Whole-Exome Sequencing Identifies Mutated C12orf57 in Recessive Corpus Callosum Hypoplasia

The corpus callosum is the principal cerebral commissure connecting the right and left hemispheres. The development of the corpus callosum is under tight genetic control, as demonstrated by abnormalities in its development in more than 1,000 genetic syndromes. We recruited more than 25 families in which members affected with corpus callosum hypoplasia (CCH) lacked syndromic features and had consanguineous parents, suggesting recessive causes. Exome sequence analysis identified C12orf57 mutations at the initiator methionine codon in four different families. C12orf57 is ubiquitously expressed and encodes a poorly annotated 126 amino acid protein of unknown function. This protein is without significant paralogs but has been tightly conserved across evolution. Our data suggest that this conserved gene is required for development of the human corpus callosum.     

Intra‐specific pollen polymorphism in Mimosa pigra (Mimosaceae)

Five different types of pollen tetrads were detected from the short and long stamens of the male and hermaphrodite flowers of the androdioecious species, Mimosa pigra L. Light (LM) and scanning electron microscopes (SEM) were used in this study to redescribe the pollen forms and to identify the various pollen types encountered. An identification key and relative percentages of these pollen types were also presented. The study showed that the long stamens of the male flowers and those of the hermaphrodite ones have five (I, II, III, IV and V) and two (I and V) pollen types respectively, whereas the short stamens of both male and hermaphrodite flowers have only one pollen type (type I). We report here the first incidence of intra‐specific pollen polymorphism in androdioecious species.     

Interleukin 6 and/or Interleukin 17A Modulate the OPG/RANKL System of MC3T3-E1 Murine Osteoblast Cell Line

Cytokines such as interleukin-6 (IL-6) and IL-17 which act as key regulators of the immune response have been identified to have a potential role in the bone remodeling mechanism. Receptor activator of NF-κB ligand (RANKL) has been shown to regulate osteoclast differentiation and function while the osteoprotegerin (OPG) blocks the binding of RANKL and inhibits the differentiation of osteoclasts, thus favoring osteogenesis. Alkaline phosphatase (ALP) on the other hand works as early mineralization indicator in bone regulation. The current study aims to determine the potential role of IL-6 and IL-17A in regulating the OPG/RANKL system of the murine osteoblast cell line (MC3T3-E1). Gene expression analysis showed significant up-regulation of OPG and ALP by all the treated groups (rIL-6, rIL-17A and rIL-6 + rIL-17A). In contrast, treatment of cells with rIL-6 and/or rIL-17A showed down-regulation of RANKL expression. Interestingly, the osteoblast cells treated with combinations of rIL-6 + rIL17A showed marked increased in OPG/RANKL ratio. Similar pattern of protein expression was observed in the osteoblasts treated with rIL-6 and/or rIL-17A as detected by western blotting and ELISA. These findings suggest a new mechanism of regulation by these cytokines on the expression of OPG and RANKL, which could promote osteogenesis and diminish osteoclastogenesis.     

Heavy metal uptake capacity of fresh water algae (Oedogonium westti) from aqueous solution: A mesocosm research

The green macroalgae present in freshwater ecosystems have attracted a great attention of the world scientists for removal of heavy metals from wastewater. In this mesocosm study, the uptake rates of heavy metals such as cadmium (Cd), nickel (Ni), chromium (Cr), and lead (Pb) by Oedogonium westi (O. westti) were measured. The equilibrium adsorption capabilities of O. westti were different for Cd, Ni, Cr, and Pb (0.974, 0.418, 0.620, and 0.261 mgg^–1, respectively) at 18°C and pH 5.0. Furthermore, the removal efficiencies for Cd, Cr, Ni and Pb were observed from 55–95%, 61–93%, 59–89%, and 61–96%, respectively. The highest removal efficiency was observed for Cd and Cr from aqueous solution at acidic pH and low initial metal concentrations. However, the removal efficiencies of Ni and Pb were higher at high pH and high concentrations of metals in aqueous solution. The results summarized that O. westti is a suitable candidate for removal of selected toxic heavy metals from the aqueous solutions.     

A unique role for nonmuscle myosin heavy chain IIA in regulation of epithelial apical junctions

The integrity and function of the epithelial barrier is dependent on the apical junctional complex (AJC) composed of tight and adherens junctions and regulated by the underlying actin filaments. A major F-actin motor, myosin II, was previously implicated in regulation of the AJC, however direct evidence of the involvement of myosin II in AJC dynamics are lacking and the molecular identity of the myosin II motor that regulates formation and disassembly of apical junctions in mammalian epithelia is unknown. We investigated the role of nonmuscle myosin II (NMMII) heavy chain isoforms, A, B, and C in regulation of epithelial AJC dynamics and function. Expression of the three NMMII isoforms was observed in model intestinal epithelial cell lines, where all isoforms accumulated within the perijunctional F-actin belt. siRNA-mediated downregulation of NMMIIA, but not NMMIIB or NMMIIC expression in SK-CO15 colonic epithelial cells resulted in profound changes of cell morphology and cell-cell adhesions. These changes included acquisition of a fibroblast-like cell shape, defective paracellular barrier, and substantial attenuation of the assembly and disassembly of both adherens and tight junctions. Impaired assembly of the AJC observed after NMMIIA knock-down involved dramatic disorganization of perijunctional actin filaments. These findings provide the first direct non-pharmacological evidence of myosin II-dependent regulation of AJC dynamics in mammalian epithelia and highlight a unique role of NMMIIA in junctional biogenesis.     

