Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrated Analysis of Quantitative Proteome and Transcriptional Profiles Reveals the Dynamic Function of Maternally Expressed Proteins After Parthenogenetic Activation of Buffalo Oocyte*

Maternal-effect genes are especially critical for early embryonic development after fertilization and until massive activation of the embryonic genome occurs. By applying a tandem mass tag (TMT)-labeled quantitative proteomics combined with RNA sequencing approach, the proteome of the buffalo was quantitatively analyzed during parthenogenesis of mature oocytes and the two-cell stage embryo. Of 1908 quantified proteins, 123 differed significantly. The transcriptome was analyzed eight stages (GV, MII, 2-cell, 4-cell, 8-cell, 16-cell, morula, blastocyst) of Buffalo using the RNA sequencing approach, and a total of 3567 unique genes were identified to be differently expressed between all consecutive stages of pre-implantation development. Validation of proteomics results (TUBB3, CTNNA1, CDH3, MAP2K1), which are involved in tight junction and gap junction, revealing that the maternal expression of the proteins possibly plays a role in the formation of cellular junctions firstly after parthenogenetic activation. Correlation and hierarchical analyses of transcriptional profiles and the expression of NPM2 and NLRP5 mRNA of buffalo in vitro developed oocytes and parthenogenetic embryos indicated that the “maternal-to-zygotic transition” (MZT) process might exist in the model of parthenogenesis, which is similar to a normally fertilized embryo, and may occur between the 8-cell to 16-cell stage. These data provide a rich resource for further studies on maternal proteins and genes and are conducive to improving nuclear transfer technology.
Heterologous Expression of Pseudomonas putida Methyl-Accepting Chemotaxis Proteins Yields Escherichia coli Cells Chemotactic to Aromatic Compounds

Bacterial chemotaxis might be harnessed for the development of rapid biosensors, in which chemical availability is deduced from cell accumulation to chemoattractants over time. Chemotaxis of Escherichia coli has been well studied, but the bacterium is not attracted to chemicals of environmental concern, such as aromatic solvents. We show here that heterologous chemoreceptors for aromatic compounds from Pseudomonas putida at least partly functionally complement the E. coli chemotaxis network, yielding cells attracted to toluene or benzoate. Complementation was still inferior to native chemoattractants, like serine, but our study demonstrates the potential for obtaining selective sensing for aromatic compounds in E. coli. ABSTRACT Escherichia coli, commonly used in chemotaxis studies, is attracted mostly by amino acids, sugars, and peptides. We envisioned modifying the chemotaxis specificity of E. coli by expressing heterologous chemoreceptors from Pseudomonas putida enabling attraction either to toluene or benzoate. The mcpT gene encoding the type 40-helical bundle (40H) methyl-accepting chemoreceptor for toluene from Pseudomonas putida MT53 and the pcaY gene for the type 40H receptor for benzoate and related molecules from P. putida F1 were expressed from the trg promoter on a plasmid in motile wild-type E. coli MG1655. E. coli cells expressing McpT accumulated in chemoattraction assays to sources with 60 to 200 μM toluene, although less strongly than the response to 100 μM serine, but statistically significantly stronger than that to sources without any added attractant. An McpT-mCherry fusion protein was detectably expressed in E. coli and yielded weak but distinguishable membranes and polar foci in 1% of cells. E. coli cells expressing PcaY showed weak attraction to 0.1 to 1 mM benzoate, but 50 to 70% of cells localized the PcaY-mCherry fusion to their membrane. We conclude that implementing heterologous receptors in the E. coli chemotaxis network is possible and, upon improvement of the compatibility of the type 40H chemoreceptors, may bear interest for biosensing. IMPORTANCE Bacterial chemotaxis might be harnessed for the development of rapid biosensors, in which chemical availability is deduced from cell accumulation to chemoattractants over time. Chemotaxis of Escherichia coli has been well studied, but the bacterium is not attracted to chemicals of environmental concern, such as aromatic solvents. We show here that heterologous chemoreceptors for aromatic compounds from Pseudomonas putida at least partly functionally complement the E. coli chemotaxis network, yielding cells attracted to toluene or benzoate. Complementation was still inferior to native chemoattractants, like serine, but our study demonstrates the potential for obtaining selective sensing for aromatic compounds in E. coli.
A Pneumatic Tactile Ring for Instantaneous Sensory Feedback in Laparoscopic Tumor Localization

