Evaluating Sex Related Differences in the Osteocyte Lacunar Canalicular Network Across the Lifespan: A Confocal Laser Scanning Microscopy Approach

Bone is a dynamic tissue with the ability to remodel itself. This capability is facilitated via communication mechanisms through the osteocyte-lacunar-canalicular (LCN) network. Osteocytes are bone cells housed in small, hollow spaces called lacunae. Lacunae are linked by canals called canaliculi. A diminished network can lead to the inability to form bone following breakdown. A decrease in osteocyte-LCN density has been shown to correlate with aging (Ashique et al. 2017). This decline leads to the development of osteoporosis. Osteoporosis preferentially affects women. Prior studies have shown that women older than 50 are four times more likely to be osteoporotic when compared to their male counterparts (Alswat 2017). However, it is unclear why women are more affected. Furthermore, there is a gap in knowledge pertaining to the timing of osteocyte-LCN decrease. We hypothesize that a significant decrease in osteocyte-LCN volume will appear in females greater than age 45, suggesting a link to changes associated with menopause. Additionally, we anticipate that females will exhibit a lower osteocyte-LCN volume than males. By comparing volumetric measurements of the osteocyte LCN network between males and females across the lifespan, we hope to elucidate the timing of the large decline and draw conclusions across sexes

Financial Development and Economic Growth in Nigeria

The study empirically evaluates the impact of financial development on economics growth in Nigeria. The paper employed annual times series data spanning through a period of 43 years (1970 to 2012). The finding of our study suggests that the theoretical modelling requirements for all the variables used in the regression satisfy the statistical requirements which determine the choice of our model. The result of the co-integration estimates in the study revealed that the selected independent variable used in this study explains long-run relationship between financial development and economic growth between the period under consideration. The result from the estimated long–run Parsimonious Error Correction Model (ECM) shows that all the variables used in the study were statistically significant. The study also reveals that lending rate did not conform to our theoretical expectation but impacts significantly on gross domestic product. Commercial bank credit to private sector has the expected a priori expectation sign and also positively affected financial development and economic growth in our study. Contrary to our expectation, MGDP negatively influenced financial development and economic growth in Nigeria. The study also indicates that commercial bank credit to non-financial private firm did not conforms to a priori expectation but significantly influenced or stimulated financial development and economic growth in the Nigerian economy. The ratio of commercial bank deposit to gross domestic product (RDEP) appeared with the right sign and also impacts significantly on financial development and economic growth in Nigeria. The evidence from our study shows that the entire model is stable within the period of study. We therefore recommend that monetary authorities should endeavour to make policies that will impact positively on the overall growth of the economy. The significant impact of lending rate on GDP does not no mean that government embark on policies measures that would improve lending rate but focus policies that would lead to employment generating, increase in income as well as conducive atmosphere for businesses to operate. Given the strong positive evidence of bank credit to private sector, government should make policies as well as provide a conducive business environment that would ensure banks provide more credit to private sector (loans) for businesses, who will invest such funds for productive purposes that will yield the desired or required return and this will lead to an improvement in the GDP growth. Keywords: Financial development, Economic growth, ECM, Stability, Granger causality.Classification Code: C22, C87,  E44, F62, O4

THE MEDIATING EFFECT OF WORK ETHICS ON THE RELATIONSHIP BETWEEN TRANSFORMATIVE LEARNING AND PROFESSIONAL DEVELOPMENT OF TEACHERS

The purpose of this study was to determine the mediating effect of work ethics on the relationship between transformative learning and the professional development of teachers. Utilizing quantitative, non-experimental design via correlational technique, data were obtained from 300 elementary public school teachers who belong to the 3 districts, Magsaysay, Bansalan and Matanao under the Division of Davao Del Sur. The researcher utilized a stratified random sampling technique and an online survey mode of data collection. The researcher also utilized the statistical tools mean, Pearson r and Sobel Z Test. From the results of the study, it was found out that the overall mean scores of work ethics, transformative learning and professional development of teachers are very high. Also, results revealed that there are significant relationships between transformative learning and professional development, between transformative learning and work ethics and between work ethics and professional development of teachers. Further, it was revealed that there was a partial mediation effect of work ethics on the relationship between transformative learning and the professional development of teachers.  Article visualizations

Cytogenetic analysis and FISH of terminal deletion of the long arm of chromosome 9 in a patient with acute promyelocytic leukemia.

Deletions of the long arm of chromosome 9, del(9)(q22), are rare aberrations specifically found in acute myeloid leukemia (AML). Yamamoto et al, 1999, reported the first case of acute promyelocytic leukemia (APL) with a terminal 9q deletion as a sole abnormality. Here we describe the second case with the same aberration, the patient, an eleven-years-old girl with APL. Chromosomal analysis by the Giemsa R-banding technique and FISH using BCR/ABL and PML/RARA probe on short-term cell cultures from bone marrow was performed. A deletion of a 9 chromosome, del(9)(q22) was detected. Deletions of 9q have been described in about 3% to 4% of the AML patients, especially in M1 and M2 myeloid leukemia. Sole 9q terminal deletions, are less common than interstitial ones and involve q21~q22 band predominantly. A recent study suggests that 9q deletion, even in the absence of t(15;17), shows a relatively good prognosis. However, our patient died during the treatment

