COVID-19 and individual genetic susceptibility/receptivity: Role of ACE1/ACE2 genes, immunity, inflammation and coagulation. might the double x-chromosome in females be protective against SARS-COV-2 compared to the single x-chromosome in males?

In December 2019, a novel severe acute respiratory syndrome (SARS) from a new coronavirus (SARS-CoV-2) was recognized in the city of Wuhan, China. Rapidly, it became an epidemic in China and has now spread throughout the world reaching pandemic proportions. High mortality rates characterize SARS-CoV-2 disease (COVID-19), which mainly affects the elderly, causing unrestrained cytokines-storm and subsequent pulmonary shutdown, also suspected micro thromboembolism events. At the present time, no specific and dedicated treatments, nor approved vaccines, are available, though very promising data come from the use of anti-inflammatory, anti-malaria, and anti-coagulant drugs. In addition, it seems that males are more susceptible to SARS-CoV-2 than females, with males 65% more likely to die from the infection than females. Data from the World Health Organization (WHO) and Chinese scientists show that of all cases about 1.7% of women who contract the virus will die compared with 2.8% of men, and data from Hong Kong hospitals state that 32% of male and 15% of female COVID-19 patients required intensive care or died. On the other hand, the long-term fallout of coronavirus may be worse for women than for men due to social and psychosocial reasons. Regardless of sex-or gender-biased data obtained from WHO and those gathered from sometimes controversial scientific journals, some central points should be considered. Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous. Secondly, the higher ACE2 expression rate in females, though controversial, might ascribe them the worst prognosis, in contrast with worldwide epidemiological data. Finally, several genes involved in inflammation are located on the X-chromosome, which also contains high number of immune-related genes responsible for innate and adaptive immune responses to infection. Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17). Unexpectedly, the higher levels of ACE2 or ACE1/ACE2 rebalancing might improve the outcome of COVID-19 in both sexes by reducing inflammation, thrombosis, and death. Moreover, X-heterozygous females might also activate a mosaic advantage and show more pronounced sex-related differences resulting in a sex dimorphism, further favoring them in counteracting the progression of the SARS-CoV-2 infection

Source/load-pull noise measurements at ka band

This paper is focused on the extraction of the noise parameters of a linear active device by exploiting both forward and reverse noise power measurements associated with different termina-tions. In order for load-pull measurements to yield a significant marginal improvement (as compared to forward measurements only) it is expected that the device under test should appreciably deviate from unidirectionality. For this reason, the source/load-pull technique is applied to frequencies at which the considered devices are still usable but their reverse noise factor exhibits a measurable dependence on the output terminations. Details on the test bench set up to the purpose, covering the 20–40 GHz frequency range, are provided. A characterization campaign on a 60 nm gate length, 4 × 35 µm GaN-on-Si HEMT fabricated by OMMIC is illustrated

MSEC2007-31127 PVA-BASED SCAFFOLDS FOR THE REPAIR OF MUSCULOSKELETAL SOFT TISSUE

ABSTRACT The objective of this study was to design a partlydegradable scaffold to repair cartilage defects. The scaffold, based on poly(vinyl alcohol), PVA, was intended to maintain long-term mechanical integrity and to facilitate cell proliferation via bioactive agent release from contained microparticles, made from either alginate, ALG or poly(lacticco-glycolic acid), PLGA. The aim of this study was to characterize the morphological features and mechanical behaviour of composite scaffolds as a function of microparticle type and percent content. Our hypothesis was that the dynamic mechanical properties (Dynamic Modulus and Phase Angle) of the composite scaffold would not be affected by microparticle type, but that Dynamic Modulus would increase as a function of increased microparticle content. Scanning Electron Microscopy confirmed that the manufacturing process homogenously dispersed microspheres within the scaffolds. For pure PVA samples Dynamic Modulus ranged from 66±3 kPa at 0.01 Hz to 83±3 kPa at 50 Hz. As ALG microsphere content increased from 25 % to 75 %, Dynamic Modulus ranged from 92±5 kPa at 0.01 Hz to 153±19 kPa at 50 Hz. As the microsphere content increased from 25 % to 75 % PLGA, Dynamic Modulus ranged from 85±9 kPa at 0.01 Hz, to 157±16 kPa at 50 Hz. As expected, Dynamic Modulus increased with increasing test frequencies. For pure PVA specimens Phase Angle ranged from 4.3±0.8 degrees at 0.01 Hz to 12±1.2 degrees at 50 Hz. Phase Angle was not affected by microsphere content. In conclusion, the addition of microspheres affected the dynamic mechanical behavior, in particular Dynamic Modulus, of PVA scaffolds. However, the dynamic mechanical properties were not affected by the polymer from which the microspheres were manufactured. These findings suggest that microsphere type can be chosen to optimize the inclusion of bioactive factors, without detrimentally affecting the mechanical properties of the composite scaffold. It also suggests that % content of included microspheres can be used to modulate the mechanical properties of the scaffold at time zero

Cross-reactivity of 4CMenB vaccine-induced antibodies against meningococci belonging to non-B serogroups in Italy