We aim to achieve intraoperative localization of an early-stage gastric tumor that cannot be visually detected during laparoscopic surgery. In this study, we developed and evaluated a pneumatic tactile ring, which is a clinically applicable tactile device to provide instantaneous feedback from a tactile sensor directly manipulated by a surgeon. It was designed to be worn on the finger of the manipulating hand and to present pressure to the finger pad. It is lightweight, cost-effective, disposable, and sterilizable. We also developed a compact pneumatic drive unit to control the pressure and investigated its fundamental performance. The bandwidth of the pressure control was at least 1.3 Hz with a controllable range of up to 79.7 kPa. Moreover, a psychophysical experiment was performed to obtain the Weber ratio of the pressure and evaluate the effectiveness of the instantaneous tactile feedback of the sensor output through the tactile ring. The Weber ratio was 0.40 at the reference pressure of 22.7 kPa. The provided tactile feedback significantly reduced the absolute localization error and increased participants’ confidence in their answers. It was shown that the tactile feedback through the ring is effective in laparoscopic tumor localization.
Apoptosis signal-regulating kinase 1 (ASK1) inhibition attenuates human airway smooth muscle growth and migration in chronic obstructive pulmonary disease (COPD)

Increased airway smooth muscle (ASM) mass is observed in chronic obstructive pulmonary disease (COPD) which is correlated with disease severity and negatively impact lung function in these patients. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase kinase kinase (MAP3K) activated by various stress stimuli, including reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and is known to regulate cell proliferation. ASM cells from COPD patients are hyper-proliferative to mitogens in vitro. However, the role of ASK1 in ASM growth is not established. Here, we aim to determine the effects of ASK1 inhibition on ASM growth and pro-mitogenic signaling using ASM cells from COPD patients. We found greater expression of ASK1 in ASM-bundles of COPD lung when compared with non-COPD. Pre-treatment of ASM cells with highly selective ASK1 inhibitor, TCASK10 resulted in a dose-dependent reduction in mitogen (FBS, PDGF and EGF; 72 hours)-induced ASM growth as measured by CyQuant assay. Further, molecular targeting of ASK1 using siRNA in ASM cells prevented mitogen-induced cell growth. In addition, to anti-mitogenic potential, ASK1 inhibitor also prevented TGFβ1-induced migration of ASM cells in vitro. Immunoblotting revealed that anti-mitogenic effects are mediated by JNK and p38MAP kinase-signaling pathways as evident by reduced phosphorylation of downstream effectors JNK1/2 and p38MAP kinases respectively with no effect on ERK1/2. Collectively, these findings establish the anti-mitogenic effect of ASK1 inhibition and identify a novel pathway that can be targeted to reduce or prevent excessive ASM mass in COPD.
Cytotoxic, DNA Cleavage and Pharmacokinetic Parameter Study of Substituted Novel Furan C-2 Quinoline Coupled 1, 2, 4-Triazole and Its Analogs

Background Furan, quinoline and triazoles are known for their wide spectrum biologically active molecules. A series of novel furan C-2 quinoline and 1, 2, 4-triazole (FQT) coupled hybrids were designed and synthesized to evaluate for their DNA cleavage and cytotoxic studies. Objectives In this work we describe the synthesis and biological evaluation of furan C-2 quinoline coupled triazoles exposed for cytotoxic and DNA cleavage study. Methods The electrophoretic DNA cleavage studies on λ-DNA (Eco-RI/Hinda-III double digest) using agarose gelelectrophoresis and the cytotoxic activity were carried out by MTT assay method. Results The results revealed that, the molecules 7(a-o) did cleave the DNA completely with no trace of fragments at 100 µg concentration, on the other hand, cytotoxic assay was achieved by two different human cancer cell lines (melanoma cell line-A375 and breast cancer cell line MDA-MB 231). Among the synthesized compounds 7a, 7b, 7c and 7k exhibited potent cytotoxic activity with IC50 values ranging from 2.9, 4.0, 7.8 and 5.1 µg/ml against A375 and 6.2, 9.5, 11.3 and 7.3 µg/ml against, MDA-MB 231, respectively. Conclusion In synthesized compounds 7(a-o) exhibited complete DNA cleavage at 100 µg/ml and the compounds 7a, 7b, 7c and 7k showed very less cytotoxic in nature. The structure activity relationship revealed that, the presence of halogen group/atoms at para position of phenyl ring remarkably enhanced the DNA cleavage and cytotoxic activities among the synthesized compounds.
Salivary Cortisol Does Not Correlate with Metabolic Syndrome Markers or Subjective Stress in Overweight Children.

