Miracle-dz/UniFAR-FTUs huggingface dataset:
Chimpanzees in an anthropogenic landscape: Examining food resources across habitat types at Bossou, Guinea, West Africa

Many primate populations occur outside protected areas in fragmented anthropogenic landscapes. Empirical data on the ecological characteristics that define an anthropogenic landscape are urgently required if conservation initiatives in such environments are to succeed. The main objective of our study was to determine the composition and availability of chimpanzee (Pan troglodytes verus) food resources across fine spatial scales in the anthropogenic landscape of Bossou, Guinea, West Africa. We examined food resources in all habitat types available in the chimpanzees’ core area. We surveyed resource composition, structure and heterogeneity (20 m × 20 m quadrats, N = 54) and assessed temporal availability of food from phenology trails (total distance 5951 m; 1073 individual trees) over 1 year (2012–2013). Over half of Bossou consists of regenerating forest and is highly diverse in terms of chimpanzee food species; large fruit bearing trees are rare and confined to primary and riverine forest. Moraceae (mulberries and figs) was the dominant family, trees of which produce drupaceous fruits favored by chimpanzees. The oil palm occurs at high densities throughout and is the only species found in all habitat types except primary forest. Our data suggest that the high densities of oil palm and fig trees, along with abundant terrestrial herbaceous vegetation and cultivars, are able to provide the chimpanzees with widely available resources, compensating for the scarcity of large fruit trees. A significant difference was found between habitat types in stem density/ha and basal area m2/ha of chimpanzee food species. Secondary, young secondary, and primary forest emerged as the most important habitat types for availability of food tree species. Our study emphasizes the importance of examining ecological characteristics of an anthropogenic landscape as each available habitat type is unlikely to be equally important in terms of spatial and temporal availability of resources. Am. J. Primatol. 78:1237–1249, 2016. © 2016 Wiley Periodicals, Inc.
Improving trainee psychiatrist's handover: standard setting and audit

Purpose – The 2006 Post Graduate Medical Education Trust Board (PMETB) trainees' survey indicated inadequacies in handover procedures amongst medical and psychiatry trainees nationwide; and in 2007 a local psychiatry trainees' survey found inadequate handover procedures. The purpose of this paper is to show how to improve handover practice through standard setting and sequential audit. Design/methodology/approach – A Trust wide Standard Operating Procedure (SOP) for handover was developed. Trainees were audited on perception of handover experiences (2008, 2009 and 2010). Findings – The audit revealed that the SOP was not consistently followed. Handing over “active problems” (AP) was perceived to occur frequently in 2008 (93.75 per cent), improved in 2009 (100 per cent for AP, 98 per cent for “problems which may arise”, (PA)); however deteriorated in 2010 (93 per cent for AP, 69 per cent for PA). Trainee satisfaction rates with handover improved each year (57 per cent in 2008, 75 per cent in 2009, 87 per c.
Determinants of 14-3-3σ Protein Dimerization and Function in Drug and Radiation Resistance*

Background: 14-3-3σ is a homodimeric protein important for drug and radiation resistance. Results: Mutation of a single hydrophobic core residue results in nonfunctional monomeric proteins. Conclusion: Hydrophobic core residues are important for 14-3-3σ dimerization, and homodimerization is required for its function. Significance: Identifying important hydrophobic core residues for homodimerization may help drug the “undruggable” protein dimers such as 14-3-3σ. Many proteins exist and function as homodimers. Understanding the detailed mechanism driving the homodimerization is important and will impact future studies targeting the “undruggable” oncogenic protein dimers. In this study, we used 14-3-3σ as a model homodimeric protein and performed a systematic investigation of the potential roles of amino acid residues in the interface for homodimerization. Unlike other members of the conserved 14-3-3 protein family, 14-3-3σ prefers to form a homodimer with two subareas in the dimeric interface that has 180° symmetry. We found that both subareas of the dimeric interface are required to maintain full dimerization activity. Although the interfacial hydrophobic core residues Leu12 and Tyr84 play important roles in 14-3-3σ dimerization, the non-core residue Phe25 appears to be more important in controlling 14-3-3σ dimerization activity. Interestingly, a similar non-core residue (Val81) is less important than Phe25 in contributing to 14-3-3σ dimerization. Furthermore, dissociating dimeric 14-3-3σ into monomers by mutating the Leu12, Phe25, or Tyr84 dimerization residue individually diminished the function of 14-3-3σ in resisting drug-induced apoptosis and in arresting cells at G2/M phase in response to DNA-damaging treatment. Thus, dimerization appears to be required for the function of 14-3-3σ.
Of lemurs and louse flies: The biogeochemical and biotic effects of forest disturbance on Propithecus edwardsi and its obligate ectoparasite Allobosca crassipes in Ranomafana National Park, southeastern Madagascar

