Sustained Ranavirus Outbreak Causes Mass Mortality and Morbidity of Imperiled Amphibians in Florida

EcoHealth - A persistent 2-month long outbreak of Ranavirus in a natural community of amphibians contributed to a mass die-off of gopher frog tadpoles (Lithobates capito) and severe disease in...     

Spontaneous meningoencephalitis by Staphylococcus aureus in an infant golden‐headed lion tamarin (Leontopithecus chrysomelas)

Non‐human primates are susceptible to many bacteria, some of which bear zoonotic potential. We report the pathologic features of spontaneous fulminating meningoencephalitis by Staphylococcus aureus in a captive infant golden‐headed lion tamarin (Leontopithecus chrysomelas) from Brazil.     

The use of electromyography for the assessment of sense of muscular effort: a test–retest reliability study

This study sought to examine the test–retest reliability to measure sense of muscular effort with electromyography (EMG). The EMG activity of the tibialis anterior muscle from 23 participants was recorded. Targets of EMG amplitudes produced at 10 and 20% of the maximum voluntary contraction (MVC) were calculated. Participants matched the target EMG level with and without visual feedback (FB). With NFB, the reliability was good to excellent when errors were represented as the average standard deviation (SD) of the error from the target (ICC_1,2 = 0.75 and 0.69 for 10 and 20% targets, respectively). Also, reliability was good when errors were presented as the average SD as a percentage of the MVC EMG (intraclass correlation coefficient (ICC_1,2) = 0.67 and 0.66, respectively, for 10 and 20% targets). Standard deviation around the target was the most reliable method to represent the error. This approach could be used as a simple cost-effective method to assess the sense of muscular effort.     

Methylglyoxal accumulation de-regulates HoxA5 expression,thereby impairing angiogenesis in glyoxalase 1 knock-down mouse aortic endothelial cells

Impaired angiogenesis leads to long-term complications and is a major contributor of the high morbidity in patients with Diabetes Mellitus (DM). Methylglyoxal (MGO) is a glycolysis byproduct that accumulates in DM and is detoxified by the Glyoxalase 1 (Glo1). Several studies suggest that MGO contributes to vascular complications through mechanisms that remain to be elucidated. In this study we have clarified for the first time the molecular mechanism involved in the impairment of angiogenesis induced by MGO accumulation.Angiogenesis was evaluated in mouse aortic endothelial cells isolated from Glo1-knockdown mice (Glo1KD MAECs) and their wild-type littermates (WT MAECs). Reduction in Glo1 expression led to an accumulation of MGO and MGO-modified proteins and impaired angiogenesis of Glo1KD MAECs. Both mRNA and protein levels of the anti-angiogenic HoxA5 gene were increased in Glo1KD MAECs and its silencing improved both their migration and invasion. Nuclear NF-?B-p65 was increased 2.5-fold in the Glo1KD as compared to WT MAECs. Interestingly, NF-?B-p65 binding to HoxA5 promoter was also 2-fold higher in Glo1KD MAECs and positively regulated HoxA5 expression in MAECs. Consistent with these data, both the exposure to a chemical inhibitor of Glo1 “SpBrBzGSHCp2” (GI) and to exogenous MGO led to the impairment of migration and the increase of HoxA5 mRNA and NF-?B-p65 protein levels in microvascular mouse coronary endothelial cells (MCECs).This study demonstrates, for the first time, that MGO accumulation increases the antiangiogenic factor HoxA5 via NF-?B-p65, thereby impairing the angiogenic ability of endothelial cells.     

Synthesis and larvicidal activity of indole derivatives against Aedes aegypti (Diptera: Culicidae)

In light of the challenges to control Aedes aegypti and the critical role that it plays as arbovirus vector, it is imperative to adopt strategies that provide fast, efficient and environmentally safe control of the insect population. In the present study, we synthesized six indole derivatives (C1‐C6) and examined their larvicidal activity and persistence against Ae. aegypti larvae, as well as their toxicity towards Raw 264.7 macrophages, Vero cells, Chlorella vulgaris BR017, Scenedesmus obliquus BR003, Caenorhabditis elegans N2 and Galleria mellonella. Among the bioactive compounds (C1, C2, C4 and C5), C2 exerted the strongest larvicidal activity against Ae. aegypti, with LC50 = 1.5 μg/ml (5.88 µM) and LC90 = 2.4 μg/ml (9.50 µM), indicating that the presence of chlorine or bromine groups in the aromatic ring improved the larvicidal activity of the indole derivatives. C1, C2, C4 and C5 did not reduce viability of RAW 264.7 macrophages, Vero cells, C. elegans N2 and G. mellonella. Compounds C1, C2 and C5 did not affect the growth of C. vulgaris BR017 and S. obliquus BR003. Analysis of larvicidal persistence under laboratory conditions revealed that the effect of compounds C1, C2, C4 and C5 lasted for 30 days and caused 100% of larvae mortality within few hours. Altogether, our findings demonstrate that the indole derivatives C1, C2, C4 and C5 effectively control Ae. aegypti larvae population, without clear signs of toxicity to mammalian cells, algae, C. elegans and G. mellonella.     

