-selective effects were observed for sentence generation. Intriguingly, activity at the time of study in the left precuneus was modulated by the self-reported quality (vividness) of the generated mental images with greater activity for trials given higher ratings of quality. These data suggest that regions of the brain support memory in accord with the encoding operations engaged at the time of study.

Task-Selective Memory Effects for Successfully Implemented Encoding Strategies

PubMed Central

Leshikar, Eric D.; Duarte, Audrey; Hertzog, Christopher

2012-01-01

Previous behavioral evidence suggests that instructed strategy use benefits associative memory formation in paired associate tasks. Two such effective encoding strategies–visual imagery and sentence generation–facilitate memory through the production of different types of mediators (e.g., mental images and sentences). Neuroimaging evidence suggests that regions of the brain support memory reflecting the mental operations engaged at the time of study. That work, however, has not taken into account self-reported encoding task success (i.e., whether participants successfully generated a mediator). It is unknown, therefore, whether task-selective memory effects specific to each strategy might be found when encoding strategies are successfully implemented. In this experiment, participants studied pairs of abstract nouns under either visual imagery or sentence generation encoding instructions. At the time of study, participants reported their success at generating a mediator. Outside of the scanner, participants further reported the quality of the generated mediator (e.g., images, sentences) for each word pair. We observed task-selective memory effects for visual imagery in the left middle occipital gyrus, the left precuneus, and the lingual gyrus. No such task-selective effects were observed for sentence generation. Intriguingly, activity at the time of study in the left precuneus was modulated by the self-reported quality (vividness) of the generated mental images with greater activity for trials given higher ratings of quality. These data suggest that regions of the brain support memory in accord with the encoding operations engaged at the time of study. PMID:22693593

Outpatient endometrial aspiration: an alternative to methotrexate for pregnancy of unknown location.

PubMed

Insogna, Iris G; Farland, Leslie V; Missmer, Stacey A; Ginsburg, Elizabeth S; Brady, Paula C

2017-08-01

Pregnancies of unknown location with abnormal beta-human chorionic gonadotropin trends are frequently treated as presumed ectopic pregnancies with methotrexate. Preliminary data suggest that outpatient endometrial aspiration may be an effective tool to diagnose pregnancy location, while also sparing women exposure to methotrexate. The purpose of this study was to evaluate the utility of an endometrial sampling protocol for the diagnosis of pregnancies of unknown location after in vitro fertilization. A retrospective cohort study of 14,505 autologous fresh and frozen in vitro fertilization cycles from October 2007 to September 2015 was performed; 110 patients were diagnosed with pregnancy of unknown location, defined as a positive beta-human chorionic gonadotropin without ultrasound evidence of intrauterine or ectopic pregnancy and an abnormal beta-human chorionic gonadotropin trend (<53% rise or <15% fall in 2 days). These patients underwent outpatient endometrial sampling with Karman cannula aspiration. Patients with a beta-human chorionic gonadotropin decline ≥15% within 24 hours of sampling and/or villi detected on pathologic analysis were diagnosed with failing intrauterine pregnancy and had weekly beta-human chorionic gonadotropin measurements thereafter. Those patients with beta-human chorionic gonadotropin declines <15% and no villi identified were diagnosed with ectopic pregnancy and treated with intramuscular methotrexate (50 mg/m 2 ) or laparoscopy. Across 8 years of follow up, among women with pregnancy of unknown location, failed intrauterine pregnancy was diagnosed in 46 patients (42%), and ectopic pregnancy was diagnosed in 64 patients (58%). Clinical variables that included fresh or frozen embryo transfer, day of embryo transfer, serum beta-human chorionic gonadotropin at the time of sampling, endometrial thickness, and presence of an adnexal mass were not significantly different between patients with failed intrauterine pregnancy or ectopic pregnancy. In patients with failed intrauterine pregnancy, 100% demonstrated adequate postsampling beta-human chorionic gonadotropin declines; villi were identified in just 46% (n=21 patients). Patients with failed intrauterine pregnancy had significantly shorter time to resolution (negative serum beta-human chorionic gonadotropin) after sampling compared with patients with ectopic pregnancy (12.6 vs 26.3 days; P<.001). With the use of this safe and effective protocol of endometrial aspiration with Karman cannula, a large proportion of women with pregnancy of unknown location are spared methotrexate, with a shorter time to pregnancy resolution than those who receive methotrexate. Copyright © 2017 Elsevier Inc. All rights reserved.

Insulin induces long-term depression of VTA dopamine neurons via an endocannabinoid-mediated mechanism

PubMed Central

Labouèbe, Gwenaël; Liu, Shuai; Dias, Carine; Zou, Haiyan; Wong, Jovi C.Y.; Karunakaran, Subashini; Clee, Susanne M.; Phillips, Anthony; Boutrel, Benjamin; Borgland, Stephanie L.

2014-01-01

The prevalence of obesity has drastically increased over the last few decades. Exploration into how hunger and satiety signals influence the reward system can help us to understand non-homeostatic mechanisms of feeding. Evidence suggests that insulin may act in the ventral tegmental area (VTA), a critical site for reward-seeking behavior, to suppress feeding. However, the neural mechanisms underlying insulin effects in the VTA remain unknown. We demonstrate that insulin, a circulating catabolic peptide that inhibits feeding, can induce a long-term depression (LTD) of excitatory synapses onto VTA dopamine neurons. This effect requires endocannabinoid-mediated presynaptic inhibition of glutamate release. Furthermore, after a sweetened high fat meal, which elevates endogenous insulin levels, insulin-induced LTD is occluded. Finally, insulin in the VTA reduces food anticipatory behavior and conditioned place preference for food. Taken together, these results suggest that insulin in the VTA suppresses excitatory synaptic transmission and reduces salience of food-related cues. PMID:23354329

Brain-wide mapping of neural activity controlling zebrafish exploratory locomotion

PubMed Central

Dunn, Timothy W; Mu, Yu; Narayan, Sujatha; Randlett, Owen; Naumann, Eva A; Yang, Chao-Tsung; Schier, Alexander F

2016-01-01

In the absence of salient sensory cues to guide behavior, animals must still execute sequences of motor actions in order to forage and explore. How such successive motor actions are coordinated to form global locomotion trajectories is unknown. We mapped the structure of larval zebrafish swim trajectories in homogeneous environments and found that trajectories were characterized by alternating sequences of repeated turns to the left and to the right. Using whole-brain light-sheet imaging, we identified activity relating to the behavior in specific neural populations that we termed the anterior rhombencephalic turning region (ARTR). ARTR perturbations biased swim direction and reduced the dependence of turn direction on turn history, indicating that the ARTR is part of a network generating the temporal correlations in turn direction. We also find suggestive evidence for ARTR mutual inhibition and ARTR projections to premotor neurons. Finally, simulations suggest the observed turn sequences may underlie efficient exploration of local environments. DOI: http://dx.doi.org/10.7554/eLife.12741.001 PMID:27003593

Enduring Mental Health: Prevalence and Prediction

PubMed Central

2016-01-01

We review epidemiological evidence indicating that most people will develop a diagnosable mental disorder, suggesting that only a minority experience enduring mental health. This minority has received little empirical study, leaving the prevalence and predictors of enduring mental health unknown. We turn to the population-representative Dunedin cohort, followed from birth to midlife, to compare people never-diagnosed with mental disorder (N = 171; 17% prevalence) to those diagnosed at 1–2 study waves, the cohort mode (N = 409). Surprisingly, compared to this modal group, never-diagnosed Study members were not born into unusually well-to-do families, nor did their enduring mental health follow markedly sound physical health, or unusually high intelligence. Instead, they tended to have an advantageous temperament/personality style, and negligible family history of mental disorder. As adults, they report superior educational and occupational attainment, greater life satisfaction, and higher-quality relationships. Our findings draw attention to “enduring mental health” as a revealing psychological phenotype and suggest it deserves further study. PMID:27929304

The protozoan pathogen Toxoplasma gondii targets the paracellular pathway to invade the intestinal epithelium.

PubMed

Weight, Caroline M; Carding, Simon R

2012-07-01

Abstract  Toxoplasma gondii is a ubiquitous parasite found within all mammals and birds worldwide that can cause fatal infections in immunocompromised persons and fetuses. The parasite causes chronic infections by residing in long-living tissues of the muscle and brain. T. gondii infects the host through contaminated meat and water consumption with the gastrointestinal tract (GI tract) being the first point of contact with the host. The mechanisms by which the parasite invades the host through the GI tract are unknown, although it has been suggested that the paracellular pathway is important for parasite dissemination. Studies indicate that epithelial tight junction-associated proteins are affected by T. gondii, although which junctional proteins are affected and the nature of host protein-parasite interactions have not been established. We have uncovered evidence that T. gondii influences the cellular distribution of occludin to transmigrate the intestinal epithelium and suggest how candidate binding partners can be identified. © 2012 New York Academy of Sciences.

Activating situation schemas: the effects of multiple thematic roles on related verbs in a continuous priming paradigm.

PubMed

Herlofsky, Stacey M; Edmonds, Lisa A

2013-02-01

Extensive evidence has shown that presentation of a word (target) following a related word (prime) results in faster reaction times compared to unrelated words. Two primes preceding a target have been used to examine the effects of multiple influences on a target. Several studies have observed greater, or additive, priming effects of multiple related primes compared to single related primes. The present study aims to eliminate attentional factors that may have contributed to findings in previous studies that used explicitly presented primes and targets. Thus, a continuous priming paradigm where targets are unknown to participants is used with noun-noun-verb triads filling agent, patient, and action roles in situation schemas (tourist, car, rent). Results replicate priming of single nouns preceding related verbs but do not suggest an additive effect for two nouns versus one. The absence of additive priming suggests that attentional processes may have been a factor in previous research.

Threshold for sand mobility on Mars calibrated from seasonal variations of sand flux.

PubMed

Ayoub, F; Avouac, J-P; Newman, C E; Richardson, M I; Lucas, A; Leprince, S; Bridges, N T

2014-09-30

Coupling between surface winds and saltation is a fundamental factor governing geological activity and climate on Mars. Saltation of sand is crucial for both erosion of the surface and dust lifting into the atmosphere. Wind tunnel experiments along with measurements from surface meteorology stations and modelling of wind speeds suggest that winds should only rarely move sand on Mars. However, evidence for currently active dune migration has recently accumulated. Crucially, the frequency of sand-moving events and the implied threshold wind stresses for saltation have remained unknown. Here we present detailed measurements of Nili Patera dune field based on High Resolution Imaging Science Experiment images, demonstrating that sand motion occurs daily throughout much of the year and that the resulting sand flux is strongly seasonal. Analysis of the seasonal sand flux variation suggests an effective threshold for sand motion for application to large-scale model wind fields (1-100 km scale) of τ(s)=0.01±0.0015 N m(-2).

Stop Saying That It Is Wrong! Psychophysiological, Cognitive, and Metacognitive Markers of Children’s Sensitivity to Punishment

PubMed Central

Gonzalez-Gadea, Maria Luz; Scheres, Anouk; Tobon, Carlos Andres; Damm, Juliane; Baez, Sandra; Huepe, David; Marino, Julian; Marder, Sandra; Manes, Facundo; Abrevaya, Sofia; Ibanez, Agustin

2015-01-01

Neurodevelopmental evidence suggests that children’s main decision-making strategy is to avoid options likely to induce punishment. However, the cognitive and affective factors contributing to children’s avoidance to high punishment frequency remain unknown. The present study explored psychophysiological, cognitive, and metacognitive processes associated with sensitivity to punishment frequency. We evaluated 54 participants (between 8 and 15 years old) with a modified Iowa Gambling Task for children (IGT-C) which included options with varying long-term profit and punishment frequencies. Skin conductance responses (SCRs) were recorded during this task. Additionally, we assessed IGT-C metacognitive knowledge, fluid intelligence, and executive functions. Participants exhibited behavioral avoidance and high anticipatory SCRs to options with high frequency of punishment. Moreover, age, IGT-C metacognitive knowledge, and inhibitory control were associated with individual differences in sensitivity to punishment frequency. Our results suggest that children’s preference for infrequently punished decisions is partially explained by psychophysiological signals as well as task complexity and development of cognitive control. PMID:26218584

Invariant U2 snRNA nucleotides form a stem loop to recognize the intron early in splicing

PubMed Central

Perriman, Rhonda; Ares, Manuel

2010-01-01

U2 snRNA-intron branchpoint pairing is a critical step in pre-mRNA recognition by the splicing apparatus, but the mechanism by which these two RNAs engage each other is unknown. Here we identify a new U2 snRNA structure, the branchpoint interaction stem-loop (BSL), that presents the U2 nucleotides that will contact the intron. We provide evidence that the BSL forms prior to interaction with the intron, and is disrupted by the DExD/H protein Prp5p during engagement of the snRNA with the intron. In vitro splicing complex assembly in a BSL-destabilized mutant extract suggests that the BSL is required at a previously unrecognized step between commitment complex and prespliceosome formation. The extreme evolutionary conservation of the BSL suggests it represents an ancient structural solution to the problem of intron branchpoint recognition by dynamic RNA elements that must serve multiple functions at other times during splicing. PMID:20471947

The Mere Co-Presence: Synchronization of Autonomic Signals and Emotional Responses across Co-Present Individuals Not Engaged in Direct Interaction

PubMed Central

Golland, Yulia; Arzouan, Yossi; Levit-Binnun, Nava

2015-01-01

Existing evidence suggests that in social contexts individuals become coupled in their emotions and behaviors. Furthermore, recent biological studies demonstrate that the physiological signals of interacting individuals become coupled as well, exhibiting temporally synchronized response patterns. However, it is yet unknown whether people can shape each other's responses without the direct, face-to-face interaction. Here we investigated whether the convergence of physiological and emotional states can occur among “merely co-present” individuals, without direct interactional exchanges. To this end, we measured continuous autonomic signals and collected emotional responses of participants who watched emotional movies together, seated side-by-side. We found that the autonomic signals of co-present participants were idiosyncratically synchronized and that the degree of this synchronization was correlated with the convergence of their emotional responses. These findings suggest that moment-to-moment emotional transmissions, resulting in shared emotional experiences, can occur in the absence of direct communication and are mediated by autonomic synchronization. PMID:26018597

Group Size Effect on Cooperation in One-Shot Social Dilemmas II: Curvilinear Effect.

PubMed

Capraro, Valerio; Barcelo, Hélène

2015-01-01

In a world in which many pressing global issues require large scale cooperation, understanding the group size effect on cooperative behavior is a topic of central importance. Yet, the nature of this effect remains largely unknown, with lab experiments insisting that it is either positive or negative or null, and field experiments suggesting that it is instead curvilinear. Here we shed light on this apparent contradiction by considering a novel class of public goods games inspired to the realistic scenario in which the natural output limits of the public good imply that the benefit of cooperation increases fast for early contributions and then decelerates. We report on a large lab experiment providing evidence that, in this case, group size has a curvilinear effect on cooperation, according to which intermediate-size groups cooperate more than smaller groups and more than larger groups. In doing so, our findings help fill the gap between lab experiments and field experiments and suggest concrete ways to promote large scale cooperation among people.

Stop Saying That It Is Wrong! Psychophysiological, Cognitive, and Metacognitive Markers of Children's Sensitivity to Punishment.

PubMed

Gonzalez-Gadea, Maria Luz; Scheres, Anouk; Tobon, Carlos Andres; Damm, Juliane; Baez, Sandra; Huepe, David; Marino, Julian; Marder, Sandra; Manes, Facundo; Abrevaya, Sofia; Ibanez, Agustin

2015-01-01

Neurodevelopmental evidence suggests that children's main decision-making strategy is to avoid options likely to induce punishment. However, the cognitive and affective factors contributing to children's avoidance to high punishment frequency remain unknown. The present study explored psychophysiological, cognitive, and metacognitive processes associated with sensitivity to punishment frequency. We evaluated 54 participants (between 8 and 15 years old) with a modified Iowa Gambling Task for children (IGT-C) which included options with varying long-term profit and punishment frequencies. Skin conductance responses (SCRs) were recorded during this task. Additionally, we assessed IGT-C metacognitive knowledge, fluid intelligence, and executive functions. Participants exhibited behavioral avoidance and high anticipatory SCRs to options with high frequency of punishment. Moreover, age, IGT-C metacognitive knowledge, and inhibitory control were associated with individual differences in sensitivity to punishment frequency. Our results suggest that children's preference for infrequently punished decisions is partially explained by psychophysiological signals as well as task complexity and development of cognitive control.

Indication for Dialysis Initiation and Mortality in Patients With Chronic Kidney Failure: A Retrospective Cohort Study

PubMed Central

Rivara, Matthew B.; Chen, Chang Huei; Nair, Anupama; Cobb, Denise; Himmelfarb, Jonathan; Mehrotra, Rajnish

2016-01-01

Background Initiation of maintenance dialysis for patients with chronic kidney failure is a period of high risk for adverse patient outcomes. Whether indications for dialysis initiation are associated with mortality among this population is unknown. Study Design Retrospective cohort study. Setting & Participants 461 patients who initiated dialysis (hemodialysis, 437; peritoneal dialysis, 24) from January 1st, 2004 through December 31st, 2012 and were treated in facilities operated by a single dialysis organization. Follow-up for the primary outcome was through December 31st, 2013. Predictor Clinically documented primary indication for dialysis initiation, as categorized into four groups: laboratory evidence of kidney function decline (reference category), uremic symptoms, volume overload or hypertension, and other/unknown. Outcomes All-cause mortality Results Over a median follow-up of 2.4 years, 183 (40%) patients died. Crude mortality rates were 10.0 (95% CI, 6.8–14.7), 12.7 (95% CI, 10.2–15.7), 21.7 (95% CI, 16.4–28.6), and 12.2 (95% CI, 6.8–14.7) per 100 patient-years among patients initiating dialysis primarily for laboratory evidence of kidney function decline, uremic symptoms, volume overload or hypertension, and other/unknown reason, respectively. Following adjustment for demographic variables, coexisting illnesses, and estimated glomerular filtration rate, initiation of dialysis for uremic symptoms, volume overload or hypertension, or for other/unknown reasons were associated with 1.12 (95% CI, 0.72–1.77), 1.71 (95% CI, 1.03–2.84), and 1.28 (95% CI, 0.73–2.26) times higher risk, respectively, for subsequent mortality compared to initiation for laboratory evidence of kidney function decline. Limitations Possibility of residual confounding by unmeasured variables; reliance on clinical documentation to ascertain exposure Conclusions Patients initiating dialysis due to volume overload may have increased risk for mortality compared to patients initiating dialysis due to laboratory evidence of kidney function decline. Further studies are needed to identify and test interventions that might reduce this risk. PMID:27637132

Gourds and squashes (Cucurbita spp.) adapted to megafaunal extinction and ecological anachronism through domestication.

PubMed

Kistler, Logan; Newsom, Lee A; Ryan, Timothy M; Clarke, Andrew C; Smith, Bruce D; Perry, George H

2015-12-08

The genus Cucurbita (squashes, pumpkins, gourds) contains numerous domesticated lineages with ancient New World origins. It was broadly distributed in the past but has declined to the point that several of the crops' progenitor species are scarce or unknown in the wild. We hypothesize that Holocene ecological shifts and megafaunal extinctions severely impacted wild Cucurbita, whereas their domestic counterparts adapted to changing conditions via symbiosis with human cultivators. First, we used high-throughput sequencing to analyze complete plastid genomes of 91 total Cucurbita samples, comprising ancient (n = 19), modern wild (n = 30), and modern domestic (n = 42) taxa. This analysis demonstrates independent domestication in eastern North America, evidence of a previously unknown pathway to domestication in northeastern Mexico, and broad archaeological distributions of taxa currently unknown in the wild. Further, sequence similarity between distant wild populations suggests recent fragmentation. Collectively, these results point to wild-type declines coinciding with widespread domestication. Second, we hypothesize that the disappearance of large herbivores struck a critical ecological blow against wild Cucurbita, and we take initial steps to consider this hypothesis through cross-mammal analyses of bitter taste receptor gene repertoires. Directly, megafauna consumed Cucurbita fruits and dispersed their seeds; wild Cucurbita were likely left without mutualistic dispersal partners in the Holocene because they are unpalatable to smaller surviving mammals with more bitter taste receptor genes. Indirectly, megafauna maintained mosaic-like landscapes ideal for Cucurbita, and vegetative changes following the megafaunal extinctions likely crowded out their disturbed-ground niche. Thus, anthropogenic landscapes provided favorable growth habitats and willing dispersal partners in the wake of ecological upheaval.

Gourds and squashes (Cucurbita spp.) adapted to megafaunal extinction and ecological anachronism through domestication

PubMed Central

Kistler, Logan; Newsom, Lee A.; Ryan, Timothy M.; Smith, Bruce D.; Perry, George H.

2015-01-01

The genus Cucurbita (squashes, pumpkins, gourds) contains numerous domesticated lineages with ancient New World origins. It was broadly distributed in the past but has declined to the point that several of the crops’ progenitor species are scarce or unknown in the wild. We hypothesize that Holocene ecological shifts and megafaunal extinctions severely impacted wild Cucurbita, whereas their domestic counterparts adapted to changing conditions via symbiosis with human cultivators. First, we used high-throughput sequencing to analyze complete plastid genomes of 91 total Cucurbita samples, comprising ancient (n = 19), modern wild (n = 30), and modern domestic (n = 42) taxa. This analysis demonstrates independent domestication in eastern North America, evidence of a previously unknown pathway to domestication in northeastern Mexico, and broad archaeological distributions of taxa currently unknown in the wild. Further, sequence similarity between distant wild populations suggests recent fragmentation. Collectively, these results point to wild-type declines coinciding with widespread domestication. Second, we hypothesize that the disappearance of large herbivores struck a critical ecological blow against wild Cucurbita, and we take initial steps to consider this hypothesis through cross-mammal analyses of bitter taste receptor gene repertoires. Directly, megafauna consumed Cucurbita fruits and dispersed their seeds; wild Cucurbita were likely left without mutualistic dispersal partners in the Holocene because they are unpalatable to smaller surviving mammals with more bitter taste receptor genes. Indirectly, megafauna maintained mosaic-like landscapes ideal for Cucurbita, and vegetative changes following the megafaunal extinctions likely crowded out their disturbed-ground niche. Thus, anthropogenic landscapes provided favorable growth habitats and willing dispersal partners in the wake of ecological upheaval. PMID:26630007

Ecological response of plant consumers to Middle-Upper Pennsylvanian extinctions in Illinois Basin coal swamps: Evidence from plant/arthropod interactions

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

Labandeira, C.; Phillips, T.

1992-01-01

Paleobotanical studies of coal-swamp vegetation during the Middle to Upper Pennsylvanian of North America indicate major changes from lycopsid dominated to tree-fern dominated coal-swamp forests as a result of extinction. This taxonomic shift from lycopsids to tree ferns should have implications on dependent feeding guilds, such as detritivores and herbivores. Comparative coal-ball evidence from the Springfield and Herrin Coals (Carbondale Fm.) and Calhoun Coal (Mattoon Fm.) is used to address this issue. The two major feeding guilds of Pennsylvanian coal-swamps were detritivores and herbivores. Detritivores were dominant throughout the interval. Evidence suggests an increasing presence of herbivores during the Desmoinesianmore » and especially during the Missourian. Based on identifications of tissue types found in coprolite types and plant tissue damage patterns, detritivores such as oribatid mites and an unknown stem-parenchyma consumer of Psaronius tree ferns occur before and after the extinction. Based on available evidence, detritivores apparently exhibited stability, particularly since the taxonomic affiliation of their food resource shifted considerably, thus indicating dietary specificities based instead on tissue type. There is evidence for herbivory by stem-miners on Missourian age tree-fern petioles; this distinctive behavior has not been reported for Desmoinesean or older deposits. The arthropod body-fossil record is consistent with this pattern: detritivore groups such as roaches survive the extinction largely intact, whereas other groups such as diverse protorthopterans,'' some of which were most likely herbivorous, experienced a significant extinction.« less

Traditional Chinese medicine for knee osteoarthritis: An overview of systematic review

PubMed Central

Wang, Qing; Chen, Hao

2017-01-01

Background Traditional Chinese medicine (TCM) has been accepted as a complementary therapy for knee osteoarthritis. However, the efficacy and safety of the intervention were still conflicting and uncertain. Meanwhile, the quality of methodology and evidence in the field was unknown. Objective To summarize the characteristics and critically evaluate the quality of methodology, as well as the evidence of systematic reviews (SRs) on TCM for knee osteoarthritis. Methods Five electronic databases were searched from inception to April 2016. The methodological quality of the included studies was assessed by AMSTAR and ROBIS. The quality of the evidence was determined using the GRADE approach. Results Ten SRs were included. The conclusions suggest that TCM provides potential benefits for patients with knee osteoarthritis. These benefits include pain relief, functional improvement, and presence of few adverse events. Limitations of the methodological quality mainly included the lack of a-priori protocol or protocol registration and incomprehensive literature search. A list of excluded studies was also not provided. The overall quality of evidence in the SRs was poor, ranging from “very low” to “low,” mainly because of the serious risk of bias of original trials, inconsistencies, and imprecision in the outcomes. Conclusions TCM generally appears to be effective for knee osteoarthritis treatment. However, the evidence is not robust enough because of the methodological flaws in SRs. Hence, these conclusions on available SRs should be treated with caution for clinical practice. PMID:29267324

Is Performance Feedback for Educators an Evidence-Based Practice? A Systematic Review and Evaluation Based on Single-Case Research

ERIC Educational Resources Information Center

Fallon, Lindsay M.; Collier-Meek, Melissa A.; Maggin, Daniel M.; Sanetti, Lisa M. H.; Johnson, Austin H.

2015-01-01

Optimal levels of treatment fidelity, a critical moderator of intervention effectiveness, are often difficult to sustain in applied settings. It is unknown whether performance feedback, a widely researched method for increasing educators' treatment fidelity, is an evidence-based practice. The purpose of this review was to evaluate the current…

Initial treatment of complete rotator cuff tear and transition to surgical treatment: systematic review of the evidence

PubMed Central

Abdul-Wahab, Taiceer A.; Betancourt, Jean P.; Hassan, Fadi; Thani, Saeed Al.; Choueiri, Hened; Jain, Nitin B.; Malanga, Gerard A.; Murrell, William D.; Prasad, Anil; Verborgt, Olivier

2016-01-01

Summary Background rotator cuff tear affects many people. Natural history, and evidence for non-operative treatment remains limited. Our objective is to assess evidence available for the efficacy and morbidity of commonly used systemic medications, physiotherapy, and injections alongside evaluating any negative long-term effects. Methods a systematic search was performed of PubMed, Cochrane, EMBASE and CINAHL dates (1 January 1960 – 1 December 2014), search terms: ‘rotator cuff tear’, ‘natural history’, ‘atraumatic’, ‘injection’, ‘physiotherapy’ or ‘physical therapy’, ‘injection’, ‘corticosteroid’, ‘PRP‘, ‘MSC’, risk of conservative treatment’, and ‘surgical indication’. Results eleven studies were included. The mean Coleman Methodology Score modified for conservative therapy is 69.21 (range 88–44) (SD 12.31). This included 2 RCTs, 7 prospective, and 2 retrospective studies. Evidence suggests it is safe to monitor symptomatic rotator cuff tears, as tear size and symptoms are not correlated with pain, function, and/or ultimate outcome. Conclusions complete rotator cuff tears may be effectively treated with injections, exercise in the short and intermediate terms respectively. Negative effect of corticosteroids on rotator cuff tissue has not been demonstrated. Timing to end conservative treatment is unknown, but likely indicated when a patient demonstrates increased weakness and loss of function not recoverable by physiotherapy. PMID:27331030

Water vascular system architecture in an Ordovician ophiuroid.

PubMed

Clark, Elizabeth G; Bhullar, Bhart-Anjan S; Darroch, Simon A F; Briggs, Derek E G

2017-12-01

Understanding the water vascular system (WVS) in early fossil echinoderms is critical to elucidating the evolution of this system in extant forms. Here we present the first report of the internal morphology of the water vascular system of a stem ophiuroid. The radial canals are internal to the arm, but protected dorsally by a plate separate to the ambulacrals. The canals zig-zag with no evidence of constrictions, corresponding to sphincters, which control pairs of tube feet in extant ophiuroids. The morphology suggests that the unpaired tube feet must have operated individually, and relied on the elasticity of the radial canals, lateral valves and tube foot musculature alone for extension and retraction. This arrangement differs radically from that in extant ophiuroids, revealing a previously unknown Palaeozoic configuration. © 2017 The Author(s).

Fibromyalgia: a stress disorder? Piecing the biopsychosocial puzzle together.

PubMed

Van Houdenhove, Boudewijn; Egle, Ulrich T

2004-01-01

Fibromyalgia (FM) is a controversial syndrome, characterised by persistent widespread pain, abnormal pain sensitivity and additional symptoms such as fatigue and sleep disturbance. The syndrome largely overlaps with other functional somatic disorders, particularly chronic fatigue syndrome (CFS). Although the exact aetiology and pathogenesis of FM are still unknown, it has been suggested that stress may play a key role in the syndrome. This article first reviews the function of the stress response system, placing special emphasis on the relationships between adverse life experiences, stress regulation and pain-processing mechanisms, and summarising the evidence for a possible aetiopathogenetic role of stress in FM. Finally, an integrative biopsychosocial model that conceptualizes FM as a stress disorder is proposed, and the clinical and research implications of the model are discussed.

Changes in the taste and textural attributes of apples in response to climate change

PubMed Central

Sugiura, Toshihiko; Ogawa, Hidekazu; Fukuda, Noriaki; Moriguchi, Takaya

2013-01-01

The effects of climate change on the taste and textural attributes of foods remain largely unknown, despite much public interest. On the basis of 30–40 years of records, we provide evidence that the taste and textural attributes of apples have changed as a result of recent global warming. Decreases in both acid concentration, fruit firmness and watercore development were observed regardless of the maturity index used for harvest date (e.g., calendar date, number of days after full bloom, peel colour and starch concentration), whereas in some cases the soluble-solids concentration increased; all such changes may have resulted from earlier blooming and higher temperatures during the maturation period. These results suggest that the qualities of apples in the market are undergoing long-term changes. PMID:23948740

Ecosystem Services Connect Environmental Change to Human Health Outcomes

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

Bayles, Brett R.; Brauman, Kate A.; Adkins, Joshua N.

Global environmental change, driven in large part by human activities, profoundly impacts the structure and functioning of Earth’s ecosystems (Millennium Ecosystem Assessment 2005). We are beginning to push beyond planetary boundaries (Steffan et al. 2015), and the consequences for human health remain largely unknown (Myers et al. 2013). Growing evidence suggests that ecological transformations can dramatically affect human health in ways that are both obvious and obscure (Myers and Patz 2009; Myers et al. 2013). The framework of ecosystem services, designed to evaluate the benefits that people derive from ecosystem products and processes, provides a compelling framework for integrating themore » many factors that influence the human health response to global change, as well as for integrating health impacts into broader analyses of the impacts of this change« less

Wnt-10b, uniquely among Wnts, promotes epithelial differentiation and shaft growth

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

Ouji, Yukiteru; Yoshikawa, Masahide; Moriya, Kei

2008-03-07

Although Wnts are expressed in hair follicles throughout life from embryo to adult, and considered to be critical for their development and maturation, their roles remain largely unknown. In the present study, we investigated the effects of Wnts (Wnt-3a, Wnt-5a, Wnt-10b, and Wnt-11) on epithelial cell differentiation using adult mouse-derived primary skin epithelial cell (MPSEC) cultures and hair growth using hair follicle organ cultures. Only Wnt-10b showed evident promotion of epithelial cell differentiation and hair shaft growth, in contrast to Wnt-3a, 5a, and 11. Our results suggest that Wnt-10b is unique and plays an important role in differentiation of epithelialmore » cells in the hair follicle.« less

The biology and function of exosomes in cancer

PubMed Central

Kalluri, Raghu

2016-01-01

Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40–150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients. PMID:27035812

Dimensions of Temperament and Depressive Symptoms: Replicating a Three-Way Interaction

PubMed Central

Vasey, Michael W.; Harbaugh, Casaundra N.; Lonigan, Chistopher J.; Phillips, Beth M.; Hankin, Benjamin L.; Willem, Lore; Bijttebier, Patricia

2014-01-01

High negative emotionality (NE), low positive emotionality (PE), and low self-regulatory capacity (i.e., effortful control or EC) are related to depressive symptoms and furthermore, may moderate one another’s relations to such symptoms. Indeed, preliminary evidence suggests they may operate in a three-way interaction (Dinovo & Vasey, 2011), but the replicability of that finding remains unknown. Therefore, we tested this NExPExEC interaction in association with depressive symptoms in 5 independent samples. This interaction was significant in 4 of the 5 samples and a combined sample and approached significance in the fifth sample. In contrast, the NExPExEC interaction was unrelated to general anxious symptoms and thus may be specific to symptoms of depression. Implications, directions for future research, and limitations are discussed. PMID:24493906

CD68 acts as a major gateway for malaria sporozoite liver infection

PubMed Central

Cha, Sung-Jae; Park, Kiwon; Srinivasan, Prakash; Schindler, Christian W.; van Rooijen, Nico; Stins, Monique

2015-01-01

After being delivered by the bite from an infected mosquito, Plasmodium sporozoites enter the blood circulation and infect the liver. Previous evidence suggests that Kupffer cells, a macrophage-like component of the liver blood vessel lining, are traversed by sporozoites to initiate liver invasion. However, the molecular determinants of sporozoite–Kupffer cell interactions are unknown. Understanding the molecular basis for this specific recognition may lead to novel therapeutic strategies to control malaria. Using a phage display library screen, we identified a peptide, P39, that strongly binds to the Kupffer cell surface and, importantly, inhibits sporozoite Kupffer cell entry. Furthermore, we determined that P39 binds to CD68, a putative receptor for sporozoite invasion of Kupffer cells that acts as a gateway for malaria infection of the liver. PMID:26216124

Content-specific evidence accumulation in inferior temporal cortex during perceptual decision-making

PubMed Central

Tremel, Joshua J.; Wheeler, Mark E.

2015-01-01

During a perceptual decision, neuronal activity can change as a function of time-integrated evidence. Such neurons may serve as decision variables, signaling a choice when activity reaches a boundary. Because the signals occur on a millisecond timescale, translating to human decision-making using functional neuroimaging has been challenging. Previous neuroimaging work in humans has identified patterns of neural activity consistent with an accumulation account. However, the degree to which the accumulating neuroimaging signals reflect specific sources of perceptual evidence is unknown. Using an extended face/house discrimination task in conjunction with cognitive modeling, we tested whether accumulation signals, as measured using functional magnetic resonance imaging (fMRI), are stimulus-specific. Accumulation signals were defined as a change in the slope of the rising edge of activation corresponding with response time (RT), with higher slopes associated with faster RTs. Consistent with an accumulation account, fMRI activity in face- and house-selective regions in the inferior temporal cortex increased at a rate proportional to decision time in favor of the preferred stimulus. This finding indicates that stimulus-specific regions perform an evidence integrative function during goal-directed behavior and that different sources of evidence accumulate separately. We also assessed the decision-related function of other regions throughout the brain and found that several regions were consistent with classifications from prior work, suggesting a degree of domain generality in decision processing. Taken together, these results provide support for an integration-to-boundary decision mechanism and highlight possible roles of both domain-specific and domain-general regions in decision evidence evaluation. PMID:25562821

Chiral Sensitivity in Electron-Molecule Interactions

NASA Astrophysics Data System (ADS)

Dreiling, Joan

2015-09-01

All molecular forms of life possess a chiral asymmetry, with amino acids and sugars found respectively in L- and D-enantiomers only. The primordial origin of this enantiomeric excess is unknown. One possible explanation is given by the Vester- Ulbricht hypothesis, which suggests that left-handed electrons present in beta-radiation, produced by parity-violating weak decays, interacted with biological precursors and preferentially destroyed one of the two enantiomers. Experimental tests of this idea have thus far yielded inconclusive results. We show direct evidence for chirally-dependent bond breaking through a dissociative electron attachment (DEA) reaction when spin-polarized electrons are incident on gas-phase chiral molecules. This provides unambiguous evidence for a well-defined, chirally-sensitive destructive molecular process and, as such, circumstantial evidence for the Vester-Ulbricht hypothesis. I will also present the results of our systematic study of the DEA asymmetry for different chiral halocamphor molecules. Three halocamphor molecules were investigated: 3-bromocamphor (C10H15BrO), 3-iodocamphor(C10H15IO), and 10-iodocamphor. The DEA asymmetries collected for bromocamphor and iodocamphor are qualitatively different, suggesting that the atomic number of the heaviest atom in the molecule plays a crucial role in the asymmetric interactions. The DEA asymmetry data for 3- and 10-iodocamphor have the same qualitative behavior, but the 10-iodocamphor asymmetry is about twice as large at the lowest energies investigated, so the location of the heavy atom in the camphor molecule also affects the asymmetries. This work was performed at the University of Nebraska-Lincoln. This project is funded by NSF Grant PHY-1206067.

Brain swelling and death in children with cerebral malaria.

PubMed

Seydel, Karl B; Kampondeni, Samuel D; Valim, Clarissa; Potchen, Michael J; Milner, Danny A; Muwalo, Francis W; Birbeck, Gretchen L; Bradley, William G; Fox, Lindsay L; Glover, Simon J; Hammond, Colleen A; Heyderman, Robert S; Chilingulo, Cowles A; Molyneux, Malcolm E; Taylor, Terrie E

2015-03-19

Case fatality rates among African children with cerebral malaria remain in the range of 15 to 25%. The key pathogenetic processes and causes of death are unknown, but a combination of clinical observations and pathological findings suggests that increased brain volume leading to raised intracranial pressure may play a role. Magnetic resonance imaging (MRI) became available in Malawi in 2009, and we used it to investigate the role of brain swelling in the pathogenesis of fatal cerebral malaria in African children. We enrolled children who met a stringent definition of cerebral malaria (one that included the presence of retinopathy), characterized them in detail clinically, and obtained MRI scans on admission and daily thereafter while coma persisted. Of 348 children admitted with cerebral malaria (as defined by the World Health Organization), 168 met the inclusion criteria, underwent all investigations, and were included in the analysis. A total of 25 children (15%) died, 21 of whom (84%) had evidence of severe brain swelling on MRI at admission. In contrast, evidence of severe brain swelling was seen on MRI in 39 of 143 survivors (27%). Serial MRI scans showed evidence of decreasing brain volume in the survivors who had had brain swelling initially. Increased brain volume was seen in children who died from cerebral malaria but was uncommon in those who did not die from the disease, a finding that suggests that raised intracranial pressure may contribute to a fatal outcome. The natural history indicates that increased intracranial pressure is transient in survivors. (Funded by the National Institutes of Health and Wellcome Trust U.K.).

Judgment of moral and social transgression in schizophrenia.

PubMed

McGuire, Jonathan; Brüne, Martin; Langdon, Robyn

2017-07-01

Despite evidence of pervasive social-cognitive deficits in schizophrenia, little is known of moral cognition in this population. While recent research indicates that impairment of explicit moral reasoning is explained by these individuals' other cognitive deficits, their capacities for basic moral judgment are unknown. 45 people with schizophrenia and 27 healthy controls completed the Moral-Conventional Distinction Task: a classic task that assesses judgment of violations of moral or social convention on permissibility, severity, and authority-contingence. Justifications of judgments were also probed. Basic cognition was indexed by measures of IQ, verbal memory, and information processing speed. Self-report inventories were used to assess different facets of 'empathy' (e.g., perspective-taking, or theory of mind, and empathic concern), and aggressive tendencies. Groups did not differ significantly in judgments of permissibility or authority-contingency, or justifications of judgments. Patients did, however, rate violations of social (but not moral) convention more harshly. They also took longer to judge impermissibility of moral (but nor social) transgressions. Slower moral judgment in patients was associated with lower levels of self-reported empathic concern, while harsher condemnation of social transgression was associated with poorer (self-reported) perspective-taking. Findings provide no evidence that moral judgment is fundamentally compromised in schizophrenia. Evidence of slower moral judgment in schizophrenia does suggest, however, that patients were less influenced by automatic aversive responses to amoral conduct. The association found between poorer (self-reported) perspective-taking and greater condemnation of social transgressions also suggests that an insensitivity to others' extenuating motives may exacerbate social misunderstandings in schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

Independent colonization and extensive cryptic speciation of freshwater amphipods in the isolated groundwater springs of Australia's Great Artesian Basin.

PubMed

Murphy, Nicholas P; Adams, Mark; Austin, Andrew D

2009-01-01

The groundwater-dependent springs of the Great Artesian Basin (GAB) in arid inland Australia represent a unique and threatened ecosystem. These incredibly isolated springs support a diverse array of endemic flora and fauna. One of the common faunal groups in the GAB springs is the freshwater amphipods of the family Chiltoniidae. The morphological conservatism and taxonomic uncertainty associated with these amphipods has ensured their true biodiversity, phylogeographical history and evolutionary affinities have remained unknown. We have used mitochondrial DNA and allozyme data to unravel a complicated history of isolation, extinction and dispersal among spring amphipod populations across the GAB. The results provide evidence for multiple independent colonizations in the GAB springs, particularly within the Lake Eyre group of springs. The inclusion of a group of Western Australian (WA) stygobitic amphipods from populations up to 1500 km away found surprising evidence for a shared evolutionary history between stygobitic and GAB spring amphipods. Approximate dating of the diversity found between major clades suggests the majority of lineages originated in the late Miocene, around the time of the aridification of inland Australia. The large number of independent lineages and the close connection between GAB spring and WA stygobitic amphipods suggest that a significantly rich amphipod fauna existed in the much wetter environment that once existed in inland Australia. The results also provide evidence for a gross underestimation of the species diversity within the springs, with 12 putative species identified, a conclusion with significant implications for the ongoing conservation of the GAB springs.

The current evidence for a biomarker-based approach in cancer of unknown primary.

PubMed

El Rassy, Elie; Pavlidis, Nicholas

2018-05-02

Cancer of unknown primary (CUP) accounts for the seventh to eighth most frequently diagnosed cancer yet its prognosis remains poor with conventional chemotherapy. The spectrum of therapeutic management includes both locoregional and systemic therapy and should intend to offer optimal benefit to favorable CUP patients and palliative care to unfavorable cases. The recent molecular advances have revolutionized the armamentarium of cancer treatments though a biomarker-based approach. Unfortunately, solid data in CUP is lacking in the absence of a CUP-specific driver molecular signature. This prompted us to screen the medical literature for clinical data that evaluates the efficacy and safety of the biomarker-based approach in CUP patients. In this review, we will summarize the available evidence for the applicability of targeted therapies in CUP. Copyright © 2018 Elsevier Ltd. All rights reserved.

DEG9, a serine protease, modulates cytokinin and light signaling by regulating the level of ARABIDOPSIS RESPONSE REGULATOR 4.

PubMed

Chi, Wei; Li, Jing; He, Baoye; Chai, Xin; Xu, Xiumei; Sun, Xuwu; Jiang, Jingjing; Feng, Peiqiang; Zuo, Jianru; Lin, Rongcheng; Rochaix, Jean-David; Zhang, Lixin

2016-06-21

Cytokinin is an essential phytohormone that controls various biological processes in plants. A number of response regulators are known to be important for cytokinin signal transduction. ARABIDOPSIS RESPONSE REGULATOR 4 (ARR4) mediates the cross-talk between light and cytokinin signaling through modulation of the activity of phytochrome B. However, the mechanism that regulates the activity and stability of ARR4 is unknown. Here we identify an ATP-independent serine protease, degradation of periplasmic proteins 9 (DEG9), which localizes to the nucleus and regulates the stability of ARR4. Biochemical evidence shows that DEG9 interacts with ARR4, thereby targeting ARR4 for degradation, which suggests that DEG9 regulates the stability of ARR4. Moreover, genetic evidence shows that DEG9 acts upstream of ARR4 and regulates the activity of ARR4 in cytokinin and light-signaling pathways. This study thus identifies a role for a ubiquitin-independent selective protein proteolysis in the regulation of the stability of plant signaling components.

Dietary fructose in nonalcoholic fatty liver disease.