From alleles to ecosystems and landscapes, anthropogenic activity continues to affect the environment, with particularly adverse effects on biodiversity hotspots such as Madagascar. Selective logging has been proposed as a “win‐win” conservation strategy, yet its effects on different components of biodiversity are still not fully understood. Here we examine biotic factors (i.e., dietary differences) that may be driving differences in biogeochemical stocks between disturbed and undisturbed forests. We present the stable nitrogen (δ15N) and carbon (δ13C) isotope composition of hair from the lemur Propithecus edwardsi and of whole bodies of its obligate ectoparasite, the louse‐fly Allobosca crassipes, from sites in Ranomafana National Park (RNP) that are comparable except for the history of logging and subsequent forest regeneration. P. edwardsi and A. crassipes from the disturbed (i.e., heavily selectively logged) site are lower in 15N and 13C relative to P. edwardsi and A. crassipes from sites that were minimally selectively logged or not commercially logged at all. There is a ∼3‰ decrease in 15N between disturbed and undisturbed sites that corresponds to a difference of nearly a full trophic level. Flowers from Bakerella clavata, a staple food source for P. edwardsi in disturbed habitats and a fallback food for P. edwardsi in primary forests, were also analyzed isotopically. B. clavata is δ15N‐depleted in both disturbed and undisturbed sites. Data from longitudinal behavioral surveys of P. edwardsi in RNP and other forests in eastern Madagascar point to significant differences in consumption patterns of B. clavata, with P. edwardsi in disturbed forests consuming almost twice as much of this plant. Depletion of 15N in animal tissues is a complex issue, but likely the result of the interaction of physiological and ecological factors. Anthropogenic disturbance in RNP from selective logging has had both biotic and biogeochemical effects that are observable trophically.
Potential population health gain of the quality and outcomes framework: report to Department of Health

Dr. Robert Fleetcroft, Honorary Senior Lecturer, Un iversity of East Anglia Dr. Sheetal Parekh, Research Associate, University of East Anglia Dr. Nicholas Steel, Senior Clinical Lecturer, Unive rsity of East Anglia Dr. Louise Swift, Statistician, University of East Anglia Dr Richard Cookson, Senior Lecturer, Department of Social Policy and Social Work, University of York Professor Amanda Howe, Professor in Primary Care, U niversity of East Anglia
Correlates of androgens in wild male Barbary macaques: Testing the challenge hypothesis

Investigating causes and consequences of variation in hormonal expression is a key focus in behavioral ecology. Many studies have explored patterns of secretion of the androgen testosterone in male vertebrates, using the challenge hypothesis (Wingfield, Hegner, Dufty, & Ball, 1990; The American Naturalist, 136(6), 829–846) as a theoretical framework. Rather than the classic association of testosterone with male sexual behavior, this hypothesis predicts that high levels of testosterone are associated with male–male reproductive competition but also inhibit paternal care. The hypothesis was originally developed for birds, and subsequently tested in other vertebrate taxa, including primates. Such studies have explored the link between testosterone and reproductive aggression as well as other measures of mating competition, or between testosterone and aspects of male behavior related to the presence of infants. Very few studies have simultaneously investigated the links between testosterone and male aggression, other aspects of mating competition and infant‐related behavior. We tested predictions derived from the challenge hypothesis in wild male Barbary macaques (Macaca sylvanus), a species with marked breeding seasonality and high levels of male‐infant affiliation, providing a powerful test of this theoretical framework. Over 11 months, 251 hr of behavioral observations and 296 fecal samples were collected from seven adult males in the Middle Atlas Mountains, Morocco. Fecal androgen levels rose before the onset of the mating season, during a period of rank instability, and were positively related to group mating activity across the mating season. Androgen levels were unrelated to rates of male–male aggression in any period, but higher ranked males had higher levels in both the mating season and in the period of rank instability. Lower androgen levels were associated with increased rates of male‐infant grooming during the mating and unstable periods. Our results generally support the challenge hypothesis and highlight the importance of considering individual species’ behavioral ecology when testing this framework.
Crystal Structure of Mycobacterium tuberculosis Polyketide Synthase 11 (PKS11) Reveals Intermediates in the Synthesis of Methyl-branched Alkylpyrones*

