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Journal of Neurovirology Jun 2024Although previous studies have suggested that subtype B HIV-1 proviruses in the brain are associated with physiological changes and immune activation accompanied with...
Although previous studies have suggested that subtype B HIV-1 proviruses in the brain are associated with physiological changes and immune activation accompanied with microgliosis and astrogliosis, and indicated that both HIV-1 subtype variation and geographical location might influence the neuropathogenicity of HIV-1 in the brain. The natural course of neuropathogenesis of the most widespread subtype C HIV-1 has not been adequately investigated, especially for people living with HIV (PLWH) in sub-Saharan Africa. To characterize the natural neuropathology of subtype C HIV-1, postmortem frontal lobe and basal ganglia tissues were collected from nine ART-naïve individuals who died of late-stage AIDS with subtype C HIV-1 infection, and eight uninfected deceased individuals as controls. Histological staining was performed on all brain tissues to assess brain pathologies. Immunohistochemistry (IHC) against CD4, p24, Iba-1, GFAP, and CD8 in all brain tissues was conducted to evaluate potential viral production and immune activation. Histological results showed mild perivascular cuffs of lymphocytes only in a minority of the infected individuals. Viral capsid p24 protein was only detected in circulating immune cells of one infected individual, suggesting a lack of productive HIV-1 infection of the brain even at the late-stage of AIDS. Notably, similar levels of Iba-1 or GFAP between HIV + and HIV- brain tissues indicated a lack of microgliosis and astrogliosis, respectively. Similar levels of CD8 + cytotoxic T lymphocyte (CTL) infiltration between HIV + and HIV- brain tissues indicated CTL were not likely to be involved within subtype C HIV-1 infected participants of this cohort. Results from this subtype C HIV-1 study suggest that there is a lack of productive infection and limited neuropathogenesis by subtype C HIV-1 even at late-stage disease, which is in contrast to what was reported for subtype B HIV-1 by other investigators.
PubMed: 38943022
DOI: 10.1007/s13365-024-01219-6 -
Nature Aging Jun 2024Investigating the genetic underpinnings of human aging is essential for unraveling the etiology of and developing actionable therapies for chronic diseases. Here, we...
Investigating the genetic underpinnings of human aging is essential for unraveling the etiology of and developing actionable therapies for chronic diseases. Here, we characterize the genetic architecture of the biological age gap (BAG; the difference between machine learning-predicted age and chronological age) across nine human organ systems in 377,028 participants of European ancestry from the UK Biobank. The BAGs were computed using cross-validated support vector machines, incorporating imaging, physical traits and physiological measures. We identify 393 genomic loci-BAG pairs (P < 5 × 10) linked to the brain, eye, cardiovascular, hepatic, immune, metabolic, musculoskeletal, pulmonary and renal systems. Genetic variants associated with the nine BAGs are predominantly specific to the respective organ system (organ specificity) while exerting pleiotropic links with other organ systems (interorgan cross-talk). We find that genetic correlation between the nine BAGs mirrors their phenotypic correlation. Further, a multiorgan causal network established from two-sample Mendelian randomization and latent causal variance models revealed potential causality between chronic diseases (for example, Alzheimer's disease and diabetes), modifiable lifestyle factors (for example, sleep duration and body weight) and multiple BAGs. Our results illustrate the potential for improving human organ health via a multiorgan network, including lifestyle interventions and drug repurposing strategies.
PubMed: 38942983
DOI: 10.1038/s43587-024-00662-8 -
Scientific Reports Jun 2024Salinity has become a major environmental concern for agricultural lands, leading to decreased crop yields. Hence, plant biology experts aim to genetically improve...
Salinity has become a major environmental concern for agricultural lands, leading to decreased crop yields. Hence, plant biology experts aim to genetically improve barley's adaptation to salinity stress by deeply studying the effects of salt stress and the responses of barley to this stress. In this context, our study aims to explore the variation in physiological and biochemical responses of five Tunisian spring barley genotypes to salt stress during the heading phase. Two salinity treatments were induced by using 100 mM NaCl (T1) and 250 mM NaCl (T2) in the irrigation water. Significant phenotypic variations were detected among the genotypes in response to salt stress. Plants exposed to 250 mM of NaCl showed an important decline in all studied physiological parameters namely, gas exchange, ions concentration and relative water content RWC. The observed decreases in concentrations ranged from, approximately, 6.64% to 40.76% for K, 5.91% to 43.67% for Na, 14.12% to 52.38% for Ca, and 15.22% to 38.48% for Mg across the different genotypes and salt stress levels. However, under salinity conditions, proline and soluble sugars increased for all genotypes with an average increase of 1.6 times in proline concentrations and 1.4 times in soluble sugars concentration. Furthermore, MDA levels rose also for all genotypes, with the biggest rise in Lemsi genotype (114.27% of increase compared to control). Ardhaoui and Rihane showed higher photosynthetic activity compared to the other genotypes across all treatments. The stepwise regression approach identified potassium content, K/Na ratio, relative water content, stomatal conductance and SPAD measurement as predominant traits for thousand kernel weight (R2 = 84.06), suggesting their significant role in alleviating salt stress in barley. Overall, at heading stage, salt accumulation in irrigated soils with saline water significantly influences the growth of barley by influencing gas exchange parameters, mineral composition and water content, in a genotype-dependent manner. These results will serve on elucidating the genetic mechanisms underlying these variations to facilitate targeted improvements in barley's tolerance to salt stress.
