Hempstead Union Free School District and United Public Service Employees Union

In the matter of the fact-finding between the Hempstead Union Free School District, employer, and the United Public Service Employees Union, union. PERB case no. M2009-300. Before: Stuart L. Bass, fact finder

The envelope gene of transmitted HIV-1 resists a late interferon gamma-induced block

Type I interferon (IFN) signaling engenders an antiviral state that likely plays an important role in constraining HIV-1 transmission and contributes to defining subsequent AIDS pathogenesis. Type II IFN (IFNγ) also induces an antiviral state but is often primarily considered to be an immunomodulatory cytokine. We report that IFNγ stimulation can induce an antiviral state that can be both distinct from that of type I interferon, and can potently inhibit HIV-1 in primary CD4+ T cells and a number of human cell lines. Strikingly, we find that transmitted/founder (TF) HIV-1 viruses can resist a late block that is induced by type II IFN, and the use of chimeric IFNγ- sensitive/resistant viruses indicates that interferon-resistance maps to the env gene. Simultaneously, in vitro evolution also revealed that just a single amino acid substitution in envelope can confer substantial resistance to IFN-mediated inhibition. Thus, the env gene of transmitted HIV-1 confers resistance to a late block that is phenotypically distinct from those previously described to be resisted by env, and is therefore mediated by unknown IFNγ-stimulated factor(s) in human CD4+ T cells and cell lines. This important unidentified block could play a key role in constraining HIV-1 transmission

Effectiveness of the global protected area network in representing species diversity

The Fifth World Parks Congress in Durban, South Africa, announced in September 2003 that the global network of protected areas now covers 11.5% of the planet's land surface. This surpasses the 10% target proposed a decade earlier, at the Caracas Congress, for 9 out of 14 major terrestrial biomes. Such uniform targets based on percentage of area have become deeply embedded into national and international conservation planning. Although politically expedient, the scientific basis and conservation value of these targets have been questioned. In practice, however, little is known of how to set appropriate targets, or of the extent to which the current global protected area network fulfils its goal of protecting biodiversity. Here, we combine five global data sets on the distribution of species and protected areas to provide the first global gap analysis assessing the effectiveness of protected areas in representing species diversity. We show that the global network is far from complete, and demonstrate the inadequacy of uniform—that is, 'one size fits all'—conservation targets

GATA-2 and GATA-3 regulate trophoblast-specific gene expression in vivo.

We previously demonstrated that the zinc finger transcription factors GATA-2 and GATA-3 are expressed in trophoblast giant cells and that they regulate transcription from the mouse placental lactogen I gene promoter in a transfected trophoblast cell line. We present evidence here that both of these factors regulate transcription of the placental lactogen I gene, as well as the related proliferin gene, in trophoblast giant cells in vivo. Placentas lacking GATA-3 accumulate placental lactogen I and proliferi

A Nuclear Export Signal in KHNYN Required for Its Antiviral Activity Evolved as ZAP Emerged in Tetrapods

The zinc finger antiviral protein (ZAP) inhibits viral replication by directly binding CpG dinucleotides in cytoplasmic viral RNA to inhibit protein synthesis and target the RNA for degradation. ZAP evolved in tetrapods and there are clear orthologs in reptiles, birds, and mammals. When ZAP emerged, other proteins may have evolved to become cofactors for its antiviral activity. KHNYN is a putative endoribonuclease that is required for ZAP to restrict retroviruses. To determine its evolutionary path after ZAP emerged, we compared KHNYN orthologs in mammals and reptiles to those in fish, which do not encode ZAP. This identified residues in KHNYN that are highly conserved in species that encode ZAP, including several in the CUBAN domain. The CUBAN domain interacts with NEDD8 and Cullin-RING E3 ubiquitin ligases. Deletion of the CUBAN domain decreased KHNYN antiviral activity, increased protein expression and increased nuclear localization. However, mutation of residues required for the CUBAN domain-NEDD8 interaction increased KHNYN abundance but did not affect its antiviral activity or cytoplasmic localization, indicating that Cullin-mediated degradation may control its homeostasis and regulation of protein turnover is separable from its antiviral activity. By contrast, the C-terminal residues in the CUBAN domain form a CRM1-dependent nuclear export signal (NES) that is required for its antiviral activity. Deletion or mutation of the NES increased KHNYN nuclear localization and decreased its interaction with ZAP. The final 2 positions of this NES are not present in fish KHNYN orthologs and we hypothesize their evolution allowed KHNYN to act as a ZAP cofactor. IMPORTANCE The interferon system is part of the innate immune response that inhibits viruses and other pathogens. This system emerged approximately 500 million years ago in early vertebrates. Since then, some genes have evolved to become antiviral interferon-stimulated genes (ISGs) while others evolved so their encoded protein could interact with proteins encoded by ISGs and contribute to their activity. However, this remains poorly characterized. ZAP is an ISG that arose during tetrapod evolution and inhibits viral replication. Because KHNYN interacts with ZAP and is required for its antiviral activity against retroviruses, we conducted an evolutionary analysis to determine how specific amino acids in KHNYN evolved after ZAP emerged. This identified a nuclear export signal that evolved in tetrapods and is required for KHNYN to traffic in the cell and interact with ZAP. Overall, specific residues in KHNYN evolved to allow it to act as a cofactor for ZAP antiviral activity

