2,2′-(2,6-Pyridinedi­yl)diquinoline

The title mol­ecule, C23H15N3, is a terpyridine derivative resulting from the Friedländer annulation between 2,6-diacetyl­pyridine and N,N′-bis­(2-amino­benz­yl)ethyl­ene­di­amine. The asymmetric unit contains one half-mol­ecule, the complete mol­ecule being generated by a mirror plane (one N atom and one C atom lie on the plane). The mol­ecule, although aromatic, is deformed from planarity as a result of crystal packing forces: mol­ecules are stacked along the short c axis, with a short separation of 3.605 (1) Å between the mean planes. The bent mol­ecular shape is reflected in the dihedral angle of 16.10 (5)° between the essentially planar quinoline groups. In addition to π⋯π inter­actions, the crystal structure features weak inter-stack C—H⋯N contacts involving atoms of the central pyridine rings which lie in a common crystallographic m plane

West Nile Virus Isolation in Human and Mosquitoes, Mexico

West Nile virus has been isolated for the first time in Mexico, from a sick person and from mosquitoes (Culex quinquefasciatus). Partial sequencing and analysis of the 2 isolates indicate that they are genetically similar to other recent isolates from northern Mexico and the western United States

Allograft Inflammatory Factor-1 Governs Hematopoietic Stem Cell Differentiation Into cDC1 and Monocyte-Derived Dendritic Cells Through IRF8 and RelB in vitro

The multistep differentiation process from hematopoietic stem cells through common myeloid progenitors into committed dendritic cell (DC) subsets remains to be fully addressed. These studies now show that Allograft Inflammatory Factor-1 (AIF1) is required for differentiation of classical DC type 1 (cDC1) subsets and monocyte-derived DC (Mo-DC). Phenotypic studies found that AIF1 expression increased in committed subsets differentiating from common myeloid progenitors (CMP). However, silencing AIF1 expression in hematopoietic stem progenitors restrained the capacity to differentiate into Mo-DC and cDC1 cell subsets under GM-CSF or Flt3-L stimuli conditions, respectively. This was further marked by restrained expression of IRF8, which is critical for development of Mo-DC and cDC1 subsets. As a result, absence of AIF1 restrained the cells at the Lin−CD117+FcγR−CD34+ CMP stage. Further biochemical studies revealed that abrogating AIF1 resulted in inhibition of the NFκB family member RelB expression and p38 MAPK phosphorylation during differentiation of Mo-DC. Lastly, protein binding studies identified that AIF1 interacts with protein kinase C (PKC) to influence downstream signaling pathways. Taken together, this is the first report showing a novel role of AIF1 as a calcium-responsive scaffold protein that supports IRF8 expression and interacts with PKC to drive NFκB-related RelB for successfully differentiating hematopoietic progenitor cells into cDC and Mo-DC subsets under Flt3-L and GM-CSF stimuli, respectively

Ecoepidemiology of Alphaviruses and Flaviviruses

Within the ecosystems, the balance is important since the populations maintain their size and the food habits that are constant over time; in contrast, the disappearance of natural sources or the alteration of habitat at different levels can cause major changes in the very structure of the ecosystem. Alterations in the habitats produced by human activity result in global warming, climatic changes, which together with globalization, increased trade, the shortening of distances thanks to transport, the increase in population and the socioeconomic activities of human cause imbalances. In many cases the vectors and hosts have adapted to the changes and have risen to higher latitudes and altitudes, which could contribute to the appearance of outbreaks or new outbreaks of new arboviruses of public health importance. Different cohabiting species can be reservoirs or vectors of arboviruses such as alphaviruses and flaviviruses. Currently, some viruses transmitted by mosquito vectors, such as dengue virus, Zika virus, and chikungunya virus, have caused epidemic outbreaks with important effects on human populations. It is possible that the expansion of vectors and their diseases reaches developed countries such as the United States and the European Union with a great impact on public health. The clinical signs of the diseases produced by arboviruses can vary from nonspecific febrile syndrome, encephalitis, hemorrhagic fever, and even death. Vectors and reservoirs in some cases are insects, such as mosquitoes and ticks; wild birds are reservoirs for the West Nile virus, small wild mammals such as rodents, bats, and domestic animals involved in food production can potentially harbor arboviruses, and the ecoepidemiological role of these is unknown. © 2020 Elsevier Inc. All rights reserved

Blockade of TRPM7 Channel Activity and Cell Death by Inhibitors of 5-Lipoxygenase

