A Seat at the Table: Minority Representation and County Governing Boards

This study focuses on minority representation on county governing boards to determine the extent of minority representation, and then to provide explanation for the exiting patterns in its representation. The dependent variable used in this paper is a count variable employing a Zero-Inflated Negative Binomial model. The results indicate that minority populations, counties located in the South, partisan elections, the size of county governing boards and urban counties have positive effects on increased minority representation, while at-large voting districts have a negative effect. Furthermore, it advances the need for greater research on county governing boards, county governments in general and a new agenda for the future study of minority representation on local governing bodies

The Hsp90 chaperone controls the biogenesis of L7Ae RNPs through conserved machinery

RNA-binding proteins of the L7Ae family are at the heart of many essential ribonucleoproteins (RNPs), including box C/D and H/ACA small nucleolar RNPs, U4 small nuclear RNP, telomerase, and messenger RNPs coding for selenoproteins. In this study, we show that Nufip and its yeast homologue Rsa1 are key components of the machinery that assembles these RNPs. We observed that Rsa1 and Nufip bind several L7Ae proteins and tether them to other core proteins in the immature particles. Surprisingly, Rsa1 and Nufip also link assembling RNPs with the AAA + adenosine triphosphatases hRvb1 and hRvb2 and with the Hsp90 chaperone through two conserved adaptors, Tah1/hSpagh and Pih1. Inhibition of Hsp90 in human cells prevents the accumulation of U3, U4, and telomerase RNAs and decreases the levels of newly synthesized hNop58, hNHP2, 15.5K, and SBP2. Thus, Hsp90 may control the folding of these proteins during the formation of new RNPs. This suggests that Hsp90 functions as a master regulator of cell proliferation by allowing simultaneous control of cell signaling and cell growth

A MANBA mutation resulting in residual beta-mannosidase activity associated with severe leukoencephalopathy: a possible pseudodeficiency variant

<p>Abstract</p> <p>Background</p> <p>β-Mannosidosis (OMIM 248510) is a rare inborn lysosomal storage disorder caused by the deficient activity of β-mannosidase, an enzyme encoded by a single gene (<it>MANBA</it>) located on chromosome 4q22-25. To date, only 20 cases of this autosomal recessive disorder have been described and 14 different <it>MANBA </it>mutations were incriminated in the disease. These are all null mutations or missense mutations that abolish β-mannosidase activity. In this study, we characterized the molecular defect of a new case of β-mannosidosis, presenting with a severe neurological disorder.</p> <p>Methods</p> <p>Genomic DNA was isolated from peripheral blood leukocytes of the patient to allow <it>MANBA </it>sequencing. The identified mutation was engineered by site-directed mutagenesis and the mutant protein was expressed through transient transfection in HEK293T cells. The β-mannosidase expression and activity were respectively assessed by Western blot and fluorometric assay in both leukocytes and HEK293T cells.</p> <p>Results</p> <p>A missense disease-associated mutation, c.1922G>A (p.Arg641His), was identified for which the patient was homozygous. In contrast to previously described missense mutations, this substitution does not totally abrogate the enzyme activity but led to a residual activity of about 7% in the patient's leukocytes, 11% in lymphoblasts and 14% in plasma. Expression studies in transfected cells also resulted in 7% residual activity.</p> <p>Conclusion</p> <p>Correlations between MANBA mutations, residual activity of β-mannosidase and the severity of the ensuing neurological disorder are discussed. Whether the c.1922G>A mutation is responsible for a yet undescribed pseudodeficiency of β-mannosidase is also discussed.</p

Guidelines for procedural pain in the newborn

Despite accumulating evidence that procedural pain experienced by newborn infants may have acute and even long-term detrimental effects on their subsequent behaviour and neurological outcome, pain control and prevention remain controversial issues. Our aim was to develop guidelines based on evidence and clinical practice for preventing and controlling neonatal procedural pain in the light of the evidence-based recommendations contained in the SIGN classification. A panel of expert neonatologists used systematic review, data synthesis and open discussion to reach a consensus on the level of evidence supported by the literature or customs in clinical practice and to describe a global analgesic management, considering pharmacological, non-pharmacological, behavioural and environmental measures for each invasive procedure. There is strong evidence to support some analgesic measures, e.g. sucrose or breast milk for minor invasive procedures, and combinations of drugs for tracheal intubation. Many other pain control measures used during chest tube placement and removal, screening and treatment for ROP, or for postoperative pain, are still based not on evidence, but on good practice or expert opinions

Combination of Nanoindentation and Quantitative Backscattered Electron Imaging Revealed Altered Bone Material Properties Associated with Femoral Neck Fragility

Osteoporotic fragility fractures were hypothesized to be related to changes in bone material properties and not solely to reduction in bone mass. We studied cortical bone from the superior and inferior sectors of whole femoral neck sections from five female osteoporotic hip fracture cases (74–92 years) and five nonfractured controls (75–88 years). The typical calcium content (CaPeak) and the mineral particle thickness parameter (T) were mapped in large areas of the superior and inferior regions using quantitative backscattered electron imaging (qBEI) and scanning small-angle X-ray scattering, respectively. Additionally, indentation modulus (E) and hardness (H) (determined by nanoindentation) were compared at the local level to the mineral content (CaInd) at the indent positions (obtained from qBEI). CaPeak (−2.2%, P = 0.002), CaInd (−1.8%, P = 0.048), E (−5.6%, P = 0.040), and H (−6.0%, P = 0.016) were significantly lower for the superior compared to the inferior region. Interestingly, CaPeak as well as CaInd were also lower (−2.6%, P = 0.006, and –3.7%, P = 0.002, respectively) in fracture cases compared to controls, while E and H did not show any significant reduction. T values were in the normal range, independent of region (P = 0.181) or fracture status (P = 0.551). In conclusion, it appears that the observed femoral neck fragility is associated with a reduced mineral content, which was not accompanied by a reduction in stiffness and hardness of the bone material. This pilot study suggests that a stiffening process in the organic matrix component contributes to bone fragility independently of mineral content

Three Dimensional Characterization of the Dentin Porous Network Using Confocal Laser Scanning Microscopy (CLSM)

International audienceIn this paper, the 3D-morphology of the porous structure in dentin is investigated by confocal laser scanning microscopy (CLSM). The porous microstructure near the dentino-enamel junction (DEJ), which consists of tubules partly connected by lateral branches, was found to exhibit a complex geometry. We revisit and challenge previous 2D studies by focusing on the 3D morphology (tubule and branching geometry) and quantification of porosity. Our work provides fundamental insight into the microstructure of dentin which could be used to study the effect of age and pathologies. Furthermore, such information is essential for the design of biomaterials used in dentistry, e.g., to ensure more efficient bonding to dentin. Finally, our analysis of the tubular network structure provides valuable data that could be used directly as inputs in a numerical model