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Genes Jul 2023The deep terrestrial subsurface, hundreds of meters to kilometers below the surface, is characterized by oligotrophic conditions, dark and often anoxic settings, with...
The deep terrestrial subsurface, hundreds of meters to kilometers below the surface, is characterized by oligotrophic conditions, dark and often anoxic settings, with fluctuating pH, salinity, and water availability. Despite this, microbial populations are detected and active, contributing to biogeochemical cycles over geological time. Because it is extremely difficult to access the deep biosphere, little is known about the identity and metabolisms of these communities, although they likely possess unknown pathways and might interfere with deep waste deposits. Therefore, we analyzed rock and groundwater microbial communities from deep, isolated brine aquifers in two regions dating back to the Ordovician and Devonian, using amplicon and whole genome sequencing. We observed significant differences in diversity and community structure between both regions, suggesting an impact of site age and composition. The deep hypersaline groundwater did not contain typical halophilic bacteria, and genomes suggested pathways involved in protein and hydrocarbon degradation, and carbon fixation. We identified mainly one strategy to cope with osmotic stress: compatible solute uptake and biosynthesis. Finally, we detected many bacteriophage families, potentially indicating that bacteria are infected. However, we also found auxiliary metabolic genes in the viral genomes, probably conferring an advantage to the infected hosts.
Topics: Humans; Quebec; Canada; Groundwater; Microbiota
PubMed: 37628582
DOI: 10.3390/genes14081529 -
Parkinsonism & Related Disorders Sep 2023Deep Brain Stimulation (DBS) is an option to treat advanced Parkinson's Disease (PD), but can cause gait disturbance due to stimulation side efffects. This study aims to...
INTRODUCTION
Deep Brain Stimulation (DBS) is an option to treat advanced Parkinson's Disease (PD), but can cause gait disturbance due to stimulation side efffects. This study aims to evaluate the objective effect of directional current steering by DBS on gait performance in PD, utilizing a three-dimensional gait analysis system.
METHODS
Eleven patients diagnosed with PD and were implanted with directional lead were recruited. The direction of the pyramidal tract (identified by the directional mode screening) was set as 0°. Patients performed the six-meter-walk test and the time up-and-go (TUG) test while an analysis system recorded gait parameters utilizing a three-dimensional motion capture camera. The gait parameters were measured for the baseline, the directional steering at eight angles (0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°), and the conventional ring mode with 1, 2, and 3 mA. Pulse width and frequency were fixed. Placebo stimulation (0 mA) was used for a control.
RESULTS
Eleven patients completed the study. No significant difference were observed between gait parameters during the directional, baseline, placebo, or ring modes during the six-meter-walk test (p > 0.05). During the TUG test, stride length was significantly different between 0° and other directions (p < 0.001), but no significant differences were observed for the other gait parameters. Stride width was non-significantly narrower in the direction of 0°.
CONCLUSION
Controlling stimulation using directional steering may improve gait in patients with PD, while avoiding pyramidal side effects.
Topics: Humans; Gait Analysis; Parkinson Disease; Deep Brain Stimulation; Gait; Gait Disorders, Neurologic
PubMed: 37499354
DOI: 10.1016/j.parkreldis.2023.105770 -
Journal For Immunotherapy of Cancer Jul 2023Most immunotherapies approved for clinical use rely on the use of recombinant proteins and cell-based approaches, rendering their manufacturing expensive and logistics...
BACKGROUND
Most immunotherapies approved for clinical use rely on the use of recombinant proteins and cell-based approaches, rendering their manufacturing expensive and logistics onerous. The identification of novel small molecule immunotherapeutic agents might overcome such limitations.
METHOD
For immunopharmacological screening campaigns, we built an artificial miniature immune system in which dendritic cells (DCs) derived from immature precursors present MHC (major histocompatibility complex) class I-restricted antigen to a T-cell hybridoma that then secretes interleukin-2 (IL-2).
