The ventilation of buildings and other mitigating measures for COVID-19: a focus on wintertime.

The year 2020 has seen the emergence of a global pandemic as a result of the disease COVID-19. This report reviews knowledge of the transmission of COVID-19 indoors, examines the evidence for mitigating measures, and considers the implications for wintertime with a focus on ventilation.This work was undertaken as a contribution to the Rapid Assistance in Modelling the Pandemic (RAMP) initiative, coordinated by the Royal Society

The Small GTPase RhoA Localizes to the Nucleus and Is Activated by Net1 and DNA Damage Signals

Rho GTPases control many cellular processes, including cell survival, gene expression and migration. Rho proteins reside mainly in the cytosol and are targeted to the plasma membrane (PM) upon specific activation by guanine nucleotide exchange factors (GEFs). Accordingly, most GEFs are also cytosolic or associated with the PM. However, Net1, a RhoA-specific GEF predominantly localizes to the cell nucleus at steady-state. Nuclear localization for Net1 has been seen as a mechanism for sequestering the GEF away from RhoA, effectively rendering the protein inactive. However, considering the prominence of nuclear Net1 and the fact that a biological stimulus that promotes Net1 translocation out the nucleus to the cytosol has yet to be discovered, we hypothesized that Net1 might have a previously unidentified function in the nucleus of cells.Using an affinity precipitation method to pulldown the active form of Rho GEFs from different cellular fractions, we show here that nuclear Net1 does in fact exist in an active form, contrary to previous expectations. We further demonstrate that a fraction of RhoA resides in the nucleus, and can also be found in a GTP-bound active form and that Net1 plays a role in the activation of nuclear RhoA. In addition, we show that ionizing radiation (IR) specifically promotes the activation of the nuclear pool of RhoA in a Net1-dependent manner, while the cytoplasmic activity remains unchanged. Surprisingly, irradiating isolated nuclei alone also increases nuclear RhoA activity via Net1, suggesting that all the signals required for IR-induced nuclear RhoA signaling are contained within the nucleus.These results demonstrate the existence of a functional Net1/RhoA signaling pathway within the nucleus of the cell and implicate them in the DNA damage response

Spring-Block Model Reveals Region-Like Structures

A mechanical spring-block model is used for realizing an objective space partition of settlements from a geographic territory in region-like structures. The method is based on the relaxation-dynamics of the spring-block system and reveals in a hierarchical manner region-like entities at different spatial scales. It takes into account in an elegant manner both the spatiality of the elements and the connectivity relations among them. Spatiality is taken into account by using the geographic coordinates of the settlements, and by detecting the neighbors with the help of a Delaunay triangulation. Connectivity between neighboring settlements are quantified using a Pearson-like correlation for the relative variation of a relevant socio-economic parameter (population size, GDP, tax payed per inhabitant, etc.). The method is implemented in an interactive JAVA application and it is applied with success for an artificially generated society and for the case of USA, Hungary and Transylvania

Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer

Conceived and designed the experiments: XFL GAC RCB. Performed the experiments: XFL MIA WM RS MSN SZ. Analyzed the data: XFL SR. Contributed reagents/materials/analysis tools: YW GAC. Wrote the paper: XFL RCB.Trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER2 oncoprotein, can effectively target HER2-positive breast cancer through several mechanisms. Although the effects of trastuzumab on cancer cell proliferation, angiogenesis and apoptosis have been investigated in depth, the effect of trastuzumab on microRNA (miRNA) has not been extensively studied. We have performed miRNA microarray profiling before and after trastuzumab treatment in SKBr3 and BT474 human breast cancer cells that overexpress HER2. We found that trastuzumab treatment of SKBr3 cells significantly decreased five miRNAs and increased three others, whereas treatment of BT474 cells significantly decreased two miRNAs and increased nine. The only change in miRNA expression observed in both cell lines following trastuzumab treatment was upregulation of miRNA-194 (miR-194) that was further validated in vitro and in vivo. Forced expression of miR-194 in breast cancer cells that overexpress HER2 produced no effect on apoptosis, modest inhibition of proliferation, significant inhibition of cell migration/invasion in vitro and significant inhibition of xenograft growth in vivo. Conversely, knockdown of miR-194 promoted cell migration. Increased miR-194 expression markedly reduced levels of the cytoskeletal protein talin2 and specifically inhibited luciferase reporter activity of a talin2 wild-type 39-untranslated region, but not that of a mutant reporter, indicating that talin2 is a direct downstream target of miR-194. Trastuzumab treatment inhibited breast cancer cell migration and reduced talin2 expression in vitro and in vivo. Knockdown of talin2 inhibited cell migration/invasion. Knockdown of trastuzumab-induced miR-194 expression with a miR-194 inhibitor compromised trastuzumab-inhibited cell migration in HER2-overexpressing breast cancer cells. Consequently, trastuzumab treatment upregulates miR-194 expression and may exert its cell migration-inhibitory effect through miR-194-mediated downregulation of cytoskeleton protein talin2 in HER2-overexpressing human breast cancer cells.This work was supported by the Anne and Henry Zarrow Foundation, kind gifts from Stuart and Gaye Lynn Zarrow and from Mrs. Delores Wilkenfeld, the Laura and John Arnold Foundation, the RGK Foundation, and the MD Anderson NCI CCSG P30 CA16672. G.A.C. is supported as a Fellow at the University of Texas MD Anderson Research Trust, as a University of Texas System Regents Research Scholar and by the CLL Global Research Foundation

