Adaptive coding occurs in object categorization and may not be associated with schizotypal personality traits

Processing more likely inputs with higher sensitivity (adaptive coding) enables the brain to represent the large range of inputs coming in from the world. Healthy individuals high in schizotypy show reduced adaptive coding in the reward domain but it is an open question whether these deficits extend to non-motivational domains, such as object categorization. Here, we develop a novel variant of a classic task to test range adaptation for face/house categorization in healthy participants on the psychosis spectrum. In each trial of this task, participants decide whether a presented image is a face or a house. Images vary on a face-house continuum and appear in both wide and narrow range blocks. The wide range block includes most of the face-house continuum (2.50–97.5% face), while the narrow range blocks limit inputs to a smaller section of the continuum (27.5–72.5% face). Adaptive coding corresponds to better performance for the overlapping smaller section of the continuum in the narrow range than in the wide range block. We find that participants show efficient use of the range in this task, with more accurate responses in the overlapping section for the narrow range blocks relative to the wide range blocks. However, we find little evidence that range adaptation in our object categorization task is reduced in healthy individuals scoring high on schizotypy. Thus, reduced range adaptation may not be a domain-general feature of schizotypy

Neural bases of reward anticipation in healthy individuals with low, mid, and high levels of schizotypy

A growing body of research has placed the ventral striatum at the center of a network of cerebral regions involved in anticipating rewards in healthy controls. However, little is known about the functional connectivity of the ventral striatum associated with reward anticipation in healthy controls. In addition, few studies have investigated reward anticipation in healthy humans with different levels of schizotypy. Here, we investigated reward anticipation in eighty-four healthy individuals (44 females) recruited based on their schizotypy scores. Participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI.Participants showed the expected decrease in response times for highly rewarded trials compared to non-rewarded trials. Whole-brain activation analyses replicated previous results, including activity in the ventral and dorsal striatum. Whole-brain psycho-physiological interaction analyses of the left and right ventral striatum revealed increased connectivity during reward anticipation with widespread regions in frontal, parietal and occipital cortex as well as the cerebellum and midbrain. Finally, we found no association between schizotypal personality severity and neural activity and cortico-striatal functional connectivity. In line with the motivational, attentional, and motor functions of rewards, our data reveal multifaceted cortico-striatal networks taking part in reward anticipation in healthy individuals. The ventral striatum is connected to regions of the salience, attentional, motor and visual networks during reward anticipation and thereby in a position to orchestrate optimal goal-directed behavior

Assessment of the stability of exogenous gamma hydroxybutyric acid (GHB) in stored blood and urine specimens

OBJECTIVE: The aim of this work is to test the stability of exogenous GHB in whole blood and urine samples collected from living and deceased GHB free-users, spiked with known concentrations of GHB and stored at different temperatures (–20°C, 4°C and 20°C) up to 4 weeks. MATERIALS AND METHODS: GHB was added to GHB-free ante-mortem blood and urine samples at the concentration of 5 and 10 mg/L, respectively whereas in post-mortem blood and urine specimens at 50 and 10 mg/L respectively. All samples were stored at three different temperatures: –20°C, 4°C and 20°C and extracted and analyzed at three days, 1 week, 2 weeks, 3 and 4 weeks in duplicate. No preservatives were added. GHB was quantified by GC-MS after LLE according to a previously published method. RESULTS: Post-mortem blood specimens showed a reduction of GHB levels higher than 10% only after a period of 4 weeks of storage for samples kept at +4°C and +20°C, whereas samples stored at –20°C showed a mean reduction of 8.7%. In post-mortem urine samples, there was a mean reduction of GHB levels higher than 20% at all storage temperatures, after 4 weeks of storage. Antemortem blood samples showed a reduction of GHB levels lower than 10% only after 3 days of storage at –20°C and at +4°C (samples stored at +20°C showed a mean reduction of 10.4%). After 4 weeks of storage, there was a mean reduction of GHB concentrations higher than 20% at all storage temperatures. Ante-mortem urine samples showed a reduction of GHB levels higher than 10% after just 3 days of storage for samples kept at all tested temperatures. After 4 weeks of storage, there was a mean reduction of GHB concentrations higher than 25% at all storage temperatures. CONCLUSIONS: According to our findings, it would be useful to perform GHB analysis both in blood and urine specimens within 3 days of sampling and the specimens should be stored at –20°C or 4°C in order to avoid instability issues

Interstitial Cell Remodeling Promotes Aberrant Adipogenesis in Dystrophic Muscles.