RESULTS
The screening of three drug libraries relevant to known signaling pathways, FDA (Food and Drug Administration)-approved drugs and neuroendocrine factors yielded two major hits, astemizole and ikarugamycin. Mechanistically, ikarugamycin turned out to act on DCs to inhibit hexokinase 2, hence stimulating their antigen presenting potential. In contrast, astemizole acts as a histamine H1 receptor (H1R1) antagonist to activate T cells in a non-specific, DC-independent fashion. Astemizole induced the production of IL-2 and interferon-γ (IFN-γ) by CD4 and CD8 T cells both in vitro and in vivo. Both ikarugamycin and astemizole improved the anticancer activity of the immunogenic chemotherapeutic agent oxaliplatin in a T cell-dependent fashion. Of note, astemizole enhanced the CD8/Foxp3 ratio in the tumor immune infiltrate as well as IFN-γ production by local CD8 T lymphocytes. In patients with cancer, high H1R1 expression correlated with low infiltration by TH1 cells, as well as with signs of T-cell exhaustion. The combination of astemizole and oxaliplatin was able to cure the majority of mice bearing orthotopic non-small cell lung cancers (NSCLC), then inducing a state of protective long-term immune memory. The NSCLC-eradicating effect of astemizole plus oxaliplatin was lost on depletion of either CD4 or CD8 T cells, as well as on neutralization of IFN-γ.
CONCLUSIONS
These findings underscore the potential utility of this screening system for the identification of immunostimulatory drugs with anticancer effects.
Topics: United States; Mice; Animals; CD8-Positive T-Lymphocytes; Interleukin-2; Astemizole; Oxaliplatin; Immunity, Cellular; Histocompatibility Antigens Class I; Interferon-gamma
PubMed: 37419511
DOI: 10.1136/jitc-2023-006785 -
The Science of the Total Environment Oct 2023Deposition of sediment in sewers decreased flow capacity, with harmful gases and pipe erosion. Sediment floating and removal remained challenges due to its gelatinous...
Deposition of sediment in sewers decreased flow capacity, with harmful gases and pipe erosion. Sediment floating and removal remained challenges due to its gelatinous structure, which induced strong erosion resistance. This study proposed an innovative alkaline treatment for destructuring gelatinous organic matters and improving hydraulic flushing capacity of sediments. At the optimal pH 11.0 condition, the gelatinous extracellular polymeric substance (EPS) and microbial cells were disrupted, with numerous outward migration and solubilization of proteins, polysaccharides and humus. The aromatic protein solubilization (tryptophan-like and tyrosine-like proteins) and humic acid-like substance deconstruction were the major driving factors for sediment cohesion reduction, which disintegrated the bio-aggregation and increased the surface electronegativity. Meanwhile, the variations of functional groups (CC, CO, COO-, CN, NH, C-O-C, C-OH, OH) also contributed to the interaction breakage and glutinous structure disruption of sediment particles. It was found that the rising pH conditions reduced sediment adhesion and promoted particle floating. Solubilizations of total suspended solids and volatile suspended solids were increased by 12.8 and 9.4 times, respectively, while the sediment adhesion was reduced by 3.8 fold. The alkaline treatment greatly improved sediment erosion and flushing capacities under shear stress of gravity sewage flow. Such sustainable strategy only cost 36.4 CNY per sewer meter length, which was 29.5-55.0 % of the high-pressure water jet flushing and perforated tube flushing approaches.
Topics: Extracellular Polymeric Substance Matrix; Sewage; Gases; Geologic Sediments
PubMed: 37329905
DOI: 10.1016/j.scitotenv.2023.164896 -
Scandinavian Journal of Medicine &... Nov 2023Maximal oxygen uptake (V̇O ) is a pivotal factor for aerobic endurance performance. Recently, aerobic high-intensity interval training (HIIT) was documented to be...
INTRODUCTION
Maximal oxygen uptake (V̇O ) is a pivotal factor for aerobic endurance performance. Recently, aerobic high-intensity interval training (HIIT) was documented to be superior to sprint interval training (SIT) in improving V̇O in well-trained males. However, as mounting evidence suggests that physiological responses to training are sex-dependent, examining the effects of HIIT versus SIT on V̇O , anaerobic capacity, and endurance performance in females is warranted.
