Structural organization of erythrocyte membrane microdomains and their relation with malaria susceptibility

Cholesterol-rich microdomains are membrane compartments characterized by specific lipid and protein composition. These dynamic assemblies are involved in several biological processes, including infection by intracellular pathogens. This work provides a comprehensive analysis of the composition of human erythrocyte membrane microdomains. Based on their floating properties, we also categorized the microdomain-associated proteins into clusters. Interestingly, erythrocyte microdomains include the vast majority of the proteins known to be involved in invasion by the malaria parasite Plasmodium falciparum. We show here that the Ecto-ADP-ribosyltransferase 4 (ART4) and Aquaporin 1 (AQP1), found within one specific cluster, containing the essential host determinant CD55, are recruited to the site of parasite entry and then internalized to the newly formed parasitophorous vacuole membrane. By generating null erythroid cell lines, we showed that one of these proteins, ART4, plays a role in P. falciparum invasion. We also found that genetic variants in both ART4 and AQP1 are associated with susceptibility to the disease in a malaria-endemic population.

Genetic Diversity of Hepatitis E Virus Type 3 in Switzerland—From Stable to Table

Hepatitis E caused by hepatitis E viruses of the genotype 3 (HEV-3) is a major health concern in industrialized countries and due to its zoonotic character requires a “One Health” approach to unravel routes and sources of transmission. Knowing the viral diversity present in reservoir hosts, i.e., pigs but also wild boars, is an important prerequisite for molecular epidemiology. The aim of this study was to gain primary information on the diversity of HEV-3 subtypes present along the food chain in Switzerland, as well as the diversity within these subtypes. To this end, samples of domestic pigs from slaughterhouses and carcass collection points, as well as from hunted wild boars, were tested for HEV RNA and antibodies. HEV positive meat products were provided by food testing labs. The HEV subtypes were determined using Sanger and next generation sequencing. The genetic analyses confirmed the predominance of a Swiss-specific cluster within subtype HEV-3h in pigs, meat products, and wild boars. This cluster, which may result from local virus evolution due to the isolated Swiss pig industry, supports fast differentiation of domestic and imported infections with HEV.

A systematic approach to analyse the impact of farm-profiles on bovine health

In this study we present systematic framework to analyse the impact of farm profiles as combinations of environmental conditions and management practices on common diseases in dairy cattle. The data used for this secondary data analysis includes observational data from 166 farms with a total of 5828 dairy cows. Each farm is characterised by features from five categories: husbandry, feeding, environmental conditions, housing, and milking systems. We combine dimension reduction with clustering techniques to identify groups of similar farm attributes, which we refer to as farm profiles. A statistical analysis of the farm profiles and their related disease risks is carried out to study the associations between disease risk, farm membership to a specific cluster as well as variables that characterise a given cluster by means of a multivariate regression model. The disease risks of five different farm profiles arise as the result of complex interactions between environmental conditions and farm management practices. We confirm previously documented relationships between diseases, feeding and husbandry. Furthermore, novel associations between housing and milking systems and specific disorders like lameness and ketosis have been discovered. Our approach contributes to paving a way towards a more holistic and data-driven understanding of bovine health and its risk factors.

Screening of Swiss Pig Herds for Hepatitis E Virus: A Pilot Study

Hepatitis E virus (HEV) is an important cause of acute hepatitis in humans worldwide. In industrialised countries, most infections are caused by the zoonotic genotype 3. The main reservoir was found in pigs, with fattening pigs as the main shedders. The aim of this study was to establish a screening tool to detect HEV in pig farms. HEV-positive samples were sequenced using Sanger sequencing. First, different sample materials, including floor swabs, slurry, dust swabs and faeces were tested for HEV. Floor swabs turned out to give the best results and, in the form of sock swabs, were used for the screening of Swiss pig herds. A total of 138 pig farms were tested, with a focus on fattening pigs. Overall, 81 farms (58.8%) were HEV positive. Most sequences belonged to subtype 3h, in which they formed a specific cluster (Swiss cluster). In addition, subtype 3 l and two unassigned sequences were detected. As a conclusion, sock swabs were found to be a helpful tool to screen pig herds for HEV and establish a sequence collection that may enable molecular epidemiology and support outbreak investigation and prevention.

Magic Numbers in Boson 4He Clusters: The Auger Evaporation Mechanism

The absence of magic numbers in bosonic 4He clusters predicted by all theories since 1984 has been challenged by high-resolution matter-wave diffraction experiments. The observed magic numbers were explained in terms of enhanced growth rates of specific cluster sizes for which an additional excitation level calculated by diffusion Monte Carlo is stabilized. The present theoretical study provides an alternative explanation based on a simple independent particle model of the He clusters. Collisions between cluster atoms in excited states within the cluster lead to selective evaporation via an Auger process. The calculated magic numbers as well as the shape of the number distributions are in quite reasonable agreement with the experiments.

Establishment of a near-contiguous genome sequence of the citric acid producing yeast Yarrowia lipolytica DSM 3286 with resolution of rDNA clusters and telomeres

Yarrowia lipolytica is an oleaginous yeast that is particularly suitable for the sustainable production of secondary metabolites. The genome of this yeast is characterized by its relatively large size and its high number of different rDNA clusters located in its telomeric regions. However, due to the presence of long repetitive elements in the sub-telomeric regions, rDNA clusters and telomeres are missing in current genome assemblies of Y. lipolytica. Here, we present the near-contiguous genome sequence of the biotechnologically relevant strain DSM 3286. We employed a hybrid assembly strategy combining Illumina and nanopore sequencing reads to integrate all six rDNA clusters as well as telomeric repeats into the genome sequence. By fine-tuning of DNA isolation and library preparation protocols, we were able to create ultra-long reads that not only contained multiples of mitochondrial genomes but also shed light on the inter- and intra-chromosomal diversity of rDNA cluster types. We show that there are ten different rDNA units present in this strain that additionally appear in a predefined order in a cluster. Based on single reads, we also demonstrate that the number of rDNA repeats in a specific cluster varies from cell to cell within a population.

