Time to match; when do homologous chromosomes become closer?

In most eukaryotes, pairing of homologous chromosomes is an essential feature of meiosis that ensures homologous recombination and segregation. However, when the pairing process begins, it is still under investigation. Contrasting data exists in Mus musculus, since both leptotene DSB-dependent and preleptotene DSB-independent mechanisms have been described. To unravel this contention, we examined homologous pairing in pre-meiotic and meiotic Mus musculus cells using a three-dimensional fluorescence in situ hybridization-based protocol, which enables the analysis of the entire karyotype using DNA painting probes. Our data establishes in an unambiguously manner that 73.83% of homologous chromosomes are already paired at premeiotic stages (spermatogonia-early preleptotene spermatocytes). The percentage of paired homologous chromosomes increases to 84.60% at mid-preleptotene-zygotene stage, reaching 100% at pachytene stage. Importantly, our results demonstrate a high percentage of homologous pairing observed before the onset of meiosis; this pairing does not occur randomly, as the percentage was higher than that observed in somatic cells (19.47%) and between nonhomologous chromosomes (41.1%). Finally, we have also observed that premeiotic homologous pairing is asynchronous and independent of the chromosome size, GC content, or presence of NOR regions.

Characterization of Quasi-Keplerian, Differentially Rotating, Free-Boundary Laboratory Plasmas.

We present results from pulsed-power driven differentially rotating plasma experiments designed to simulate physics relevant to astrophysical disks and jets. In these experiments, angular momentum is injected by the ram pressure of the ablation flows from a wire array Z pinch. In contrast to previous liquid metal and plasma experiments, rotation is not driven by boundary forces. Axial pressure gradients launch a rotating plasma jet upward, which is confined by a combination of ram, thermal, and magnetic pressure of a surrounding plasma halo. The jet has subsonic rotation, with a maximum rotation velocity 23±3 km/s. The rotational velocity profile is quasi-Keplerian with a positive Rayleigh discriminant κ^{2}∝r^{-2.8±0.8} rad^{2}/s^{2}. The plasma completes 0.5-2 full rotations in the experimental time frame (∼150 ns).

Molecular phylogeny and evolution of inflorescence types in Eperua.

PREMISE: The Amazonian hyperdominant genus Eperua (Fabaceae) currently holds 20 described species and has two strongly different inflorescence and flower types, with corresponding different pollination syndrome. The evolution of these vastly different inflorescence types within this genus was unknown and the main topic in this study. METHODS: We constructed a molecular phylogeny, based on the full nuclear ribosomal DNA and partial plastome, using Bayesian inference and maximum likelihood methods, to test whether the genus is monophyletic, whether all species are monophyletic and if the shift from bat to bee pollination (or vice versa) occurred once in this genus. RESULTS: All but two species are well supported by the nuclear ribosomal phylogeny. The plastome phylogeny, however, shows a strong geographic signal suggesting strong local hybridization or chloroplast capture, rendering chloroplast barcodes meaningless in this genus. CONCLUSIONS: With our data, we cannot fully resolve the backbone of the tree to clarify sister genera relationships and confirm monophyly of the genus Eperua. Within the genus, the shift from bat to bee and bee to bat pollination has occurred several times but, with the bee to bat not always leading to a pendant inflorescence.

Carbapenem alternatives for treatment of bloodstream infections due to AmpC producing enterobacterales.

