Keeping Earth Healthy Together

This project is a book for young children to be exposed to sustainable practices. Practices range from simple daily activities to career options. There is also a parents\u27 section in the back for additional resources. The book can be accessed at: https://flipbookpdf.net/web/site/c2637bb1d14d17cf91b7262fb3fa2bf6a7f5fbec202104.pdf.html

Henipaviruses Employ a Multifaceted Approach to Evade the Antiviral Interferon Response

Hendra and Nipah virus, which constitute the genus Henipavirus, are zoonotic paramyxoviruses that have been associated with sporadic outbreaks of severe disease and mortality in humans since their emergence in the late 1990s. Similar to other paramyxoviruses, their ability to evade the host interferon (IFN) response is conferred by the P gene. The henipavirus P gene encodes four proteins; the P, V, W and C proteins, which have all been described to inhibit the antiviral response. Further studies have revealed that these proteins have overlapping but unique properties which enable the virus to block multiple signaling pathways in the IFN response. The best characterized of these is the JAK-STAT signaling pathway which is targeted by the P, V and W proteins via an interaction with the transcription factor STAT1. In addition the V and W proteins can both limit virus-induced induction of IFN but they appear to do this via distinct mechanisms that rely on unique sequences in their C-terminal domains. The ability to generate recombinant Nipah viruses now gives us the opportunity to determine the precise role for each of these proteins and address their contribution to pathogenicity. Additionally, the question of whether these multiple anti-IFN strategies are all active in the different mammalian hosts for henipaviruses, particularly the fruit bat reservoir, warrants further exploration

When the Fourth Estate’s Well Runs Dry

The press is under fire. Members of the press often face subpoenas or similar court orders, compelling the disclosure of a source’s identity. By issuing media subpoenas, the government has effectively censored the press—the exact type of censorship that the Supreme Court held presumptively unconstitutional over eight decades ago in Near v. Minnesota. Yet the least protected—and most complicated—aspect of the newsgathering process is a reporter’s relationship with her source. For decades, journalists have tried to assert defenses to government compulsions on First Amendment grounds as well as by invoking a “reporter’s privilege,” a testimonial privilege similar to that of a physician or an attorney. But the reporter’s privilege is far from well-settled law. The ambiguities at the federal level as to the bounds of the press’ First Amendment protections have significantly burdened the newsgathering process. Today’s chaotic political climate demands that the Supreme Court address the fragmented framework currently used to analyze the existence of a reporter privilege. The federal judiciary must begin analyzing media subpoenas as prior restraints. If courts apply the prior restraint balancing test—a test which permits censorship only under extremely compelling circumstances—the federal judiciary can accommodate the interests of the government without chilling the press. Absent a framework in which members of the press can consistently protect confidential information, sources will stop disclosing valuable information for fear of retribution, leaving journalists with less accurate and less timely facts from which to report to the public

Synthesis and Applications of Rhodacyclopentanones Derived From C-C Bond Activation

Rhodacyclopentanones, an “sp(3)-rich” class of metallacycle, underpin an emerging range of catalytic methodologies for the direct generation of complex scaffolds. This review highlights strategies for accessing rhodacyclopentanones (and related species) by C-C bond activation of cyclobutanones or cyclopropanes. The scope and mechanism of methodologies that exploit these activation modes is outlined

Directed carbonylative (3+1+2) cycloadditions of amino-substituted cyclopropanes and alkynes: reaction development and increased efficiencies using a cationic rhodium system

AbstractUrea-directed carbonylative insertion of Rh(I)-catalysts into one of the two proximal C–C bonds of aminocyclopropanes generates rhodacyclopentanone intermediates. These are trapped by N-tethered alkynes to provide a (3+1+2) cycloaddition protocol that accesses N-heterobicyclic enones. Stoichiometric studies on a series of model rhodacyclopentanone complexes outline key structural features and provide a rationale for the efficacy of urea directing groups. A comprehensive evaluation of cycloaddition scope and a ‘second generation’ cationic Rh(I)-system, which provides enhanced yields and reaction rates for challenging substrates, are presented