PubMed

Vos, Miriam B; Lavine, Joel E

2013-06-01

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in adults and children. A number of genetic and environmental factors are known to predispose individuals to NAFLD. Certain dietary sugars, particularly fructose, are suspected to contribute to the development of NAFLD and its progression. The increasing quantity of fructose in the diet comes from sugar additives (most commonly sucrose and high fructose corn syrup) in beverages and processed foods. Substantial links have been demonstrated between increased fructose consumption and obesity, dyslipidemia, and insulin resistance. Growing evidence suggests that fructose contributes to the development and severity of NAFLD. In human studies, fructose is associated with increasing hepatic fat, inflammation, and possibly fibrosis. Whether fructose alone can cause NAFLD or if it serves only as a contributor when consumed excessively in the setting of insulin resistance, positive energy balance, and sedentary lifestyle is unknown. Sufficient evidence exists to support clinical recommendations that fructose intake be limited through decreasing foods and drinks high in added (fructose-containing) sugars. Copyright © 2013 American Association for the Study of Liver Diseases.

Technological advances and changing indications for lumbar puncture in neurological disorders.

PubMed

Costerus, Joost M; Brouwer, Matthijs C; van de Beek, Diederik

2018-03-01

Technological advances have changed the indications for and the way in which lumbar puncture is done. Suspected CNS infection remains the most common indication for lumbar puncture, but new molecular techniques have broadened CSF analysis indications, such as the determination of neuronal autoantibodies in autoimmune encephalitis. New screening techniques have increased sensitvity for pathogen detection and can be used to identify pathogens that were previously unknown to cause CNS infections. Evidence suggests that potential treatments for neurodegenerative diseases, such as Alzheimer's disease, will rely on early detection of the disease with the use of CSF biomarkers. In addition to being used as a diagnostic tool, lumbar puncture can also be used to administer intrathecal treatments as shown by studies of antisense oligonucleotides in patients with spinal muscular atrophy. Lumbar puncture is generally a safe procedure but complications can occur, ranging from minor (eg, back pain) to potentially devastating (eg, cerebral herniation). Evidence that an atraumatic needle tip design reduces complications of lumbar puncture is compelling, and reinforces the need to change clinical practice. Copyright © 2018 Elsevier Ltd. All rights reserved.

Aberrant Classopollis pollen reveals evidence for unreduced (2n) pollen in the conifer family Cheirolepidiaceae during the Triassic–Jurassic transition

PubMed Central

Kürschner, Wolfram M.; Batenburg, Sietske J.; Mander, Luke

2013-01-01

Polyploidy (or whole-genome doubling) is a key mechanism for plant speciation leading to new evolutionary lineages. Several lines of evidence show that most species among flowering plants had polyploidy ancestry, but it is virtually unknown for conifers. Here, we study variability in pollen tetrad morphology and the size of the conifer pollen type Classopollis extracted from sediments of the Triassic–Jurassic transition, 200 Ma. Classopollis producing Cheirolepidiaceae were one of the most dominant and diverse groups of conifers during the Mesozoic. We show that aberrant pollen Classopollis tetrads, triads and dyads, and the large variation in pollen size indicates the presence of unreduced (2n) pollen, which is one of the main mechanisms in modern polyploid formation. Polyploid speciation may explain the high variability of growth forms and adaptation of these conifers to different environments and their resistance to extreme growth conditions. We suggest that polyploidy may have also reduced the extinction risk of these conifers during the End-Triassic biotic crisis. PMID:23926159

An endocannabinoid hypothesis of drug reward and drug addiction.

PubMed

Onaivi, Emmanuel S

2008-10-01

Pharmacologic treatment of drug and alcohol dependency has largely been disappointing, and new therapeutic targets and hypotheses are needed. There is accumulating evidence indicating a central role for the previously unknown but ubiquitous endocannabinoid physiological control system (EPCS) in the regulation of the rewarding effects of abused substances. Thus an endocannabinoid hypothesis of drug reward is postulated. Endocannabinoids mediate retrograde signaling in neuronal tissues and are involved in the regulation of synaptic transmission to suppress neurotransmitter release by the presynaptic cannabinoid receptors (CB-Rs). This powerful modulatory action on synaptic transmission has significant functional implications and interactions with the effects of abused substances. Our data, along with those from other investigators, provide strong new evidence for a role for EPCS modulation in the effects of drugs of abuse, and specifically for involvement of cannabinoid receptors in the neural basis of addiction. Cannabinoids and endocannabinoids appear to be involved in adding to the rewarding effects of addictive substances, including, nicotine, opiates, alcohol, cocaine, and BDZs. The results suggest that the EPCS may be an important natural regulatory mechanism for drug reward and a target for the treatment of addictive disorders.

Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment.

PubMed

Escobar-Morreale, Héctor F

2018-05-01

Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in premenopausal women. Heterogeneous by nature, PCOS is defined by a combination of signs and symptoms of androgen excess and ovarian dysfunction in the absence of other specific diagnoses. The aetiology of this syndrome remains largely unknown, but mounting evidence suggests that PCOS might be a complex multigenic disorder with strong epigenetic and environmental influences, including diet and lifestyle factors. PCOS is frequently associated with abdominal adiposity, insulin resistance, obesity, metabolic disorders and cardiovascular risk factors. The diagnosis and treatment of PCOS are not complicated, requiring only the judicious application of a few well-standardized diagnostic methods and appropriate therapeutic approaches addressing hyperandrogenism, the consequences of ovarian dysfunction and the associated metabolic disorders. This article aims to provide a balanced review of the latest advances and current limitations in our knowledge about PCOS while also providing a few clear and simple principles, based on current evidence-based clinical guidelines, for the proper diagnosis and long-term clinical management of women with PCOS.

Lack of genetic linkage evidence for a trans-acting factor having a large effect on plasma lipoprotein[a] levels in African Americans.

PubMed

Barkley, Ruth Ann; Brown, Andrew C; Hanis, Craig L; Kardia, Sharon L; Turner, Stephen T; Boerwinkle, Eric

2003-07-01

The distribution of plasma lipoprotein[a] (Lp[a]) concentrations, a risk factor for cardiovascular disease, varies greatly among racial groups, with African Americans having values that are shifted toward higher levels than those of whites. The underlying cause of this heterogeneity is unknown, but a role for "trans-acting" factors has been hypothesized. This study used genetic linkage analysis to localize genetic factors influencing Lp[a] levels in African Americans that were absent in other populations; linkage results were analyzed separately in non-Hispanic whites, Hispanic whites, and African Americans. As expected, all three samples showed highly significant linkage at the approximate location of the lysophosphatidic acid locus. The white populations also independently had regions of significant linkage on chromosome 19 (LOD 3.80) and suggestive linkage on chromosomes 12 (LOD 1.60), 14 (LOD 2.56), and 19 (LOD 2.52). No linkage evidence was found to support the hypothesis of another single gene with large effects specifically segregating in African Americans that may account for their elevated Lp[a] levels.

Stimulation of PPC Affects the Mapping between Motion and Force Signals for Stiffness Perception But Not Motion Control

PubMed Central

Mawase, Firas; Karniel, Amir; Donchin, Opher; Rothwell, John; Nisky, Ilana; Davare, Marco

2016-01-01

How motion and sensory inputs are combined to assess an object's stiffness is still unknown. Here, we provide evidence for the existence of a stiffness estimator in the human posterior parietal cortex (PPC). We showed previously that delaying force feedback with respect to motion when interacting with an object caused participants to underestimate its stiffness. We found that applying theta-burst transcranial magnetic stimulation (TMS) over the PPC, but not the dorsal premotor cortex, enhances this effect without affecting movement control. We explain this enhancement as an additional lag in force signals. This is the first causal evidence that the PPC is not only involved in motion control, but also has an important role in perception that is disassociated from action. We provide a computational model suggesting that the PPC integrates position and force signals for perception of stiffness and that TMS alters the synchronization between the two signals causing lasting consequences on perceptual behavior. SIGNIFICANCE STATEMENT When selecting an object such as a ripe fruit or sofa, we need to assess the object's stiffness. Because we lack dedicated stiffness sensors, we rely on an as yet unknown mechanism that generates stiffness percepts by combining position and force signals. Here, we found that the posterior parietal cortex (PPC) contributes to combining position and force signals for stiffness estimation. This finding challenges the classical view about the role of the PPC in regulating position signals only for motion control because we highlight a key role of the PPC in perception that is disassociated from action. Altogether this sheds light on brain mechanisms underlying the interaction between action and perception and may help in the development of better teleoperation systems and rehabilitation of patients with sensory impairments. PMID:27733607

Stimulation of PPC Affects the Mapping between Motion and Force Signals for Stiffness Perception But Not Motion Control.

PubMed

Leib, Raz; Mawase, Firas; Karniel, Amir; Donchin, Opher; Rothwell, John; Nisky, Ilana; Davare, Marco

2016-10-12

How motion and sensory inputs are combined to assess an object's stiffness is still unknown. Here, we provide evidence for the existence of a stiffness estimator in the human posterior parietal cortex (PPC). We showed previously that delaying force feedback with respect to motion when interacting with an object caused participants to underestimate its stiffness. We found that applying theta-burst transcranial magnetic stimulation (TMS) over the PPC, but not the dorsal premotor cortex, enhances this effect without affecting movement control. We explain this enhancement as an additional lag in force signals. This is the first causal evidence that the PPC is not only involved in motion control, but also has an important role in perception that is disassociated from action. We provide a computational model suggesting that the PPC integrates position and force signals for perception of stiffness and that TMS alters the synchronization between the two signals causing lasting consequences on perceptual behavior. When selecting an object such as a ripe fruit or sofa, we need to assess the object's stiffness. Because we lack dedicated stiffness sensors, we rely on an as yet unknown mechanism that generates stiffness percepts by combining position and force signals. Here, we found that the posterior parietal cortex (PPC) contributes to combining position and force signals for stiffness estimation. This finding challenges the classical view about the role of the PPC in regulating position signals only for motion control because we highlight a key role of the PPC in perception that is disassociated from action. Altogether this sheds light on brain mechanisms underlying the interaction between action and perception and may help in the development of better teleoperation systems and rehabilitation of patients with sensory impairments. Copyright © 2016 Leib et al.

Oxygen Isotopes and Meltwater: Younger Dryas and 8.2 ka Event

NASA Astrophysics Data System (ADS)

Keigwin, L. D.

2015-12-01

Delta 18-O is one of our most powerful and widely used proxies, with, arguably, the fewest likely unknown unknowns. Here I will consider the d18-O evidence for the two best-known floods of mostly liquid water to the ocean, the Younger Dryas (YD) and the 8.2 ka event. The first d18-O signal of a meltwater flood in the ocean was reported 40 years ago by Kennett and Shackleton (1975) and that paper led directly to the meltwater diversion hypothesis for the origin of the YD cooling. It was later suggested by Rooth (1982) that such a flood could interrupt Nordic seas convection and trigger the YD cold episode. It was reported at this meeting last year that a candidate flood has been found in the Mackenzie River region of the western Arctic based on low d18-O and multiple other lines of evidence. The 8.2 ka event was about one-tenth the duration of the YD but with possibly higher transport, and is more difficult to detect in open marine sediments. As with the YD, it has been modeled by hosing and low salinities have been derived by temperature correcting the d18-O. The resulting low salinity was shown not to follow the prediction of the highest resolution modeling, and theory, that the fresh water would be transported mostly equatorward along the continental shelf. However, I report here that the low d18-O signal of the 8.2 ka flooding is present in new cores from near Logan Canyon on the Scotian shelf break, and in Jordan Basin, Gulf of Maine. These results substantially validate the modeling of Condron and Winsor that fresh water transport must have been along the continental shelf.

Gender medicine in gastroenterology.

PubMed

Niv, Yaron

2011-04-01

The cause for gender differences in the epidemiology, natural history and response to therapy in many diseases is unknown and has seldom been investigated in depth. Sex hormones are blamed for many of these changes, mostly without any scientific evidence. In this review I will describe some of the evidence for gender differences in gastrointestinal diseases. Gender medicine and its application for gastroenterology is a new field and one warranting research.

Evidence-Based Biosafety: a Review of the Principles and Effectiveness of Microbiological Containment Measures

PubMed Central

Kimman, Tjeerd G.; Smit, Eric; Klein, Michèl R.

2008-01-01

We examined the available evidence on the effectiveness of measures aimed at protecting humans and the environment against the risks of working with genetically modified microorganisms (GMOs) and with non-GMO pathogenic microorganisms. A few principles and methods underlie the current biosafety practice: risk assessment, biological containment, concentration and enclosure, exposure minimization, physical containment, and hazard minimization. Many of the current practices are based on experience and expert judgment. The effectiveness of biosafety measures may be evaluated at the level of single containment equipment items and procedures, at the level of the laboratory as a whole, or at the clinical-epidemiological level. Data on the containment effectiveness of equipment and laboratories are scarce and fragmented. Laboratory-acquired infections (LAIs) are therefore important for evaluating the effectiveness of biosafety. For the majority of LAIs there appears to be no direct cause, suggesting that failures of biosafety were not noticed or that containment may have been insufficient. The number of reported laboratory accidents associated with GMOs is substantially lower than that of those associated with non-GMOs. It is unknown to what extent specific measures contribute to the overall level of biosafety. We therefore recommend that the evidence base of biosafety practice be strengthened. PMID:18625678

Genetics of Tinnitus: An Emerging Area for Molecular Diagnosis and Drug Development

PubMed Central

Lopez-Escamez, Jose A.; Bibas, Thanos; Cima, Rilana F. F.; Van de Heyning, Paul; Knipper, Marlies; Mazurek, Birgit; Szczepek, Agnieszka J.; Cederroth, Christopher R.

2016-01-01

Subjective tinnitus is the perception of sound in the absence of external or bodily-generated sounds. Chronic tinnitus is a highly prevalent condition affecting over 70 million people in Europe. A wide variety of comorbidities, including hearing loss, psychiatric disorders, neurodegenerative disorders, and temporomandibular joint (TMJ) dysfunction, have been suggested to contribute to the onset or progression of tinnitus; however, the precise molecular mechanisms of tinnitus are not well understood and the contribution of genetic and epigenetic factors remains unknown. Human genetic studies could enable the identification of novel molecular therapeutic targets, possibly leading to the development of novel pharmaceutical therapeutics. In this article, we briefly discuss the available evidence for a role of genetics in tinnitus and consider potential hurdles in designing genetic studies for tinnitus. Since multiple diseases have tinnitus as a symptom and the supporting genetic evidence is sparse, we propose various strategies to investigate the genetic underpinnings of tinnitus, first by showing evidence of heritability using concordance studies in twins, and second by improving patient selection according to phenotype and/or etiology in order to control potential biases and optimize genetic data output. The increased knowledge resulting from this endeavor could ultimately improve the drug development process and lead to the preventive or curative treatment of tinnitus. PMID:27594824

Evidence-based biosafety: a review of the principles and effectiveness of microbiological containment measures.

PubMed

Kimman, Tjeerd G; Smit, Eric; Klein, Michèl R

2008-07-01

We examined the available evidence on the effectiveness of measures aimed at protecting humans and the environment against the risks of working with genetically modified microorganisms (GMOs) and with non-GMO pathogenic microorganisms. A few principles and methods underlie the current biosafety practice: risk assessment, biological containment, concentration and enclosure, exposure minimization, physical containment, and hazard minimization. Many of the current practices are based on experience and expert judgment. The effectiveness of biosafety measures may be evaluated at the level of single containment equipment items and procedures, at the level of the laboratory as a whole, or at the clinical-epidemiological level. Data on the containment effectiveness of equipment and laboratories are scarce and fragmented. Laboratory-acquired infections (LAIs) are therefore important for evaluating the effectiveness of biosafety. For the majority of LAIs there appears to be no direct cause, suggesting that failures of biosafety were not noticed or that containment may have been insufficient. The number of reported laboratory accidents associated with GMOs is substantially lower than that of those associated with non-GMOs. It is unknown to what extent specific measures contribute to the overall level of biosafety. We therefore recommend that the evidence base of biosafety practice be strengthened.

Marijuana.

PubMed

Ammerman, Seth

2014-04-01

Marijuana use in pediatric populations remains an ongoing concern, and marijuana use by adolescents had known medical, psychological, and cognitive side effects. Marijuana alters brain development and has detrimental effects on brain structure and function in ways that are incompletely understood at this point in time. Furthermore, marijuana smoke contains tar and other harmful chemicals, so marijuana cannot be recommended by physicians. At this time, no studies suggest a benefit of marijuana use by children and adolescents. In the context of limited but clear evidence showing harm or potential harm from marijuana use by adolescents, any recommendations for medical marijuana use by adolescents are based on research studies with adults and on anecdotal evidence. Criminal prosecution for marijuana possession adversely affects hundreds of thousands of youth yearly in the United States, particularly minority youth. Current evidence does not support a focus on punishment for youth who use marijuana. Rather, drug education and treatment programs should be encouraged to better help youth who are experimenting with or are dependent on marijuana. Decriminalization of recreational use of marijuana by adults has not led to an increase in youth use rates of recreational marijuana. Thus, decriminalization may be a reasonable alternative to outright criminalization, as long as it is coupled with drug education and treatment programs. The effect of outright legalization of adult recreational use of marijuana on youth use is unknown.

Recombination in feline immunodeficiency virus from feral and companion domestic cats.

PubMed

Hayward, Jessica J; Rodrigo, Allen G

2008-06-17

Recombination is a relatively common phenomenon in retroviruses. We investigated recombination in Feline Immunodeficiency Virus from naturally-infected New Zealand domestic cats (Felis catus) by sequencing regions of the gag, pol and env genes. The occurrence of intragenic recombination was highest in env, with evidence of recombination in 6.4% (n = 156) of all cats. A further recombinant was identified in each of the gag (n = 48) and pol (n = 91) genes. Comparisons of phylogenetic trees across genes identified cases of incongruence, indicating intergenic recombination. Three (7.7%, n = 39) of these incongruencies were found to be significantly different using the Shimodaira-Hasegawa test.Surprisingly, our phylogenies from the gag and pol genes showed that no New Zealand sequences group with reference subtype C sequences within intrasubtype pairwise distances. Indeed, we find one and two distinct unknown subtype groups in gag and pol, respectively. These observations cause us to speculate that these New Zealand FIV strains have undergone several recombination events between subtype A parent strains and undefined unknown subtype strains, similar to the evolutionary history hypothesised for HIV-1 "subtype E".Endpoint dilution sequencing was used to confirm the consensus sequences of the putative recombinants and unknown subtype groups, providing evidence for the authenticity of these sequences. Endpoint dilution sequencing also resulted in the identification of a dual infection event in the env gene. In addition, an intrahost recombination event between variants of the same subtype in the pol gene was established. This is the first known example of naturally-occurring recombination in a cat with infection of the parent strains. Evidence of intragenic recombination in the gag, pol and env regions, and complex intergenic recombination, of FIV from naturally-infected domestic cats in New Zealand was found. Strains of unknown subtype were identified in all three gene regions. These results have implications for the use of the current FIV vaccine in New Zealand.

Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma

PubMed Central

Madeira, Maria H.; Ortin-Martinez, Arturo; Nadal-Nícolas, Francisco; Ambrósio, António F.; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Santiago, Ana Raquel

2016-01-01

Glaucoma is the second leading cause of blindness worldwide, being characterized by progressive optic nerve damage and loss of retinal ganglion cells (RGCs), accompanied by increased inflammatory response involving retinal microglial cells. The etiology of glaucoma is still unknown, and despite elevated intraocular pressure (IOP) being a major risk factor, the exact mechanisms responsible for RGC degeneration remain unknown. Caffeine, which is an antagonist of adenosine receptors, is the most widely consumed psychoactive drug in the world. Several evidences suggest that caffeine can attenuate the neuroinflammatory responses and afford protection upon central nervous system (CNS) injury. We took advantage of a well characterized animal model of glaucoma to investigate whether caffeine administration controls neuroinflammation and elicits neuroprotection. Caffeine or water were administered ad libitum and ocular hypertension (OHT) was induced by laser photocoagulation of the limbal veins in Sprague Dawley rats. Herein, we show that caffeine is able to partially decrease the IOP in ocular hypertensive animals. More importantly, we found that drinking caffeine prevented retinal microglia-mediated neuroinflammatory response and attenuated the loss of RGCs in animals with ocular hypertension (OHT). This study opens the possibility that caffeine or adenosine receptor antagonists might be a therapeutic option to manage RGC loss in glaucoma. PMID:27270337

A metagenomic-based survey of microbial (de)halogenation potential in a German forest soil

PubMed Central

Weigold, Pascal; El-Hadidi, Mohamed; Ruecker, Alexander; Huson, Daniel H.; Scholten, Thomas; Jochmann, Maik; Kappler, Andreas; Behrens, Sebastian

2016-01-01

In soils halogens (fluorine, chlorine, bromine, iodine) are cycled through the transformation of inorganic halides into organohalogen compounds and vice versa. There is evidence that these reactions are microbially driven but the key enzymes and groups of microorganisms involved are largely unknown. Our aim was to uncover the diversity, abundance and distribution of genes encoding for halogenating and dehalogenating enzymes in a German forest soil by shotgun metagenomic sequencing. Metagenomic libraries of three soil horizons revealed the presence of genera known to be involved in halogenation and dehalogenation processes such as Bradyrhizobium or Pseudomonas. We detected a so far unknown diversity of genes encoding for (de)halogenating enzymes in the soil metagenome including specific and unspecific halogenases as well as metabolic and cometabolic dehalogenases. Genes for non-heme, no-metal chloroperoxidases and haloalkane dehalogenases were the most abundant halogenase and dehalogenase genes, respectively. The high diversity and abundance of (de)halogenating enzymes suggests a strong microbial contribution to natural halogen cycling. This was also confirmed in microcosm experiments in which we quantified the biotic formation of chloroform and bromoform. Knowledge on microorganisms and genes that catalyze (de)halogenation reactions is critical because they are highly relevant to industrial biotechnologies and bioremediation applications. PMID:27353292

Genetics Home Reference: L1 syndrome

MedlinePlus

... X-linked hydrocephalus: evidence for closely related clinical entities of unknown molecular bases. Acta Neuropathol. 2013 Sep; ... F. Three cases with L1 syndrome and two novel mutations in the L1CAM gene. Eur J Pediatr. ...

HEALTH ASSESSMENT OF 1,3-BUTADIENE | Science ...

EPA Pesticide Factsheets

This assessment was conducted to review the new information that has become available since EPA's 1985 health assessment of 1,3-butadiene.1,3-Butadiene is a gas used commercially in the production of styrene-butadiene rubber, plastics, and thermoplastic resins. The major environmental source of 1,3-butadiene is the incomplete combustion of fuels from mobile sources (e.g., automobile exhaust). Tobacco smoke can be a significant source of 1,3-butadiene in indoor air.This assessment concludes that 1,3-butadiene is carcinogenic to humans by inhalation, based on the total weight of evidence. The specific mechanisms of 1,3-butadiene-induced carcinogenesis are unknown; however, it is virtually certain that the carcinogenic effects are mediated by genotoxic metabolites of 1,3-butadiene.Animal data suggest that females may be more sensitive than males for cancer effects; nevertheless, there are insufficient data from which to draw any conclusions on potentially sensitive subpopulations.The human incremental lifetime unit cancer (incidence) risk estimate is based on extrapolation from leukemias observed in an occupational epidemiologic study. A twofold adjustment to the epidemiologic-based unit cancer risk is then applied to reflect evidence from the rodent bioassays suggesting that the epidemiologic-based estimate may underestimate total cancer risk from 1,3-butadiene exposure in the general population. 1,3-Butadiene also causes a variety of reproductive and develop

A re-assessment of high elevation treeline positions and their explanation.

PubMed

Körner, Christian

1998-07-01

In this review I first compile data for the worldwide position of climate-driven alpine treelines. Causes for treeline formation are then discussed with a global perspective. Available evidence suggests a combination of a general thermal boundary for tree growth, with regionally variable "modulatory" forces, including the presence of certain taxa. Much of the explanatory evidence found in the literature relates to these modulatory aspects at regional scales, whereas no good explanations emerged for the more fundamental global pattern related to temperature per se, on which this review is focused. I hypothesize that the life form "tree" is limited at treeline altitudes by the potential investment, rather than production, of assimilates (growth as such, rather than photosynthesis or the carbon balance, being limited). In shoots coupled to a cold atmosphere, meristem activity is suggested to be limited for much of the time, especially at night. By reducing soil heat flux during the growing season the forest canopy negatively affects root zone temperature. The lower threshold temperature for tissue growth and development appears to be higher than 3°C and lower than 10°C, possibly in the 5.5-7.5°C range, most commonly associated with seasonal means of air temperature at treeline positions. The physiological and developmental mechanisms responsible have yet to be analyzed. Root zone temperature, though largely unknown, is likely to be most critical.

Eggspot number and sexual selection in the cichlid fish Astatotilapia burtoni.

PubMed

Henning, Frederico; Meyer, Axel

2012-01-01

Sexual selection on male coloration is one of the main mechanisms proposed to explain the explosive speciation rates in East African cichlid fish. True eggspots are color patterns characteristic of the most species-rich lineage of cichlids, the Haplochromini, and have been suggested to be causally related to the speciation processes. Eggspots are thought to have originated by sensory exploitation and subsequently gained several roles in sexual advertisement. However, for most of these functions the evidence is equivocal. In addition, the genetic architecture of this trait still is largely unknown. We conducted bidirectional selective breeding experiments for eggspot numbers in the model cichlid, Astatotilapia burtoni. After two generations, low lines responded significantly, whereas the high lines did not. Body size was both phenotypically and genotypically correlated with eggspot number and showed correlated response to selection. Males with higher numbers of eggspots were found to sire larger offspring. Despite the potential to act as honest indicators of fitness, the behavioral experiments showed no evidence of a role in either intra- or inter-sexual selection. Visual-based female preference was instead explained by courtship intensity. The evolution of this trait has been interpreted in light of adaptive theories of sexual selection, however the present and published results suggest the influence of non-adaptive factors such as sensory exploitation, environmental constraints and sexual antagonism.

Stable isotope evidence of meat eating and hunting specialization in adult male chimpanzees

PubMed Central

Fahy, Geraldine E.; Richards, Michael; Riedel, Julia; Hublin, Jean-Jacques; Boesch, Christophe

2013-01-01

Observations of hunting and meat eating in our closest living relatives, chimpanzees (Pan troglodytes), suggest that among primates, regular inclusion of meat in the diet is not a characteristic unique to Homo. Wild chimpanzees are known to consume vertebrate meat, but its actual dietary contribution is, depending on the study population, often either unknown or minimal. Constraints on continual direct observation throughout the entire hunting season mean that behavioral observations are limited in their ability to accurately quantify meat consumption. Here we present direct stable isotope evidence supporting behavioral observations of frequent meat eating among wild adult male chimpanzees (Pan troglodytes verus) in Taï National Park, Côte d’Ivoire. Meat eating among some of the male chimpanzees is significant enough to result in a marked isotope signal detectable on a short-term basis in their hair keratin and long-term in their bone collagen. Although both adult males and females and juveniles derive their dietary protein largely from daily fruit and seasonal nut consumption, our data indicate that some adult males also derive a large amount of dietary protein from hunted meat. Our results reinforce behavioral observations of male-dominated hunting and meat eating in adult Taï chimpanzees, suggesting that sex differences in food acquisition and consumption may have persisted throughout hominin evolution, rather than being a recent development in the human lineage. PMID:23530185

Muscle protein turnover in the elderly and its potential contribution to the development of sarcopenia.

PubMed

Murton, Andrew J

2015-11-01

The underlying aetiology of sarcopenia appears multifaceted and not yet fully defined, but ultimately involves the gradual loss of muscle protein content over time. The present evidence suggests that the loss of lean tissue in the elderly is exacerbated by low dietary protein intake. Moreover, acute stable-isotope-based methodologies have demonstrated that the muscle anabolic response to a given amount of protein may decline with age, a phenomenon that has been termed anabolic resistance. Although the mechanism responsible for the inability of muscle to mount a satisfactory anabolic response to protein provision with increasing age is presently unknown, it does not appear due to impaired digestion or absorption of dietary protein. Rather, the issue could reside with any combination of: a diminished delivery of amino acids to peripheral tissues, impaired uptake of amino acids into muscle cells, or an inability of amino acids to elicit intracellular events pivotal for anabolism to occur. Despite the presence of anabolic resistance to dietary protein, present evidence suggests that protein supplementation may be able to overcome these issues, particularly when combined with resistance exercise programmes. As such, protein supplementation may prove to be an effective approach to delay the loss of muscle mass with age and has led to calls for the recommended daily intake of protein to be increased for the elderly population.

Disordered eating, menstrual disturbances, and low bone mineral density in dancers: a systematic review.

PubMed

Hincapié, Cesar A; Cassidy, J David

2010-11-01

To assemble and synthesize the best evidence on the epidemiology, diagnosis, prognosis, treatment, and prevention of disordered eating, menstrual disturbances, and low bone mineral density in dancers. Medline, CINAHL, PsycINFO, Embase, and other electronic databases were searched from 1966 to 2010 using key words such as "dance," "dancer," "dancing," "eating disorders," "menstruation disturbances," and "bone density." In addition, the reference lists of relevant studies were examined, specialized journals were hand-searched, and the websites of major dance associations were scanned for relevant information. Citations were screened for relevance using a priori criteria, and relevant studies were critically reviewed for scientific merit by the best evidence synthesis method. After 2748 abstracts were screened, 124 articles were reviewed, and 23 (18.5%) of these were accepted as scientifically admissible (representing 19 unique studies). Data from accepted studies were abstracted into evidence tables relating to prevalence and associated factors; incidence and risk factors; diagnosis; and prevention of disordered eating, menstrual disturbances, and/or low bone mineral density in dancers. The scientifically admissible studies consisted of 13 (68%) cross-sectional studies and 6 (32%) cohort studies. Disordered eating and menstrual disturbances are common in dancers. The lifetime prevalence of any eating disorder was 50% in professional dancers, while the point prevalence ranged between 13.6% and 26.5% in young student dancers. In their first year of intensive dance training, 32% of university-level dancers developed a menstrual disturbance. The incidence of disordered eating and low bone mineral density in dancers is unknown. Several potential risk factors are suggested by the literature, but there is little compelling evidence for any of these. There is preliminary evidence that multifaceted sociocultural prevention strategies may help decrease the incidence of disordered eating. The dance medicine literature is heterogeneous. The best available evidence suggests that disordered eating, menstrual disturbances, and low bone mineral density are important health issues for dancers at all skill levels. Future research would benefit from clear and relevant research questions being addressed with appropriate study designs and better reporting of studies in line with current scientific standards. Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Family network size and survival across the lifespan of female macaques

PubMed Central

Ruiz-Lambides, A.; Platt, M. L.

2017-01-01

Two decades of research suggest social relationships have a common evolutionary basis in humans and other gregarious mammals. Critical to the support of this idea is growing evidence that mortality is influenced by social integration, but when these effects emerge and how long they last is mostly unknown. Here, we report in adult female macaques that the impact of number of close adult female relatives, a proxy for social integration, on survival is not experienced uniformly across the life course; prime-aged females with a greater number of relatives had better survival outcomes compared with prime-aged females with fewer relatives, whereas no such effect was found in older females. Group size and dominance rank did not influence this result. Older females were less frequent targets of aggression, suggesting enhanced experience navigating the social landscape may obviate the need for social relationships in old age. Only one study of humans has found age-based dependency in the association between social integration and survival. Using the largest dataset for any non-human animal to date, our study extends support for the idea that sociality promotes survival and suggests strategies employed across the life course change along with experience of the social world. PMID:28515205

Sensory processing and corollary discharge effects in posterior caudal lobe Purkinje cells in a weakly electric mormyrid fish.

PubMed

Alviña, Karina; Sawtell, Nathaniel B

2014-07-15

Although it has been suggested that the cerebellum functions to predict the sensory consequences of motor commands, how such predictions are implemented in cerebellar circuitry remains largely unknown. A detailed and relatively complete account of predictive mechanisms has emerged from studies of cerebellum-like sensory structures in fish, suggesting that comparisons of the cerebellum and cerebellum-like structures may be useful. Here we characterize electrophysiological response properties of Purkinje cells in a region of the cerebellum proper of weakly electric mormyrid fish, the posterior caudal lobe (LCp), which receives the same mossy fiber inputs and projects to the same target structures as the electrosensory lobe (ELL), a well-studied cerebellum-like structure. We describe patterns of simple spike and climbing fiber activation in LCp Purkinje cells in response to motor corollary discharge, electrosensory, and proprioceptive inputs and provide evidence for two functionally distinct Purkinje cell subtypes within LCp. Protocols that induce rapid associative plasticity in ELL fail to induce plasticity in LCp, suggesting differences in the adaptive functions of the two structures. Similarities and differences between LCp and ELL are discussed in light of these results. Copyright © 2014 the American Physiological Society.

Sudden suffocation with cancer of unknown primary: a case report and review of diagnostic approach.

PubMed

Tehrani, Omid S; Ahmad, Omar; Vypritskaya, Ekaterina; Chen, Emily; Hasan, Saba

2012-10-01

A case of a 31-year-old woman with sudden respiratory distress is presented. Preliminary evaluations and imaging studies did not reveal the underlying cause. Workup during hospital stay showed advanced metastatic cancer of unknown primary origin. This is an unusual presentation of cancer of an unknown primary involving the thyroid with sudden suffocation. It suggests that malignancies involving the thyroid gland should be considered in patients with abrupt onset of respiratory distress. Also, this case shows the application of fine needle aspiration in diffuse thyroid enlargements mimicking thyroiditis without nodules. Diagnostic approach to cancer of unknown primary origin (CUP) is reviewed in further detail.

Treatment Patterns for Cervical Carcinoma In Situ in Michigan, 1998-2003

PubMed Central

Patel, Divya A.; Saraiya, Mona; Copeland, Glenn; Cote, Michele L.; Datta, S. Deblina; Sawaya, George F.

2015-01-01

Objective To characterize population-level surgical treatment patterns for cervical carcinoma in situ (CIS) reported to the Michigan Cancer Surveillance Program (MCSP), and to inform data collection strategies. Methods All cases of cervical carcinoma in situ (CIS) (including cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ [AIS]) reported to the MCSP during 1998–2003 were identified. First course of treatment (ablative procedure, cone biopsy, loop electrosurgical excisional procedure [LEEP], hysterectomy, unspecified surgical treatment, no surgical treatment, unknown if surgically treated) was described by histology, race, and age at diagnosis. Results Of 17,022 cases of cervical CIS, 82.8% were squamous CIS, 3% AIS/adenosquamous CIS, and 14.2% unspecified/other CIS. Over half (54.7%) of cases were diagnosed in women under age 30. Excisional treatments (LEEP, 32.3% and cone biopsy, 17.3%) were most common, though substantial proportions had no reported treatment (17.8%) or unknown treatment (21.1%). Less common were hysterectomy (7.2%) and ablative procedures (2.6%). LEEP was the most common treatment for squamous cases, while hysterectomy was the most treatment for AIS/adenosquamous CIS cases. Across histologic types, a sizeable proportion of women diagnosed ≤30 years of age underwent excision, either LEEP (20%–38.7%) or cone biopsy (13.7%–44%). Conclusion Despite evidence suggesting it may be safer and equally effective as excision, ablation was rarely used for treating cervical squamous CIS. These population-based data indicate some notable differences in treatment by histology and age at diagnosis, with observed patterns appearing consistent with consensus guidelines in place at the time of study, but favoring more aggressive procedures. Future data collection strategies may need to validate treatment information, including the large proportion of no or unknown treatment. PMID:24002133

Predicting the Functional Impact of KCNQ1 Variants of Unknown Significance.

PubMed

Li, Bian; Mendenhall, Jeffrey L; Kroncke, Brett M; Taylor, Keenan C; Huang, Hui; Smith, Derek K; Vanoye, Carlos G; Blume, Jeffrey D; George, Alfred L; Sanders, Charles R; Meiler, Jens

2017-10-01

An emerging standard-of-care for long-QT syndrome uses clinical genetic testing to identify genetic variants of the KCNQ1 potassium channel. However, interpreting results from genetic testing is confounded by the presence of variants of unknown significance for which there is inadequate evidence of pathogenicity. In this study, we curated from the literature a high-quality set of 107 functionally characterized KCNQ1 variants. Based on this data set, we completed a detailed quantitative analysis on the sequence conservation patterns of subdomains of KCNQ1 and the distribution of pathogenic variants therein. We found that conserved subdomains generally are critical for channel function and are enriched with dysfunctional variants. Using this experimentally validated data set, we trained a neural network, designated Q1VarPred, specifically for predicting the functional impact of KCNQ1 variants of unknown significance. The estimated predictive performance of Q1VarPred in terms of Matthew's correlation coefficient and area under the receiver operating characteristic curve were 0.581 and 0.884, respectively, superior to the performance of 8 previous methods tested in parallel. Q1VarPred is publicly available as a web server at http://meilerlab.org/q1varpred. Although a plethora of tools are available for making pathogenicity predictions over a genome-wide scale, previous tools fail to perform in a robust manner when applied to KCNQ1. The contrasting and favorable results for Q1VarPred suggest a promising approach, where a machine-learning algorithm is tailored to a specific protein target and trained with a functionally validated data set to calibrate informatics tools. © 2017 American Heart Association, Inc.

The proposed 9th planet of Solar System at a distance less than 1000AU is absent

NASA Astrophysics Data System (ADS)

Vidmachenko, A. P.

2017-05-01

In 2016 Brown and Batygin reported about indirect evidence of the existence of so far unknown ninth planet in the Solar system. They suggested, that orbits of 6 known trans-Neptunian objects (TNO) of scattered disk are oriented so, that they can be influenced by a large, yet unknown body. We draw attention to the fact, that these 6 objects in close to their discovering moments were located at perihelion. We assume that for many orders of magnitude a larger number of the same TNOs should be located at a greater distance from the perihelion. Therefore, a possible number of the same TNOs should be counted in many thousands. We used the observation data obtained by Space Telescope (WISE). It was established that there is no analogue of the giant planet Saturn at distances up to 30000 AU. This circumstance allowed us to calculate that at distances up to 1000 AU it would be clearly visible planetary body with a radius of more than 11000 km. That is, a planet with a possible mass of about 10 Earth masses and an "earth" density (5.52 t/m3). If we take into account that the density of the "average" TNO differs little from 2 t/m3, the radius of such a body will increase to 19200 km. And then the limit of detection of the body will increase by almost 4 times: up to 4000 AU. (!) Thus, either unknown 9th planet is now even further, or our results cannot be directly scaled for the planet "Super-Earth", which at such large distance can have a disproportionately low source of internal heat.

Comets as parent bodies of CI1 carbonaceous meteorites and possible habitats of ice-microbes

NASA Astrophysics Data System (ADS)

Wickramasinghe, N. Chandra; Wickramasinghe, Janaki T.; Wallis, Jamie; Hoover, Richard B.; Rozanov, Alexei Y.

2011-10-01

Recent studies of comets and cometary dust have confirmed the presence of biologically relevant organic molecules along with clay minerals and water ice. It is also now well established by deuterium/hydrogen ratios that the CI1 carbonaceous meteorites contain indigenous extraterrestrial water. The evidence of extensive aqueous alteration of the minerals in these meteorites led to the hypothesis that water-bearing asteroids or comets represent the parent bodies of the CI1 (and perhaps CM2) carbonaceous meteorites. These meteorites have also been shown to possess a diverse array of complex organics and chiral and morphological biomarkers. Stable isotope studies by numerous independent investigators have conclusively established that the complex organics found in these meteorites are both indigenous and extraterrestrial in nature. Although the origin of these organics is still unknown, some researchers have suggested that they originated by unknown abiotic mechanisms and may have played a role in the delivery of chiral biomolecules and the origin of life on Early Earth. In this paper we review these results and investigate the thermal history of comets. We show that permanent as well as transient domains of liquid water can be maintained on a comet under a plausible set of assumptions. With each perihelion passage of a comet volatiles are preferentially released, and during millions of such passages the comet could shed crustal debris that may survive transit through the Earth's atmosphere as a carbonaceous meteorite. We review the current state of knowledge of comets and carbonaceous meteorites. We also present the results of recent studies on the long-term viability of terrestrial ice-microbiota encased in ancient glacial ice and permafrost. We suggest that the conditions which have been observed to prevail on many comets do not preclude either survivability (or even the active metabolism and growth) of many types of eukaryotic and prokaryotic microbial extremophiles-including algae, cyanobacteria, bacteria and archaea. It is argued that the chemical and morphological biomarkers detected on comets and carbonaceous meteorites can be explained by ancient microbial activity without the need to invoke unknown abiotic production mechanisms.

Comets as Parent Bodies of CI1 Carbonaceous Meteorites and Possible Habitats of Ice-Microbiota

NASA Technical Reports Server (NTRS)

Wickramasinghe, N. Chandra; Wallis, Daryl H.; Rozanov, Alexei Yu.; Hoover, Richard B.

2011-01-01

Recent studies of comets and cometary dust have confirmed the presence of biologically relevant organic molecules along with clay minerals and water ice. It is also now well established by deuterium/hydrogen ratios that the CI1 carbonaceous meteorites contain indigenous extraterrestrial water. The evidence of extensive aqueous alteration of the minerals in these meteorites led to the hypothesis that water-bearing asteroids or comets represent the parent bodies of the CI1 (and perhaps CM2) carbonaceous meteorites. These meteorites have also been shown to possess a diverse array of complex organics and chiral and morphological biomarkers. Stable isotope studies by numerous independent investigators have conclusively established that the complex organics found in these meteorites are both indigenous and extraterrestrial in nature. Although the origin of these organics is still unknown, some researchers have suggested that they originated by unknown abiotic mechanisms and may have played a role in the delivery of chiral biomolecules and the origin of life on Early Earth. In this paper we review these results and investigate the thermal history of comets. We show that permanent as well as transient domains of liquid water can be maintained on a comet under a plausible set of assumptions. With each perihelion passage of a comet volatiles are preferentially released, and during millions of such passages the comet could shed crustal debris that may survive transit through the Earth s atmosphere as a carbonaceous meteorite. We review the current state of knowledge of comets and carbonaceous meteorites. We also present the results of recent studies on the long-term viability of terrestrial ice-microbiota encased in ancient glacial ice and permafrost. We suggest that the conditions which have been observed to prevail on many comets do not preclude either survivability (or even the active metabolism and growth) of many types of eukaryotic and prokaryotic microbial extremophiles-including algae, cyanobacteria, bacteria and archaea. It is argued that the chemical and morphological biomarkers detected on comets and carbonaceous meteorites can be explained by ancient microbial activity without the need to invoke unknown abiotic production mechanisms.

Bidirectional control of social hierarchy by synaptic efficacy in medial prefrontal cortex.

PubMed

Wang, Fei; Zhu, Jun; Zhu, Hong; Zhang, Qi; Lin, Zhanmin; Hu, Hailan

2011-11-04

Dominance hierarchy has a profound impact on animals' survival, health, and reproductive success, but its neural circuit mechanism is virtually unknown. We found that dominance ranking in mice is transitive, relatively stable, and highly correlates among multiple behavior measures. Recording from layer V pyramidal neurons of the medial prefrontal cortex (mPFC) showed higher strength of excitatory synaptic inputs in mice with higher ranking, as compared with their subordinate cage mates. Furthermore, molecular manipulations that resulted in an increase and decrease in the synaptic efficacy in dorsal mPFC neurons caused an upward and downward movement in the social rank, respectively. These results provide direct evidence for mPFC's involvement in social hierarchy and suggest that social rank is plastic and can be tuned by altering synaptic strength in mPFC pyramidal cells.

No allelic association between Parkinson`s disease and dopamine D2, D3, and D4 receptor gene polymorphisms

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

Nanko, S.; Hattori, M.; Dai, X.Y.

1994-12-15

Parkinson`s disease is thought to be caused by a combination of unknown environmental, genetic, and degenerative factors. Evidence from necropsy brain samples and pharmacokinetics suggests involvement of dopamine receptors in the pathogenesis or pathophysiology of Parkinson`s disease. Genetic association studies between Parkinson`s disease and dopamine D2, D3 and D4 receptor gene polymorphisms were conducted. The polymorphism was examined in 71 patients with Parkinson`s disease and 90 controls. There were no significant differences between two groups in allele frequencies at the D2, D3, and D4 dopamine receptor loci. Our findings do not support the hypothesis that susceptibility to Parkinson`s disease ismore » associated with the dopamine receptor polymorphisms examined. 35 refs., 2 tabs.« less

Modeling the integration of bacterial rRNA fragments into the human cancer genome.

