Miracle-dz/UniFAR-FTUs huggingface dataset:
2A-DUB/Mysm1 Regulates Epidermal Development in Part by Suppressing p53-Mediated Programs

Development and homeostasis of the epidermis are governed by a complex network of sequence-specific transcription factors and epigenetic modifiers cooperatively regulating the subtle balance of progenitor cell self-renewal and terminal differentiation. To investigate the role of histone H2A deubiquitinase 2A-DUB/Mysm1 in the skin, we systematically analyzed expression, developmental functions, and potential interactions of this epigenetic regulator using Mysm1-deficient mice and skin-derived epidermal cells. Morphologically, skin of newborn and young adult Mysm1-deficient mice was atrophic with reduced thickness and cellularity of epidermis, dermis, and subcutis, in context with altered barrier function. Skin atrophy correlated with reduced proliferation rates in Mysm1−/− epidermis and hair follicles, and increased apoptosis compared with wild-type controls, along with increases in DNA-damage marker γH2AX. In accordance with diminished α6-Integrinhigh+CD34+ epidermal stem cells, reduced colony formation of Mysm1−/− epidermal progenitors was detectable in vitro. On the molecular level, we identified p53 as potential mediator of the defective Mysm1-deficient epidermal compartment, resulting in increased pro-apoptotic and anti-proliferative gene expression. In Mysm1−/−p53−/− double-deficient mice, significant recovery of skin atrophy was observed. Functional properties of Mysm1−/− developing epidermis were assessed by quantifying the transepidermal water loss. In summary, this investigation uncovers a role for 2A-DUB/Mysm1 in suppression of p53-mediated inhibitory programs during epidermal development.
The Rapid Emergence of Tigecycline Resistance in blaKPC–2 Harboring Klebsiella pneumoniae, as Mediated in Vivo by Mutation in tetA During Tigecycline Treatment

Tigecycline is one of the last resort treatments for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. Tigecycline resistance often occurs during the clinical treatment of CRKP, yet its mechanism has still not been clearly elucidated. This study presents an analysis of a tigecycline resistance mechanism that developed in clinical isolates from a 56-year-old female patient infected with CRKP during tigecycline treatment. Consecutive clonal consistent K. pneumoniae isolates were obtained during tigecycline treatment. Whole genome sequencing of the isolates was performed, and putative single nucleotide polymorphisms and insertion and deletion mutations were analyzed in susceptible and resistant isolates. The identified gene of interest was examined through experiments involving transformations and conjugations. Four isolates, two of which were susceptible and two resistant, were collected from the patient. All of the isolates belonged to Sequence Type 11 (ST11) and were classified as extensively drug resistant (XDR). One amino acid substitution S251A in TetA was identified in the tigecycline-resistant isolates. Subsequent transformation experiments confirmed the contribution of the TetA variant (S251A) to tigecycline resistance. The transfer capacity of tigecycline resistance via this mutation was confirmed by conjugation experiments. Using southern blot hybridization and PCR assays, we further proved that the tetA gene was located on a transferable plasmid of ca. 65 kb in an Escherichia coli EC600 transconjugant. Our results provide direct in vivo evidence that evolution in the tetA gene can lead to tigecycline treatment failure in CRKP clinical strains that carry tetA. Moreover, the transfer capacity of tigecycline resistance mediated by mutated tetA is a threat.
The Three-Month Effects of a Ketogenic Diet on Body Composition, Blood Parameters, and Performance Metrics in CrossFit Trainees: A Pilot Study

Adopting low carbohydrate, ketogenic diets remains a controversial issue for individuals who resistance train given that this form of dieting has been speculated to reduce skeletal muscle glycogen levels and stifle muscle anabolism. We sought to characterize the effects of a 12-week ketogenic diet (KD) on body composition, metabolic, and performance parameters in participants who trained recreationally at a local CrossFit facility. Twelve participants (nine males and three females, 31 ± 2 years of age, 80.3 ± 5.1 kg body mass, 22.9 ± 2.3% body fat, 1.37 back squat: body mass ratio) were divided into a control group (CTL; n = 5) and a KD group (n = 7). KD participants were given dietary guidelines to follow over 12 weeks while CTL participants were instructed to continue their normal diet throughout the study, and all participants continued their CrossFit training routine for 12 weeks. Pre, 2.5-week, and 12-week anaerobic performance tests were conducted, and pre- and 12-week tests were performed for body composition using dual X-ray absorptiometry (DXA) and ultrasound, resting energy expenditure (REE), blood-serum health markers, and aerobic capacity. Additionally, blood beta hydroxybutyrate (BHB) levels were measured weekly. Blood BHB levels were 2.8- to 9.5-fold higher in KD versus CTL throughout confirming a state of nutritional ketosis. DXA fat mass decreased by 12.4% in KD (p = 0.053). DXA total lean body mass changes were not different between groups, although DXA dual-leg lean mass decreased in the KD group by 1.4% (p = 0.068), and vastus lateralis thickness values decreased in the KD group by ~8% (p = 0.065). Changes in fasting glucose, HDL cholesterol, and triglycerides were similar between groups, although LDL cholesterol increased ~35% in KD (p = 0.048). Between-group changes in REE, one-repetition maximum (1-RM) back squat, 400 m run times, and VO2peak were similar between groups. While our n-sizes were limited, these preliminary data suggest that adopting a ketogenic diet causes marked reductions in whole-body adiposity while not impacting performance measures in recreationally-trained CrossFit trainees. Whether decrements in dual-leg muscle mass and vastus lateralis thickness in KD participants were due to fluid shifts remain unresolved, and increased LDL-C in these individuals warrants further investigation.
Effect of Lures and Trap Placement on Sand Fly and Mosquito Traps

