Bone Microenvironment Specific Roles of ITAM Adapter Signaling during Bone Remodeling Induced by Acute Estrogen-Deficiency

Immunoreceptor tyrosine-based activation motif (ITAM) signaling mediated by DAP12 or Fcε receptor Iγ chain (FcRγ) have been shown to be critical for osteoclast differentiation and maturation under normal physiological conditions. Their function in pathological conditions is unknown. We studied the role of ITAM signaling during rapid bone remodeling induced by acute estrogen-deficiency in wild-type (WT), DAP12-deficient (DAP12-/-), FcRγ-deficient (FcRγ-/-) and double-deficient (DAP12-/-FcRγ-/-) mice. Six weeks after ovariectomy (OVX), DAP12-/-FcRγ-/- mice showed resistance to lumbar vertebral body (LVB) trabecular bone loss, while WT, DAP12-/- and FcRγ-/- mice had significant LVB bone loss. In contrast, all ITAM adapter-deficient mice responded to OVX with bone loss in both femur and tibia of approximately 40%, relative to basal bone volumes. Only WT mice developed significant cortical bone loss after OVX. In vitro studies showed microenvironmental changes induced by OVX are indispensable for enhanced osteoclast formation and function. Cytokine changes, including TGFβ and TNFα, were able to induce osteoclastogenesis independent of RANKL in BMMs from WT but not DAP12-/- and DAP12-/-FcRγ-/- mice. FSH stimulated RANKL-induced osteoclast differentiation from BMMs in WT, but not DAP12-/- and DAP12-/-FcRγ-/- mice. Our study demonstrates that although ITAM adapter signaling is critical for normal bone remodeling, estrogen-deficiency induces an ITAM adapter-independent bypass mechanism allowing for enhanced osteoclastogenesis and activation in specific bony microenvironments

Education can improve the negative perception of a threatened long-lived scavenging bird, the Andean condor

Human-wildlife conflicts currently represent one of the main conservation problems for wildlife species around the world. Vultures have serious conservation concerns, many of which are related to people's adverse perception about them due to the belief that they prey on livestock. Our aim was to assess local perception and the factors influencing people's perception of the largest scavenging bird in South America, the Andean condor. For this, we interviewed 112 people from Valle Fértil, San Juan province, a rural area of central west Argentina. Overall, people in the area mostly have an elementary education, and their most important activity is livestock rearing. The results showed that, in general, most people perceive the Andean condor as an injurious species and, in fact, some people recognize that they still kill condors. We identified two major factors that affect this perception, the education level of villagers and their relationship with livestock ranching. Our study suggests that conservation of condors and other similar scavengers depends on education programs designed to change the negative perception people have about them. Such programs should be particularly focused on ranchers since they are the ones who have the worst perception of these scavengers. We suggest that highlighting the central ecological role of scavengers and recovering their cultural value would be fundamental to reverse their persecution and their negative perception by people.Fil: Cailly Arnulphi, Verónica Beatríz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Lambertucci, Sergio Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Borghi, Carlos Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; Argentin

The Winter Worries of Bats : Past and Present Perspectives on Winter Habitat and Management of Cave Hibernating Bats

Winter is a time of fascinating changes in biology for cave-hibernating bats, but it is also a time of vulnerability. Unsurprisingly, assessments of winter habitat for these mammals and how it can be managed have been a focus of many researchers involved with the North American Society for Bat Research over the last 50 years. Over this time, a paradigm shift has occurred in the way scientists think about factors driving selection of winter habitat, especially temperature. To illustrate this change, we review three hypotheses seeking to explain microclimate selection in cavernicolous bats. The first, which we call the “Colder is Better Hypothesis,” posits that bats should select cold microclimates that minimize energy expenditure. The “Hibernation Optimization Hypothesis” suggests that bats should select microclimates that reduce expression of torpor to balance energy conservation against non-energetic costs of hibernation. Finally, the “Thrifty Female Hypothesis” asserts that females should select colder microclimates than males to conserve energy for reproduction. We discuss these hypotheses and the shift from viewing hibernation as a phenomenon driven solely by the need to conserve energy in the context of hibernacula management in North America. We focus on both historical and recent conservation threats, most notably alteration of thermal regimes and the disease white-nose syndrome. We urge against returning to an over-simplified view of winter habitat selection in response to our current conservation challenges.Peer reviewe

ParaHaplo: A program package for haplotype-based whole-genome association study using parallel computing