PubMed

Sieber, Karsten B; Gajer, Pawel; Dunning Hotopp, Julie C

2016-03-21

Cancer is a disease driven by the accumulation of genomic alterations, including the integration of exogenous DNA into the human somatic genome. We previously identified in silico evidence of DNA fragments from a Pseudomonas-like bacteria integrating into the 5'-UTR of four proto-oncogenes in stomach cancer sequencing data. The functional and biological consequences of these bacterial DNA integrations remain unknown. Modeling of these integrations suggests that the previously identified sequences cover most of the sequence flanking the junction between the bacterial and human DNA. Further examination of these reads reveals that these integrations are rich in guanine nucleotides and the integrated bacterial DNA may have complex transcript secondary structures. The models presented here lay the foundation for future experiments to test if bacterial DNA integrations alter the transcription of the human genes.

Extracorporeal shock wave treatment for chronic plantar fasciitis (heel pain).

PubMed

Ho, C

2007-01-01

(1) Electrohydraulic, electromagnetic, or piezoelectric devices are used to translate energy into acoustic waves during extracorporeal shock wave treatment (ESWT) for chronic plantar fasciitis (or heel pain). These waves may help to accelerate the healing process via an unknown mechanism. (2) ESWT, which is performed as an outpatient procedure, is intended to alleviate the pain due to chronic plantar fasciitis. (3) Results from randomized controlled trials have been conflicting. Six trials reported data that favour ESWT over placebo or conservative treatment for efficacy outcomes, while three trials showed no significant difference between the ESWT group and the placebo group. (4) The lack of convergent findings from randomized trials of ESWT for chronic plantar fasciitis suggests uncertainty about its effectiveness. The evidence reviewed in this bulletin does not support the use of this technology for this condition.

Infective Endocarditis of the Left Main to Right Atrial Coronary Cameral Fistula.

PubMed

Mishra, Ramesh Chandra; Barik, Ramachandra; Patnaik, Amar Narayana

2016-01-01

A 7-year-old female child presented with pyrexia of unknown origin. She had received an empirical regimen of antibiotic for possible endocarditis. Evaluation included multiple imaging supports and blood culture. She had left main coronary artery to right atrium coronary cameral fistula, restricted patent ductus arteriosus, vegetation at the right atrial exit of fistula and negative blood culture. Ongoing fever more than 2 weeks, oscillating vegetation in the echo and histopathological evidence of healing vegetation suggested definite diagnosis of infective endocarditis. She was treated successfully by surgical closure of fistula from the right atrial approach. Device closure in this case would have resulted in a large residual cul-de-sac with or without tiny residual high-velocity jets, either being a threat for future enlargement, rupture of the residual aneurysmal sac, thromboembolism, prolonged anticoagulation, and infective endocarditis.

Unmarried motherhood in twentieth-century England.

PubMed

Thane, Pat

2011-01-01

This article explores the experiences of unmarried mothers who kept and tried to raise their children between World War One and the end of the twentieth century. It argues that there has not been a simple progression from their experiencing social stigma and ostracism to more enlightened attitudes since the 1970s. Rather there is a great deal that has hitherto been unknown about what the evidence suggests were very diverse experiences and attitudes throughout the period. A major change since the 1970s has been from pervasive secrecy about unmarried motherhood, cohabitation, adultery and similar 'irregular' practices, especially among the middle classes, to greater openness. The article uses a variety of sources, including the records of the National Council for the Unmarried Mother and Her Child (founded in 1918, now One Parent Families), oral histories, contemporary interviews and official and unofficial investigations.

Pain Part 8: Burning Mouth Syndrome.

PubMed

Beneng, Kiran; Renton, Tara

2016-04-01

Burning mouth syndrome (BMS) is a rare but impactful condition affecting mainly post-menopausal women resulting in constant pain and significant difficulty with eating, drinking and daily function. The aetiology of BMS remains an enigma. Recent evidence suggests it likely to be neuropathic in origin, the cause of which remains unknown. There is no cure for this condition and the unfortunate patients remain managed on a variety of neuropathic pain medication, salivary substitutes and other non-medical interventions that help the patient 'get through the day'. Some simple strategies can assist both clinician and patient to manage this debilitating condition. CPD/Clinical Relevance: The dental team will recognize patients presenting with burning mouth syndrome. They are difficult patients to manage and are often referred to secondary care and, ultimately, depend on their general medical practitioners for pain management.

Glial response to polyglutamine-mediated stress

PubMed Central

Vig, Parminder J.S.; Shao, Qingmei; Lopez, Maripar E

2009-01-01

Neurodegenerative trinucleotide (CAG) repeat disorders are caused by the expansion of polyglutamine tracts within the disease proteins. Some of these proteins have an unknown function. How does expanded polyglutamine cause target neurons to degenerate, is not clear. Recent evidence suggests that intercellular miscommunication may contribute to polyglutamine pathogenesis in CAG repeat disorders. Polyglutamine induced degeneration of the target neuron can be mediated via glia-neuron interactions. Here we hypothesize during neurodegenerative process the failure of cell: cell interactions have more severe consequences than alterations in intracellular neuron biology. We further believe that bidirectional communication between neurons and glia are prerequisite for the normal development and function of either cell-type. Understanding intercellular signaling mechanisms such as glial trophic factors and their receptors, cell adhesion or other well-defined signaling molecules provide opportunities for developing potential therapies. PMID:20046986

The High Price of Debt: Household financial debt and its impact on mental and physical health

PubMed Central

Nandi, Arijit; Adam, Emma; McDade, Thomas

2013-01-01

Household financial debt in America has risen dramatically in recent years. While there is evidence that debt is associated with adverse psychological health, its relationship with other health outcomes is relatively unknown. We investigate the associations of multiple indices of financial debt with psychological and general health outcomes among 8400 young adult respondents from the National Longitudinal Study of Adolescent Health (Add Health). Our findings show that reporting high financial debt relative to available assets is associated with higher perceived stress and depression, worse selfreported general health, and higher diastolic blood pressure. These associations remain significant when controlling for prior socioeconomic status, psychological and physical health, and other demographic factors. The results suggest that debt is an important socioeconomic determinant of health that should be explored further in social epidemiology research. PMID:23849243

CD68 acts as a major gateway for malaria sporozoite liver infection.

PubMed

Cha, Sung-Jae; Park, Kiwon; Srinivasan, Prakash; Schindler, Christian W; van Rooijen, Nico; Stins, Monique; Jacobs-Lorena, Marcelo

2015-08-24

After being delivered by the bite from an infected mosquito, Plasmodium sporozoites enter the blood circulation and infect the liver. Previous evidence suggests that Kupffer cells, a macrophage-like component of the liver blood vessel lining, are traversed by sporozoites to initiate liver invasion. However, the molecular determinants of sporozoite-Kupffer cell interactions are unknown. Understanding the molecular basis for this specific recognition may lead to novel therapeutic strategies to control malaria. Using a phage display library screen, we identified a peptide, P39, that strongly binds to the Kupffer cell surface and, importantly, inhibits sporozoite Kupffer cell entry. Furthermore, we determined that P39 binds to CD68, a putative receptor for sporozoite invasion of Kupffer cells that acts as a gateway for malaria infection of the liver. © 2015 Cha et al.

Abdominal obesity and metabolic syndrome: exercise as medicine?

PubMed

Paley, Carole A; Johnson, Mark I

2018-01-01

Metabolic syndrome is defined as a cluster of at least three out of five clinical risk factors: abdominal (visceral) obesity, hypertension, elevated serum triglycerides, low serum high-density lipoprotein (HDL) and insulin resistance. It is estimated to affect over 20% of the global adult population. Abdominal (visceral) obesity is thought to be the predominant risk factor for metabolic syndrome and as predictions estimate that 50% of adults will be classified as obese by 2030 it is likely that metabolic syndrome will be a significant problem for health services and a drain on health economies.Evidence shows that regular and consistent exercise reduces abdominal obesity and results in favourable changes in body composition. It has therefore been suggested that exercise is a medicine in its own right and should be prescribed as such. This review provides a summary of the current evidence on the pathophysiology of dysfunctional adipose tissue (adiposopathy). It describes the relationship of adiposopathy to metabolic syndrome and how exercise may mediate these processes, and evaluates current evidence on the clinical efficacy of exercise in the management of abdominal obesity. The review also discusses the type and dose of exercise needed for optimal improvements in health status in relation to the available evidence and considers the difficulty in achieving adherence to exercise programmes. There is moderate evidence supporting the use of programmes of exercise to reverse metabolic syndrome although at present the optimal dose and type of exercise is unknown. The main challenge for health care professionals is how to motivate individuals to participate and adherence to programmes of exercise used prophylactically and as a treatment for metabolic syndrome.

New insight into pecan boron nutrition

USDA-ARS?s Scientific Manuscript database

Alternate bearing by individual pecan [Carya illinoinensis (Wangenh.) K. Koch] trees is problematic for nut producers and processors. There are many unknowns regarding alternate bearing physiology, such as the relationship between boron and fruit set, nutmeat quality, and kernel maladies. Evidence...

Acetylcholine and the alpha 7 nicotinic receptor: a potential therapeutic target for the treatment of periodontal disease?

PubMed Central

2013-01-01

Objectives The aim of this review is to examine the evidence for a functional cholinergic system operating within the periodontium and determine the evidence for its role in periodontal immunity. Introduction Acetylcholine can influence the immune system via the ‘cholinergic anti-inflammatory pathway’. This pathway is mediated by the vagus nerve which releases acetylcholine to interact with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR) on proximate immuno-regulatory cells. Activation of the α7nAChR on these cells leads to down-regulated expression of pro-inflammatory mediators and thus regulates localised inflammatory responses. The role of the vagus nerve in periodontal pathophysiology is currently unknown. However, non-neuronal cells can also release acetylcholine and express the α7nAChR; these include keratinocytes, fibroblasts, T cells, B cells and macrophages. Therefore, by both autocrine and paracrine methods non-neuronal acetylcholine can also be hypothesised to modulate the localised immune response. Methods A Pubmed database search was performed for studies providing evidence for a functional cholinergic system operating in the periodontium. In addition, literature on the role of the ‘cholinergic anti-inflammatory pathway’ in modulating the immune response was extrapolated to hypothesise that similar mechanisms of immune regulation occur within the periodontium. Conclusion The evidence suggests a functional nonneuronal ‘cholinergic anti-inflammatory pathway’ may operate in the periodontium and that this may be targeted therapeutically to treat periodontal disease. PMID:22777144

Evidence of West Nile virus infection in Nepal.

PubMed

Rutvisuttinunt, Wiriya; Chinnawirotpisan, Piyawan; Klungthong, Chonticha; Shrestha, Sanjaya Kumar; Thapa, Amod Bahadur; Pant, Arjun; Yingst, Samuel L; Yoon, In-Kyu; Fernandez, Stefan; Pavlin, Julie A

2014-11-27

Acute febrile illness is common among those seeking medical care and is frequently treated empirically with the underlying illness remaining undiagnosed in resource-poor countries. A febrile illness study was conducted 2009-2010 to identify known and unknown pathogens circulating in Nepal. Study methods included diagnostic testing and preliminary ELISA screening of acute and convalescent samples for diseases both known and unknown to be circulating in Nepal, including West Nile virus (WNV). The molecular assays including Polymerase Chain Reaction (PCR), Sanger sequencing and ultra deep sequencing on MiSeq Illumina Platform were conducted to further confirm the presence of WNV. The study enrolled 2,046 patients presenting undifferentiated febrile illness with unknown etiology. Sera from 14 out of 2,046 patients were tested positive for west nile virus (WNV) by nested Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Only two out of 14 cases were confirmed for the presence of WNV by sequencing and identified as WNV lineage 1 phylogentically. The two patients were adult males with fever and no neurological symptoms from Kathmandu and Bharatpur, Nepal. Two out of 2,046 serum samples contained fragments of WNV genome resembling WNV lineage 1, which is evidence of the continued spread of WNV which should be considered a possible illness cause in Nepal.

Epistemic and aleatory uncertainty in the study of dynamic human-water systems

NASA Astrophysics Data System (ADS)

Di Baldassarre, Giuliano; Brandimarte, Luigia; Beven, Keith

2016-04-01

Here we discuss epistemic and aleatory uncertainty in the study of dynamic human-water systems (e.g. socio-hydrology), which is one of the main topics of Panta Rhei, the current scientific decade of the International Association of Hydrological Sciences (IAHS). In particular, we identify three types of lack of understanding: (i) known unknowns, which are things we know we don't know; (ii) unknown unknowns, which are things we don't know we don't know; and (iii) wrong assumptions, things we think we know, but we actually don't know. We posit that a better understanding of human-water interactions and feedbacks can help coping with wrong assumptions and known unknowns. Moreover, being aware of the existence of unknown unknowns, and their potential capability to generate surprises or black swans, suggest the need to rely more on bottom-up approaches, based on social vulnerabilities and possibilities of failures, and less on top-down approaches, based on optimization and quantitative predictions.

Characterization of antennal sensilla, larvae morphology and olfactory genes of Melipona scutellaris stingless bee

PubMed Central

de Carvalho, Washington João; Fujimura, Patrícia Tieme; Bonetti, Ana Maria; Goulart, Luiz Ricardo; Cloonan, Kevin; da Silva, Neide Maria; Araújo, Ester Cristina Borges; Ueira-Vieira, Carlos; Leal, Walter S.

2017-01-01

There is growing evidence in the literature suggesting that caste differentiation in the stingless bee, Melipona scutellaris, and other bees in the genus Melipona, is triggered by environmental signals, particularly a primer pheromone. With the proper amount of food and a chemical stimulus, 25% of females emerge as queens, in agreement with a long-standing “two loci/two alleles model” proposed in the 1950s. We surmised that these larvae must be equipped with an olfactory system for reception of these chemical signals. Here we describe for the first time the diversity of antennal sensilla in adults and the morphology of larvae of M. scutellaris. Having found evidence for putative olfactory sensilla in larvae, we next asked whether olfactory proteins were expressed in larvae. Since the molecular basis of M. scutellaris is still unknown, we cloned olfactory genes encoding chemosensory proteins (CSP) and odorant-binding proteins (OBPs) using M. scutellaris cDNA template and primers designed on the basis CSPs and OBPs previously reported from the European honeybee, Apis mellifera. We cloned two CSP and two OBP genes and then attempted to express the proteins encoded by these genes. With a recombinant OBP, MscuOBP8, and a combinatorial single-chain variable fragment antibody library, we generated anti-MscuOBP8 monoclonal antibody. By immunohistochemistry we demonstrated that the anti-MscuOBP8 binds specifically to the MscuOBP8. Next, we found evidence that MscuOBP8 is expressed in M. scutellaris larvae and it is located in the mandibular region, thus further supporting the hypothesis of olfactory function in immature stages. Lastly, molecular modeling suggests that MscuOBP8 may function as a carrier of primer pheromones or other ligands. PMID:28423045

Characterization of antennal sensilla, larvae morphology and olfactory genes of Melipona scutellaris stingless bee.

PubMed

Carvalho, Washington João de; Fujimura, Patrícia Tieme; Bonetti, Ana Maria; Goulart, Luiz Ricardo; Cloonan, Kevin; da Silva, Neide Maria; Araújo, Ester Cristina Borges; Ueira-Vieira, Carlos; Leal, Walter S

2017-01-01

There is growing evidence in the literature suggesting that caste differentiation in the stingless bee, Melipona scutellaris, and other bees in the genus Melipona, is triggered by environmental signals, particularly a primer pheromone. With the proper amount of food and a chemical stimulus, 25% of females emerge as queens, in agreement with a long-standing "two loci/two alleles model" proposed in the 1950s. We surmised that these larvae must be equipped with an olfactory system for reception of these chemical signals. Here we describe for the first time the diversity of antennal sensilla in adults and the morphology of larvae of M. scutellaris. Having found evidence for putative olfactory sensilla in larvae, we next asked whether olfactory proteins were expressed in larvae. Since the molecular basis of M. scutellaris is still unknown, we cloned olfactory genes encoding chemosensory proteins (CSP) and odorant-binding proteins (OBPs) using M. scutellaris cDNA template and primers designed on the basis CSPs and OBPs previously reported from the European honeybee, Apis mellifera. We cloned two CSP and two OBP genes and then attempted to express the proteins encoded by these genes. With a recombinant OBP, MscuOBP8, and a combinatorial single-chain variable fragment antibody library, we generated anti-MscuOBP8 monoclonal antibody. By immunohistochemistry we demonstrated that the anti-MscuOBP8 binds specifically to the MscuOBP8. Next, we found evidence that MscuOBP8 is expressed in M. scutellaris larvae and it is located in the mandibular region, thus further supporting the hypothesis of olfactory function in immature stages. Lastly, molecular modeling suggests that MscuOBP8 may function as a carrier of primer pheromones or other ligands.

The eastern arm of the Midcontinent Rift: Progress and problems

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

Hinze, W.J.

1994-04-01

The extent and nature of the Midcontinent Rift System (MCR) was initially determined by potential-field mapping and extrapolation of geologic information from the Lake Superior region. Early interpretation suggested a rift origin which is well supported by deep crustal reflection seismic data and isotopic evidence from the related volcanic rocks that became available during the past decade. A rift origin of the eastern arm of the MCR was corroborated by sub-Phanerozoic drilling into the clastic sediment and volcanic rocks in the McClure-Sparks drill hole located on a massive anticlinal feature in the Precambrian rocks mapped by seismic reflection data. Subsequentmore » seismic profiling further detailed the character of the rift. However, these studies also indicate that the eastern arm is unlike the western, e.g., adjacent clastic rock basins are absent, late-stage compressional features are present, but definite evidence for high-angle reverse faulting is missing, and volcanic basins are not continuous. The termination of this arm of the rift also remains problematic. There is no direct evidence of the rift SE of the McClure-Sparks hole in central Michigan. Geophysical anomalies and deep drilling in the Howell anticline region suggest that the 1,100 Ma old rift is covered by Grenville-age thrusts. If the rift extends farther to the SE, its nature must have been altered by the Grenville orogeny. The hypothesized extension across Ohio east of the Grenville Front is unsupported by seismic reflection profiling and anomaly modeling. Grabens identified at the basement surface in Ohio and to the south are of unknown age, but appear to be more clearly related to late-stage Grenville activity and/or continuation of Eocambrian rifts of the Mississippi Embayment.« less

An immunological perspective on rheumatic heart disease pathogenesis: more questions than answers.

PubMed

Bright, Philip David; Mayosi, Bongani M; Martin, William John

2016-10-01

Acute rheumatic fever (ARF) and the related rheumatic heart disease (RHD) are autoimmune diseases thought to be triggered by group A streptococcal (GAS) pharyngitis. RHD is a leading cause of mortality in the developing world. The strong epidemiological association between GAS throat infection and ARF is highly suggestive of causation, but does not exclude other infections as contributory. There is good evidence of both humoral and cellular autoreactivity and GAS/self cross-reactivity in established RHD. RHD pathogenesis could feasibly be triggered and driven by humoral and/or cellular molecular cross-reactivity between GAS and host cardiac tissues (molecular mimicry). However, good evidence of humoral pathogenicity is lacking and the specific triggering event for RHD remains unknown. It is likely that the critical immunological events leading to ARF/RHD occur at the point of contact between GAS and the immune system in the throat, strongly implicating the mucosal immune system in RHD pathogenesis. Additionally, there is circumstantial evidence that continued live GAS may play a role in ARF/RHD pathogenesis. We suggest that future avenues for study should include the exclusion of GAS components directly contributing to RHD pathogenesis; large genome-wide association studies of patients with RHD looking for candidate genes involved in RHD pathogenesis; genome-wide association studies of GAS from patients with ARF taken at diagnosis to look for characteristics of rheumatogenic strains; and performing case/control studies of GAS pharyngitis/ARF/patients with RHD, and controls to identify microbiological, immunological and environmental differences to elucidate RHD pathogenesis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The KTB apatite fission-track profiles: Building on a firm foundation?

NASA Astrophysics Data System (ADS)

Wauschkuhn, B.; Jonckheere, R.; Ratschbacher, L.

2015-10-01

Deep boreholes serve as natural laboratories for testing thermochronometers under geological conditions. The Kontinentale Tiefbohrung (KTB) is an interesting candidate because the geological evidence suggests that approximate isothermal holding since the last documented exhumation in the Late Cretaceous to Palaeocene is a reasonable assumption for the thermal histories of the KTB samples. We report 30 new apatite fission-track ages and 50 new mean confined track lengths determined on cores from the 4 km deep pilot hole. The ϕ- and ζ-external detector ages are consistent with the population ages from earlier studies and together define a clear age profile. The mean track lengths from this and earlier studies reveal the effects of experimental factors. The measured age and length profiles are compared with the predictions of 24 annealing models for isothermal holding. There are clear discrepancies between the measured and calculated profiles. Down to 1.5 km depth, the measured mean track lengths are shorter than the predicted. The balance of methodological evidence indicates that this is due to seasoning, i.e., a shortening of the fossil confined tracks without attendant age reduction. From 2.5 to 4.0 km depth, the mean track lengths are longer than the predictions. This suggests that the bias model that weights the probabilities of observing tracks of different length and which is based on experiments relating surface track densities to mean track lengths is not appropriate for confined tracks. Experimental and methodological factors are sometimes difficult to disentangle, but present a sufficient margin for there to be no need to go against the independent geological evidence. Unknown geological events cannot be ruled out but their existence cannot be inferred from the fission-track data alone, much less can the nature or magnitude of such events be specified.

Effects of omega-3 polyunsaturated fatty acids on human brain morphology and function: What is the evidence?

PubMed

Bos, Dienke J; van Montfort, Simone J T; Oranje, Bob; Durston, Sarah; Smeets, Paul A M

2016-03-01

Public opinion and media coverage suggest that there are benefits of long-chain ω-3 polyunsaturated fatty acid (LC-PUFA) intake on brain functioning. However, it is an open question whether this is indeed the case. Therefore, we reviewed the evidence for effects of ω-3 LC-PUFA on human brain morphology and function. We included studies on (1) naturalistic long-term ω-3 LC-PUFA intake during life (2) the effects of short-term ω-3 LC-PUFA supplementation in healthy subjects and (3) the effects of ω-3 LC-PUFA supplementation as alternative or add-on treatment for psychiatric or neurological disorders. To date, 24 studies have been published on the effect of ω-3 LC-PUFA on brain function and structure. Findings from naturalistic studies and clinical trials in healthy individuals indicate that ω-3 LC-PUFA intake may be associated with increased functional activation of the prefrontal cortex in children, and greater gray matter volume and white matter integrity during aging. However, most naturalistic studies were cross-sectional or did not find any effect on cognition. As such, it is hard to estimate the magnitude of any beneficial effects. Furthermore, there is only limited evidence to support that ω-3 LC-PUFA supplementation is beneficial in brain disorders, such as Alzheimer's Disease, Attention Deficit/Hyperactivity Disorder, Major Depressive Disorder and schizophrenia. Overall, the literature suggests that sensitivity to supplementation may vary over development, and as a consequence of brain disorders. The biological mechanisms underlying any (beneficial) effects ω-3 LC-PUFAs on the brain are currently unknown and need to be investigated. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Functional specialization in nucleotide sugar transporters occurred through differentiation of the gene cluster EamA (DUF6) before the radiation of Viridiplantae

PubMed Central

2011-01-01

Background The drug/metabolite transporter superfamily comprises a diversity of protein domain families with multiple functions including transport of nucleotide sugars. Drug/metabolite transporter domains are contained in both solute carrier families 30, 35 and 39 proteins as well as in acyl-malonyl condensing enzyme proteins. In this paper, we present an evolutionary analysis of nucleotide sugar transporters in relation to the entire superfamily of drug/metabolite transporters that considers crucial intra-protein duplication events that have shaped the transporters. We use a method that combines the strengths of hidden Markov models and maximum likelihood to find relationships between drug/metabolite transporter families, and branches within families. Results We present evidence that the triose-phosphate transporters, domain unknown function 914, uracil-diphosphate glucose-N-acetylglucosamine, and nucleotide sugar transporter families have evolved from a domain duplication event before the radiation of Viridiplantae in the EamA family (previously called domain unknown function 6). We identify previously unknown branches in the solute carrier 30, 35 and 39 protein families that emerged simultaneously as key physiological developments after the radiation of Viridiplantae, including the "35C/E" branch of EamA, which formed in the lineage of T. adhaerens (Animalia). We identify a second cluster of DMTs, called the domain unknown function 1632 cluster, which has non-cytosolic N- and C-termini, and thus appears to have been formed from a different domain duplication event. We identify a previously uncharacterized motif, G-X(6)-G, which is overrepresented in the fifth transmembrane helix of C-terminal domains. We present evidence that the family called fatty acid elongases are homologous to transporters, not enzymes as had previously been thought. Conclusions The nucleotide sugar transporters families were formed through differentiation of the gene cluster EamA (domain unknown function 6) before Viridiplantae, showing for the first time the significance of EamA. PMID:21569384

Arf Suppresses Hepatic Vascular Neoplasia in a Carcinogen-Exposed Murine Model

PubMed Central

Busch, Stephanie E; Gurley, Kay E; Moser, Russell D; Kemp, Christopher J

2013-01-01

Hepatic haemangiosarcoma is a deadly malignancy whose aetiology remains poorly understood. Inactivation of the CDKN2A locus, which houses the ARF and p16INK4a tumour suppressor genes, is a common event in haemangiosarcoma patients, but the precise role of ARF in vascular tumourigenesis is unknown. To determine the extent to which ARF suppresses vascular neoplasia, we examined the incidence of hepatic vascular lesions in Arf-deficient mice exposed to the carcinogen urethane (i.p. 1 mg/g). Loss of Arf resulted in elevated morbidity and increased the incidence of both haemangiomas and incipient haemangiosarcomas. Suppression of vascular lesion development by ARF was heavily dependent on both Arf gene-dosage and the genetic strain of the mouse. Trp53-deficient mice also developed hepatic vascular lesions after exposure to urethane, suggesting that ARF signals through a p53-dependent pathway to inhibit the development of hepatic haemangiosarcoma. Our findings provide strong evidence that inactivation of Arf is a causative event in vascular neoplasia and suggest that the ARF pathway may be a novel molecular target for therapeutic intervention in haemangiosarcoma patients. PMID:22430984

Human Subject Effects on Torsion Pendulum Oscillations: Further Evidence of Mediation by Convection Currents.

PubMed

Hammerschlag, Richard; Linda Baldwin, Ann; Schwartz, Gary E

When a human subject sits beneath a wire mesh, hemispheric torsion pendulum (TP) a rapid-onset series of oscillations at frequencies both higher and lower than the fundamental frequency of the TP have been consistently observed. This study was designed to replicate and extend prior findings that suggest the human subject effect on TP behavior is due to subject-generated, heat-induced convection currents. Effects on pendulum behavior were tested after draping an aluminized "space blanket" over the subject and by replacing the subject with a thermal mattress pad shaped to approximate the human form. Experiments were performed in a basic science university research laboratory. Real-time recordings and Fast Fourier Transform frequency spectra of pendulum oscillatory movement. The space blanket blocked, while the mattress pad mimicked, the human subject induced complex array of pendulum oscillations. Our findings support and strengthen previous results that suggest the effects of human subjects on behavior of a torsion pendulum are mediated by body-heat-induced air convection rather than an unknown type of biofield. Copyright © 2016 Elsevier Inc. All rights reserved.

Brefeldin A Inhibits Cell-Free, De Novo Synthesis of Poliovirus

PubMed Central

Cuconati, Andrea; Molla, Akhteruzzaman; Wimmer, Eckard

1998-01-01

Brefeldin A (BFA), an inhibitor of intracellular vesicle-dependent secretory transport, is a potent inhibitor of poliovirus RNA replication in infected cells. We have determined that the unknown mechanism of BFA inhibition of replication is reproduced in the cell-free poliovirus translation, replication, and encapsidation system. Furthermore, we provide evidence suggesting that the cellular mechanism targeted by BFA, the GTP-dependent synthesis of secretory transport vesicles, may be involved in viral RNA replication in the system via a soluble cellular GTP-binding and -hydrolyzing activity. This activity is related to the ARF (ADP-ribosylation factor) family of GTP-binding proteins. ARFs are required for the formation of several classes of secretory vesicles, and some family members are indirectly inactivated by BFA. Peptides that function as competitive inhibitors of ARF activity in cell-free transport systems also inhibit poliovirus RNA replication, and this inhibitory effect can be countered by the addition of exogenous ARF. We suggest that BFA inhibition of replication is diagnostic of a requirement for ARF activity in the cell-free system. PMID:9658088

Physiologically mediated self/non-self discrimination in roots

PubMed Central

Gruntman, Michal; Novoplansky, Ariel

2004-01-01

Recent evidence suggests that self/non-self discrimination exists among roots; its mechanisms, however, are still unclear. We compared the growth of Buchloe dactyloides cuttings that were grown in the presence of neighbors that belonged to the same physiological individual, were separated from each other for variable periods, or originated from adjacent or remote tillers on the same clone. The results demonstrate that B. dactyloides plants are able to differentiate between self and non-self neighbors and develop fewer and shorter roots in the presence of other roots of the same individual. Furthermore, once cuttings that originate from the very same node are separated, they become progressively alienated from each other and eventually relate to each other as genetically alien plants. The results suggest that the observed self/non-self discrimination is mediated by physiological coordination among roots that developed on the same plant rather than allogenetic recognition. The observed physiological coordination is based on an as yet unknown mechanism and has important ecological implications, because it allows the avoidance of competition with self and the allocation of greater resources to alternative functions. PMID:15004281

Using latent effects to determine the ecological importance of dissolved organic matter to marine invertebrates.

PubMed

Wendt, Dean E; Johnson, Collin H

2006-10-01

The uptake and utilization of dissolved organic matter (DOM) by marine invertebrates is a field that has received significant attention over the past 100 years. Although it is well established that DOM is taken up by marine invertebrates, the extent to which it contributes to an animal's survival, growth, and reproduction (that is, the ecological benefits) remains largely unknown. Previous work seeking to demonstrate the putative ecological benefits of DOM uptake have examined them within a single life stage of an animal. Moreover, most of the benefits are demonstrated through indirect approaches by examining (1) mass balance, or (2) making comparisons of oxyenthalpic conversions of transport rates to metabolic rate as judged by oxygen consumption. We suggest that directly examining delayed metamorphosis or the latent effects associated with nutritional stress of larvae is a better model for investigating the ecological importance of DOM to marine invertebrates. We also provide direct evidence that availability of DOM enhances survival and growth of the bryozoan Bugula neritina. That DOM offsets latent effects in B. neritina suggests that the underlying mechanisms are at least in part energetic.

Empirically evaluating the impact of adjudicative tribunals in the health sector: context, challenges and opportunities.

PubMed

Hoffman, Steven J; Sossin, Lorne

2012-04-01

Adjudicative tribunals are an integral part of health system governance, yet their real-world impact remains largely unknown. Most assessments focus on internal accountability and use anecdotal methodologies; few, studies if any, empirically evaluate their external impact and use these data to test effectiveness, track performance, inform service improvements and ultimately strengthen health systems. Given that such assessments would yield important benefits and have been conducted successfully in similar settings (e.g. specialist courts), their absence is likely attributable to complexity in the health system, methodological difficulties and the legal environment within which tribunals operate. We suggest practical steps for potential evaluators to conduct empirical impact evaluations along with an evaluation matrix template featuring possible target outcomes and corresponding surrogate endpoints, performance indicators and empirical methodologies. Several system-level strategies for supporting such assessments have also been suggested for academics, health system institutions, health planners and research funders. Action is necessary to ensure that policymakers do not continue operating without evidence but can rather pursue data-driven strategies that are more likely to achieve their health system goals in a cost-effective way.

Root phonotropism: Early signalling events following sound perception in Arabidopsis roots.

PubMed

Rodrigo-Moreno, Ana; Bazihizina, Nadia; Azzarello, Elisa; Masi, Elisa; Tran, Daniel; Bouteau, François; Baluska, Frantisek; Mancuso, Stefano

2017-11-01

Sound is a fundamental form of energy and it has been suggested that plants can make use of acoustic cues to obtain information regarding their environments and alter and fine-tune their growth and development. Despite an increasing body of evidence indicating that it can influence plant growth and physiology, many questions concerning the effect of sound waves on plant growth and the underlying signalling mechanisms remains unknown. Here we show that in Arabidopsis thaliana, exposure to sound waves (200Hz) for 2 weeks induced positive phonotropism in roots, which grew towards to sound source. We found that sound waves triggered very quickly (within  minutes) an increase in cytosolic Ca 2+ , possibly mediated by an influx through plasma membrane and a release from internal stock. Sound waves likewise elicited rapid reactive oxygen species (ROS) production and K + efflux. Taken together these results suggest that changes in ion fluxes (Ca 2+ and K + ) and an increase in superoxide production are involved in sound perception in plants, as previously established in animals. Copyright © 2017 Elsevier B.V. All rights reserved.

Reevaluation of the Dentary Structures of Caenagnathid Oviraptorosaurs (Dinosauria, Theropoda).

PubMed

Wang, Shuo; Zhang, Qiyue; Yang, Rui

2018-01-10

Among the characters of caenagnathid oviraptorosaurians, the lateral occlusal grooves and ridges on the occlusal surface of the jaw bones often receive special attention. Recent studies demonstrated that ontogenetic edentulism is present in caenagnathids, and therefore the lateral occlusal grooves and ridges are vestigial alveoli and interdental septa, respectively. In the present paper, the dentary structures of caenagnathids were reevaluated based on CT images of Caenagnathiasia sp. IVPP V20377. Several previously unknown features including crateriform vestigial alveoli, the morphology of the dentary interior hollow space, and the paired blind tubes beneath the dentary symphyseal shelf are recognized. Current lines of evidence suggest different jaw bone morphologies are likely produced by various tooth reduction patterns, which indicates ontogenetic dietary shift, if once presented in caenagnathids and Sapeornis, may have been different from the condition seen in Limusaurus. The 3D images of dentary interior spaces suggest that while tooth reduction progresses, the empty alveoli are partially modified into structures accommodating blood vessels that nourish the rhamphotheca, probably representing a functional compensation for the insufficient blood supply in toothed jaw bones.

Diagnosis and Treatment of Acute Retinal Necrosis: A Report by the American Academy of Ophthalmology.

PubMed

Schoenberger, Scott D; Kim, Stephen J; Thorne, Jennifer E; Mruthyunjaya, Prithvi; Yeh, Steven; Bakri, Sophie J; Ehlers, Justis P

2017-03-01

To evaluate the available evidence in peer-reviewed publications about the diagnosis and treatment of acute retinal necrosis (ARN). Literature searches of the PubMed and Cochrane Library databases were last conducted on July 27, 2016. The searches identified 216 unique citations, and 49 articles of possible clinical relevance were reviewed in full text. Of these 49 articles, 27 were deemed sufficiently relevant or of interest, and they were rated according to strength of evidence. An additional 6 articles were identified from the reference lists of these articles and included. All 33 studies were retrospective. Polymerase chain reaction (PCR) testing of aqueous or vitreous humor was positive for herpes simplex virus (HSV) or varicella zoster virus (VZV) in 79% to 100% of cases of suspected ARN. Aqueous and vitreous specimens are both sensitive and specific. There is level II and III evidence supporting the use of intravenous and oral antiviral therapy for the treatment of ARN. Data suggest that equivalent plasma drug levels of acyclovir can be achieved after administration of oral valacyclovir or intravenous acyclovir. There is level II and III evidence suggesting that the combination of intravitreal foscarnet and systemic antiviral therapy may have greater therapeutic efficacy than systemic therapy alone. The effectiveness of prophylactic laser or early pars plana vitrectomy (PPV) in preventing retinal detachment (RD) remains unclear. Polymerase chain reaction testing of ocular fluid is useful in supporting a clinical diagnosis of ARN, but treatment should not be delayed while awaiting PCR results. Initial oral or intravenous antiviral therapy is effective in treating ARN. The adjunctive use of intravitreal foscarnet may be more effective than systemic therapy alone. The role of prophylactic laser retinopexy or early PPV is unknown at this time. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Sequential sampling of visual objects during sustained attention.

PubMed

Jia, Jianrong; Liu, Ling; Fang, Fang; Luo, Huan

2017-06-01

In a crowded visual scene, attention must be distributed efficiently and flexibly over time and space to accommodate different contexts. It is well established that selective attention enhances the corresponding neural responses, presumably implying that attention would persistently dwell on the task-relevant item. Meanwhile, recent studies, mostly in divided attentional contexts, suggest that attention does not remain stationary but samples objects alternately over time, suggesting a rhythmic view of attention. However, it remains unknown whether the dynamic mechanism essentially mediates attentional processes at a general level. Importantly, there is also a complete lack of direct neural evidence reflecting whether and how the brain rhythmically samples multiple visual objects during stimulus processing. To address these issues, in this study, we employed electroencephalography (EEG) and a temporal response function (TRF) approach, which can dissociate responses that exclusively represent a single object from the overall neuronal activity, to examine the spatiotemporal characteristics of attention in various attentional contexts. First, attention, which is characterized by inhibitory alpha-band (approximately 10 Hz) activity in TRFs, switches between attended and unattended objects every approximately 200 ms, suggesting a sequential sampling even when attention is required to mostly stay on the attended object. Second, the attentional spatiotemporal pattern is modulated by the task context, such that alpha-mediated switching becomes increasingly prominent as the task requires a more uniform distribution of attention. Finally, the switching pattern correlates with attentional behavioral performance. Our work provides direct neural evidence supporting a generally central role of temporal organization mechanism in attention, such that multiple objects are sequentially sorted according to their priority in attentional contexts. The results suggest that selective attention, in addition to the classically posited attentional "focus," involves a dynamic mechanism for monitoring all objects outside of the focus. Our findings also suggest that attention implements a space (object)-to-time transformation by acting as a series of concatenating attentional chunks that operate on 1 object at a time.

Sequential sampling of visual objects during sustained attention

PubMed Central

Jia, Jianrong; Liu, Ling; Fang, Fang

2017-01-01

In a crowded visual scene, attention must be distributed efficiently and flexibly over time and space to accommodate different contexts. It is well established that selective attention enhances the corresponding neural responses, presumably implying that attention would persistently dwell on the task-relevant item. Meanwhile, recent studies, mostly in divided attentional contexts, suggest that attention does not remain stationary but samples objects alternately over time, suggesting a rhythmic view of attention. However, it remains unknown whether the dynamic mechanism essentially mediates attentional processes at a general level. Importantly, there is also a complete lack of direct neural evidence reflecting whether and how the brain rhythmically samples multiple visual objects during stimulus processing. To address these issues, in this study, we employed electroencephalography (EEG) and a temporal response function (TRF) approach, which can dissociate responses that exclusively represent a single object from the overall neuronal activity, to examine the spatiotemporal characteristics of attention in various attentional contexts. First, attention, which is characterized by inhibitory alpha-band (approximately 10 Hz) activity in TRFs, switches between attended and unattended objects every approximately 200 ms, suggesting a sequential sampling even when attention is required to mostly stay on the attended object. Second, the attentional spatiotemporal pattern is modulated by the task context, such that alpha-mediated switching becomes increasingly prominent as the task requires a more uniform distribution of attention. Finally, the switching pattern correlates with attentional behavioral performance. Our work provides direct neural evidence supporting a generally central role of temporal organization mechanism in attention, such that multiple objects are sequentially sorted according to their priority in attentional contexts. The results suggest that selective attention, in addition to the classically posited attentional “focus,” involves a dynamic mechanism for monitoring all objects outside of the focus. Our findings also suggest that attention implements a space (object)-to-time transformation by acting as a series of concatenating attentional chunks that operate on 1 object at a time. PMID:28658261

LONG-TERM SURVEILLANCE OF LANGUR ALPHAHERPESVIRUS IN A ZOO POPULATION OF SILVERED LANGURS ( TRACHYPITHECUS CRISTATUS).

PubMed

Gustavsen, Kate A; Raphael, Bonnie L; Wildes, Martin J; McAloose, Denise; McCann, Colleen M; Hilliard, Julia K; Calle, Paul P

2018-06-01

  Langur alphaherpesvirus (HVL), a provisionally named alphaherpesvirus in the Simplexvirus genus, was first identified in 1991 at the Bronx Zoo in wild-origin silvered langurs ( Trachypithecus cristatus) and their descendants. HVL is closely related to B virus ( Macacine alphaherpesvirus 1) based on serologic and genetic data, but its natural history and zoonotic potential remain unknown. A cohort study was undertaken to describe the epidemiology, clinical impact, and potential management implications of this virus in a naturally infected, zoo-based population of silvered langurs. Opportunistic surveillance sampling from 1991 through 2015 resulted in 235 serum samples and 225 mucosal swabs from 75 individuals. A total of 43 individuals (57.3%) were seropositive for HVL within this period. Seroprevalence increased significantly with age, and indirect evidence suggested a peak in transmission at the onset of sexual maturity. These findings were similar to the behavior of other simplexviruses in their adapted hosts. Yearly cumulative incidence declined significantly through the study period, with zero or one new case detected each year from 2007 through 2015. The density of this population decreased within the study period for management reasons unrelated to HVL infection, and a change in age distribution or less-frequent contacts may have contributed to low transmission. In addition, clinical signs of simplexvirus infection were rare, and virus isolation was negative on all mucosal swabs, suggesting that viral shedding was infrequent. Yearly period seroprevalence remained relatively constant with a median of 45.8%, likely because of the extended survival of infected individuals within the population. Maintenance of a naturally occurring, novel virus with unknown zoonotic potential in a zoo population for over 25 yr highlights the importance of biosecurity and biosafety for management of silvered langurs and all primate species.

Inflammation and Tissue Remodeling in the Bladder and Urethra in Feline Interstitial Cystitis

PubMed Central

Kullmann, F. Aura; McDonnell, Bronagh M.; Wolf-Johnston, Amanda S.; Lynn, Andrew M.; Getchell, Samuel E.; Ruiz, Wily G.; Zabbarova, Irina V.; Ikeda, Youko; Kanai, Anthony J.; Roppolo, James R.; Bastacky, Sheldon I.; Apodaca, Gerard; Buffington, C. A. Tony; Birder, Lori A.

2018-01-01

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disease of unknown etiology. A naturally occurring disease termed feline interstitial cystitis (FIC) reproduces many features of IC/BPS patients. To gain insights into mechanisms underlying IC/BPS, we investigated pathological changes in the lamina propria (LP) of the bladder and proximal urethra in cats with FIC, using histological and molecular methods. Compared to control cat tissue, we found an increased number of de-granulated mast cells, accumulation of leukocytes, increased cyclooxygenase (COX)-1 expression in the bladder LP, and increased COX-2 expression in the urethra LP from cats with FIC. We also found increased suburothelial proliferation, evidenced by mucosal von Brunn’s nests, neovascularization and alterations in elastin content. Scanning electron microscopy revealed normal appearance of the superficial urethral epithelium, including the neuroendocrine cells (termed paraneurons), in FIC urethrae. Together, these histological findings suggest the presence of chronic inflammation of unknown origin leading to tissue remodeling. Since the mucosa functions as part of a “sensory network” and urothelial cells, nerves and other cells in the LP are influenced by the composition of the underlying tissues including the vasculature, the changes observed in the present study may alter the communication of sensory information between different cellular components. This type of mucosal signaling can also extend to the urethra, where recent evidence has revealed that the urethral epithelium is likely to be part of a signaling system involving paraneurons and sensory nerves. Taken together, our data suggest a more prominent role for chronic inflammation and tissue remodeling than previously thought, which may result in alterations in mucosal signaling within the urinary bladder and proximal urethra that may contribute to altered sensations and pain in cats and humans with this syndrome. PMID:29706873

Systematic toxicological analysis: computer-assisted identification of poisons in biological materials.

