Miracle-dz/UniFAR-FTUs huggingface dataset:
Variants in Doublecortin- and Calmodulin Kinase Like 1, a Gene Up-Regulated by BDNF, Are Associated with Memory and General Cognitive Abilities

Background Human memory and general cognitive abilities are complex functions of high heritability and wide variability in the population. The brain-derived neurotrophic factor (BDNF) plays an important role in mammalian memory formation. Methodology / Principal Finding Based on the identification of genes markedly up-regulated during BDNF-induced synaptic consolidation in the hippocampus, we selected genetic variants that were tested in three independent samples, from Norway and Scotland, of adult individuals examined for cognitive abilities. In all samples, we show that markers in the doublecortin- and calmodulin kinase like 1 (DCLK1) gene, are significantly associated with general cognition (IQ scores) and verbal memory function, resisting multiple testing. DCLK1 is a complex gene with multiple transcripts which vary in expression and function. We show that the short variants are all up-regulated after BDNF treatment in the rat hippocampus, and that they are expressed in the adult human brain (mostly in cortices and hippocampus). We demonstrate that several of the associated variants are located in potential alternative promoter- and cis-regulatory elements of the gene and that they affect BDNF-mediated expression of short DCLK1 transcripts in a reporter system. Conclusion These data present DCLK1 as a functionally pertinent gene involved in human memory and cognitive functions.
Key experimental evidence of chromosomal DNA transfer among selected tuberculosis-causing mycobacteria

Significance Whereas most of the more than 130 described mycobacterial species are harmless saprophytes, Mycobacterium tuberculosis, the human tuberculosis-causing agent, represents one of the deadliest bacterial pathogens in the history of humankind. To explore the mechanisms behind this spectacular evolutionary trajectory toward pathogenicity, we have experimentally investigated the faculty of different tuberculosis-causing mycobacteria in conducting horizontal gene transfer (HGT). Our studies identified unique chromosomal DNA transfer between strains of the Mycobacterium canettii clade, which resemble most closely the putative common ancestor of the M. tuberculosis complex. This outstanding feature suggests that during the evolution of M. tuberculosis, HGT might have represented the major mechanism for acquisition of genes that helped these mycobacteria to increasingly resist host defenses and become major pathogens. Horizontal gene transfer (HGT) is a major driving force of bacterial diversification and evolution. For tuberculosis-causing mycobacteria, the impact of HGT in the emergence and distribution of dominant lineages remains a matter of debate. Here, by using fluorescence-assisted mating assays and whole genome sequencing, we present unique experimental evidence of chromosomal DNA transfer between tubercle bacilli of the early-branching Mycobacterium canettii clade. We found that the obtained recombinants had received multiple donor-derived DNA fragments in the size range of 100 bp to 118 kbp, fragments large enough to contain whole operons. Although the transfer frequency between M. canettii strains was low and no transfer could be observed among classical Mycobacterium tuberculosis complex (MTBC) strains, our study provides the proof of concept for genetic exchange in tubercle bacilli. This outstanding, now experimentally validated phenomenon presumably played a key role in the early evolution of the MTBC toward pathogenicity. Moreover, our findings also provide important information for the risk evaluation of potential transfer of drug resistance and fitness mutations among clinically relevant mycobacterial strains.
Potential Role for Regulatory B Cells as a Major Source of Interleukin-10 in Spleen from Plasmodium chabaudi-Infected Mice

ABSTRACT Interleukin-10 (IL-10)-producing regulatory B (Breg) cells were found to be induced in a variety of infectious diseases. However, its importance in the regulation of immune response to malaria is still unclear. Here, we investigated the dynamics, phenotype, and function of Breg cells using Plasmodium chabaudi chabaudi AS-infected C57BL/6 and BALB/c mice. BALB/c mice were more susceptible to infection and had a stronger IL-10 response in spleen than C57BL/6 mice. Analysis of the surface markers of IL-10-producing cells with flow cytometry showed that CD19+ B cells were one of the primary IL-10-producing populations in P. c. chabaudi AS-infected C57BL/6 and BALB/c mice, especially in the latter one. The Breg cells had a heterogeneous phenotype which shifted during infection. The well-established Breg subset, CD19+ CD5+ CD1dhi cells, accounted for less than 20% of IL-10-producing B cells in both strains during the course of infection. Most Breg cells were IgG+ and CD138− from day 0 to day 8 postinfection. Adoptive transfer of Breg cells to C57BL/6 mice infected with P. c. chabaudi AS led to a transient increase of parasitemia without an impact on survival rate. Our finding reveals that B cells play an active and important regulatory role in addition to mediating humoral immunity in immune response against malaria, which should be paid more attention in developing therapeutic or vaccine strategies against malaria involving stimulation of B cells.
Barents Sea inflow shutdown: A new mechanism for rapid climate changes