<p>Abstract</p> <p>Background</p> <p>Since more than a million single-nucleotide polymorphisms (SNPs) are analyzed in any given genome-wide association study (GWAS), performing multiple comparisons can be problematic. To cope with multiple-comparison problems in GWAS, haplotype-based algorithms were developed to correct for multiple comparisons at multiple SNP loci in linkage disequilibrium. A permutation test can also control problems inherent in multiple testing; however, both the calculation of exact probability and the execution of permutation tests are time-consuming. Faster methods for calculating exact probabilities and executing permutation tests are required.</p> <p>Methods</p> <p>We developed a set of computer programs for the parallel computation of accurate P-values in haplotype-based GWAS. Our program, ParaHaplo, is intended for workstation clusters using the Intel Message Passing Interface (MPI). We compared the performance of our algorithm to that of the regular permutation test on JPT and CHB of HapMap.</p> <p>Results</p> <p>ParaHaplo can detect smaller differences between 2 populations than SNP-based GWAS. We also found that parallel-computing techniques made ParaHaplo 100-fold faster than a non-parallel version of the program.</p> <p>Conclusion</p> <p>ParaHaplo is a useful tool in conducting haplotype-based GWAS. Since the data sizes of such projects continue to increase, the use of fast computations with parallel computing--such as that used in ParaHaplo--will become increasingly important. The executable binaries and program sources of ParaHaplo are available at the following address: <url>http://sourceforge.jp/projects/parallelgwas/?_sl=1</url></p

Digital Work Design

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)More and more academic studies and practitioner reports claim that human work is increasingly disrupted or even determined by information and communication technology (ICT) (Cascio and Montealegre 2016). This will make a considerable share of jobs currently performed by humans susceptible to automation (e.g., Frey and Osborne 2017; Manyika et al. 2017). These reports often sketch a picture of ‘machines taking over’ traditional domains like manufacturing, while ICT advances and capabilities seem to decide companies’ fate. Consequently, ICT is often put at the core of innovative efforts. While this applies to nearly all areas of workplace design, a recent popular example of increasing technology centricity is ‘Industry 4.0’, which is often delineated as ‘machines talking to computers’

Use, acceptability and impact of booklets designed to support mental health self-management and help seeking in schools:Results of a large randomised controlled trial in England

Mental health booklets may provide a low-cost means of promoting mental health self-management and help seeking in schools. The aim of the study was to assess the (a) use, (b) acceptability and (c) impact of booklets for students in primary (10-11 years) and secondary school (12-13 years) alone and in conjunction with funding for targeted mental health support. This was a 2 × 2 factorial cluster randomized controlled trial, in which 846 schools in England were randomly allocated to receive/not receive: (1) booklets for students containing information on mental health self-management and help seeking, and (2) funding for mental health support as part of a national mental health initiative. 14,690 students (8139 primary, 6551 secondary) provided self-report on mental health, quality of life (baseline and 1 year follow-up) and help seeking (follow-up). (a) Approximately, 40 % primary school students and 20 % secondary school students reported seeing the booklets. (b) Of these, 87 % of primary school students reported that the booklet was 'very helpful' or 'quite helpful', compared with 73 % in secondary school. (c) There was no detectable impact of booklets on mental health, quality of life or help seeking, either alone or in conjunction with additional funding through the national mental health initiative. Lack of discernable impact of booklets underscores the need for caution in adopting such an approach. However, it is feasible that the impact was obscured by low uptake or that booklets may be more effective when used in a targeted way

Visualization of Allostery in P-Selectin Lectin Domain Using MD Simulations

Allostery of P-selectin lectin (Lec) domain followed by an epithelial growth factor (EGF)-like domain is essential for its biological functionality, but the underlying pathways have not been well understood. Here the molecular dynamics simulations were performed on the crystallized structures to visualize the dynamic conformational change for state 1 (S1) or state 2 (S2) Lec domain with respective bent (B) or extended (E) EGF orientation. Simulations illustrated that both S1 and S2 conformations were unable to switch from one to another directly. Instead, a novel S1' conformation was observed from S1 when crystallized B-S1 or reconstructed “E-S1” structure was employed, which was superposed well with that of equilibrated S1 Lec domain alone. It was also indicated that the corresponding allosteric pathway from S1 to S1' conformation started with the separation between residues Q30 and K67 and terminated with the release of residue N87 from residue C109. These results provided an insight into understanding the structural transition and the structure-function relationship of P-selectin allostery