A consecutive process for C–C and C–N bond formation with high enantio-and diastereocontrol : direct reductive amination of chiral ketones using hydrogenation catalysts

Authors thank the University of St Andrews, and the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT) for financial support [PhD studentship to SG; Grant code: EP/L016419/1].High diastereoselectivity was observed in the Rh-catalysed reductive amination of 3-arylcyclohexanones to form tertiary amines. This was incorporated into a one-pot enantioselective conjugate addition and diastereoselective reductive amination, including an example of assisted tandem catalysis.PostprintPeer reviewe

Tragic trade-offs accompany carnivore coexistence in the modern world

Two vital policy aims—biodiversity conservation and food production—are increasingly in conflict. Efforts to evaluate trade-offs between agriculture and conservation have shaped scholarly discourse around two broad strategies to agricultural production that seek to either “share” land with biodiversity or “spare” land from agriculture. However, efforts to negotiate these trade-offs are challenged by rising concern for the welfare of individual animals, both wild and domestic. We use recent efforts to “coexist” with large carnivores to illustrate how sharing and sparing strategies both create tragic, and often unacknowledged trade-offs between livestock production and carnivore conservation. We conclude the best means of conserving carnivores while feeding the world\u27s growing population requires explicitly confronting and adjudicating ethical trade-offs associated with sharing and sparing approaches. To accomplish this, we recommend engaging scholars trained in ethics and social justice and use of deliberative processes to synthesize disparate facts and competing values when evaluating trade-offs

Opportunities and Challenges in Functional Genomics Research in Osteoporosis:Report From a Workshop Held by the Causes Working Group of the Osteoporosis and Bone Research Academy of the Royal Osteoporosis Society on October 5th 2020

The discovery that sclerostin is the defective protein underlying the rare heritable bone mass disorder, sclerosteosis, ultimately led to development of anti-sclerostin antibodies as a new treatment for osteoporosis. In the era of large scale GWAS, many additional genetic signals associated with bone mass and related traits have since been reported. However, how best to interrogate these signals in order to identify the underlying gene responsible for these genetic associations, a prerequisite for identifying drug targets for further treatments, remains a challenge. The resources available for supporting functional genomics research continues to expand, exemplified by “multi-omics” database resources, with improved availability of datasets derived from bone tissues. These databases provide information about potential molecular mediators such as mRNA expression, protein expression, and DNA methylation levels, which can be interrogated to map genetic signals to specific genes based on identification of causal pathways between the genetic signal and the phenotype being studied. Functional evaluation of potential causative genes has been facilitated by characterization of the “osteocyte signature”, by broad phenotyping of knockout mice with deletions of over 7,000 genes, in which more detailed skeletal phenotyping is currently being undertaken, and by development of zebrafish as a highly efficient additional in vivo model for functional studies of the skeleton. Looking to the future, this expanding repertoire of tools offers the hope of accurately defining the major genetic signals which contribute to osteoporosis. This may in turn lead to the identification of additional therapeutic targets, and ultimately new treatments for osteoporosis

Opportunities and Challenges in Functional Genomics Research in Osteoporosis: Report From a Workshop Held by the Causes Working Group of the Osteoporosis and Bone Research Academy of the Royal Osteoporosis Society on October 5th 2020.

The discovery that sclerostin is the defective protein underlying the rare heritable bone mass disorder, sclerosteosis, ultimately led to development of anti-sclerostin antibodies as a new treatment for osteoporosis. In the era of large scale GWAS, many additional genetic signals associated with bone mass and related traits have since been reported. However, how best to interrogate these signals in order to identify the underlying gene responsible for these genetic associations, a prerequisite for identifying drug targets for further treatments, remains a challenge. The resources available for supporting functional genomics research continues to expand, exemplified by "multi-omics" database resources, with improved availability of datasets derived from bone tissues. These databases provide information about potential molecular mediators such as mRNA expression, protein expression, and DNA methylation levels, which can be interrogated to map genetic signals to specific genes based on identification of causal pathways between the genetic signal and the phenotype being studied. Functional evaluation of potential causative genes has been facilitated by characterization of the "osteocyte signature", by broad phenotyping of knockout mice with deletions of over 7,000 genes, in which more detailed skeletal phenotyping is currently being undertaken, and by development of zebrafish as a highly efficient additional in vivo model for functional studies of the skeleton. Looking to the future, this expanding repertoire of tools offers the hope of accurately defining the major genetic signals which contribute to osteoporosis. This may in turn lead to the identification of additional therapeutic targets, and ultimately new treatments for osteoporosis