Background: Polyketide synthases (PKSs) synthesize complex lipid components of the cell wall in M. tuberculosis. Results: We determined the crystal structure of M. tuberculosis PKS11 and identified its substrate, intermediates, and product. Conclusion: M. tuberculosis PKS11 synthesizes a unique cyclic methyl-branched alkylpyrone. Significance: Our identification of alkylpyrones as the product of this PKS suggests a previously unknown component of the mycobacterial cell wall. PKS11 is one of three type III polyketide synthases (PKSs) identified in Mycobacterium tuberculosis. Although many PKSs in M. tuberculosis have been implicated in producing complex cell wall glycolipids, the biological function of PKS11 is unknown. PKS11 has previously been proposed to synthesize alkylpyrones from fatty acid substrates. We solved the crystal structure of M. tuberculosis PKS11 and found the overall fold to be similar to other type III PKSs. PKS11 has a deep hydrophobic tunnel proximal to the active site Cys-138 to accommodate substrates. We observed electron density in this tunnel from a co-purified molecule that was identified by mass spectrometry to be palmitate. Co-crystallization with malonyl-CoA (MCoA) or methylmalonyl-CoA (MMCoA) led to partial turnover of the substrate, resulting in trapped intermediates. Reconstitution of the reaction in solution confirmed that both co-factors are required for optimal activity, and kinetic analysis shows that MMCoA is incorporated first, then MCoA, followed by lactonization to produce methyl-branched alkylpyrones.
The Lhs1/GRP170 Chaperones Facilitate the Endoplasmic Reticulum-associated Degradation of the Epithelial Sodium Channel*

Background: The epithelial sodium channel (ENaC) is a substrate for the endoplasmic reticulum associated degradation (ERAD) quality control system. Results: The chaperone Lhs1/GRP170 selects the nonglycosylated form of the α subunit for ERAD. Conclusion: This study is the first to show a role for Lhs1/GRP170 in ERAD substrate selection. Significance: Mutations in ENaC are associated with human disease; therefore, Lhs1/GRP170, as a modulator of ENaC expression, may be a target for new therapeutic agents. The epithelial sodium channel, ENaC, plays a critical role in maintaining salt and water homeostasis, and not surprisingly defects in ENaC function are associated with disease. Like many other membrane-spanning proteins, this trimeric protein complex folds and assembles inefficiently in the endoplasmic reticulum (ER), which results in a substantial percentage of the channel being targeted for ER-associated degradation (ERAD). Because the spectrum of factors that facilitates the degradation of ENaC is incomplete, we developed yeast expression systems for each ENaC subunit. We discovered that a conserved Hsp70-like chaperone, Lhs1, is required for maximal turnover of the ENaC α subunit. By expressing Lhs1 ATP binding mutants, we also found that the nucleotide exchange properties of this chaperone are dispensable for ENaC degradation. Consistent with the precipitation of an Lhs1-αENaC complex, Lhs1 holdase activity was instead most likely required to support the ERAD of αENaC. Moreover, a complex containing the mammalian Lhs1 homolog GRP170 and αENaC co-precipitated, and GRP170 also facilitated ENaC degradation in human, HEK293 cells, and in a Xenopus oocyte expression system. In both yeast and higher cell types, the effect of Lhs1 on the ERAD of αENaC was selective for the unglycosylated form of the protein. These data establish the first evidence that Lhs1/Grp170 chaperones can act as mediators of ERAD substrate selection.
EFFECT OF MODIFIED ELBOW BRACE OVER CUSTOM MADE ELBOW BINDER ON PAIN, HAND FUNCTIONS IN PATIENTS WITH TENNIS ELBOW