PubMed

Stimpfl, Th; Demuth, W; Varmuza, K; Vycudilik, W

2003-06-05

A new software was developed to improve the chances for identification of a "general unknown" in complex biological materials. To achieve this goal, the total ion current chromatogram was simplified by filtering the acquired mass spectra via an automated subtraction procedure, which removed mass spectra originating from the sample matrix, as well as interfering substances from the extraction procedure. It could be shown that this tool emphasizes mass spectra of exceptional compounds, and therefore provides the forensic toxicologist with further evidence-even in cases where mass spectral data of the unknown compound are not available in "standard" spectral libraries.

Imidacloprid Decreases Honey Bee Survival Rates but Does Not Affect the Gut Microbiome.

PubMed

Raymann, Kasie; Motta, Erick V S; Girard, Catherine; Riddington, Ian M; Dinser, Jordan A; Moran, Nancy A

2018-07-01

Accumulating evidence suggests that pesticides have played a role in the increased rate of honey bee colony loss. One of the most commonly used pesticides in the United States is the neonicotinoid imidacloprid. Although the primary mode of action of imidacloprid is on the insect nervous system, it has also been shown to cause changes in insects' digestive physiology and alter the microbiota of Drosophila melanogaster larvae. The honey bee gut microbiome plays a major role in bee health. Although many studies have shown that imidacloprid affects honey bee behavior, its impact on the microbiome has not been fully elucidated. Here, we investigated the impact of imidacloprid on the gut microbiome composition, survivorship, and susceptibility to pathogens of honey bees. Consistent with other studies, we show that imidacloprid exposure results in an elevated mortality of honey bees in the hive and increases the susceptibility to infection by pathogens. However, we did not find evidence that imidacloprid affects the gut bacterial community of honey bees. Our in vitro experiments demonstrated that honey bee gut bacteria can grow in the presence of imidacloprid, and we found some evidence that imidacloprid can be metabolized in the bee gut environment. However, none of the individual bee gut bacterial species tested could metabolize imidacloprid, suggesting that the observed metabolism of imidacloprid within in vitro bee gut cultures is not caused by the gut bacteria. Overall, our results indicate that imidacloprid causes increased mortality in honey bees, but this mortality does not appear to be linked to the microbiome. IMPORTANCE Growing evidence suggests that the extensive use of pesticides has played a large role in the increased rate of honey bee colony loss. Despite extensive research on the effects of imidacloprid on honey bees, it is still unknown whether it impacts the community structure of the gut microbiome. Here, we investigated the impact of imidacloprid on the gut microbiome composition, survivorship, and susceptibility to pathogens of honey bees. We found that the exposure to imidacloprid resulted in an elevated mortality of honey bees and increased the susceptibility to infection by opportunistic pathogens. However, we did not find evidence that imidacloprid affects the gut microbiome of honey bees. We found some evidence that imidacloprid can be metabolized in the bee gut environment in vitro , but because it is quickly eliminated from the bee, it is unlikely that this metabolism occurs in nature. Thus, imidacloprid causes increased mortality in honey bees, but this does not appear to be linked to the microbiome. Copyright © 2018 American Society for Microbiology.

Sleep-disordered breathing in epilepsy: epidemiology, mechanisms, and treatment.

PubMed

Sivathamboo, Shobi; Perucca, Piero; Velakoulis, Dennis; Jones, Nigel C; Goldin, Jeremy; Kwan, Patrick; O'Brien, Terence J

2018-04-01

Epilepsy is a group of neurological conditions in which there is a pathological and enduring predisposition to generate recurrent seizures. Evidence over the last few decades suggests that epilepsy may be associated with increased sleep-disordered breathing, which may contribute towards sleep fragmentation, daytime somnolence, reduced seizure control, and cardiovascular-related morbidity and mortality. Chronic sleep-disordered breathing can result in loss of gray matter and cause deficits to memory and global cognitive function. Sleep-disordered breathing is a novel and independent predictor of sudden cardiac death and, as such, may be involved in the mechanisms leading to sudden unexpected death in epilepsy. Despite this, the long-term consequences of sleep-disordered breathing in epilepsy remain unknown, and there are no guidelines for screening or treating this population. There is currently insufficient evidence to indicate continuous positive airway pressure (CPAP) for the primary or secondary prevention of cardiovascular disease, and recent evidence has failed to show any reduction of fatal or nonfatal cardiovascular endpoints. Treatment of sleep-disordered breathing may potentially improve seizure control, daytime somnolence, and neurocognitive outcomes, but few studies have examined this relationship. In this review, we examine sleep-disordered breathing in epilepsy, and discuss the potential effect of epilepsy treatments. We consider the role of CPAP and other interventions for sleep-disordered breathing and discuss their implications for epilepsy management.

Using a higher criticism statistic to detect modest effects in a genome-wide study of rheumatoid arthritis

PubMed Central

2009-01-01

In high-dimensional studies such as genome-wide association studies, the correction for multiple testing in order to control total type I error results in decreased power to detect modest effects. We present a new analytical approach based on the higher criticism statistic that allows identification of the presence of modest effects. We apply our method to the genome-wide study of rheumatoid arthritis provided in the Genetic Analysis Workshop 16 Problem 1 data set. There is evidence for unknown bias in this study that could be explained by the presence of undetected modest effects. We compared the asymptotic and empirical thresholds for the higher criticism statistic. Using the asymptotic threshold we detected the presence of modest effects genome-wide. We also detected modest effects using 90th percentile of the empirical null distribution as a threshold; however, there is no such evidence when the 95th and 99th percentiles were used. While the higher criticism method suggests that there is some evidence for modest effects, interpreting individual single-nucleotide polymorphisms with significant higher criticism statistics is of undermined value. The goal of higher criticism is to alert the researcher that genetic effects remain to be discovered and to promote the use of more targeted and powerful studies to detect the remaining effects. PMID:20018032

Evidence for foliar endophytic nitrogen fixation in a widely distributed subalpine conifer

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

Moyes, Andrew B.; Kueppers, Lara M.; Pett-Ridge, Jennifer

Coniferous forest nitrogen (N) budgets indicate unknown sources of N. A consistent association between limber pine ( Pinus flexilis) and potential N 2-fixing acetic acid bacteria (AAB) indicates that native foliar endophytes may supply subalpine forests with N.

Evidence for foliar endophytic nitrogen fixation in a widely distributed subalpine conifer

DOE PAGES

Moyes, Andrew B.; Kueppers, Lara M.; Pett-Ridge, Jennifer; ...

2016-02-01

Coniferous forest nitrogen (N) budgets indicate unknown sources of N. A consistent association between limber pine ( Pinus flexilis) and potential N 2-fixing acetic acid bacteria (AAB) indicates that native foliar endophytes may supply subalpine forests with N.

Soluble Components of Ultraflne Particulate Matter Stimulate Endothelial H202 Production

EPA Science Inventory

A growing body of evidence shows a strong association between particulate matter (PM) exposure and adverse cardiovascular health effects such as atherosclerosis and myocardial ischemia. The mechanisms by which PM causes cardiovascular dysfunction is unknown, but there is increasi...

Wildlife-friendly farming benefits rare birds, bees and plants.

PubMed

Pywell, Richard F; Heard, Matthew S; Bradbury, Richard B; Hinsley, Shelley; Nowakowski, Marek; Walker, Kevin J; Bullock, James M

2012-10-23

Agricultural intensification is a leading cause of global biodiversity loss, especially for threatened and near-threatened species. One widely implemented response is 'wildlife-friendly farming', involving the close integration of conservation and extensive farming practices within agricultural landscapes. However, the putative benefits from this controversial policy are currently either unknown or thought unlikely to extend to rare and declining species. Here, we show that new, evidence-based approaches to habitat creation on intensively managed farmland in England can achieve large increases in plant, bee and bird species. In particular, we found that habitat enhancement methods designed to provide the requirements of sensitive target biota consistently increased the richness and abundance of both rare and common species, with 10-fold to greater than 100-fold more rare species per sample area than generalized conventional conservation measures. Furthermore, targeting landscapes of high species richness amplified beneficial effects on the least mobile taxa: plants and bees. Our results provide the first unequivocal support for a national wildlife-friendly farming policy and suggest that this approach should be implemented much more extensively to address global biodiversity loss. However, to be effective, these conservation measures must be evidence-based, and developed using sound knowledge of the ecological requirements of key species.

Proteomic Characterization of Cellular and Molecular Processes that Enable the Nanoarchaeum equitans-Ignicoccus hospitalis Relationship

PubMed Central

Giannone, Richard J.; Huber, Harald; Karpinets, Tatiana; Heimerl, Thomas; Küper, Ulf; Rachel, Reinhard; Keller, Martin; Hettich, Robert L.; Podar, Mircea

2011-01-01

Nanoarchaeum equitans, the only cultured representative of the Nanoarchaeota, is dependent on direct physical contact with its host, the hyperthermophile Ignicoccus hospitalis. The molecular mechanisms that enable this relationship are unknown. Using whole-cell proteomics, differences in the relative abundance of >75% of predicted protein-coding genes from both Archaea were measured to identify the specific response of I. hospitalis to the presence of N. equitans on its surface. A purified N. equitans sample was also analyzed for evidence of interspecies protein transfer. The depth of cellular proteome coverage achieved here is amongst the highest reported for any organism. Based on changes in the proteome under the specific conditions of this study, I. hospitalis reacts to N. equitans by curtailing genetic information processing (replication, transcription) in lieu of intensifying its energetic, protein processing and cellular membrane functions. We found no evidence of significant Ignicoccus biosynthetic enzymes being transported to N. equitans. These results suggest that, under laboratory conditions, N. equitans diverts some of its host's metabolism and cell cycle control to compensate for its own metabolic shortcomings, thus appearing to be entirely dependent on small, transferable metabolites and energetic precursors from I. hospitalis. PMID:21826220

Evidence for a plant-associated natural habitat for Cronobacter spp.

PubMed

Schmid, Michael; Iversen, Carol; Gontia, Iti; Stephan, Roger; Hofmann, Andreas; Hartmann, Anton; Jha, Bhavanath; Eberl, Leo; Riedel, Kathrin; Lehner, Angelika

2009-10-01

Cronobacter (Enterobacter sakazakii) species are responsible for rare cases of necrotising enterocolitis and bacteraemia in infants, as well as cases of meningitis with high case fatality rates in neonates and immunocompromised infants. Some physiological features, such as the production of a yellow pigment, the formation of a gum-like extracellular polysaccharide and the ability to persist in a desiccated state, suggest an environmental niche for these organisms. To date, the natural habitat of Cronobacter spp. remains unknown. In this report, the isolation and characterisation of two Cronobacter sakazakii strains from plant roots is described. Also, the root colonisation behaviour of Cronobacter strains originating from clinical and plant sources is assessed. The nine strains investigated showed features often found in plant-associated and rhizosphere microorganisms, including solubilisation of mineral phosphate and production of indole acetic acid. Siderophore production was observed for all except one strain. In addition, the capability to endophytically colonise tomato and maize roots was demonstrated for several strains, either by fluorescence in situ hybridisation, using fluorescently labelled oligonucleotide probes, or by using strains tagged with green fluorescent protein and confocal laser scanning microscopy. The results provide evidence that plants may be the natural habitat of Cronobacter spp.

Understanding Clicker Discussions: Student Reasoning and the Impact of Instructional Cues

PubMed Central

Knight, Jennifer K.; Wise, Sarah B.; Southard, Katelyn M.

2013-01-01

Previous research has shown that undergraduate science students learn from peer discussions of in-class clicker questions. However, the features that characterize such discussions are largely unknown, as are the instructional factors that may lead students into productive discussions. To explore these questions, we recorded and transcribed 83 discussions among groups of students discussing 34 different clicker questions in an upper-level developmental biology class. Discussion transcripts were analyzed for features such as making claims, questioning, and explaining reasoning. In addition, transcripts were categorized by the quality of reasoning students used and for performance features, such as percent correct on initial vote, percent correct on revote, and normalized learning change. We found that the majority of student discussions included exchanges of reasoning that used evidence and that many such exchanges resulted in students achieving the correct answer. Students also had discussions in which ideas were exchanged, but the correct answer not achieved. Importantly, instructor prompts that asked students to use reasoning resulted in significantly more discussions containing reasoning connected to evidence than without such prompts. Overall, these results suggest that these upper-level biology students readily employ reasoning in their discussions and are positively influenced by instructor cues. PMID:24297291

Emissions from Pre-Hispanic Metallurgy in the South American Atmosphere

PubMed Central

De Vleeschouwer, François; Vanneste, Heleen; Mauquoy, Dmitri; Piotrowska, Natalia; Torrejón, Fernando; Roland, Thomas; Stein, Ariel; Le Roux, Gaël

2014-01-01

Metallurgical activities have been undertaken in northern South America (NSA) for millennia. However, it is still unknown how far atmospheric emissions from these activities have been transported. Since the timing of metallurgical activities is currently estimated from scarce archaeological discoveries, the availability of reliable and continuous records to refine the timing of past metal deposition in South America is essential, as it provides an alternative to discontinuous archives, as well as evidence for global trace metal transport. We show in a peat record from Tierra del Fuego that anthropogenic metals likely have been emitted into the atmosphere and transported from NSA to southern South America (SSA) over the last 4200 yrs. These findings are supported by modern time back-trajectories from NSA to SSA. We further show that apparent anthropogenic Cu and Sb emissions predate any archaeological evidence for metallurgical activities. Lead and Sn were also emitted into the atmosphere as by-products of Inca and Spanish metallurgy, whereas local coal-gold rushes and the industrial revolution contributed to local contamination. We suggest that the onset of pre-Hispanic metallurgical activities is earlier than previously reported from archaeological records and that atmospheric emissions of metals were transported from NSA to SSA. PMID:25353346

Emissions from pre-Hispanic metallurgy in the South American atmosphere.

PubMed

De Vleeschouwer, François; Vanneste, Heleen; Mauquoy, Dmitri; Piotrowska, Natalia; Torrejón, Fernando; Roland, Thomas; Stein, Ariel; Le Roux, Gaël

2014-01-01

Metallurgical activities have been undertaken in northern South America (NSA) for millennia. However, it is still unknown how far atmospheric emissions from these activities have been transported. Since the timing of metallurgical activities is currently estimated from scarce archaeological discoveries, the availability of reliable and continuous records to refine the timing of past metal deposition in South America is essential, as it provides an alternative to discontinuous archives, as well as evidence for global trace metal transport. We show in a peat record from Tierra del Fuego that anthropogenic metals likely have been emitted into the atmosphere and transported from NSA to southern South America (SSA) over the last 4200 yrs. These findings are supported by modern time back-trajectories from NSA to SSA. We further show that apparent anthropogenic Cu and Sb emissions predate any archaeological evidence for metallurgical activities. Lead and Sn were also emitted into the atmosphere as by-products of Inca and Spanish metallurgy, whereas local coal-gold rushes and the industrial revolution contributed to local contamination. We suggest that the onset of pre-Hispanic metallurgical activities is earlier than previously reported from archaeological records and that atmospheric emissions of metals were transported from NSA to SSA.

Environmental Exposures and Parkinson’s Disease

PubMed Central

Nandipati, Sirisha; Litvan, Irene

2016-01-01

Parkinson’s disease (PD) affects millions around the world. The Braak hypothesis proposes that in PD a pathologic agent may penetrate the nervous system via the olfactory bulb, gut, or both and spreads throughout the nervous system. The agent is unknown, but several environmental exposures have been associated with PD. Here, we summarize and examine the evidence for such environmental exposures. We completed a comprehensive review of human epidemiologic studies of pesticides, selected industrial compounds, and metals and their association with PD in PubMed and Google Scholar until April 2016. Most studies show that rotenone and paraquat are linked to increased PD risk and PD-like neuropathology. Organochlorines have also been linked to PD in human and laboratory studies. Organophosphates and pyrethroids have limited but suggestive human and animal data linked to PD. Iron has been found to be elevated in PD brain tissue but the pathophysiological link is unclear. PD due to manganese has not been demonstrated, though a parkinsonian syndrome associated with manganese is well-documented. Overall, the evidence linking paraquat, rotenone, and organochlorines with PD appears strong; however, organophosphates, pyrethroids, and polychlorinated biphenyls require further study. The studies related to metals do not support an association with PD. PMID:27598189

Evidence of recycling of lead battery waste into highly leaded jewelry.

PubMed

Weidenhamer, Jeffrey D; Clement, Michael L

2007-11-01

Inexpensive highly leaded jewelry, much of it imported from China, remains widely available in the United States. The source materials for these items are unknown. Due to the low cost of much of this trinket jewelry, it seems likely that scrap materials may be used in their manufacture. Thirty-nine jewelry items previously determined to contain 90% or more lead by weight were analyzed for antimony content. The average antimony content of these thirty-nine items was 3.0%. The range of antimony content in the samples was from 0.3% to 6.2% antimony by weight, with twenty-seven of the samples in the range of 2-4% antimony by weight. By comparison, battery lead standard reference material obtained from the US National Institute of Standards and Technology contains 2.95% antimony by weight. While the evidence is circumstantial, the similarity in composition of these samples to battery lead is striking and supports the hypothesis that some battery lead is being recycled into highly leaded jewelry items. These results suggest that the recycling of this waste in China needs to be investigated, as the use of lead battery waste as a source material for children's jewelry poses a clear threat to children's health.

A Multi-Omic View of Host-Pathogen-Commensal Interplay in Salmonella-Mediated Intestinal Infection

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

Kaiser, Brooke LD; Li, Jie; Sanford, James A.

The potential for commensal microorganisms indigenous to a host (the ‘microbiome’ or ‘microbiota’) to alter infection outcome by influencing host-pathogen interplay is largely unknown. We used a multi-omics “systems” approach, incorporating proteomics, metabolomics, glycomics, and metagenomics, to explore the molecular interplay between the murine host, the pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), and commensal gut microorganisms during intestinal infection with S. Typhimurium. We find proteomic evidence that S. Typhimurium thrives within the infected 129/SvJ mouse gut without antibiotic pre-treatment, inducing inflammation and disrupting the intestinal microbiome (e.g., suppressing Bacteroidetes and Firmicutes while promoting growth of Salmonella and Enterococcus). Alterationmore » of the host microbiome population structure was highly correlated with gut environmental changes, including the accumulation of metabolites normally consumed by commensal microbiota. Finally, the less characterized phase of S. Typhimurium’s lifecycle was investigated, and both proteomic and glycomic evidence suggests S. Typhimurium may take advantage of increased fucose moieties to metabolize fucose while growing in the gut. The application of multiple omics measurements to Salmonella-induced intestinal inflammation provides insights into complex molecular strategies employed during pathogenesis between host, pathogen, and the microbiome.« less

A role for a neo-sex chromosome in stickleback speciation

PubMed Central

Kitano, Jun; Ross, Joseph A.; Mori, Seiichi; Kume, Manabu; Jones, Felicity C.; Chan, Yingguang F.; Absher, Devin M.; Grimwood, Jane; Schmutz, Jeremy; Myers, Richard M.; Kingsley, David M.; Peichel, Catherine L.

2009-01-01

Sexual antagonism, or conflict between the sexes, has been proposed as a driving force in both sex chromosome turnover and speciation. Although closely related species often have different sex chromosome systems, it is unknown whether sex chromosome turnover contributes to the evolution of reproductive isolation between species. In this study, we show that a newly evolved sex chromosome harbours genes that contribute to speciation in threespine stickleback fish (Gasterosteus aculeatus). We first identified a neo-sex chromosome system found only in one member of a sympatric species pair in Japan. We then performed genetic linkage mapping of male-specific traits important for reproductive isolation between the Japanese species pair. The neo-X chromosome harbours loci for male courtship display traits that contribute to behavioural isolation, while the ancestral X chromosome contains loci for both behavioural isolation and hybrid male sterility. Our work not only provides strong evidence for a large-X effect on reproductive isolation in a vertebrate system, but also provides direct evidence that a young neo-X chromosome contributes to reproductive isolation between closely related species. Our data suggest that sex chromosome turnover might play a greater role in speciation than previously appreciated. PMID:19783981

Adrenal suppression in bronchiectasis and the impact of inhaled corticosteroids.

PubMed

Holme, J; Tomlinson, J W; Stockley, R A; Stewart, P M; Barlow, N; Sullivan, A L

2008-10-01

The present study identified three patients with bronchiectasis receiving inhaled corticosteroids (ICSs) who had symptomatic adrenal suppression secondary to ICS. The prevalence of adrenal suppression is unknown in bronchiectasis. The frequency of adrenal suppression and the impact of ICS use in bronchiectasis patients were examined. In total, 50 outpatients (33 receiving ICSs) underwent a short Synacthen test and completed a St George's Respiratory Questionnaire (SGRQ). Symptoms of adrenal suppression, steroid use and lung function were compared between subjects who were suppressed and those who were not. Adrenal suppression was evident in 23.5% of subjects who did not receive ICSs and 48.5% of those who did. Basal cortisol and the increments by which cortisol increased 30 min after Synacthen were lower in suppressed than in nonsuppressed subjects. The incremental cortisol rise was negatively correlated with SGRQ impacts and total score, suggesting a worse quality of life in those who had an impaired adrenal response. The greatest frequency of generalised symptoms was seen in the suppressed group. A significant proportion of subjects with bronchiectasis have evidence of adrenal suppression, and this is increased when inhaled corticosteroids are also used. Impairment of the cortisol response to stimulation is associated with poorer health status.

Quaternary extensional growth folding beneath Reno, Nevada, imaged by urban seismic profiling

USGS Publications Warehouse

Stephenson, William J.; Frary, Roxy N.; Louie, John; Odum, Jackson K.

2013-01-01

We characterize shallow subsurface faulting and basin structure along a transect through heavily urbanized Reno, Nevada, with high‐resolution seismic reflection imaging. The 6.8 km of P‐wave data image the subsurface to approximately 800 m depth and delineate two subbasins and basin uplift that are consistent with structure previously inferred from gravity modeling in this region of the northern Walker Lane. We interpret two primary faults that bound the uplift and deform Quaternary deposits. The dip of Quaternary and Tertiary strata in the western subbasin increases with greater depth to the east, suggesting recurrent fault motion across the westernmost of these faults. Deformation in the Quaternary section of the western subbasin is likely evidence of extensional growth folding at the edge of the Truckee River through Reno. This deformation is north of, and on trend with, previously mapped Quaternary fault strands of the Mt. Rose fault zone. In addition to corroborating the existence of previously inferred intrabasin structure, these data provide evidence for an active extensional Quaternary fault at a previously unknown location within the Truckee Meadows basin that furthers our understanding of both the seismotectonic framework and earthquake hazards in this urbanized region.

Estimation of divergence times in cnidarian evolution based on mitochondrial protein-coding genes and the fossil record.

PubMed

Park, Eunji; Hwang, Dae-Sik; Lee, Jae-Seong; Song, Jun-Im; Seo, Tae-Kun; Won, Yong-Jin

2012-01-01

The phylum Cnidaria is comprised of remarkably diverse and ecologically significant taxa, such as the reef-forming corals, and occupies a basal position in metazoan evolution. The origin of this phylum and the most recent common ancestors (MRCAs) of its modern classes remain mostly unknown, although scattered fossil evidence provides some insights on this topic. Here, we investigate the molecular divergence times of the major taxonomic groups of Cnidaria (27 Hexacorallia, 16 Octocorallia, and 5 Medusozoa) on the basis of mitochondrial DNA sequences of 13 protein-coding genes. For this analysis, the complete mitochondrial genomes of seven octocoral and two scyphozoan species were newly sequenced and combined with all available mitogenomic data from GenBank. Five reliable fossil dates were used to calibrate the Bayesian estimates of divergence times. The molecular evidence suggests that cnidarians originated 741 million years ago (Ma) (95% credible region of 686-819), and the major taxa diversified prior to the Cambrian (543 Ma). The Octocorallia and Scleractinia may have originated from radiations of survivors of the Permian-Triassic mass extinction, which matches their fossil record well. Copyright © 2011 Elsevier Inc. All rights reserved.

Observations of territorial breeding common ravens caching eggs of greater sage-grouse

USGS Publications Warehouse

Howe, Kristy B.; Coates, Peter S.

2015-01-01

Previous investigations using continuous video monitoring of greater sage-grouse Centrocercus urophasianus nests have unambiguously identified common ravens Corvus corax as an important egg predator within the western United States. The quantity of greater sage-grouse eggs an individual common raven consumes during the nesting period and the extent to which common ravens actively hunt greater sage-grouse nests are largely unknown. However, some evidence suggests that territorial breeding common ravens, rather than nonbreeding transients, are most likely responsible for nest depredations. We describe greater sage-grouse egg depredation observations obtained opportunistically from three common raven nests located in Idaho and Nevada where depredated greater sage-grouse eggs were found at or in the immediate vicinity of the nest site, including the caching of eggs in nearby rock crevices. We opportunistically monitored these nests by counting and removing depredated eggs and shell fragments from the nest sites during each visit to determine the extent to which the common raven pairs preyed on greater sage-grouse eggs. To our knowledge, our observations represent the first evidence that breeding, territorial pairs of common ravens cache greater sage-grouse eggs and are capable of depredating multiple greater sage-grouse nests.

How clinicians make (or avoid) moral judgments of patients: implications of the evidence for relationships and research

PubMed Central

2010-01-01

Physicians, nurses, and other clinicians readily acknowledge being troubled by encounters with patients who trigger moral judgments. For decades social scientists have noted that moral judgment of patients is pervasive, occurring not only in egregious and criminal cases but also in everyday situations in which appraisals of patients' social worth and culpability are routine. There is scant literature, however, on the actual prevalence and dynamics of moral judgment in healthcare. The indirect evidence available suggests that moral appraisals function via a complex calculus that reflects variation in patient characteristics, clinician characteristics, task, and organizational factors. The full impact of moral judgment on healthcare relationships, patient outcomes, and clinicians' own well-being is yet unknown. The paucity of attention to moral judgment, despite its significance for patient-centered care, communication, empathy, professionalism, healthcare education, stereotyping, and outcome disparities, represents a blind spot that merits explanation and repair. New methodologies in social psychology and neuroscience have yielded models for how moral judgment operates in healthcare and how research in this area should proceed. Clinicians, educators, and researchers would do well to recognize both the legitimate and illegitimate moral appraisals that are apt to occur in healthcare settings. PMID:20618947

HDL cholesterol and bone mineral density: Is there a genetic link?

PubMed Central

Ackert-Bicknell, Cheryl L.

2011-01-01

Overwhelming evidence has linked cardiovascular disease and osteoporosis, but the shared root cause of these two diseases of the elderly remains unknown. Low levels of high-density lipoprotein cholesterol (HDL) and bone mineral density (BMD) are risk factors for cardiovascular disease and osteoporosis respectively. A number of correlation studies have attempted to determine if there is a relationship between serum HDL and BMD but these studies are confounded by a number of variables including age, diet, genetic background, gender and hormonal status. Collectively, these data suggest that there is a relationship between these two phenotypes, but that the nature of this relationship is context specific. Studies in mice plainly demonstrate that genetic loci for BMD and HDL co-map and transgenic mouse models have been used to show that a single gene can affect both serum HDL and BMD. Work completed to date has demonstrated that HDL can interact directly with both osteoblasts and osteoclasts, but no direct evidence links bone back to the regulation of HDL levels. Understanding the genetic relationship between BMD and HDL has huge implications for understanding the clinical relationship between CVD and osteoporosis and for the development of safe treatment options for both diseases. PMID:21810493

Cedar Grove Historic Cemetry: A Study in Bio-History.

DTIC Science & Technology

1983-10-31

1978). This disparity indicates a developmental ( hormonal ) disturbance. Sex: Unknown. 159 ,4 ’ - Race: Unknown. "" - Preservation Condition: Good...age and long bone growth suggests hormonal disfunction most likely somatotrophic. Degenerative: None. Neoplasm: None. Traumatic: None. MORTUARY...as consisting of nothing but fatback and corn, Fogel and Engerman (1974:111) add: Among the other plantation products which slaves consumed were beef

Model-based analyses of whole-genome data reveal a complex evolutionary history involving archaic introgression in Central African Pygmies.

PubMed

Hsieh, PingHsun; Woerner, August E; Wall, Jeffrey D; Lachance, Joseph; Tishkoff, Sarah A; Gutenkunst, Ryan N; Hammer, Michael F

2016-03-01

Comparisons of whole-genome sequences from ancient and contemporary samples have pointed to several instances of archaic admixture through interbreeding between the ancestors of modern non-Africans and now extinct hominids such as Neanderthals and Denisovans. One implication of these findings is that some adaptive features in contemporary humans may have entered the population via gene flow with archaic forms in Eurasia. Within Africa, fossil evidence suggests that anatomically modern humans (AMH) and various archaic forms coexisted for much of the last 200,000 yr; however, the absence of ancient DNA in Africa has limited our ability to make a direct comparison between archaic and modern human genomes. Here, we use statistical inference based on high coverage whole-genome data (greater than 60×) from contemporary African Pygmy hunter-gatherers as an alternative means to study the evolutionary history of the genus Homo. Using whole-genome simulations that consider demographic histories that include both isolation and gene flow with neighboring farming populations, our inference method rejects the hypothesis that the ancestors of AMH were genetically isolated in Africa, thus providing the first whole genome-level evidence of African archaic admixture. Our inferences also suggest a complex human evolutionary history in Africa, which involves at least a single admixture event from an unknown archaic population into the ancestors of AMH, likely within the last 30,000 yr. © 2016 Hsieh et al.; Published by Cold Spring Harbor Laboratory Press.

Evidence for Altered Ca2+ Handling in Growth Associated Protein 43-Knockout Skeletal Muscle

PubMed Central

Caprara, Giusy A.; Morabito, Caterina; Perni, Stefano; Navarra, Riccardo; Guarnieri, Simone; Mariggiò, Maria A.

2016-01-01

Neuronal growth-associated protein 43 (GAP43) has crucial roles in the nervous system, and during development, regeneration after injury, and learning and memory. GAP43 is expressed in mouse skeletal muscle fibers and satellite cells, with suggested its involvement in intracellular Ca2+ handling. However, the physiological role of GAP43 in muscle remains unknown. Using a GAP43-knockout (GAP43−/−) mouse, we have defined the role of GAP43 in skeletal muscle. GAP43−/− mice showed low survival beyond weaning, reduced adult body weight, decreased muscle strength, and changed myofiber ultrastructure, with no significant differences in the expression of markers of satellite cell and myotube progression through the myogenic program. Thus, GAP43 expression is involved in timing of muscle maturation in-vivo. Intracellular Ca2+ measurements in-vitro in myotubes revealed GAP43 involvement in Ca2+ handling. In the absence of GAP43 expression, the spontaneous Ca2+ variations had greater amplitudes and higher frequency. In GAP43−/− myotubes, also the intracellular Ca2+ variations induced by the activation of dihydropyridine and ryanodine Ca2+ channels, resulted modified. These evidences suggested dysregulation of Ca2+ homeostasis. The emerging hypothesis indicates that GAP43 interacts with calmodulin to indirectly modulate the activities of dihydropyridine and ryanodine Ca2+ channels. This thus influences intracellular Ca2+ dynamics and its related intracellular patterns, from functional excitation-contraction coupling, to cell metabolism, and gene expression. PMID:27833566

Amygdala lesions do not compromise the cortical network for false-belief reasoning.

PubMed

Spunt, Robert P; Elison, Jed T; Dufour, Nicholas; Hurlemann, René; Saxe, Rebecca; Adolphs, Ralph

2015-04-14

The amygdala plays an integral role in human social cognition and behavior, with clear links to emotion recognition, trust judgments, anthropomorphization, and psychiatric disorders ranging from social phobia to autism. A central feature of human social cognition is a theory-of-mind (ToM) that enables the representation other people's mental states as distinct from one's own. Numerous neuroimaging studies of the best studied use of ToM--false-belief reasoning--suggest that it relies on a specific cortical network; moreover, the amygdala is structurally and functionally connected with many components of this cortical network. It remains unknown whether the cortical implementation of any form of ToM depends on amygdala function. Here we investigated this question directly by conducting functional MRI on two patients with rare bilateral amygdala lesions while they performed a neuroimaging protocol standardized for measuring cortical activity associated with false-belief reasoning. We compared patient responses with those of two healthy comparison groups that included 480 adults. Based on both univariate and multivariate comparisons, neither patient showed any evidence of atypical cortical activity or any evidence of atypical behavioral performance; moreover, this pattern of typical cortical and behavioral response was replicated for both patients in a follow-up session. These findings argue that the amygdala is not necessary for the cortical implementation of ToM in adulthood and suggest a reevaluation of the role of the amygdala and its cortical interactions in human social cognition.

Amygdala lesions do not compromise the cortical network for false-belief reasoning

PubMed Central

Elison, Jed T.; Dufour, Nicholas; Hurlemann, René; Saxe, Rebecca; Adolphs, Ralph

2015-01-01

The amygdala plays an integral role in human social cognition and behavior, with clear links to emotion recognition, trust judgments, anthropomorphization, and psychiatric disorders ranging from social phobia to autism. A central feature of human social cognition is a theory-of-mind (ToM) that enables the representation other people's mental states as distinct from one's own. Numerous neuroimaging studies of the best studied use of ToM—false-belief reasoning—suggest that it relies on a specific cortical network; moreover, the amygdala is structurally and functionally connected with many components of this cortical network. It remains unknown whether the cortical implementation of any form of ToM depends on amygdala function. Here we investigated this question directly by conducting functional MRI on two patients with rare bilateral amygdala lesions while they performed a neuroimaging protocol standardized for measuring cortical activity associated with false-belief reasoning. We compared patient responses with those of two healthy comparison groups that included 480 adults. Based on both univariate and multivariate comparisons, neither patient showed any evidence of atypical cortical activity or any evidence of atypical behavioral performance; moreover, this pattern of typical cortical and behavioral response was replicated for both patients in a follow-up session. These findings argue that the amygdala is not necessary for the cortical implementation of ToM in adulthood and suggest a reevaluation of the role of the amygdala and its cortical interactions in human social cognition. PMID:25825732

The Glutamatergic Aspects of Schizophrenia Molecular Pathophysiology: Role of the Postsynaptic Density, and Implications for Treatment

PubMed Central

Iasevoli, Felice; Tomasetti, Carmine; Buonaguro, Elisabetta F.; de Bartolomeis, Andrea

2014-01-01

Schizophrenia is one of the most debilitating psychiatric diseases with a lifetime prevalence of approximately 1%. Although the specific molecular underpinnings of schizophrenia are still unknown, evidence has long linked its pathophysiology to postsynaptic abnormalities. The postsynaptic density (PSD) is among the molecular structures suggested to be potentially involved in schizophrenia. More specifically, the PSD is an electron-dense thickening of glutamatergic synapses, including ionotropic and metabotropic glutamate receptors, cytoskeletal and scaffolding proteins, and adhesion and signaling molecules. Being implicated in the postsynaptic signaling of multiple neurotransmitter systems, mostly dopamine and glutamate, the PSD constitutes an ideal candidate for studying dopamine-glutamate disturbances in schizophrenia. Recent evidence suggests that some PSD proteins, such as PSD-95, Shank, and Homer are implicated in severe behavioral disorders, including schizophrenia. These findings, further corroborated by genetic and animal studies of schizophrenia, offer new insights for the development of pharmacological strategies able to overcome the limitations in terms of efficacy and side effects of current schizophrenia treatment. Indeed, PSD proteins are now being considered as potential molecular targets against this devastating illness. The current paper reviews the most recent hypotheses on the molecular mechanisms underlying schizophrenia pathophysiology. First, we review glutamatergic dysfunctions in schizophrenia and we provide an update on postsynaptic molecules involvement in schizophrenia pathophysiology by addressing both human and animal studies. Finally, the possibility that PSD proteins may represent potential targets for new molecular interventions in psychosis will be discussed. PMID:24851087

Relation of pretreatment sequence diversity in NS5A region of HCV genotype 1 with immune response between pegylated-INF/ribavirin therapy outcomes.

PubMed

de Queiróz, A T L; Maracaja-Coutinho, V; Jardim, A C G; Rahal, P; de Carvalho-Mello, I M V G; Matioli, S R

2011-02-01

Hepatitis C virus (HCV) infection frequently persists despite substantial virus-specific immune responses and the combination of pegylated interferon (INF)-α and ribavirin therapy. Major histocompatibility complex class I restricted CD8(+) T cells are responsible for the control of viraemia in HCV infection, and several studies suggest protection against viral infection associated with specific HLAs. The reason for low rates of sustained viral response (SVR) in HCV patients remains unknown. Escape mutations in response to cytotoxic T lymphocyte are widely described; however, its influence in the treatment outcome is ill understood. Here, we investigate the differences in CD8 epitopes frequencies from the Los Alamos database between groups of patients that showed distinct response to pegylated α-INF with ribavirin therapy and test evidence of natural selection on the virus in those who failed treatment, using five maximum likelihood evolutionary models from PAML package. The group of sustained virological responders showed three epitopes with frequencies higher than Non-responders group, all had statistical support, and we observed evidence of selection pressure in the last group. No escape mutation was observed. Interestingly, the epitope VLSDFKTWL was 100% conserved in SVR group. These results suggest that the response to treatment can be explained by the increase in immune pressure, induced by interferon therapy, and the presence of those epitopes may represent an important factor in determining the outcome of therapy. © 2010 Blackwell Publishing Ltd.

MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4

PubMed Central

Walsh, James T.; Hendrix, Sven; Boato, Francesco; Smirnov, Igor; Zheng, Jingjing; Lukens, John R.; Gadani, Sachin; Hechler, Daniel; Gölz, Greta; Rosenberger, Karen; Kammertöns, Thomas; Vogt, Johannes; Vogelaar, Christina; Siffrin, Volker; Radjavi, Ali; Fernandez-Castaneda, Anthony; Gaultier, Alban; Gold, Ralf; Kanneganti, Thirumala-Devi; Nitsch, Robert; Zipp, Frauke; Kipnis, Jonathan

2015-01-01

A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell–mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4–producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4–deficient animals had decreased functional recovery following CNS injury; however, transfer of CD4+ T cells from wild-type mice, but not from IL-4–deficient mice, enhanced neuronal survival. Using a culture-based system, we determined that T cell–derived IL-4 protects and induces recovery of injured neurons by activation of neuronal IL-4 receptors, which potentiated neurotrophin signaling via the AKT and MAPK pathways. Together, these findings demonstrate that damage-associated molecules from the injured CNS induce a neuroprotective T cell response that is independent of MHCII/TCR interactions and is MyD88 dependent. Moreover, our results indicate that IL-4 mediates neuroprotection and recovery of the injured CNS and suggest that strategies to enhance IL-4–producing CD4+ T cells have potential to attenuate axonal damage in the course of CNS injury in trauma, inflammation, or neurodegeneration. PMID:25607842

The Novel Candida albicans Transporter Dur31 Is a Multi-Stage Pathogenicity Factor

PubMed Central

Mayer, François L.; Wilson, Duncan; Jacobsen, Ilse D.; Miramón, Pedro; Große, Katharina; Hube, Bernhard

2012-01-01

Candida albicans is the most frequent cause of oral fungal infections. However, the exact pathogenicity mechanisms that this fungus employs are largely unknown and many of the genes expressed during oral infection are uncharacterized. In this study we sought to functionally characterize 12 previously unknown function genes associated with oral candidiasis. We generated homozygous knockout mutants for all 12 genes and analyzed their interaction with human oral epithelium in vitro. Eleven mutants caused significantly less epithelial damage and, of these, deletion of orf19.6656 (DUR31) elicited the strongest reduction in pathogenicity. Interestingly, DUR31 was not only involved in oral epithelial damage, but in multiple stages of candidiasis, including surviving attack by human neutrophils, endothelial damage and virulence in vivo. In silico analysis indicated that DUR31 encodes a sodium/substrate symporter with 13 transmembrane domains and no human homologue. We provide evidence that Dur31 transports histatin 5. This is one of the very first examples of microbial driven import of this highly cytotoxic antimicrobial peptide. Also, in contrast to wild type C. albicans, dur31Δ/Δ was unable to actively increase local environmental pH, suggesting that Dur31 lies in the extracellular alkalinization hyphal auto-induction pathway; and, indeed, DUR31 was required for morphogenesis. In agreement with this observation, dur31Δ/Δ was unable to assimilate the polyamine spermidine. PMID:22438810

Chronic kidney disease of unknown etiology in Sri Lanka

PubMed Central

2016-01-01

Introduction In the last two decades, chronic kidney disease of unknown etiology (CKDu) has emerged as a significant contributor to the burden of chronic kidney disease (CKD) in rural Sri Lanka. It is characterized by the absence of identified causes for CKD. The prevalence of CKDu is 15.1–22.9% in some Sri Lankan districts, and previous research has found an association with farming occupations. Methods A systematic literature review in Pubmed, Embase, Scopus, and Lilacs databases identified 46 eligible peer-reviewed articles and one conference abstract. Results Geographical mapping indicates a relationship between CKDu and agricultural irrigation water sources. Health mapping studies, human biological studies, and environment-based studies have explored possible causative agents. Most studies focused on likely causative agents related to agricultural practices, geographical distribution based on the prevalence and incidence of CKDu, and contaminants identified in drinking water. Nonetheless, the link between agrochemicals or heavy metals and CKDu remains to be established. No definitive cause for CKDu has been identified. Discussion Evidence to date suggests that the disease is related to one or more environmental agents, however pinpointing a definite cause for CKDu is challenging. It is plausible that CKDu is multifactorial. No specific guidelines or recommendations exist for treatment of CKDu, and standard management protocols for CKD apply. Changes in agricultural practices, provision of safe drinking water, and occupational safety precautions are recommended by the World Health Organization. PMID:27399161

Chronic kidney disease of unknown etiology in Sri Lanka.

PubMed

Rajapakse, Senaka; Shivanthan, Mitrakrishnan Chrishan; Selvarajah, Mathu

2016-07-01

In the last two decades, chronic kidney disease of unknown etiology (CKDu) has emerged as a significant contributor to the burden of chronic kidney disease (CKD) in rural Sri Lanka. It is characterized by the absence of identified causes for CKD. The prevalence of CKDu is 15.1-22.9% in some Sri Lankan districts, and previous research has found an association with farming occupations. A systematic literature review in Pubmed, Embase, Scopus, and Lilacs databases identified 46 eligible peer-reviewed articles and one conference abstract. Geographical mapping indicates a relationship between CKDu and agricultural irrigation water sources. Health mapping studies, human biological studies, and environment-based studies have explored possible causative agents. Most studies focused on likely causative agents related to agricultural practices, geographical distribution based on the prevalence and incidence of CKDu, and contaminants identified in drinking water. Nonetheless, the link between agrochemicals or heavy metals and CKDu remains to be established. No definitive cause for CKDu has been identified. Evidence to date suggests that the disease is related to one or more environmental agents, however pinpointing a definite cause for CKDu is challenging. It is plausible that CKDu is multifactorial. No specific guidelines or recommendations exist for treatment of CKDu, and standard management protocols for CKD apply. Changes in agricultural practices, provision of safe drinking water, and occupational safety precautions are recommended by the World Health Organization.

Environmental contaminants in Texas, USA, wetland reptiles: Evaluation using blood samples

USGS Publications Warehouse

Clark, D.R.; Bickham, J.W.; Baker, D.L.; Cowman, D.F.

2000-01-01

Four species of reptiles (diamondback water snake [Nerodia rhombifer], blotched water snake [N. erythrogaster], cottonmouth [Agkistrodon piscivorus], and red-eared slider [Trachemys scripta]) were collected at two contaminated and three reference sites in Texas, USA. Old River Slough has received intensive applications of agricultural chemicals since the 1950s. Municipal Lake received industrial arsenic wastes continuously from 1940 to 1993. Blood samples were analyzed for organochlorines, potentially toxic elements, genetic damage, and plasma cholinesterase (ChE). Dichlorodiphenyldichloroethylene (DDE) concentrations reached as high as 3.0 ppm (wet weight) in whole blood of a diamondback water snake at Old River Slough, a level probably roughly equivalent to the maximum concentration found in plasma of peregrine falcons (Falco peregrinus) in 1978 to 1979 when DDE peaked in this sensitive species. Possible impacts on diamondback water snakes are unknown, but at least one diamondback water snake was gravid when captured, indicating active reproduction. Arsenic was not found in red-eared sliders (only species sampled) from Municipal Lake. Red-eared sliders of both sexes at Old River Slough showed declining levels of ChE with increasing mass, suggesting a life-long decrease of ChE levels. Possible negative population consequences are unknown, but no evidence was found in body condition (mass relative to carapace length) that red-eared sliders at either contaminated site were harmed.

Skeletal muscle mechanics: questions, problems and possible solutions.

PubMed

Herzog, Walter

2017-09-16

Skeletal muscle mechanics have been studied ever since people have shown an interest in human movement. However, our understanding of muscle contraction and muscle mechanical properties has changed fundamentally with the discovery of the sliding filament theory in 1954 and associated cross-bridge theory in 1957. Nevertheless, experimental evidence suggests that our knowledge of the mechanisms of contraction is far from complete, and muscle properties and muscle function in human movement remain largely unknown.In this manuscript, I am trying to identify some of the crucial challenges we are faced with in muscle mechanics, offer possible solutions to questions, and identify problems that might be worthwhile exploring in the future. Since it is impossible to tackle all (worthwhile) problems in a single manuscript, I identified three problems that are controversial, important, and close to my heart. They may be identified as follows: (i) mechanisms of muscle contraction, (ii) in vivo whole muscle mechanics and properties, and (iii) force-sharing among synergistic muscles. These topics are fundamental to our understanding of human movement and movement control, and they contain a series of unknowns and challenges to be explored in the future.It is my hope that this paper may serve as an inspiration for some, may challenge current beliefs in selected areas, tackle important problems in the area of muscle mechanics, physiology and movement control, and may guide and focus some of the thinking of future muscle mechanics research.

Source memory for action in young and older adults: self vs. close or unknown others.

PubMed

Rosa, Nicole M; Gutchess, Angela H

2011-09-01

The present study examines source memory for actions (e.g., placing items in a suitcase). For both young and older adult participants, source memory for actions performed by the self was better than memory for actions performed by either a known (close) or unknown other. In addition, neither young nor older adults were more likely to confuse self with close others than with unknown others. Results suggest an advantage in source memory for actions performed by the self compared to others, possibly associated with sensorimotor cues that are relatively preserved in aging.

The impact of physical activity and nutrition on inflammatory bowel disease: the potential role of cross talk between adipose tissue and skeletal muscle.

PubMed

Bilski, J; Mazur-Bialy, A I; Wierdak, M; Brzozowski, T

2013-04-01

Crohn's disease and ulcerative colitis are both chronic inflammatory bowel diseases (IBDs) characterized by a cyclical nature, which alternates between active and quiescent states, ultimately impairing a patients' quality of life. The etiology of IBD is not known but it likely involves a combination of genetic predisposition and environmental risk factors. Physical exercise has been suggested to provide protection against the onset of IBD, but there are inconsistencies in the findings of the published literature. Current research recommends exercise to help counteract some IBD-specific complications and preliminary studies suggest that physical activity may be beneficial in reducing the symptoms of IBD. Obesity is becoming more prevalent in patients diagnosed with IBD and may be associated with higher disease activity. There is evidence that adipokines are involved in the inflammatory and metabolic pathways. Hypertrophy of the mesenteric white adipose tissue has been long recognized as a characteristic feature of Crohn's disease; however its importance is unknown. Recent data suggest that dysregulation of adipokine secretion by white adipose tissue is involved in the pathogenesis of Crohn's disease. Skeletal muscle was shown to produce biologically active myokines, which could be a important contributor to the beneficial effects of exercise. There is mounting evidence for the bi-directional endocrine cross talk between adipose tissue and skeletal muscle. The objective of the present review is to explore the role of exercise and its impact on IBD. Also, we discuss how current discoveries regarding the importance of adipokines and myokines and their cross talk expand our view of the pathological changes and the therapeutic options for IBD.

Concentration-dependent Cu(II) binding to prion protein

NASA Astrophysics Data System (ADS)

Hodak, Miroslav; Lu, Wenchang; Bernholc, Jerry

2008-03-01

The prion protein plays a causative role in several neurodegenerative diseases, including mad cow disease in cattle and Creutzfeldt-Jakob disease in humans. The normal function of the prion protein is unknown, but it has been linked to its ability to bind copper ions. Experimental evidence suggests that copper can be bound in three distinct modes depending on its concentration, but only one of those binding modes has been fully characterized experimentally. Using a newly developed hybrid DFT/DFT method [1], which combines Kohn-Sham DFT with orbital-free DFT, we have examined all the binding modes and obtained their detailed binding geometries and copper ion binding energies. Our results also provide explanation for experiments, which have found that when the copper concentration increases the copper binding mode changes, surprisingly, from a stronger to a weaker one. Overall, our results indicate that prion protein can function as a copper buffer. 1. Hodak, Lu, Bernholc, JCP, in press.

Rheology of U-Shaped Granular Particles

NASA Astrophysics Data System (ADS)

Hill, Matthew; Franklin, Scott

We study the response of cylindrical samples of U-shaped granular particles (staples) to extensional loads. Samples elongate in discrete bursts (events) corresponding to particles rearranging and re-entangling. Previous research on samples of constant cross-sectional area found a Weibullian weakest-link theory could explain the distribution of yield points. We now vary the cross-sectional area, and find that the maximum yield pressure (force/area) is a function of particle number density and independent of area. The probability distribution function of important event characteristics -- the stress increase before an event and stress released during an event -- both fall of inversely with magnitude, reminiscent of avalanche dynamics. Fourier transforms of the fluctuating force (or stress) scales inversely with frequency, suggesting dry friction plays a role in the rearrangements. Finally, there is some evidence that dynamics are sensitive to the stiffness of the tensile testing machine, although an explanation for this behavior is unknown.

Has the connection between polyploidy and diversification actually been tested?

PubMed

Kellogg, Elizabeth A

2016-04-01

Many major clades of angiosperms have several whole genome duplications (polyploidization events) in their distant past, suggesting that polyploidy drives or at least permits diversification. However, data on recently diverged groups are more equivocal, finding little evidence of elevated diversification following polyploidy. The discrepancy may be attributable at least in part to methodology. Many studies use indirect methods, such as chromosome numbers, genome size, and Ks plots, to test polyploidy, although these approaches can be misleading, and often lack sufficient resolution. A direct test of diversification following polyploidy requires a sequence-based approach that traces the history of nuclear genomes rather than species. These methods identify the point of coalescence of ancestral genomes, but may be misleading about the time and thus the extent of diversification. Limitations of existing methods mean that the connection between polyploidy and diversification has not been rigorously tested and remains unknown. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ontogeny of the maxilla in Neanderthals and their ancestors

PubMed Central

Lacruz, Rodrigo S.; Bromage, Timothy G.; O'Higgins, Paul; Arsuaga, Juan-Luis; Stringer, Chris; Godinho, Ricardo Miguel; Warshaw, Johanna; Martínez, Ignacio; Gracia-Tellez, Ana; de Castro, José María Bermúdez; Carbonell, Eudald

2015-01-01

Neanderthals had large and projecting (prognathic) faces similar to those of their putative ancestors from Sima de los Huesos (SH) and different from the retracted modern human face. When such differences arose during development and the morphogenetic modifications involved are unknown. We show that maxillary growth remodelling (bone formation and resorption) of the Devil's Tower (Gibraltar 2) and La Quina 18 Neanderthals and four SH hominins, all sub-adults, show extensive bone deposition, whereas in modern humans extensive osteoclastic bone resorption is found in the same regions. This morphogenetic difference is evident by ∼5 years of age. Modern human faces are distinct from those of the Neanderthal and SH fossils in part because their postnatal growth processes differ markedly. The growth remodelling identified in these fossil hominins is shared with Australopithecus and early Homo but not with modern humans suggesting that the modern human face is developmentally derived. PMID:26639346

Distinguishing Motor Weakness From Impaired Spatial Awareness: A Helping Hand!

PubMed

Raju, Suneil A; Swift, Charles R; Bardhan, Karna Dev

2017-01-01

Our patient, aged 73 years, had background peripheral neuropathy of unknown cause, stable for several years, which caused some difficulty in walking on uneven ground. He attended for a teaching session but now staggered in, a new development. He had apparent weakness of his right arm, but there was difficulty in distinguishing motor weakness from impaired spatial awareness suggestive of parietal lobe dysfunction. With the patient seated, eyes closed, and left arm outstretched, S.A.R. lifted the patient's right arm and asked him to indicate when both were level. This confirmed motor weakness. Urgent computed tomographic scan confirmed left subdural haematoma and its urgent evacuation rapidly resolved the patient's symptoms. Intrigued by our patient's case, we explored further and learnt that in rehabilitation medicine, the awareness of limb position is commonly viewed in terms of joint position sense. We present recent literature evidence indicating that the underlying mechanisms are more subtle.

Distinguishing Motor Weakness From Impaired Spatial Awareness: A Helping Hand!

PubMed Central

Raju, Suneil A; Swift, Charles R; Bardhan, Karna Dev

2017-01-01

Our patient, aged 73 years, had background peripheral neuropathy of unknown cause, stable for several years, which caused some difficulty in walking on uneven ground. He attended for a teaching session but now staggered in, a new development. He had apparent weakness of his right arm, but there was difficulty in distinguishing motor weakness from impaired spatial awareness suggestive of parietal lobe dysfunction. With the patient seated, eyes closed, and left arm outstretched, S.A.R. lifted the patient’s right arm and asked him to indicate when both were level. This confirmed motor weakness. Urgent computed tomographic scan confirmed left subdural haematoma and its urgent evacuation rapidly resolved the patient’s symptoms. Intrigued by our patient’s case, we explored further and learnt that in rehabilitation medicine, the awareness of limb position is commonly viewed in terms of joint position sense. We present recent literature evidence indicating that the underlying mechanisms are more subtle. PMID:28579860

Tagging the neuronal entrainment to beat and meter.

PubMed

Nozaradan, Sylvie; Peretz, Isabelle; Missal, Marcus; Mouraux, André

2011-07-13

Feeling the beat and meter is fundamental to the experience of music. However, how these periodicities are represented in the brain remains largely unknown. Here, we test whether this function emerges from the entrainment of neurons resonating to the beat and meter. We recorded the electroencephalogram while participants listened to a musical beat and imagined a binary or a ternary meter on this beat (i.e., a march or a waltz). We found that the beat elicits a sustained periodic EEG response tuned to the beat frequency. Most importantly, we found that meter imagery elicits an additional frequency tuned to the corresponding metric interpretation of this beat. These results provide compelling evidence that neural entrainment to beat and meter can be captured directly in the electroencephalogram. More generally, our results suggest that music constitutes a unique context to explore entrainment phenomena in dynamic cognitive processing at the level of neural networks.

The Effect of Age, Race, and Sex on Social Cognitive Performance in Individuals With Schizophrenia.

PubMed

Pinkham, Amy E; Kelsven, Skylar; Kouros, Chrystyna; Harvey, Philip D; Penn, David L

2017-05-01

Age, race, and sex are linked to social cognitive performance among healthy individuals, but whether similar effects are evident in schizophrenia is unknown. Data from 170 individuals with schizophrenia or schizoaffective disorder and 98 healthy controls were used to examine relations between these demographic factors and performance across multiple domains and measures of social cognition. Sex was not related to performance on any domain, but older age was related to poorer emotion recognition from dynamic stimuli in both patients and controls. In patients, older age was also associated with better abilities to decipher hints. Both Caucasian patients and controls performed better than African American individuals on emotion recognition and mental state attribution tasks that use only Caucasian individuals as visual stimuli. Findings suggest rather limited influences of demographic factors but do demonstrate normative age and race effects among patients. Findings also highlight important methodological considerations for measurement of social cognition.

Topological relationships between brain and social networks.

PubMed

Sakata, Shuzo; Yamamori, Tetsuo

2007-01-01

Brains are complex networks. Previously, we revealed that specific connected structures are either significantly abundant or rare in cortical networks. However, it remains unknown whether systems from other disciplines have similar architectures to brains. By applying network-theoretical methods, here we show topological similarities between brain and social networks. We found that the statistical relevance of specific tied structures differs between social "friendship" and "disliking" networks, suggesting relation-type-specific topology of social networks. Surprisingly, overrepresented connected structures in brain networks are more similar to those in the friendship networks than to those in other networks. We found that balanced and imbalanced reciprocal connections between nodes are significantly abundant and rare, respectively, whereas these results are unpredictable by simply counting mutual connections. We interpret these results as evidence of positive selection of balanced mutuality between nodes. These results also imply the existence of underlying common principles behind the organization of brain and social networks.

Hepatorenal syndrome.

PubMed

Papper, S

1980-01-01

Renal failure without apparent cause (the hepatorenal syndrome) may develop in the course of cirrhosis of the liver. While the development of renal failure bears a poor prognosis, spontaneous recovery can occur. The data suggest that for the most part patients die in rather than of renal failure. The latter seems to be only part of a broader more fundamental disturbance. The pathogenesis of HRS is unknown, but the evidence supports an impairment of effective renal perfusion. The two major hypotheses concerning the nature of the impaired perfusion are that it is a physiologic response to alterations in the extrarenal circulation, and that there is an unidentified humoral agent(s) produced by or inadequately inactivated by or bypassing the diseased liver and causing circulatory changes in the kidney as well as in other organs. It is possible that both mechanisms are operative. Treatment is unsatisfactory and emphasis is presently best placed upon searching for more treatable causes of renal functional impairment in individual patients.

Stem cells are dispensable for lung homeostasis but restore airways after injury.

PubMed

Giangreco, Adam; Arwert, Esther N; Rosewell, Ian R; Snyder, Joshua; Watt, Fiona M; Stripp, Barry R

2009-06-09

Local tissue stem cells have been described in airways of the lung but their contribution to normal epithelial maintenance is currently unknown. We therefore developed aggregation chimera mice and a whole-lung imaging method to determine the relative contributions of progenitor (Clara) and bronchiolar stem cells to epithelial maintenance and repair. In normal and moderately injured airways chimeric patches were small in size and not associated with previously described stem cell niches. This finding suggested that single, randomly distributed progenitor cells maintain normal epithelial homeostasis. In contrast we found that repair following severe lung injury resulted in the generation of rare, large clonal cell patches that were associated with stem cell niches. This study provides evidence that epithelial stem cells are dispensable for normal airway homeostasis. We also demonstrate that stem cell activation and robust clonal cellular expansion occur only during repair from severe lung injury.

Evidence for an electrostatic mechanism of force generation by the bacteriophage T4 DNA packaging motor.

PubMed

Migliori, Amy D; Keller, Nicholas; Alam, Tanfis I; Mahalingam, Marthandan; Rao, Venigalla B; Arya, Gaurav; Smith, Douglas E

2014-06-17

How viral packaging motors generate enormous forces to translocate DNA into viral capsids remains unknown. Recent structural studies of the bacteriophage T4 packaging motor have led to a proposed mechanism wherein the gp17 motor protein translocates DNA by transitioning between extended and compact states, orchestrated by electrostatic interactions between complimentarily charged residues across the interface between the N- and C-terminal subdomains. Here we show that site-directed alterations in these residues cause force dependent impairments of motor function including lower translocation velocity, lower stall force and higher frequency of pauses and slips. We further show that the measured impairments correlate with computed changes in free-energy differences between the two states. These findings support the proposed structural mechanism and further suggest an energy landscape model of motor activity that couples the free-energy profile of motor conformational states with that of the ATP hydrolysis cycle.

Evidence for an electrostatic mechanism of force generation by the bacteriophage T4 DNA packaging motor

NASA Astrophysics Data System (ADS)

Migliori, Amy D.; Keller, Nicholas; Alam, Tanfis I.; Mahalingam, Marthandan; Rao, Venigalla B.; Arya, Gaurav; Smith, Douglas E.

2014-06-01

How viral packaging motors generate enormous forces to translocate DNA into viral capsids remains unknown. Recent structural studies of the bacteriophage T4 packaging motor have led to a proposed mechanism wherein the gp17 motor protein translocates DNA by transitioning between extended and compact states, orchestrated by electrostatic interactions between complimentarily charged residues across the interface between the N- and C-terminal subdomains. Here we show that site-directed alterations in these residues cause force dependent impairments of motor function including lower translocation velocity, lower stall force and higher frequency of pauses and slips. We further show that the measured impairments correlate with computed changes in free-energy differences between the two states. These findings support the proposed structural mechanism and further suggest an energy landscape model of motor activity that couples the free-energy profile of motor conformational states with that of the ATP hydrolysis cycle.

The impact of Fli1 deficiency on the pathogenesis of systemic sclerosis

PubMed Central

Asano, Yoshihide; Bujor, Andreea M.; Trojanowska, Maria

2013-01-01

Systemic sclerosis (SSc) is an autoimmune inflammatory disease with unknown etiology characterized by microvascular injury and fibrosis of the skin and internal organs. A growing body of evidence suggests that deficiency of the transcription factor Fli1 (Friend leukemia integration-1) has a pivotal role in the pathogenesis of SSc. Fli1 is expressed in fibroblasts, endothelial cells, and immune cells, and has important roles in the activation, differentiation, development, and survival of these cells. Previous studies demonstrated that Fli1 is downregulated in SSc fibroblasts by an epigenetic mechanism and a series of experiments with Fli1-deficient animal models revealed that Fli1 deficiency in fibroblasts and endothelial cells reproduces the histopathologic features of fibrosis and vasculopathy in SSc, respectively. In this article, we review the impact of Fli1 deficiency on the pathogenesis of SSc and discuss a new therapeutic strategy for SSc by targeting the transcription factor Fli1. PMID:20663647

Lassa Virus Seroprevalence in Sibirilia Commune, Bougouni District, Southern Mali.

PubMed

Sogoba, Nafomon; Rosenke, Kyle; Adjemian, Jennifer; Diawara, Sory Ibrahim; Maiga, Ousmane; Keita, Moussa; Konaté, Drissa; Keita, Abdoul Salam; Sissoko, Ibrahim; Boisen, Matt; Nelson, Diana; Oottamasathien, Darin; Millett, Molly; Garry, Robert F; Branco, Luis M; Traoré, Sékou F; Doumbia, Seydou; Feldmann, Heinz; Safronetz, David

2016-04-01

Lassa virus (LASV) is endemic to several nations in West Africa. In Mali, LASV was unknown until an exported case of Lassa fever was reported in 2009. Since that time, rodent surveys have found evidence of LASV-infected Mastomys natalensis rats in several communities in southern Mali, near the border with Côte d'Ivoire. Despite increased awareness, to date only a single case of Lassa fever has been confirmed in Mali. We conducted a survey to determine the prevalence of LASV exposure among persons in 3 villages in southern Mali where the presence of infected rodents has been documented. LASV IgG seroprevalence ranged from 14.5% to 44% per village. No sex bias was noted; however, seropositivity rates increased with participant age. These findings confirm human LASV exposure in Mali and suggest that LASV infection/Lassa fever is a potential public health concern in southern Mali.

Cultivating characters (moral value) through internalization strategy in science classroom

NASA Astrophysics Data System (ADS)

Ibrahim, M.; Abadi

2018-01-01

It is still in a crucial debate that characters play an important learning outcome to be realized by design. So far, most people think that characters were reached as nurturance effect with the assumption that students who are knowledgeable and skillful will have good characters automatically. Lately, obtained evidence that this assumption is not true. Characters should be taught deliberately or by design. This study was designed to culture elementary school students’ characters through science classroom. The teaching-learning process was conducted to facilitate and bridge the students from the known (concrete images: Science phenomena) to the unknown (abstract ideas: characters: care, and tolerance. Characters were observed five weeks before and after the intervention. Data were analyzed from observation of 24 students in internalization strategy-based courses. Qualitative and quantitative data suggested that the internalization strategy that use of science phenomena to represent abstract ideas (characters) in science classroom positively cultivating characters.

A network property necessary for concentration robustness

NASA Astrophysics Data System (ADS)

Eloundou-Mbebi, Jeanne M. O.; Küken, Anika; Omranian, Nooshin; Kleessen, Sabrina; Neigenfind, Jost; Basler, Georg; Nikoloski, Zoran

2016-10-01

Maintenance of functionality of complex cellular networks and entire organisms exposed to environmental perturbations often depends on concentration robustness of the underlying components. Yet, the reasons and consequences of concentration robustness in large-scale cellular networks remain largely unknown. Here, we derive a necessary condition for concentration robustness based only on the structure of networks endowed with mass action kinetics. The structural condition can be used to design targeted experiments to study concentration robustness. We show that metabolites satisfying the necessary condition are present in metabolic networks from diverse species, suggesting prevalence of this property across kingdoms of life. We also demonstrate that our predictions about concentration robustness of energy-related metabolites are in line with experimental evidence from Escherichia coli. The necessary condition is applicable to mass action biological systems of arbitrary size, and will enable understanding the implications of concentration robustness in genetic engineering strategies and medical applications.

Electrophysiological and biochemical evidence that DEG/ENaC cation channels are composed of nine subunits.

PubMed

Snyder, P M; Cheng, C; Prince, L S; Rogers, J C; Welsh, M J

1998-01-09

Members of the DEG/ENaC protein family form ion channels with diverse functions. DEG/ENaC subunits associate as hetero- and homomultimers to generate channels; however the stoichiometry of these complexes is unknown. To determine the subunit stoichiometry of the human epithelial Na+ channel (hENaC), we expressed the three wild-type hENaC subunits (alpha, beta, and gamma) with subunits containing mutations that alter channel inhibition by methanethiosulfonates. The data indicate that hENaC contains three alpha, three beta, and three gamma subunits. Sucrose gradient sedimentation of alphahENaC translated in vitro, as well as alpha-, beta-, and gammahENaC coexpressed in cells, was consistent with complexes containing nine subunits. FaNaCh and BNC1, two related DEG/ENaC channels, produced complexes of similar mass. Our results suggest a novel nine-subunit stoichiometry for the DEG/ENaC family of ion channels.

Evidence for an upper mantle low velocity zone beneath the southern Basin and Range-Colorado Plateau transition zone

USGS Publications Warehouse

Benz, H.M.; McCarthy, J.

1994-01-01

A 370-km-long seismic refraction/wide-angle reflection profile recorded during the Pacific to Arizona Crustal Experiment (PACE) detected an upper mantle P-wave low-velocity zone (LVZ) in the depth range 40 to 55 km beneath the Basin and Range in southern Arizona. Interpretation of seismic data places constraints on the sub-crustal lithosphere of the southern Basin and Range Province, which is important in light of the active tectonics of the region and the unknown role of the sub-crustal lithosphere in the development of the western United States. Forward travel time and synthetic seismogram techniques are used to model this shallow upper mantle LVZ. Modeling results show that the LVZ is defined by a 5% velocity decrease relative to a Pn velocity of 7.95 km s−1, suggesting either a ∼3–5% mafic partial melt or high-temperature, sub-solidus peridotite.

PSYCHOLOGY. Estimating the reproducibility of psychological science.

PubMed

2015-08-28

Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams. Copyright © 2015, American Association for the Advancement of Science.

Ontogeny of the maxilla in Neanderthals and their ancestors.

PubMed

Lacruz, Rodrigo S; Bromage, Timothy G; O'Higgins, Paul; Arsuaga, Juan-Luis; Stringer, Chris; Godinho, Ricardo Miguel; Warshaw, Johanna; Martínez, Ignacio; Gracia-Tellez, Ana; de Castro, José María Bermúdez; Carbonell, Eudald

2015-12-07

Neanderthals had large and projecting (prognathic) faces similar to those of their putative ancestors from Sima de los Huesos (SH) and different from the retracted modern human face. When such differences arose during development and the morphogenetic modifications involved are unknown. We show that maxillary growth remodelling (bone formation and resorption) of the Devil's Tower (Gibraltar 2) and La Quina 18 Neanderthals and four SH hominins, all sub-adults, show extensive bone deposition, whereas in modern humans extensive osteoclastic bone resorption is found in the same regions. This morphogenetic difference is evident by ∼5 years of age. Modern human faces are distinct from those of the Neanderthal and SH fossils in part because their postnatal growth processes differ markedly. The growth remodelling identified in these fossil hominins is shared with Australopithecus and early Homo but not with modern humans suggesting that the modern human face is developmentally derived.

Concreteness and Psychological Distance in Natural Language Use

PubMed Central

Snefjella, Bryor; Kuperman, Victor

2015-01-01

Existing evidence shows that more abstract mental representations are formed, and more abstract language is used, to characterize phenomena which are more distant from self. Yet the precise form of the functional relationship between distance and linguistic abstractness has been unknown. In four studies, we test whether more abstract language is used in textual references to more geographically distant cities (Study 1), times further into the past or future (Study 2), references to more socially distant people (Study 3), and references to a specific topic (Study 4). Using millions of linguistic productions from thousands of social media users, we determine that linguistic concreteness is a curvilinear function of the logarithm of distance and discuss psychological underpinnings of the mathematical properties of the relationship. We also demonstrate that gradient curvilinear effects of geographic and temporal distance on concreteness are near-identical, suggesting uniformity in representation of abstractness along multiple dimensions. PMID:26239108

Concreteness and Psychological Distance in Natural Language Use.

PubMed

Snefjella, Bryor; Kuperman, Victor

2015-09-01

Existing evidence shows that more abstract mental representations are formed and more abstract language is used to characterize phenomena that are more distant from the self. Yet the precise form of the functional relationship between distance and linguistic abstractness is unknown. In four studies, we tested whether more abstract language is used in textual references to more geographically distant cities (Study 1), time points further into the past or future (Study 2), references to more socially distant people (Study 3), and references to a specific topic (Study 4). Using millions of linguistic productions from thousands of social-media users, we determined that linguistic concreteness is a curvilinear function of the logarithm of distance, and we discuss psychological underpinnings of the mathematical properties of this relationship. We also demonstrated that gradient curvilinear effects of geographic and temporal distance on concreteness are nearly identical, which suggests uniformity in representation of abstractness along multiple dimensions. © The Author(s) 2015.

Social wasps are a Saccharomyces mating nest.

PubMed

Stefanini, Irene; Dapporto, Leonardo; Berná, Luisa; Polsinelli, Mario; Turillazzi, Stefano; Cavalieri, Duccio

2016-02-23

The reproductive ecology of Saccharomyces cerevisiae is still largely unknown. Recent evidence of interspecific hybridization, high levels of strain heterozygosity, and prion transmission suggest that outbreeding occurs frequently in yeasts. Nevertheless, the place where yeasts mate and recombine in the wild has not been identified. We found that the intestine of social wasps hosts highly outbred S. cerevisiae strains as well as a rare S. cerevisiae×S. paradoxus hybrid. We show that the intestine of Polistes dominula social wasps favors the mating of S. cerevisiae strains among themselves and with S. paradoxus cells by providing a succession of environmental conditions prompting cell sporulation and spores germination. In addition, we prove that heterospecific mating is the only option for European S. paradoxus strains to survive in the gut. Taken together, these findings unveil the best hidden secret of yeast ecology, introducing the insect gut as an environmental alcove in which crosses occur, maintaining and generating the diversity of the ascomycetes.

The presence of migraines and its association with sensory hyperreactivity and anxiety symptomatology in children with autism spectrum disorder.

PubMed

Sullivan, Jillian C; Miller, Lucy J; Nielsen, Darcy M; Schoen, Sarah A

2014-08-01

Migraine headaches are associated with sensory hyperreactivity and anxiety in the general population, but it is unknown whether this is also the case in autism spectrum disorders. This pilot study asked parents of 81 children (aged 7-17 years) with autism spectrum disorders to report their child's migraine occurrence, sensory hyperreactivity (Sensory Over-Responsivity Inventory), and anxiety symptoms (Spence Child Anxiety Scale). Children with autism spectrum disorders who experienced migraine headaches showed greater sensory hyperreactivity and anxiety symptomatology (p < 0.01; medium effect size for both) than those without migraines. Sensory hyperreactivity and anxiety symptomatology were additionally correlated (ρ = 0.31, p = 0.005). This study provides preliminary evidence for a link between migraine headaches, sensory hyperreactivity, and anxiety symptomatology in autism spectrum disorders, which may suggest strategies for subtyping and exploring a common pathogenesis. © The Author(s) 2013.

Expert Users' Perceptions of Racing Wheelchair Design and Setup: The Knowns, Unknowns, and Next Steps.

PubMed

Bundon, Andrea; Mason, Barry S; Goosey-Tolfrey, Victoria L

2017-04-01

This paper demonstrates how a qualitative methodology can be used to gain novel insights into the demands of wheelchair racing and the impact of particular racing chair configurations on optimal sport performance via engagement with expert users (wheelchair racers, coaches, and manufacturers). We specifically explore how expert users understand how wheels, tires, and bearings impact sport performance and how they engage, implement, or reject evidence-based research pertaining to these components. We identify areas where participants perceive there to be an immediate need for more research especially pertaining to the ability to make individualized recommendations for athletes. The findings from this project speak to the value of a qualitative research design for capturing the embodied knowledge of expert users and also make suggestions for "next step" projects pertaining to wheels, tires, and bearings drawn directly from the comments of participants.

The Role of Hydrogen for Sulfurimonas denitrificans’ Metabolism

PubMed Central

Han, Yuchen; Perner, Mirjam

2014-01-01

Sulfurimonas denitrificans was originally isolated from coastal marine sediments. It can grow with thiosulfate and nitrate or sulfide and oxygen. Recently sequencing of its genome revealed that it encodes periplasmic and cytoplasmic [NiFe]-hydrogenases but the role of hydrogen for its metabolism has remained unknown. We show the first experimental evidence that S. denitrificans can indeed express a functional hydrogen uptake active hydrogenase and can grow on hydrogen. In fact, under the provided conditions it grew faster and denser on hydrogen than on thiosulfate alone and even grew with hydrogen in the absence of reduced sulfur compounds. In our experiments, at the time points tested, the hydrogen uptake activity appeared to be related to the periplasmic hydrogenase and not to the cytoplasmic hydrogenase. Our data suggest that under the provided conditions S. denitrificans can grow more efficiently with hydrogen than with thiosulfate. PMID:25170905

A retrospective study of postmortem findings in red-tailed hawks

USGS Publications Warehouse

Franson, J.C.; Thomas, N.J.; Smith, M.R.; Robbins, A.H.; Newman, S.; McCartin, P.C.

1996-01-01

We studied necropsy results from carcasses of 163 red-tailed hawks (Buteo jamaicensis) submitted to the National Wildlife Health Center from 1975 through 1992. The most frequent postmortem finding was emaciation of unknown etiology, diagnosed in 33 (20%) carcasses. Proportionally more juveniles than adults were emaciated. Evidence of non-gunshot trauma, often suggestive of collision with vehicles or structures near roadways, was found in 29 (18%) birds. Of 25 (15%) toxicoses, 20 were attributed to agricultural pesticides, including famphur (4), fenthion (3), carbofuran (2), phosphamidon (2), endrin (1), and unidentified organophosphorus compounds (8). Lead and strychnine poisoning were diagnosed in two birds each, and selenium poisoning in one. Diseases, including aspergillosis, tuberculosis, pasteurellosis, and pox, were found in 21 (13%) hawks. Gunshot and electrocution were each diagnosed in six (4%) birds, one (0.6%) was trapped, miscellaneous conditions were found in 10 (6%), and no diagnosis could be determined for 32 (19%) of the carcasses.

Origins of eponymous orthopaedic equipment.

PubMed

Meals, Clifton; Wang, Jeffrey

2010-06-01

Orthopaedists make great use of eponymous equipment, however the origins of these tools are unknown to many users. This history enriches, enlightens, and enhances surgical education, and may inspire modern innovation. We explored the origins of common and eponymous orthopaedic equipment. We selected pieces of equipment named for their inventors and in the broadest use by modern orthopaedists. We do not describe specialized orthopaedic implants and instruments owing to the overwhelming number of these devices. The history of this equipment reflects the coevolution of orthopaedics and battlefield medicine. Additionally, these stories evidence the primacy of elegant design and suggest that innovation is often a process of revision and refinement rather than sudden inspiration. Their history exposes surgical innovators as brilliant, lucky, hardworking, and sometimes odd. These stories amuse, enlighten, and may inspire modern orthopaedists to develop creative solutions of their own. The rich history of the field's eponymous instruments informs an ongoing tradition of innovation in orthopaedics.

The Increased Incidence of Thyrotoxicosis in Immigrants

PubMed Central

Spaulding, W. B.

1963-01-01

Evidence is presented that, in Toronto, hyperthyroidism is significantly more prevalent in immigrants than in native-born patients. In a series of 4000 outpatients only eight of 1854 native-born patients were thyrotoxic, whereas 33 of 2146 immigrants proved to be so (p < 0.001). There is little likelihood that a genetic or nutritional predisposition accounted for the findings, because the immigrants came from widely scattered parts of the world. Possibly, the immigrants were reluctant to seek medical attention for minor illnesses, thereby giving rise to an apparent but not real increase of thyrotoxicosis in the foreignborn. There was less mental illness diagnosed in the immigrants than in the nativeborn patients, a point against relating the thyroid overactivity to emotional stress. It is suggested that the adjustment of settling in a strange country may be physiologically disturbing in some unknown way and may give rise to an increased incidence of thyrotoxicosis in immigrants. PMID:13989936

Hypoconnectivity and hyperfrontality in retired American football players.

PubMed

Hampshire, Adam; MacDonald, Alex; Owen, Adrian M

2013-10-17

Recent research has raised concerns about the long-term neurological consequences of repetitive concussive and sub-concussive injuries in professional players of American Football. Despite this interest, the neural and psychological status of retired players remains unknown. Here, we evaluated the performances and brain activation patterns of retired National Football League players (NFL alumni) relative to controls using an fMRI-optimised neuropsychological test of executive function. Behaviourally, the NFL alumni showed only modest performance deficits on the executive task. By contrast, they showed pronounced hyperactivation and hypoconnectivity of the dorsolateral frontal and frontopolar cortices. Critically, abnormal frontal-lobe function was correlated with the number of times that NFL alumni reported having been removed from play after head injury and was evident in individual players. These results support the hypothesis that NFL alumni have a heightened probability of developing executive dysfunction and suggest that fMRI provides the most sensitive biomarker of the underlying neural abnormality.

The high price of debt: household financial debt and its impact on mental and physical health.

PubMed

Sweet, Elizabeth; Nandi, Arijit; Adam, Emma K; McDade, Thomas W

2013-08-01

Household financial debt in America has risen dramatically in recent years. While there is evidence that debt is associated with adverse psychological health, its relationship with other health outcomes is relatively unknown. We investigate the associations of multiple indices of financial debt with psychological and general health outcomes among 8400 young adult respondents from the National Longitudinal Study of Adolescent Health (Add Health). Our findings show that reporting high financial debt relative to available assets is associated with higher perceived stress and depression, worse self-reported general health, and higher diastolic blood pressure. These associations remain significant when controlling for prior socioeconomic status, psychological and physical health, and other demographic factors. The results suggest that debt is an important socioeconomic determinant of health that should be explored further in social epidemiology research. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Schizophrenia and toxoplasmosis].

PubMed

Dion, Sarah; Barbe, Pierre Guillaume; Leman, Samuel; Camus, Vincent; Dimier-Poisson, Isabelle

2009-01-01

Schizophrenia is one of the most severe and disabling psychiatric disease that affects about 1 % of the adult worldwide population. Aetiology of schizophrenia is still unknown but genetic and environmental factors are suspected to play a major role in its onset. Recent epidemiologic studies indicate that infectious agents may contribute to some cases of schizophrenia. In particular, several epidemiological, behavioural and neurochemical studies suggested the existence of an association between schizophrenia and past history of primo-infection by the Toxoplasma gondii. However, they are some limitations for this hypothesis among which the lack of correlation between the geographic distribution of both diseases and of direct evidence for the presence of the parasite in schizophrenic patients. Nevertheless the identification of physiopathological mechanisms related to the parasite could provide a better comprehension to the outcome of schizophrenia. Studies on the link between toxoplasmosis and schizophrenia may provide interesting data for the diagnosis and the development of new treatments for this disorder.

Cancer-related fatigue in palliative care: a global perspective.

PubMed

Vilchynska, Tetyana; Beard, Barbara

2016-05-01

Cancer-related fatigue (CRF) in a palliative care setting is a distressing symptom that can have a negative impact on a patient's quality of life. A range of setting- and disease-specific factors, unknown aetiology and absence of unilateral guidelines make CRF treatment a challenge for clinicians. In the absence of high-quality evidence in favour of any pharmacological and nonpharmacological measures, except exercise, cognitive behavioural therapy and psychosocial interventions, a personalised integrative oncology approach can lead to effective management. Findings suggest adoption of a severity-based symptom-stage adjusted CRF management care pathway, highlighting best practices to illustrate the lived experience of this symptom. Overcoming barriers by staff training, patient education, facilitating communication and patients' self-care, will increase CRF management effectiveness. Future CRF multisymptom or multidimensional nature investigation trials of its underlying mechanisms and new pharmacological and nonpharmacological strategies applied separately or in combination, will help reveal the best approach to CRF diagnosis, assessment and management.

An Acute Bout of Exercise Improves the Cognitive Performance of Older Adults.

PubMed

Johnson, Liam; Addamo, Patricia K; Selva Raj, Isaac; Borkoles, Erika; Wyckelsma, Victoria; Cyarto, Elizabeth; Polman, Remco C

2016-10-01

There is evidence that an acute bout of exercise confers cognitive benefits, but it is largely unknown what the optimal mode and duration of exercise is and how cognitive performance changes over time after exercise. We compared the cognitive performance of 31 older adults using the Stroop test before, immediately after, and at 30 and 60 min after a 10 and 30 min aerobic or resistance exercise session. Heart rate and feelings of arousal were also measured before, during, and after exercise. We found that, independent of mode or duration of exercise, the participants improved in the Stroop Inhibition task immediately postexercise. We did not find that exercise influenced the performance of the Stroop Color or Stroop Word Interference tasks. Our findings suggest that an acute bout of exercise can improve cognitive performance and, in particular, the more complex executive functioning of older adults.

Neuro-cognitive foundations of word stress processing - evidence from fMRI

PubMed Central

2011-01-01

Background To date, the neural correlates of phonological word stress processing are largely unknown. Methods In the present study, we investigated the processing of word stress and vowel quality using an identity matching task with pseudowords. Results In line with previous studies, a bilateral fronto-temporal network comprising the superior temporal gyri extending into the sulci as well as the inferior frontal gyri was observed for word stress processing. Moreover, we found differences in the superior temporal gyrus and the superior temporal sulcus, bilaterally, for the processing of different stress patterns. For vowel quality processing, our data reveal a substantial contribution of the left intraparietal cortex. All activations were modulated by task demands, yielding different patterns for same and different pairs of stimuli. Conclusions Our results suggest that the left superior temporal gyrus represents a basic system underlying stress processing to which additional structures including the homologous cortex site are recruited with increasing difficulty. PMID:21575209

Bacopa monnieri as an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain

PubMed Central

Simpson, Tamara; Pase, Matthew; Stough, Con

2015-01-01

The detrimental effect of neuronal cell death due to oxidative stress and mitochondrial dysfunction has been implicated in age-related cognitive decline and neurodegenerative disorders such as Alzheimer's disease. The Indian herb Bacopa monnieri is a dietary antioxidant, with animal and in vitro studies indicating several modes of action that may protect the brain against oxidative damage. In parallel, several studies using the CDRI08 extract have shown that extracts of Bacopa monnieri improve cognitive function in humans. The biological mechanisms of this cognitive enhancement are unknown. In this review we discuss the animal studies and in vivo evidence for Bacopa monnieri as a potential therapeutic antioxidant to reduce oxidative stress and improve cognitive function. We suggest that future studies incorporate neuroimaging particularly magnetic resonance spectroscopy into their randomized controlled trials to better understand whether changes in antioxidant status in vivo cause improvements in cognitive function. PMID:26413126

Infective Endocarditis of the Left Main to Right Atrial Coronary Cameral Fistula

PubMed Central

Mishra, Ramesh Chandra; Barik, Ramachandra; Patnaik, Amar Narayana

2016-01-01

A 7-year-old female child presented with pyrexia of unknown origin. She had received an empirical regimen of antibiotic for possible endocarditis. Evaluation included multiple imaging supports and blood culture. She had left main coronary artery to right atrium coronary cameral fistula, restricted patent ductus arteriosus, vegetation at the right atrial exit of fistula and negative blood culture. Ongoing fever more than 2 weeks, oscillating vegetation in the echo and histopathological evidence of healing vegetation suggested definite diagnosis of infective endocarditis. She was treated successfully by surgical closure of fistula from the right atrial approach. Device closure in this case would have resulted in a large residual cul-de-sac with or without tiny residual high-velocity jets, either being a threat for future enlargement, rupture of the residual aneurysmal sac, thromboembolism, prolonged anticoagulation, and infective endocarditis. PMID:28465978

Genesis and growth of extracellular vesicle-derived microcalcification in atherosclerotic plaques

PubMed Central

Hutcheson, Joshua D.; Goettsch, Claudia; Bertazzo, Sergio; Maldonado, Natalia; Ruiz, Jessica L.; Goh, Wilson; Yabusaki, Katsumi; Faits, Tyler; Bouten, Carlijn; Franck, Gregory; Quillard, Thibaut; Libby, Peter; Aikawa, Masanori; Weinbaum, Sheldon; Aikawa, Elena

2015-01-01

Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification zones. We also show that calcification morphology and the plaque’s collagen content – two determinants of atherosclerotic plaque stability - are interlinked. PMID:26752654

A network property necessary for concentration robustness.

PubMed

Eloundou-Mbebi, Jeanne M O; Küken, Anika; Omranian, Nooshin; Kleessen, Sabrina; Neigenfind, Jost; Basler, Georg; Nikoloski, Zoran

2016-10-19

Maintenance of functionality of complex cellular networks and entire organisms exposed to environmental perturbations often depends on concentration robustness of the underlying components. Yet, the reasons and consequences of concentration robustness in large-scale cellular networks remain largely unknown. Here, we derive a necessary condition for concentration robustness based only on the structure of networks endowed with mass action kinetics. The structural condition can be used to design targeted experiments to study concentration robustness. We show that metabolites satisfying the necessary condition are present in metabolic networks from diverse species, suggesting prevalence of this property across kingdoms of life. We also demonstrate that our predictions about concentration robustness of energy-related metabolites are in line with experimental evidence from Escherichia coli. The necessary condition is applicable to mass action biological systems of arbitrary size, and will enable understanding the implications of concentration robustness in genetic engineering strategies and medical applications.

A network property necessary for concentration robustness

PubMed Central

Eloundou-Mbebi, Jeanne M. O.; Küken, Anika; Omranian, Nooshin; Kleessen, Sabrina; Neigenfind, Jost; Basler, Georg; Nikoloski, Zoran

2016-01-01

Maintenance of functionality of complex cellular networks and entire organisms exposed to environmental perturbations often depends on concentration robustness of the underlying components. Yet, the reasons and consequences of concentration robustness in large-scale cellular networks remain largely unknown. Here, we derive a necessary condition for concentration robustness based only on the structure of networks endowed with mass action kinetics. The structural condition can be used to design targeted experiments to study concentration robustness. We show that metabolites satisfying the necessary condition are present in metabolic networks from diverse species, suggesting prevalence of this property across kingdoms of life. We also demonstrate that our predictions about concentration robustness of energy-related metabolites are in line with experimental evidence from Escherichia coli. The necessary condition is applicable to mass action biological systems of arbitrary size, and will enable understanding the implications of concentration robustness in genetic engineering strategies and medical applications. PMID:27759015

The wMel strain of Wolbachia Reduces Transmission of Zika virus by Aedes aegypti.

PubMed

Aliota, Matthew T; Peinado, Stephen A; Velez, Ivan Dario; Osorio, Jorge E

2016-07-01

Zika virus (ZIKV) is causing an explosive outbreak of febrile disease in the Americas. There are no effective antiviral therapies or licensed vaccines for this virus, and mosquito control strategies have not been adequate to contain the virus. A promising candidate for arbovirus control and prevention relies on the introduction of the intracellular bacterium Wolbachia into Aedes aegypti mosquitoes. This primarily has been proposed as a tool to control dengue virus (DENV) transmission; however, evidence suggests Wolbachia infections confer protection for Ae. aegypti against other arboviruses. At present, it is unknown whether or not ZIKV can infect, disseminate, and be transmitted by Wolbachia-infected Ae. aegypti. Using Ae. aegypti infected with the wMel strain of Wolbachia that are being released in Medellin, Colombia, we report that these mosquitoes have reduced vector competence for ZIKV. These results support the use of Wolbachia biocontrol as a multivalent strategy against Ae. aegypti-transmitted viruses.