Objective Being overweight is a risk factor for metabolic syndrome in children, but not all overweight children develop metabolic syndrome. Cortisol excess from chronic psychological stress has been proposed as an independent risk factor for metabolic syndrome in this already at-risk population. The present study assesses the relationship of biochemical and body composition radiographic markers of metabolic syndrome to salivary cortisol and self-report of chronic psychological stress in a cohort of overweight children. Methods This cross-sectional study took place in a multi-disciplinary pediatric obesity clinic at a tertiary care hospital, and involved fifteen children with BMI at or above the 85th percentile for age and sex, 10 of whom provided salivary cortisol samples. The main outcomes measured were salivary bedtime cortisol, first-waking cortisol, and cortisol awakening response (CAR-the rise in cortisol in the first half hour after waking); fasting serum triglycerides, HDL cholesterol, glucose and insulin for HOMA-IR; the ratio of abdominal fat to total body fat by DXA scan; and scores of validated stress and bullying questionnaires (PANAS-C, PSS, and SEC-Q). Results In this pilot study, no correlation was found between salivary cortisol measures and questionnaire scores of subjective stress or bullying, and no correlation was found between any of these measures and markers of metabolic syndrome (dyslipidemia, insulin resistance, increased abdominal fat). Conclusions These results suggest that measures of psychological stress, whether biochemical or subjective, do not appear to predict risk of metabolic syndrome in overweight children. While ease of collection and demonstrated utility both in detection of pediatric Cushing disease and in adult psychological research make salivary cortisol assessment an attractive clinical tool, further investigation into the value of salivary measures in pediatric stress research is needed.
Nicotinamide riboside supplementation dysregulates redox and energy metabolism in rats: Implications for exercise performance

What is the central question of this study? The aim was to investigate the potential metabolic and redox mechanisms that impaired exercise performance after 21 days of supplementation with 300 mg (kg body weight)−1 of nicotinamide riboside in rats. What is the main finding and its importance? Nicotinamide riboside disturbed energy and redox metabolism and impaired exercise performance in heathy rats. Exogenously administered redox agents in heathy populations might lead to adverse effects.
HIV RNA persists in rectal tissue despite rapid plasma virologic suppression with dolutegravir-based therapy

Objectives: Despite plasma virologic suppression with antiretroviral therapy (ART), HIV persists in gut tissue. The objectives of this study were to compare plasma and rectal tissue HIV RNA dynamics and to assess relationships with dolutegravir (DTG) plasma and tissue concentrations. Design: A longitudinal cohort study of HIV-infected treatment-naïve individuals initiating DTG-based ART was conducted over 12 weeks with plasma and rectal tissue sampling (Clinicaltrials.gov:NCT02924389). Methods: HIV RNA and DTG concentrations were quantified in plasma and rectal tissue samples collected pre-ART (baseline) and post-ART at weeks 2, 6, and 12 using Abbott Real-Time HIV-1 assays and high-performance liquid chromatography tandem mass spectroscopy, respectively. Relationships between rectal tissue RNA and DTG concentrations were modeled using binary logistic regression, controlling for repeated measures. Results: Twelve participants were enrolled: six (50.0%) women, nine (75.0%) black, median age 42.0 years (Q1 31.2, Q3 52.0). All attained plasma virologic suppression by week 6. 11 of 12 (91.7%) had detectable rectal tissue HIV RNA at baseline, and only three of 11 (27.3%) achieved rectal tissue virologic suppression at any time-point. Compared with rectal tissue nonsuppressors, three of three (100.0%) of rectal tissue suppressors were women, had higher BMI, 35.9 kg/m2 (range 24.9–38.5) versus 20.6 (17.7–29.9), P = 0.05, and lower baseline log plasma HIV RNA: 3.7 copies/ml (range 3.6–4.4) versus 4.7 (3.8–5.4), P = 0.02. No significant relationships between rectal tissue RNA suppression and DTG concentrations were seen. Conclusion: Rectal tissue HIV RNA persisted in most participants and was not predicted by DTG concentrations. Impact of host factors, particularly sex, on tissue HIV viral dynamics warrants further exploration.
Membrane Fluidity Is Regulated Cell Nonautonomously by Caenorhabditis elegans PAQR-2 and Its Mammalian Homolog AdipoR2

