Screening cDNA expression libraries in lambda gt11 with a T cell hybridoma.

A T cell hybridoma specific for a protein of Plasmodium chabaudi chabaudi has been used to test a system for direct T cell screening of a cDNA library of P. chabaudi in the phage lambda gt11. The technique is based upon the rapid separation of the recombinant beta-galactosidase fusion protein from the bacterial mixtures using polystyrene beads coated with anti-beta-galactosidase antibodies. These coated beads are cultured with antigen-presenting cells and the T cell hybridoma. The technique is sufficiently sensitive to pick up the products of one recombinant phage in a pool of 1000-10,000 other phages. Individual plaques or clones of recombinant phage can be selected after testing of sequential dilutions of pools containing positive recombinant phages. This technique will be generally applicable and should be useful for the identification of important T cell peptides in infectious diseases.     

High-dose 131I-metaiodobenzylguanidine therapy in patients with high-risk neuroblastoma in Japan

Annals of Nuclear Medicine - The aim of the study was to investigate the outcomes and prognostic factors of high-dose 131I-metaiodobenzylguanidine (131I-MIBG) therapy in patients with refractory or...     

Role of triggering receptor expressed on myeloid cells-1 (TREM-1) in COVID-19 and other viral pneumonias: a systematic review and meta-analysis of clinical studies

Inflammopharmacology - Triggering receptor expressed on myeloid cells-1 (TREM-1) has emerged as an important inflammatory marker of immune response associated with severity and mortality outcomes...     

Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation

Selective loss of dopaminergic neurons is the final common pathway in Parkinson's disease. Expression of Parkin associated endothelin-receptor like receptor (Pael-R) in mouse brain was achieved by injecting adenoviral vectors carrying a modified neuron-specific promoter and Cre recombinase into the striatum. Upregulation of Pael-R in the substantia nigra pars compacta of mice by retrograde infection induced endoplasmic reticulum (ER) stress leads to death of dopaminergic neurons. The role of ER stress in dopaminergic neuronal vulnerability was highlighted by their decreased survival in mice deficient in the ubiquitin-protein ligase Parkin and the ER chaperone ORP150 (150 kDa oxygen-regulated protein). Dopamine-related toxicity was also a key factor, as a dopamine synthesis inhibitor blocked neuronal death in parkin null mice. These data suggest a model in which ER- and dopamine-related stress are major contributors to decreased viability of dopaminergic neurons in a setting relevant to Parkinson's disease.     

Dynamic spatiotemporal gene expression in embryonic mouse thalamus

The anatomy of the mammalian thalamus is characterized by nuclei, which can be readily identified in postnatal animals. However, the molecular mechanisms that guide specification and differentiation of neurons in specific thalamic nuclei are still largely unknown, and few molecular markers are available for most of these thalamic subregions at early stages of development. We therefore searched for patterned gene expression restricted to specific mouse thalamic regions by in situ hybridization during the onset of thalamic neurogenesis (embryonic [E] days E10.5-E12.5). To obtain correct regional information, we used Shh as a landmark and compared spatial relationships with the zona limitans intrathalamica (Zli), the border of the p2 and p3 compartments of the diencephalon. We identified genes that are expressed specifically in the ventricular zone of the thalamic neuroepithelium and also identified a number of genes that already exhibited regional identity at E12.5. Although many genes expressed in the mantle regions of the thalamus at E12.5 showed regionally restricted patterns, none of these clearly corresponded to individual thalamic nuclei. We next examined gene expression at E15.5, when thalamocortical axons (TCAs) project from distinct regions of the thalamus and reach their targets in the cerebral cortex. Regionally restricted patterns of gene expression were again seen for many genes, but some regionally bounded expression patterns in the early postnatal thalamus had shifted substantially by E15.5. These findings reveal that nucleogenesis in the developing thalamus is associated with selective and complex changes in gene expression and provide a list of genes that may actively regulate the development of thalamic nuclei.     

Mediating role of instrumental activities of daily living ability on cognitive function of older adults living alone: A 4-year longitudinal study from the Kasama study

The aim of this study was to clarify the effect of living alone on the cognitive function of older people and the mediating effect of instrumental activities of daily living (IADL) ability.The data for a final sample of 3276 participants aged 65 years and above who did not require long-term care at the baseline were used from a 4-year prospective cohort study conducted in Kasama City, Japan. Demographic data including age, sex, and depression at baseline were used as covariates. The Kihon checklist evaluated the IADL ability at baseline and cognitive function at follow-up. The characteristics of those living alone and with others were compared using the student t test and χ² test. The effect of living alone on cognitive function was analyzed using logistic regression analysis. Mediation analyses determined the mediating effects of IADL.A total of 325 participants were living alone; they were significantly older than those living with others, more likely to be female, not provide emotional support, and have low physical function, more severe depression, and lower IADL disability. Living alone had a significantly lower risk of cognitive decline at follow-up than living with others. The mediation analysis revealed that IADL disability at follow-up was significantly associated with cognitive decline. Thus, greater IADL ability decreased cognitive decline risk.Older people living alone had a significantly lower risk of cognitive decline, and cognitive function significantly mediated IADL ability. Health support for enhancing IADL abilities may help older people living alone maintain good cognitive function.     