INTRODUCTION: Carbapenems (CR) have traditionally been the first line treatment for bacteremia caused by AmpC-producing Enterobacterales. However, CR have a high ecological impact, and carbapenem-resistant strains continue rising. Thus, other treatment alternatives like Piperacillin-Tazobactam (P-T) or Cefepime (CEF) and oral sequential therapy (OST) are being evaluated. METHODS: We conducted a retrospective, single-centre observational study. All adult patients with AmpC-producing Enterobacterales bacteremia were included. The primary endpoint was clinical success defined as a composite of clinical cure, 14-day survival, and no adverse events. We evaluated the evolution of patients in whom OST was performed. RESULTS: Seventy-seven patients were included, 22 patients in the CR group and 55 in the P-T/CEF group (37 patients received CEF and 18 P-T). The mean age of the patients was higher in the P-T/CEF group (71 years in CR group vs. 76 years in P-T/CEF group, p = 0.053). In the multivariate analysis, age ≥ 70 years (OR 0.08, 95% CI [0.007-0.966], p = 0.047) and a Charlson index ≥ 3 (OR 0.16, 95% CI [0.026-0.984], p = 0.048), were associated with a lower clinical success. Treatment with P-T/CEF was associated with higher clinical success (OR 7.75, 95% CI [1.273-47.223], p = 0.026). OST was performed in 47% of patients. This was related with a shorter in-hospital stay (OST 14 days [7-22] vs. non-OST 18 days [13-38], p = 0.005) without difference in recurrence (OST 3% vs. non-OST 5%, p = 0.999). CONCLUSIONS: Targeted treatment with P-T/CEF and OST could be safe and effective treatments for patients with AmpC-producing Enterobacterales bacteremia.

Fusobacterium nucleatum and Prevotella in women with periodontitis and preterm birth.

BACKGROUND: Studies try to explain the hypothesis that maternal periodontitis may be associated with preterm birth. MATERIAL AND METHODS: This is a case-control study with 120, 40 cases (gestational age <37 weeks) and 80 controls (gestational age ≥37 weeks), that were submitted to the clinical periodontal examination and subgingival biofilm collection. Bacterial DNA of subgingival biofilm was performed and processed by qPCR. RESULTS: Periodontitis was statistically significant in the Case group (35%) when compared to the Control group (11.2%) and Gingival Bleeding Index (GBI), sites with PS ≥ 4mm and sites with CAL ≥ 5mm were statistically higher in the Case group (p < 0.05). The proportions of Pi (p = 0.026) and Fn (p = 0.041) of subgingival biofilm were higher in the Case group. A greater number of sites with PS ≥ 4mm (r = -0.202; p = 0.026) and CAL ≥ 5mm (r = -0.322; p < 0.001) were correlated to lower gestational age. CONCLUSIONS: Periodontitis, preterm delivery, and/or low birth weight may have a possible relationship based on clinical parameters and the ratio of Pi and Fn at periodontal sites.

Chromosomal positioning in spermatogenic cells is influenced by chromosomal factors associated with gene activity, bouquet formation and meiotic sex chromosome inactivation.

Chromosome territoriality is not random along the cell cycle and it is mainly governed by intrinsic chromosome factors and gene expression patterns. Conversely, very few studies have explored the factors that determine chromosome territoriality and its influencing factors during meiosis. In this study, we analysed chromosome positioning in murine spermatogenic cells using three-dimensionally fluorescence in situ hybridization-based methodology, which allows the analysis of the entire karyotype. The main objective of the study was to decipher chromosome positioning in a radial axis (all analysed germ-cell nuclei) and longitudinal axis (only spermatozoa) and to identify the chromosomal factors that regulate such an arrangement. Results demonstrated that the radial positioning of chromosomes during spermatogenesis was cell-type specific and influenced by chromosomal factors associated to gene activity. Chromosomes with specific features that enhance transcription (high GC content, high gene density and high numbers of predicted expressed genes) were preferentially observed in the inner part of the nucleus in virtually all cell types. Moreover, the position of the sex chromosomes was influenced by their transcriptional status, from the periphery of the nucleus when its activity was repressed (pachytene) to a more internal position when it is partially activated (spermatid). At pachytene, chromosome positioning was also influenced by chromosome size due to the bouquet formation. Longitudinal chromosome positioning in the sperm nucleus was not random either, suggesting the importance of ordered longitudinal positioning for the release and activation of the paternal genome after fertilisation.

Ceftazidime-avibactam treatment in bacteremia caused by OXA-48 carbapenemase-producing Klebsiella pneumoniae.