Expression and localization of DNA topoisomerase II during rat spermatogenesis

The potential role(s) of DNA topoiosmerase II (topo II) during chromatin changes that characterize different stages of spermatogenesis was investigated in the rat by an analysis of the expression and localization of topo II mRNA and protein in individual spermatogenic cells. Expression of topo II was restricted to spermatogonia, spermatocytes, and round and early-elongating spermatids. Two protein bands of 177 and 170 kDa were detected in immunoblots of spermatocytes and round spermatids, while bands of 148 and 142 kDa were prominent in preparations of elongating spermatids. Topo II levels and distribution patterns, as observed by immunofluorescent microscopy, exhibited cell type-specific variations. Differences in topo II staining patterns were also apparent when nuclear matrices of spermatogenic cells were prepared with different extraction conditions. In addition to its possible function as a structural component, topo II, associated with nuclear matrix preparations from spermatogenic cells, possessed catalytic activity. These observations indicate that both the 177 and 170 kDa and the 148 and 142 kDa forms of topo II share similar structural and functional properties. Topo IIβ mRNA was transcribed in rat spermatogenic cells at 6.2 kb. Relative levels of topo IIβ mRNA were high in spermatogonia and spermatocytes, and decreased in both round and early-elongating spermatids. Changes in topo II expression levels and localization patterns represent distinct stage-specific markers for the maturation of spermatogenic cells, and are consistent with the involvement of topo II in mediating DNA modifications and chromatin changes during spermatogenesis. © 1996 Wiley-Liss, Inc.     

Evidence for the emergence of β-trefoils by ‘Peptide Budding’ from an IgG-like β-sandwich

As sequence and structure comparison algorithms gain sensitivity, the intrinsic interconnectedness of the protein universe has become increasingly apparent. Despite this general trend, β-trefoils have emerged as an uncommon counterexample: They are an isolated protein lineage for which few, if any, sequence or structure associations to other lineages have been identified. If β-trefoils are, in fact, remote islands in sequence-structure space, it implies that the oligomerizing peptide that founded the β-trefoil lineage itself arose de novo. To better understand β-trefoil evolution, and to probe the limits of fragment sharing across the protein universe, we identified both ‘β-trefoil bridging themes’ (evolutionarily-related sequence segments) and ‘β-trefoil-like motifs’ (structure motifs with a hallmark feature of the β-trefoil architecture) in multiple, ostensibly unrelated, protein lineages. The success of the present approach stems, in part, from considering β-trefoil sequence segments or structure motifs rather than the β-trefoil architecture as a whole, as has been done previously. The newly uncovered inter-lineage connections presented here suggest a novel hypothesis about the origins of the β-trefoil fold itself–namely, that it is a derived fold formed by ‘budding’ from an Immunoglobulin-like β-sandwich protein. These results demonstrate how the evolution of a folded domain from a peptide need not be a signature of antiquity and underpin an emerging truth: few protein lineages escape nature’s sewing table.     

ZMAT3 hypomethylation contributes to early senescence of preadipocytes from healthy first‐degree relatives of type 2 diabetics

Senescence of adipose precursor cells (APC) impairs adipogenesis, contributes to the age‐related subcutaneous adipose tissue (SAT) dysfunction, and increases risk of type 2 diabetes (T2D). First‐degree relatives of T2D individuals (FDR) feature restricted adipogenesis, reflecting the detrimental effects of APC senescence earlier in life and rendering FDR more vulnerable to T2D. Epigenetics may contribute to these abnormalities but the underlying mechanisms remain unclear. In previous methylome comparison in APC from FDR and individuals with no diabetes familiarity (CTRL), ZMAT3 emerged as one of the top‐ranked senescence‐related genes featuring hypomethylation in FDR and associated with T2D risk. Here, we investigated whether and how DNA methylation changes at ZMAT3 promote early APC senescence. APC from FDR individuals revealed increases in multiple senescence markers compared to CTRL. Senescence in these cells was accompanied by ZMAT3 hypomethylation, which caused ZMAT3 upregulation. Demethylation at this gene in CTRL APC led to increased ZMAT3 expression and premature senescence, which were reverted by ZMAT3 siRNA. Furthermore, ZMAT3 overexpression in APC determined senescence and activation of the p53/p21 pathway, as observed in FDR APC. Adipogenesis was also inhibited in ZMAT3‐overexpressing APC. In FDR APC, rescue of ZMAT3 methylation through senolytic exposure simultaneously downregulated ZMAT3 expression and improved adipogenesis. Interestingly, in human SAT, aging and T2D were associated with significantly increased expression of both ZMAT3 and the P53 senescence marker. Thus, DNA hypomethylation causes ZMAT3 upregulation in FDR APC accompanied by acquisition of the senescence phenotype and impaired adipogenesis, which may contribute to FDR predisposition for T2D.