Diffuse Peritoneal Malignant Mesothelioma Presenting with Abnormal Uterine Bleeding: Case Report

This report describes a highly unusual case of malignant peritoneal mesothelioma (MPM), who presented with abnormal menstrual bleeding due to diffuse infiltration of the uterus. MPM is a rare entity, which on initial clinical presentation can be indistinguishable from a primary gynecological malignancy such as ovarian cancer. As differential diagnosis is challenging among primary care physicians, gynecologists, gynecological oncologists, and pathologists, misdiagnosis and subsequent mismanagement are not uncommon. Immunohistochemical stains were required in our case to help to make the final diagnosis. We included multiple mesothelial markers such as calretinin, CK5/6, WT-1, and D240 in our analysis, in addition to epithelial markers such as Claudin-4, BerEP4, B72.3, and PAX-8, to exclude metastatic adenocarcinoma.Ivana Rizzuto, Theresa Power, Martin Klaus Oehle

Maedi Visna virus infection and TMEM154 genotypes in Valle del Belìce sheep breed

Maedi Visna (MV) is a viral infection in sheep caused by Lentivirus and characterised by a long incubation period, slow progression, weight loss and eventually death. TMEM154 was reported in the ovine as major candidate gene associated with host susceptibility/resistance. The aim of this study was to verify the prevalence of MV infection within Sicilian herds of Valle del Belìce breed using an ELISA serological test and to estimate the frequencies of the resistant/susceptible genotypes to the TMEM154 gene. Finally, we investigated the association between TMEM154 E/K genotype and MV infectious status. A total of 1,083 animals from different flocks were tested. The ELISA method showed 15.33% (n = 166) of infected individuals. Analyses of the sequences showed the presence of both K and E alleles with frequencies of 0.151 and 0.849, respectively. On the total individuals, only 23 carried KK genotype while 280 were heterozigous EK, and 780 homozygous EE. The locus was in Hardy-Weinberg equilibrium in the breed (p-value <0.05) and observed and expected heterozygosity values were 0.258 and 0.256, respectively. Moreover, a significant association (p-value < 0.001) between TMEM154 genotypes and seroprevalence status (positive vs. negative) was found. This study allowed us to know the prevalence of MV infection in Sicilian flocks of Valle del Belìce breed and could be helpful in establishing selection programs aimed at controlling and eradicating this virus

Are inner disc misalignments common? ALMA reveals an isotropic outer disc inclination distribution for young dipper stars

Dippers are a common class of young variable star exhibiting day-long dimmings with depths of up to several tens of per cent. A standard explanation is that dippers host nearly edge-on (id ≈ 70°) protoplanetary discs that allow close-in (10 au) disc resolved by ALMA and that inner disc misalignments may be common during the protoplanetary phase. More than one mechanism may contribute to the dipper phenomenon, including accretion-driven warps and ‘broken’ discs caused by inclined (sub-)stellar or planetary companions

Identification of Copy Number Variations and Genetic Diversity in Italian Insular Sheep Breeds

Copy number variants (CNVs) are one of the major contributors to genetic diversity and phenotypic variation in livestock. The aim of this work is to identify CNVs and perform, for the first time, a CNV-based population genetics analysis with five Italian sheep breeds (Barbaresca, Comisana, Pinzirita, Sarda, and Valle del Belìce). We identified 10,207 CNVs with an average length of 1.81 Mb. The breeds showed similar mean numbers of CNVs, ranging from 20 (Sarda) to 27 (Comisana). A total of 365 CNV regions (CNVRs) were determined. The length of the CNVRs varied among breeds from 2.4 Mb to 124.1 Mb. The highest number of shared CNVRs was between Comisana and Pinzirita, and only one CNVR was shared among all breeds. Our results indicated that segregating CNVs expresses a certain degree of diversity across all breeds. Despite the low/moderate genetic differentiation among breeds, the different approaches used to disclose the genetic relationship showed that the five breeds tend to cluster in distinct groups, similar to the previous studies based on single-nucleotide polymorphism markers. Gene enrichment was described for the 37 CNVRs selected, considering the top 10%. Out of 181 total genes, 67 were uncharacterized loci. Gene Ontology analysis showed that several of these genes are involved in lipid metabolism, immune response, and the olfactory pathway. Our results corroborated previous studies and showed that CNVs represent valuable molecular resources for providing useful information for separating the population and could be further used to explore the function and evolutionary aspect of sheep genome

High-density SNP markers elucidate the genetic divergence and population structure of Noticiana sheep breed in the Mediterranean context

Among livestock species, sheep have played an early major role in the Mediterranean area. Italy has a long history of sheep breeding and, despite a dramatic contraction in numbers, still raise several local populations that may represent a unique source of genetic diversity. The Noticiana is a breed of the south-eastern part of Sicily appreciated both for its dairy products and for its resistance to harsh environment. In this study, the high-density Illumina Ovine SNP600K BeadChip array was used for the first genome-wide characterization of 48 individuals of Noticiana sheep to investigate its diversity, the genome structure and the relationship within the context of worldwide and Italian breeds. Moreover, the runs of homozygosity (ROH) pattern and the pairwise FST-outliers were examined. Noticiana reported moderate levels of genetic diversity. The high percentage of short and medium length ROH segments (93% under 4 Mb) is indicative of a within breed relatedness dating back to ancient times, despite the absence of management for the mating plans and the reduced population size. In the worldwide context, the Southern Italian, Spanish and Albanian breeds overlapped in a macro cluster which also included the Noticiana sheep. The results highlighted ancestral genetic components of Noticiana shared with Comisana breed, and showed the clear separation from the other Italian sheep. This is likely the consequence of the combined effects of genetic drift, small population size and reproductive isolation. ROH islands and FST-outliers approaches in Noticiana identified genes and QTLs involved in milk and meat production, as well as related to the local adaptation, and therefore are consistent with the phenotypic traits of the studied breed. Although a wider sampling could be useful to deepen the genomic survey on Noticiana, these results represent a crucial starting point for the characterization of an important local genetic resource, with a view of supporting the local economy and preserving the biodiversity of the sheep species

The mitochondrial calcium uniporter regulates breast cancer progression via HIF-1α

Triple-negative breast cancer (TNBC) represents the most aggressive breast tumor subtype. However, the molecular determinants responsible for the metastatic TNBC phenotype are only partially understood. We here show that expression of the mitochondrial calcium uniporter (MCU), the selective channel responsible for mitochondrial Ca(2+) uptake, correlates with tumor size and lymph node infiltration, suggesting that mitochondrial Ca(2+) uptake might be instrumental for tumor growth and metastatic formation. Accordingly, MCU downregulation hampered cell motility and invasiveness and reduced tumor growth, lymph node infiltration, and lung metastasis in TNBC xenografts. In MCU-silenced cells, production of mitochondrial reactive oxygen species (mROS) is blunted and expression of the hypoxia-inducible factor-1α (HIF-1α) is reduced, suggesting a signaling role for mROS and HIF-1α, downstream of mitochondrial Ca(2+) Finally, in breast cancer mRNA samples, a positive correlation of MCU expression with HIF-1α signaling route is present. Our results indicate that MCU plays a central role in TNBC growth and metastasis formation and suggest that mitochondrial Ca(2+) uptake is a potential novel therapeutic target for clinical intervention