GABAergic activity is thought to influence developing neocortical sensory circuits. Yet the late postnatal maturation of local layer (L)4 circuits suggests alternate sources of GABAergic control in ...nascent thalamocortical networks. We show that a population of L5b, somatostatin (SST)-positive interneuron receives early thalamic synaptic input and, using laser-scanning photostimulation, identify an early transient circuit between these cells and L4 spiny stellates (SSNs) that disappears by the end of the L4 critical period. Sensory perturbation disrupts the transition to a local GABAergic circuit, suggesting a link between translaminar and local control of SSNs. Conditional silencing of SST+ interneurons or conversely biasing the circuit toward local inhibition by overexpression of neuregulin-1 type 1 results in an absence of early L5b GABAergic input in mutants and delayed thalamic innervation of SSNs. These data identify a role for L5b SST+ interneurons in the control of SSNs in the early postnatal neocortex.
•Early postnatal thalamic synaptic input onto L5b somatostatin interneurons•Transient reciprocal connectivity between L5b INs and L4 spiny stellate cells•Sensory activity is required for the transition to a local L4 GABAergic circuit•Molecular bias toward early local IN synapses delays thalamic innervation of SSNs
Marques-Smith et al. identify a transient, early postnatal GABAergic interneuron circuit involved in thalamocortical integration in primary somatosensory cortex. Perturbation of sensory and molecular cues alters the temporal dynamics of this circuit and thereby maturation of thalamocortical afferent input.
Aerosols, both natural and anthropogenic, are an important but complex component of the Earth’s climate system. Their net impact on climate is about equal in magnitude to that of greenhouse gases but ...can vary significantly by region and type. Understanding and quantifying these aerosol effects is critical for accurate climate modeling and for developing strategies to mitigate climate change. In this paper, we utilize AERONET (Aerosol Robotic NETwork) data from 10 stations situated in the dust belt region to characterize aerosol properties essential for climate change assessment. Aerosol optical depth (AOD) data at 500 nm and Ångström exponent (α) data at the pair of wavelengths of 440 and 870 nm (α440-870) in the study region are analyzed to discriminate among different types of aerosols. The annual and monthly variabilities in AODs are analyzed to see the aerosols trend in the study region. In addition, the AOD and α440-870 data are utilized in order to determine different aerosol types during the period of study. Furthermore, the correlation coefficient between AODs and various meteorological parameters (temperature, wind speed, wind direction, relative humidity, and visibility) is analyzed. The results of the study indicate that Tamanrasset (2.49%), KAUST (1.29%), Solar Village (1.67%), and Dalanzadgad (0.64%) indicate an increasing trend, while Cairo (−0.38%), Masdar (−2.31%), Dushanbe (−1.18%), and Lahore (−0.10%) indicate a decreasing trend in AODs during the study period. Similarly, the results of characterizing aerosol types show that the highest percentage of desert dust aerosols (68%), mixed aerosols (86%), and biomass burning aerosols (15%) are found over Tamanrasset, Lahore, and Dalanzadgad AERONET stations. The study revealed a strong correlation between AODs and visibility, a moderate correlation with temperature, and a low correlation with other meteorological parameters (wind speed, wind direction, and relative humidity) in the study region. The results of the study are very encouraging and enhance our confidence in using historical AERONET data to improve our understanding of atmospheric aerosols’ characteristics.
The biochemical mechanisms by which microbes interact with extracellular soluble metal ions and insoluble redox-active minerals have been the focus of intense research over the last three decades. ...The process presents two challenges to the microorganism. Firstly, electrons have to be transported at the cell surface, which in Gram-negative bacteria presents an additional problem of electron transfer across the ~6nm of the outer membrane. Secondly, the electrons must be transferred to or from the terminal electron acceptors or donors. This review covers the known mechanisms that bacteria use to transport electrons across the cell envelope to external electron donors/acceptors. In Gram-negative bacteria, electron transfer across the outer membrane involves the use of an outer membrane β-barrel and cytochrome. These can be in the form of a porin-cytochrome protein, such as Cyc2 of Acidithiobacillus ferrooxidans, or a multiprotein porin-cytochrome complex like MtrCAB of Shewanella oneidensis MR-1. For mineral-respiring organisms, there is the additional challenge of transferring the electrons from the cell to mineral surface. For the strict anaerobe Geobacter sulfurreducens this requires electron transfer through conductive pili to associated cytochrome OmcS that directly reduces Fe(III)oxides, while the facultative anaerobe S. oneidensis MR-1 accomplishes mineral reduction through direct membrane contact, contact through filamentous extensions and soluble flavin shuttles, all of which require the outer membrane cytochromes MtrC and OmcA in addition to secreted flavin.
This study aimed to explore return to work after COVID-19 and how disease severity affects this.
This is a Nationwide Danish registry–based cohort study using a retrospective follow-up design.
...Patients with a first-time positive SARS-CoV-2 polymerase chain reaction test between 1 January 2020 and 30 May 2020, including 18–64 years old, 30-day survivors, and available to the workforce at the time of the first positive test were included. Admission types (i.e. no admission, admission to non–intensive care unit ICU department and admission to ICU) and return to work was investigated using Cox regression standardised to the age, sex, comorbidity and education-level distribution of all included subjects with estimates at 3 months from positive test displayed.
Among the 7466 patients included in the study, 81.9% (6119/7466) and 98.4% (7344/7466) returned to work within 4 weeks and 6 months, respectively, with 1.5% (109/7466) not returning. Of the patients admitted, 72.1% (627/870) and 92.6% (805/870) returned 1 month and 6 months after admission to the hospital, with 6.6% (58/870) not returning within 6 months. Of patients admitted to the ICU, 36% (9/25) did not return within 6 months. Patients with an admission had a lower chance of return to work 3 months from positive test (relative risk RR 0.95, 95% confidence interval CI 0.94–0.96), with the lowest chance in patients admitted to an ICU department (RR 0.54, 95% CI 0.35–0.72). Female sex, older age, and comorbidity were associated with a lower chance of returning to work.
