Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration

Type 2 diabetes (T2D) is a disease characterized by impaired insulin secretion. The Wnt signaling transcription factor Tcf7l2 is to date the T2D-associated gene with the largest effect on disease susceptibility. However, the mechanisms by which TCF7L2 variants affect insulin release from \u3b2-cells are not yet fully understood. By taking advantage of a tcf7l2 zebrafish mutant line, we first show that these animals are characterized by hyperglycemia and impaired islet development. Moreover, we demonstrate that the zebrafish tcf7l2 gene is highly expressed in the exocrine pancreas, suggesting potential bystander effects on \u3b2-cell growth, differentiation and regeneration. Finally, we describe a peculiar vascular phenotype in tcf7l2 mutant larvae, characterized by significant reduction in the average number and diameter of pancreatic islet capillaries. Overall, the zebrafish Tcf7l2 mutant, characterized by hyperglycemia, pancreatic and vascular defects, and reduced regeneration proves to be a suitable model to study the mechanism of action and the pleiotropic effects of Tcf7l2, the most relevant T2D GWAS hit in human populations

The roles of the classical and alternative nuclear factor-kappaB pathways: potential implications for autoimmunity and rheumatoid arthritis

Nuclear factor-κB (NF-κB) is an inducible transcription factor controlled by two principal signaling cascades, each activated by a set of signal ligands: the classical/canonical NF-κB activation pathway and the alternative/noncanonical pathway. The former pathway proceeds via phosphorylation and degradation of inhibitor of NF-κB (IκB) and leads most commonly to activation of the heterodimer RelA/NF-κB1(p50). The latter pathway proceeds via phosphorylation and proteolytic processing of NF-κB2 (p100) and leads to activation, most commonly, of the heterodimer RelB/NF-κB2 (p52). Both pathways play critical roles at multiple levels of the immune system in both health and disease, including the autoimmune inflammatory response. These roles include cell cycle progression, cell survival, adhesion, and inhibition of apoptosis. NF-κB is constitutively activated in many autoimmune diseases, including diabetes type 1, systemic lupus erythematosus, and rheumatoid arthritis (RA). In this review we survey recent developments in the involvement of the classical and alternative pathways of NF-κB activation in autoimmunity, focusing particularly on RA. We discuss the involvement of NF-κB in self-reactive T and B lymphocyte development, survival and proliferation, and the maintenance of chronic inflammation due to cytokines such as tumor necrosis factor-α, IL-1, IL-6, and IL-8. We discuss the roles played by IL-17 and T-helper-17 cells in the inflammatory process; in the activation, maturation, and proliferation of RA fibroblast-like synovial cells; and differentiation and activation of osteoclast bone-resorbing activity. The prospects of therapeutic intervention to block activation of the NF-κB signaling pathways in RA are also discussed

Multi-Round Attacks on Structural Controllability Properties for Non-Complete Random Graphs

The notion of controllability, informally the ability to force a systeminto a desired state in a finite time or number of steps, is most closely associatedwith control systems such as those used to maintain power networks andother critical infrastructures, but has wider relevance in distributed systems. Itis clearly highly desirable to understand under which conditions attackers maybe able to disrupt legitimate control, or to force overriding controllability themselves.Following recent results by Liu et al., there has been considerable interestalso in graph-theoretical interpretation of Kalman controllability originally introducedby Lin, structural controllability. This permits the identification of sets ofdriver nodes with the desired state-forcing property, but determining such nodesis a W[2]-hard problem. To extract these nodes and represent the control relation,here we apply the POWER DOMINATING SET problem and investigate the effectsof targeted iterative multiple-vertex removal. We report the impact that differentattack strategies with multiple edge and vertex removal will have, based on underlyingnon-complete graphs, with an emphasis on power-law random graphswith different degree sequences

Detection of microbial contamination in potable water by Nanowire technology

It is well known that the lack of control and sanitation of water in developing countries has cause very significant epidemiological events. In the last decades the situation of water supplies and sanitation has improve all over the world. Despite of it, in the European Union there are a considerable number of confirmed cases of water-borne infections even though the restrictive law. Electronic Noses (ENs) has shown to be a very effective and fast tool for monitoring microbiological spoilage and quality control. The aim of this study was test the ability of a novel EN for the detection of bacterial presence in potable water in cooperation with analytical (pH) and optical (photometer) techniques. The achieved results notably advocate the use of EN in industry laboratories as a very important tool in water quality control

Comparison of Conventional Polyethylene Wear and Signs of Cup Failure in Two Similar Total Hip Designs

Multiple factors have been identified as contributing to polyethylene wear and debris generation of the acetabular lining. Polyethylene wear is the primary limiting factor in the functional behavior and consequent longevity of a total hip arthroplasty (THA). This retrospective study reviewed the clinical and radiographic data of 77 consecutive THAs comparing in vivo polyethylene wear of two similar acetabular cup liners. Minimum follow-up was 7 years (range 7–15). The incidence of measurable wear in a group of machined liners sterilized with ethylene oxide and composed of GUR 1050 stock resin was significantly higher (61%) than the compression-molded, GUR 1020, O(2)-free gamma irradiation sterilized group (24%) (P = 0.0004). Clinically, at a 9-year average followup, both groups had comparable HHS scores and incidence of thigh or groin pain, though the machined group had an increased incidence of osteolysis and annual linear wear rate

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

2020-04-06 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: NM case updates. Several NM policy and legislative actions. Federal vs. state conflict over medical supply lines. Healthcare workers sleep in cars to prevent family exposure. Same-day in-house testing at Cedars-Sinai. Debate over hydroxychloroquine Tx. Death rate differences: Germany and Italy. African innovations. Testing recommended with mild symptoms. CDC guidelines for law enforcement PPE. New WHO first responder training and CDC sign language resources. COVID-19 droplets can travel up to 27 feet. Transmission from the asymptomatic. Humidifiers help. Drug and vaccine progress

Probing the Sub-Parsec Dust of a Supermassive Black Hole with the Tidal Disruption Event AT 2020mot

AT 2020mot is a typical UV/optical tidal disruption event (TDE) with no radio or X-ray signatures in a quiescent host. We find an i-band excess and re-brightening along the decline of the light curve which could be due to two consecutive dust echoes from a TDE. We model our observations following van Velzen et al. (2016) and find that the near-infrared light curve can be explained by concentric rings of thin dust within $\sim$0.1 parsecs of a 6e6 M$_{\odot}$ supermassive black hole (SMBH), among the smallest scales at which dust has been inferred near SMBHs. We find dust covering factors of order fc $\leq$ 2%, much lower than found for dusty tori of active galactic nuclei. These results highlight the potential of TDEs for uncovering the environments around black holes when including near-infrared observations in high-cadence transient studies