Characterisation of the Hepatitis C Virus Genotype 3 Glycoproteins

Hepatitis C virus (HCV) can be classified into six genotypes (1-6) which show 30% nucleotide sequence variability throughout the genome. HCV genotypes 1, 2 and 3 have a world-wide distribution but their prevalence differs from one geographical area to another. In Scotland there is an approximate 50/50 split between individuals infected with HCV genotype 1 and genotype 3. There is little evidence that disease progression or severity differs between the genotypes. On the other hand, one difference which has been consistently demonstrated is the better response of patients infected with genotypes 2 and 3 to interferon treatment than those infected with genotype 1. HCV encodes three structural proteins, core, E1 and E2. The two glycoproteins, E1 and E2, are bE1ieved to be the envE1ope proteins. The lack of a cE1l culture system for the production of HCV virions has meant that the proteins within the envE1ope of the HCV virion remain uncharacterised. However, recombinant forms of the E1 and E2 proteins have been shown to localise to the endoplasmic reticulum (ER) when expressed in cultured cE1ls and to interact with one another to form a complex (Ralston et al., 1993). E2 has also recently been shown to bind to the cE1l-surface molecule, CD81, which, as a result, has been proposed to be an HCV receptor (Pileri et al., 1998). These characteristics of the HCV glycoproteins have been described using constructs derived from genotype 1 only. Comparison of the properties of E1 and E2 with those of other genotypes would identify both conserved features, which are possibly essential to the virus life cycle, and genotype-specific features. In this study, the E1 and E2 proteins of genotype 3 were compared with those of genotype 1 with respect to antibody recognition, subcE1lular localisation, complex formation, glycosylation status and CD81-binding. The role of E2 in mediating resistance to interferon (IFN) through a proposed interaction with PKR (Taylor et al., 1999) was also investigated. The genotype 3 structural genes were amplified by reverse-transcription polymerase chain reaction (RT-PCR) from the serum of an HCV genotype 3a-infected patient. This isolate was named HCV 3a-Gla (Gla-3a) and was used as the genotype 3 representative, whereas genotype 1 was represented by the H77 isolate. Sequence comparison of Gla-3a with four published genotype 3a isolates and the genotype 1 isolate revealed that the genotype 3 E2 protein was 6 amino acids longer and had one fewer cysteine residue than that of genotype 1. In terms of length and the number of cysteine residues, the E1 proteins of genotypes 1 and 3 were identical. E2 of Gla-3a (and three other genotype 3 isolates) had one fewer predicted glycosylation site compared to genotype 1, whereas the predicted glycosylation sites in E1 were identical between genotypes 3 and 1. Expression of the core, E1 and E2 proteins was achieved using either the Semliki Forest Virus (SFV) expression system for production of large amounts of recombinant protein or the pcDNA system, in which recombinant gene expression is under control of a cytomegalovirus (CMV) promoter. None of the genotype 1 anti-E1 antibodies were able to recognise genotype 3 E1. Three genotype 1 anti-E2 monoclonal antibodies recognised genotype 3 E2 and they all recognised epitopes in a highly conserved sixteen amino acid region. The genotype 3 glycoproteins localised to the ER and showed evidence of both aggregate and native complex formation as described for those of genotype 1. The rE1ative mobilities of untreated and glycosidase-treated proteins confirmed the predicted glycosylation status of the E2 proteins of genotypes 1 and 3 but the genotype 3 E1 protein appeared to have one additional glycan compared to genotype 1 E1. The deglycosylated genotype 1 E1 protein also seemed smaller than that of genotype 3. Neither of these observations was predicted from the sequence comparison. In contrast to genotype 1 E2, the recombinant genotype 3 E2 protein did not bind to human CD81, although interestingly, prE1iminary results on the ability of virions in human sera to bind CD81 suggested that genotype 3 virions did bind but that genotype 1 virions did not. The ability of the PKR-eIF2alpha phosphorylation homology domain (PePHD) in the E2 protein to predict response to IFN treatment was not validated for genotype 3 and the proposed interaction of genotype 1 E2 with PKR was not confirmed, either by co-localisation or immunoprecipitation. Therefore the role of E2 in mediating IFN resistance remains unclear. In conclusion, the glycoproteins of both genotypes 1 and 3 behave similarly with respect to ER localisation and complex formation in this experimental system. Glycosylation status of the glycoproteins varies between the genotypes and further investigation is required to determine the true glycosylation status of genotype 3 E1. The lack of CD81 binding of the genotype 3 E2 protein is intriguing. This will have to be confirmed with additional genotype 3 isolates but it does highlight the need to include representatives of other genotypes when analysing interactions between viral and cE1lular proteins

Dichotomous mechanistic behaviour in Narasaka-Heck cyclizations: electron rich Pd-catalysts generate iminyl radicals

Pd-catalyzed cyclizations of oxime esters with pendant alkenes undergo ligand controlled mechanistic divergence. Electron deficient phosphines promote aza-Heck cyclization; electron rich systems favour a SET pathway. Mechanistic experiments differentiate the two manifolds.</p

New Initiation Modes for Directed Carbonylative C-C Bond Activation:Rhodium-Catalyzed (3+1+2) Cycloadditions of Aminomethylcyclopropanes

Under carbonylative conditions, neutral Rh­(I)-systems modified with weak donor ligands (AsPh₃ or 1,4-oxathiane) undergo N-Cbz, N-benzoyl, or N-Ts directed insertion into the proximal C–C bond of amino­methyl­cyclo­propanes to generate rhodacyclo­pentanone intermediates. These are trapped by N-tethered alkenes to provide complex perhydroisoindoles

The neonatal Fc receptor (FcRn) is a pan-arterivirus receptor

Arteriviruses infect a variety of mammalian hosts, but the receptors used by these viruses to enter cells are poorly understood. We identified the neonatal Fc receptor (FcRn) as an important pro-viral host factor via comparative genome-wide CRISPR-knockout screens with multiple arteriviruses. Using a panel of cell lines and divergent arteriviruses, we demonstrate that FcRn is required for the entry step of arterivirus infection and serves as a molecular barrier to arterivirus cross-species infection. We also show that FcRn synergizes with another known arterivirus entry factor, CD163, to mediate arterivirus entry. Overexpression of FcRn and CD163 sensitizes non-permissive cells to infection and enables the culture of fastidious arteriviruses. Treatment of multiple cell lines with a pre-clinical anti-FcRn monoclonal antibody blocked infection and rescued cells from arterivirus-induced death. Altogether, this study identifies FcRn as a novel pan-arterivirus receptor, with implications for arterivirus emergence, cross-species infection, and host-directed pan-arterivirus countermeasure development

Modular access to substituted azocanes via a rhodium-catalyzed cycloaddition-fragmentation strategy

A short entry to substituted azocanes by a Rh-catalyzed cycloaddition–fragmentation process is described. Specifically, exposure of diverse <i>N</i>-cyclopropylacrylamides to phosphine-ligated cationic Rh­(I) catalyst systems under a CO atmosphere enables the directed generation of rhodacyclopentanone intermediates. Subsequent insertion of the alkene component is followed by fragmentation to give the heterocyclic target. Stereochemical studies show, for the first time, that alkene insertion into rhodacyclopentanones can be reversible