A new mechanism for rapid climate transitions in the high latitudes is presented which involves complex ocean‐sea ice‐atmosphere interactions. A shutdown of the Barents Sea Inflow (BSI) which carries a vast amount of heat into the Arctic Ocean is at the heart of the mechanism. The BSI shutdown is studied in a multi‐millennium integration with a global climate model forced by periodically (1000 yr) varying solar constant (±2 W/m2). A positive feedback between the inflow and sea ice cover is revealed in the model, which triggers rapid climate changes. The BSI shutdown events are associated with strong cooling in the northern latitudes and subsequent rearrangement of the Arctic Ocean surface current system. The results reveal the existence of a bifurcation point in the Arctic climate system and demonstrate that rapid climate transitions may be caused by local feedbacks and restricted to confined areas without significant global impacts.
Magnetic Fields and Rotations of Protostars

The early evolution of the magnetic field and angular momentum of newly formed protostars are studied, using three-dimensional resistive MHD nested grid simulations. Starting with a Bonnor-Ebert isothermal cloud rotating in a uniform magnetic field, we calculate the cloud evolution from the molecular cloud core (nc ≃ 104 cm-3 and r = 4.6 × 105 AU, where nc and r are the central density and radius, respectively) to the stellar core (nc ≃ 1022 cm-3; r ~ 1 R☉). The magnetic field strengths at the centers of clouds with the same initial angular momentum but different magnetic field strengths converge to a certain value as the clouds collapse for nc ≲ 1012 cm-3. For 1012 cm-3 ≲ nc ≲ 1016 cm-3, ohmic dissipation largely removes the magnetic field from a collapsing cloud core, and the magnetic field lines, which are strongly twisted for nc ≲ 1012 cm-3, are decollimated. The magnetic field lines are twisted and amplified again for nc ≳ 1016 cm-3, because the magnetic field is recoupled with warm gas. Finally, protostars at their formation epoch (nc ≃ 1021 cm-3) have magnetic fields of ~0.1-1 kG, which is comparable to observations. The magnetic field strength of a protostar depends slightly on the angular momentum of the host cloud. A protostar formed from a slowly rotating cloud core has a stronger magnetic field. The evolution of the angular momentum is closely related to the evolution of the magnetic field. The angular momentum in a collapsing cloud is removed by magnetic effects such as magnetic braking, outflow, and jets. The formed protostars have rotation periods of 0.1-2 days at their formation epoch, which is slightly shorter than observations. This indicates that a further removal mechanism for the angular momentum, such as interactions between the protostar and the disk, wind, or jets, is important in the further evolution of protostars.
Predation Risk Shapes Social Networks in Fission-Fusion Populations

Predation risk is often associated with group formation in prey, but recent advances in methods for analysing the social structure of animal societies make it possible to quantify the effects of risk on the complex dynamics of spatial and temporal organisation. In this paper we use social network analysis to investigate the impact of variation in predation risk on the social structure of guppy shoals and the frequency and duration of shoal splitting (fission) and merging (fusion) events. Our analyses revealed that variation in the level of predation risk was associated with divergent social dynamics, with fish in high-risk populations displaying a greater number of associations with overall greater strength and connectedness than those from low-risk sites. Temporal patterns of organisation also differed according to predation risk, with fission events more likely to occur over two short time periods (5 minutes and 20 minutes) in low-predation fish and over longer time scales (>1.5 hours) in high-predation fish. Our findings suggest that predation risk influences the fine-scale social structure of prey populations and that the temporal aspects of organisation play a key role in defining social systems.
Structure of Parasite Component Communities of Didelphid Marsupials: Insights From a Comparative Study

