3D interrelationship between osteocyte network and forming mineral during human bone remodeling

During bone remodeling, osteoblasts are known to deposit unmineralized collagenous tissue (osteoid), which mineralizes after some time lag. Some of the osteoblasts differentiate into osteocytes, forming a cell network within the lacunocanalicular network (LCN) of bone. To get more insight into the potential role of osteocytes in the mineralization process of osteoid, sites of bone formation are three-dimensionally imaged in nine forming human osteons using focused ion beam-scanning electron microscopy (FIB-SEM). In agreement with previous observations, the mineral concentration is found to gradually increase from the central Haversian canal toward pre-existing mineralized bone. Most interestingly, a similar feature is discovered on a length scale more than 100-times smaller, whereby mineral concentration increases from the LCN, leaving around the canaliculi a zone virtually free of mineral, the size of which decreases with progressing mineralization. This suggests that the LCN controls mineral formation but not just by diffusion of mineralization precursors, which would lead to a continuous decrease of mineral concentration from the LCN. The observation is, however, compatible with the codiffusion and reaction of precursors and inhibitors from the LCN into the bone matrix

The ATF6-Met [67] Val substitution is associated with increased plasma cholesterol levels

Objective— Activating transcription factor 6 (ATF6) is a sensor of the endoplasmic reticulum stress response and regulates expression of several key lipogenic genes. We used a 2-stage design to investigate whether ATF6 polymorphisms are associated with lipids in subjects at increased risk for cardiovascular disease (CVD). Methods and Results— In stage 1, 13 tag-SNPs were tested for association in Dutch samples ascertained for familial combined hyperlipidemia (FCHL) or increased risk for CVD (CVR). In stage 2, we further investigated the SNP with the strongest association from stage 1, a Methionine/Valine substitution at amino-acid 67, in Finnish FCHL families and in subjects with CVR from METSIM, a Finnish population-based cohort. The combined analysis of both stages reached region-wide significance (P=9x10–4), but this association was not seen in the entire METSIM cohort. Our functional analysis demonstrated that Valine at position 67 augments ATF6 protein and its targets Grp78 and Grp94 as well as increases luciferase expression through Grp78 promoter. Conclusions— A common nonsynonymous variant in ATF6 increases ATF6 protein levels and is associated with cholesterol levels in subjects at increased risk for CVD, but this association was not seen in a population-based cohort. Further replication is needed to confirm the role of this variant in lipids. We report the association of the ATF6-methionine [67]valine amino-acid substitution with plasma cholesterol levels. Association analyses in 2674 subjects and functional data suggest that the ATF6 gene may influence cholesterol levels in subjects at increased risk to develop cardiovascular disease

Leadership and decision-making practices in public versus private universities in Pakistan

The goal of this study is to examine differences in leadership and decision-making practices in public and private universities in Pakistan, with a focus on transformational leadership (TL) and participative decision-making (PDM). We conducted semi-structured interviews with 46 deans and heads of department from two public and two private universities in Pakistan. Our findings indicate that leadership and decision-making practices are different in public and private universities. While differences were observed in all six types of TL-behaviour, the following three approaches emerged to be crucial in both public and private universities: (1) articulating a vision, (2) fostering the acceptance of group goals, and (3) high-performance expectations. In terms of PDM, deans and heads of department in public and private universities adopt a collaborative approach. However, on a practical level this approach is limited to teacher- and student-related matters. Overall, our findings suggest that the leadership and decision-making practices in Pakistani public and private universities are transformational and participative in nature

EST-PAC a web package for EST annotation and protein sequence prediction

With the decreasing cost of DNA sequencing technology and the vast diversity of biological resources, researchers increasingly face the basic challenge of annotating a larger number of expressed sequences tags (EST) from a variety of species. This typically consists of a series of repetitive tasks, which should be automated and easy to use. The results of these annotation tasks need to be stored and organized in a consistent way. All these operations should be self-installing, platform independent, easy to customize and amenable to using distributed bioinformatics resources available on the Internet. In order to address these issues, we present EST-PAC a web oriented multi-platform software package for expressed sequences tag (EST) annotation. EST-PAC provides a solution for the administration of EST and protein sequence annotations accessible through a web interface. Three aspects of EST annotation are automated: 1) searching local or remote biological databases for sequence similarities using Blast services, 2) predicting protein coding sequence from EST data and, 3) annotating predicted protein sequences with functional domain predictions. In practice, EST-PAC integrates the BLASTALL suite, EST-Scan2 and HMMER in a relational database system accessible through a simple web interface. EST-PAC also takes advantage of the relational database to allow consistent storage, powerful queries of results and, management of the annotation process. The system allows users to customize annotation strategies and provides an open-source data-management environment for research and education in bioinformatics

Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice

miR-29 is expressed strongly in the brain and alterations in expression have been linked to several neurological disorders. To further explore the function of this miRNA in the brain, we generated miR-29a/b-1 knockout animals. Knockout mice develop a progressive disorder characterized by locomotor impairment and ataxia. The different members of the miR-29 family are strongly expressed in neurons of the olfactory bulb, the hippocampus and in the Purkinje cells of the cerebellum. Morphological analysis showed that Purkinje cells are smaller and display less dendritic arborisation compared to their wildtype littermates. In addition, a decreased number of parallel fibers form synapses on the Purkinje cells. We identified several mRNAs significantly up-regulated in the absence of the miR-29a/b-1 cluster. At the protein level, however, the voltage-gated potassium channel Kcnc3 (Kv3.3) was significantly up-regulated in the cerebella of the miR-29a/b knockout mice. Dysregulation of KCNC3 expression may contribute to the ataxic phenotype

Structural Sensitivity of Neural and Genetic Networks

International audienceThis paper aims at giving new results on the structural sensitivity of biological networks represented by threshold Boolean networks and ruled by Hopfield-like evolution laws classically used in the context of neural and genetic networks. Indeed, the objective is to present how certain changes and/or perturbations in such networks can modify signicantly their asymptotic behaviour. More precisely, this work has been focused on three diferent kinds of what we think to be relevant in the biological area of robustness (in both theoretical and applied frameworks): the boundary sensitivity (external fields, hormone flows, ...), the state sensitivity (axonal or somatic modulations, microRNAs actions, ...) and the updating sensitivity

Binding energies of ground and isomeric states in neutron-rich ruthenium isotopes: measurements at JYFLTRAP and comparison to theory

We report on precision mass measurements of $^{113,115,117}$Ru performed with the JYFLTRAP double Penning trap mass spectrometer at the Accelerator Laboratory of University of Jyv\"askyl\"a. The phase-imaging ion-cyclotron-resonance technique was used to resolve the ground and isomeric states in $^{113,115}$Ru and enabled for the first time a measurement of the isomer excitation energies, $E_x(^{113}$Ru$^{m})=100.5(8)$ keV and $E_x(^{115}$Ru$^{m})=129(5)$ keV. The ground state of $^{117}$Ru was measured using the time-of-flight ion-cyclotron-resonance technique. The new mass-excess value for $^{117}$Ru is around 36 keV lower and 7 times more precise than the previous literature value. With the more precise ground-state mass values, the evolution of the two-neutron separation energies is further constrained and a similar trend as predicted by the BSkG1 model is obtained up to the neutron number $N=71$.Comment: 12 pages, 9 figures, submitted to Physical Review

High-precision measurements of low-lying isomeric states in 120−124^{120-124}In with JYFLTRAP double Penning trap

Neutron-rich $^{120-124}$In isotopes have been studied utilizing the double Penning trap mass spectrometer JYFLTRAP at the IGISOL facility. Using the phase-imaging ion-cyclotron-resonance technique, the isomeric states were resolved from ground states and their excitation energies measured with high precision in $^{121,123,124}$In. In $^{120,122}$In, the $1^+$ states were separated and their masses were measured while the energy difference between the unresolved $5^+$ and $8^-$ states, whose presence was confirmed by post-trap decay spectroscopy was determined to be $\leq15$ keV. In addition, the half-life of $^{122}$Cd, $T_{1/2} = 5.98(10)$ s, was extracted. Experimental results were compared with energy density functionals, density functional theory and shell-model calculations.Comment: 11 pages, 7 figure

Universities’ pursuit of inclusion and its effects on professional staff: the case of the United Kingdom

This paper explores the proliferation of non-academic professionals as a cultural response to universities’ mission of inclusion. Departing from a neo-institutionalist perspective, the author argues that the diffusion of highly rationalised models of institutional action shapes universities as formal organisations who engage with new levels of professional expertise in the pursuit of goals and missions. The United Kingdom (UK) offers an illustrative example, the emergence of statutory equality duties on public institutions (race equality duty 2001, disability equality duty 2006 and gender equality duty 2007) nurturing an image of universities as strategic for the pursuit of demographic inclusion. Using yearly longitudinal data on 109 UK universities from 2003 to 2011, the author shows that universities increase their professional staff in catering for demographic inclusion in terms of ethnicity and disability, revealing highly rationalised institutional responses to the aforementioned equality duties. The findings contribute to the neo-institutionalist literature drawing attention to the transformation of universities into organisational actors (i.e. highly integrated entities, strategically oriented towards the pursuit of formally articulated goals and targets), which contrasts with traditional conceptions of the university as an institution with a taken-for-granted societal role and loosely defined organisational backbone. The findings provide the impetuous for further empirical research into the role of professional staff as universities assimilate new goals and missions