Fibrosis and fat replacement in skeletal muscle are major complications that lead to a loss of mobility in chronic muscle disorders, such as muscular dystrophy. However, the in vivo properties of adipogenic stem and precursor cells remain unclear, mainly due to the high cell heterogeneity in skeletal muscles. Here, we use single-cell RNA sequencing to decomplexify interstitial cell populations in healthy and dystrophic skeletal muscles. We identify an interstitial CD142-positive cell population in mice and humans that is responsible for the inhibition of adipogenesis through GDF10 secretion. Furthermore, we show that the interstitial cell composition is completely altered in muscular dystrophy, with a near absence of CD142-positive cells. The identification of these adipo-regulatory cells in the skeletal muscle aids our understanding of the aberrant fat deposition in muscular dystrophy, paving the way for treatments that could counteract degeneration in patients with muscular dystrophy

Epidemiology and pattern of resistance of gram-negative bacteria isolated from blood samples in hospitalized patients: A single center retrospective analysis from southern italy

Background: Blood culturing remains the mainstream tool to inform an appropriate treatment in hospital-acquired bloodstream infections and to diagnose any bacteremia. Methods: A retrospective investigation on the prevalence of Gram-negative bacteria (GNB) and their resistance in hospitalized patients by age, sex, and units from blood cultures (BCs) was conducted from January 2018 to April 2020 at Sant’Elia hospital, Caltanissetta, southern Italy. We divided the patient age range into four equal intervals. Results: Multivariate demographic and microbiological variables did not show an association between bacteria distributions and gender and age. The distribution by units showed a higher prevalence of Klebsiella pneumoniae and Acinetobacter baumannii in the intensive care unit (ICU) and Escherichia coli in the non-intensive care units (non-ICUs). The analysis of antibiotic resistance showed that E. coli was susceptible to a large class of antibiotics such as carbapenem and trimethoprim-sulfamethoxazole. K. pneumoniae showed a significant susceptibility to colistin, tigecycline, and trimethoprim-sulfamethoxazole. From the survival analysis, patients with E. coli had a higher survival rate. Conclusions: The authors stress the importance of the implementation of large community-level programs to prevent E. coli bacteremia. K. pneumoniae and E. coli susceptibility patterns to antibiotics, including in the prescription patterns of general practitioners, suggest that the local surveillance and implementation of educational programs remain essential measures to slow down the spread of resistance and, consequently, increase the antibiotic lifespan

Establishment of Mouse Embryonic Stem Cell-Derived Erythroid Progenitor Cell Lines Able to Produce Functional Red Blood Cells

BACKGROUND: The supply of transfusable red blood cells (RBCs) is not sufficient in many countries. If erythroid cell lines able to produce transfusable RBCs in vitro were established, they would be valuable resources. However, such cell lines have not been established. To evaluate the feasibility of establishing useful erythroid cell lines, we attempted to establish such cell lines from mouse embryonic stem (ES) cells. METHODOLOGY/PRINCIPAL FINDINGS: We developed a robust method to obtain differentiated cell lines following the induction of hematopoietic differentiation of mouse ES cells and established five independent hematopoietic cell lines using the method. Three of these lines exhibited characteristics of erythroid cells. Although their precise characteristics varied, each of these lines could differentiate in vitro into more mature erythroid cells, including enucleated RBCs. Following transplantation of these erythroid cells into mice suffering from acute anemia, the cells proliferated transiently, subsequently differentiated into functional RBCs, and significantly ameliorated the acute anemia. In addition, we did not observe formation of any tumors following transplantation of these cells. CONCLUSION/SIGNIFICANCE: To the best of our knowledge, this is the first report to show the feasibility of establishing erythroid cell lines able to produce mature RBCs. Considering the number of human ES cell lines that have been established so far, the intensive testing of a number of these lines for erythroid potential may allow the establishment of human erythroid cell lines similar to the mouse erythroid cell lines described here. In addition, our results strongly suggest the possibility of establishing useful cell lines committed to specific lineages other than hematopoietic progenitors from human ES cells

Panning for gold, but finding helium: discovery of the ultra-stripped supernova SN2019wxt from gravitational-wave follow-up observations