Changes in the Gut Bacteria Composition of Healthy Men with the Same Nutritional Profile Undergoing 10-Week Aerobic Exercise Training: A Randomized Controlled Trial

Nutrient consumption and body mass index (BMI) are closely related to the gut microbiota, and exercise effects on gut bacteria composition may be related to those variables. Thus, we aimed to investigate the effect of 10-week moderate aerobic exercise on the cardiorespiratory fitness and gut bacteria composition of non-obese men with the same nutritional profile. Twenty-four previously sedentary men (age 25.18 [SD 4.66] years, BMI 24.5 [SD 3.72] kg/m²) were randomly assigned into Control (CG; n = 12) or Exercise Groups (EG; n = 12). Body composition, cardiorespiratory parameters, blood markers, dietary habits and gut bacteria composition were evaluated. EG performed 150 min per week of supervised moderate (60–65% of VO₂peak) aerobic exercise, while CG maintained their daily routine. The V4 16S rRNA gene was sequenced and treated using QIIME software. Only EG demonstrated marked improvements in cardiorespiratory fitness (VO₂peak, p < 0.05; Effect Size = 0.971) without changes in other gut bacteria-affecting variables. Exercise did not promote clustering based on diversity indices (p > 0.05), although significant variations in an unclassified genus from Clostridiales order and in Streptococcus genus were observed (p < 0.05). Moreover, α-diversity was correlated with VO₂peak (Pearson’s R: 0.47; R² 0.23: 95%CI: 0.09 to 0.74, p = 0.02) and BMI (Pearson’s R: −0.50; R² 0.25: 95%CI: −0.75 to −0.12, p = 0.01). Roseburia, Sutterella and Odoribacter genera were associated with VO₂peak, while Desulfovibrio and Faecalibacterium genera were associated with body composition (p < 0.05). Our study indicates that aerobic exercise at moderate intensity improved VO₂peak and affected gut bacteria composition of non-obese men who maintained a balanced consumption of nutrients.     

Use of ginger to control nausea and vomiting caused by chemotherapy in patients with cervical cancer undergoing treatment: An experiment

Introduction:Uterine cervix tumors have an invasive nature, with the capacity to proliferate to surrounding organs such as the vagina, bladder, and rectum, as well as the capacity for dissemination and involvement of structures distant from its place of origin. According to the International Federation of Gynecology and Obstetrics, patients with stages IB I, IB I microscopic (small dimension <4 cm) are indicated for radiotherapy or adjuvant chemoradiotherapy with cisplatin (40 mg/m²). However, cisplatin has side effects such as hematological implications (anemia, neutropenia, and thrombocytopenia), gastrointestinal disorders (nausea, vomiting, diarrhea, constipation), and fatigue. Zingiber officinale contains bioactive compounds that act on pregnancy and postoperative nausea, chemotherapy-induced nausea and vomiting, and also in the management of fatigue, myalgia, and insomnia. This study aimed to evaluate the effects of ginger on chemotherapy-induced nausea and vomiting in patients with cervical cancer undergoing treatment with cisplatin and radiotherapy.Methods and analyses:A randomized intervention clinical and controlled trial with a triple-blind design is described, comparing the effects of institutional antiemetic therapy alone, as well as in combination with 2 different ginger concentrations.Ethics and dissemination:Due to the nature of the study, we obtained approval from the Division Ethics Committee of Liga Contra o Câncer. All participants signed an informed consent form prior to randomization. The results of this study will be published in peer-reviewed journals. The data collected will also be available in a public repository of data.Trial registration number:This study is registered in the Brazilian Registry of Clinical Trials under number RBR-47yx6p9. This study was approved by the Division Ethics Committee of Liga Contra o Câncer under CAAE 40602320.0.0000.5293.     

Systemic Fluorescent Gentamicin Enters Neonatal Mouse Hair Cells Predominantly Through Sensory Mechanoelectrical Transduction Channels

Journal of the Association for Research in Otolaryngology - Systemically administered aminoglycoside antibiotics can enter inner ear hair cells and trigger apoptosis. However, the in vivo route(s)...