Inside-Out Regulation of ICAM-1 Dynamics in TNF-α-Activated Endothelium

Background: During transendothelial migration, leukocytes use adhesion molecules, such as ICAM-1, to adhere to the endothelium. ICAM-1 is a dynamic molecule that is localized in the apical membrane of the endothelium and clusters upon binding to leukocytes. However, not much is known about the regulation of ICAM-1 clustering and whether membrane dynamics are linked to the ability of ICAM-1 to cluster and bind leukocyte integrins. Therefore, we studied the dynamics of endothelial ICAM-1 under non-clustered and clustered conditions. Principal Findings: Detailed scanning electron and fluorescent microscopy showed that the apical surface of endothelial cells constitutively forms small filopodia-like protrusions that are positive for ICAM-1 and freely move within the lateral plane of the membrane. Clustering of ICAM-1, using anti-ICAM-1 antibody-coated beads, efficiently and rapidly recruits ICAM-1. Using fluorescence recovery after photo-bleaching (FRAP), we found that clustering increased the immobile fraction of ICAM-1, compared to non-clustered ICAM-1. This shift required the intracellular portion of ICAM-1. Moreover, biochemical assays showed that ICAM-1 clustering recruited beta-actin and filamin. Cytochalasin B, which interferes with actin polymerization, delayed the clustering of ICAM-1. In addition, we could show that cytochalasin B decreased the immobile fraction of clustered ICAM-1-GFP, but had no effect on non-clustered ICAM-1. Also, the motor protein myosin-II is recruited to ICAM-1 adhesion sites and its inhibition increased the immobile fraction of both non-clustered and clustered ICAM-1. Finally, blocking Rac1 activation, the formation of lipid rafts, myosin-II activity or actin polymerization, but not Src, reduced the adhesive function of ICAM-1, tested under physiological flow conditions. Conclusions: Together, these findings indicate that ICAM-1 clustering is regulated in an inside-out fashion through the actin cytoskeleton. Overall, these data indicate that signaling events within the endothelium are required for efficient ICAM-1-mediated leukocyte adhesio

Identifying Canadian Freshwater Fishes through DNA Barcodes

BACKGROUND: DNA barcoding aims to provide an efficient method for species-level identifications using an array of species specific molecular tags derived from the 5' region of the mitochondrial cytochrome c oxidase I (COI) gene. The efficiency of the method hinges on the degree of sequence divergence among species and species-level identifications are relatively straightforward when the average genetic distance among individuals within a species does not exceed the average genetic distance between sister species. Fishes constitute a highly diverse group of vertebrates that exhibit deep phenotypic changes during development. In this context, the identification of fish species is challenging and DNA barcoding provide new perspectives in ecology and systematics of fishes. Here we examined the degree to which DNA barcoding discriminate freshwater fish species from the well-known Canadian fauna, which currently encompasses nearly 200 species, some which are of high economic value like salmons and sturgeons. METHODOLOGY/PRINCIPAL FINDINGS: We bi-directionally sequenced the standard 652 bp "barcode" region of COI for 1360 individuals belonging to 190 of the 203 Canadian freshwater fish species (95%). Most species were represented by multiple individuals (7.6 on average), the majority of which were retained as voucher specimens. The average genetic distance was 27 fold higher between species than within species, as K2P distance estimates averaged 8.3% among congeners and only 0.3% among concpecifics. However, shared polymorphism between sister-species was detected in 15 species (8% of the cases). The distribution of K2P distance between individuals and species overlapped and identifications were only possible to species group using DNA barcodes in these cases. Conversely, deep hidden genetic divergence was revealed within two species, suggesting the presence of cryptic species. CONCLUSIONS/SIGNIFICANCE: The present study evidenced that freshwater fish species can be efficiently identified through the use of DNA barcoding, especially the species complex of small-sized species, and that the present COI library can be used for subsequent applications in ecology and systematics