Linear predictability vs. bull and bear market models in strategic asset allocation decisions: evidence from UK data

Most papers in the portfolio choice literature have examined linear predictability frameworks based on the idea that simple but flexible Vector Autoregressive (VAR) models can be expanded to produce portfolio allocations that hedge against the bull and bear dynamics typical of financial markets through careful selection of predictor variables that capture business cycles and market sentiment. Yet, a distinct literature exists that shows that non-linear econometric frameworks, such as Markov switching, are also natural tools to compute optimal portfolios arising from the existence of good and bad market states. This paper examines whether and how simple VARs can produce portfolio rules similar to those obtained under a simple Markov switching, by studying the effects of expanding both the order of the VAR and the number/selection of predictor variables included. In a typical stock-bond strategic asset allocation problem for UK data, we compute the out-of-sample certainty equivalent returns for a wide range of VARs and compare these measures of performance with those of non-linear models. We conclude that most VARs cannot produce portfolio rules, hedging demands or (net of transaction costs) out-of-sample performances that approximate those obtained from simple non-linear frameworks

Disrupted Peyer’s Patch Microanatomy in COVID-19 Including Germinal Centre Atrophy Independent of Local Virus

Confirmed SARS-coronavirus-2 infection with gastrointestinal symptoms and changes in microbiota associated with coronavirus disease 2019 (COVID-19) severity have been previously reported, but the disease impact on the architecture and cellularity of ileal Peyer’s patches (PP) remains unknown. Here we analysed post-mortem tissues from throughout the gastrointestinal (GI) tract of patients who died with COVID-19. When virus was detected by PCR in the GI tract, immunohistochemistry identified virus in epithelium and lamina propria macrophages, but not in lymphoid tissues. Immunohistochemistry and imaging mass cytometry (IMC) analysis of ileal PP revealed depletion of germinal centres (GC), disruption of B cell/T cell zonation and decreased potential B and T cell interaction and lower nuclear density in COVID-19 patients. This occurred independent of the local viral levels. The changes in PP demonstrate that the ability to mount an intestinal immune response is compromised in severe COVID-19, which could contribute to observed dysbiosis

Future directions and priorities for Arctic bryophyte research

The development of evidence-based international strategies for the conservation and management of Arctic ecosystems in the face of climate change is hindered by critical knowledge gaps in Arctic floristic diversity and evolution. Particularly poorly studied are the bryophytes, which dominant the vegetation across vast areas of the Arctic, and consequently, play an important role in global biogeochemical cycles. Currently, much of what is known about Arctic floristic evolution is based on studies of vascular plants. Bryophytes, however, possess a number of features, such as poikilohydry, totipotency, several reproductive strategies, and the ability to disperse through microscopic diaspores, which may cause their responses to Arctic environments to differ from those of the vascular plants. Here we discuss several priority areas identified in the Arctic Council's ‘Arctic Biodiversity Assessment’ that are necessary to illuminate patterns of Arctic bryophyte evolution and diversity, including dispersal, glacial refugia, local adaptation, and ecological interactions within bryophyte-associated microbiomes. A survey of digitally available herbarium data archived in the largest online aggregate, GBIF, across the Arctic to boreal zones, indicates that sampling coverage of mosses is heterogeneous, and relatively sparse in the Arctic sensu stricostricto. A coordinated international effort across the Arctic will be necessary to address knowledge gaps in Arctic bryophyte diversity and evolution in the context of ongoing climate change