METHODS
We randomized 81 aerobically well-trained females (22 ± 2 years, 51.8 ± 3.6 mL∙kg ∙min V̇O ), training three times weekly for 8 weeks, to well-established protocols: (1) HIIT 4 × 4 min at ~95% of maximal aerobic speed (MAS), with 3 min active recovery (2) SIT 8 × 20 s at ~150% of MAS, with 10 s passive recovery (3) SIT 10 × 30 s at ~175% of MAS, with 3.5 min active recovery.
RESULTS
Only HIIT 4 × 4 min increased V̇O (7.3 ± 3.1%), different from both SIT groups (all p < 0.001). Anaerobic capacity (maximal accumulated oxygen deficit) increased following SIT 8 × 20 s (6.5 ± 10.5%, p < 0.05), SIT 10 × 30 s (14.4 ± 13.7%, p < 0.05; different from HIIT 4 × 4 min, p < 0.05). SIT 10 × 30 s resulted in eight training-induced injuries, different from no injuries following HIIT 4 × 4 min and SIT 8 × 20 s (p < 0.001). All groups improved long-distance (3000-meter) and sprint (300-meter) running performance (all p < 0.001). SIT protocols improved sprint performance more than HIIT 4 × 4 min (p < 0.05). Compared to previous male results, no increase in V̇O following SIT 8 × 20 s (p < 0.01), and a higher injury rate for SIT 10 × 30 s (p < 0.001), were evident.
CONCLUSIONS
In aerobically well-trained women, HIIT is superior to SIT in increasing V̇O while all-out treadmill running SIT is potentially more harmful.
Topics: Humans; Male; Female; Oxygen Consumption; Adaptation, Physiological; High-Intensity Interval Training; Running; Oxygen
PubMed: 37608507
DOI: 10.1111/sms.14470 -
Heliyon Jul 2023The objective of this research was to investigate the variation of water quality parameters at different depths of the Gilgel Gibe I reservoir in Oromia Jimma zone...
The objective of this research was to investigate the variation of water quality parameters at different depths of the Gilgel Gibe I reservoir in Oromia Jimma zone during wet seasons. Five stations within the reservoir were selected, and water quality parameters were determined at four different depths (surface, 5 m, 10 m, and 15 m). Water quality parameters were analyzed on-site using a HACH, HQ40d portable multi-meter, and turbidity was measured using Wag tech turbidity meter and in the laboratory using the standard method. Comparison of water quality parameters among depths were conducted using one-way ANOVA and Tukey's pairwise comparisons with 5% significance level. The probable contributing source of the investigated physicochemical water quality parameters at different depth was identified using Principal components analysis. The results show that depth wise except for total suspended solids (TSS), total dissolved solids (TDS), total phosphorus (TP) and soluble reactive phosphorus (SRP) the rest showed statistically significant difference at p < 0.05 level. Negative correlations were found between depth and dissolved oxygen (DO), water temperature, pH, nitrate (N0) and chlorophyll (Chl.a) while positive correlations were found between electrical conductivity (EC), biochemical oxygen demand (BOD), turbidity and N0. The study revealed that the release of nutrients associated with increased concentration of BOD5 at the bottom depth caused low concentration of dissolved oxygen due to oxygen consumption. This was further aggravated through the decomposition of organic matter, indicating organic pollution resulting from runoff from the catchment. The presence of dense masses of blue-green algae in the pelagic zone of Gilgel Gibe I reservoir suggested the presence of ample nutrients for its blooming and significant reduction of water quality, indicating possible eutrophic conditions. Therefore, catchment management is required to protect aquatic life and the reservoir function as a whole from reservoir water quality degradation.