Nudel and FAK as Antagonizing Strength Modulators of Nascent Adhesions through Paxillin

Competition for binding to the cellular protein paxillin by the proteins Nudel and focal adhesion kinase is important for the proper regulation of cell adhesion and migration

Mechanisms and in vivo functions of contact inhibition of locomotion

Contact inhibition of locomotion (CIL) is a process whereby a cell ceases motility or changes its trajectory upon collision with another cell. CIL was initially characterized more than half a century ago and became a widely studied model system to understand how cells migrate and dynamically interact. Although CIL fell from interest for several decades, the scientific community has recently rediscovered this process. We are now beginning to understand the precise steps of this complex behaviour and to elucidate its regulatory components, including receptors, polarity proteins and cytoskeletal elements. Furthermore, this process is no longer just in vitro phenomenology; we now know from several different in vivo models that CIL is essential for embryogenesis and in governing behaviours such as cell dispersion, boundary formation and collective cell migration. In addition, changes in CIL responses have been associated with other physiological processes, such as cancer cell dissemination during metastasis

The ventilation of buildings and other mitigating measures for COVID-19: a focus on wintertime.

The year 2020 has seen the emergence of a global pandemic as a result of the disease COVID-19. This report reviews knowledge of the transmission of COVID-19 indoors, examines the evidence for mitigating measures, and considers the implications for wintertime with a focus on ventilation

Cryptic Diversity of African Tigerfish (Genus Hydrocynus) Reveals Palaeogeographic Signatures of Linked Neogene Geotectonic Events

The geobiotic history of landscapes can exhibit controls by tectonics over biotic evolution. This causal relationship positions ecologically specialized species as biotic indicators to decipher details of landscape evolution. Phylogeographic statistics that reconstruct spatio-temporal details of evolutionary histories of aquatic species, including fishes, can reveal key events of drainage evolution, notably where geochronological resolution is insufficient. Where geochronological resolution is insufficient, phylogeographic statistics that reconstruct spatio-temporal details of evolutionary histories of aquatic species, notably fishes, can reveal key events of drainage evolution. This study evaluates paleo-environmental causes of mitochondrial DNA (mtDNA) based phylogeographic records of tigerfishes, genus Hydrocynus, in order to reconstruct their evolutionary history in relation to landscape evolution across Africa. Strong geographical structuring in a cytochrome b (cyt-b) gene phylogeny confirms the established morphological diversity of Hydrocynus and reveals the existence of five previously unknown lineages, with Hydrocynus tanzaniae sister to a clade comprising three previously unknown lineages (Groups B, C and D) and H. vittatus. The dated phylogeny constrains the principal cladogenic events that have structured Hydrocynus diversity from the late Miocene to the Plio-Pleistocene (ca. 0–16 Ma). Phylogeographic tests reveal that the diversity and distribution of Hydrocynus reflects a complex history of vicariance and dispersals, whereby range expansions in particular species testify to changes to drainage basins. Principal divergence events in Hydrocynus have interfaced closely with evolving drainage systems across tropical Africa. Tigerfish evolution is attributed to dominant control by pulses of geotectonism across the African plate. Phylogenetic relationships and divergence estimates among the ten mtDNA lineages illustrates where and when local tectonic events modified Africa's Neogene drainage. Haplotypes shared amongst extant Hydrocynus populations across northern Africa testify to recent dispersals that were facilitated by late Neogene connections across the Nilo-Sahelian drainage. These events in tigerfish evolution concur broadly with available geological evidence and reveal prominent control by the African Rift System, evident in the formative events archived in phylogeographic records of tigerfish