abstract: The parasite fauna of the gray four-eyed opossum, Philander opossum (Linnaeus, 1758), and the common opossum, Didelphis marsupialis Linnaeus, 1758, in Camp du Tigre, French Guiana, is characterized. Nine species from the gastrointestinal system were recovered from both species, which shared 80% of their parasites. The parasite fauna comprised several monoxenous species (63%) and was dominated by Aspidodera raillieti Travassos, 1914, which exhibited high levels of prevalence and abundance in both communities. Only 2 species (Moennigia sp. and Spirura guianensis) had been recorded in other species of mammals. Both species richness and taxonomic composition at the level of component communities from this locality were compared against 11 communities present in the Virginia (Didelphis virginiana), white-bellied (Didelphis albiventris), and common opossum from Argentina, Brazil, Mexico, and the United States. Neither host phylogeny nor taxonomy accounted for statistical differences in species richness. There was no statistical difference among species richness values among the 9 localities studied. Taxonomic similarity was analyzed by means of the Jaccard's similarity index, including all, and only common species (occurring in prevalence >10%). The results suggest that sympatric species of marsupials share more species of parasites than parasite communities occurring in conspecific marsupials from different localities. As a consequence, taxonomic composition of these parasite communities varied depending on the locality. Probably, marsupials of the monophyletic Didelphini offer the same compatibility toward their parasites, by presenting them with similar habitats. Subtle differences in lifestyles of the marsupials may determine the chance of encounter between the symbionts and prevent some parasites from completing their life cycles. Further and more rigorous tests are necessary to determine the roles of encounter and compatibility filters, as well as the role of chance, in the structuring of parasite communities in marsupials.
Optimal support techniques when providing mechanical ventilation to patients with acute respiratory distress syndrome

BACKGROUND Adult respiratory distress syndrome (ARDS) is a type of acute diffuse lung injury characterized by severe inflammation, increased pulmonary vascular permeability and a loss of aerated lung tissue. The effects of high fraction of inspired oxygen (FiO2 ) include oxygen toxicity manifested by damage to the lung parenchyma in the acute phase of lung injury. There is still a high mortality rate among this group of patients, so clinically sensitive evidence-based interventions are paramount to maximize survival chances during critical care. AIMS AND OBJECTIVES The aim of this article is to explore the current opinion concerning optimal mechanical ventilation support techniques for patients with acute respiratory distress syndrome. SEARCH STRATEGY, INCLUSION AND EXCLUSION CRITERIA A literature search of clinical trials and observation studies, reviews, discussion papers, meta-analyses and clinical guidelines written in English up to 2015, derived from the databases of Scopus, CINAHL, Cochrane Library databases and PubMed was conducted. CONCLUSIONS Low tidal volume, pressure limitation and prone positioning in severe ARDS patients appear to be of some benefit. More research is required and further development and use of standardized protocols is an important strategy for reducing practice variations across disciplines, as well as giving clear guidelines to nurses practising in critical care. There is also evidence that this syndrome is under-diagnosed and the utilization of lung protective ventilation is still variable. RELEVANCE TO CLINICAL PRACTICE It is important that nurses have underlying knowledge of both aetiology of ARDS and ventilation management, and that they monitor patients very closely. The adoption of a low tidal ventilation protocol, which is based on quality evidence guidelines, the value of rescue therapies and patient observation practices in the overall patient management, and the need to place emphasis on long-term patient outcomes, all these emerge as key factors for consideration and future research. However, there is also a need for more research that would explore the unique contribution of nurses in the management of this patient group, as it is difficult to discern this in the current literature.
An Exotic Species Is the Favorite Prey of a Native Enemy