Background and purpose: Lack of knowledge and professional skills among Physiotherapists in decision making for a right orthosis for pain relief and improving hand functions in patients with tennis elbow. Understanding the biomechanical mechanism behind the orthotic principles will help Physiotherapist in finding the better solution for improving functions in patients with tennis elbow. Methods: Pre test-post test experimental design, which intended to find out the effectiveness of the modified elbow brace over custom made elbow binder in reducing pain and improving grip strength and hand function among subjects with tennis elbow was implemented. A sample consists of 30 adult population with lateral epicondylitis (15 male & 15 female) participated in the study. All the subjects who were assessed by Orthopaedic surgeon and referred to physiotherapy department for further management. The subjects who met eligibility criteria included in this study. The allocated patients were assigned to groups 1 or 2. Group 1 received the modified elbow brace wrapped around 5cm below lateral epicondyle maintaining pressure 40mmHg (6). Group 2 received the custom made elbow binder applied at same level. Subjects were advised to wear the orthotic device as much as possible for (2 weeks) during most of daily activities at home and work place. No restriction in providing activity was given. A baseline assessment was made at the level of pain and hand function was documented before application of modified elbow brace and custom made elbow binder. Before starting the intervention approach the consent permission was taken. The present study included age between group 20 to 60 years with diagnosis of lateral epicondylitis with less than 3 months duration and recurrence of symptoms after initial treatment. The subjects who able to understand English language and able to complete PRTEE of mentioned exercise in English and history of functional limitation due to pain and impaired hand function. The study excluded history of previous physiotherapeutic intervention, elbow surgery, bilateral lateral epicondylitis, neurologic and rheumatic disorder to the lower arm and wrist apart from lateral epicondylitis, muscular, neural and bony injuries to lower arm and wrist, fractures of upper limb and ligament injury to elbow and wrist. Result and conclusion: The experimental group reveled shows significantly better results in this study (P = 0.045) than the control group. The modified elbow brace with a pressure maintained 40mmHg was highly beneficial for patients with tennis elbow due to its biomechanical reasons by diverging the forces or load on the painful site of elbow. Thus reducing pain and improving function in daily life than the custom made elbow binder.
Non-destructive and Selective Imaging of the Functionally Active, Pro-invasive Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) Enzyme in Cancer Cells*

Background: MT1-matrix metalloproteinase (MMP) is directly related to cell migration, invasion, and metastasis. Results: We developed a fluorescent reporter that targets the active cellular MT1-MMP enzyme alone. Conclusion: The reporter quantifies the active MT1-MMP enzyme levels in multiple cell types. Significance: The reporter will contribute to the design of novel, more efficient prognostic approaches and personalized cancer therapies. Proteolytic activity of cell surface-associated MT1-matrix metalloproteinase (MMP) (MMP-14) is directly related to cell migration, invasion, and metastasis. MT1-MMP is regulated as a proteinase by activation and conversion of the latent proenzyme into the active enzyme, and also via inhibition by tissue inhibitors of MMPs (TIMPs) and self-proteolysis. MT1-MMP is also regulated as a membrane protein through its internalization and recycling. Routine immunohistochemistry, flow cytometry, reverse transcription-PCR, and immunoblotting methodologies do not allow quantitative imaging and assessment of the cell-surface levels of the active, TIMP-free MT1-MMP enzyme. Here, we developed a fluorescent reporter prototype that targets the cellular active MT1-MMP enzyme alone. The reporter (MP-3653) represents a liposome tagged with a fluorochrome and functionalized with a PEG chain spacer linked to an inhibitory hydroxamate warhead. Our studies using the MP-3653 reporter and its inactive derivative demonstrated that MP-3653 can be efficiently used not only to visualize the trafficking of MT1-MMP through the cell compartment, but also to quantify the femtomolar range amounts of the cell surface-associated active MT1-MMP enzyme in multiple cancer cell types, including breast carcinoma, fibrosarcoma, and melanoma. Thus, the levels of the naturally expressed, fully functional, active cellular MT1-MMP enzyme are roughly equal to 1 × 105 molecules/cell, whereas these levels are in a 1 × 106 range in the cells with the enforced MT1-MMP expression. We suggest that the reporter we developed will contribute to the laboratory studies of MT1-MMP and then, ultimately, to the design of novel, more efficient prognostic approaches and personalized cancer therapies.
Structural and Biophysical Characterization of the Interactions between the Death Domain of Fas Receptor and Calmodulin*