The four-component meningococcal serogroup B vaccine (4CMenB) contains antigens present in the majority of meningococci causing invasive meningococcal disease (IMD) and may potentially offer protection against strains belonging to non-B serogroups. This study aimed to evaluate the ability of 4CMenB-induced antibodies to kill, in a human serum bactericidal assay (hSBA), non-B meningococci belonging to the main genotypes responsible for IMD in Italy. Meningococci, collected between 2015 and 2017, was characterized for PorA, FetA and sequence type, and for clonal complex. Twenty non-B isolates, representative of the most frequent genotypes, were molecularly characterized for 4CMenB antigens and tested in hSBA with sera from 4CMenB-vaccinated infants and adolescents. Among twenty isolates, eleven were serogroup C, five were Y, two W and two X. All isolates contained genes encoding for fHbp and NHBA antigens and four harbored the NadA full-length encoding gene. Positive hSBA titers were obtained against all serogroup W, X and Y isolates and against five serogroup C isolates. These data show that the 4CMenB vaccine can induce bactericidal antibodies against genetically representative meningococcal W, Y and X strains from Italy. For serogroup C, different susceptibilities to killing were observed for strains with similar antigenic repertoires

Cotranslational N-degron masking by acetylation promotes proteome stability in plants

N-terminal protein acetylation (NTA) is a prevalent protein modification essential for viability in animals and plants. The dominant executor of NTA is the ribosome tethered N-alpha-acetyltransferase A (NatA) complex. However, the impact of NatA on protein fate is still enigmatic. Here, we demonstrate that depletion of NatA activity leads to a 4-fold increase in global protein turnover via the ubiquitin-proteasome system in Arabidopsis. Surprisingly, a concomitant increase in translation, actioned via enhanced Target-of-Rapamycin activity, is also observed, implying that defective NTA triggers feedback mechanisms to maintain steady-state protein abundance. Quantitative analysis of the proteome, the translatome, and the ubiquitome reveals that NatA substrates account for the bulk of this enhanced turnover. A targeted analysis of NatA substrate stability uncovers that NTA absence triggers protein destabilization via a previously undescribed and widely conserved nonAc/N-degron in plants. Hence, the imprinting of the proteome with acetylation marks is essential for coordinating proteome stability. N-terminal protein acetylation is required for plant viability. Here the authors show that reducing N-terminal acetylation by NatA leads to an increase in global protein turnover that is facilitated by absent masking of a novel N-degro

A three-dimensional model of primary bovine endometrium using an electrospun scaffold

Endometrial stromal and epithelial cell function is typically studied in vitro using standard two-dimensional monocultures, but these cultures fail to reflect the complex three-dimensional (3D) architecture of tissue. A 3D model of bovine endometrium that reflects the architectural arrangement of in vivo tissue would beneficially assist the study of tissue function. An electrospun polyglycolide (PGA) scaffold was selected to grow a 3D model of primary bovine endometrial epithelial and stromal cells, that reflects the architecture of the endometrium for the study of pathophysiology. Electrospun scaffolds were seeded with stromal and epithelial cells, and growth was assessed using histological techniques. Prostaglandin E2 and prostaglandin F2α responsiveness of endometrial scaffold constructs was tested using oxytocin plus arachidonic acid (OT + AA) or lipopolysaccharide (LPS). Stromal and epithelial cells growing on the electrospun scaffold had an architectural arrangement that mimicked whole tissue, deposited fibronectin, had appropriate expression of vimentin and cytokeratin and were responsive to OT + AA and LPS, as measured by prostaglandin accumulation. In conclusion, a functional 3D model of stromal and epithelial cells was developed using a PGA electrospun scaffold which may be used to study endometrial pathophysiology

Poly(Vinyl alcohol)/gelatin scaffolds allow regeneration of nasal tissues

Need for regeneration and repair of nasal tissues occurs as a consequence of several pathologies affecting the nose, including, but not limited to infective diseases, traumas and tumor resections. A platform for nasal tissue regeneration was set up using poly(vinyl alcohol)/gelatin sponges with 20%–30% (w/w) gelatin content to be used as scaffolds, for their intrinsic hydrophilic, cell adhesive and shape recovery properties. We propose mesodermal progenitor cells (MPCs) isolated from the bone marrow as a unique stem cell source for obtaining different connective tissues of the nose, including vascular tissue. Finally, epithelial cell immune response to these scaffolds was assessed in vitro in an environment containing inflammatory molecules. The results showed that mesenchymal stromal cells (MSCs) deriving from MPCs could be used to differentiate into cartilage and fibrous tissue; whereas, in combination with endothelial cells still deriving from MPCs, into pre-vascularized bone. Finally, the scaffold did not significantly alter the epithelial cell response to inflammatory insults derived from interaction with bacterial molecules

I Feel what You Feel if You Are Similar to Me

Social interactions are influenced by the perception of others as similar or dissimilar to the self. Such judgements could depend on physical and semantic characteristics, such as membership in an ethnic or political group. In the present study we tested whether social representations of the self and of others could affect the perception of touch. To this aim, we assessed tactile perception on the face when subjects observed a face being touched by fingers. In different conditions we manipulated the identity of the shown face. In a first experiment, Caucasian and Maghrebian participants viewed a face belonging either to their own or to a different ethnic group; in a second experiment, Liberal and Conservative politically active participants viewed faces of politicians belonging to their own or to the opposite political party. The results showed that viewing a touched face most strongly enhanced the perception of touch on the observer's face when the observed face belonged to his/her own ethnic or political group