Therapeutic options for bacteremia caused by carbapenem-resistant Enterobacterales (CRE) OXA-48-type are limited. The objective of this study was to analyze clinical success of CAZ-AVI compared with best available therapy (BAT) in patients with Klebsiella pneumoniae carbapenemase-producing OXA-48-type bacteremia (CRKp-OXA-48). We conducted a retrospective, single-center observational study in adult patients with CRKp-OXA-48 between December 2015 and May 2019. We collected the patients' clinical and epidemiological characteristics, antibiotic treatment (CAZ-AVI vs. BAT), and evolution. Factors associated with clinical success were analyzed using binary logistic regression. The study included 76 patients with CRKp-OXA-48-type bacteremia 33 received CAZ-AVI and 43 BAT. CAZ-AVI was mainly used in monotherapy (91%). Clinical success was more common in patients < 70-year-old (OR 4.79, 95% CI [1.435-16.002], p = 0.011) and CAZ-AVI treatment (OR 6.69, 95% CI [1.68-26.604], p = 0.007). Kaplan-Meier survival curve of 14-day mortality showed a lower mortality in patients who received CAZ-AVI (log rank 0.013). However, CAZ-AVI did not achieve statistical difference in IPTW for 14- and 30-day mortality (aOR 0.1, 95% CI [0.02-1.22], p = 0.076 and aOR 1.7, 95% CI [0.48-5.98], p = 0.413, respectively). CAZ-AVI treatment might be associated with a greater clinical success in CRKp-OXA-48 bacteremia.

Robot-assisted laparoscopy for deep infiltrating endometriosis: a retrospective French multicentric study (2008-2019) using the Society of European Robotic Gynecological Surgery endometriosis database.

OBJECTIVE: This study aimed at assessing perioperative results of robot-assisted laparoscopy (RAL) in the context of deep infiltrating endometriosis (DIE). METHODS: This retrospective French multicentric study included all patients with DIE who underwent surgical treatment managed by RAL (Da Vinci® System). From November 2008 to June 2019, patients were included in a single European database, in Robotic Assisted Laparoscopic Gynecologic Surgery, with Society of European Robotic Gynecological Surgery collaboration. Patients had different DIE sites as follows: gynecological, urological, or digestive, or combinations of these. Surgical procedures and perioperative complications were evaluated. To assess complications, patients were divided into the following four groups according to surgical procedure and DIE site: gynecological only; gynecological and urological; gynecological and digestive; and gynecological, urological, and digestive. RESULTS: A total of 460 patients treated at one of eight health-care facilities from November 2008 to June 2019 were included. Median operative time was 245 min (IQR 186-320), surgeon console time was 138 ± 75 min and estimated blood loss was 70.0 mL ± 107 mL. Among this patient sample, 42.1% had a multidisciplinary surgical approach with a digestive or urology surgeon in addition to gynecology surgeon (25.5% and 16.6% of cases, respectively). Among those with intraoperative complications (n = 25, 5.4%) were primarily conversion to laparotomy (n = 6, 2.0%), transfusion (n = 2, 0.6%), and organ wounds (n = 8, 1.7%). Overall, 5.6% had severe postoperative complications (Clavien-Dindo classification ≥ Grade 3). CONCLUSION: This is among the largest published series addressing RAL for DIE. Interest in this procedure appears promising, with no observed increases in blood loss or in peri- or post-operative complications. DIE laparoscopic surgery can require complex surgical procedures performed by multidisciplinary surgical teams. Thus, it may be one of the best candidates for RAL within gynecology surgery.

The role of government policies for Italian firms during the COVID-19 crisis.

This paper aims to respond to this research question: "How effective have government incentives been in preserving firm profitability and growth during the COVID-19 crisis?". We used a large, representative sample of Italian companies, which has produced a deeper study than the macro analyses provided by national statistics. Results shows that government policies alleviated the negative effects of the pandemic on troubled companies, but it was not enough to maintain the same financial health as firms that did not need this support. Small companies were the most adversely affected by the pandemic.

The RNA content of human sperm reflects prior events in spermatogenesis and potential post-fertilization effects.