Hospitalised patients with COVID-19 infection have a lower chance of returning to work with potential implications for postinfection follow-up and rehabilitation.
Previous work has demonstrated that the character of mouse cortical interneuron subtypes can be directly related to their embryonic temporal and spatial origins. The relationship between embryonic ...origin and the character of mature interneurons is likely reflected by the developmental expression of genes that direct cell fate. However, a thorough understanding of the early genetic events that specify subtype identity has been hampered by the perinatal lethality resulting from the loss of genes implicated in the determination of cortical interneurons. Here, we employ a conditional loss-of-function approach to demonstrate that the transcription factor Nkx2-1 is required for the proper specification of specific interneuron subtypes. Removal of this gene at distinct neurogenic time points results in a switch in the subtypes of neurons observed at more mature ages. Our strategy reveals a causal link between the embryonic genetic specification by Nkx2-1 in progenitors and the functional attributes of their neuronal progeny in the mature nervous system.
Micrometer-sized monodisperse polystyrene (PS) particles carrying a pH-responsive poly2-(diethylamino)ethyl methacrylate (PDEA) colloidal stabilizer were synthesized via free radical dispersion ...polymerization. X-ray photoelectron spectroscopy and electrophoretic measurements verified that PDEA covered the PS particle surface. At pH 3.0 and 6.3, where the PDEA is protonated and cationically charged, the PDEA-PS particles were well dispersed in aqueous media thanks to the water soluble PDEA stabilizer and slowly sedimented due to gravity and enriched at the bottom of the glass vials. At pH 10.0, where the PDEA is non-protonated and neutral, the PDEA-PS particles weakly aggregated due to non-hydrated and collapsed PDEA. These PDEA-PS particles and aggregates sedimented to the bottom. The sediment height observed at pH 10.0 was higher than those observed at pH 3.0 and 6.3 in both wet and dry systems, which indicated that a larger porosity was formed at pH 10.0. Mechanical testing experiments confirmed that the fracture toughness of the dried materials decreased with an increase of pH. The fracture toughness was found to be correlated with the degree of particle ordering in the dried particulate materials: more ordered, dense packings lead to a higher fracture toughness compared to amorphous, less dense packings. Thus, we could tune fracture toughness and degree of particle ordering by controlling the pH.
Fundamental research into early circuits of the neocortex provides insight into the etiology of mental illness. In this issue of Neuron, Chini et al. (2020) probe the consequences of combined genetic ...and environmental perturbation on emergent network activity in the prefrontal cortex, identifying a window for possible intervention.
Fundamental research into early circuits of the neocortex provides insight into the etiology of mental illness. In this issue of Neuron, Chini et al. (2020) probe the consequences of combined genetic and environmental perturbation on emergent network activity in the prefrontal cortex, identifying a window for possible intervention.
GABAergic interneurons play key roles in cortical circuits, yet little is known about their early connectivity. Here we use glutamate uncaging and a novel optogenetic strategy to track changes in the ...afferent and efferent synaptic connections of developing neocortical interneuron subtypes. We find that Nkx2-1-derived interneurons possess functional synaptic connections before emerging pyramidal cell networks. Subsequent interneuron circuit maturation is both subtype and layer dependent. Glutamatergic input onto fast spiking (FS), but not somatostatin-positive, non-FS interneurons increases over development. Interneurons of both subtype located in layers (L) 4 and 5b engage in transient circuits that disappear after the somatosensory critical period. These include a pathway mediated by L5b somatostatin-positive interneurons that specifically targets L4 during the first postnatal week. The innervation patterns of immature cortical interneuron circuits are thus neither static nor progressively strengthened but follow a layer-specific choreography of transient connections that differ from those of the adult brain.
Hexa‐peri‐hexabenzocoronene derivatives show a record high negative volumetric thermal expansion coefficient within the crystalline phase. Responsible for the negative thermal expansion is the ...increase of the tilt angle and the improved packing of the discotic cores with temperature and this has implications in the design of organic electronic devices as well as in advanced nanocomposites with controlled thermal properties.
Background. An increase in vulvar cancer in young women is attributed to infection with oncogenic human papillomavirus (HPV). South Africa (SA) has a high prevalence of HPV, and it was therefore ...hypothesised that women with vulvar cancer here would be younger than in high-income countries (HICs). Objective. To describe age, cancer stage, treatment and outcome of patients with vulvar cancer at a tertiary referral centre in SA. Methods. In a retrospective observational study, patient records of women diagnosed with vulvar cancer between 2001 and 2014 were reviewed and demographic and surgical details captured. Histology results of vulvar biopsies and resected specimens were checked for HPV changes, koilocytes and usual-type vulval intraepithelial neoplasia. Patients were restaged using the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system to allow for comparison of outcomes. Five-year disease-specific survival probability curves were generated using Kaplan-Meier analysis. Results. The mean age of the 180 patients in the study was 52.5 years. Those who had documented HPV changes on histological specimens had a mean age of 50.4 years. More than 50% of the patients had advanced-stage disease, and 62.7% were treated with primary surgery. Five-year disease-specific survival probabilities were similar to those reported in the literature. Conclusions. Vulvar cancer should not be regarded as a disease of the elderly in SA, as women with vulvar cancer are 10 - 15 years younger than in HICs. A large proportion of patients present with advanced-stage disease. Health professionals should be alert to vulvar lesions, especially in women with abnormal Pap smears, to reduce the morbidity and mortality of this disease.
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