Background: Calmodulin (CaM) is recruited into the death-inducing signaling complex in cholangiocarcinoma cells. Results: CaM binds to FasDD in a 2:1 CaM:FasDD model. CaM antagonists abolish FasDD-CaM interactions. Conclusion: Data offer a structural basis for Fas-CaM interactions and mechanisms of inhibition. Significance: Elucidating the structural determinants of Fas-CaM interaction is critical to understanding the functional role of CaM in Fas-mediated apoptosis. The extrinsic apoptotic pathway is initiated by cell surface death receptors such as Fas. Engagement of Fas by Fas ligand triggers a conformational change that allows Fas to interact with adaptor protein Fas-associated death domain (FADD) via the death domain, which recruits downstream signaling proteins to form the death-inducing signaling complex (DISC). Previous studies have shown that calmodulin (CaM) is recruited into the DISC in cholangiocarcinoma cells, suggesting a novel role of CaM in Fas-mediated signaling. CaM antagonists induce apoptosis through a Fas-related mechanism in cholangiocarcinoma and other cancer cell lines possibly by inhibiting Fas-CaM interactions. The structural determinants of Fas-CaM interaction and the underlying molecular mechanisms of inhibition, however, are unknown. Here we employed NMR and biophysical techniques to elucidate these mechanisms. Our data show that CaM binds to the death domain of Fas (FasDD) with an apparent dissociation constant (Kd) of ∼2 μm and 2:1 CaM:FasDD stoichiometry. The interactions between FasDD and CaM are endothermic and entropically driven, suggesting that hydrophobic contacts are critical for binding. We also show that both the N- and C-terminal lobes of CaM are important for binding. NMR and surface plasmon resonance data show that three CaM antagonists (N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide, tamoxifen, and trifluoperazine) greatly inhibit Fas-CaM interactions by blocking the Fas-binding site on CaM. Our findings provide the first structural evidence for Fas-CaM interactions and mechanism of inhibition and provide new insight into the molecular basis for a novel role of CaM in regulating Fas-mediated apoptosis.
The ATP-dependent Chromatin Remodeling Enzyme Fun30 Represses Transcription by Sliding Promoter-proximal Nucleosomes*

Background: The conserved ATP-dependent chromatin remodeling enzyme Fun30 regulates heterochromatin silencing and DNA repair. Results: Gene expression is up-regulated, and nucleosome positioning is altered in fun30Δ cells, and purified Fun30 slides nucleosome in vitro. Conclusion: Fun30 represses gene expression by sliding promoter-proximal nucleosomes. Significance: The function of Fun30 is expanded to regulation of transcription and chromatin remodeling by nucleosome sliding. The evolutionarily conserved ATP-dependent chromatin remodeling enzyme Fun30 has recently been shown to play important roles in heterochromatin silencing and DNA repair. However, how Fun30 remodels nucleosomes is not clear. Here we report a nucleosome sliding activity of Fun30 and its role in transcriptional repression. We observed that Fun30 repressed the expression of genes involved in amino acid and carbohydrate metabolism, the stress response, and meiosis. In addition, Fun30 was localized at the 5′ and 3′ ends of genes and within the open reading frames of its targets. Consistent with its role in gene repression, we observed that Fun30 target genes lacked histone modifications often associated with gene activation and showed an increased level of ubiquitinated histone H2B. Furthermore, a genome-wide nucleosome mapping analysis revealed that the length of the nucleosome-free region at the 5′ end of a subset of genes was changed in Fun30-depleted cells. In addition, the positions of the −1, +2, and +3 nucleosomes at the 5′ end of target genes were shifted significantly, whereas the position of the +1 nucleosome remained largely unchanged in the fun30Δ mutant. Finally, we demonstrated that affinity-purified, single-component Fun30 exhibited a nucleosome sliding activity in an ATP-dependent manner. These results define a role for Fun30 in the regulation of transcription and indicate that Fun30 remodels chromatin at the 5′ end of genes by sliding promoter-proximal nucleosomes.