TRPM7 is a ubiquitous divalent-selective ion channel with its own kinase domain. Recent studies have shown that suppression of TRPM7 protein expression by RNA interference increases resistance to ischemia-induced neuronal cell death in vivo and in vitro, making the channel a potentially attractive pharmacological target for molecular intervention. Here, we report the identification of the 5-lipoxygenase inhibitors, NDGA, AA861, and MK886, as potent blockers of the TRPM7 channel. Using a cell-based assay, application of these compounds prevented cell rounding caused by overexpression of TRPM7 in HEK-293 cells, whereas inhibitors of 12-lipoxygenase and 15-lipoxygenase did not prevent the change in cell morphology. Application of the 5-lipoxygenase inhibitors blocked heterologously expressed TRPM7 whole-cell currents without affecting the protein's expression level or its cell surface concentration. All three inhibitors were also effective in blocking the native TRPM7 current in HEK-293 cells. However, two other 5-lipoxygenase specific inhibitors, 5,6-dehydro-arachidonic acid and zileuton, were ineffective in suppressing TRPM7 channel activity. Targeted knockdown of 5-lipoxygenase did not reduce TRPM7 whole-cell currents. In addition, application of 5-hydroperoxyeicosatetraenoic acid (5-HPETE), the product of 5-lipoxygenase, or 5-HPETE's downstream metabolites, leukotriene B4 and leukotriene D4, did not stimulate TRPM7 channel activity. These data suggested that NDGA, AA861, and MK886 reduced the TRPM7 channel activity independent of their effect on 5-lipoxygenase activity. Application of AA861 and NDGA reduced cell death for cells overexpressing TRPM7 cultured in low extracellular divalent cations. Moreover, treatment of HEK-293 cells with AA861 increased cell resistance to apoptotic stimuli to a level similar to that obtained for cells in which TRPM7 was knocked down by RNA interference. In conclusion, NDGA, AA861, and MK886 are potent blockers of the TRPM7 channel capable of attenuating TRPM7's function during cell stress, making them effective tools for the biophysical characterization and suppression of TRPM7 channel conductance in vivo

Alfvén wave heating and runaway discharges in the TCABR tokamak

Recent results of experiments on Alfvén wave heating and runaway discharges carried out in the TCABR tokamak are presented. A new antenna type has been installed to allow wave excitation with higher RF currents and lower dynamic polarization of the antenna straps than for the one previously used. In spite of edge plasma heating, which causes influx of impurities, we have obtained a clear confirmation of wave deposition inside the plasma from a localized increase of the electron temperature measured with the ECE radiometer. Detailed profiles of the plasma density and Ha emission were obtained in runaway disharges with currents around 100 kA. These profiles confirm our model of a low-temperature plasma maintained in equilibrium by the relativistic electron beam. Analysis of the Ha and density spikes indicate that recombination plays a substantial role in the particle and energy balance

A Positive Regulatory Loop between foxi3a and foxi3b Is Essential for Specification and Differentiation of Zebrafish Epidermal Ionocytes

BACKGROUND: Epidermal ionocytes play essential roles in the transepithelial transportation of ions, water, and acid-base balance in fish embryos before their branchial counterparts are fully functional. However, the mechanism controlling epidermal ionocyte specification and differentiation remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: In zebrafish, we demonstrated that Delta-Notch-mediated lateral inhibition plays a vital role in singling out epidermal ionocyte progenitors from epidermal stem cells. The entire epidermal ionocyte domain of genetic mutants and morphants, which failed to transmit the DeltaC-Notch1a/Notch3 signal from sending cells (epidermal ionocytes) to receiving cells (epidermal stem cells), differentiates into epidermal ionocytes. The low Notch activity in epidermal ionocyte progenitors is permissive for activating winged helix/forkhead box transcription factors of foxi3a and foxi3b. Through gain- and loss-of-function assays, we show that the foxi3a-foxi3b regulatory loop functions as a master regulator to mediate a dual role of specifying epidermal ionocyte progenitors as well as of subsequently promoting differentiation of Na(+),K(+)-ATPase-rich cells and H(+)-ATPase-rich cells in a concentration-dependent manner. CONCLUSIONS/SIGNIFICANCE: This study provides a framework to show the molecular mechanism controlling epidermal ionocyte specification and differentiation in a low vertebrate for the first time. We propose that the positive regulatory loop between foxi3a and foxi3b not only drives early ionocyte differentiation but also prevents the complete blockage of ionocyte differentiation when the master regulator of foxi3 function is unilaterally compromised

Calf health from birth to weaning. I. General aspects of disease prevention

Calfhood diseases have a major impact on the economic viability of cattle operations. This is the first in a three part review series on calf health from birth to weaning, focusing on preventive measures. The review considers both pre- and periparturient management factors influencing calf health, colostrum management in beef and dairy calves and further nutrition and weaning in dairy calves