p75 Neurotrophin receptor expression defines a population of BDNF-responsive neurogenic precursor cells

Although our understanding of adult neurogenesis has increased dramatically over the last decade, confusion still exists regarding both the identity of the stem cell responsible for neuron production and the mechanisms that regulate its activity. Here we show, using flow cytometry, that a small population of cells (0.3%) within the stem cell niche of the rat subventricular zone (SVZ) expresses the p75 neurotrophin receptor (p75(NTR)) and that these cells are responsible for neuron production in both newborn and adult animals. In the adult, the p75(NTR)-positive population contains all of the neurosphere-producing precursor cells, whereas in the newborn many of the precursor cells are p75(NTR) negative. However, at both ages, only the neurospheres derived from p75(NTR)-positive cells are neurogenic. We also show that neuron production from p75(NTR)-positive but not p75(NTR)-negative precursors is greatly enhanced after treatment with brain-derived neurotrophic factor (BDNF) or nerve growth factor. This effect appears to be mediated specifically by p75(NTR), because precursor cells from p75(NTR)-deficient mice show a 70% reduction in their neurogenic potential in vitro and fail to respond to BDNF treatment. Furthermore, adult p75(NTR)-deficient mice have significantly reduced numbers of PSA-NCAM ( polysialylated neural cell adhesion molecule)-positive SVZ neuroblasts in vivo and a lower olfactory bulb weight. Thus, p75(NTR) defines a discrete population of highly proliferative SVZ precursor cells that are able to respond to neurotrophin activation by increasing neuroblast generation, making this pathway the most likely mechanism for the increased neurogenesis that accompanies raised BDNF levels in a variety of disease and behavioral situations

The transcriptional coactivator Querkopf controls adult neurogenesis

The adult mammalian brain maintains populations of neural stem cells within discrete proliferative zones. Understanding of the molecular mechanisms regulating adult neural stem cell function is limited. Here, we show that MYST family histone acetyltransferase Querkopf (Qkf, Myst4, Morf)-deficient mice have cumulative defects in adult neurogenesis in vivo, resulting in declining numbers of olfactory bulb interneurons, a population of neurons produced in large numbers during adulthood. Qkf-deficient mice have fewer neural stem cells and fewer migrating neuroblasts in the rostral migratory stream. Qkf gene expression is strong in the neurogenic subventricular zone. A population enriched in multipotent cells can be isolated from this region on the basis of Qkf gene expression. Neural stem cells/progenitor cells isolated from Qkf mutant mice exhibited a reduced self-renewal capacity and a reduced ability to produce differentiated neurons. Together, our data show that Qkf is essential for normal adult neurogenesis

Hungry for change: the Sydney Food Fairness Alliance

The Sydney Food Fairness Alliance is one of a growing number of nascent food movements in Australia to have emerged out of concern for the country’s food future, as well as the deleterious effect the present food system is having on its citizens’ health and the continent’s fragile environment. The Alliance’s structure and activities clearly position it as a new social movement (NSM) engaged in collective action on a specific issue, in this instance, food security/justice, and operating outside the political sphere while aiming to influence and affect societal change. Food security as a human right lies at the heart of the Alliance’s philosophy, and equitable, sustainable food policies for New South Wales are a core focus of its advocacy work. The authors argue that the Alliance is a distinctive food movement in that it positions itself as an \u27umbrella\u27 organization representing a wide range of stakeholders in the food system. This chapter reflects on the values, achievements, issues of concern, strengths and weaknesses, and future of the Sydney Food Fairness Alliance. This resource is Chapter 8 in \u27Food Security in Australia: Challenges and Prospects for the Future\u27 published by Springer in 2013

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Photometric redshifts and clustering of emission line galaxies selected jointly by DES and eBOSS

We present the results of the first test plates of the extended Baryon Oscillation Spectroscopic Survey. This paper focuses on the emission line galaxies (ELG) population targetted from the Dark Energy Survey (DES) photometry. We analyse the success rate, efficiency, redshift distribution, and clustering properties of the targets. From the 9000 spectroscopic redshifts targetted, 4600 have been selected from the DES photometry. The total success rate for redshifts between 0.6 and 1.2 is 71\% and 68\% respectively for a bright and faint, on average more distant, samples including redshifts measured from a single strong emission line. We find a mean redshift of 0.8 and 0.87, with 15 and 13\% of unknown redshifts respectively for the bright and faint samples. In the redshift range 0.6<z<1.2, for the most secure spectroscopic redshifts, the mean redshift for the bright and faint sample is 0.85 and 0.9 respectively. Star contamination is lower than 2\%. We measure a galaxy bias averaged on scales of 1 and 10~Mpc/h of 1.72 \pm 0.1 for the bright sample and of 1.78 \pm 0.12 for the faint sample. The error on the galaxy bias have been obtained propagating the errors in the correlation function to the fitted parameters. This redshift evolution for the galaxy bias is in agreement with theoretical expectations for a galaxy population with MB-5\log h < -21.0. We note that biasing is derived from the galaxy clustering relative to a model for the mass fluctuations. We investigate the quality of the DES photometric redshifts and find that the outlier fraction can be reduced using a comparison between template fitting and neural network, or using a random forest algorithm

Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis

BACKGROUND Tuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients. METHODS We performed a randomized, double-blind, placebo-controlled trial involving human immunodeficiency virus (HIV)-infected adults and HIV-uninfected adults with a clinical diagnosis of tuberculous meningitis who were admitted to one of two Vietnamese hospitals. We compared a standard, 9-month antituberculosis regimen (which included 10 mg of rifampin per kilogram of body weight per day) with an intensified regimen that included higher-dose rifampin (15 mg per kilogram per day) and levofloxacin (20 mg per kilogram per day) for the first 8 weeks of treatment. The primary outcome was death by 9 months after randomization. RESULTS A total of 817 patients (349 of whom were HIV-infected) were enrolled; 409 were randomly assigned to receive the standard regimen, and 408 were assigned to receive intensified treatment. During the 9 months of follow-up, 113 patients in the intensified-treatment group and 114 patients in the standard-treatment group died (hazard ratio, 0.94; 95% confidence interval, 0.73 to 1.22; P=0.66). There was no evidence of a significant differential effect of intensified treatment in the overall population or in any of the subgroups, with the possible exception of patients infected with isoniazid-resistant M. tuberculosis. There were also no significant differences in secondary outcomes between the treatment groups. The overall number of adverse events leading to treatment interruption did not differ significantly between the treatment groups (64 events in the standard-treatment group and 95 events in the intensified-treatment group, P=0.08). CONCLUSIONS Intensified antituberculosis treatment was not associated with a higher rate of survival among patients with tuberculous meningitis than standard treatment. (Funded by the Wellcome Trust and the Li Ka Shing Foundation; Current Controlled Trials number, ISRCTN61649292.)

The Early Postnatal Nonhuman Primate Neocortex Contains Self-Renewing Multipotent Neural Progenitor Cells

The postnatal neocortex has traditionally been considered a non-neurogenic region, under non-pathological conditions. A few studies suggest, however, that a small subpopulation of neural cells born during postnatal life can differentiate into neurons that take up residence within the neocortex, implying that postnatal neurogenesis could occur in this region, albeit at a low level. Evidence to support this hypothesis remains controversial while the source of putative neural progenitors responsible for generating new neurons in the postnatal neocortex is unknown. Here we report the identification of self-renewing multipotent neural progenitor cells (NPCs) derived from the postnatal day 14 (PD14) marmoset monkey primary visual cortex (V1, striate cortex). While neuronal maturation within V1 is well advanced by PD14, we observed cells throughout this region that co-expressed Sox2 and Ki67, defining a population of resident proliferating progenitor cells. When cultured at low density in the presence of epidermal growth factor (EGF) and/or fibroblast growth factor 2 (FGF-2), dissociated V1 tissue gave rise to multipotent neurospheres that exhibited the ability to differentiate into neurons, oligodendrocytes and astrocytes. While the capacity to generate neurones and oligodendrocytes was not observed beyond the third passage, astrocyte-restricted neurospheres could be maintained for up to 6 passages. This study provides the first direct evidence for the existence of multipotent NPCs within the postnatal neocortex of the nonhuman primate. The potential contribution of neocortical NPCs to neural repair following injury raises exciting new possibilities for the field of regenerative medicine

Galaxy and Mass Assembly (GAMA): the GAMA galaxy group catalogue (G3Cv1)

Using the complete Galaxy and Mass Assembly I (GAMA-I) survey covering ∼142 deg2 to rAB= 19.4, of which ∼47 deg2 is to rAB= 19.8, we create the GAMA-I galaxy group catalogue (G3Cv1), generated using a friends-of-friends (FoF) based grouping algorithm. Our algorithm has been tested extensively on one family of mock GAMA lightcones, constructed from Λ cold dark matter N-body simulations populated with semi-analytic galaxies. Recovered group properties are robust to the effects of interlopers and are median unbiased in the most important respects. G3Cv1 contains 14 388 galaxy groups (with multiplicity ≥2), including 44 186 galaxies out of a possible 110 192 galaxies, implying ∼40 per cent of all galaxies are assigned to a group. The similarities of the mock group catalogues and G3Cv1 are multiple: global characteristics are in general well recovered. However, we do find a noticeable deficit in the number of high multiplicity groups in GAMA compared to the mocks. Additionally, despite exceptionally good local spatial completeness, G3Cv1 contains significantly fewer compact groups with five or more members, this effect becoming most evident for high multiplicity systems. These two differences are most likely due to limitations in the physics included of the current GAMA lightcone mock. Further studies using a variety of galaxy formation models are required to confirm their exact origin. The G3Cv1 catalogue will be made publicly available as and when the relevant GAMA redshifts are made available at http://www.gama-survey.or