Transcriptome analyses using high-throughput methodologies allow a deeper understanding of biological functions in different cell types/tissues. The present study provides an RNA-seq profiling of human sperm mRNAs and lncRNAs (messenger and long non-coding RNAs) in a well-characterized population of fertile individuals. Sperm RNA was extracted from twelve ejaculate samples under strict quality controls. Poly(A)-transcripts were sequenced and aligned to the human genome. mRNAs and lncRNAs were classified according to their mean expression values (FPKM: Fragments Per Kilobase of transcript per Million mapped reads) and integrity. Gene Ontology analysis of the Expressed and Highly Expressed mRNAs showed an involvement in diverse reproduction processes, while the Ubiquitously Expressed and Highly Stable mRNAs were mainly involved in spermatogenesis. Transcription factor enrichment analyses revealed that the Highly Expressed and Ubiquitously Expressed sperm mRNAs were primarily regulated by zinc-fingers and spermatogenesis-related proteins. Regarding the Expressed lncRNAs, only one-third of their potential targets corresponded to Expressed mRNAs and were enriched in cell-cycle regulation processes. The remaining two-thirds were absent in sperm and were enriched in embryogenesis-related processes. A significant amount of post-testicular sperm mRNAs and lncRNAs was also detected. Even though our study is solely directed to the poly-A fraction of sperm transcripts, results indicate that both sperm mRNAs and lncRNAs constitute a footprint of previous spermatogenesis events and are configured to affect the first stages of embryo development.

Optical-component-only adaptive optics.

This Letter introduces a technique for performing binary adaptive optics, which is carried out by optical components only, without the help of any electronic or optoelectronic device. In this technique, the interferogram produced by a point diffraction interferometer modulates a light-driven crystal. The modulated light-driven crystal may produce pupil-plane only-phase or only-amplitude binary masks to mitigate phase aberrations. The capability of working unsupported makes it suitable for application in hard-to-reach or hazardous locations such as satellites, underwater, or contaminated places. The Letter includes an experimental validation where the ability of the technique to produce pupil amplitude masking is confirmed.

Diagnostic challenges in von Willebrand disease. Report of two cases with emphasis on multimeric and molecular analysis.

Identification of qualitative variants of von Willebrand disease (VWD) can be a diagnostic challenge because of discrepant results obtained in the multiple laboratory tests available for its appropriate classification. We report two cases of infrequent inherited variants of VWD with unclear preliminary results with the test panel available at the time of first consultation and that were finally diagnosed as a VWD type 2A/IID with a c.8318 G > C, p.Cys2773Ser mutation and a VWD type 2M with c.4225 T > G, p.Val1409Phe mutation, respectively. The description of these two cases highlights that despite the limited diagnostic panel for the evaluation of von Willebrand Factor (VWF) functionality, the multimeric analysis and genetic family studies were fundamental tools to achieve the final diagnosis.

Quaternary adaptive optics.

We present a new Point Diffraction Interferometer (PDI). Binary adaptive optics (BAO) and Quaternary Adaptive Optics (QAO) can be performed with the help of this PDI as a wavefront sensor. The PDI interferogram, once binarized, is used in two consecutive steps to produce a quaternary mask with phase values 0, π/2, π and 3π/2. The addition of the quaternary mask compensates for the aberrated wavefront and allows us to reach a Strehl ratio of about 0.81. We have verified through computer simulations that the use of QAO depends on the number of actuators of the compensating device to achieve effective compensation. The technique was successfully validated through an experiment.

Novel Method for the Direct Measurement of the τ Lepton Dipole Moments.

A novel method for the direct measurement of the elusive magnetic and electric dipole moments of the τ lepton is presented. The experimental approach relies on the production of τ^{+} leptons from D_{s}^{+}→τ^{+}ν_{τ} decays, originating in fixed-target collisions at the LHC. A sample of polarized τ^{+} leptons is kinematically selected and subsequently channeled in a bent crystal. The magnetic and electric dipole moments of the τ^{+} lepton are measured by determining the rotation of the spin-polarization vector induced by the intense electromagnetic field between crystal atomic planes. The experimental technique is discussed along with the expected sensitivities.

Detection of periodontal pathogens in mothers of preterm birth and/or low weight.