Although native enemies in an exotic species' new range are considered to affect its ability to invade, few studies have evaluated predation pressures from native enemies on exotic species in their new range. The exotic prey naiveté hypothesis (EPNH) states that exotic species may be at a disadvantage because of its naïveté towards native enemies and, therefore, may suffer higher predation pressures from the enemy than native prey species. Corollaries of this hypothesis include the native enemy preferring exotic species over native species and the diet of the enemy being influenced by the abundance of the exotic species. We comprehensively tested this hypothesis using introduced North American bullfrogs (Lithobates catesbeianus, referred to as bullfrog), a native red-banded snake (Dinodon rufozonatum, the enemy) and four native anuran species in permanent still water bodies as a model system in Daishan, China. We investigated reciprocal recognition between snakes and anuran species (bullfrogs and three common native species) and the diet preference of the snakes for bullfrogs and the three species in laboratory experiments, and the diet preference and bullfrog density in the wild. Bullfrogs are naive to the snakes, but the native anurans are not. However, the snakes can identify bullfrogs as prey, and in fact, prefer bullfrogs over the native anurans in manipulative experiments with and without a control for body size and in the wild, indicating that bullfrogs are subjected to higher predation pressures from the snakes than the native species. The proportion of bullfrogs in the snakes' diet is positively correlated with the abundance of bullfrogs in the wild. Our results provide strong evidence for the EPNH. The results highlight the biological resistance of native enemies to naïve exotic species.
Assessing biomass diversity and performance of an activated sludge process treating saline table olive processing wastewater

ABSTRACT This study aimed to determine the effects of salinity on the biomass behavior and its diversity in activated sludge process (ASP) treating the table olive processing wastewater (TOPW), and to evaluate ASP performances under increased TOPW concentration feeding, the numerical abundance, diversity and activity of the biomass, removal efficiencies of chemical oxygen demand (COD), phenolic compounds, nitrogen and phosphorus were evaluated. Results showed that biomass growth is very high and became faster according to an increase in the percentage of TOPW feeding and reached 5.2 gMLVSS l−1. The specific oxygen uptake rate (SOUR) analysis revealed that salinity up to 10 g l−1 provides an increase in biomass activity. SOUR reached a maximum of 20.3 gO2 gMLVSS−1 h−1. The increasing percentages of TOPW induce actually an evolution of microorganism's biodiversity; the microorganism communities were characterized by the abundance of halotolerant, Pseudomonas and Yeast genus that became the most abundant in the bioreactor as adaptation response against salinity. Furthermore, COD, phenolic compounds, nitrogen and phosphorus removal efficiencies attained 92.3%, 84.5%, 80% and 60%, respectively. A satisfactory release of extracellular polymeric substances is found to occur in the reactor with regard to increased saline TOPW, providing significant removal efficiencies and best settling of sludge.
TrkB‐mediated activation of the phosphatidylinositol‐3‐kinase/Akt cascade reduces the damage inflicted by oxygen–glucose deprivation in area CA3 of the rat hippocampus

The selective vulnerability of hippocampal area CA1 to ischemia‐induced injury is a well‐known phenomenon. However, the cellular mechanisms that confer resistance to area CA3 against ischemic damage remain elusive. Here, we show that oxygen–glucose deprivation–reperfusion (OGD‐RP), an in vitro model that mimic the pathological conditions of the ischemic stroke, increases the phosphorylation level of tropomyosin receptor kinase B (TrkB) in area CA3. Slices preincubated with brain‐derived neurotrophic factor (BDNF) or 7,8‐dihydroxyflavone (7,8‐DHF) exhibited reduced depression of the electrical activity triggered by OGD‐RP. Consistently, blockade of TrkB suppressed the resistance of area CA3 to OGD‐RP. The protective effect of TrkB activation was limited to area CA3, as OGD‐RP caused permanent suppression of CA1 responses. At the cellular level, TrkB activation leads to phosphorylation of the accessory proteins SHC and Gab as well as the serine/threonine kinase Akt, members of the phosphoinositide 3‐kinase/Akt (PI‐3‐K/Akt) pathway, a cascade involved in cell survival. Hence, acute slices pretreated with the Akt antagonist MK2206 in combination with BDNF lost the capability to resist the damage inflicted with OGD‐RP. Consistently, with these results, CA3 pyramidal cells exhibited reduced propidium iodide uptake and caspase‐3 activity in slices pretreated with BDNF and exposed to OGD‐RP. We propose that PI‐3‐K/Akt downstream activation mediated by TrkB represents an endogenous mechanism responsible for the resistance of area CA3 to ischemic damage.
Bmc Medical Informatics and Decision Making Utilization of the Pico Framework to Improve Searching Pubmed for Clinical Questions

