Alien parakeets as a potential threat to the common noctule Nyctalus noctula

The ring-necked parakeet Psittacula krameri (Aves: Psittaciformes) is a widely distributed species of Asian and African origin, which occurs with over 40 alien populations in the rest of the world. Most established populations of this species are showing a clear trend of territorial expansion and numerical growth. Recent reviews highlighted that one of the main impacts by alien ring-necked parakeets is the competition with threatened bat spe cies using trunk cavities as roosts. In Italy, the only known reproductive population of Nyctalus bats (Mammalia: Chiroptera) occurs in an urban area in the central part of the country, surrounded by increasing and expanding populations of ring-necked parakeets. In this work, we updated the population status of both ring-necked and Alexandrine parakeets and breeding noctule bats in the region. Then, we ran a species distribution model using Maxent software to analyze the environmental suitability of the region for the ring-necked parakeet and a connectivity model using Circuitscape software to predict the possibility of its expansion in the area occupied by breeding noctule bats. We recorded a high number of individual parakeets and breeding colonies, together with a remarkable noctule popula tion decline, from about 400 to about 120 individuals, in the last 20 years, possibly due to urban green management practices. Although some ring-necked parakeets have already been observed in the study area, there is no evidence of reproduction in the surroundings of the noctule colony. However, our model showed a high environmental suitability for the ring-necked parakeet in the area occupied by breeding noctules. As well, the connectivity model showed the potential for a direct fow of individuals from the main urban centers to the area used by noctule bats. The arrival of alien parakeets to the area occupied by the bat breeding colony should be tightly monitored by surveying the suitable areas for this bird, as well as the identifed ecological corridors. Early detection of new invasions, together with a sustainable urban green management practice, may prevent the extinction of the southernmost breeding colony of the common noctule

Functional Interaction Between BRCA1 and DNA Repair in Yeast May Uncover a Role of RAD50, RAD51, MRE11A, and MSH6 Somatic Variants in Cancer Development

In this study, we determined if BRCA1 partners involved in DNA double-strand break (DSB) and mismatch repair (MMR) may contribute to breast and ovarian cancer development. Taking advantage the functional conservation of DNA repair pathways between yeast and human, we expressed several BRCA1 missense variants in DNA repair yeast mutants to identify functional interaction between BRCA1 and DNA repair in BRCA1-induced genome instability. The pathogenic p.C61G, pA1708E, p.M775R, and p.I1766S, and the neutral pS1512I BRCA1 variants increased intra-chromosomal recombination in the DNA-repair proficient strain RSY6. In the mre11, rad50, rad51, and msh6 deletion strains, the BRCA1 variants p.C61G, pA1708E, p.M775R, p.I1766S, and pS1215I did not increase intra-chromosomal recombination suggesting that a functional DNA repair pathway is necessary for BRCA1 variants to determine genome instability. The pathogenic p.C61G and p.I1766S and the neutral p.N132K, p.Y179C, and p.N550H variants induced a significant increase of reversion in the msh2Δ strain; the neutral p.Y179C and the pathogenic p.I1766S variant induced gene reversion also, in the msh6Δ strain. These results imply a functional interaction between MMR and BRCA1 in modulating genome instability. We also performed a somatic mutational screening of MSH6, RAD50, MRE11A, and RAD51 genes in tumor samples from 34 patients and identified eight pathogenic or predicted pathogenic rare missense variants: four in MSH6, one in RAD50, one in MRE11A, and two in RAD51. Although we found no correlation between BRCA1 status and these somatic DNA repair variants, this study suggests that somatic missense variants in DNA repair genes may contribute to breast and ovarian tumor development

Characterization of three alternative transcripts of the BRCA1 gene in patients with breast cancer and a family history of breast and/or ovarian cancer who tested negative for pathogenic mutations

The study of BRCA1 and BRCA2 genes and their alterations has been essential to the understanding of the development of familial breast and ovarian cancers. Many of the variants identified have an unknown pathogenic significance. These include variants which determine alternative mRNA splicing, identified in the intronic regions and those are capable of destroying the splicing ability. The aim of this study was to detect BRCA1/BRCA2 aberrant transcripts resulting from alternative splicing, in women with a known family history and/or early onset of breast and/or ovarian cancer, tested wild-type for BRCA1 and BRCA2. The identification and characterization of aberrant transcripts through the analysis of mRNA levels in blood lymphocytes may help us to recognize families otherwise misclassified as wild-type BRCA1 and BRCA2. Blood samples were collected from 13 women that had a family history of breast and/or ovarian cancer and tested negative for pathogenic mutations in the BRCA1 and BRCA2 genes. Total RNA was analyzed for the presence of BRCA1 and BRCA2 naturally occuring and pathological transcripts using RT-PCR. In 2 out of the 13 samples, 2 alternative transcripts of the BRCA1 gene were identified. These were probably pathogenic as they lacked exon 17 and exon 15, respectively, giving rise to a truncated protein. In addition to these, we identified the Δ17–19 transcript in 1 patient, which gives rise to a protein with an in-frame deletion of 69 amino acids. In conclusion, this study on alternative transcripts of the BRCA1 and BRCA2 genes revealed the presence of isoforms (prevalence of 15%) in blood samples from women with breast and ovarian cancer that were probably pathogenic, that were not detected by conventional methods of mutation screening based on direct sequencing of all coding regions, intron-exons junctions and MLPA analysis

