Structural basis of template-boundary definition in Tetrahymena telomerase.

Telomerase is required to maintain repetitive G-rich telomeric DNA sequences at chromosome ends. To do so, the telomerase reverse transcriptase (TERT) subunit reiteratively uses a small region of the integral telomerase RNA (TER) as a template. An essential feature of telomerase catalysis is the strict definition of the template boundary to determine the precise TER nucleotides to be reverse transcribed by TERT. We report the 3-Å crystal structure of the Tetrahymena TERT RNA-binding domain (tTRBD) bound to the template boundary element (TBE) of TER. tTRBD is wedged into the base of the TBE RNA stem-loop, and each of the flanking RNA strands wraps around opposite sides of the protein domain. The structure illustrates how the tTRBD establishes the template boundary by positioning the TBE at the correct distance from the TERT active site to prohibit copying of nontemplate nucleotides

A Well‐Defined Anionic Dicopper(I) Monohydride Complex that Reacts like a Cluster**

Low-nuclearity copper hydrides are rare and few well-defined dicopper hydrides have been reported. Herein, we describe the first example of a structurally characterized anionic dicopper hydride complex. This complex does not display typical reactivity associated with low-nuclearity copper hydrides, such as alcoholysis or insertion reactions. Instead, its stoichiometric and catalytic reactivity is akin to that of copper hydride clusters. The distinct reactivity is ascribed to the robust dinuclear core that is bound tightly within the dinucleating ligand scaffold

When to start antiretroviral therapy in resource-limited settings: a human rights analysis

<p>Abstract</p> <p>Background</p> <p>Recent evidence from developed and developing countries shows clear clinical and public health benefit to starting antiretroviral therapy (ART) earlier. While discussions about when to start ART have often focused on the clinical risks and benefits, the main issue is one of fair limit-setting. We applied a human rights framework to assess a policy of early treatment initiation according to the following criteria: public-health purpose; likely effectiveness; specificity; human rights burdens and benefits; potential for less restrictive approaches; and fair administration.</p> <p>Discussion</p> <p>According to our analysis, a policy of earlier ART initiation would better serve both public health and human rights objectives. We highlight a number of policy approaches that could be taken to help meet this aim, including increased international financial support, alternative models of care, and policies to secure the most affordable sources of appropriate antiretroviral drugs.</p> <p>Summary</p> <p>Widespread implementation of earlier ART initiation is challenging in resource-limited settings. Nevertheless, rationing of essential medicines is a restriction of human rights, and the principle of least restriction serves to focus attention on alternative measures such as adapting health service models to increase capacity, decreasing costs, and seeking additional international funding. Progressive realisation using well-defined steps will be necessary to allow for a phased implementation as part of a framework of short-term targets towards nationwide policy adoption, and will require international technical and financial support.</p

A Well‐Defined Anionic Dicopper(I) Monohydride Complex that Reacts like a Cluster

Low‐nuclearity copper hydrides are rare and few well‐defined dicopper hydrides have been reported. Herein, we describe the first example of a structurally characterized anionic dicopper monohydride complex. This complex does not display typical reactivity associated with low‐nuclearity copper hydrides, such as alcoholysis or insertion reactions. Instead, its stoichiometric and catalytic reactivity is akin to that of copper hydride clusters. The distinct reactivity is ascribed to the robust dinuclear core that is bound tightly within the dinucleating ligand scaffold

Structural basis of template-boundary definition in Tetrahymena telomerase.

Telomerase is required to maintain repetitive G-rich telomeric DNA sequences at chromosome ends. To do so, the telomerase reverse transcriptase (TERT) subunit reiteratively uses a small region of the integral telomerase RNA (TER) as a template. An essential feature of telomerase catalysis is the strict definition of the template boundary to determine the precise TER nucleotides to be reverse transcribed by TERT. We report the 3-Å crystal structure of the Tetrahymena TERT RNA-binding domain (tTRBD) bound to the template boundary element (TBE) of TER. tTRBD is wedged into the base of the TBE RNA stem-loop, and each of the flanking RNA strands wraps around opposite sides of the protein domain. The structure illustrates how the tTRBD establishes the template boundary by positioning the TBE at the correct distance from the TERT active site to prohibit copying of nontemplate nucleotides

Global Social Policy Digest 21.2: Turning the tide in the battle against COVID-19?

Shriwise A, Babirye M, Berten J, et al. Global Social Policy Digest 21.2: Turning the tide in the battle against COVID-19? . Global Social Policy. Vol 21.2. London: SAGE Publications; 2021

A Well‐Defined Anionic Dicopper(I) Monohydride Complex that Reacts like a Cluster**

Low-nuclearity copper hydrides are rare and few well-defined dicopper hydrides have been reported. Herein, we describe the first example of a structurally characterized anionic dicopper hydride complex. This complex does not display typical reactivity associated with low-nuclearity copper hydrides, such as alcoholysis or insertion reactions. Instead, its stoichiometric and catalytic reactivity is akin to that of copper hydride clusters. The distinct reactivity is ascribed to the robust dinuclear core that is bound tightly within the dinucleating ligand scaffold

Solidarity in the wake of COVID-19 : reimagining the International Health Regulations

Amid frenzied national responses to COVID-19, the world could soon reach a critical juncture to revisit and strengthen the International Health Regulations (IHR), the multilateral instrument that governs how 196 states and WHO collectively address the global spread of disease.1, 2 In many countries, IHR obligations that are vital to an effective pandemic response remain unfulfilled, and the instrument has been largely side-lined in the COVID-19 pandemic, the largest global health crisis in a century. It is time to reimagine the IHR as an instrument that will compel global solidarity and national action against the threat of emerging and re-emerging pathogens. We call on state parties to reform the IHR to improve supervision, international assistance, dispute resolution, and overall textual clarity