Background: Supporting 21 st century health care and the practice of evidence-based medicine (EBM) requires ubiquitous access to clinical information and to knowledge-based resources to answer clinical questions. Many questions go unanswered, however, due to lack of skills in formulating questions, crafting effective search strategies, and accessing databases to identify best levels of evidence.
The Generalized Stochastic Preference Choice Model

We propose a new discrete choice model that generalizes the random utility model (RUM). We show that this model, called the \emph{Generalized Stochastic Preference} (GSP) model can explain several choice phenomena that can't be represented by a RUM. In particular, the model can easily (and also exactly) replicate some well known examples that are not RUM, as well as controlled choice experiments carried since 1980's that possess strong regularity violations. One such regularity violation is the \emph{decoy effect} in which the probability of choosing a product increases when a similar, but inferior product is added to the choice set. An appealing feature of the GSP is that it is non-parametric and therefore it has very high flexibility. The model has also a simple description and interpretation: it builds upon the well known representation of RUM as a stochastic preference, by allowing some additional consumer types to be non-rational.
Dystrophin's central domain forms a complex filament that becomes disorganized by in-frame deletions

Dystrophin, encoded by the DMD gene, is critical for maintaining plasma membrane integrity during muscle contraction events. Mutations in the DMD gene disrupting the reading frame prevent dystrophin production and result in severe Duchenne muscular dystrophy (DMD); in-frame internal deletions allow production of partly functional internally deleted dystrophin and result in less severe Becker muscular dystrophy (BMD). Many known BMD deletions occur in dystrophin's central domain, generally considered to be a monotonous rod-shaped domain based on the knowledge of spectrin family proteins. However, the effects caused by these deletions, ranging from asymptomatic to severe BMD, argue against the central domain serving only as a featureless scaffold. We undertook structural studies combining small-angle X-ray scattering and molecular modeling in an effort to uncover the structure of the central domain, as dystrophin has been refractory to characterization. We show that this domain appears to be a tortuous and complex filament that is profoundly disorganized by the most severe BMD deletion (loss of exons 45–47). Despite the preservation of large parts of the binding site for neuronal nitric oxide synthase (nNOS) in this deletion, computational approaches failed to recreate the association of dystrophin with nNOS. This observation is in agreement with a strong decrease of nNOS immunolocalization in muscle biopsies, a parameter related to the severity of BMD phenotypes. The structural description of the whole dystrophin central domain we present here is a first necessary step to improve the design of microdystrophin constructs toward the goal of a successful gene therapy for DMD.
The Effect of Cleft Lip on Adults' Responses to Faces: Cross-Species Findings

Cleft lip and palate is the most common of the congenital conditions affecting the face and cranial bones and is associated with a raised risk of difficulties in infant-caregiver interaction; the reasons for such difficulties are not fully understood. Here, we report two experiments designed to explore how adults respond to infant faces with and without cleft lip, using behavioural measures of attractiveness appraisal (‘liking’) and willingness to work to view or remove the images (‘wanting’). We found that infants with cleft lip were rated as less attractive and were viewed for shorter durations than healthy infants, an effect that was particularly apparent where the cleft lip was severe. Women rated the infant faces as more attractive than men did, but there were no differences in men and women's viewing times of these faces. In a second experiment, we found that the presence of a cleft lip in domestic animals affected adults' ‘liking’ and ‘wanting’ responses in a comparable way to that seen for human infants. Adults' responses were also remarkably similar for images of infants and animals with cleft lip, although no gender difference in attractiveness ratings or viewing times emerged for animals. We suggest that the presence of a cleft lip can substantially change the way in which adults respond to human and animal faces. Furthermore, women may respond in different ways to men when asked to appraise infant attractiveness, despite the fact that men and women ‘want’ to view images of infants for similar durations.