MSH2 role in BRCA1-driven tumorigenesis: A preliminary study in yeast and in human tumors from BRCA1-VUS carriers

BRCA1 interacts with several proteins implicated in homologous and non homologous recombination and in mismatch repair.The aim of this study is to determine if MSH2, a well known partner of BRCA1 involved in DNA repair, may contribute to breast and ovarian cancer development and progression.To better understand the functional interaction between BRCA1 and MSH2, we studied the effect of the deletion of MSH2 gene on BRCA1-induced genome instability in yeast. Preliminary results in yeast indicated that MSH2 and BRCA1 may interact to modulate homologous recombination (HR). We also carried out a genetic and epigenetic profiling of MSH2 gene by mutational analysis and promoter methylation evaluation in 9 breast and 2 ovarian tumors from carriers of BRCA1 unknown significance variants (VUS).2/2 ovarian and 2/9 breast tumors carried MSH2 somatic mutations possible pathogenics (4/11, 36%): a missense mutation in exon 3 (p.G162R), a duplication of exon 1 and a deletion of exon 2. In addition, two germline synonymous variants in exon 11 were identified. None of the tumors showed promoter methylation.In conclusion, a surprisingly high frequency of MSH2 gene mutations has been found in tumor tissues from BRCA1 VUS carrier patients. This result supports the indication deriving from the yeast model that BRCA1 driven tumorigenesis may be modulated by MSH2

Mid-term follow-up chest CT findings in recovered COVID-19 patients with residual symptoms

Objectives: More than a year has passed since the initial outbreak of SARS-CoV-2, which caused many hospitalizations worldwide due to COVID-19 pneumonia and its complications. However, there is still a lack of information detailing short- and long-term outcomes of previously hospitalized patients. The purpose of this study is to analyze the most frequent lung CT findings in recovered COVID-19 patients at mid-term follow-ups. Methods: A total of 407 consecutive COVID-19 patients who were admitted to the Fondazione IRCCS Policlinico San Matteo, Pavia and discharged between February 27, 2020, and June 26, 2020 were recruited into this study. Out of these patients, a subset of 108 patients who presented with residual asthenia and dyspnea at discharge, altered spirometric data, positive lung ultrasound and positive chest X-ray was subsequently selected, and was scheduled to undergo a mid-term chest CT study, which was evaluated for specific lung alterations and morphological patterns. Results: The most frequently observed lung CT alterations, in order of frequency, were ground-glass opacities (81%), linear opacities (74%), bronchiolectases (64.81%), and reticular opacities (63.88%). The most common morphological pattern was the non-specific interstitial pneumonia pattern (63.88%). Features consistent with pulmonary fibrosis were observed in 32 patients (29.62%). Conclusions: Our work showed that recovered COVID-19 patients who were hospitalized and who exhibited residual symptoms after discharge had a slow radiological recovery with persistent residual lung alterations. Advances in knowledge: This slow recovery process should be kept in mind when determining the follow-up phases in order to improve the long-term management of patients affected by COVID-19

Venous thromboembolism and COVID-19: a single center experience from an academic tertiary referral hospital of Northern Italy

Preliminary evidence supports the notion that COVID-19 patients may have an increased susceptibility to develop venous thromboembolism (VTE). However, the magnitude of this association still needs to be defined. Furthermore, clinical predictors of thrombogenesis, and the relationship with the inflammatory status are currently unknown. On this basis, we conducted a retrospective, observational study on 259 consecutive COVID-19 patients admitted to an academic tertiary referral hospital in Northern Italy between March 19th and April 6th, 2020. Records of COVID-19 patients with a definite VTE event were reviewed for demographic information, co-morbidities, risk factors for VTE, laboratory tests, and anticoagulation treatment. Twenty-five cases among 259 COVID-19 patients developed VTE (9.6%), all of them having a Padua score > 4, although being under standard anticoagulation prophylaxis since hospital admission. In the VTE subcohort, we found a significant positive correlation between platelet count (PLT) and either C reactive protein (CRP) (p < 0.0001) or lactate dehydrogenase (LDH) (p = 0.0013), while a significant inverse correlation was observed between PLT and mean platelet volume (p < 0.0001). Platelet-to-lymphocyte ratio significantly correlated with CRP (p < 0.0001). The majority of VTE patients was male and younger compared to non-VTE patients (p = 0.002 and p = 0.005, respectively). No significant difference was found in d-dimer levels between VTE and non VTE patients, while significantly higher levels of LDH (p = 0.04) and IL-6 (p = 0.04) were observed in VTE patients in comparison to non-VTE patients. In conclusion, our findings showed a quite high prevalence of VTE in COVID-19 patients. Raised inflammatory indexes and increased serum levels of pro-inflammatory cytokines should raise the clinical suspicion of VTE