Publication

Sex-distinct microglial activation and myeloid cell infiltration in the spinal cord after painful peripheral injury

Chronic pain is a common and often debilitating problem that affects 100 million Americans. A better understanding of pain’s molecular mechanisms is necessary for developing safe and effective therapeutics. Microglial activation has been implicated as a mediator of chronic pain in numerous preclinical studies; unfortunately, translational efforts using known glial modulators have largely failed, perhaps at least in part due to poor specificity of the compounds pursued, or an incomplete understanding of microglial reactivity.

Alzheimer’s disease-associated U1 snRNP splicing dysfunction causes neuronal hyperexcitability and cognitive impairment

A, Representative co-immunofluorescence staining of 5xFAD and dTg brain slides with Thioflavin S for plaques and the U1-70K C-terminal antibody for U1-70K depletion. Scale bar, 100 µm. The immunostaining was repeated from three animals. B, PCA for RNA-seq and proteomics studies. C, Distribution of splicing deficiency scores of mapped transcripts. Statistical comparisons between different genotypes are shown (Kolmogorov-Smirnov test). D, Relative Aβ level in 5xFAD and dTg by the proteomics analysis (mean ± SEM, Student’s _t_-test, two-tailed, ns: not significant).

Mutant huntingtin messenger RNA forms neuronal nuclear clusters in rodent and human brains

Mutant mRNA and protein contribute to the clinical manifestation of many repeat-associated neurological disorders, with the presence of nuclear RNA clusters being a common pathological feature. Yet, investigations into Huntington's disease - caused by a CAG repeat expansion in exon 1 of the huntingtin (HTT) gene - have primarily focused on toxic protein gain-of-function as the primary disease-causing feature. To date, mutant HTT mRNA has not been identified as an in vivo hallmark of Huntington’s disease.

Influenza versus COVID-19-associated pulmonary aspergillosis: Profiling lower respiratory tract epithelial and myeloid innate immunity in patient samples

Objectives: Up to 20% and 15% of critically ill influenza and coronavirus disease 2019 (COVID-19) patients are affected by influenza- and COVID-19-associated pulmonary aspergillosis (IAPA and CAPA) respectively. These viral-fungal coinfections are difficult to diagnose and are associated with increased mortality. Mechanistic insights into the development of IAPA and CAPA are a prerequisite for the development of new biomarkers and novel immunomodulatory therapeutic targets. However, data on the pathophysiology are scarce.

Nasopharyngeal Carcinoma Ecology Theory: Cancer as Multidimensional Spatiotemporal “Unity of Ecology and Evolution” Pathological Ecosystem

Nasopharyngeal carcinoma (NPC) is generally regarded as a genetic disease with diverse extent of intertumor and intratumor heterogeneity. Here we propose that, NPC is not only a genetic disease; it could be conceptualized as a multidimensional spatiotemporal “unity of ecology and evolution” pathological ecosystem.

Osteoprogenitor Recruitment and Differentiation During Intracortical Bone Remodeling of Adolescent Humans

Background: Recruitment and proliferation of osteoprogenitors during the reversal-resorption phase, and their differentiation into mature bone-forming osteoblasts is crucial for initiation of bone formation during bone remodeling. This study investigates the osteoprogenitors’ gradual recruitment, proliferation, and differentiation into bone-forming osteoblasts within intracortical remodeling events of healthy adolescent humans. Methods: The study was conducted on cortical bone specimens from 11 healthy adolescent humans.

Fluoxetine plus lithium for treatment of mental health impairment in Long Covid

Mental disability is a serious and often disabling symptom of Long Covid, for which currently there is no recommendable pharmacotherapy for those patients whose response to psychotherapy is suboptimal. Treatment could be formulated by using drugs that address the brain cell-types that have been demonstrated as dominantly affected in Long Covid. Those cell-types are astrocytes, oligodendrocytes, endothelial cells/pericytes, and microglia. Lithium and fluoxetine each address all of those four cell-types.

COVID-19 y placenta: afectación histopatológica y materno fetal

La infección por COVID-19 es de reciente aparición, por lo que son escasos los datos sobre la presentación clínica durante el embarazo y los resultados perinatales. Los tipos de células de la placenta que expresan ECA2 son el sinciciotrofoblasto y el citotrofoblasto de las vellosidades coriónicas, las células del estroma decidual, las células perivasculares deciduales y las células del músculo liso vascular y endotelial.

A Low Grade Nasopharyngeal sarcoma With FUS::NACC1 Fusion and Immunohistochemical Evidence of Epithelial Differentiation: Expanding the Clinicopathologic Spectrum of an Emerging Entity

RNA sequencing of unclassified soft tissue tumors has allowed for definition of multiple new entities. Antonescu et al. recently reported three case of low grade sarcoma with recurrent EWSR1/FUS::NACC1 fusion and distinctive storiform architecture that were suggestive of a novel tumor type.Here, we present a case of an additional sarcoma with FUS::NACC1 fusion that arose in the head and neck and showed immunohistochemical evidence of epithelial differentiation.A 41 year old woman presented with throat and inner ear pain and was found to have a nasopharyngeal mass.

Radiochemical In Situ Hybridization in Developmental Studies of the Pineal Gland

Radiochemical in situ hybridization enables detection of gene expression in small areas of the brain, such as the developing pineal gland in rodents. The method combines determination of spatial and temporal gene expression profiles with semiquantitative analyses. We here describe the procedure of radiochemical in situ hybridization on the developing rat pineal gland ranging from preparation of fetal tissue for in situ hybridization to principles of quantification.

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