PubMed: 37501970
DOI: 10.1016/j.heliyon.2023.e17474 -
Scandinavian Journal of Medicine &... Dec 2023Hamstring strain injury (HSI) remains a performance, economic, and player availability burden in sport. High-speed running (HSR) is cited as a common mechanism for HSI.... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Hamstring strain injury (HSI) remains a performance, economic, and player availability burden in sport. High-speed running (HSR) is cited as a common mechanism for HSI. While evidence exists regarding the high physical demands on the hamstring muscles in HSR, meta-analytical synthesis of related activation and kinetic variables is lacking.
METHODS
A systematic search of Medline, Embase, Scopus, CINAHL, SportDiscus, and Cochrane library databases was conducted in accordance with the PRISMA 2020 guidelines. Studies reporting hamstring activation (electromyographic [EMG]) or hamstring muscle/related joint kinetics were included where healthy adult participants ran at or beyond 60% of maximum speed (activation studies) or 4 m per second (m/s) (kinetic studies).
RESULTS
A total of 96 studies met the inclusion criteria. Run intensities were categorized as "slow," "moderate," or "fast" in both activation and kinetic based studies with appropriate relative, and raw measures, respectively. Meta-analysis revealed pooled mean lateral hamstring muscle activation levels of 108.1% (95% CI: 84.4%-131.7%) of maximal voluntary isometric contraction (MVIC) during "fast" running. Meta-analysis found swing phase peak knee flexion internal moment and power at 2.2 Newton meters/kilogram (Nm/kg) (95% CI: 1.9-2.5) and 40.3 Watts/kilogram (W/kg) (95% CI: 31.4-49.2), respectively. Hip extension peak moment and power was estimated as 4.8 Nm/kg (95% CI: 3.9-5.7) and 33.1 W/kg (95% CI: 17.4-48.9), respectively.
CONCLUSIONS
As run intensity/speed increases, so do the activation and kinetic demands on the hamstrings. The presented data will enable clinicians to incorporate more objective measures into the design of injury prevention and return-to-play decision-making strategies.
Topics: Adult; Humans; Hamstring Muscles; Kinetics; Isometric Contraction; Muscle Strength; Running; Soft Tissue Injuries
PubMed: 37668346
DOI: 10.1111/sms.14478 -
Obesity Reviews : An Official Journal... Mar 2024Social jetlag, the weekly variation in sleep timing, is proposed to contribute to increased obesity risk, potentially because of the misalignment of behavioral cycles... (Meta-Analysis)
Meta-Analysis Review
Social jetlag, the weekly variation in sleep timing, is proposed to contribute to increased obesity risk, potentially because of the misalignment of behavioral cycles relative to the endogenous circadian timing system. This systematic review and meta-analysis aim to determine the association between social jetlag and adiposity-related measures using observational studies. We reviewed 477 references, of which 43 studies met inclusion criteria with a total sample size of 231,648. There was a positive association between social jetlag and body mass index (correlation coefficient [r]: 0.12; 95%CI, 0.07, 0.17; P < 0.001; I = 94.99%), fat mass (r: 0.10; 95%CI, 0.05, 0.15; P < 0.001; I = 0.00%), fat mass index (fat mass divided by height in meter squared, β: 0.14 kg/m ; 95%CI, 0.05, 0.23; P < 0.001; I = 56.50%), percent of body fat (r: 0.37; 95%CI, 0.33, 0.41; P < 0.001; I = 96.17%), waist circumference (r: 0.15; 95%CI, 0.06, 0.24; P = 0.001; I = 90.83%), and the risk of having overweight/obesity (odds ratio: 1.20; 95%CI, 1.02, 1.140; P = 0.039; I = 98.25%). Social jetlag is positively and consistently associated with multiple obesity-related anthropometric measures. Further studies are needed to test causality, underlying mechanisms, and whether obesity interventions based on increasing regularity of the sleep/wake cycle can aid in the battle against the obesity pandemic.
Topics: Humans; Circadian Rhythm; Obesity; Sleep; Jet Lag Syndrome; Body Mass Index; Observational Studies as Topic
PubMed: 38072635
DOI: 10.1111/obr.13664 -
Sensors (Basel, Switzerland) Nov 2023In the pursuit of enhancing the wine production process through the utilization of new technologies in viticulture, this study presents a novel approach for the rapid...