BACKGROUND: The present study aims to estimate the possible relationship between periodontal pathogens in the oral cavity and the birth of Preterm Birth (PTB) and/or Low Birth Weight (LBW). MATERIAL AND METHODS: It's a case- control study with the subgengival biofilm samples were collected from four sites up deeper until 48 hours postpartum and were processes by Polymerase Chain Reaction (PCR) for presence the periodontal pathogens Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), Porphyromonas gingivalis (Pg), Treponema denticola (Td), Tannerella forsythia (Tf) e Aggregatibacter actinomycetemcomitans (Aa). The mothers were divided into case grup (babies weighing < 2500g and/or gestational age < 37 weeks) and control group (babies weighing ≥ 2500g and gestational age ≥ 37 weeks). Chi-square test and the measure of association obtained by Odds Ratio (OR) were used to estimate the association between the variables. RESULTS: Microbial analyses results showed no significant association between PTB and LBW with most periodontal pathogens in the oral cavity, even with association with the clinical presence of periodontitis. CONCLUSIONS: given the high presence of periodontal pathogens in the biofilm subgengival of recent mothers, it is suggested that the findings of this research serve as the basis for future studies on the pathophysiology involved in the relationship between periodontitis and PTB and/or LBW.

Polariton Anomalous Hall Effect in Transition-Metal Dichalcogenides.

We analyze the properties of strongly coupled excitons and photons in systems made of semiconducting two-dimensional transition-metal dichalcogenides embedded in optical cavities. Through a detailed microscopic analysis of the coupling, we unveil novel, highly tunable features of the spectrum that result in polariton splitting and a breaking of light-matter selection rules. The dynamics of the composite polaritons is influenced by the Berry phase arising both from their constituents and from the confinement-enhanced coupling. We find that light-matter coupling emerges as a mechanism that enhances the Berry phase of polaritons well beyond that of its elementary constituents, paving the way to achieve a polariton anomalous Hall effect.

Influence of 3 calcium channel blockers on gingival overgrowth in a population of severe refractory hypertensive patients.

OBJECTIVE: The aim of the current study was to assess the association between 3 different calcium channel blockers (CCBs) (nifedipine, amlodipine and felodipine) and gingival overgrowth in patients with a diagnosis of severe refractory hypertension. METHODS: One hundred and sixty-two patients with severe refractory hypertension, taking CCBs, were selected. Gingival overgrowth was graded and periodontal measurements were recorded (probing pocket depth, clinical attachment level, plaque index and bleeding on probing). Unconditional multivariable binary logistic regression analyses were performed to assess the association between CCB intake and gingival overgrowth after adjusting for potential confounders. RESULTS: Of the 162 patients, 26 (16.0%) were current smokers and 101 (62.3%) were females. The mean age (SD) was 54.1 (8.5) years and the median age (range) 52.5 (39-78) years. Gingival overgrowth was observed in 55 patients (34.0%). Nifedipine was the most common medication (35.2%; 57 of 162). The results of multiple binary logistic regression showed statistically significant associations between CCB intake (exposure) and gingival overgrowth (outcome) after adjusting for the variables treatment time with antihypertensive and plaque index. Patients with gingival overgrowth were 2.5 (odds ratio = 2.46; 95% confidence interval: 1.04-5.82) and 4.0 (odds ratio = 3.90; 95% confidence interval: 1.47-10.35) times more likely to be taking nifedipine and amlodipine, respectively, than patients without gingival overgrowth. On the other hand, this significant association was not observed for felodipine. CONCLUSION: Nifedipine and amlodipine, but not felodipine, were associated with gingival overgrowth in patients with severe refractory hypertension.

Prospective study feasibility: Screening of antenatal total abnormal pulmonary venous return.

