Runs of homozygosity in the Italian goat breeds: impact of management practices in low‑input systems

Background Climate and farming systems, several of which are considered as low-input agricultural systems, vary between goat populations from Northern and Southern Italy and have led to different management practices. These processes have impacted genome shaping in terms of inbreeding and regions under selection and resulted in differences between the northern and southern populations. Both inbreeding and signatures of selection can be pinpointed by the analysis of runs of homozygosity (ROH), which provides useful information to assist the management of this species in different rural areas. Results We analyzed the ROH distribution and inbreeding (FROH) in 902 goats from the Italian Goat Consortium2 dataset. We evaluated the differences in individual ROH number and length between goat breeds from Northern (NRD) and Central-southern (CSD) Italy. Then, we identified the signatures of selection that differentiate these two groups using three methods: ROH, ΔROH, and averaged FST. ROH analyses showed that some Italian goat breeds have a lower inbreeding coefficient, which is attributable to their management and history. ROH are longer in breeds that are undergoing non-optimal management or with small population size. In several small breeds, the ROH length classes are balanced, reflecting more accurate mating planning. The differences in climate and management between the NRD and CSD groups have resulted in different ROH lengths and numbers: the NRD populations bred in isolated valleys present more and shorter ROH segments, while the CSD populations have fewer and longer ROH, which is likely due to the fact that they have undergone more admixture events during the horizontal transhumance practice followed by a more recent standardization. We identified four genes within signatures of selection on chromosome 11 related to fertility in the NRD group, and 23 genes on chromosomes 5 and 6 related to growth in the CSD group. Finally, we identified 17 genes on chromosome 12 related to environmental adaptation and body size with high homozygosity in both groups. Conclusions These results show how different management practices have impacted the level of genomic inbreeding in two Italian goat groups and could be useful to assist management in a low-input system while safeguarding the diversity of small populations

Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy

Background: Breast cancer (BC) is a heterogeneous disease made up of clones with different metastatic potential. Intratumoral heterogeneity may cause metastases to show divergent biomarker expression, potentially affecting chemotherapy response. Methods: We investigated the immunohistochemical (IHC) and FISH profile of estrogen receptors (ER), progesterone (PR) receptors, Ki67, and HER2 in a series of BC-matched primary tumors (PTs) and axillary lymph node (ALN) metastases in pre-operative core needle biopsies (CNBs). Phenotypical findings were correlated to morphological features and their clinical implications. Results: Divergent expression between PTs and ALNs was found in 10% of the tumors, often involving multiple biomarkers (12/31, 39%). Most (52%) displayed significant differences in ER and PR staining. HER2 divergences were observed in almost three-quarters of the cases (23/31, 74%), with five (16%) switching from negativity to overexpression/amplification in ALNs. Roughly 90% of disparities reflected significant morphological differences between PTs and ALN metastases. Less than half of the discrepancies (12/31, 39%) modified pre/post-operative treatment options. Conclusions: We observed relevant discrepancies in biomarker expression between PTs and metastatic ALNs in a noteworthy proportion (10%) of preoperative BC CNBs, which were often able to influence therapies. Hence, our data suggest routine preoperative assessment of biomarkers in both PTs and ALNs in cases showing significant morphological differences