Aspirin inhibits cancer stem cells properties and growth of glioblastoma multiforme through Rb1 pathway modulation

Several clinical studies indicated that the daily use of aspirin or acetylsalicylic acid reduces the cancer risk via cyclooxygenases (Cox-1 and Cox-2) inhibition. In addition, aspirin-induced Cox-dependent and -independent antitumor effects have also been described. Here we report, for the first time, that aspirin treatment of human glioblastoma cancer (GBM) stem cells, a small population responsible for tumor progression and recurrence, is associated with reduced cell proliferation and motility. Aspirin did not interfere with cell viability but induced cell-cycle arrest. Exogenous prostaglandin E₂ significantly increased cell proliferation but did not abrogate the aspirin-mediated growth inhibition, suggesting a Cox-independent mechanism. These effects appear to be mediated by the increase of p21 ^waf1 and p27 ^Kip1, associated with a reduction of Cyclin D1 and Rb1 protein phosphorylation, and involve the downregulation of key molecules responsible for tumor development, that is, Notch1, Sox2, Stat3, and Survivin. Our results support a possible role of aspirin as adjunctive therapy in the clinical management of GBM patients.     

Two case reports of unusual phimosis in rhesus monkeys (Macaca Mulatta)

Phimosis is the inability of the penis to protrude from the prepuce. In the present report, we present two cases of phimosis in two rhesus monkeys. Surgical enlargement of preputial orifice was performed for unrestricted movement of penis. The exact cause of this condition is unknown to us.     

Performance evaluation measures for protein complex prediction

Protein complexes play a dominant role in cellular organization and function. Prediction of protein complexes from the network of physical interactions between proteins (PPI networks) has thus become one of the important research areas. Recently, many computational approaches have been developed to identify these complexes. Various performance assessment measures have been proposed for evaluating the efficiency of these methods. However, there are many inconsistencies in the definitions and usage of the measures across the literature. To address this issue, we have gathered and presented the most important performance evaluation measures and developed a tool, named CompEvaluator, to critically assess the protein complex prediction methods. The tool and documentation are publicly available at https://sourceforge.net/projects/compevaluator/files/.     

Targeting human telomeric DNA quadruplex with novel berberrubine derivatives: insights from spectroscopic and docking studies

Study on bioactive molecules, capable of stabilizing G-Quadruplex structures is considered to be a potential strategy for anticancer drug development. Berberrubine (BER) and two of its analogs bearing alkyl phenyl and biphenyl substitutions at 13-position were studied for targeting human telomeric G-quadruplex DNA sequence. The structures of berberrubine and analogs were optimized by density functional theory (DFT) calculations. Time-dependent DFT (B3LYP) calculations were used to establish and understand the nature of the electronic transitions observed in UV–vis spectra of the alkaloid. The interaction of berberrubine and its analogs with human telomeric G-quadruplex DNA sequence 5′-(GGGTTAGGGTTAGGGTTAGGG)-3′ was investigated by biophysical techniques and molecular docking study. Both the analogs were found to exhibit higher binding affinity than natural precursor berberrrubine. 13-phenylpropyl analog (BER1) showed highest affinity [(1.45 ± 0.03) × 10⁵ M^?1], while the affinity of the 13-diphenyl analog (BER2) was lower at (1.03 ± 0.05) × 10⁵ M^?1, and that of BER was (0.98 ± 0.03) × 10⁵ M^?1. Comparative fluorescence quenching studies gave evidence for a stronger stacking interaction of the analog compared to berberrubine. The thiazole orange displacement assay has clearly established that the analogs were more effective in displacing the end stacked dye in comparison to berberrubine. Molecular docking study showed that each alkaloid ligand binds primarily at the G rich regions of hTelo G4 DNA which makes them G specific binder towards hTelo G4 DNA. Isothermal titration calorimetry studies of quadruplex–berberrubine analog interaction revealed an exothermic binding that was favored by both enthalpy and entropy changes in BER in contrast to the analogs where the binding was majorly enthalpy dominated. A 1:1 binding stoichiometry was revealed in all the systems. This study establishes the potentiality of berberrubine analogs as a promising natural product based compounds as G-quadruplex-specific ligands.     

Upper Cenomanian bivalves from the Guir Basin (southwestern Algeria): Order Veneroida

The Upper Cretaceous rocks are widely distributed and well exposed in south Algeria and consist in beds rich in macrofauna. For the first time, twenty veneroid species (Bivalvia) are systematically described from the upper Cenomanian deposits of the Guir Basin. While three species were reported since long before [Granocardium desvauxi (Coquand), G. productum (J. de C. Sowerby) and Glossus aquilinus (Coquand)]; Lucina fallax Forbes, Crassatella (Rochella) tenuicostata (Seguenza), Protocardia hillana (J. Sowerby), G. productum (J. de C. Sowerby) var. byzacenica (Pervinquière), Arctica cordata (Sharpe), A. humei (Cox), A. inornata (d’Orbigny), A. picteti (Coquand), Tenea delettrei (Coquand), Paraesa faba (J. de C. Sowerby), Meretrix desvauxi (Coquand) were previously unknown from the Cretaceous of Algerian Sahara. Because of reduced degree of preservation, Sphaera cf. corrugata J. Sowerby, Maghrebella cf. forgemoli (Coquand), Maghrebella sp., Granocardium cf. carolinum (d’Orbigny), Protocardia sp. and Meretrix sp. are tentatively determined. The studied material, found in the lower part of the “Calcaires de Sidi Mohamed Ben Bouziane” Formation, evidences palaeobiogeographic affinities occurring over a wide geographical area: from North Africa, southern Europe to Middle East and India. The present study provides new information to the knowledge of the upper Cenomanian palaeobiology of the studied region.