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

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

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

VLBI observations of GRB 201015A, a relatively faint GRB with a hint of very high-energy gamma-ray emission

Context. A total of four long-duration gamma-ray bursts (GRBs) have been confirmed at very high-energy (≥100GeV) with high significance, and any possible peculiarities of these bursts will become clearer as the number of detected events increases. Multi-wavelength follow-up campaigns are required to extract information on the physical conditions within the jets that lead to the very high-energy counterpart, hence they are crucial to reveal the properties of this class of bursts. Aims. GRB 201015A is a long-duration GRB detected using the MAGIC telescopes from ~40 s after the burst. If confirmed, this would be the fifth and least luminous GRB ever detected at these energies. The goal of this work is to constrain the global and microphysical parameters of its afterglow phase, and to discuss the main properties of this burst in a broader context. Methods. Since the radio band, together with frequent optical and X-ray observations, proved to be a fundamental tool for overcoming the degeneracy in the afterglow modelling, we performed a radio follow-up of GRB 201015A over 12 different epochs, from 1.4 days (2020 October 17) to 117 days (2021 February 9) post-burst, with the Karl G. Jansky Very Large Array, e-MERLIN, and the European VLBI Network. We include optical and X-ray observations, performed respectively with the Multiple Mirror Telescope and the Chandra X-ray Observatory, together with publicly available data, in order to build multi-wavelength light curves and to compare them with the standard fireball model. Results. We detected a point-like transient, consistent with the position of GRB 201015A until 23 and 47 days post-burst at 1.5 and 5 GHz, respectively. No emission was detected in subsequent radio observations. The source was also detected in optical (1.4 and 2.2 days post-burst) and in X-ray (8.4 and 13.6 days post-burst) observations. Conclusions. The multi-wavelength afterglow light curves can be explained with the standard model for a GRB seen on-axis, which expands and decelerates into a medium with a homogeneous density. A circumburst medium with a wind-like profile is disfavoured. Notwithstanding the high resolution provided by the VLBI, we could not pinpoint any expansion or centroid displacement of the outflow. If the GRB is seen at the viewing angle θ that maximises the apparent velocity βapp (i.e. θ ~ βapp-1), we estimate that the Lorentz factor for the possible proper motion is Гα ≤ 40 in right ascension and Гδ ≤ 61 in declination. On the other hand, if the GRB is seen on-axis, the size of the afterglow is ≤5pc and ≤16pc at 25 and 47 days. Finally, the early peak in the optical light curve suggests the presence of a reverse shock component before 0.01 days from the burst

Erythroid-Specific Expression of β-globin from Sleeping Beauty-Transduced Human Hematopoietic Progenitor Cells

Gene therapy for sickle cell disease will require efficient delivery of a tightly regulated and stably expressed gene product to provide an effective therapy. In this study we utilized the non-viral Sleeping Beauty (SB) transposon system using the SB100X hyperactive transposase to transduce human cord blood CD34+ cells with DsRed and a hybrid IHK–β-globin transgene. IHK transduced cells were successfully differentiated into multiple lineages which all showed transgene integration. The mature erythroid cells had an increased β-globin to γ-globin ratio from 0.66±0.08 to 1.05±0.12 (p = 0.05), indicating expression of β-globin from the integrated SB transgene. IHK–β-globin mRNA was found in non-erythroid cell types, similar to native β-globin mRNA that was also expressed at low levels. Additional studies in the hematopoietic K562 cell line confirmed the ability of cHS4 insulator elements to protect DsRed and IHK–β-globin transgenes from silencing in long-term culture studies. Insulated transgenes had statistically significant improvement in the maintenance of long term expression, while preserving transgene regulation. These results support the use of Sleeping Beauty vectors in carrying an insulated IHK–β-globin transgene for gene therapy of sickle cell disease

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&

Risk propensity in the foreign direct investment location decision of emerging multinationals

A distinguishing feature of emerging economy multinationals is their apparent tolerance for host country institutional risk. Employing behavioral decision theory and quasi-experimental data, we find that managers’ domestic experience satisfaction increases their relative risk propensity regarding controllable risk (legally protectable loss), but decreases their tendency to accept non-controllable risk (e.g., political instability). In contrast, firms’ potential slack reduces relative risk propensity regarding controllable risk, yet amplifies the tendency to take non-controllable risk. We suggest that these counterbalancing effects might help explain observation that risk-taking in FDI location decisions is influenced by firm experience and context. The study provides a new understanding of why firms exhibit heterogeneous responses to host country risks, and the varying effects of institutions

Genetic programming of macrophages generates an in vitro model for the human erythroid island niche

In vitro differentiation of red blood cells (RBCs) is a desirable therapy for various disorders. Here the authors develop a culture system using stem cell-derived macrophages to show that inducible expression of a transcription factor, KLF1, enhances RBC production, potentially through the induction of three soluble factors, ANGPTL7, IL33 and SERPINB2