Undifferentiated Embryonal Sarcoma of the Liver With Rhabdoid Morphology Mimicking Carcinoma: Expanding the Morphologic Spectrum or a Distinct Variant?

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare aggressive neoplasm that occurs predominantly in children. Like mesenchymal hamartoma of the liver (MHL), UESL harbors recurrent rearrangements involving 19q13.3 and 19q13.4, a region of the genome that contains a primate-specific cluster of micro-RNAs. Here, we present a case of a high-grade neoplasm that arose in the left hepatic lobe of a 5-year-old male and gave rise to widespread lymph node, visceral, and soft tissue metastases. The tumor was composed of sheets, tubules, and papillae of epithelioid cells with rhabdoid morphology. INI1 and BRG1 expression were retained. Tumor cells diffusely expressed epithelial markers, including multiple keratins. While the morphologic and immunophenotypic features were suggestive of poorly differentiated carcinoma with rhabdoid features, the tumor was found to harbor the t(11;19)(q13;q13.3) translocation characteristic of UESL, as well as a TP53 mutation. Given the clinical presentation, imaging, clinical course, the tumor was classified as UESL with unusual, carcinoma-like histopathologic features. In the context of an unclassified high-grade hepatic tumor in a young child, molecular or cytogenetic testing for chromosome 19q13 alterations should be considered.

In addressing the question about the Samoyedic substrate in the South Siberian populations: the phylogeography of Y-chromosome haplogroup N-L666

We studied the diversity of Y-chromosomal haplogroup N-L666 in Southern Siberia, where this lineage itself is an approximate equivalent to N2-P43. The whole sample included 590 representatives of western, central, southern, southeastern and northeastern (Tojin) Tuvans, who identified themselves as one of 21 tribal groups, as well as Tofalars. The N-L666 subsample consisted of 138 individuals and was studied using 15 STR markers in two scales: local (considering the areal groups and tribal clans of Tuvans) and regional (in comparison with the populations of Southern and Western Siberia). Results. Two clusters of N-L666 STR haplotypes were identified: cluster A, specific for Tuvans and Tofalars (covering 19% and 16% of their gene pools respectively) and cluster B, widely scattered throughout Siberia from the West to the Transbaikalia (reaching ~30% in Tofalars). The ubiquity and a greater age of the cluster B favor the idea of its origin in the ancestral population – the ultimate source of the haplogroup N-L666 in Siberia – commonly alleged to be Samoyedic by language. On the contrary, the narrow geographic range and a relatively recent age of the cluster A indicate its formation in the area inhabited by Tuvans and Tofalars during the last thousand years. The emergence of subclusters A1, A2, B1 may be the result of demographic growth in the populations of Tuvans, southern Altaians and Khakas about 300-450 years ago. The spread of the same haplotypes, clusters and subclusters among different regional groups and clans of Tuvans indicates a common source of haplogroup N-L666 for them, which existed in the gene pool long before the separation of the studied populations. Conclusions. A specific cluster of haplogroup N-L666 in Tuvans was presumably founded by a representative of one of the Samoyedic tribes, whose numerous descendants participated in the formation of the Tuvans, Tofalars and southern Altaians over the last thousand years.

“To be or not to be” located in a cluster?—A descriptive meta-analysis of the firm-specific cluster effect

In the twenty-first century, clusters can be observed in most developed economies. However, the scientific results regarding the effect of clusters on firm performance are highly contradictive. The inconsistencies in the empirical results make it difficult to infer general conclusions about the firm-specific cluster effect, or in other words, the effect from being located in a cluster on firm performance (e.g. derived through the externalities within clusters). Therefore, this paper aims to reconcile the contradictory empirical findings. It investigates whether the prevalent assumption that clusters are a beneficial location for firms is unconditionally true or whether doubts about the alleged positive effect of clusters on firm performance are justified. By conducting a descriptive meta-analysis of the empirical literature, based on four different performance variables from four separate publication databases, the study investigates the direction of the effect as well as possible moderating influences. We find evidence for a rather positive firm-specific cluster effect. However, we identify several variables from the micro-, meso- and macro-level that directly or interactively moderate the relationship between clusters and firm success. For example, the results demonstrate that a negative firm-specific cluster effect occurs more frequently in low-tech industries than in high-tech industries. “To be or not to be” located in a cluster is therefore not the question, but it rather depends on the specific conditions.

Integrative functional analysis uncovers metabolic differences between Candida species

Candida species are a dominant constituent of the human mycobiome and a better understanding of their metabolism from a fungal perspective can provide key insights into their ability to cause pathogenesis. Here, we have developed the BioFung database a fungal specific tool for functional annotation using the KEGG database that provides an efficient method for annotation of protein-encoding gene. Analysis of carbohydrate-active enzyme (CAZymes) and BioFung, uncovered core and accessory features across Candida species demonstrating plasticity, adaptation to the environment and acquired features. Integerative functional analysis revealed that all Candida species can employ amino acid metabolism. However, metabolomics revealed that only a specific cluster of species (AGAu species; C. albicans, C. glabrata and C. auris) utilised amino acid metabolism. We identified critical metabolic pathways in the AGAu clusters with biomarkers and antifungal target potential in the CAZyme profile, polyamine, choline and fatty acid biosynthesis pathways. This study, combining genomic analysis, metabolomics and gene expression validation, highlights the metabolic diversity within AGAu species that underlies their remarkable ability to dominate the mycobiome and cause disease.