INTRODUCTION: Total abnormal pulmonary venous return is a heart defect often missed prenatally, yet at birth, it is a surgical emergency. Antenatal detection could be improved by sonographic visualization of the anastomosis of 2 pulmonary veins in a sinus into the left atrium. The objective of this study is to evaluate the feasibility of this screening method. METHOD: Prospective observational study. Five operators selected one representative image taken during morphological ultrasound screening. Anonymized images were later assessed for quality by an expert. Both the operator and the expert were asked to rate the picture and collect clinical data. Feasibility corresponded to the percentage of images judged satisfactory by the expert; reliability corresponded to the percentage judged satisfactory by both the expert and the sonographer. RESULTS: A total of 192 patients were included. Feasibility was 73% (95% confidence interval, 67.1%-79.7%) and reliability was 81.4% (95% confidence interval, 75.9%-86.9%). There was no learning curve. CONCLUSION: This study confirms that visualization of the 2 pulmonary veins in a sinus into the left atrium at midtrimester screening is simple and reproducible. The next stage is to evaluate the sensitivity and specificity as a screening test of total abnormal pulmonary venous return and whether that would improve morbidity and mortality.

HLA-B*57 and IFNL4-related polymorphisms are associated with protection against HIV-1 disease progression in controllers.

Background: HIV-1-controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1-controllers have evidence of immunologic progression with marked CD4+T-cell decline. We investigated host genetic factors associated with protection against CD4+T-cell loss in HIV-1-controllers. Methods: We analysed the association of interferon lambda 4 (IFNL4)-related polymorphisms and HLA-B haplotypes within Long Term Non-Progressor HIV-1-controllers ((LTNP-C), defined by maintaining CD4+T-cells counts >500 cells/mm3 for more than 7 years after HIV-1 diagnosis) versus non-LTNP-C, who developed CD4+T-cells counts <500 cells/mm3 Both a Spanish study cohort (n=140) and an international validation cohort (n=914) were examined. Additionally, in a subgroup of individuals HIV-1-specific T-cell responses and soluble cytokines were analysed RESULTS: HLA-B*57 was independently associated with the LTNP-C phenotype (OR=3.056 (1.029-9.069) p=0.044 and OR=1.924 (1.252-2.957) p=0.003) while IFNL4 genotypes represented independent factors for becoming non-LTNP-C (TT/TT, ss469415590, OR=0.401 (0.171-0.942) p=0.036 or A/A, rs12980275, OR=0.637 (0.434-0.934) p=0.021) in the Spanish and validation cohort, respectively, after adjusting for sex, age at HIV-1 diagnosis, IFNL4-related polymorphisms and different HLA-B haplotypes. LTNP-C showed lower plasma IP-10 (p=0.019) and higher IFN-γ (p=0.02) levels than the HIV-1-controllers with diminished CD4+T-cell numbers. Moreover, LTNP-C exhibited higher quantities of IL2+CD57- and IFN-γ+CD57- HIV-1-specific CD8+T-cells (p=0.002 and 0.041, respectively) than non-LTNP-C. Conclusions: We have defined genetic markers able to segregate stable HIV-1-controllers from those who experience CD4+T-cell decline. These findings allow for identification of HIV-1-controllers at risk for immunologic progression, and provide avenues for personalized therapeutic interventions and precision medicine for optimizing clinical care of these individuals.

A Lower Baseline CD4/CD8 T-Cell Ratio Is Independently Associated with Immunodiscordant Response to Antiretroviral Therapy in HIV-Infected Subjects.

We explored if baseline CD4/CD8 T-cell ratio is associated with immunodiscordant response to antiretroviral therapy in HIV-infected subjects. Comparing immunodiscordant and immunoconcordant subjects matched by pretreatment CD4 counts, we observed a lower pretreatment CD4/CD8 T-cell ratio in immunodiscordant subjects. Furthermore, pretreatment CD4/CD8 T-cell ratio, but not CD4 counts, correlated with the main immunological alterations observed in immunodiscordants, including increased regulatory T-cell (Treg) frequency and T-cell turnover-related markers. Then, in a larger cohort, only baseline CD4/CD8 T-cell ratio was independently associated with immunodiscordance, after adjusting by the viral CXCR4-tropic HIV variants. Our results suggest that the CD4/CD8 T-cell ratio could be an accurate biomarker of the subjacent immunological damage triggering immunodiscordance.