Demodex canis regulates cholinergic system mediated immunosuppressive pathways in canine demodicosis.

PubMed

Kumari, P; Nigam, R; Singh, A; Nakade, U P; Sharma, A; Garg, S K; Singh, S K

2017-09-01

Demodex canis infestation in dogs remains one of the main challenges in veterinary dermatology. The exact pathogenesis of canine demodicosis is unknown but an aberration in immune status is considered very significant. No studies have underpinned the nexus between induction of demodicosis and neural immunosuppressive pathways so far. We have evaluated the involvement of cholinergic pathways in association with cytokines regulation as an insight into the immuno-pathogenesis of canine demodicosis in the present study. Remarkable elevations in circulatory immunosuppressive cytokine interleukin-10 and cholinesterase activity were observed in dogs with demodicosis. Simultaneously, remarkable reduction in circulatory pro-inflammatory cytokine tumour necrosis factor-alpha level was observed in dogs with demodicosis. Findings of the present study evidently suggest that Demodex mites might be affecting the cholinergic pathways to induce immunosuppression in their host and then proliferate incessantly in skin microenvironment to cause demodicosis.

Gap junction- and hemichannel-independent actions of connexins.

PubMed

Jiang, Jean X; Gu, Sumin

2005-06-10

Connexins have been known to be the protein building blocks of gap junctions and mediate cell-cell communication. In contrast to the conventional dogma, recent evidence suggests that in addition to forming gap junction channels, connexins possess gap junction-independent functions. One important gap junction-independent function for connexins is to serve as the major functional component for hemichannels, the un-apposed halves of gap junctions. Hemichannels, as independent functional units, play roles that are different from that of gap junctions in the cell. The other functions of connexins appear to be gap junction- and hemichannel-independent. Published studies implicate the latter functions of connexins in cell growth, differentiation, tumorigenicity, injury, and apoptosis, although the mechanistic aspects of these actions remain largely unknown. In this review, gap junction- and hemichannel-independent functions of connexins are summarized, and the molecular mechanisms underlying these connexin functions are speculated and discussed.

Selenium nanoparticles inhibit Staphylococcus aureus growth

PubMed Central

Tran, Phong A; Webster, Thomas J

2011-01-01

Staphylococcus aureus is a key bacterium commonly found in numerous infections. S. aureus infections are difficult to treat due to their biofilm formation and documented antibiotic resistance. While selenium has been used for a wide range of applications including anticancer applications, the effects of selenium nanoparticles on microorganisms remain largely unknown to date. The objective of this in vitro study was thus to examine the growth of S. aureus in the presence of selenium nanoparticles. Results of this study provided the first evidence of strongly inhibited growth of S. aureus in the presence of selenium nanoparticles after 3, 4, and 5 hours at 7.8, 15.5, and 31 μg/mL. The percentage of live bacteria also decreased in the presence of selenium nanoparticles. Therefore, this study suggests that selenium nanoparticles may be used to effectively prevent and treat S. aureus infections and thus should be further studied for such applications. PMID:21845045

Primary sclerosing cholangitis and the microbiota: current knowledge and perspectives on etiopathogenesis and emerging therapies.

PubMed

Tabibian, James H; O'Hara, Steven P; Lindor, Keith D

2014-08-01

Primary sclerosing cholangitis (PSC) is a chronic, fibroinflammatory, cholestatic liver disease of unknown etiopathogenesis. PSC generally progresses to liver cirrhosis, is a major risk factor for hepatobiliary and colonic neoplasia, and confers a median survival to death or liver transplantation of only 12 years. Although it is well recognized that approximately 75% of patients with PSC also have inflammatory bowel disease (IBD), the significance of this association remains elusive. Accumulating evidence now suggests a potentially important role for the intestinal microbiota, and enterohepatic circulation of molecules derived therefrom, as a putative mechanistic link between PSC and IBD and a central pathobiological driver of PSC. In this concise review, we provide a summary of and perspectives regarding the relevant basic, translational, and clinical data, which, taken together, encourage further investigation of the role of the microbiota and microbial metabolites in the etiopathogenesis of PSC and as a potential target for novel pharmacotherapies.

The spectrotemporal filter mechanism of auditory selective attention

PubMed Central

Lakatos, Peter; Musacchia, Gabriella; O’Connell, Monica N.; Falchier, Arnaud Y.; Javitt, Daniel C.; Schroeder, Charles E.

2013-01-01

SUMMARY While we have convincing evidence that attention to auditory stimuli modulates neuronal responses at or before the level of primary auditory cortex (A1), the underlying physiological mechanisms are unknown. We found that attending to rhythmic auditory streams resulted in the entrainment of ongoing oscillatory activity reflecting rhythmic excitability fluctuations in A1. Strikingly, while the rhythm of the entrained oscillations in A1 neuronal ensembles reflected the temporal structure of the attended stream, the phase depended on the attended frequency content. Counter-phase entrainment across differently tuned A1 regions resulted in both the amplification and sharpening of responses at attended time points, in essence acting as a spectrotemporal filter mechanism. Our data suggest that selective attention generates a dynamically evolving model of attended auditory stimulus streams in the form of modulatory subthreshold oscillations across tonotopically organized neuronal ensembles in A1 that enhances the representation of attended stimuli. PMID:23439126

Serotonin Affects Movement Gain Control in the Spinal Cord

PubMed Central

Glaser, Joshua I.; Deng, Linna; Thompson, Christopher K.; Stevenson, Ian H.; Wang, Qining; Hornby, Thomas George; Heckman, Charles J.; Kording, Konrad P.

2014-01-01

A fundamental challenge for the nervous system is to encode signals spanning many orders of magnitude with neurons of limited bandwidth. To meet this challenge, perceptual systems use gain control. However, whether the motor system uses an analogous mechanism is essentially unknown. Neuromodulators, such as serotonin, are prime candidates for gain control signals during force production. Serotonergic neurons project diffusely to motor pools, and, therefore, force production by one muscle should change the gain of others. Here we present behavioral and pharmaceutical evidence that serotonin modulates the input–output gain of motoneurons in humans. By selectively changing the efficacy of serotonin with drugs, we systematically modulated the amplitude of spinal reflexes. More importantly, force production in different limbs interacts systematically, as predicted by a spinal gain control mechanism. Psychophysics and pharmacology suggest that the motor system adopts gain control mechanisms, and serotonin is a primary driver for their implementation in force production. PMID:25232107

The role of Myc-induced protein synthesis in cancer

PubMed Central

Ruggero, Davide

2009-01-01

Deregulation in different steps of translational control is an emerging mechanism for cancer formation. One example of an oncogene with a direct role in control of translation is the Myc transcription factor. Myc directly increases protein synthesis rates by controlling the expression of multiple components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, Pol III and rDNA. However, the contribution of Myc-dependent increases in protein synthesis towards the multi-step process leading to cancer has remained unknown. Recent evidence strongly suggests that Myc oncogenic signaling may monopolize the translational machinery to elicit cooperative effects on cell growth, cell cycle progression, and genome instability as a mechanism for cancer initiation. Moreover, new genetic tools to restore aberrant increases in protein synthesis control are now available, which should enable the dissection of important mechanisms in cancer that rely on the translational machinery. PMID:19934336

Marijuana, the Endocannabinoid System and the Female Reproductive System.

PubMed

Brents, Lisa K

2016-06-01

Marijuana use among women is highly prevalent, but the societal conversation on marijuana rarely focuses on how marijuana affects female reproduction and endocrinology. This article reviews the current scientific literature regarding marijuana use and hypothalamic-pituitary-ovarian (HPO) axis regulation, ovarian hormone production, the menstrual cycle, and fertility. Evidence suggests that marijuana can reduce female fertility by disrupting hypothalamic release of gonadotropin releasing hormone (GnRH), leading to reduced estrogen and progesterone production and anovulatory menstrual cycles. Tolerance to these effects has been shown in rhesus monkeys, but the effects of chronic marijuana use on human female reproduction are largely unknown. Marijuana-induced analgesia, drug reinforcement properties, tolerance, and dependence are influenced by ovarian hormones, with estrogen generally increasing and progesterone decreasing sensitivity to marijuana. Carefully controlled regulation of the Endocannabinoid System (ECS) is required for successful reproduction, and the exogenous cannabinoids in marijuana may disrupt the delicate balance of the ECS in the female reproductive system.

Hypoconnectivity and Hyperfrontality in Retired American Football Players

NASA Astrophysics Data System (ADS)

Hampshire, Adam; MacDonald, Alex; Owen, Adrian M.

2013-10-01

Recent research has raised concerns about the long-term neurological consequences of repetitive concussive and sub-concussive injuries in professional players of American Football. Despite this interest, the neural and psychological status of retired players remains unknown. Here, we evaluated the performances and brain activation patterns of retired National Football League players (NFL alumni) relative to controls using an fMRI-optimised neuropsychological test of executive function. Behaviourally, the NFL alumni showed only modest performance deficits on the executive task. By contrast, they showed pronounced hyperactivation and hypoconnectivity of the dorsolateral frontal and frontopolar cortices. Critically, abnormal frontal-lobe function was correlated with the number of times that NFL alumni reported having been removed from play after head injury and was evident in individual players. These results support the hypothesis that NFL alumni have a heightened probability of developing executive dysfunction and suggest that fMRI provides the most sensitive biomarker of the underlying neural abnormality.

Concise Review: Amniotic Fluid Stem Cells: The Known, the Unknown, and Potential Regenerative Medicine Applications.

PubMed

Loukogeorgakis, Stavros P; De Coppi, Paolo

2017-07-01

The amniotic fluid has been identified as an untapped source of cells with broad potential, which possess immunomodulatory properties and do not have the ethical and legal limitations of embryonic stem cells. CD117(c-Kit)+ cells selected from amniotic fluid have been shown to differentiate into cell lineages representing all three embryonic germ layers without generating tumors, making them ideal candidates for regenerative medicine applications. Moreover, their ability to engraft in injured organs and modulate immune and repair responses of host tissues, suggest that transplantation of such cells may be useful for the treatment of various degenerative and inflammatory diseases. Although significant questions remain regarding the origin, heterogeneous phenotype, and expansion potential of amniotic fluid stem cells, evidence to date supports their potential role as a valuable stem cell source for the field of regenerative medicine. Stem Cells 2017;35:1663-1673. © 2016 AlphaMed Press.

Amicoumacin A inhibits translation by stabilizing mRNA interaction with the ribosome

PubMed Central

Polikanov, Yury S.; Osterman, Ilya A.; Szal, Teresa; Tashlitsky, Vadim N.; Serebryakova, Marina V.; Kusochek, Pavel; Bulkley, David; Malanicheva, Irina A.; Efimenko, Tatyana A.; Efremenkova, Olga V.; Konevega, Andrey L.; Shaw, Karen J.; Bogdanov, Alexey A.; Rodnina, Marina V.; Dontsova, Olga A.; Mankin, Alexander S.; Steitz, Thomas A.; Sergiev, Petr V.

2014-01-01

SUMMARY We demonstrate that the antibiotic amicoumacin A (AMI) whose cellular target was unknown, is a potent inhibitor of protein synthesis. Resistance mutations in helix 24 of the 16S rRNA mapped the AMI binding site to the small ribosomal subunit. The crystal structure of bacterial ribosome in complex with AMI solved at 2.4 Å resolution revealed that the antibiotic makes contacts with universally conserved nucleotides of 16S rRNA in the E site and the mRNA backbone. Simultaneous interactions of AMI with 16S rRNA and mRNA and the in vivo experimental evidence suggest that it may inhibit the progression of the ribosome along mRNA. Consistent with this proposal, binding of AMI interferes with translocation in vitro. The inhibitory action of AMI can be partly compensated by mutations in the translation elongation factor G. PMID:25306919

Neural correlates of fixation duration in natural reading: Evidence from fixation-related fMRI.

PubMed

Henderson, John M; Choi, Wonil; Luke, Steven G; Desai, Rutvik H

2015-10-01

A key assumption of current theories of natural reading is that fixation duration reflects underlying attentional, language, and cognitive processes associated with text comprehension. The neurocognitive correlates of this relationship are currently unknown. To investigate this relationship, we compared neural activation associated with fixation duration in passage reading and a pseudo-reading control condition. The results showed that fixation duration was associated with activation in oculomotor and language areas during text reading. Fixation duration during pseudo-reading, on the other hand, showed greater involvement of frontal control regions, suggesting flexibility and task dependency of the eye movement network. Consistent with current models, these results provide support for the hypothesis that fixation duration in reading reflects attentional engagement and language processing. The results also demonstrate that fixation-related fMRI provides a method for investigating the neurocognitive bases of natural reading. Copyright © 2015 Elsevier Inc. All rights reserved.

Cyanobacterial Toxins as Allelochemicals with Potential Applications as Algaecides, Herbicides and Insecticides

PubMed Central

Berry, John P.; Gantar, Miroslav; Perez, Mario H.; Berry, Gerald; Noriega, Fernando G.

2008-01-01

Cyanobacteria (“blue-green algae”) from marine and freshwater habitats are known to produce a diverse array of toxic or otherwise bioactive metabolites. However, the functional role of the vast majority of these compounds, particularly in terms of the physiology and ecology of the cyanobacteria that produce them, remains largely unknown. A limited number of studies have suggested that some of the compounds may have ecological roles as allelochemicals, specifically including compounds that may inhibit competing sympatric macrophytes, algae and microbes. These allelochemicals may also play a role in defense against potential predators and grazers, particularly aquatic invertebrates and their larvae. This review will discuss the existing evidence for the allelochemical roles of cyanobacterial toxins, as well as the potential for development and application of these compounds as algaecides, herbicides and insecticides, and specifically present relevant results from investigations into toxins of cyanobacteria from the Florida Everglades and associated waterways. PMID:18728763

Gray Matter Is Targeted in First-Attack Multiple Sclerosis

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

Schutzer, Steven E.; Angel, Thomas E.; Liu, Tao

The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To determine if there was objective molecular evidence of gray matter involvement in early MS we used high-resolution mass spectrometry to identify proteins in the cerebrospinal fluid (CSF) of first-attack MS patients (two independent groups) compared to established relapsing remitting (RR) MS and controls. We foundmore » that the CSF proteins in first-attack patients were differentially enriched for gray matter components (axon, neuron, synapse). Myelin components did not distinguish these groups. The results support that gray matter dysfunction is involved early in MS, and also may be integral for the initial clinical presentation.« less

Perception and selection of macrophyte detrital falls by the bathyal echinoid Stylocidaris lineata

NASA Astrophysics Data System (ADS)

Young, C. M.; Tyler, P. A.; Emson, R. H.; Gage, J. D.

1993-07-01

Many deep-sea animals are known to exploit patchy food resources such as animal carcasses and sunken plant remains, but the mechanisms by which such foods are located remain generally unknown. The bathyal echinoid Stylocidaris lineata is an omnivorous deposit feeder that ingests sediment, dead animal remains, seagrass blades, and macroalgae such as Sargassum spp. Using a submersible, we investigated the ability of urchins to locate and exploit large falls of detritus. Individuals quickly arrived at packets of Thalassia testudinum and Sargassum spp. placed on the bottom, and they preferred these food items significantly over inert controls. However, the echinoids demonstrated no significant tendency to move toward the scent of upstream T. testudinum, either in situ or in laboratory flume experiments. Individuals moved at net speeds up to 30 m day -1. The existing evidence suggests that S. lineata locate food by chance encounter, not distant chemoreception.

Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility

NASA Technical Reports Server (NTRS)

Morfini, Gerardo; Szebenyi, Gyorgyi; Elluru, Ravindhra; Ratner, Nancy; Brady, Scott T.

2002-01-01

Membrane-bounded organelles (MBOs) are delivered to different domains in neurons by fast axonal transport. The importance of kinesin for fast antero grade transport is well established, but mechanisms for regulating kinesin-based motility are largely unknown. In this report, we provide biochemical and in vivo evidence that kinesin light chains (KLCs) interact with and are in vivo substrates for glycogen synthase kinase 3 (GSK3). Active GSK3 inhibited anterograde, but not retrograde, transport in squid axoplasm and reduced the amount of kinesin bound to MBOs. Kinesin microtubule binding and microtubule-stimulated ATPase activities were unaffected by GSK3 phosphorylation of KLCs. Active GSK3 was also localized preferentially to regions known to be sites of membrane delivery. These data suggest that GSK3 can regulate fast anterograde axonal transport and targeting of cargos to specific subcellular domains in neurons.

Leukodystrophies with late disease onset: an update.

PubMed

Köhler, Wolfgang

2010-06-01

Knowledge of the metabolic and genetic basis of known and previously unknown leukodystrophies is constantly increasing, opening new treatment options such as enzyme replacement or cell-based therapies. This brief review highlights some recent work, particularly emphasizing results from studies in adulthood leukodystrophies. Evidence from recent studies suggests increasing importance of metabolic dysfunctions, for example, in peroxisomal lipid metabolism or energy homeostasis, influencing axonal integrity and oligodendrocyte function and leading to white matter demyelination. In addition, diagnostic and therapeutic progress in metachromatic leukodystrophy, X-linked adrenoleukodystrophy, Krabbe diseases and other rare leukodystrophies with late onset are summarized. Better understanding of leukodystrophies in neurological routine practice is of crucial importance for differentiating between other white matter diseases such as toxic, inflammatory or vascular leukoencephalopathies. Many leukodystrophies are particularly important to recognize because specific treatments already exist or are currently under investigation. The article also provides an overview of currently known leukodystrophies in adulthood.

Evidence for an electrostatic mechanism of force generation by the bacteriophage T4 DNA packaging motor

PubMed Central

Migliori, Amy D.; Keller, Nicholas; Alam, Tanfis I.; Mahalingam, Marthandan; Rao, Venigalla B.; Arya, Gaurav; Smith, Douglas E

2014-01-01

How viral packaging motors generate enormous forces to translocate DNA into viral capsids remains unknown. Recent structural studies of the bacteriophage T4 packaging motor have led to a proposed mechanism wherein the gp17 motor protein translocates DNA by transitioning between extended and compact states, orchestrated by electrostatic interactions between complimentarily charged residues across the interface between the N- and C-terminal subdomains. Here, we show that site-directed alterations in these residues cause force dependent impairments of motor function including lower translocation velocity, lower stall force, and higher frequency of pauses and slips. We further show that the measured impairments correlate with computed changes in free energy differences between the two states. These findings support the proposed structural mechanism and further suggest an energy landscape model of motor activity that couples the free energy profile of motor conformational states with that of the ATP hydrolysis cycle. PMID:24937091

Retrospective attention enhances visual working memory in the young but not the old: an ERP study

PubMed Central

Duarte, Audrey; Hearons, Patricia; Jiang, Yashu; Delvin, Mary Courtney; Newsome, Rachel N.; Verhaeghen, Paul

2013-01-01

Behavioral evidence from the young suggests spatial cues that orient attention toward task relevant items in visual working memory (VWM) enhance memory capacity. Whether older adults can also use retrospective cues (“retro-cues”) to enhance VWM capacity is unknown. In the current event-related potential (ERP) study, young and old adults performed a VWM task in which spatially informative retro-cues were presented during maintenance. Young but not older adults’ VWM capacity benefitted from retro-cueing. The contralateral delay activity (CDA) ERP index of VWM maintenance was attenuated after the retro-cue, which effectively reduced the impact of memory load. CDA amplitudes were reduced prior to retro-cue onset in the old only. Despite a preserved ability to delete items from VWM, older adults may be less able to use retrospective attention to enhance memory capacity when expectancy of impending spatial cues disrupts effective VWM maintenance. PMID:23445536

Neural representations of close others in collectivistic brains

PubMed Central

Wang, Gang; Mao, Lihua; Ma, Yina; Yang, Xuedong; Cao, Jingqian; Liu, Xi; Wang, Jinzhao; Wang, Xiaoying

2012-01-01

Our recent work showed that close relationships result in shared cognitive and neural representations of the self and one’s mother in collectivistic individuals (Zhu et al., 2007, Neuroimage, 34, 1310–7). However, it remains unknown whether close others, such as mother, father and best friend, are differentially represented in collectivistic brains. Here, using functional magnetic resonance imaging and a trait judgment task, we showed evidence that, while trait judgments of the self and mother generated comparable activity in the medial prefrontal cortex (MPFC) and anterior cingulate (ACC) of Chinese adults, trait judgments of mother induced greater MPFC/ACC activity than trait judgments of father and best friend. Our results suggest that, while neural representations of the self and mother overlapped in the MPFC/ACC, close others such as mother, father and best friend are unequally represented in the MPFC/ACC of collectivistic brains. PMID:21382966

In search of the motor engram: motor map plasticity as a mechanism for encoding motor experience.

PubMed

Monfils, Marie-H; Plautz, Erik J; Kleim, Jeffrey A

2005-10-01

Motor skill acquisition occurs through modification and organization of muscle synergies into effective movement sequences. The learning process is reflected neurophysiologically as a reorganization of movement representations within the primary motor cortex, suggesting that the motor map is a motor engram. However, the specific neural mechanisms underlying map plasticity are unknown. Here the authors review evidence that 1) motor map topography reflects the capacity for skilled movement, 2) motor skill learning induces reorganization of motor maps in a manner that reflects the kinematics of acquired skilled movement, 3) map plasticity is supported by a reorganization of cortical microcircuitry involving changes in synaptic efficacy, and 4) motor map integrity and topography are influenced by various neurochemical signals that coordinate changes in cortical circuitry to encode motor experience. Finally, the role of motor map plasticity in recovery of motor function after brain damage is discussed.

Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease.

PubMed

Venderova, Katerina; Kabbach, Ghassan; Abdel-Messih, Elizabeth; Zhang, Yi; Parks, Robin J; Imai, Yuzuru; Gehrke, Stephan; Ngsee, Johnny; Lavoie, Matthew J; Slack, Ruth S; Rao, Yong; Zhang, Zhuohua; Lu, Bingwei; Haque, M Emdadul; Park, David S

2009-11-15

Mutations in the LRRK2 gene are the most common genetic cause of familial Parkinson's disease (PD). However, its physiological and pathological functions are unknown. Therefore, we generated several independent Drosophila lines carrying WT or mutant human LRRK2 (mutations in kinase, COR or LRR domains, resp.). Ectopic expression of WT or mutant LRRK2 in dopaminergic neurons caused their significant loss accompanied by complex age-dependent changes in locomotor activity. Overall, the ubiquitous expression of LRRK2 increased lifespan and fertility of the flies. However, these flies were more sensitive to rotenone. LRRK2 expression in the eye exacerbated retinal degeneration. Importantly, in double transgenic flies, various indices of the eye and dopaminergic survival were modified in a complex fashion by a concomitant expression of PINK1, DJ-1 or Parkin. This evidence suggests a genetic interaction between these PD-relevant genes.

Metagenomic recovery of phage genomes of uncultured freshwater actinobacteria.

PubMed

Ghai, Rohit; Mehrshad, Maliheh; Mizuno, Carolina Megumi; Rodriguez-Valera, Francisco

2017-01-01

Low-GC Actinobacteria are among the most abundant and widespread microbes in freshwaters and have largely resisted all cultivation efforts. Consequently, their phages have remained totally unknown. In this work, we have used deep metagenomic sequencing to assemble eight complete genomes of the first tailed phages that infect freshwater Actinobacteria. Their genomes encode the actinobacterial-specific transcription factor whiB, frequently found in mycobacteriophages and also in phages infecting marine pelagic Actinobacteria. Its presence suggests a common and widespread strategy of modulation of host transcriptional machinery upon infection via this transcriptional switch. We present evidence that some whiB-carrying phages infect the acI lineage of Actinobacteria. At least one of them encodes the ADP-ribosylating component of the widespread bacterial AB toxins family (for example, clostridial toxin). We posit that the presence of this toxin reflects a 'trojan horse' strategy, providing protection at the population level to the abundant host microbes against eukaryotic predators.

Coping and negative appraisal as mediators between control beliefs and psychological symptoms in children of divorce.

PubMed

Sandler, I N; Kim-Bae, L S; MacKinnon, D

2000-09-01

Examined control beliefs of children of divorce as predictors of their coping, negative appraisals for stressful events, and mental health problems. We tested whether coping and negative appraisal for stressful events mediated the relations between multiple dimensions of control beliefs and mental health problems. Different dimensions of control beliefs were related to different aspects of coping and negative stress appraisal. Internal control beliefs for positive events were related to both active and avoidant coping. Unknown control beliefs for positive events were related to higher active coping and higher negative appraisal. Unknown control beliefs for negative events were related to higher avoidant coping. In addition, evidence for mediation was found such that the effect of unknown control beliefs for positive events on mental health problems was mediated by negative appraisal. Implications and directions for further research are discussed.

Proteins of Unknown Biochemical Function: A Persistent Problem and a Roadmap to Help Overcome It.

PubMed

Niehaus, Thomas D; Thamm, Antje M K; de Crécy-Lagard, Valérie; Hanson, Andrew D

2015-11-01

The number of sequenced genomes is rapidly increasing, but functional annotation of the genes in these genomes lags far behind. Even in Arabidopsis (Arabidopsis thaliana), only approximately 40% of enzyme- and transporter-encoding genes have credible functional annotations, and this number is even lower in nonmodel plants. Functional characterization of unknown genes is a challenge, but various databases (e.g. for protein localization and coexpression) can be mined to provide clues. If homologous microbial genes exist-and about one-half the genes encoding unknown enzymes and transporters in Arabidopsis have microbial homologs-cross-kingdom comparative genomics can powerfully complement plant-based data. Multiple lines of evidence can strengthen predictions and warrant experimental characterization. In some cases, relatively quick tests in genetically tractable microbes can determine whether a prediction merits biochemical validation, which is costly and demands specialized skills. © 2015 American Society of Plant Biologists. All Rights Reserved.

A novel animal model linking adiposity to altered circadian rhythms

USDA-ARS?s Scientific Manuscript database

Researchers have provided evidence for a link between obesity and altered circadian rhythms (e.g., shift work, disrupted sleep), but the mechanism for this association is still unknown. Adipocytes possess an intrinsic circadian clock, and circadian rhythms in adipocytokines and adipose tissue metab...

[Parental alienation syndrome (PAS): unknown in medical settings, endemic in courts].

PubMed

Pignotti, Maria Serenella

2013-02-01

A purposed syndrome of so-called parental alienation (PAS), unsupported by any evidence-based data, unknown in medical settings, unquoted in medical books, absent in DSM and ICD, never demonstrated by controlled studies published in high scientific level journals, is rampant in Courts where it can lead to loose parental custody. During a divorce trial, almost always the mothers and the children, become joint in a sort of folie au deux, in a denigration campaign of ex-husband/father. From a review on this issue it seems evident its theoretical roots lie on a theory that justify gender violence and children sexual abuse. The bias that both of them are layers and that he children have not autonomy block their possibility of any defence in front of a Court. In severe cases, PAS becomes a new and efficient tool of intra-familiar violence. The treatment of severe cases is to stop any contact between mother and children. The resort to PAS in Courts must be strongly rejected.

Transactional Database Transformation and Its Application in Prioritizing Human Disease Genes

PubMed Central

Xiang, Yang; Payne, Philip R.O.; Huang, Kun

2013-01-01

Binary (0,1) matrices, commonly known as transactional databases, can represent many application data, including gene-phenotype data where “1” represents a confirmed gene-phenotype relation and “0” represents an unknown relation. It is natural to ask what information is hidden behind these “0”s and “1”s. Unfortunately, recent matrix completion methods, though very effective in many cases, are less likely to infer something interesting from these (0,1)-matrices. To answer this challenge, we propose IndEvi, a very succinct and effective algorithm to perform independent-evidence-based transactional database transformation. Each entry of a (0,1)-matrix is evaluated by “independent evidence” (maximal supporting patterns) extracted from the whole matrix for this entry. The value of an entry, regardless of its value as 0 or 1, has completely no effect for its independent evidence. The experiment on a gene-phenotype database shows that our method is highly promising in ranking candidate genes and predicting unknown disease genes. PMID:21422495

Leaf proteomic analysis in cassava (Manihot esculenta, Crantz) during plant development, from planting of stem cutting to storage root formation.

PubMed

Mitprasat, Mashamon; Roytrakul, Sittiruk; Jiemsup, Surasak; Boonseng, Opas; Yokthongwattana, Kittisak

2011-06-01

Tuberization in cassava (Manihot esculenta Crantz) occurs simultaneously with plant development, suggesting competition of photoassimilate partitioning between the shoot and the root organs. In potato, which is the most widely studied tuber crop, there is ample evidence suggesting that metabolism and regulatory processes in leaf may have an impact on tuber formation. To search for leaf proteins putatively involved in regulating tuber generation and/or development in cassava, comparative proteomic approaches have been applied to monitor differentially expressed leaf proteins during root transition from fibrous to tuberous. Stringent cross comparison and statistical analysis between two groups with different plant ages using Student's t test with 95% significance level revealed a number of protein spots whose abundance were significantly altered (P < 0.05) during week 4 to week 8 of growth. Of these, 39 spots were successfully identified by ion trap LC-MS/MS. The proteins span various functional categories from antioxidant and defense, carbohydrate metabolism, cyanogenesis, energy metabolism, miscellaneous and unknown proteins. Results suggested possible metabolic switches in the leaf that may trigger/regulate storage root initiation and growth. This study provides a basis for further functional characterization of differentially expressed leaf proteins, which can help understand how biochemical processes in cassava leaves may be involved in storage root development.

The price of your soul: neural evidence for the non-utilitarian representation of sacred values

PubMed Central

Berns, Gregory S.; Bell, Emily; Capra, C. Monica; Prietula, Michael J.; Moore, Sara; Anderson, Brittany; Ginges, Jeremy; Atran, Scott

2012-01-01

Sacred values, such as those associated with religious or ethnic identity, underlie many important individual and group decisions in life, and individuals typically resist attempts to trade off their sacred values in exchange for material benefits. Deontological theory suggests that sacred values are processed based on rights and wrongs irrespective of outcomes, while utilitarian theory suggests that they are processed based on costs and benefits of potential outcomes, but which mode of processing an individual naturally uses is unknown. The study of decisions over sacred values is difficult because outcomes cannot typically be realized in a laboratory, and hence little is known about the neural representation and processing of sacred values. We used an experimental paradigm that used integrity as a proxy for sacredness and which paid real money to induce individuals to sell their personal values. Using functional magnetic resonance imaging (fMRI), we found that values that people refused to sell (sacred values) were associated with increased activity in the left temporoparietal junction and ventrolateral prefrontal cortex, regions previously associated with semantic rule retrieval. This suggests that sacred values affect behaviour through the retrieval and processing of deontic rules and not through a utilitarian evaluation of costs and benefits. PMID:22271790

The price of your soul: neural evidence for the non-utilitarian representation of sacred values.

PubMed

Berns, Gregory S; Bell, Emily; Capra, C Monica; Prietula, Michael J; Moore, Sara; Anderson, Brittany; Ginges, Jeremy; Atran, Scott

2012-03-05

Sacred values, such as those associated with religious or ethnic identity, underlie many important individual and group decisions in life, and individuals typically resist attempts to trade off their sacred values in exchange for material benefits. Deontological theory suggests that sacred values are processed based on rights and wrongs irrespective of outcomes, while utilitarian theory suggests that they are processed based on costs and benefits of potential outcomes, but which mode of processing an individual naturally uses is unknown. The study of decisions over sacred values is difficult because outcomes cannot typically be realized in a laboratory, and hence little is known about the neural representation and processing of sacred values. We used an experimental paradigm that used integrity as a proxy for sacredness and which paid real money to induce individuals to sell their personal values. Using functional magnetic resonance imaging (fMRI), we found that values that people refused to sell (sacred values) were associated with increased activity in the left temporoparietal junction and ventrolateral prefrontal cortex, regions previously associated with semantic rule retrieval. This suggests that sacred values affect behaviour through the retrieval and processing of deontic rules and not through a utilitarian evaluation of costs and benefits.

Radiotherapy induces cell cycle arrest and cell apoptosis in nasopharyngeal carcinoma via the ATM and Smad pathways.

PubMed

Li, Ming-Yi; Liu, Jin-Quan; Chen, Dong-Ping; Li, Zhou-Yu; Qi, Bin; He, Lu; Yu, Yi; Yin, Wen-Jin; Wang, Meng-Yao; Lin, Ling

2017-09-02

Nasopharyngeal carcinoma (NPC) is a common malignant neoplasm of the head and neck which is harmful to human's health. Radiotherapy is commonly used in the treatment of NPC and it induces immediate cell cycle arrest and cell apoptosis. However, the mechanism remains unknown. Evidences suggested the activation of Ataxia telangiectasia mutated (ATM) pathway and Smad pathway are 2 of the important crucial mediators in the function of radiotherapy. In this study, we performed in vitro assays with human nasopharyngeal carcinoma CNE-2 cells and in vivo assays with nude mice to investigate the role of the ATM and Smad pathways in the treatment of nasopharyngeal carcinoma with radiotherapy. The results suggested that radiation induced activation of ATM pathway by inducing expression of p-ATM, p-CHK1, p-CHK2, p15 and inhibiting expression of p-Smad3. In addition, Caspase3 expression was increased while CDC25A was decreased, leading to cell cycle arrest and cell apoptosis. On the other hand, activation of Smad3 can inhibited the ATM pathway and attenuated the efficacy of radiation. In summary, we suggest that both ATM and Smad pathways contribute to the cell cycle arrest and cell apoptosis during nasopharyngeal carcinoma cells treated with radiation.

Microsomal metabolism of trenbolone acetate metabolites ...

EPA Pesticide Factsheets

Trenbolone acetate (TBA) is a synthetic growth promoter widely used in animal agriculture, and its metabolites are suspected endocrine disrupting compounds in agriculturally impacted receiving waters. However, beyond the three widely recognized TBA metabolites (17-trenbolone, 17-trenbolone and trendione), little is known about other metabolites formed in vivo and subsequently discharged into the environment, with some evidence suggesting these unknown metabolites comprise a majority of the TBA mass dosed to the animal. Here, we explored the metabolism of the three known TBA metabolites using rat liver microsome studies. All TBA metabolites are transformed into a complex mixture of monohydroxylated products. Based on product characterization, the majority are more polar than the parent metabolites but maintain their characteristic trienone backbone. A minor degree of interconversion between known metabolites was also observed, as were higher order hydroxylated products with a greater extent of reaction. Notably, the distribution and yield of products were generally comparable across a series of variably induced rat liver microsomes, as well as during additional studies with human and bovine liver microsomes. Bioassays conducted with mixtures of these transformation products suggest that androgen receptor (AR) binding activity is diminished as a result of the microsomal treatment, suggesting that the transformation products are generally less potent than

Pulsar statistics and their interpretations

NASA Technical Reports Server (NTRS)

Arnett, W. D.; Lerche, I.

1981-01-01

It is shown that a lack of knowledge concerning interstellar electron density, the true spatial distribution of pulsars, the radio luminosity source distribution of pulsars, the real ages and real aging rates of pulsars, the beaming factor (and other unknown factors causing the known sample of about 350 pulsars to be incomplete to an unknown degree) is sufficient to cause a minimum uncertainty of a factor of 20 in any attempt to determine pulsar birth or death rates in the Galaxy. It is suggested that this uncertainty must impact on suggestions that the pulsar rates can be used to constrain possible scenarios for neutron star formation and stellar evolution in general.

Measurement properties of gait-related outcomes in youth with neuromuscular diagnoses: a systematic review.

PubMed

Ammann-Reiffer, Corinne; Bastiaenen, Caroline H G; de Bie, Rob A; van Hedel, Hubertus J A

2014-08-01

Sound measurement properties of outcome tools are essential when evaluating outcomes of an intervention, in clinical practice and in research. The purpose of this study was to review the evidence on reliability, measurement error, and responsiveness of measures of gait function in children with neuromuscular diagnoses. The MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched up to June 15, 2012. Studies evaluating reliability, measurement error, or responsiveness of measures of gait function in 1- to 18-year-old children and youth with neuromuscular diagnoses were included. Quality of the studies was independently rated by 2 raters using a modified COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. Studies with a fair quality rating or better were considered for best evidence synthesis. Regarding the methodological quality, 32 out of 35 reliability studies, all of the 13 measurement error studies, and 5 out of 10 responsiveness studies were of fair or good quality. Best evidence synthesis revealed moderate to strong evidence for reliability for several measures in children and youth with cerebral palsy (CP) but was limited or unknown in other diagnoses. The Functional Mobility Scale (FMS) and the Gross Motor Function Measure (GMFM) dimension E showed limited positive evidence for responsiveness in children with CP, but it was unknown or controversial in other diagnoses. No information was reported on the minimal important change; thus, evidence on measurement error remained undetermined. As studies on validity were not included in the review, a comprehensive appraisal of the best available gait-related outcome measure per diagnosis is not possible. There is moderate to strong evidence on reliability for several measures of gait function in children and youth with CP, whereas evidence on responsiveness exists only for the FMS and the GMFM dimension E. © 2014 American Physical Therapy Association.

A sting from an unknown jellyfish species associated with persistent symptoms and raised troponin I levels.

PubMed

McD Taylor, David; Pereira, Peter; Seymour, Jamie; Winkel, Kenneth D

2002-06-01

We describe a patient stung by an unknown jellyfish species offshore in Far North Queensland. The sting caused immediate and severe pain, multiple whip-like skin lesions and constitutional symptoms. The jellyfish tentacular nematocysyts were similar to, but distinct from, those of Carukia barnesi, a cause of the 'Irukandji' syndrome. The patients symptoms largely resolved over seven months and were associated with elevated cardiac troponin levels, in the absence of other evidence of cardiac disease. This case highlights the envenomation risks associated with marine recreation, and the need for critical evaluation of cardiac troponin assays and for further research in marine toxicology.

Motor excitability during visual perception of known and unknown spoken languages.

PubMed

Swaminathan, Swathi; MacSweeney, Mairéad; Boyles, Rowan; Waters, Dafydd; Watkins, Kate E; Möttönen, Riikka

2013-07-01

It is possible to comprehend speech and discriminate languages by viewing a speaker's articulatory movements. Transcranial magnetic stimulation studies have shown that viewing speech enhances excitability in the articulatory motor cortex. Here, we investigated the specificity of this enhanced motor excitability in native and non-native speakers of English. Both groups were able to discriminate between speech movements related to a known (i.e., English) and unknown (i.e., Hebrew) language. The motor excitability was higher during observation of a known language than an unknown language or non-speech mouth movements, suggesting that motor resonance is enhanced specifically during observation of mouth movements that convey linguistic information. Surprisingly, however, the excitability was equally high during observation of a static face. Moreover, the motor excitability did not differ between native and non-native speakers. These findings suggest that the articulatory motor cortex processes several kinds of visual cues during speech communication. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Violent Deaths of Iraqi Civilians, 2003–2008: Analysis by Perpetrator, Weapon, Time, and Location

PubMed Central

Hicks, Madelyn Hsiao-Rei; Dardagan, Hamit; Guerrero Serdán, Gabriela; Bagnall, Peter M.; Sloboda, John A.; Spagat, Michael

2011-01-01

Background Armed violence is a major public health and humanitarian problem in Iraq. In this descriptive statistical analysis we aimed to describe for the first time Iraqi civilian deaths caused by perpetrators of armed violence during the first 5 years of the Iraq war: over time; by weapon used; by region (governorate); and by victim demographics. Methods and Findings We analyzed the Iraq Body Count database of 92,614 Iraqi civilian direct deaths from armed violence occurring from March 20, 2003 through March 19, 2008, of which Unknown perpetrators caused 74% of deaths (n = 68,396), Coalition forces 12% (n = 11,516), and Anti-Coalition forces 11% (n = 9,954). We analyzed the subset of 60,481 civilian deaths from 14,196 short-duration events of lethal violence to link individual civilian deaths to events involving perpetrators and their methods. One-third of civilian violent death was from extrajudicial executions by Unknown perpetrators; quadratic regression shows these deaths progressively and disproportionately increased as deaths from other forms of violence increased across Iraq's governorates. The highest average number of civilians killed per event in which a civilian died were in Unknown perpetrator suicide bombings targeting civilians (19 per lethal event) and Coalition aerial bombings (17 per lethal event). In temporal analysis, numbers of civilian deaths from Coalition air attacks, and woman and child deaths from Coalition forces, peaked during the invasion. We applied a Woman and Child “Dirty War Index” (DWI), measuring the proportion of women and children among civilian deaths of known demographic status, to the 22,066 civilian victims identified as men, women, or children to indicate relatively indiscriminate perpetrator effects. DWI findings suggest the most indiscriminate effects on women and children were from Unknown perpetrators using mortar fire (DWI  = 79) and nonsuicide vehicle bombs (DWI  = 54) and from Coalition air attacks (DWI  = 69). Coalition forces had higher Woman and Child DWIs than Anti-Coalition forces, with no evidence of decrease over 2003–2008, for all weapons combined and for small arms gunfire, specifically. Conclusions Most Iraqi civilian violent deaths during 2003–2008 of the Iraq war were inflicted by Unknown perpetrators, primarily through extrajudicial executions that disproportionately increased in regions with greater numbers of violent deaths. Unknown perpetrators using suicide bombs, vehicle bombs, and mortars had highly lethal and indiscriminate effects on the Iraqi civilians they targeted. Deaths caused by Coalition forces of Iraqi civilians, women, and children peaked during the invasion period, with relatively indiscriminate effects from aerial weapons. Please see later in the article for the Editors' Summary PMID:21358813

Thermoregulatory and Immune Responses During Cold Exposure: Effects of Repeated Cold Exposure and Acute Exercise

DTIC Science & Technology

2000-03-01

shivering thermogenesis and vasoconstriction) during cold exposure is unknown. Thus, a series of experiments were executed to determine if serial cold ...to cold exposure? The results of these studies suggest that 1) serial cold water blunts shivering leadmg™ower core temperatures, 2) thermoregulatory...fatigues (i.e., causes blunted shivering thermogenesis and vasoconstriction) during cold exposure is unknown. Thus, a series of experiments were

ERP profiles for face and word recognition are based on their status in semantic memory not their stimulus category.

PubMed

Nie, Aiqing; Griffin, Michael; Keinath, Alexander; Walsh, Matthew; Dittmann, Andrea; Reder, Lynne

2014-04-04

Previous research has suggested that faces and words are processed and remembered differently as reflected by different ERP patterns for the two types of stimuli. Specifically, face stimuli produced greater late positive deflections for old items in anterior compared to posterior regions, while word stimuli produced greater late positive deflections in posterior compared to anterior regions. Given that words have existing representations in subjects׳ long-term memories (LTM) and that face stimuli used in prior experiments were of unknown individuals, we conducted an ERP study that crossed face and letter stimuli with the presence or absence of a prior (stable or existing) memory representation. During encoding, subjects judged whether stimuli were known (famous face or real word) or not known (unknown person or pseudo-word). A surprise recognition memory test required subjects to distinguish between stimuli that appeared during the encoding phase and stimuli that did not. ERP results were consistent with previous research when comparing unknown faces and words; however, the late ERP pattern for famous faces was more similar to that for words than for unknown faces. This suggests that the critical ERP difference is mediated by whether there is a prior representation in LTM, and not whether the stimulus involves letters or faces. Published by Elsevier B.V.

Presence of virulent Newcastle disease virus in vaccinated chickens in farms in Pakistan

USDA-ARS?s Scientific Manuscript database

The sites where virulent Newcastle disease virus persists in endemic countries are unknown. Evidence presented here shows that the same strain that caused a previous outbreak was present in both apparently healthy and sick vaccinated birds from multiple farms that had high average specific antibody...

Unconscious Evaluation of Faces on Social Dimensions

ERIC Educational Resources Information Center

Stewart, Lorna H.; Ajina, Sara; Getov, Spas; Bahrami, Bahador; Todorov, Alexander; Rees, Geraint

2012-01-01

It has been proposed that two major axes, dominance and trustworthiness, characterize the social dimensions of face evaluation. Whether evaluation of faces on these social dimensions is restricted to conscious appraisal or happens at a preconscious level is unknown. Here we provide behavioral evidence that such preconscious evaluations exist and…

Toward Diagnostic and Phenotype Markers for Genetically Transmitted Speech Delay

ERIC Educational Resources Information Center

Shriberg, Lawrence D.; Lewis, Barbara A.; Tomblin, J. Bruce; McSweeny, Jane L.; Karlsson, Heather B.; Scheer, Alison R.