Topics: Hordeum; Salt Stress; Water; Minerals; Genotype; Salinity; Sodium Chloride
PubMed: 38942909
DOI: 10.1038/s41598-024-65967-5 -
Scientific Reports Jun 2024Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1...
Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1 (SLC14A1) is a member of urea transporters which are important for the regulation of urine concentration. However, the physiological significance of SLC14A1 in PCa still remains unclear. In the present study, via bioinformatics analysis and experiments, we found that expression of SLC14A1 is significantly decreased in PCa progression, which could be attributed to hypermethylation on SLC14A1 promoter region. Moreover, its low expression and hypermethylation on SLC14A1 promoter are closely related to the poor prognosis of PCa patients. On the other hand, overexpression of SLC14A1 inhibited cell proliferation and metastasis while its overexpression also suppressed CDK1/CCNB1 pathway and mTOR/MMP-9 signaling pathway. Additionally, SLC14A1 expression is enriched in prostate basal-type cells. In summary, our study indicates that its low expression level and promoter hypermethylation of SLC14A1 may represent novel indicators for PCa progression and prognosis, and SLC14A1 could inhibit the progression of PCa.
Topics: Humans; Male; Prostatic Neoplasms; TOR Serine-Threonine Kinases; Gene Expression Regulation, Neoplastic; Disease Progression; Signal Transduction; Cell Line, Tumor; CDC2 Protein Kinase; DNA Methylation; Promoter Regions, Genetic; Cell Proliferation; Down-Regulation; Prognosis; Cell Movement
PubMed: 38942821
DOI: 10.1038/s41598-024-66020-1 -
Scientific Reports Jun 2024Anthropological and biophysical processes have shaped livestock genomes over Millenia and can explain their current geographic distribution and genetic divergence. We...
Anthropological and biophysical processes have shaped livestock genomes over Millenia and can explain their current geographic distribution and genetic divergence. We analyzed 57 Ethiopian indigenous domestic goat genomes alongside 67 equivalents of east, west, and north-west African, European, South Asian, Middle East, and wild Bezoar goats. Cluster, ADMIXTURE (K = 4) and phylogenetic analysis revealed four genetic groups comprising African, European, South Asian, and wild Bezoar goats. The Middle Eastern goats had an admixed genome of these four genetic groups. At K = 5, the West African Dwarf and Moroccan goats were separated from East African goats demonstrating a likely historical legacy of goat arrival and dispersal into Africa via the coastal Mediterranean Sea and the Horn of Africa. F, XP-EHH, and Hp analysis revealed signatures of selection in Ethiopian goats overlaying genes for thermo-sensitivity, oxidative stress response, high-altitude hypoxic adaptation, reproductive fitness, pathogen defence, immunity, pigmentation, DNA repair, modulation of renal function and integrated fluid and electrolyte homeostasis. Notable examples include TRPV1 (a nociception gene); PTPMT1 (a critical hypoxia survival gene); RETREG (a regulator of reticulophagy during starvation), and WNK4 (a molecular switch for osmoregulation). These results suggest that human-mediated translocations and adaptation to contrasting environments are shaping indigenous African goat genomes.
Topics: Animals; Goats; Ethiopia; Genome; Phylogeny; Stress, Physiological; Genetic Variation
PubMed: 38942813
DOI: 10.1038/s41598-024-65303-x -
Nature Communications Jun 2024Lipid droplets (LDs) are dynamic lipid storage organelles. They are tightly linked to metabolism and can exert protective functions, making them important players in...