Genetic diversity of Italian goat breeds assessed with a medium-density SNP chip

Background: Among the European countries, Italy counts the largest number of local goat breeds. Thanks to the recent availability of a medium-density SNP (single nucleotide polymorphism) chip for goat, the genetic diversity of Italian goat populations was characterized by genotyping samples from 14 Italian goat breeds that originate from different geographical areas with more than 50 000 SNPs evenly distributed on the genome. Results: Analysis of the genotyping data revealed high levels of genetic polymorphism and an underlying North-south geographic pattern of genetic diversity that was highlighted by both the first dimension of the multi-dimensional scaling plot and the Neighbour network reconstruction. We observed a moderate and weak population structure in Northern and Central-Southern breeds, respectively, with pairwise FST values between breeds ranging from 0.013 to 0.164 and 7.49 % of the total variance assigned to the between-breed level. Only 2.11 % of the variance explained the clustering of breeds into geographical groups (Northern, Central and Southern Italy and Islands). Conclusions: Our results indicate that the present-day genetic diversity of Italian goat populations was shaped by the combined effects of drift, presence or lack of gene flow and, to some extent, by the consequences of traditional management systems and recent demographic history. Our findings may constitute the starting point for the development of marker-assisted approaches, to better address future breeding and management policies in a species that is particularly relevant for the medium-and long-term sustainability of marginal regions

MoS2 nanosheets via electrochemical lithium-ion intercalation under ambient conditions

Two-dimensional (2D) transition metal dichalcogenides (TMDs) are continuously attracting attention for both fundamental studies and technological applications. The physical and chemical properties of ultrathin TMD sheets are extraordinarily different from those of the corresponding bulk materials and for this reason their production is a stimulating topic, especially when the preparation method enables to obtain a remarkable yield of nanosheets with large area and high quality. Herein, we present a fast (<1 h) electrochemical exfoliation of molybdenum disulfide (MoS2) via lithium-ion intercalation, by using a solution of lithium chloride in dimethyl sulfoxide (DMSO). Unlike the conventional intercalation methods based on dangerous organolithium compounds, our approach leads to the possibility to obtain mono-, bi- and tri-layer thick MoS2 nanosheets with a large fraction of the semiconducting 2H phase (∼60%), as estimated by X-ray photoelectron spectroscopy (XPS). The electrical properties of the exfoliated material were investigated through the fabrication and characterization of back-gated field-effect transistors (FETs) based on individual MoS2 nanosheets. As-fabricated devices displayed unipolar semiconducting behavior (n-type) with field-effect mobility µFE ≤ 10−3 cm2 V−1 s−1 and switching ratio Ion/Ioff ≤ 10, likely limited by 1T/2H polymorphism and defects (e.g. sulfur vacancies) induced during the intercalation/exfoliation process. A significant enhancement of the electrical performances could be achieved through a combination of vacuum annealing (150 °C) and sulfur-vacancy healing with vapors of short-chain alkanethiols, resulting in µFE up to 2 × 10−2 cm2 V−1 s−1 and Ion/Ioff ≈ 100. Our results pave the way towards the fast preparation – under ambient conditions – of semiconducting MoS2 nanosheets, suitable for application in low cost (opto-)electronic devices

Microsatellite diversity of the Nordic type of goats in relation to breed conservation: how relevant is pure ancestry?

In the last decades, several endangered breeds of livestock species have been re-established effectively. However, the successful revival of the Dutch and Danish Landrace goats involved crossing with exotic breeds and the ancestry of the current populations is therefore not clear. We have generated genotypes for 27 FAO-recommended microsatellites of these landraces and three phenotypically similar Nordic-type landraces and compared these breeds with central European, Mediterranean and south-west Asian goats. We found decreasing levels of genetic diversity with increasing distance from the south-west Asian domestication site with a south-east-to-north-west cline that is clearly steeper than the Mediterranean east-to-west cline. In terms of genetic diversity, the Dutch Landrace comes next to the isolated Icelandic breed, which has an extremely low diversity. The Norwegian coastal goat and the Finnish and Icelandic landraces are clearly related. It appears that by a combination of mixed origin and a population bottleneck, the Dutch and Danish Land-races are separated from the other breeds. However, the current Dutch and Danish populations with the multicoloured and long-horned appearance effectively substitute for the original breed, illustrating that for conservation of cultural heritage, the phenotype of a breed is more relevant than pure ancestry and the genetic diversity of the original breed. More in general, we propose that for conservation, the retention of genetic diversity of an original breed and of the visual phenotype by which the breed is recognized and defined needs to be considered separately

Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems

Background. Innovative drugs targeting the PD1/PD-L1 axis have opened promising scenarios in modern cancer therapy. Plenty of assays and scoring systems have been developed for the evaluation of PD-L1 immunohistochemical expression, so far considered the most reliable therapeutic predictive marker. Methods. By gathering the opinion of acknowledged experts in dedicated fields of pathology, we sought to update the currently available evidence on PD-L1 assessment in various types of tumors. Results. Robust data were progressively collected for several anatomic districts and leading international agencies to approve specific protocols: among these, TPS with 22C3, SP142 and SP263 clones in lung cancer; IC with SP142 antibody in breast, lung and urothelial tumors; and CPS with 22C3/SP263 assays in head and neck and urothelial carcinomas. On the other hand, for other malignancies, such as gastroenteric neoplasms, immunotherapy has been only recently introduced, often for particular histotypes, so specific guidelines are still lacking. Conclusions. PD-L1 immunohistochemical scoring is currently the basis for allowing many cancer patients to receive properly targeted therapies. While protocols supported by proven data are already available for many tumors, dedicated studies and clinical trials focusing on harmonization of the topic in other still only partially explored fields are surely yet advisable

Microsimulazione di Reti Stradali in presenza di Sistemi di Infomobilità

Il presente studio si prepone di esaminare l effettiva capacità da parte dei moderni softwares di simulazione del traffico di implementare la presenza di sistemi di disseminazione dell informazione in tempo reale ed al contempo indagare, attraverso la simulazione, gli effetti dell informazione sull utenza dei sistema di trasporto, con riferimento al solo modo di trasporto su veicolo privato

Commentary: The Digital Fate of Glomeruli in Renal Biopsy

No abstract available; Comment on J Pathol Inform. 12(1):13

A novel identification system for potentially counterfeit medical devices based on the visual analysis through evaluation sheet .

Background. The counterfeiting of medical devices has been a growing problem for several years, especially since the extension of the internet. Regulatory authorities are responsible, in collaboration with relevant national and international stakeholders, for establishing mechanisms to detect falsified products circulating in their territories and for removing them from the market. Thus it might be useful develop a simple and affordable preliminary screening methods to be used by inspectors to decide in the field whether to collect a sample for further laboratory analysis or not. We here report a new method to compare the physical appearances of suspected samples with those of known genuine products based on the new regulation 2017/745 on medical devices. Methods. According to the new Regulation (EU) 2017/745 on medical devices, we have collected all the requirements regarding the information supplied with the device, including: qualitative composition of the device and quantitative information on the main constituent or constituents responsible for achieving the principal intended action, the labeling and packaging and the CE marking of conformity. Thanks to these pieces of information, along with those concerning the physical characteristics of the product, permit us to compare the potentially counterfeit medical devices with the known genuine products. Results. We developed a new and quick method to provide evidence that the sample comes from a falsified product. We have designed a table (Table 1) containing a list of questions to ask yourself to compare potentially counterfeit medical device with the known genuine products. The questions include the visual analysis of packaging and the information reported on the package (Does it reflect the appearance of the original form and colour? Is the packaging size the same as the original? Is this system homologous to the original? Do the information on the packaging reflect the appearance of the original colour and form?...), including qualitative and quantitative information (Since it is a substance-based medical device, is the overall qualitative composition of the device reported? Does this match that of its original counterpart?...), the presence and the conformity of CE marking (Is there an EC marking? Is the marking clear, legible and indelible?...) and the physical analysis of the characteristics of the product (Do they all have the same shape if they are tablets/capsules? Do all tablets/capsules have the same size among them and compared to the original? Do all the tablets have the same type of surface coating?...).The questions provide a simple yes or no answer. Conclusions. Visual analysis is an important part of the inspection process in the pharmaceutical industry. Falsified medical devices may be identified from this simple and quick method