The properties of cell membranes are determined mostly by the types of fatty acids that they contain. Bodhicharla et al. report that a key regulator of membrane fluidity, the PAQR-2/IGLR-2 protein complex. Maintenance of membrane properties is an essential aspect of cellular homeostasis of which the regulatory mechanisms remain mostly uncharacterized. In Caenorhabditis elegans, the PAQR-2 and IGLR-2 proteins act together as a plasma membrane sensor that responds to decreased fluidity by promoting fatty acid desaturation, hence restoring membrane fluidity. Here, we used mosaic analysis for paqr-2 and iglr-2, and tissue-specific paqr-2 expression, to show that membrane homeostasis is achieved cell nonautonomously. Specifically, we found that expression of paqr-2 in the hypodermis, gonad sheath cells, or intestine is sufficient to suppress systemic paqr-2 mutant phenotypes, including tail tip morphology, membrane fluidity in intestinal cells, cold and glucose intolerance, vitellogenin transport to the germline, germ cell development, and brood size. Finally, we show that the cell nonautonomous regulation of membrane homeostasis is conserved in human cells: HEK293 cells that express AdipoR2, a homolog of paqr-2, are able to normalize membrane fluidity in distant cells where AdipoR2 has been silenced. Finally, using C. elegans mutants and small interfering RNA against Δ9 stearoyl-CoA desaturase in HEK293 cells, we show that Δ9 desaturases are essential for the cell nonautonomous maintenance of membrane fluidity. We conclude that cells are able to share membrane components even when they are not in direct contact with each other, and that this contributes to the maintenance of membrane homeostasis in C. elegans and human cells.
Heading Through a Crowd

The ability to navigate through crowds of moving people accurately, efficiently, and without causing collisions is essential for our day-to-day lives. Vision provides key information about one’s own self-motion as well as the motions of other people in the crowd. These two types of information (optic flow and biological motion) have each been investigated extensively; however, surprisingly little research has been dedicated to investigating how they are processed when presented concurrently. Here, we showed that patterns of biological motion have a negative impact on visual-heading estimation when people within the crowd move their limbs but do not move through the scene. Conversely, limb motion facilitates heading estimation when walkers move independently through the scene. Interestingly, this facilitation occurs for crowds containing both regular and perturbed depictions of humans, suggesting that it is likely caused by low-level motion cues inherent in the biological motion of other people.
Regulators of the transsulfuration pathway

The transsulfuration pathway is a metabolic pathway where transfer of sulfur from homocysteine to cysteine occurs. The pathway leads to the generation of several sulfur metabolites, which include cysteine, GSH and the gaseous signalling molecule hydrogen sulfide (H2S). Precise control of this pathway is critical for maintenance of optimal cellular function and, therefore, the key enzymes of the pathway, cystathionine β‐synthase and cystathionine γ‐lyase, are regulated at multiple levels. Disruption of the transsulfuration pathway contributes to the pathology of several conditions such as vascular dysfunction, Huntington's disease and during ageing. Treatment with donors of hydrogen sulfide and/or stimulation of this pathway have proved beneficial in several of these disorders. In this review, we focus on the regulation of the transsulfuration pathway pertaining to cysteine and H2S, which could be targeted to develop novel therapeutics.
Highly diverged novel subunit composition of apicomplexan F-type ATP synthase identified from Toxoplasma gondii

The mitochondrial F-type ATP synthase, a multi-subunit nanomotor, is critical for maintaining cellular ATP levels. In Toxoplasma gondii and other apicomplexan parasites, many subunit components, necessary for proper assembly and functioning of this enzyme, appear to be missing. Here, we report the identification of 20 novel subunits of T. gondii F-type ATP synthase from mass spectrometry analysis of partially purified monomeric (~600 kDa) and dimeric (>1 MDa) forms of the enzyme. Despite extreme sequence diversification, key FO subunits, a, b and d, can be identified from conserved structural features. Orthologs for these proteins are restricted to apicomplexan, chromerid and dinoflagellate species. Interestingly, their absence in ciliates indicates a major diversion, with respect to subunit composition of this enzyme, within the alveolate clade. Discovery of these highly diversified novel components of the apicomplexan F-type ATP synthase complex could facilitate the development of novel anti-parasitic agents. Structural and functional characterization of this unusual enzyme complex will advance our fundamental understanding of energy metabolism in apicomplexan species.
Binding and structural studies of the complexes of type 1 ribosome inactivating protein from Momordica balsamina with uracil and uridine

Ribosome inactivating protein (RIP) catalyzes the cleavage of glycosidic bond formed between adenine and ribose sugar of ribosomal RNA to inactivate ribosomes. Previous structural studies have shown that RNA bases, adenine, guanine, and cytosine tend to bind to RIP in the substrate binding site. However, the mode of binding of uracil with RIP was not yet known. Here, we report crystal structures of two complexes of type 1 RIP from Momordica balsamina (MbRIP1) with base, uracil and nucleoside, uridine. The binding studies of MbRIP1 with uracil and uridine as estimated using fluorescence spectroscopy showed that the equilibrium dissociation constants (KD) were 1.2 × 10−6 M and 1.4 × 10−7 M respectively. The corresponding values obtained using surface plasmon resonance (SPR) were found to be 1.4 × 10−6 M and 1.1 × 10−7 M, respectively. Structures of the complexes of MbRIP1 with uracil (Structure‐1) and uridine (Structure‐2) were determined at 1.70 and 1.98 Å resolutions respectively. Structure‐1 showed that uracil bound to MbRIP1 at the substrate binding site but its mode of binding was significantly different from those of adenine, guanine and cytosine. However, the mode of binding of uridine was found to be similar to those of cytidine. As a result of binding of uracil to MbRIP1 at the substrate binding site, three water molecules were expelled while eight water molecules were expelled when uridine bound to MbRIP1.
Estimation of Human Body Vital Signs Based on 60 GHz Doppler Radar Using a Bound-Constrained Optimization Algorithm

In this study, a bound-constrained optimization algorithm is applied for estimating physiological data (pulse and breathing rate) of human body using 60 GHz Doppler radar, by detecting displacements induced by breathing and the heartbeat of a human subject. The influence of mutual phasing between the two movements is analyzed in a theoretical framework and the application of optimization algorithms is proved to be able to accurately detect both breathing and heartbeat rates, despite intermodulation effects between them. Different optimization procedures are compared and shown to be more robust to receiver noise and artifacts of random body motion than a direct spectrum analysis. In case of a large-scale constrained bound, a parallel optimization procedure executed in subranges is proposed to realize accurate detection in a reduced span of time.
Dropout from interpersonal psychotherapy for mental health disorders: A systematic review and meta-analysis

Abstract Objective: Dropout is one factor that might limit the effectiveness of interpersonal psychotherapy (IPT). Improved understanding of IPT dropout is an important research priority. This meta-analysis examined dropout rates from IPT in randomized controlled trials. Method: Seventy-two trials met inclusion criteria. Results: The weighted mean dropout rate from IPT was 20.6% (95% CI = 17.4–24.2). Dropout rates were similar for depressive (20.9%; 95% CI = 17.2–25.2), anxiety (16.1%; 95% CI = 11.1–22.9), and eating disorders (18.7%; 95% CI = 11.6–28.8). Dropout was highest when more stringent definitions of dropout were applied (e.g., failure to complete the entire IPT protocol versus failure to complete at least 50% of sessions) and was lowest when adolescent patients were sampled. There was some evidence that IPT was associated with significantly lower rates of dropout than both CBT and non-specific supportive therapies. These effects were generally replicated when analysing trials that provided a clear definition of treatment (rather than study) dropout. Conclusions: Overall, findings provide preliminary evidence to suggest that IPT may be an accepted and tolerated treatment option for patients with common mental health disorders. This review also highlights the need for future trials to rigorously report detail pertaining to patient dropout.