Lipid droplets (LDs) are dynamic lipid storage organelles. They are tightly linked to metabolism and can exert protective functions, making them important players in health and disease. Most LD studies in vivo rely on staining methods, providing only a snapshot. We therefore developed a LD-reporter mouse by labelling the endogenous LD coat protein perilipin 2 (PLIN2) with tdTomato, enabling staining-free fluorescent LD visualisation in living and fixed tissues and cells. Here we validate this model under standard and high-fat diet conditions and demonstrate that LDs are highly abundant in various cell types in the healthy brain, including neurons, astrocytes, ependymal cells, neural stem/progenitor cells and microglia. Furthermore, we also show that LDs are abundant during brain development and can be visualized using live imaging of embryonic slices. Taken together, our tdTom-Plin2 mouse serves as a novel tool to study LDs and their dynamics under both physiological and diseased conditions in all tissues expressing Plin2.
Topics: Animals; Perilipin-2; Lipid Droplets; Brain; Mice; Neurons; Gene Knock-In Techniques; Mice, Transgenic; Female; Luminescent Proteins; Male; Astrocytes; Diet, High-Fat; Mice, Inbred C57BL; Neural Stem Cells; Microglia
PubMed: 38942786
DOI: 10.1038/s41467-024-49449-w -
Physiological Reports Jul 2024The hemodynamic response during the transition from the supine to standing position in idiopathic atrial fibrillation (AF) patients is not completely understood. This...
The hemodynamic response during the transition from the supine to standing position in idiopathic atrial fibrillation (AF) patients is not completely understood. This study aimed to analyze the hemodynamic changes that occur during the head-up tilt test in idiopathic AF patients. We investigated the hemodynamic changes during the head-up tilt test with impedance cardiography in 40 AF patients (12 with AF rhythm-AFr and 28 with sinus rhythm-AFsr) and 38 non-AF controls. Patients with AFr had attenuated SVI decrease after standing when compared to AFsr and non-AF [ΔSVI in mL/m: -1.3 (-3.4 to 1.7) vs. -6.4 (-17.3 to -0.1) vs. -11.8 (-18.7 to -8.0), respectively; p < 0.001]. PVRI decreased in AFr but increased in AFsr and non-AF [ΔPVRI in dyne.seg.m/cm: -477 (-1148 to 82.5) vs. 131 (-525 to 887) vs. 357 (-29 to 681), respectively; p < 0.01]. Similarly, compared with non-AF patients, AFr patients also had a greater HR and greater CI increase after standing. The haemodynamic response to orthostatic challenge suggests differential adaptations between patients with AF rhythm and those reverted to sinus rhythm or healthy controls. Characterizing the hemodynamic phenotype may be relevant for the individualized treatment of AF patients.
Topics: Humans; Atrial Fibrillation; Male; Female; Tilt-Table Test; Middle Aged; Hemodynamics; Aged; Adaptation, Physiological; Cardiography, Impedance; Heart Rate
PubMed: 38942728
DOI: 10.14814/phy2.16131 -
Injury Jun 2024The number of pediatric trauma patients requiring surgical interventions has been steadily decreasing allowing for a judicious approach to immediately available...
OBJECTIVE
The number of pediatric trauma patients requiring surgical interventions has been steadily decreasing allowing for a judicious approach to immediately available resources. This study aimed to derive and validate a prediction rule that reliably identifies injured children who are at very low risk for requiring emergency surgery upon emergency department (ED) arrival.
METHODS
A retrospective cohort study of data included in the Israeli National Trauma Registry from January 1, 2011, through December 31, 2020, was conducted. We included children aged 0-14 years who presented to EDs from the scene of injury and were hospitalized. We excluded patients transferred between facilities or with isolated burns. The primary outcome was emergency operative intervention (EOI) performed within one hour of ED arrival. We tested mechanism, GCS, heart rate, and blood pressure as candidate predictors. We then randomized patients to two cohorts, derived and internally validated a prediction rule.
RESULTS
During the study period, 83,859 children met enrollment criteria. The median age was 6 years (IQR 2-10) and 56,867 (67.8 %) were male; 75,450 (90.0 %) sustained blunt trauma. One hundred sixty-nine (0.20 %) children underwent EOI. In the derivation and validation cohorts, 34,138 (81.4 %) and 34,271 (81.7 %) patients, were classified as low risk based on blunt trauma mechanism, normal GCS (15), and low-risk heart rate (according to age). Of those, 8 (0.02 %) and 13 (0.04 %) required an EOI, respectively. In the validation cohort, the prediction rule for EOI had a sensitivity of 84 % (95 % CI 75-91), a specificity of 82 % (95 % CI 81-82), and a negative predictive value of 99.96 % (95 % CI 99.94-99.98). Among children with an Injury Severity Score>15, the sensitivity was 87 % (95 % CI 77-94), the specificity of 57 % (95 % CI 54-59), and the negative predictive value was 98.97 % (95 % CI 98.13-99.44).
