Cyclisation of Cell Penetrating PDZ-Binding Peptides Directed to PSD95

Excitatory glutamatergic neurotransmission via N-methyl-D-aspartate receptor (NMDAR) is critical for synaptic plasticity and survival of neurons. Excessive NMDAR activity, however can cause excitotoxicity and promote cell death, underlying a potential mechanism of neurodegeneration occurring in Alzheimer’s disease (AD). The regulation of calcium levels at synapses is important for pre- and post-synaptic activation in the hippocampus, where glutamate is the primary neurotransmitter, acting via metabotropic and ionotropic receptors

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Diversidad de los macroinvertebrados acuáticos de la laguna de Sonso, valle del Cauca, Colombia

Se evaluó la diversidad de macroinvertebrados acuáticos bentónicos y asociados a macrofitas en la laguna de Sonso entre 2007 y 2008. Se tomaron muestras en diferentes estaciones con una pala draga de 500 ml de capacidad y con redes de 4 m² Y 0.5 µm de ojo de malla respectivamente. Se realizó un análisis cualitativo de la variación temporal de los macroinvertebrados acuáticos de la laguna de Sonso y descripción de algunos aspectos sobre la ecología de estos organismos usando la literatura científica e institucional disponible. Entre 1998 y 2006 se reportaron aproximadamente 45 familias pertenecientes a diferentes gremios tróficos y características de calidades de agua que van desde muy contaminadas (Tubificidae y Chironomidae) hasta muy limpias y propias de cuerpos de agua lóticos (Blephariceridae y Psephenidae). En los muestreos realizados entre 2007 y 2008 se reportan principalmente organismos característicos de aguas con cierto nivel de materia orgánica (Hydrophilidae, Curculionidae, Chironomidae, Oligochaeta e Hirudinea). También se crecolectaron moluscos gasterópodos y bibalvos. La familia Dytiscidae se colectó principalmente asociada al buchón de agua Eichornia Crassipes. Los resultados presentados son un aporte para el conocimiento de la biodiversidad de los ecosistemas lénticos y constituye información básica para el establecimiento de políticas de normatividad e implementación de planes de manejo en la laguna

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

Information in resource management: Ward managers' perceptions

With the third wave of UK National Health Service reforms now several years old and resource management firmly established, this study investigated ward managers' perceptions of their clinical information needs and their information processes in relation to the management of resources. A convenience sample of 13 ward managers were interviewed, using semi-structured schedules, for between 20 and 45 minutes. The results were subjected to thematic and relationship analysis. Ward managers' information needs appeared to be mainly influenced by the content of the budget statement. They also indicated that they had initial difficulty in reading the statement. They used several informal methods to obtain information but research literature and information technology were not perceived as valuable sources of information. The role of information in relation to resource management appears not to be wholly understood by ward managers

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease