Miracle-dz/UniFAR-FTUs huggingface dataset:
RhoA- and Actin-Dependent Functions of Macrophages from the Rodent Cardiac Transplantation Model Perspective -Timing Is the Essence

Simple Summary The functions of animal and human cells depend on the actin cytoskeleton and its regulating protein called the RhoA. The actin cytoskeleton and RhoA also regulate the response of the immune cells such as macrophages to the microbial invasion and/or the presence of a non-self, such as a transplanted organ. The immune response against transplant occurs in several steps. The early step occurring within days post-transplantation is called the acute rejection and the late step, occurring months to years post-transplantation, is called the chronic rejection. In clinical transplantation, acute rejection is easily manageable by the anti-rejection drugs. However, there is no cure for chronic rejection, which is caused by the macrophages entering the transplant and promoting blockage of its blood vessels and destruction of tissue. We discuss here how the inhibition of the RhoA and actin cytoskeleton polymerization in the macrophages, either by genetic interference or pharmacologically, prevents macrophage entry into the transplanted organ and prevents chronic rejection, and also how it affects the anti-microbial function of the macrophages. We also focus on the importance of timing of the macrophage functions in chronic rejection and how the circadian rhythm may affect the anti-chronic rejection and anti-microbial therapies. Abstract The small GTPase RhoA, and its down-stream effector ROCK kinase, and the interacting Rac1 and mTORC2 pathways, are the principal regulators of the actin cytoskeleton and actin-related functions in all eukaryotic cells, including the immune cells. As such, they also regulate the phenotypes and functions of macrophages in the immune response and beyond. Here, we review the results of our and other’s studies on the role of the actin and RhoA pathway in shaping the macrophage functions in general and macrophage immune response during the development of chronic (long term) rejection of allografts in the rodent cardiac transplantation model. We focus on the importance of timing of the macrophage functions in chronic rejection and how the circadian rhythm may affect the anti-chronic rejection therapies.
Comparing the Incidence of Buccal Mucosa Cancer in South Asian, White, and Black Populations Residing in the United States: A Cross-Sectional Analysis

Background: Recreational use of the betel nut, which is common among the South Asian population, is a known risk factor for developing Head and Neck cancer. As South Asians comprise a significant proportion of the United States population, we seek to determine if those living within the country experience a higher rate of head and neck cancers compared to other races. Methods: Data of patients diagnosed with head & neck cancers from 2010-2016 was collected from the National Cancer Database® and compared to race-matched US census data for each corresponding year to calculate incidence. Pairwise comparisons were performed between the incidence for South Asians versus Whites and South Asians versus Blacks using one sided Chi-square tests. Results: South Asians experienced a significantly higher incidence of buccal mucosa/vestibule cancers when compared to Whites or Blacks for every year between 2010-2016, but a comparatively lower incidence of larynx or oropharynx cancers. Conclusions: South Asians residing within the United States have a higher incidence of buccal mucosa/vestibule cancers, but a lower incidence of more common cancers, such as larynx or oropharynx cancer. This may suggest that the etiology behind the high buccal mucosa/vestibule cancer incidence is due to a social habit, as opposed to an inherent racial susceptibility.
Influence of cesium on the plasma parameters in front of the plasma grid in sources for negative hydrogen ions

The cesium dynamics in ion sources for negative hydrogen ions based on surface conversion mainly determine the performance of the neutral beam injection (NBI) heating system for fusion. To investigate the role of the evaporated cesium in the hydrogen plasma, which e.g. causes a decrease of the co-extracted electron current, experiments at a flexible laboratory setup (planar inductively coupled plasma) have been performed aiming at the direct influence of cesium on the plasma parameters in the plasma volume. In order to distinguish between effects resulting from the high atomic mass and those from plasma and surface chemistry, xenon admixtures (similar mass to Cs) were also investigated. A comprehensive set of diagnostics is applied simultaneously: optical emission and white light absorption spectroscopy, Langmuir probe measurements and residual gas analysis. As expected admixtures of xenon lead to a reduction of Te and an increase of ne. For cesium, however, the major effect is a remarkably reduction of n.
Detection of pathogenic Salmonella with nanobiosensors

Rapid detection methods are needed to identify pathogenic Salmonella spp. in food products to protect against outbreaks of salmonellosis. The objective of this study was to explore the feasibility of using quantum dot nanoparticles to rapidly detect pathogenic Salmonella. Selective detection was achieved with anti-Salmonella polyclonal antibodies immobilized by streptavidin–biotin binding or covalent binding to the quantum dot surface. Superparamagnetic particles were used to separate and concentrate cells from each sample. A portable fluorometer was developed to measure fluorescence signals from quantum dot nanoparticles adhered to Salmonella in the samples. The fluorometer was composed of a 415 nm UV LED, a bifurcated fiber, optical filters, and a silicon photomultiplier. Detection sensitivity was evaluated with serially diluted Salmonella typhimurium in phosphate-buffered saline containing 1% bovine serum albumin (PBS–BSA) or food extracts. Fluorescence of the nanobiosensor increased with increasing concentrations of bacteria. Salmonella detection limits were 1.4 × 103 CFU mL−1 in PBS–BSA and 4 × 103 CFU mL−1 in food extracts.
Structural Interplays in the Flexible N-Terminus and Scaffolding Domain of Human Membrane Protein Caveolin 3

Caveolins are critical for the formation of caveolae, which are small invaginations of the plasma membrane involved in a variety of biological processes. Caveolin 3 (Cav3), one of three caveolin isoforms, is an integral membrane protein mainly expressed in muscle tissues. Although various human diseases associated with Cav3 have been reported, structural characterization of Cav3 in the membrane has not been investigated in enough depth to understand the structure–function relationship. Here, using solution NMR, we characterized membrane association, structural communications, and molecular dynamics of the monomeric Cav3 in detergent micelle environment, particularly focused on the whole N-terminal part that is composed of the flexible N-terminus and the scaffolding domain. The results revealed a complicated structural interplay of the individual segments composing the whole N-terminal part, including the pH-dependent helical region, signature motif-like region, signature motif, and scaffolding domain. Collectively, the present study provides novel structural insights into the whole N-terminal part of Cav3 that plays important biological roles in cellular processes and diseases. In particular, given that several disease-related mutations are located at the whole N-terminal part of Cav3, the sophisticated communications in the whole N-terminal segments are likely to have relevance to the molecular basis of Cav3-related disease.
Oral Health Status in Older People with Dementia: A Case-Control Study

Dementia is characterized by a range of cognitive defects with impaired activities of daily living that have implications for patient oral health. Objectives. A case-control study was made of the impact of dementia upon oral health. A total of 152 patients were included: 69 with dementia and 83 controls from the region of Murcia (Spain). The Global Deterioration Scale (GDS) was used to classify the patients and an oral exploration was carried out. Odds ratios (ORs) and confidence intervals (CIs) were estimated using regression models. The patients with more severe disease were significantly more likely to have fewer natural teeth (OR 11.00, 95%CI 1.28–23.22; p = 0.001), a higher plaque index (p = 0.001), and a greater bleeding index (p = 0.001) than the control group. These findings suggest that older adults with dementia have deficient oral health. A higher bleeding index increases the risk of deterioration of cognitive function. The oral hygiene and health of older people with dementia need to be improved.
Multi-Dimensional Underwater Point Cloud Detection Based on Deep Learning

Numerous sensors can obtain images or point cloud data on land, however, the rapid attenuation of electromagnetic signals and the lack of light in water have been observed to restrict sensing functions. This study expands the utilization of two- and three-dimensional detection technologies in underwater applications to detect abandoned tires. A three-dimensional acoustic sensor, the BV5000, is used in this study to collect underwater point cloud data. Some pre-processing steps are proposed to remove noise and the seabed from raw data. Point clouds are then processed to obtain two data types: a 2D image and a 3D point cloud. Deep learning methods with different dimensions are used to train the models. In the two-dimensional method, the point cloud is transferred into a bird’s eye view image. The Faster R-CNN and YOLOv3 network architectures are used to detect tires. Meanwhile, in the three-dimensional method, the point cloud associated with a tire is cut out from the raw data and is used as training data. The PointNet and PointConv network architectures are then used for tire classification. The results show that both approaches provide good accuracy.
The Effect of Unsupervised Home-Based Exercise Training on Physical Functioning Outcomes in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Exercise training such as balance, aerobic, and resistance training is able to improve physical functioning of older adults. Delivering such exercise regimes at home without supervision may be useful for older adults because they do not have to leave their homes. Objective: This systematic review and meta-analysis of randomized controlled trials aimed to establish the effect of unsupervised home-based exercise training regimes on physical functioning (balance and muscle strength) in older adults. Data sources: PubMed, CINAHL, Medline, Google Scholar, and Scopus databases and reference lists of included investigations were searched. Study selection: Thirteen randomized controlled trials (RCTs) of exercise training impact on balance and upper body strength with concurrent control groups were included in the analysis. Results: Our analyses revealed that in older adults, unsupervised home-based various exercise training was effective in improving measures of proactive balance (mean difference (MD) = −1.37 s; 95% confidence interval (CI), −2.24, −0.51 s; p = 0.002) and balance test battery (MD: 1.80; 95% CI, 0.46, 3.14 s; p = 0.009). There were no significant differences between the experimental and control groups for upper body strength (p > 0.05). Conclusion: Unsupervised home-based exercise training improves balance in older adults. Future investigations are needed to clarify the mechanisms underlying unsupervised home-based exercise training’s effect on this population’s physical functioning outcomes.
Management of Ralstonia solanacearum in tomato using ZnO nanoparticles synthesized through Matricaria chamomilla.

Matricaria chamomilla flower extract was used as a biocompatible material for synthesis of zinc oxide nanoparticles (ZnONPs). The synthesized NPs were evaluated for their antibacterial potential in vitro and in vivo against Ralstonia solanacearum that causes devastating bacterial wilt disease in tomato and other crops. Synthesized ZnONPs were further analyzed by UV-Visible spectroscopy, fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS). The synthesized polydisperse ZnONPs were found to be in the size range of 8.9 to 32.6 nm, and at 18.0 µg ml-1 exhibited maximum in vitro growth inhibition of R. solanacearum. SEM analysis of affected bacterial cells showed morphological deformation such as disruption of cell membrane, cell wall and leakage of cell contents. Results of in vivo studies also showed that application of ZnONPs to the artificially inoculated tomato plants with R. solanacearum significantly enhanced the plant growth by reducing bacterial soil population and disease severity as compared to untreated control. Biosynthesized ZnONPs could be an effective approach to control R. solanacearum.
Transcranial direct current stimulation and repeated sprint ability: No effect on sprint performance or ratings of perceived exertion

ABSTRACT The role of transcranial direct current stimulation (tDCS) as an ergogenic aid is receiving attention from scientists to optimize sport performance. Most studies have examined the effects of tDCS on endurance performance during continuous tasks, while the effect of tDCS on high-intensity intermittent tasks has been less investigated. Therefore, this study aimed to explore the acute effects of tDCS on sprint performance and ratings of perceived exertion (RPE) during a repeated sprint ability (RSA) task. Twenty-five healthy males (age: 22.0 ± 2.5 years) participated in a randomized crossover study consisting of three experimental sessions (anodal, cathodal or sham tDCS) separated by 1 week. Each session consisted of (I) tDCS protocol (15 min at 2 mA applied over the dorsolateral prefrontal cortex [DLPFC]), (II) warm-up and (III) RSA task (ten 30-m running sprints separated by 30 s). Total time and RPE values were recorded for each sprint. The two-way ANOVA applied on sprint time did not reveal a significant main effect of tDCS condition (p = .200) neither a significant tDCS condition × number of sprint interaction (p = .716). Similarly, no significant differences were observed for the fatigue index (p = .449), RSAmean (p = .200) or RPE after each sprint (p range = .116–.890). The magnitude of the differences between the tDCS conditions ranged from negligible to small (effect sizes ≤ 0.33). These results suggest that the application of tDCS over the DLPFC is not effective to increase sprint performance or reduce RPE during a RSA task. HIGHLIGHTS Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that could modulate neuromuscular performance. This study aimed to explore the short-term effects of tDCS on sprint performance and ratings of perceived exertion (RPE) during a repeated sprint ability (RSA) task. The application of either ANODAL or CATHODAL tDCS over the DLPFC for 15 minutes did not affect the sprint time of single repeated sprints or the overall metrics of RSA performance (RSAmean and fatigue index). The application of either ANODAL or CATHODAL tDCS over the DLPFC for 15 minutes did not affect the ratings of perceived exertion measured during the repeated sprints task.
Guide-target mismatch effects on dCas9–sgRNA binding activity in living bacterial cells

Abstract As an effective programmable DNA targeting tool, CRISPR–Cas9 system has been adopted in varieties of biotechnological applications. However, the off-target effects, derived from the tolerance towards guide-target mismatches, are regarded as the major problems in engineering CRISPR systems. To understand this, we constructed two sgRNA libraries carrying saturated single- and double-nucleotide mismatches in living bacteria cells, and profiled the comprehensive landscape of in vivo binding affinity of dCas9 toward DNA target guided by each individual sgRNA with particular mismatches. We observed a synergistic effect in seed, where combinatorial double mutations caused more severe activity loss compared with the two corresponding single mutations. Moreover, we found that a particular mismatch type, dDrG (D = A, T, G), only showed moderate impairment on binding. To quantitatively understand the causal relationship between mismatch and binding behaviour of dCas9, we further established a biophysical model, and found that the thermodynamic properties of base-pairing coupled with strand invasion process, to a large extent, can account for the observed mismatch-activity landscape. Finally, we repurposed this model, together with a convolutional neural network constructed based on the same mechanism, as a predictive tool to guide the rational design of sgRNA in bacterial CRISPR interference.
Metabolic Transition of Milk Triacylglycerol Synthesis in Response to Varying Levels of Three 18-Carbon Fatty Acids in Porcine Mammary Epithelial Cells

This study aimed to examine the effects of increasing levels of three 18-carbon fatty acids (stearate, oleate and linoleate) on mammary lipogenesis, and to evaluate their effects on the milk lipogenic pathway in porcine mammary epithelial cells (pMECs). We found that increasing the three of 18-carbon fatty acids enhanced the cellular lipid synthesis in a dose-dependent manner, as reflected by the increased (triacylglycerol) TAG content and cytosolic lipid droplets in pMECs. The increased lipid synthesis by the three 18-carbon fatty acids was probably caused by the up-regulated expression of major genes associated with milk fat biosynthesis, including CD36 (long chain fatty acid uptake); GPAM, AGPAT6, DGAT1 (TAG synthesis); PLIN2 (lipid droplet formation); and PPARγ (regulation of transcription). Western blot analysis of CD36, DGAT1 and PPARγ proteins confirmed this increase with the increasing incubation of 18-carbon fatty acids. Interestingly, the mRNA expressions of ACSL3 and FABP3 (fatty acids intracellular activation and transport) were differentially affected by the three 18-carbon fatty acids. The cellular mRNA expressions of ACSL3 and FABP3 were increased by stearate, but were decreased by oleate or linoleate. However, the genes involved in fatty acid de novo synthesis (ACACA and FASN) and the regulation of transcription (SREBP1) were decreased by incubation with increasing concentrations of 18-carbon fatty acids. In conclusion, our findings provided evidence that 18-carbon fatty acids (stearate, oleate and linoleate) significantly increased cytosolic TAG accumulation in a dose-dependent manner, probably by promoting lipogenic genes and proteins that regulate the channeling of fatty acids towards milk TAG synthesis in pMECs.
Comparative Evaluation of Novel 177Lu-Labeled PNA Probes for Affibody-Mediated PNA-Based Pretargeting

Simple Summary Affibody molecules are small, engineered affinity proteins based on a nonimmunoglobulin scaffold. Affibody-based radionuclide imaging probes have demonstrated excellent tumor targeting. However, the renal clearance of affibody molecules is accompanied by high reabsorption and retention of activity in the kidney, which prevents their use for radionuclide therapy. We have previously shown the feasibility of overcoming the high renal uptake using a pretargeting approach for affibody-mediated therapy based on peptide nucleic acid (PNA) hybridization. In this study, we test the hypothesis that shortening the PNA pretargeting probes would further increase the difference between the accumulation of radiometals in tumor xenografts and in kidneys. A series of novel PNA probes has been designed and evaluated in vitro and in vivo. We have found that a variant containing 9 nucleobases enables a two-fold increase of the tumor-to-kidney dose ratio compared with a variant containing 15 nucleobases. This creates preconditions for more efficient therapy of cancer. Abstract Affibody-mediated PNA-based pretargeting is a promising approach to radionuclide therapy of HER2-expressing tumors. In this study, we test the hypothesis that shortening the PNA pretargeting probes would increase the tumor-to-kidney dose ratio. The primary probe ZHER2:342-SR-HP15 and the complementary secondary probes HP16, HP17, and HP18, containing 9, 12, and 15 nucleobases, respectively, and carrying a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator were designed, synthesized, characterized in vitro, and labeled with 177Lu. In vitro pretargeting was studied in HER2-expressing SKOV3 and BT474 cell lines. The biodistribution of these novel probes was evaluated in immunodeficient mice bearing SKOV3 xenografts and compared to the previously studied [177Lu]Lu-HP2. Characterization confirmed the formation of high-affinity duplexes between HP15 and the secondary probes, with the affinity correlating with the length of the complementary PNA sequences. All the PNA-based probes were bound specifically to HER2-expressing cells in vitro. In vivo studies demonstrated HER2-specific uptake of all 177Lu-labeled probes in xenografts in a pretargeting setting. The ratio of cumulated radioactivity in the tumor to the radioactivity in kidneys was dependent on the secondary probe’s size and decreased with an increased number of nucleobases. The shortest PNA probe, [177Lu]Lu-HP16, showed the highest tumor-to-kidney ratio. [177Lu]Lu-HP16 is the most promising secondary probe for affibody-mediated tumor pretargeting.
Electrophysiology Read-Out Tools for Brain-on-Chip Biotechnology

Brain-on-Chip (BoC) biotechnology is emerging as a promising tool for biomedical and pharmaceutical research applied to the neurosciences. At the convergence between lab-on-chip and cell biology, BoC couples in vitro three-dimensional brain-like systems to an engineered microfluidics platform designed to provide an in vivo-like extrinsic microenvironment with the aim of replicating tissue- or organ-level physiological functions. BoC therefore offers the advantage of an in vitro reproduction of brain structures that is more faithful to the native correlate than what is obtained with conventional cell culture techniques. As brain function ultimately results in the generation of electrical signals, electrophysiology techniques are paramount for studying brain activity in health and disease. However, as BoC is still in its infancy, the availability of combined BoC–electrophysiology platforms is still limited. Here, we summarize the available biological substrates for BoC, starting with a historical perspective. We then describe the available tools enabling BoC electrophysiology studies, detailing their fabrication process and technical features, along with their advantages and limitations. We discuss the current and future applications of BoC electrophysiology, also expanding to complementary approaches. We conclude with an evaluation of the potential translational applications and prospective technology developments.