Ureaplasma diversum is an opportunistic Mollicute associated with reproductive losses in cattle. Reports of this disease are scarce in South America. This study documents three sporadic cases of U. diversum–associated abortion and/or stillbirth occurring in three different beef cattle herds, as well as a cluster of three neonatal losses affecting a fourth herd in Uruguay. Diagnosis was based on histopathological findings, PCR, and systematic exclusion of other major abortifacient pathogens. The cases of abortion/stillbirth had fibrinosuppurative and necrotizing placentitis and fetal bronchopneumonia, whereas neonatal cases presented mild polyarthritis, interstitial pneumonia, and, in one calf, multisystemic inflammation. Ureaplasma diversum was detected by PCR in the placenta and/or lung in all six cases, and intralesional localization of U. diversum was demonstrated, for the first time, by in situ hybridization in two abortion cases. PCR was also performed from endometrial samples taken by cytobrush from 80 cows in the herd with the cluster of cases of perinatal mortality, showing no differences (p = 0.56) in the presence of U. diversum between affected (20
Promyelomonocytic leukemia (PML) is a prominent oncosuppressor whose inactivation is involved in the pathogenesis of hematological and epithelial cancers. Here, we report that PML aggregated in nuclear bodies in syncytia elicited by the envelope glycoprotein complex (Env) of human immunodeficiency virus-1 (HIV-1) in vitro. PML aggregation occurred after the fusion of nuclei (karyogamy) within syncytia but before the apoptotic program was activated. The aggregation of PML was detectable in syncytia present in the brain or lymph nodes from patients with HIV-1 infection, as well as in a fraction of blood leukocytes, correlating with viral status. Using a range of specific inhibitors of PML (the oncogenic PML/RARα fusion product or specific small interfering RNAs), we demonstrated that, in Env-elicited syncytia, PML was required for activating phosphorylation of ataxia telangiectasia mutated (ATM), which colocalized with PML in nuclear bodies, in a molecular complex that also involved topoisomerase IIβ-binding protein 1. PML knockdown thus inhibited the ATM-dependent DNA damage response that culminates in the activation of p53, p53-dependent transcription of pro-apoptotic genes and cell death. Infection of CD4-expressing cells with HIV-1 also induced syncytial apoptosis, which could be suppressed by inhibiting PML. Altogether, these data indicate that PML activation is a critical early event that participates in the apoptotic demise of HIV-1-elicited syncytia.
Immune responsiveness at barrier surfaces is tailored to the exposures of each tissue. In the oral mucosa, mechanisms by which a permeable epithelium coexists with diverse microbiota and maintains integrity during inflammatory pathology remain poorly understood. We compile a multiomics spatial map of this exposed mucosal microenvironment and uncover remarkable immune zonation with organization that is preserved even during inflammatory disease. At the tooth interface, we identify a dynamic epithelium underlined by a layer of neutrophils and a zone of antigen-presenting cell-lymphocyte aggregates. During disease, inflammatory zones expand and organize into immature tertiary lymphoid structures, suggesting local antibody production. Location-specific transcriptomes support a role for the stromal compartment in the spatial organization of immunity. This preserved immune zonation meets the demands for continuous protection of this vulnerable interface and suggests unique tissue-specific wiring of immunity at the human oral mucosal barrier.
Shigella sonnei is rapidly emerging as the dominant agent of shigellosis, an enteric disease responsible for a significant burden of morbidity and mortality worldwide. Whole-genome sequencing of S. sonnei isolated over the last three decades has revealed phylogenomic diversity within the population and the emergence of multiple lineages associated with distinct epidemiological patterns such as resistance to critical antimicrobials and/or transmission within different groups. However, most experimental work on S. sonnei biology and pathogenicity has focused on a single laboratory strain (53G), which is phylogenetically distant from currently circulating strains. Here, we introduce a set of phylogenetically diverse and epidemiologically relevant S. sonnei isolates made available through publicly accessible culture collections as a resource for laboratory science. We present their complete whole-genome sequences, including the pINV invasion plasmid (missing from a large proportion of public genome data due to loss during laboratory culture). Finally, the characterization and comparison of these complete genome sequences highlight evidence for ongoing adaptive evolution in S. sonnei, featuring the accumulation of insertion sequences, gene pseudogenization and structural variation.
Low-cost, high-throughput DNA and RNA sequencing (HTS) data is the main workforce for the life sciences. Genome sequencing is now becoming a part of Predictive, Preventive, Personalized, and Participatory (termed 'P4') medicine. All genomic data are currently processed in energy-hungry computer clusters and centers, necessitating data transfer, consuming substantial energy, and wasting valuable time. Therefore, there is a need for fast, energy-efficient, and cost-efficient technologies that enable genomics research without requiring data centers and cloud platforms. We recently started the BioPIM Project to leverage the emerging processing-in-memory (PIM) technologies to enable energy and cost-efficient analysis of bioinformatics workloads. The BioPIM Project focuses on co-designing algorithms and data structures commonly used in genomics with several PIM architectures for the highest cost, energy, and time savings benefit.