A Systemically-Administered Small Molecule Antagonist of CCR9 Acts as a Tissue-Selective Inhibitor of Lymphocyte Trafficking

A goal for developers of immunomodulatory drugs has long been a systemically administered small molecule that can selectively inhibit inflammation in specific tissues. The chemokine receptor CCR9 is an attractive target for this approach, as entry of T cells into the small intestine from blood requires interaction between CCR9 and its ligand CCL25. We have tested the ability of a small molecule CCR9 antagonist, CCX8037, to inhibit antigen-mediated T cell accumulation in the intestine. This compound prevented accumulation of gut-imprinted antigen-specific CD8 T cells within epithelium of the small intestine. Interestingly, the antagonist did not affect the robust generation of gut-imprinted CD8 T cells within mesenteric lymph nodes. To distinguish “gut-selective” from “general” T cell inhibition, we tested the drug’s ability to influence accumulation of T cells within skin, a tissue in which CCR9 plays no known role, and we found no appreciable effect. This study demonstrates the feasibility of creating systemically-administered pharmaceuticals capable of tissue-selective immune modulation. This proof of concept is of utmost importance for designing effective treatments against various autoimmune disorders localized to a specific tissue

A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei

Tissue-specific patterns of methylated deoxycytidine residues in the mammalian genome are preserved by postreplicative methylation of newly synthesized DNA. DNA methyltransferase (MTase) is here shown to associate with replication foci during S phase but to display a diffuse nucleoplasmic distribution in non-S phase cells. Analysis of DNA MTase-β-galactosidase fusion proteins has shown that association with replication foci is mediated by a novel targeting sequence located near the N-terminus of DNA MTase. This sequence has the properties expected of a targeting sequence in that it is not required for enzymatic activity, prevents proper targeting when deleted, and, when fused to β-galactosidase, causes the fusion protein to associate with replication foci in a cell cycle-dependent manner

Dynamics of DNA Replication Factories in Living Cells

DNA replication occurs in microscopically visible complexes at discrete sites (replication foci) in the nucleus. These foci consist of DNA associated with replication machineries, i.e., large protein complexes involved in DNA replication. To study the dynamics of these nuclear replication foci in living cells, we fused proliferating cell nuclear antigen (PCNA), a central component of the replication machinery, with the green fluorescent protein (GFP). Imaging of stable cell lines expressing low levels of GFP-PCNA showed that replication foci are heterogeneous in size and lifetime. Time-lapse studies revealed that replication foci clearly differ from nuclear speckles and coiled bodies as they neither show directional movements, nor do they seem to merge or divide. These four dimensional analyses suggested that replication factories are stably anchored in the nucleus and that changes in the pattern occur through gradual, coordinated, but asynchronous, assembly and disassembly throughout S phase

Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells

Valency requirements for B cell activation upon antigen encounter are poorly understood. OB1 transnuclear B cells express an IgG1 B cell receptor (BCR) specific for ovalbumin (OVA), the epitope of which can be mimicked using short synthetic peptides to allow antigen-specific engagement of the BCR. By altering length and valency of epitope-bearing synthetic peptides, we examined the properties of ligands required for optimal OB1 B cell activation. Monovalent engagement of the BCR with an epitope-bearing 17-mer synthetic peptide readily activated OB1 B cells. Dimers of the minimal peptide epitope oriented in an N to N configuration were more stimulatory than their C to C counterparts. Although shorter length correlated with less activation, a monomeric 8-mer peptide epitope behaved as a weak agonist that blocked responses to cell-bound peptide antigen, a blockade which could not be reversed by CD40 ligation. The 8-mer not only delivered a suboptimal signal, which blocked subsequent responses to OVA, anti-IgG, and anti-kappa, but also competed for binding with OVA. Our results show that fine-tuning of BCR-ligand recognition can lead to B cell nonresponsiveness, activation, or inhibition

Diversity of the CD4 T Cell Alloresponse: The Short and the Long of It.

MHC alloantigen is recognized by two pathways: "directly," intact on donor cells, or "indirectly," as self-restricted allopeptide. The duration of each pathway, and its relative contribution to allograft vasculopathy, remain unclear. Using a murine model of chronic allograft rejection, we report that direct-pathway CD4 T cell alloresponses, as well as indirect-pathway responses against MHC class II alloantigen, are curtailed by rapid elimination of donor hematopoietic antigen-presenting cells. In contrast, persistent presentation of epitope resulted in continual division and less-profound contraction of the class I allopeptide-specific CD4 T cell population, with approximately 10,000-fold more cells persisting than following acute allograft rejection. This expanded population nevertheless displayed sub-optimal anamnestic responses and was unable to provide co-stimulation-independent help for generating alloantibody. Indirect-pathway CD4 T cell responses are heterogeneous. Appreciation that responses against particular alloantigens dominate at late time points will likely inform development of strategies aimed at improving transplant outcomes.This work was supported by a British Heart Foundation project grant, the National Institute of Health Research Cambridge Biomedical Research Centre, and the National Institute of Health Research Blood and Transplant Research Unit. J.M.A. was supported by a Wellcome Trust Clinical Research Training Fellowship and Raymond and Beverly Sackler Scholarships. K.S.-P. was supported by an Academy of Medical Sciences/Wellcome Trust starter grant