2005-01-01

Converging evidence supports the hypothesis that the most common subtype of childhood speech sound disorder (SSD) of currently unknown origin is genetically transmitted. We report the first findings toward a set of diagnostic markers to differentiate this proposed etiological subtype (provisionally termed "speech delay-genetic") from other…

Enhanced Left Frontal Involvement during Novel Metaphor Comprehension in Schizophrenia: Evidence from Functional Neuroimaging

ERIC Educational Resources Information Center

Mashal, N.; Vishne, T.; Laor, N.; Titone, D.

2013-01-01

The neural basis involved in novel metaphor comprehension in schizophrenia is relatively unknown. Fourteen people with schizophrenia and fourteen controls were scanned while they silently read novel metaphors, conventional metaphors, literal expressions, and meaningless word-pairs. People with schizophrenia showed reduced comprehension of both…

Quantitative Relationships Involving Additive Differences: Numerical Resilience

ERIC Educational Resources Information Center

Ramful, Ajay; Ho, Siew Yin

2014-01-01

This case study describes the ways in which problems involving additive differences with unknown starting quantities, constrain the problem solver in articulating the inherent quantitative relationship. It gives empirical evidence to show how numerical reasoning takes over as a Grade 6 student instantiates the quantitative relation by resorting to…

Everyday Cognitive Failures and Memory Problems in Parkinson's Patients without Dementia

ERIC Educational Resources Information Center

Poliakoff, Ellen; Smith-Spark, James H.

2008-01-01

There is growing evidence that Parkinson's disease patients without dementia exhibit cognitive deficits in some executive, memory and selective attention tasks. However, the impact of these deficits on their everyday cognitive functioning remains largely unknown. This issue was explored using self-report questionnaires. Twenty-four Parkinson's…

Striatal Sensitivity during Reward Processing in Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Paloyelis, Yannis; Mehta, Mitul A.; Faraone, Stephen V.; Asherson, Philip; Kuntsi, Jonna

2012-01-01

Objective: Attention-deficit/hyperactivity disorder (ADHD) has been linked to deficits in the dopaminergic reward-processing circuitry; yet, existing evidence is limited, and the influence of genetic variation affecting dopamine signaling remains unknown. We investigated striatal responsivity to rewards in ADHD combined type (ADHD-CT) using…

Skin testing for immediate hypersensitivity to corticosteroids: a case series and literature review.

PubMed

Baker, A; Empson, M; The, R; Fitzharris, P

2015-03-01

Immediate hypersensitivity to corticosteroids is reported to occur with an incidence of 0.1%. The largest previous case series reporting corticosteroid skin testing has seven patients. We identified 23 patients (mean age 50 years, 65% female) from Auckland City Hospital who underwent skin testing (ST) for suspected corticosteroid hypersensitivity between July 2005 and April 2012. We performed a retrospective clinical case note review detailing clinical history of reaction, skin test results and subsequent management. Most patients (21/23) had a standard panel of testing with prednisolone, triamcinolone, methylprednisolone, hydrocortisone and dexamethasone. Skin tests used a 10% steroid stock concentration for skin prick tests (SPT) and dilutions of 1 : 1000, 1 : 100 and 1 : 10 for subsequent intradermal testing. A weal 3 mm greater than the negative control was considered positive. A total of 23 patients were identified who had skin testing for suspected acute hypersensitivity to corticosteroids, eight of which had a history of anaphylaxis. From 28 reactions (in 23 patients), the most common route of administration was intra-articular (13), followed by oral (7), intravenous (3) and other (5). Skin tests were positive in 8/23 patients, and 7/8 of these patients had a history of corticosteroid-associated anaphylaxis. Skin tests were positive at either the skin prick test or intradermal stages. There was evidence suggesting clinical and skin test cross-reactivity between corticosteroids in one patient. One patient had a positive skin test, but negative oral challenge suggesting the skin test was false positive. Skin tests were negative in 15/23 patients. One patient had a negative prednisolone skin test and positive unblinded oral challenge, suggesting a false-negative skin test. Skin testing can provide sufficient evidence to diagnose allergy in patients with a clear history of immediate hypersensitivity to corticosteroids such as anaphylaxis. Both skin prick and intradermal tests should be used. There is evidence of cross-reactivity between steroids, so a panel is recommended. False-positive and false-negative reactions do occur; however, the frequency is unknown. Challenge remains the only definitive way to demonstrate a safe alternative to use. As the largest case series described, this article provides new evidence for the interpretation of skin tests when investigating possible immediate hypersensitivity to corticosteroids. © 2014 John Wiley & Sons Ltd.

An assessment of the information content of likelihood ratios derived from complex mixtures.

PubMed

Marsden, Clare D; Rudin, Norah; Inman, Keith; Lohmueller, Kirk E

2016-05-01

With the increasing sensitivity of DNA typing methodologies, as well as increasing awareness by law enforcement of the perceived capabilities of DNA typing, complex mixtures consisting of DNA from two or more contributors are increasingly being encountered. However, insufficient research has been conducted to characterize the ability to distinguish a true contributor (TC) from a known non-contributor (KNC) in these complex samples, and under what specific conditions. In order to investigate this question, sets of six 15-locus Caucasian genotype profiles were simulated and used to create mixtures containing 2-5 contributors. Likelihood ratios were computed for various situations, including varying numbers of contributors and unknowns in the evidence profile, as well as comparisons of the evidence profile to TCs and KNCs. This work was intended to illustrate the best-case scenario, in which all alleles from the TC were detected in the simulated evidence samples. Therefore the possibility of drop-out was not modeled in this study. The computer program DNAMIX was then used to compute LRs comparing the evidence profile to TCs and KNCs. This resulted in 140,000 LRs for each of the two scenarios. These complex mixture simulations show that, even when all alleles are detected (i.e. no drop-out), TCs can generate LRs less than 1 across a 15-locus profile. However, this outcome was rare, 7 of 140,000 replicates (0.005%), and associated only with mixtures comprising 5 contributors in which the numerator hypothesis includes one or more unknown contributors. For KNCs, LRs were found to be greater than 1 in a small number of replicates (75 of 140,000 replicates, or 0.05%). These replicates were limited to 4 and 5 person mixtures with 1 or more unknowns in the numerator. Only 5 of these 75 replicates (0.004%) yielded an LR greater than 1,000. Thus, overall, these results imply that the weight of evidence that can be derived from complex mixtures containing up to 5 contributors, under a scenario in which no drop-out is required to explain any of the contributors, is remarkably high. This is a useful benchmark result on top of which to layer the effects of additional factors, such as drop-out, peak height, and other variables. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Online security and cyberbystander relations in mobilizing sex abuse intervention.

PubMed

Palasinski, Marek

2012-10-01

Two studies examined men's interventions in a virtual reality situation involving child grooming. In Study 1, 92 men observed an online encounter between an apparent minor and a sex offender. The results suggest that the bystander effect was stronger under computerized rather than user-assisted surveillance, and when the fellow cyberbystander was unknown rather than known. In Study 2, where 100 men observed the same encounter, the effect also emerged under computerized surveillance as long as the number unknown cyberbystanders was increased. Thus, vesting more responsibility for security in the average netizen rather than just in the automated abuse-detection technology is cautiously suggested, the relevance of which lies in increasing minors' health and safety.

High glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR.

PubMed

Han, Liang; Ma, Qingyong; Li, Junhui; Liu, Han; Li, Wei; Ma, Guodong; Xu, Qinhong; Zhou, Shuang; Wu, Erxi

2011-01-01

Multiple lines of evidence suggest that a large portion of pancreatic cancer patients suffer from either hyperglycemia or diabetes, both of which are characterized by high blood glucose level. However, the underlying biological mechanism of this phenomenon is largely unknown. In the present study, we demonstrated that the proliferative ability of two human pancreatic cancer cell lines, BxPC-3 and Panc-1, was upregulated by high glucose in a concentration-dependent manner. Furthermore, the promoting effect of high glucose levels on EGF transcription and secretion but not its receptors in these PC cell lines was detected by using an EGF-neutralizing antibody and RT-PCR. In addition, the EGFR transactivation is induced by high glucose levels in concentration- and time-dependent manners in PC cells in the presence of the EGF-neutralizing antibody. These results suggest that high glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR. Our findings may provide new insight on the links between high glucose level and PC in terms of the molecular mechanism and reveal a novel therapeutic strategy for PC patients who simultaneously suffer from either diabetes or hyperglycemia.

Prognostic Effect of Low Subcutaneous Adipose Tissue on Survival Outcome in Patients With Multiple Myeloma.

PubMed

Takeoka, Yasunobu; Sakatoku, Kazuki; Miura, Akiko; Yamamura, Ryosuke; Araki, Taku; Seura, Hirotaka; Okamura, Terue; Koh, Hideo; Nakamae, Hirohisa; Hino, Masayuki; Ohta, Kensuke

2016-08-01

Increasing evidence suggests that decreased skeletal muscle mass (sarcopenia) or adipose tissue assessed using computed tomography (CT) predicts negative outcomes in patients with solid tumors. However, the prognostic value of such an assessment in multiple myeloma (MM) remains unknown. Consecutive patients with newly diagnosed symptomatic MM were retrospectively analyzed. The cross-sectional area of skeletal muscles and subcutaneous or visceral adipose tissue was measured using CT. Body composition indexes (skeletal muscle index, subcutaneous adipose tissue index [SAI], and visceral adipose tissue index) were calculated. The association between these indexes and overall survival (OS) was examined. Of 56 evaluable patients, 37 (66%) had sarcopenia. The 2-year OS in patients with SAI < median was 58% compared with 91% in those with SAI ≥ median (P = .006). In multivariate analyses, SAI < median was significantly associated with poor OS (hazard ratio, 4.05; P = .02). Sarcopenia was not associated with OS. The maximum value of the standardized uptake value was significantly higher in patients with SAI < median (P = .02). The findings of this study suggest that low subcutaneous adipose tissue at baseline predicts poor survival outcome in patients with MM. Copyright © 2016 Elsevier Inc. All rights reserved.

Association between toll-like receptors expression and major depressive disorder.

PubMed

Hung, Yi-Yung; Kang, Hong-Yo; Huang, Kai-Wei; Huang, Tiao-Lai

2014-12-15

Accumulating evidences suggest that Toll-like receptors (TLRs) were involved in the pathophysiology of major depressive disorder. TLR4 was thought to be associated with major depressive disorder in animal model, but the others were still unknown. In order to examine TLR1-9 mRNA expression levels in peripheral blood and their relationships with the psychopathology of major depressive disorder, 30 patients with major depressive disorder were compared with 29 healthy controls. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to assess the severity of major depression. The mRNA expression levels of TLRs were examined in parallel with a housekeeping gene using real-time polymerase chain reaction (RT-PCR). Analysis of covariance with age and body mass index adjustment revealed a significantly higher expression of TLR3, 4, 5 and 7 mRNA but lower expression of TLR1 and 6 in patients with major depressive disorder as compared with healthy controls. Multiple linear regression analysis revealed that TLR4 was an independent risk factor relating to severity of major depression. These findings suggest that TLRs, especially TLR4, may be involved in the psychopathology of major depression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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.

The cost of selective attention in category learning: Developmental differences between adults and infants

PubMed Central

Best, Catherine A.; Yim, Hyungwook; Sloutsky, Vladimir M.

2013-01-01

Selective attention plays an important role in category learning. However, immaturities of top-down attentional control during infancy coupled with successful category learning suggest that early category learning is achieved without attending selectively. Research presented here examines this possibility by focusing on category learning in infants (6–8 months old) and adults. Participants were trained on a novel visual category. Halfway through the experiment, unbeknownst to participants, the to-be-learned category switched to another category, where previously relevant features became irrelevant and previously irrelevant features became relevant. If participants attend selectively to the relevant features of the first category, they should incur a cost of selective attention immediately after the unknown category switch. Results revealed that adults demonstrated a cost, as evidenced by a decrease in accuracy and response time on test trials as well as a decrease in visual attention to newly relevant features. In contrast, infants did not demonstrate a similar cost of selective attention as adults despite evidence of learning both to-be-learned categories. Findings are discussed as supporting multiple systems of category learning and as suggesting that learning mechanisms engaged by adults may be different from those engaged by infants. PMID:23773914

[Bartonella henselae vertebral osteomyelitis: report of a case].

PubMed

Juan Zepeda, T; Jorge Morales, S; Hugo Letelier, A; Luis Delpiano, M

2016-01-01

Cat scratch disease (CSD) is caused by Bartonella henselae, with unknown prevalence and incidence in the Chilean paediatric population. Regional lymphadenopathy is the most common presentation, while atypical forms constitute a diagnostic challenge. To report a case of CSD with osteomyelitis and present guidelines regarding treatment. An eight year-old patient, with prolonged febrile illness, back pain and neck stiffness. Laboratory studies highlight positive IgG for Bartonella henselae. The abdominal ultrasound showed splenic micro-abscesses, and the MRI showing vertebral lesions suggestive of osteomyelitis. The diagnosis of atypical forms requires a high rate of suspicion, as in this case, in which the patient manifested the musculoskeletal symptoms simultaneously with the febrile syndrome, which led us to study possible complications of the disease. Current knowledge of the treatment of atypical or complicated CSD is derived from the observation of case studies, rather than randomized trials. It is suggested that antibiotic therapy is analysed individually, with the help of a specialist. The importance of high clinical suspicion are emphasised and discussed, as well presenting some treatment options based on the evidence from the current literature. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Potential Role of Aminoprocalcitonin in the Pathogenesis of Alzheimer Disease.

PubMed

Tavares, Eva; Antequera, Desiree; López-González, Irene; Ferrer, Isidro; Miñano, Francisco J; Carro, Eva

2016-10-01

Increasing evidence suggests that inflammatory responses cause brain atrophy and play a prominent and early role in the progression of Alzheimer disease. Recent findings show that the neuroendocrine peptide aminoprocalcitonin (NPCT) plays a critical role in the development of systemic inflammatory response; however, the presence, possible function, regulation, and mechanisms by which NPCT may be involved in Alzheimer disease neuropathology remain unknown. We explored the expression of NPCT and its interaction with amyloid-β (Aβ), and proinflammatory and neurogenic effects. By using brain samples of Alzheimer disease patients and APP/PS1 transgenic mice, we evaluated the potential role of NPCT on Aβ-related pathology. We found that NPCT is expressed in hippocampal and cortical neurons and Aβ-induced up-regulation of NPCT expression. Peripherally administered antibodies against NPCT decreased microglial activation, decreased circulating levels of proinflammatory cytokines, and prevented Aβ-induced neurotoxicity in experimental models of Alzheimer disease. Remarkably, anti-NPTC therapy resulted in a significant improvement in the behavioral status of APP/PS1 mice. Our results indicate a central role of NPCT in Alzheimer disease pathogenesis and suggest NPCT as a potential biomarker and therapeutic target. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Worlds and Anti-worlds Revisted

NASA Astrophysics Data System (ADS)

Wolff, Milo

1996-05-01

In =D2Worlds and Anti-worlds=D3 (1960) Hannes Alfven=20 described a universe symmetric in matter and anti-matter. Today we cannot decide if galaxies and anti-galaxies exist because radiation from both=20 is alike. If matter attracts anti-matter by gravity, intense annihilation= =20 radiation is expected. Since this is not observed, cosmologists concluded the universe is un-symmetrical and tailored the big-bang accordingly. But there is another possibility. The anti-symmetry of particles and anti-particles, suggests repulsive gravity. The rarity of anti-matter and the weakness of gravity makes tesing difficult. But indeed if it is repulsive, galaxies and anti-galaxies would separate and the annihilation radiation would be small as observed. A first guess is 50-50 that anti-gravity exists but there is other evidence: Gamma-ray bursts observed by NASA satellites, solar anti-neutrino flux, and a proposed wave-structure of the electron: =D2Exploring the Physics of the Unknown Universe=D3(1991), ISBN 0-9627787-0-2, suggest that anti-gravity may exist. If true, expect a rush back to the drawing board to revise the expansion and structure of the universe.

Delaying Onset of Dementia: Are Two Languages Enough?

PubMed Central

Freedman, Morris; Alladi, Suvarna; Chertkow, Howard; Bialystok, Ellen; Craik, Fergus I. M.; Phillips, Natalie A.; Duggirala, Vasanta; Raju, Surampudi Bapi; Bak, Thomas H.

2014-01-01

There is an emerging literature suggesting that speaking two or more languages may significantly delay the onset of dementia. Although the mechanisms are unknown, it has been suggested that these may involve cognitive reserve, a concept that has been associated with factors such as higher levels of education, occupational status, social networks, and physical exercise. In the case of bilingualism, cognitive reserve may involve reorganization and strengthening of neural networks that enhance executive control. We review evidence for protective effects of bilingualism from a multicultural perspective involving studies in Toronto and Montreal, Canada, and Hyderabad, India. Reports from Toronto and Hyderabad showed a significant effect of speaking two or more languages in delaying onset of Alzheimer's disease by up to 5 years, whereas the Montreal study showed a significant protective effect of speaking at least four languages and a protective effect of speaking at least two languages in immigrants. Although there were differences in results across studies, a common theme was the significant effect of language use history as one of the factors in determining the onset of Alzheimer's disease. Moreover, the Hyderabad study extended the findings to frontotemporal dementia and vascular dementia. PMID:24959001

Economic principles motivating social attention in humans.

PubMed

Hayden, Benjamin Y; Parikh, Purak C; Deaner, Robert O; Platt, Michael L

2007-07-22

We know little about the processes by which we evaluate the opportunity to look at another person. We propose that behavioural economics provides a powerful approach to understanding this basic aspect of social attention. We hypothesized that the decision process culminating in attention to another person follows the same economic principles that govern choices about rewards such as food, drinks and money. Specifically, such rewards are discounted as a function of time, are tradable for other rewards, and reinforce work. Behavioural and neurobiological evidence suggests that looking at other people can also be described as rewarding, but to what extent these economic principles apply to social orienting remains unknown. Here, we show that the opportunity to view pictures of the opposite sex is discounted by delay to viewing, substitutes for money and reinforces work. The reward value of photos of the opposite sex varied with physical attractiveness and was greater in men, suggesting differential utility of acquiring visual information about the opposite sex in men and women. Together, these results demonstrate that choosing whom to look at follows a general set of economic principles, implicating shared neural mechanisms in both social and non-social decision making.

Mechanical evidence that flamingos can support their body on one leg with little active muscular force.

PubMed

Chang, Young-Hui; Ting, Lena H

2017-05-01

Flamingos (Phoenicopteridae) often stand and sleep on one leg for long periods, but it is unknown how much active muscle contractile force they use for the mechanical demands of standing on one leg: body weight support and maintaining balance. First, we demonstrated that flamingo cadavers could passively support body weight on one leg without any muscle activity while adopting a stable, unchanging, joint posture resembling that seen in live flamingos. By contrast, the cadaveric flamingo could not be stably held in a two-legged pose, suggesting a greater necessity for active muscle force to stabilize two-legged versus one-legged postures. Our results suggest that flamingos engage a passively engaged gravitational stay apparatus (proximally located) for weight support during one-legged standing. Second, we discovered that live flamingos standing on one leg have markedly reduced body sway during quiescent versus alert behaviours, with the point of force application directly under the distal joint, reducing the need for muscular joint torque. Taken together, our results highlight the possibility that flamingos stand for long durations on one leg without exacting high muscular forces and, thus, with little energetic expenditure. © 2017 The Author(s).

Truncated hexa-octahedral magnetite crystals in ALH84001: Presumptive biosignatures

PubMed Central

Thomas-Keprta, Kathie L.; Clemett, Simon J.; Bazylinski, Dennis A.; Kirschvink, Joseph L.; McKay, David S.; Wentworth, Susan J.; Vali, Hojatollah; Gibson, Everett K.; McKay, Mary Fae; Romanek, Christopher S.

2001-01-01

McKay et al. [(1996) Science 273, 924–930] suggested that carbonate globules in the meteorite ALH84001 contained the fossil remains of Martian microbes. We have characterized a subpopulation of magnetite (Fe3O4) crystals present in abundance within the Fe-rich rims of these carbonate globules. We find these Martian magnetites to be both chemically and physically identical to terrestrial, biogenically precipitated, intracellular magnetites produced by magnetotactic bacteria strain MV-1. Specifically, both magnetite populations are single-domain and chemically pure, and exhibit a unique crystal habit we describe as truncated hexa-octahedral. There are no known reports of inorganic processes to explain the observation of truncated hexa-octahedral magnetites in a terrestrial sample. In bacteria strain MV-1 their presence is therefore likely a product of Natural Selection. Unless there is an unknown and unexplained inorganic process on Mars that is conspicuously absent on the Earth and forms truncated hexa-octahedral magnetites, we suggest that these magnetite crystals in the Martian meteorite ALH84001 were likely produced by a biogenic process. As such, these crystals are interpreted as Martian magnetofossils and constitute evidence of the oldest life yet found. PMID:11226210

Virgin queen attraction toward males in honey bees.

PubMed

Bastin, Florian; Cholé, Hanna; Lafon, Grégory; Sandoz, Jean-Christophe

2017-07-24

Although the honeybee is a crucial agricultural agent and a prominent scientific model organism, crucial aspects of its reproductive behaviour are still unknown. During the mating season, honeybee males, the drones, gather in congregations 10-40 m above ground. Converging evidence suggests that drones emit a pheromone that can attract other drones, thereby increasing the size of the congregation. Virgin queens join the vicinity of the congregation after it has formed, and mate with as many as 20 males in mid-air. It is still unclear which sensory cues help virgin queens find drone congregations in the first place. Beside visual cues for long-range orientation, queens may use olfactory cues. We thus tested virgin queens' olfactory orientation on a walking simulator in which they have full control over odour stimulation. We show that sexually-mature virgin queens are attracted to the odour bouquet from a group of living drones. They are not attracted to the bouquet from a group of workers. In addition, non-sexually receptive females (workers) of the same age are not attracted to the drone odour bouquet. Interpreted in the context of mating, these results may suggest that virgin queens use volatile olfactory cues from the drones to find the congregations.

Disturbed vesicular trafficking of membrane proteins in prion disease.

PubMed

Uchiyama, Keiji; Miyata, Hironori; Sakaguchi, Suehiro

2013-01-01

The pathogenic mechanism of prion diseases remains unknown. We recently reported that prion infection disturbs post-Golgi trafficking of certain types of membrane proteins to the cell surface, resulting in reduced surface expression of membrane proteins and abrogating the signal from the proteins. The surface expression of the membrane proteins was reduced in the brains of mice inoculated with prions, well before abnormal symptoms became evident. Prions or pathogenic prion proteins were mainly detected in endosomal compartments, being particularly abundant in recycling endosomes. Some newly synthesized membrane proteins are delivered to the surface from the Golgi apparatus through recycling endosomes, and some endocytosed membrane proteins are delivered back to the surface through recycling endosomes. These results suggest that prions might cause neuronal dysfunctions and cell loss by disturbing post-Golgi trafficking of membrane proteins via accumulation in recycling endosomes. Interestingly, it was recently shown that delivery of a calcium channel protein to the cell surface was impaired and its function was abrogated in a mouse model of hereditary prion disease. Taken together, these results suggest that impaired delivery of membrane proteins to the cell surface is a common pathogenic event in acquired and hereditary prion diseases.

Truncated hexa-octahedral magnetite crystals in ALH84001: presumptive biosignatures

NASA Technical Reports Server (NTRS)

Thomas-Keprta, K. L.; Clemett, S. J.; Bazylinski, D. A.; Kirschvink, J. L.; McKay, D. S.; Wentworth, S. J.; Vali, H.; Gibson, E. K. Jr; McKay, M. F.; Romanek, C. S.

2001-01-01

McKay et al. [(1996) Science 273, 924-930] suggested that carbonate globules in the meteorite ALH84001 contained the fossil remains of Martian microbes. We have characterized a subpopulation of magnetite (Fe(3)O(4)) crystals present in abundance within the Fe-rich rims of these carbonate globules. We find these Martian magnetites to be both chemically and physically identical to terrestrial, biogenically precipitated, intracellular magnetites produced by magnetotactic bacteria strain MV-1. Specifically, both magnetite populations are single-domain and chemically pure, and exhibit a unique crystal habit we describe as truncated hexa-octahedral. There are no known reports of inorganic processes to explain the observation of truncated hexa-octahedral magnetites in a terrestrial sample. In bacteria strain MV-1 their presence is therefore likely a product of Natural Selection. Unless there is an unknown and unexplained inorganic process on Mars that is conspicuously absent on the Earth and forms truncated hexa-octahedral magnetites, we suggest that these magnetite crystals in the Martian meteorite ALH84001 were likely produced by a biogenic process. As such, these crystals are interpreted as Martian magnetofossils and constitute evidence of the oldest life yet found.

Pseudotachylyte increases the post-slip strength of faults

USGS Publications Warehouse

Proctor, Brooks; Lockner, David A.

2016-01-01

Solidified frictional melts, or pseudotachylytes, are observed in exhumed faults from across the seismogenic zone. These unique fault rocks, and many experimental studies, suggest that frictional melting can be an important process during earthquakes. However, it remains unknown how melting affects the post-slip strength of the fault and why many exhumed faults do not contain pseudotachylyte. Analyses of triaxial stick-slip events on Westerly Granite (Rhode Island, USA) sawcuts at confining pressures from 50 to 400 MPa show evidence for frictional heating, including some events energetic enough to generate surface melt. Total and partial stress drops were observed with slip as high as 6.5 mm. We find that in dry samples following melt-producing stick slip, the shear failure strength increased as much as 50 MPa, while wet samples had <10 MPa strengthening. Microstructural analysis indicates that the strengthening is caused by welding of the slip surface during melt quenching, suggesting that natural pseudotachylytes may also strengthen faults after earthquakes. These results predict that natural pseudotachylyte will inhibit slip reactivation and possibly generate stress heterogeneities along faults. Wet samples do not exhibit melt welding, possibly because of thermal pressurization of water reducing frictional heating during slip.

A mitocentric view of Alzheimer's disease suggests multi-faceted treatments.

PubMed

Gibson, Gary E; Shi, Qingli

2010-01-01

Alzheimer's disease (AD) is defined by senile plaques made of amyloid-beta peptide (Abeta), neurofibrillary tangles made of hyperphosphorylated tau proteins, and memory deficits. Thus, the events initiating the cascade leading to these end points may be more effective therapeutic targets than treating each facet individually. In the small percentage of cases of AD that are genetic (or animal models that reflect this form of AD), the factor initiating AD is clear (e.g., genetic mutations lead to high Abeta1-42 or hyperphosphorylated tau proteins). In the vast majority of AD cases, the cause is unknown. Substantial evidence now suggests that abnormalities in glucose metabolism/mitochondrial function/oxidative stress (GMO) are an invariant feature of AD and occur at an early stage of the disease process in both genetic and non-genetic forms of AD. Indeed, decreases in brain glucose utilization are diagnostic for AD. Changes in calcium homeostasis also precede clinical manifestations of AD. Abnormal GMO can lead to plaques, tangles, and the calcium abnormalities that accompany AD. Abnormalities in GMO diminish the ability of the brain to adapt. Therapies targeting mitochondria may ameliorate abnormalities in plaques, tangles, calcium homeostasis, and cognition that comprise AD.

Endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1.

PubMed

Abán, C; Martinez, N; Carou, C; Albamonte, I; Toro, A; Seyahian, A; Franchi, A; Leguizamón, G; Trigubo, D; Damiano, A; Farina, M

2016-10-01

During pregnancy, apoptosis is a physiological event critical in the remodeling and aging of the placenta. Increasing evidence has pointed towards the relevance of endocannabinoids (ECs) and hypoxia as modulators of trophoblast cell death. However, the relation between these factors is still unknown. In this report, we evaluated the participation of ECs in placental apoptosis induced by cobalt chloride (CoCl2), a hypoxia mimicking agent that stabilizes the expression of hypoxia inducible factor-1 alpha (HIF-1α). We found that HIF-1α stabilization decreased FAAH mRNA and protein levels, suggesting an increase in ECs tone. Additionally, CoCl2 incubation and Met-AEA treatment reduced cell viability and increased TUNEL-positive staining in syncytiotrophoblast layer. Immunohistochemical analysis demonstrated Bax and Bcl-2 protein expression in the cytoplasm of syncytiotrophoblast. Finally, HIF-1α stabilization produced an increase in Bax/Bcl-2 ratio, activation of caspase 3 and PARP cleavage. All these changes in apoptotic parameters were reversed with AM251, a CB1 antagonist. These results demonstrate that HIF-1α may induce apoptosis in human placenta via intrinsic pathway by a mechanism that involves activation of CB1 receptor suggesting a role of the ECs in this process.

Delaying onset of dementia: are two languages enough?

PubMed

Freedman, Morris; Alladi, Suvarna; Chertkow, Howard; Bialystok, Ellen; Craik, Fergus I M; Phillips, Natalie A; Duggirala, Vasanta; Raju, Surampudi Bapi; Bak, Thomas H

2014-01-01

There is an emerging literature suggesting that speaking two or more languages may significantly delay the onset of dementia. Although the mechanisms are unknown, it has been suggested that these may involve cognitive reserve, a concept that has been associated with factors such as higher levels of education, occupational status, social networks, and physical exercise. In the case of bilingualism, cognitive reserve may involve reorganization and strengthening of neural networks that enhance executive control. We review evidence for protective effects of bilingualism from a multicultural perspective involving studies in Toronto and Montreal, Canada, and Hyderabad, India. Reports from Toronto and Hyderabad showed a significant effect of speaking two or more languages in delaying onset of Alzheimer's disease by up to 5 years, whereas the Montreal study showed a significant protective effect of speaking at least four languages and a protective effect of speaking at least two languages in immigrants. Although there were differences in results across studies, a common theme was the significant effect of language use history as one of the factors in determining the onset of Alzheimer's disease. Moreover, the Hyderabad study extended the findings to frontotemporal dementia and vascular dementia.

Interactions between colour-producing mechanisms and their effects on the integumentary colour palette.

PubMed

Shawkey, Matthew D; D'Alba, Liliana

2017-07-05

Animal integumentary coloration plays a crucial role in visual communication and camouflage, and varies extensively among and within species and populations. To understand the pressures underlying such diversity, it is essential to elucidate the mechanisms by which animals have created novel integumentary coloration. Colours can be produced by selective absorption of light by skin pigments, through light scattering by structured or unstructured tissues, or by a combination of pigments and nanostructures. In this review, we highlight our current understanding of the interactions between pigments and structural integumentary tissues and molecules. We analyse the available evidence suggesting that these combined mechanisms are capable of creating colours and optical properties unachievable by either mechanism alone, thereby effectively expanding the animal colour palette. Moreover, structural and pigmentary colour mechanisms frequently interact in unexpected and overlooked ways, suggesting that classification of colours as being of any particular type may be difficult. Finally, we discuss how these mixtures are useful for investigating the largely unknown genetic, developmental and physical processes generating phenotypic diversity.This article is part of the themed issue 'Animal coloration: production, perception, function and application'. © 2017 The Author(s).

Phonological reduplication in sign language: Rules rule

PubMed Central

Berent, Iris; Dupuis, Amanda; Brentari, Diane

2014-01-01

Productivity—the hallmark of linguistic competence—is typically attributed to algebraic rules that support broad generalizations. Past research on spoken language has documented such generalizations in both adults and infants. But whether algebraic rules form part of the linguistic competence of signers remains unknown. To address this question, here we gauge the generalization afforded by American Sign Language (ASL). As a case study, we examine reduplication (X→XX)—a rule that, inter alia, generates ASL nouns from verbs. If signers encode this rule, then they should freely extend it to novel syllables, including ones with features that are unattested in ASL. And since reduplicated disyllables are preferred in ASL, such a rule should favor novel reduplicated signs. Novel reduplicated signs should thus be preferred to nonreduplicative controls (in rating), and consequently, such stimuli should also be harder to classify as nonsigns (in the lexical decision task). The results of four experiments support this prediction. These findings suggest that the phonological knowledge of signers includes powerful algebraic rules. The convergence between these conclusions and previous evidence for phonological rules in spoken language suggests that the architecture of the phonological mind is partly amodal. PMID:24959158

Comparative genomics of Eucalyptus and Corymbia reveals low rates of genome structural rearrangement.

PubMed

Butler, J B; Vaillancourt, R E; Potts, B M; Lee, D J; King, G J; Baten, A; Shepherd, M; Freeman, J S

2017-05-22

Previous studies suggest genome structure is largely conserved between Eucalyptus species. However, it is unknown if this conservation extends to more divergent eucalypt taxa. We performed comparative genomics between the eucalypt genera Eucalyptus and Corymbia. Our results will facilitate transfer of genomic information between these important taxa and provide further insights into the rate of structural change in tree genomes. We constructed three high density linkage maps for two Corymbia species (Corymbia citriodora subsp. variegata and Corymbia torelliana) which were used to compare genome structure between both species and Eucalyptus grandis. Genome structure was highly conserved between the Corymbia species. However, the comparison of Corymbia and E. grandis suggests large (from 1-13 MB) intra-chromosomal rearrangements have occurred on seven of the 11 chromosomes. Most rearrangements were supported through comparisons of the three independent Corymbia maps to the E. grandis genome sequence, and to other independently constructed Eucalyptus linkage maps. These are the first large scale chromosomal rearrangements discovered between eucalypts. Nonetheless, in the general context of plants, the genomic structure of the two genera was remarkably conserved; adding to a growing body of evidence that conservation of genome structure is common amongst woody angiosperms.

Quaking and PTB control overlapping splicing regulatory networks during muscle cell differentiation

PubMed Central

Hall, Megan P.; Nagel, Roland J.; Fagg, W. Samuel; Shiue, Lily; Cline, Melissa S.; Perriman, Rhonda J.; Donohue, John Paul; Ares, Manuel

2013-01-01

Alternative splicing contributes to muscle development, but a complete set of muscle-splicing factors and their combinatorial interactions are unknown. Previous work identified ACUAA (“STAR” motif) as an enriched intron sequence near muscle-specific alternative exons such as Capzb exon 9. Mass spectrometry of myoblast proteins selected by the Capzb exon 9 intron via RNA affinity chromatography identifies Quaking (QK), a protein known to regulate mRNA function through ACUAA motifs in 3′ UTRs. We find that QK promotes inclusion of Capzb exon 9 in opposition to repression by polypyrimidine tract-binding protein (PTB). QK depletion alters inclusion of 406 cassette exons whose adjacent intron sequences are also enriched in ACUAA motifs. During differentiation of myoblasts to myotubes, QK levels increase two- to threefold, suggesting a mechanism for QK-responsive exon regulation. Combined analysis of the PTB- and QK-splicing regulatory networks during myogenesis suggests that 39% of regulated exons are under the control of one or both of these splicing factors. This work provides the first evidence that QK is a global regulator of splicing during muscle development in vertebrates and shows how overlapping splicing regulatory networks contribute to gene expression programs during differentiation. PMID:23525800

A theoretical perspective on running-related injuries.

PubMed

Gallant, Jodi Lynn; Pierrynowski, Michael Raymond

2014-03-01

The etiology of running-related injuries remains unknown; however, an implicit theory underlies much of the conventional research and practice in the prevention of these injuries. This theory posits that the cause of running-related injuries lies in the high-impact forces experienced when the foot contacts the ground and the subsequent abnormal movement of the subtalar joint. The application of this theory is seen in the design of the modern running shoe, with cushioning, support, and motion control. However, a new theory is emerging that suggests that it is the use of these modern running shoes that has caused a maladaptive running style, which contributes to a high incidence of injury among runners. The suggested application of this theory is to cease use of the modern running shoe and transition to barefoot or minimalist running. This new running paradigm, which is at present inadequately defined, is proposed to avoid the adverse biomechanical effects of the modern running shoe. Future research should rigorously define and then test both theories regarding their ability to discover the etiology of running-related injury. Once discovered, the putative cause of running-related injury will then provide an evidence-based rationale for clinical prevention and treatment.

Drosophila Torsin Protein Regulates Motor Control and Stress Sensitivity and Forms a Complex with Fragile-X Mental Retardation Protein

PubMed Central

Ahn, Hyo-Min; Koh, Young Ho

2016-01-01

We investigated unknown in vivo functions of Torsin by using Drosophila as a model. Downregulation of Drosophila Torsin (DTor) by DTor-specific inhibitory double-stranded RNA (RNAi) induced abnormal locomotor behavior and increased susceptibility to H2O2. In addition, altered expression of DTor significantly increased the numbers of synaptic boutons. One important biochemical consequence of DTor-RNAi expression in fly brains was upregulation of alcohol dehydrogenase (ADH). Altered expression of ADH has also been reported in Drosophila Fragile-X mental retardation protein (DFMRP) mutant flies. Interestingly, expression of DFMRP was altered in DTor mutant flies, and DTor and DFMRP were present in the same protein complexes. In addition, DTor and DFMRP immunoreactivities were partially colocalized in several cellular organelles in larval muscles. Furthermore, there were no significant differences between synaptic morphologies of dfmrp null mutants and dfmrp mutants expressing DTor-RNAi. Taken together, our evidences suggested that DTor and DFMRP might be present in the same signaling pathway regulating synaptic plasticity. In addition, we also found that human Torsin1A and human FMRP were present in the same protein complexes, suggesting that this phenomenon is evolutionarily conserved. PMID:27313903

Formation and Degradation of Beta-casomorphins in Dairy Processing.

PubMed

Nguyen, Duc Doan; Johnson, Stuart Keith; Busetti, Francesco; Solah, Vicky Ann

2015-01-01

Milk proteins including casein are sources of peptides with bioactivity. One of these peptides is beta-casomorphin (BCM) which belongs to a group of opioid peptides formed from β-casein variants. Beta-casomorphin 7 (BCM7) has been demonstrated to be enzymatically released from the A1 or B β-casein variant. Epidemiological evidence suggests the peptide BCM 7 is a risk factor for development of human diseases, including increased risk of type 1 diabetes and cardiovascular diseases but this has not been thoroughly substantiated by research studies. High performance liquid chromatography coupled to UV-Vis and mass spectrometry detection as well as enzyme-linked immunosorbent assay (ELISA) has been used to analyze BCMs in dairy products. BCMs have been detected in raw cow's milk and human milk and a variety of commercial cheeses, but their presence has yet to be confirmed in commercial yoghurts. The finding that BCMs are present in cheese suggests they could also form in yoghurt, but be degraded during yoghurt processing. Whether BCMs do form in yoghurt and the amount of BCM forming or degrading at different processing steps needs further investigation and possibly will depend on the heat treatment and fermentation process used, but it remains an intriguing unknown.

Tracking fusion of human mesenchymal stem cells after transplantation to the heart.

PubMed

Freeman, Brian T; Kouris, Nicholas A; Ogle, Brenda M

2015-06-01

Evidence suggests that transplanted mesenchymal stem cells (MSCs) can aid recovery of damaged myocardium caused by myocardial infarction. One possible mechanism for MSC-mediated recovery is reprogramming after cell fusion between transplanted MSCs and recipient cardiac cells. We used a Cre/LoxP-based luciferase reporter system coupled to biophotonic imaging to detect fusion of transplanted human pluripotent stem cell-derived MSCs to cells of organs of living mice. Human MSCs, with transient expression of a viral fusogen, were delivered to the murine heart via a collagen patch. At 2 days and 1 week later, living mice were probed for bioluminescence indicative of cell fusion. Cell fusion was detected at the site of delivery (heart) and in distal tissues (i.e., stomach, small intestine, liver). Fusion was confirmed at the cellular scale via fluorescence in situ hybridization for human-specific and mouse-specific centromeres. Human cells in organs distal to the heart were typically located near the vasculature, suggesting MSCs and perhaps MSC fusion products have the ability to migrate via the circulatory system to distal organs and engraft with local cells. The present study reveals previously unknown migratory patterns of delivered human MSCs and associated fusion products in the healthy murine heart. The study also sets the stage for follow-on studies to determine the functional effects of cell fusion in a model of myocardial damage or disease. Mesenchymal stem cells (MSCs) are transplanted to the heart, cartilage, and other tissues to recover lost function or at least limit overactive immune responses. Analysis of tissues after MSC transplantation shows evidence of fusion between MSCs and the cells of the recipient. To date, the biologic implications of cell fusion remain unclear. A newly developed in vivo tracking system was used to identify MSC fusion products in living mice. The migratory patterns of fusion products were determined both in the target organ (i.e., the heart) and in distal organs. This study shows, for the first time, evidence of fusion products at sites distal from the target organ and data to suggest that migration occurs via the vasculature. These results will inform and improve future, MSC-based therapeutics. ©AlphaMed Press.

Early cranial ultrasound findings among infants with neonatal encephalopathy in Uganda: an observational study.

PubMed

Tann, Cally J; Nakakeeto, Margaret; Hagmann, Cornelia; Webb, Emily L; Nyombi, Natasha; Namiiro, Flaviah; Harvey-Jones, Kelly; Muhumuza, Anita; Burgoine, Kathy; Elliott, Alison M; Kurinczuk, Jennifer J; Robertson, Nicola J; Cowan, Frances M

2016-08-01

In sub-Saharan Africa, the timing and nature of brain injury and their relation to mortality in neonatal encephalopathy (NE) are unknown. We evaluated cranial ultrasound (cUS) scans from term Ugandan infants with and without NE for evidence of brain injury. Infants were recruited from a national referral hospital in Kampala. Cases (184) had NE and controls (100) were systematically selected unaffected term infants. All had cUS scans <36 h reported blind to NE status. Scans were performed at median age 11.5 (interquartile range (IQR): 5.2-20.2) and 8.4 (IQR: 3.6-13.5) hours, in cases and controls respectively. None had established antepartum injury. Major evolving injury was reported in 21.2% of the cases vs. 1.0% controls (P < 0.001). White matter injury was not significantly associated with bacteremia in encephalopathic infants (odds ratios (OR): 3.06 (95% confidence interval (CI): 0.98-9.60). Major cUS abnormality significantly increased the risk of neonatal death (case fatality 53.9% with brain injury vs. 25.9% without; OR: 3.34 (95% CI: 1.61-6.95)). In this low-resource setting, there was no evidence of established antepartum insult, but a high proportion of encephalopathic infants had evidence of major recent and evolving brain injury on early cUS imaging, suggesting prolonged or severe acute exposure to hypoxia-ischemia (HI). Early abnormalities were a significant predictor of death.

Early cranial ultrasound findings among infants with neonatal encephalopathy in Uganda: an observational study

PubMed Central

Tann, Cally J.; Nakakeeto, Margaret; Hagmann, Cornelia; Webb, Emily L.; Nyombi, Natasha; Namiiro, Flaviah; Harvey-Jones, Kelly; Muhumuza, Anita; Burgoine, Kathy; Elliott, Alison M.; Kurinczuk, Jennifer J.; Robertson, Nicola J.; Cowan, Frances M.

2016-01-01

Background: In sub-Saharan Africa, the timing and nature of brain injury and their relation to mortality in neonatal encephalopathy (NE) are unknown. We evaluated cranial ultrasound (cUS) scans from term Ugandan infants with and without NE for evidence of brain injury. Methods: Infants were recruited from a national referral hospital in Kampala. Cases (184) had NE and controls (100) were systematically selected unaffected term infants. All had cUS scans <36 h reported blind to NE status. Results: Scans were performed at median age 11.5 (interquartile range (IQR): 5.2–20.2) and 8.4 (IQR: 3.6–13.5) hours, in cases and controls respectively. None had established antepartum injury. Major evolving injury was reported in 21.2% of the cases vs. 1.0% controls (P < 0.001). White matter injury was not significantly associated with bacteremia in encephalopathic infants (odds ratios (OR): 3.06 (95% confidence interval (CI): 0.98–9.60). Major cUS abnormality significantly increased the risk of neonatal death (case fatality 53.9% with brain injury vs. 25.9% without; OR: 3.34 (95% CI: 1.61–6.95)). Conclusion: In this low-resource setting, there was no evidence of established antepartum insult, but a high proportion of encephalopathic infants had evidence of major recent and evolving brain injury on early cUS imaging, suggesting prolonged or severe acute exposure to hypoxia–ischemia (HI). Early abnormalities were a significant predictor of death. PMID:27064242

The knowns and unknowns of human milk banking.