Behavioral modifications by a large-northern herbivore to mitigate warming conditions

Background Temperatures in arctic-boreal regions are increasing rapidly and pose significant challenges to moose (Alces alces), a heat-sensitive large-bodied mammal. Moose act as ecosystem engineers, by regulating forest carbon and structure, below ground nitrogen cycling processes, and predator-prey dynamics. Previous studies showed that during hotter periods, moose displayed stronger selection for wetland habitats, taller and denser forest canopies, and minimized exposure to solar radiation. However, previous studies regarding moose behavioral thermoregulation occurred in Europe or southern moose range in North America. Understanding whether ambient temperature elicits a behavioral response in high-northern latitude moose populations in North America may be increasingly important as these arctic-boreal systems have been warming at a rate two to three times the global mean. Methods We assessed how Alaska moose habitat selection changed as a function of ambient temperature using a step-selection function approach to identify habitat features important for behavioral thermoregulation in summer (June–August). We used Global Positioning System telemetry locations from four populations of Alaska moose (n = 169) from 2008 to 2016. We assessed model fit using the quasi-likelihood under independence criterion and conduction a leave-one-out cross validation. Results Both male and female moose in all populations increasingly, and nonlinearly, selected for denser canopy cover as ambient temperature increased during summer, where initial increases in the conditional probability of selection were initially sharper then leveled out as canopy density increased above ~ 50%. However, the magnitude of selection response varied by population and sex. In two of the three populations containing both sexes, females demonstrated a stronger selection response for denser canopy at higher temperatures than males. We also observed a stronger selection response in the most southerly and northerly populations compared to populations in the west and central Alaska. Conclusions The impacts of climate change in arctic-boreal regions increase landscape heterogeneity through processes such as increased wildfire intensity and annual area burned, which may significantly alter the thermal environment available to an animal. Understanding habitat selection related to behavioral thermoregulation is a first step toward identifying areas capable of providing thermal relief for moose and other species impacted by climate change in arctic-boreal regions

Vaccine-mediated protection of pigs against infection with pandemic H1N1 2009 swine influenza A virus requires a close antigenic match between the vaccine antigen and challenge virus

Swineandnbsp;influenza A virusandnbsp;(SwIV) infection has considerable economic and animal welfare consequences and, because of the zoonotic potential, can also have public health implications. The 2009 pandemicandnbsp;H1N1andnbsp;andlsquo;swine-originandrsquo; infection is now endemic in both pigs and humans. In Europe, avian-like H1avN1, human-like H1huN2, human-like swineandnbsp;H3N2andnbsp;and, since 2009, pandemic H1N1 (pH1N1) lineage viruses andandnbsp;reassortants, constitute the dominant subtypes. In this study, we used a swine pH1N1 challenge virus to investigate the efficacy ofandnbsp;whole inactivated virus vaccinesandnbsp;homologous or heterologous to the challenge virus as well as a commercial vaccine. We found that vaccine-mediated protection was most effective when vaccine antigen and challenge virus were homologous and correlated with the specific production ofandnbsp;neutralising antibodiesandnbsp;and a cellular response to the challenge virus. We conclude that a conventional whole inactivated SwIV vaccine must be antigenically matched to the challenge strain to be an effective control measure.</p

New living evidence resource of human and non-human studies for early intervention and research prioritisation in anxiety, depression and psychosis

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying mechanisms of mental health conditions, develop safe and effective interventions that target these mechanisms, and improve our capabilities in timely diagnosis and reliable prediction of symptom trajectories. Better synthesis of existing evidence is one way to reduce waste and improve efficiency in research towards these ends. Living systematic reviews produce rigorous, up-to-date and informative evidence summaries that are particularly important where research is emerging rapidly, current evidence is uncertain and new findings might change policy or practice. Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis (GALENOS) aims to tackle the challenges of mental health science research by cataloguing and evaluating the full spectrum of relevant scientific research including both human and preclinical studies. GALENOS will also allow the mental health community-including patients, carers, clinicians, researchers and funders-to better identify the research questions that most urgently need to be answered. By creating open-access datasets and outputs in a state-of-the-art online resource, GALENOS will help identify promising signals early in the research process. This will accelerate translation from discovery science into effective new interventions for anxiety, depression and psychosis, ready to be translated in clinical practice across the world