We present the results from multi-wavelength observations of a transient discovered during the follow-up of S191213g, a gravitational wave (GW) event reported by the LIGO-Virgo Collaboration as a possible binary neutron star merger in a low latency search. This search yielded SN2019wxt, a young transient in a galaxy whose sky position (in the 80\% GW contour) and distance ($\sim$150\,Mpc) were plausibly compatible with the localisation uncertainty of the GW event. Initially, the transient's tightly constrained age, its relatively faint peak magnitude ($M_i \sim -16.7$\,mag) and the $r-$band decline rate of $\sim 1$\,mag per 5\,days appeared suggestive of a compact binary merger. However, SN2019wxt spectroscopically resembled a type Ib supernova, and analysis of the optical-near-infrared evolution rapidly led to the conclusion that while it could not be associated with S191213g, it nevertheless represented an extreme outcome of stellar evolution. By modelling the light curve, we estimated an ejecta mass of $\sim 0.1\,M_\odot$, with $^{56}$Ni comprising $\sim 20\%$ of this. We were broadly able to reproduce its spectral evolution with a composition dominated by helium and oxygen, with trace amounts of calcium. We considered various progenitors that could give rise to the observed properties of SN2019wxt, and concluded that an ultra-stripped origin in a binary system is the most likely explanation. Disentangling electromagnetic counterparts to GW events from transients such as SN2019wxt is challenging: in a bid to characterise the level of contamination, we estimated the rate of events with properties comparable to those of SN2019wxt and found that $\sim 1$ such event per week can occur within the typical GW localisation area of O4 alerts out to a luminosity distance of 500\,Mpc, beyond which it would become fainter than the typical depth of current electromagnetic follow-up campaigns.Comment: By the ENGRAVE collaboration (engrave-eso.org). 35 pages, 20 figures, final version accepted by A&

THE ROLE OF MICAL2 IN PHYSIOLOGICAL AND PATHOLOGICAL MYOGENIC COMMITMENT

Muscle tissue represents 40% of human body mass and provides locomotion, posture support and breathing. Contractile myofibre units are mainly composed of two crucial components: thick myosin and thin actin (F-actin) filaments. F-Actin interacts with Microtubule Associated Monooxygenase, Calponin And LIM Domain Containing 2 (MICAL2), capable to make oxidation-reduction reactions by its FAD domain. Indeed, MICAL2 modifies actin subunits and promotes actin turnover by severing disaggregation and preventing repolymerisation. An adequate supply of oxygen is essential during myogenesis and muscle fibres need to modify their oxygen demand from rest to cell contraction. The striking capability of MICAL2 to directly and mechanistically connect oxygen availability with F-actin depolymerisation, and hence cytoskeleton dynamics, was thought to be implicated into the process of myogenic differentiation. Therefore, we hypothesised that MICAL2 is involved in smooth, skeletal and cardiac muscle differentiations. Gaining this knowledge might help to understand the role of MICAL2 in muscle pathological conditions, including muscular dystrophies and rhabdomyosarcoma (RMS). Hence, unravelling MICAL2 involvement in muscle differentiation in physiological and pathological conditions was the main aim of this project. The role of MICAL2 was deciphered firstly during differentiation to skeletal, smooth and cardiac muscle cells from myogenic progenitors. In this setting, MICAL2 was found more expressed in myogenic differentiated cells compared to their relative progenitors. Secondly, MICAL2 expression was assessed in dystrophic conditions where the pool of adult stem cells was exhausted. In this case, MICAL2 was more present when a degeneration/regeneration process occurred, localising in centrally-nucleated fibres, in both acute and chronic conditions. Loss and gain of function studies in C2C12 and satellite cells demonstrated that silencing or overexpressing MICAL2 had an impact on both proliferation and myogenic differentiation potential. Indeed, silencing MICAL2 resulted in an enhanced proliferation state of progenitor cells, with a consequent skeletal muscle differentiation impairment. While, on the contrary, overexpressing MICAL2 inmyogenic precursors differentiating towards skeletal muscle positively impacted on myotube formation compared to control cells. Moreover, RMS cell lines were explored for MICAL2 expression, showing an abundant presence of MICAL2 in these cancer cells. Loss of function experiments were performed to unveil the molecular impact of MICAL2, resulting in a slower and decreased proliferative stage. Further modulation of MICAL2 might reduce the tumorigenic capacity of RMS cells and might induce differentiation towards skeletal muscle. In conclusion, our data indicate that MICAL2 is a novel regulator of myogenic differentiation, also outlining its multifaceted effects in determining the cellular response to the environment. In particular, in the pathophysiological context MICAL2 affects proliferation and cell migration, and controls muscle regeneration. Thus, we propose MICAL2 as potent modulator of skeletal myogenesis and perhaps crucial also for cardiac and smooth muscle progenitor cell fate.status: publishe