CONCLUSIONS
A limited set of physiologic parameters, readily available at hospital admission can effectively identify injured children at very low risk for emergent surgery. For these children, immediate deployment of surgical resources may not be necessary.
PubMed: 38942725
DOI: 10.1016/j.injury.2024.111678 -
Integrative and Comparative Biology Jun 2024To humans, the diverse array of display behaviors that animals use for communication can easily seem peculiar or bizarre. While ample research delves into the...
To humans, the diverse array of display behaviors that animals use for communication can easily seem peculiar or bizarre. While ample research delves into the evolutionary principles that shape these signals' effectiveness, little attention is paid to evolutionary patterning of signal design across taxa, particularly when it comes to the potential convergent evolution of many elaborate behavioral displays. By taking a mechanistic perspective, we explore the physiological and neurobiological mechanisms that likely influence the evolution of communication signals, emphasizing the utilization of pre-existing structures over novel adaptations. Central to this investigation are the concepts of perceptual bias and ritualization, which we propose contribute to the convergence of elaborate display designs across species. Perceptual bias explains a phenomenon where pre-existing perceptual systems of receivers, used for innate behaviors such as food and predator recognition, select for certain traits of a communication signal from a signaler. Ritualization occurs when traits with no functional role in communication are co-opted through selection and transformed into a new communicative signal. Importantly, susceptibility for ritualization can be brought about through physiological modifications that occurred early in evolutionary time. In this way, perceptual bias can be a selective force that causes the co-option of non-communicative traits into a new communication signal through ritualization involving pre-existing modifications to physiological systems. If the perceptual bias, non-communicative signal, and physiological modifications that increase susceptibility to ritualization are highly conserved, then we may see the convergent evolution of the new communication signal with unrelated taxa facing similar sensory constraints. We explore this idea here using the foot-flagging frog system as a theoretical case study.
PubMed: 38942486
DOI: 10.1093/icb/icae091 -
PDA Journal of Pharmaceutical Science... Jun 2024Microbiological contamination may cause microbial proliferation and consequently additional problems for pharmaceutical companies through production stoppage, product...
Quantitative and qualitative evaluation of microorganism profile identified in bioburden analysis in a biopharmaceutical facility in Brazil: Criteria for classification and management of results.
Microbiological contamination may cause microbial proliferation and consequently additional problems for pharmaceutical companies through production stoppage, product contamination, investigations of process deviations, out-of-specification results and product disposal. This is one of the major concerns of the regulatory health agencies. Microbiological load (bioburden) may represent a potential risk for patients if the sterilization process is not effective and/or due to the production of toxins. Although bioburden can be eliminated by terminal sterilization or filtration processes, it is important to monitor the amount and determine the identity and characteristics of the microorganisms present prior to final processing. The application of microorganism identification systems is crucial for identifying the type of contamination, which can be extremely useful for investigating. The aim of this study was to evaluate the profiles of microorganisms identified in bioburden assays from solutions, culture medias, and products (SCP) from a pharmaceutical industry facility. From 2018-2020, a total of 1,078 samples from 857 different lots of SCP were analyzed and isolated microorganisms were identified. A prefiltering step was included after March 2020, in order to reduce the bioburden before sterilizing filtration. Criteria for the definition and management of microorganisms identified were evaluated after an integrative bibliographic review, and three groups were proposed (critical, objectionable, and nonobjectionable microorganisms). For the samples that did not include prefiltering (n=636), 227 (35.7%) presented microbial growth. For those that included prefiltering, before prefiltering (n=221), 60.6% presented microbial growth, and after prefiltering, this value was reduced to 4.1%, which can be attributed to a contamination during the sampling or a wrong filtering. From the samples that presented microbial growth, 678 microorganisms were identified as bacteria and 59 as molds and yeasts. A total of 120 microorganisms (56 and 27 Gram-positive and negative bacteria, respectively, 31 yeasts, and six filamentous molds) could not be identified, and the remaining microorganisms were classified as objectionable (n=507; 82.2%), nonobjectionable (n=103; 16.7%) and critical (n=7; 1.1%). Most of the bioburden species (>80.0%) were considered objectionable microorganisms. A process for classification and management of bioburden analysis results based on a literature review of pathogenic and physiological characteristics of the microorganisms was proposed.
PubMed: 38942484
DOI: 10.5731/pdajpst.2023.012883