Rapid Determination of Wine Grape Maturity Level from pH, Titratable Acidity, and Sugar Content Using Non-Destructive In Situ Infrared Spectroscopy and Multi-Head Attention Convolutional Neural Networks.
In the pursuit of enhancing the wine production process through the utilization of new technologies in viticulture, this study presents a novel approach for the rapid assessment of wine grape maturity levels using non-destructive, in situ infrared spectroscopy and artificial intelligence techniques. Building upon our previous work focused on estimating sugar content (∘Brix) from the visible and near-infrared (VNIR) and short-wave infrared (SWIR) regions, this research expands its scope to encompass pH and titratable acidity, critical parameters determining the grape maturity degree, and in turn, wine quality, offering a more representative estimation pathway. Data were collected from four grape varieties-Chardonnay, Malagouzia, Sauvignon Blanc, and Syrah-during the 2023 harvest and pre-harvest phenological stages in the vineyards of Ktima Gerovassiliou, northern Greece. A comprehensive spectral library was developed, covering the VNIR-SWIR spectrum (350-2500 nm), with measurements performed in situ. Ground truth data for pH, titratable acidity, and sugar content were obtained using conventional laboratory methods: total soluble solids (TSS) (∘Brix) by refractometry, titratable acidity by titration (expressed as mg tartaric acid per liter of must) and pH by a pH meter, analyzed at different maturation stages in the must samples. The maturity indicators were predicted from the point hyperspectral data by employing machine learning algorithms, including Partial Least Squares regression (PLS), Random Forest regression (RF), Support Vector Regression (SVR), and Convolutional Neural Networks (CNN), in conjunction with various pre-processing techniques. Multi-output models were also considered to simultaneously predict all three indicators to exploit their intercorrelations. A novel multi-input-multi-output CNN model was also proposed, incorporating a multi-head attention mechanism and enabling the identification of the spectral regions it focuses on, and thus having a higher interpretability degree. Our results indicate high accuracy in the estimation of sugar content, pH, and titratable acidity, with the best models yielding mean R2 values of 0.84, 0.76, and 0.79, respectively, across all properties. The multi-output models did not improve the prediction results compared to the best single-output models, and the proposed CNN model was on par with the next best model. The interpretability analysis highlighted that the CNN model focused on spectral regions associated with the presence of sugars (i.e., glucose and fructose) and of the carboxylic acid group. This study underscores the potential of portable spectrometry for real-time, non-destructive assessments of wine grape maturity, thereby providing valuable tools for informed decision making in the wine production industry. By integrating pH and titratable acidity into the analysis, our approach offers a holistic view of grape quality, facilitating more comprehensive and efficient viticultural practices.
Topics: Vitis; Wine; Sugars; Artificial Intelligence; Spectroscopy, Near-Infrared; Fruit; Carbohydrates; Neural Networks, Computer; Hydrogen-Ion Concentration
PubMed: 38067909
DOI: 10.3390/s23239536 -
Methods in Cell Biology 2024Cellular senescence is a molecular process that is activated in response to a large variety of distinct stress signals. Mechanistically, cellular senescence is...
Cellular senescence is a molecular process that is activated in response to a large variety of distinct stress signals. Mechanistically, cellular senescence is characterized by an arrest in cell cycle accompanied by phenotypic adaptations and physiological alterations including changes in the secretory profile of senescent cells termed the senescence-associated secretory phenotype (SASP). Here we describe a detailed, automation- compatible method for the detection of senescence-associated beta galactosidase (SA-β-gal) activity as a hallmark of cellular senescence using a conventional fluorescent microscope equipped with a transmitted light module. Moreover, we outline a protocol for the automated analysis of cellular senescence using convolutional neural networks (CNNs) and mathematical morphology. In sum, we provide a toolset for the high throughput assessment of cellular senescence based on light microscopy and automated image analysis.
Topics: Cellular Senescence; Cell Cycle; Cell Division
PubMed: 38302236
DOI: 10.1016/bs.mcb.2023.02.017