PubMed

Simmer, Karen; Hartmann, Ben

2009-11-01

The PREM Bank has been providing pasteurised donor human milk (PDHM) to very preterm for the past 3 years. It is the first human milk bank (HMB) to operate in Australia in over 20 years. Our community has rapidly embraced the concept of human milk banking, with both donations and demand for PDHM exceeding expectations. Providing PDHM in 'exceptional circumstances' where a mothers' own milk is unavailable is supported by the WHO and UNICEF. We submit that neonatal intensive care is an exceptional circumstance. Although evidence supporting PDHM use from randomised control trial (RCT) is limited, the latest systematic reviews suggest a lower risk of necrotising enterocolitis with PDHM as opposed to artificial formula. Study design and ethical issues may limit future evidence from RCT. We therefore support the ongoing use of PDHM in neonatal care, where provided by an appropriately managed HMB. Internationally many HMBs operate unregulated, and this is also the case in Australia. To ensure safety the PREM Bank has committed to meet the appropriate standards recommended in the Code of Good Manufacturing Practices (Blood and Tissues) in Australia and models risk management during processing on Codex HACCP (Hazard Analysis Critical Control Point) requirements. There is scope to continually re-evaluate the screening of donors and quality standards recommended during HMB. This will be most effective if strong networks of HMBs are developed with regional reference laboratories to encourage compliance with safety guidelines. HMB networks will facilitate collection of evidence for refining HMB practice and improving outcomes for preterm and sick infants.

Clonal population structure of Legionella pneumophila inferred from allelic profiling.

PubMed

Edwards, Martin T; Fry, Norman K; Harrison, Timothy G

2008-03-01

The population structure of Legionella pneumophila was investigated by analysing nucleotide sequences from six loci (flaA, pilE, asd, mip, mompS and proA) of 335 globally distributed isolates from clinical and environmental sources over a 29-year period (1977-2006). Data were obtained from unrelated isolates from Europe (n=270), Japan (n=31), Canada (n=7), the USA (n=24) and Australia (n=1). The country of origin of two strains was unknown. Analysis of these isolates indicated significant linkage disequilibrium between the six loci. Application of six sequence-based recombination detection tests did not reveal evidence of recombination, but estimates of rates of recombination and mutation made by a seventh test suggested that recombination could have occurred at a rate similar to, but probably lower than, that of mutation. Genealogies inferred under models with and without recombination were congruent with each other, providing no definitive evidence regarding recombination, and were in agreement with sequence clusters identified by graph methods. Further evidence supporting the distinct nature of two of the three subspecies of L. pneumophila, subsp. fraseri and subsp. pascullei, was also found. The ratios of non-synonymous to synonymous nucleotide polymorphisms for each of the allele sets were examined and revealed that the putative virulence loci mompS and pilE are under diversifying pressure, while the allelic regions of three other loci linked to virulence (flaA, proA and mip) do not appear to be.

Independent walking as a major skill for the development of anticipatory postural control: evidence from adjustments to predictable perturbations.

PubMed

Cignetti, Fabien; Zedka, Milan; Vaugoyeau, Marianne; Assaiante, Christine

2013-01-01

Although there is suggestive evidence that a link exists between independent walking and the ability to establish anticipatory strategy to stabilize posture, the extent to which this skill facilitates the development of anticipatory postural control remains largely unknown. Here, we examined the role of independent walking on the infants' ability to anticipate predictable external perturbations. Non-walking infants, walking infants and adults were sitting on a platform that produced continuous rotation in the frontal plane. Surface electromyography (EMG) of neck and lower back muscles and the positions of markers located on the platform, the upper body and the head were recorded. Results from cross-correlation analysis between rectified and filtered EMGs and platform movement indicated that although muscle activation already occurred before platform movement in non-walking infants, only walking infants demonstrated an adult-like ability for anticipation. Moreover, results from further cross-correlation analysis between segmental angular displacement and platform movement together with measures of balance control at the end-points of rotation of the platform evidenced two sorts of behaviour. The adults behaved as a non-rigid non-inverted pendulum, rather stabilizing head in space, while both the walking and non-walking infants followed the platform, behaving as a rigid inverted pendulum. These results suggest that the acquisition of independent walking plays a role in the development of anticipatory postural control, likely improving the internal model for the sensorimotor control of posture. However, despite such improvement, integrating the dynamics of an external object, here the platform, within the model to maintain balance still remains challenging in infants.

Inferred global connectivity of whale shark Rhincodon typus populations.

PubMed

Sequeira, A M M; Mellin, C; Meekan, M G; Sims, D W; Bradshaw, C J A

2013-02-01

Ten years have passed since the last synopsis of whale shark Rhincodon typus biogeography. While a recent review of the species' biology and ecology summarized the vast data collected since then, it is clear that information on population geographic connectivity, migration and demography of R. typus is still limited and scattered. Understanding R. typus migratory behaviour is central to its conservation management considering the genetic evidence suggesting local aggregations are connected at the generational scale over entire ocean basins. By collating available data on sightings, tracked movements and distribution information, this review provides evidence for the hypothesis of broad-scale connectivity among populations, and generates a model describing how the world's R. typus are part of a single, global meta-population. Rhincodon typus occurrence timings and distribution patterns make possible a connection between several aggregation sites in the Indian Ocean. The present conceptual model and validating data lend support to the hypothesis that R. typus are able to move among the three largest ocean basins with a minimum total travelling time of around 2-4 years. The model provides a worldwide perspective of possible R. typus migration routes, and suggests a modified focus for additional research to test its predictions. The framework can be used to trim the hypotheses for R. typus movements and aggregation timings, thereby isolating possible mating and breeding areas that are currently unknown. This will assist endeavours to predict the longer-term response of the species to ocean warming and changing patterns of human-induced mortality. © 2013 The Authors. Journal of Fish Biology © 2013 The Fisheries Society of the British Isles.

Detection of eight BRCA1 mutations in 10 breast/ovarian cancer families, including 1 family with male breast cancer

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

Sruewing, J.P.; Brody, L.C.; Erdos, M.R.

Genetic epidemiological evidence suggests that mutations in BRCA1 may be responsible for approximately one half of early onset familial breast cancer and the majority of familial breast/ovarian cancer. The recent cloning of BRCA1 allows for the direct detection of mutations, but the feasibility of presymptomatic screening for cancer susceptibility is unknown. We analyzed genomic DNA from one affected individual from each of 24 families with at least three cases of ovarian or breast cancer, using SSCP assays. Variant SSCP bands were subcloned and sequenced. Allele-specific oligonucleotide hybridization was used to verify sequence changes and to screen DNA from control individuals.more » Six frameshift and two missense mutations were detected in 10 different families. A frameshift mutation was detected in a male proband affected with both breast and prostate cancer. A 40-bp deletion was detected in a patient who developed intra-abdominal carcinomatosis 1 year after prophylactic oophorectomy. Mutations were detected throughout the gene, and only one was detected in more than a single family. These results provide further evidence that inherited breast and ovarian cancer can occur as a consequence of a wide array of BRCA1 mutations. These results suggests that development of a screening test for BRCA1 mutations will be technically challenging. The finding of a mutation in a family with male breast cancer, not previously thought to be related to BRCA1, also illustrates the potential difficulties of genetic counseling for individuals known to carry mutations. 37 refs., 1 fig., 1 tab.« less

Cytokine-independent growth and clonal expansion of a primary human CD8+ T-cell clone following retroviral transduction with the IL-15 gene

PubMed Central

Hsu, Cary; Jones, Stephanie A.; Cohen, Cyrille J.; Zheng, Zhili; Kerstann, Keith; Zhou, Juhua; Robbins, Paul F.; Peng, Peter D.; Shen, Xinglei; Gomes, Theotonius J.; Dunbar, Cynthia E.; Munroe, David J.; Stewart, Claudia; Cornetta, Kenneth; Wangsa, Danny; Ried, Thomas; Rosenberg, Steven A.

2007-01-01

Malignancies arising from retrovirally transduced hematopoietic stem cells have been reported in animal models and human gene therapy trials. Whether mature lymphocytes are susceptible to insertional mutagenesis is unknown. We have characterized a primary human CD8+ T-cell clone, which exhibited logarithmic ex vivo growth in the absence of exogenous cytokine support for more than 1 year after transduction with a murine leukemia virus–based vector encoding the T-cell growth factor IL-15. Phenotypically, the clone was CD28−, CD45RA−, CD45RO+, and CD62L−, a profile consistent with effector memory T lymphocytes. After gene transfer with tumor-antigen–specific T-cell receptors, the clone secreted IFN-γ upon encountering tumor targets, providing further evidence that they derived from mature lymphocytes. Gene-expression analyses revealed no evidence of insertional activation of genes flanking the retroviral insertion sites. The clone exhibited constitutive telomerase activity, and the presence of autocrine loop was suggested by impaired cell proliferation following knockdown of IL-15Rα expression. The generation of this cell line suggests that nonphysiologic expression of IL-15 can result in the long-term in vitro growth of mature human T lymphocytes. The cytokine-independent growth of this line was a rare event that has not been observed in other IL-15 vector transduction experiments or with any other integrating vector system. It does not appear that the retroviral vector integration sites played a role in the continuous growth of this cell clone, but this remains under investigation. PMID:17353346

Bioreactor microbial ecosystems with differentiated methanogenic phenol biodegradation and competitive metabolic pathways unraveled with genome-resolved metagenomics.

PubMed

Ju, Feng; Wang, Yubo; Zhang, Tong

2018-01-01

Methanogenic biodegradation of aromatic compounds depends on syntrophic metabolism. However, metabolic enzymes and pathways of uncultured microorganisms and their ecological interactions with methanogenic consortia are unknown because of their resistance to isolation and limited genomic information. Genome-resolved metagenomics approaches were used to reconstruct and dissect 23 prokaryotic genomes from 37 and 20 °C methanogenic phenol-degrading reactors. Comparative genomic evidence suggests that temperature difference leads to the colonization of two distinct cooperative sub-communities that can respire sulfate/sulfite/sulfur or nitrate/nitrite compounds and compete for uptake of methanogenic substrates (e.g., acetate and hydrogen). This competition may differentiate methanogenesis. The uncultured ε - Proteobacterium G1, whose close relatives have broad ecological niches including the deep-sea vents, aquifers, sediment, limestone caves, spring, and anaerobic digesters, is implicated as a Sulfurovum -like facultative anaerobic diazotroph with metabolic versatility and remarkable environmental adaptability. We provide first genomic evidence for butyrate, alcohol, and carbohydrate utilization by a Chloroflexi T78 clade bacterium, and phenol carboxylation and assimilatory sulfite reduction in a Cryptanaerobacter bacterium. Genome-resolved metagenomics enriches our view on the differentiation of microbial community composition, metabolic pathways, and ecological interactions in temperature-differentiated methanogenic phenol-degrading bioreactors. These findings suggest optimization strategies for methanogenesis on phenol, such as temperature control, protection from light, feed desulfurization, and hydrogen sulfide removal from bioreactors. Moreover, decoding genome-borne properties (e.g., antibiotic, arsenic, and heavy metal resistance) of uncultured bacteria help to bring up alternative schemes to isolate them.

Amplification of the enzyme-linked immunosorbent assay (ELISA) in the detection of class-specific antibodies.

PubMed

Butler, J E; McGivern, P L; Swanson, P

1978-01-01

A modification of the standard enzyme-linked immunosorbent assay (ELISA) is described which circumvents the requirement for specifically purified antibodies from which antibody-enzyme complexes are made. The assay utilizes the principle of a soluble anti-alkaline phosphatase immune complex (AP-A-AP) and has been called the amplified ELISA. Methods for preparing and evidence for the specificity of rabbit anti-rat gamma-FC, IgM (mu) and IgA (alpha) are presented. These reagents are used to measure anti-DNP antibodies belonging to classes IgG, IgM and IgA in rat serum. Using antiglobulin and anti-enzyme reagents prepared in guinea pigs, anti-ovalbumin antibodies are measured in rabbit serum. Titration curves are similar when the amplified ELISA is compared to the standard ELISA. A change in slope suggesting an effect of saturation of antigen sites, occurs at the same input antibody concentration for both assays. Determination of the anti-DNP concentration of unknown sera by extrapopulation from titration graphs of a known serum suggests that the value is overestimated, i.e., amplified when the amplified ELISA is used. In addition, the amplified ELISA has an improved ability to detect low levels of antibody. Evidence is presented which illustrates how the use of optimally conjugated DNP-proteins, age of conjugates, and optimal dilutions of secondary antiglobulins and the AP-A-AP reduce non-specific binding in the amplified ELISA. The amplified ELISA is capable of detecting 2.4 ng of antibody to ovalbumin in a one: one million dilution of rabbit serum with high reproducibility and low background.

First North American fossil monkey and early Miocene tropical biotic interchange

NASA Astrophysics Data System (ADS)

Bloch, Jonathan I.; Woodruff, Emily D.; Wood, Aaron R.; Rincon, Aldo F.; Harrington, Arianna R.; Morgan, Gary S.; Foster, David A.; Montes, Camilo; Jaramillo, Carlos A.; Jud, Nathan A.; Jones, Douglas S.; MacFadden, Bruce J.

2016-05-01

New World monkeys (platyrrhines) are a diverse part of modern tropical ecosystems in North and South America, yet their early evolutionary history in the tropics is largely unknown. Molecular divergence estimates suggest that primates arrived in tropical Central America, the southern-most extent of the North American landmass, with several dispersals from South America starting with the emergence of the Isthmus of Panama 3-4 million years ago (Ma). The complete absence of primate fossils from Central America has, however, limited our understanding of their history in the New World. Here we present the first description of a fossil monkey recovered from the North American landmass, the oldest known crown platyrrhine, from a precisely dated 20.9-Ma layer in the Las Cascadas Formation in the Panama Canal Basin, Panama. This discovery suggests that family-level diversification of extant New World monkeys occurred in the tropics, with new divergence estimates for Cebidae between 22 and 25 Ma, and provides the oldest fossil evidence for mammalian interchange between South and North America. The timing is consistent with recent tectonic reconstructions of a relatively narrow Central American Seaway in the early Miocene epoch, coincident with over-water dispersals inferred for many other groups of animals and plants. Discovery of an early Miocene primate in Panama provides evidence for a circum-Caribbean tropical distribution of New World monkeys by this time, with ocean barriers not wholly restricting their northward movements, requiring a complex set of ecological factors to explain their absence in well-sampled similarly aged localities at higher latitudes of North America.

Putting the brakes on reproduction: Implications for conservation, global climate change and biomedicine.

PubMed

Wingfield, John C; Perfito, Nicole; Calisi, Rebecca; Bentley, George; Ubuka, T; Mukai, M; O'Brien, Sara; Tsutsui, K

2016-02-01

Seasonal breeding is widespread in vertebrates and involves sequential development of the gonads, onset of breeding activities (e.g. cycling in females) and then termination resulting in regression of the reproductive system. Whereas males generally show complete spermatogenesis prior to and after onset of breeding, females of many vertebrate species show only partial ovarian development and may delay onset of cycling (e.g. estrous), yolk deposition or germinal vesicle breakdown until conditions conducive for ovulation and onset of breeding are favorable. Regulation of this "brake" on the onset of breeding remains relatively unknown, but could have profound implications for conservation efforts and for "mismatches" of breeding in relation to global climate change. Using avian models it is proposed that a brain peptide, gonadotropin-inhibitory hormone (GnIH), may be the brake to prevent onset of breeding in females. Evidence to date suggests that although GnIH may be involved in the regulation of gonadal development and regression, it plays more regulatory roles in the process of final ovarian development leading to ovulation, transitions from sexual to parental behavior and suppression of reproductive function by environmental stress. Accumulating experimental evidence strongly suggests that GnIH inhibits actions of gonadotropin-releasing hormones on behavior (central effects), gonadotropin secretion (central and hypophysiotropic effects), and has direct actions in the gonad to inhibit steroidogenesis. Thus, actual onset of breeding activities leading to ovulation may involve environmental cues releasing an inhibition (brake) on the hypothalamo-pituitary-gonad axis. Copyright © 2015 Elsevier Inc. All rights reserved.

First North American fossil monkey and early Miocene tropical biotic interchange.

PubMed

Bloch, Jonathan I; Woodruff, Emily D; Wood, Aaron R; Rincon, Aldo F; Harrington, Arianna R; Morgan, Gary S; Foster, David A; Montes, Camilo; Jaramillo, Carlos A; Jud, Nathan A; Jones, Douglas S; MacFadden, Bruce J

2016-05-12

New World monkeys (platyrrhines) are a diverse part of modern tropical ecosystems in North and South America, yet their early evolutionary history in the tropics is largely unknown. Molecular divergence estimates suggest that primates arrived in tropical Central America, the southern-most extent of the North American landmass, with several dispersals from South America starting with the emergence of the Isthmus of Panama 3-4 million years ago (Ma). The complete absence of primate fossils from Central America has, however, limited our understanding of their history in the New World. Here we present the first description of a fossil monkey recovered from the North American landmass, the oldest known crown platyrrhine, from a precisely dated 20.9-Ma layer in the Las Cascadas Formation in the Panama Canal Basin, Panama. This discovery suggests that family-level diversification of extant New World monkeys occurred in the tropics, with new divergence estimates for Cebidae between 22 and 25 Ma, and provides the oldest fossil evidence for mammalian interchange between South and North America. The timing is consistent with recent tectonic reconstructions of a relatively narrow Central American Seaway in the early Miocene epoch, coincident with over-water dispersals inferred for many other groups of animals and plants. Discovery of an early Miocene primate in Panama provides evidence for a circum-Caribbean tropical distribution of New World monkeys by this time, with ocean barriers not wholly restricting their northward movements, requiring a complex set of ecological factors to explain their absence in well-sampled similarly aged localities at higher latitudes of North America.

Historical Human Footprint on Modern Tree Species Composition in the Purus-Madeira Interfluve, Central Amazonia

PubMed Central

Levis, Carolina; de Souza, Priscila Figueira; Schietti, Juliana; Emilio, Thaise; Pinto, José Luiz Purri da Veiga; Clement, Charles R.; Costa, Flavia R. C.

2012-01-01

Background Native Amazonian populations managed forest resources in numerous ways, often creating oligarchic forests dominated by useful trees. The scale and spatial distribution of forest modification beyond pre-Columbian settlements is still unknown, although recent studies propose that human impact away from rivers was minimal. We tested the hypothesis that past human management of the useful tree community decreases with distance from rivers. Methodology/Principal Findings In six sites, we inventoried trees and palms with DBH≥10 cm and collected soil for charcoal analysis; we also mapped archaeological evidence around the sites. To quantify forest manipulation, we measured the relative abundance, richness and basal area of useful trees and palms. We found a strong negative exponential relationship between forest manipulation and distance to large rivers. Plots located from 10 to 20 km from a main river had 20–40% useful arboreal species, plots between 20 and 40 km had 12–23%, plots more than 40 km had less than 15%. Soil charcoal abundance was high in the two sites closest to secondary rivers, suggesting past agricultural practices. The shortest distance between archaeological evidence and plots was found in sites near rivers. Conclusions/Significance These results strongly suggest that past forest manipulation was not limited to the pre-Columbian settlements along major rivers, but extended over interfluvial areas considered to be primary forest today. The sustainable use of Amazonian forests will be most effective if it considers the degree of past landscape domestication, as human-modified landscapes concentrate useful plants for human sustainable use and management today. PMID:23185264

The Neural Basis of Maternal Bonding

PubMed Central

Wan, Ming Wai; Downey, Darragh; Strachan, Hilary; Elliott, Rebecca; Williams, Steve R.; Abel, Kathryn M.

2014-01-01

Background Accumulating evidence suggests that mothers show a different pattern of brain responses when viewing their own compared to other infants. However, there is inconsistency across functional imaging studies regarding the key areas involved, and none have examined relationships between brain and behavioural responses to infants. We examined the brain regions activated when mothers viewed videos of their own infant contrasted with an unknown infant, and whether these are associated with behavioural and self-reported measures of mother-infant relations. Method Twenty right-handed mothers viewed alternating 30-sec blocks of video of own 4–9 month infant and an unfamiliar matched infant, interspersed with neutral video. Whole brain functional magnetic resonance images (fMRI) were acquired on a 1.5T Philips Intera scanner using a TR of 2.55 s. Videotaped mother-infant interactions were systematically evaluated blind to family information to generate behavioural measures for correlational analysis. Results Enhanced blood oxygenation functional imaging responses were found in the own versus unknown infant contrast in the bilateral precuneus, right superior temporal gyrus, right medial and left middle frontal gyri and left amygdala. Positive mother-infant interaction (less directive parent behaviour; more positive/attentive infant behaviour) was significantly associated with greater activation in several regions on viewing own versus unknown infant, particularly the middle frontal gyrus. Mothers' perceived warmth of her infant was correlated with activations in the same contrast, particularly in sensory and visual areas. Conclusion This study partially replicates previous reports of the brain regions activated in mothers in response to the visual presentation of their own infant. It is the first to report associations between mothers' unique neural responses to viewing their own infant with the quality of her concurrent behaviour when interacting with her infant and with her perceptions of infant warmth. These findings provide support for developing fMRI as a potential biomarker of parenting risk and change. PMID:24594508

Use of a surgical helmet system to minimize splash injury during percutaneous renal surgery in high-risk patients.

PubMed

Eandi, Jonathan A; Nanigian, Dana K; Smith, William H; Low, Roger K

2008-12-01

The transmission risk to surgeons performing percutaneous renal surgery on patients who are infected with human immunodeficiency virus/acquired immunodeficiency syndrome, hepatitis B, or hepatitis C is unknown. A recent study found 55% of surgeons' masks contain evidence of blood splash contamination after percutaneous nephrolithotomy. While the risk of infectious disease transmission to the surgeon after mucocutaneous exposure is unknown, the incapacitating disease these pathogens cause can have a devastating and permanent effect on a surgeon's career. We describe our use of a surgical helmet system when performing percutaneous renal surgery on high-risk patients to minimize risk of splash injury and transmission of blood-borne pathogens.

[Kawasaki disease in children and adolescents].

PubMed

Neudorf, U

2011-12-01

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The diagnostic criteria are fulfilled with fever of unknown origin and 4 of the following 5 criteria: bilateral conjunctival injection, cervical lymphadenopathy, polymorphous rash, oral mucous membrane changes (injected lips, strawberry tongue) and peripheral extremity changes (erythema, edema, desquamation). If less than 4 criteria are found incomplete KD can be diagnosed. The therapy is 2 g/kg body weight single dose intravenous immunoglobulin and acetylsalicylic acid (ASS). In the long-term follow-up the main focus is on the coronary arteries because coronary changes play a key role in the intensity of long-term management. There is some evidence that KD is a risk factor for cardiovascular diseases in adults.

Ureaplasma Transmitted From Donor Lungs Is Pathogenic After Lung Transplantation.

PubMed

Fernandez, Ramiro; Ratliff, Amy; Crabb, Donna; Waites, Ken B; Bharat, Ankit

2017-02-01

Hyperammonemia is a highly fatal syndrome in lung recipients that is usually refractory to medical therapy. We recently reported that infection by a Mollicute, Ureaplasma, is causative for hyperammonemia and can be successfully treated with antimicrobial agents. However, it remains unknown whether the pathogenic strain of Ureaplasma is donor or recipient derived. Here we provide evidence that donor-derived Ureaplasma infection can be pathogenic. As such, we uncover a previously unknown lethal donor-derived opportunistic infection in lung recipients. Given the high mortality associated with hyperammonemia, strategies for routine donor screening or prophylaxis should be further evaluated in prospective studies. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

[Clinical diagnosis of primary unknown cancer-the present situation and problems].

PubMed

Mukai, Hirofumi

2009-06-01

The first step of diagnosis of primary unknown cancer(PUC)the detailed history intake and physical examination including breast, genitourinary system and rectum. Laboratory test, chest X-p and systemic computed tomography are allowed to be performed for all patients with PUC. Other tests should be performed according to the results of clinical and pathological evaluation. Utility of the tumor marker is limited, and this test is not recommended as a routine usage. There is not enough evidence on the utility of FDG-PTT or FDG-PET/CT for patients with PUC. Diagnosis of PUC should be made within one month from a patient's first visit to a hospital.

Absence of endemic measles transmission in a highly vaccinated population from 1999 to 2008: implications of sustained measles elimination in Taiwan.

PubMed

Chang, Yu-Kang; Chen, Jacky Y H; Chang, Hsiao-Ling; Yu, Mei-Ching; Hsiao, Hsu-Feng; Hou, Ching-Cheng; Liu, Shyun-Yeu; Chen, Kow-Tong

2010-07-19

Measles remains a leading vaccine-preventable cause of child mortality worldwide. The impact of vaccination programs can be seen in the increasingly low incidence of measles. However, cases of measles continue to occur in low numbers every year in Taiwan. We assessed the epidemiology of measles in Taiwan from 1999 to 2008 with a focus on domestic versus imported cases. We analyzed the data reported to surveillance systems at the Taiwan Center for Disease Control, where viral isolation was performed. A total of 84 measles cases were reported from 1999 to 2008 in Taiwan with the incidence of measles varying from 0 to 1.5 per 1,000,000 people per year, peaking in 2002 and again in 2008. The incidence decreased with increasing age in both males and females. Among the 84 reported measles cases, 39 (46%) originated internationally, 8 (10%) were epidemiologically linked to imported cases and the source was unknown in 37 (44%) of the cases. The unknown-source cases were analyzed for potential evidence of endemic measles transmission. Most of the measles cases that occurred in Taiwan from 1999 to 2008 were associated with imported cases. No endemic transmission of measles in Taiwan was identified. This study suggests that maintaining the high rate of vaccination coverage is needed to prevent future outbreak and sustain the elimination of measles in Taiwan. (c) 2010 Elsevier Ltd. All rights reserved.

Friending, IMing, and hanging out face-to-face: overlap in adolescents' online and offline social networks.

PubMed

Reich, Stephanie M; Subrahmanyam, Kaveri; Espinoza, Guadalupe

2012-03-01

Many new and important developmental issues are encountered during adolescence, which is also a time when Internet use becomes increasingly popular. Studies have shown that adolescents are using these online spaces to address developmental issues, especially needs for intimacy and connection to others. Online communication with its potential for interacting with unknown others, may put teens at increased risk. Two hundred and fifty-one high school students completed an in-person survey, and 126 of these completed an additional online questionnaire about how and why they use the Internet, their activities on social networking sites (e.g., Facebook, MySpace) and their reasons for participation, and how they perceive these online spaces to impact their friendships. To examine the extent of overlap between online and offline friends, participants were asked to list the names of their top interaction partners offline and online (Facebook and instant messaging). Results reveal that adolescents mainly use social networking sites to connect with others, in particular with people known from offline contexts. While adolescents report little monitoring by their parents, there was no evidence that teens are putting themselves at risk by interacting with unknown others. Instead, adolescents seem to use the Internet, especially social networking sites, to connect with known others. While the study found moderate overlap between teens' closest online and offline friends, the patterns suggest that adolescents use online contexts to strengthen offline relationships. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Causes of mortality in California sea otters during periods of population growth and decline

USGS Publications Warehouse

Estes, J.A.; Hatfield, B.B.; Ralls, K.; Ames, J.

2003-01-01

Elevated mortality appears to be the main reason for both sluggish growth and periods of decline in the threatened California sea otter population. We assessed causes of mortality from salvage records of 3,105 beach-cast carcasses recovered from 1968 through 1999, contrasting two periods of growth with two periods of decline. Overall, an estimated 40%-60% of the deaths were not recovered and 70% of the recovered carcasses died from unknown causes. Nonetheless, several common patterns were evident in the salvage records during the periods of population decline. These included greater percentages of (1) prime age animals (3-10 yr), (2) carcasses killed by great white shark attacks, (3) carcasses recovered in spring and summer, and (4) carcasses for which the cause of death was unknown. Neither sex composition nor the proportion of carcasses dying of infectious disease varied consistently between periods of population increase and decline. The population decline from 1976 to 1984 was likely due to incidental mortality in a set-net fishery, and the decline from 1995 to 1999 may be related to a developing live-fish fishery. Long-term trends unrelated to periods of growth and decline included a decrease in per capita pup production and mass/length ratios of adult carcasses over the 31-yr study. The generally high proportion of deaths from infectious disease suggests that this factor has contributed to the chronically sluggish growth rate of the California sea otter population.

Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration

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

Ngalame, Ntube N.O., E-mail: ngalamenn@niehs.nih.g

Inorganic arsenic, an environmental contaminant and a human carcinogen is associated with prostate cancer. Emerging evidence suggests that cancer stem cells (CSCs) are the driving force of carcinogenesis. Chronic arsenic exposure malignantly transforms the human normal prostate stem/progenitor cell (SC) line, WPE-stem to arsenic-cancer SCs (As-CSCs), through unknown mechanisms. MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the posttranscriptional level. In prior work, miR-143 was markedly downregulated in As-CSCs, suggesting a role in arsenic-induced malignant transformation. In the present study, we investigated whether loss of miR-143 expression is important in arsenic-induced transformation of prostate SCs. Restorationmore » of miR-143 in As-CSCs was achieved by lentivirus-mediated miR-143 overexpression. Cells were assessed bi-weekly for up to 30 weeks to examine mitigation of cancer phenotype. Secreted matrix metalloproteinase (MMP) activity was increased by arsenic-induced malignant transformation, but miR-143 restoration decreased secreted MMP-2 and MMP-9 enzyme activities compared with scramble controls. Increased cell proliferation and apoptotic resistance, two hallmarks of cancer, were decreased upon miR-143 restoration. Increased apoptosis was associated with decreased BCL2 and BCL-XL expression. miR-143 restoration dysregulated the expression of SC/CSC self-renewal genes including NOTCH-1, BMI-1, OCT4 and ABCG2. The anticancer effects of miR-143 overexpression appeared to be mediated by targeting and inhibiting LIMK1 protein, and the phosphorylation of cofilin, a LIMK1 substrate. These findings clearly show that miR-143 restoration mitigated multiple cancer characteristics in the As-CSCs, suggesting a potential role in arsenic-induced transformation of prostate SCs. Thus, miR-143 is a potential biomarker and therapeutic target for arsenic-induced prostate cancer. - Highlights: • Chronic arsenic exposure malignantly transforms human prostate stem cells (SCs) to arsenic-cancer SCs via unknown mechanisms. • miR-143 was several fold downregulated in the arsenic-cancer SCs (As-CSCs), suggesting a likely role in transformation. • miR-143 restoration reduced cancer characteristics in the As-CSC, suggesting a role in arsenic-induced SC transformation. • miR-143 appears to exert its anticancer effect by inhibiting expression and activity of LIMK1, its predicted gene target. • These findings suggest miR-143 is a potential biomarker and therapeutic target for arsenic-induced prostate cancer.« less

Assessing pathogenicity for novel mutation/sequence variants: the value of healthy older individuals.

PubMed

Zatz, Mayana; Pavanello, Rita de Cassia M; Lourenço, Naila Cristina V; Cerqueira, Antonia; Lazar, Monize; Vainzof, Mariz

2012-12-01

Improvement in DNA technology is increasingly revealing unexpected/unknown mutations in healthy persons and generating anxiety due to their still unknown health consequences. We report a 44-year-old healthy father of a 10-year-old daughter with bilateral coloboma and hearing loss, but without muscle weakness, in whom a whole-genome CGH revealed a deletion of exons 38-44 in the dystrophin gene. This mutation was inherited from her asymptomatic father, who was further clinically and molecularly evaluated for prognosis and genetic counseling (GC). This deletion was never identified by us in 982 Duchenne/Becker patients. To assess whether the present case represents a rare case of non-penetrance, and aiming to obtain more information for prognosis and GC, we suggested that healthy older relatives submit their DNA for analysis, to which several complied. Mutation analysis revealed that his mother, brother, and 56-year-old maternal uncle also carry the 38-44 deletion, suggesting it an unlikely cause of muscle weakness. Genome sequencing will disclose mutations and variants whose health impact are still unknown, raising important problems in interpreting results, defining prognosis, and discussing GC. We suggest that, in addition to family history, keeping the DNA of older relatives could be very informative, in particular for those interested in having their genome sequenced.

Fibromyalgia in Primary Care.

PubMed

Higgs, Jay B

2018-06-01

Fibromyalgia is a common disorder and has substantial impact on quality of life. The cause remains unknown, but current evidence points to multifactorial involvement of pain processing. Clinical diagnosis is aided by evidence-based diagnostic criteria with subscores for widespread pain and symptom severity. Nonpharmacologic treatments, including cognitive behavioral therapy, sleep hygiene, and regular aerobic exercise, form the cornerstone of management. Pharmacologic intervention is an important adjunct, but benefit is variable. There is no cure for fibromyalgia at this time, but persistence and patience in management may lead to a satisfactory lifestyle. Published by Elsevier Inc.

Healing and medicine in the Aegean Bronze Age.

PubMed

Arnott, R

1996-05-01

Since the discovery of the Minoan and Mycenaean civilizations of Crete and Greek mainland, a systematic understanding has been gained of their material culture and social structures. Nevertheless, because of the absence of textual and pictorial evidence of medicine of the kind which exists in the contemporary societies of Egypt and the Near East, little work has been produced on the subject of disease and the practice of medicine in the period. However, new pathological evidence throws much light on this hitherto largely unknown aspect of their civilization.

Healing and medicine in the Aegean Bronze Age.

PubMed Central

Arnott, R

1996-01-01

Since the discovery of the Minoan and Mycenaean civilizations of Crete and Greek mainland, a systematic understanding has been gained of their material culture and social structures. Nevertheless, because of the absence of textual and pictorial evidence of medicine of the kind which exists in the contemporary societies of Egypt and the Near East, little work has been produced on the subject of disease and the practice of medicine in the period. However, new pathological evidence throws much light on this hitherto largely unknown aspect of their civilization. Images Figure 1 PMID:8778434

Urinary long noncoding RNAs in nonmuscle-invasive bladder cancer: new architects in cancer prognostic biomarkers.

PubMed

Terracciano, Daniela; Ferro, Matteo; Terreri, Sara; Lucarelli, Giuseppe; D'Elia, Carolina; Musi, Gennaro; de Cobelli, Ottavio; Mirone, Vincenzo; Cimmino, Amelia

2017-06-01

Several reports over the last 10 years provided evidence that long noncoding RNAs (lncRNAs) are often altered in bladder cancers. lncRNAs are longer than 200 nucleotides and function as important regulators of gene expression, interacting with the major pathways of cell growth, proliferation, differentiation, and survival. A large number of lncRNAs has oncogenic function and is more expressed in tumor compared with normal tissues. Their overexpression may be associated with tumor formation, progression, and metastasis in a variety of tumors including bladder cancer. Although lncRNAs have been shown to have critical regulatory roles in cancer biology, the biological functions and prognostic values in nonmuscle-invasive bladder cancer remain largely unknown. Nevertheless, a growing body of evidence suggests that several lncRNAs expression profiles in bladder malignancies are associated with poor prognosis, and they can be detected in biological fluids, such as urines. Here, we review current progress in the biology and the implication of lncRNAs associated with bladder cancer, and we discuss their potential use as diagnosis and prognosis biomarkers in bladder malignancies with a focus on their role in high-risk nonmuscle-invasive tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

Predator effects on reef fish settlement depend on predator origin and recruit density.

PubMed

Benkwitt, Cassandra E

2017-04-01

During major life-history transitions, animals often experience high mortality rates due to predation, making predator avoidance particularly advantageous during these times. There is mixed evidence from a limited number of studies, however, regarding how predator presence influences settlement of coral-reef fishes and it is unknown how other potentially mediating factors, including predator origin (native vs. nonnative) or interactions among conspecific recruits, mediate the non-consumptive effects of predators on reef fish settlement. During a field experiment in the Caribbean, approximately 52% fewer mahogany snapper (Lutjanus mahogoni) recruited to reefs with a native predator (graysby grouper, Cephalopholis cruentata) than to predator-free control reefs and reefs with an invasive predator (red lionfish, Pterois volitans) regardless of predator diet. These results suggest that snapper recruits do not recognize nonnative lionfish as a threat. However, these effects depended on the density of conspecific recruits, with evidence that competition may limit the response of snapper to even native predators at the highest recruit densities. In contrast, there was no effect of predator presence or conspecific density on the recruitment of bicolor damselfish (Stegastes partitus). These context-dependent responses of coral-reef fishes to predators during settlement may influence individual survival and shape subsequent population and community dynamics. © 2017 by the Ecological Society of America.

Patterns of sugar feeding and host plant preferences in adult males of An. gambiae (Diptera: Culicidae).

PubMed

Gouagna, Louis-Clément; Poueme, Rodrigue S; Dabiré, Kounbobr Roch; Ouédraogo, Jean-Bosco; Fontenille, Didier; Simard, Frédéric

2010-12-01

Sugar feeding by male mosquitoes is critical for their success in mating competition. However, the facets of sugar source finding under natural conditions remain unknown. Here, evidence obtained in Western Burkina Faso indicated that the distribution of An. gambiae s.s. (M and S molecular forms) males across different peri-domestic habitats is dependent on the availability of potential sugar sources from which they obtain more favorable sites for feeding or resting. Among field-collected anophelines, a higher proportion of specimens containing fructose were found on flowering Mangifera indica (Anacardiaceae), Dolonix regia (Fabaceae), Thevetia neriifolia (Apocynaceae), Senna siamea, and Cassia sieberiana (both Fabaceae) compared to that recorded on other nearby plants, suggesting that some plants are favored for use as a sugar source over others. Y-tube olfactometer assays with newly-emerged An. gambiae s.s. exposed to odors from individual plants and some combinations thereof showed that males use odor cues to guide their preference. The number of sugar-positive males was variable in a no-choice cage assay, consistent with the olfactory response patterns towards corresponding odor stimuli. These experiments provide the first evidence both in field and laboratory conditions for previously unstudied interactions between males of An. gambiae and natural sugar sources. © 2010 The Society for Vector Ecology.

Hybridization between genetically modified Atlantic salmon and wild brown trout reveals novel ecological interactions

PubMed Central

Oke, Krista B.; Westley, Peter A. H.; Moreau, Darek T. R.; Fleming, Ian A.

2013-01-01

Interspecific hybridization is a route for transgenes from genetically modified (GM) animals to invade wild populations, yet the ecological effects and potential risks that may emerge from such hybridization are unknown. Through experimental crosses, we demonstrate transmission of a growth hormone transgene via hybridization between a candidate for commercial aquaculture production, GM Atlantic salmon (Salmo salar) and closely related wild brown trout (Salmo trutta). Transgenic hybrids were viable and grew more rapidly than transgenic salmon and other non-transgenic crosses in hatchery-like conditions. In stream mesocosms designed to more closely emulate natural conditions, transgenic hybrids appeared to express competitive dominance and suppressed the growth of transgenic and non-transgenic (wild-type) salmon by 82 and 54 per cent, respectively. To the best of our knowledge, this is the first demonstration of environmental impacts of hybridization between a GM animal and a closely related species. These results provide empirical evidence of the first steps towards introgression of foreign transgenes into the genomes of new species and contribute to the growing evidence that transgenic animals have complex and context-specific interactions with wild populations. We suggest that interspecific hybridization be explicitly considered when assessing the environmental consequences should transgenic animals escape to nature. PMID:23720549

Neurotransmitters as food supplements: the effects of GABA on brain and behavior

PubMed Central

Boonstra, Evert; de Kleijn, Roy; Colzato, Lorenza S.; Alkemade, Anneke; Forstmann, Birte U.; Nieuwenhuis, Sander

2015-01-01

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human cortex. The food supplement version of GABA is widely available online. Although many consumers claim that they experience benefits from the use of these products, it is unclear whether these supplements confer benefits beyond a placebo effect. Currently, the mechanism of action behind these products is unknown. It has long been thought that GABA is unable to cross the blood–brain barrier (BBB), but the studies that have assessed this issue are often contradictory and range widely in their employed methods. Accordingly, future research needs to establish the effects of oral GABA administration on GABA levels in the human brain, for example using magnetic resonance spectroscopy. There is some evidence in favor of a calming effect of GABA food supplements, but most of this evidence was reported by researchers with a potential conflict of interest. We suggest that any veridical effects of GABA food supplements on brain and cognition might be exerted through BBB passage or, more indirectly, via an effect on the enteric nervous system. We conclude that the mechanism of action of GABA food supplements is far from clear, and that further work is needed to establish the behavioral effects of GABA. PMID:26500584

Neurotransmitters as food supplements: the effects of GABA on brain and behavior.

PubMed

Boonstra, Evert; de Kleijn, Roy; Colzato, Lorenza S; Alkemade, Anneke; Forstmann, Birte U; Nieuwenhuis, Sander

2015-01-01

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human cortex. The food supplement version of GABA is widely available online. Although many consumers claim that they experience benefits from the use of these products, it is unclear whether these supplements confer benefits beyond a placebo effect. Currently, the mechanism of action behind these products is unknown. It has long been thought that GABA is unable to cross the blood-brain barrier (BBB), but the studies that have assessed this issue are often contradictory and range widely in their employed methods. Accordingly, future research needs to establish the effects of oral GABA administration on GABA levels in the human brain, for example using magnetic resonance spectroscopy. There is some evidence in favor of a calming effect of GABA food supplements, but most of this evidence was reported by researchers with a potential conflict of interest. We suggest that any veridical effects of GABA food supplements on brain and cognition might be exerted through BBB passage or, more indirectly, via an effect on the enteric nervous system. We conclude that the mechanism of action of GABA food supplements is far from clear, and that further work is needed to establish the behavioral effects of GABA.

Henslow's sparrow winter-survival estimates and response to prescribed burning

USGS Publications Warehouse

Thatcher, B.S.; Krementz, D.G.; Woodrey, M.S.

2006-01-01

Wintering Henslow's sparrow (Ammodramus henslowii) populations rely on lands managed with prescribed burning, but the effects of various burn regimes on their overwinter survival are unknown. We studied wintering Henslow's sparrows in coastal pine savannas at the Mississippi Sandhill Crane National Wildlife Refuge, Jackson County, Mississippi, USA, during January and February 2001 and 2002. We used the known-fate modeling procedure in program MARK to evaluate the effects of burn age (1 or 2 growing seasons elapsed), burn season (growing, dormant), and calendar year on the survival rates of 83 radiomarked Henslow's sparrows. We found strong evidence that Henslow's sparrow survival rates differed by burn age (with higher survival in recently burned sites) and by year (with lower survival rates in 2001 likely because of drought conditions). We found some evidence that survival rates also differed by bum season (with higher survival in growing-season sites), although the effects of burn season were only apparent in recently burned sites. Avian predation was the suspected major cause of mortality (causing 6 of 14 deaths) with 1 confirmed loggerhead shrike (Lanius ludovicianus) depredation. Our results indicated that recently burned savannas provide high-quality wintering habitats and suggested that managers can improve conditions for wintering Henslow's sparrows by burning a large percentage of savannas each year.

DNA barcoding in diverse educational settings: five case studies

PubMed Central

Imondi, Ralph; James, Karen; Spencer, Diana; Steinke, Dirk

2016-01-01

Despite 250 years of modern taxonomy, there remains a large biodiversity knowledge gap. Most species remain unknown to science. DNA barcoding can help address this gap and has been used in a variety of educational contexts to incorporate original research into school curricula and informal education programmes. A growing body of evidence suggests that actively conducting research increases student engagement and retention in science. We describe case studies in five different educational settings in Canada and the USA: a programme for primary and secondary school students (ages 5–18), a year-long professional development programme for secondary school teachers, projects embedding this research into courses in a post-secondary 2-year institution and a degree-granting university, and a citizen science project. We argue that these projects are successful because the scientific content is authentic and compelling, DNA barcoding is conceptually and technically straightforward, the workflow is adaptable to a variety of situations, and online tools exist that allow participants to contribute high-quality data to the international research effort. Evidence of success includes the broad adoption of these programmes and assessment results demonstrating that participants are gaining both knowledge and confidence. There are exciting opportunities for coordination among educational projects in the future. This article is part of the themed issue ‘From DNA barcodes to biomes’. PMID:27481792