Abstract : Catches of mosquitoes and sand flies in CO2 traps baited with three different lures and an unbaited control were compared. The lures examined were carbon dioxide, carbon dioxide plus 1-octen-3-ol, and carbon dioxide plus human hair in ethanol. Studies using a 4 x 4 Latin square design, with 3 sets of 4 consecutive trap nights, were conducted between August 6 and September 10, 2007. The study site was the Bahrif Village, Aswan, Egypt. This location had high percentage of Phlebotomus papatasi in sand fly populations, and the low incidence of human cases of leishmaniasis. There were 2,152 sand flies caught over the 12 total nights (48 trap-nights) of this study. Mean numbers of sand flies captured in traps baited with any lure were significantly greater than sand those caught in the unbaited control trap. The mean numbers of sand flies trapped using each lure did not differ significantly.
Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease

Touring the kidney, cell by cell Our kidneys play a critical role in keeping us healthy, a fact of which we are reminded several times each day. This organ's cellular complexity has hindered progress in understanding the mechanisms underlying chronic kidney disease, which affects 10% of the world's population. Using single-cell transcriptional profiling, Park et al. produced a comprehensive cell atlas of the healthy mouse kidney (see the Perspective by Humphreys). An unexpected cell type in the collecting duct appears to be a transitional state between two known cell types. The transition from one cell type to the other is regulated by the Notch signaling pathway and is associated with metabolic acidosis. The authors also find that genetically distinct kidney diseases with common clinical features share common cellular origins. Science, this issue p. 758; see also p. 709 A single-cell atlas of the mouse kidney reveals an unexpected cell type that likely contributes to kidney disease. Our understanding of kidney disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ’s multiple homeostatic functions. To help fill this knowledge gap, we characterized 57,979 cells from healthy mouse kidneys by using unbiased single-cell RNA sequencing. On the basis of gene expression patterns, we infer that inherited kidney diseases that arise from distinct genetic mutations but share the same phenotypic manifestation originate from the same differentiated cell type. We also found that the collecting duct in kidneys of adult mice generates a spectrum of cell types through a newly identified transitional cell. Computational cell trajectory analysis and in vivo lineage tracing revealed that intercalated cells and principal cells undergo transitions mediated by the Notch signaling pathway. In mouse and human kidney disease, these transitions were shifted toward a principal cell fate and were associated with metabolic acidosis.
Non-adherence to inhaled corticosteroids and the risk of asthma exacerbations in children

Background Non-adherence to inhaled corticosteroids (ICSs) is a major risk factor for poor asthma control in children. However, little is known about the effect of adherence to ICS on the incidence of asthma exacerbations. The objective of this study was to examine the effect of poor adherence to ICS on the risk of exacerbations in children with asthma. Methods In this nested case–control study using data from the Dutch PHARMO Record Linkage System, children aged 5–12 years who had an asthma exacerbation needing oral corticosteroids or hospital admission were matched to patients without exacerbations. Refill adherence was calculated as medication possession ratio from ICS-dispensing records. Data were analyzed using a multivariable multiplicative intensity regression model. Results A total of 646 children were included, of whom 36 had one or more asthma exacerbations. The medication possession ratio was 67.9% (standard deviation [SD] 30.2%) in children with an exacerbation versus 54.2% (SD 35.6%) in the control group. In children using long-acting beta-agonist, good adherence to ICS was associated with a higher risk of asthma exacerbations: relative risk 4.34 (95% confidence interval: 1.20–15.64). Conclusion In children with persistent asthma needing long-acting beta-agonist, good adherence to ICS was associated with an increased risk of asthma exacerbations. Possible explanations include better motivation for adherence to ICS in children with more severe asthma, and reduced susceptibility to the consequences of non-adherence to ICS due to overprescription of ICS to children who are in clinical remission. Further study into the background of the complex interaction between asthma and medication adherence is needed.
Inductive power transfer in e-textile applications: Reducing the effects of coil misalignment

Wireless power transfer (WPT) is an attractive approach for recharging wearable technologies and therefore textile implementations are of interest. Such textile WPT systems are inherently flexible and prone to misalignments of the inductively coupled coils which affects performance. This paper investigates two methods to reduce the effect of coil misalignment in inductive WPT in e-textile applications: a single large transmitter coil and a switched transmitter coil array. Transmission efficiency and maximum received power are determined for both methods, and compared against the baseline system that uses a single small transmitter coil. All coils used in this study were fabricated using automated stitching of PTFE insulated flexible wire onto a polyester/cotton textile. This fabrication method allows coils to be sewn directly to existing garments.
Radiation Induced Corrosion of Nuclear Fuel and Materials

In some cases, a corrosion system may be exposed to radiation field. Most usually, it occurs as a part of atmospheric corrosion, when materials are, besides other factors, exposed also to visible and ultraviolet radiation. Technical significance of corrosion caused by such types of radiation is rather small. On the other hand, metallic materials may be exposed to high energy ionizing radiation (IR), emitted e.g. during operation of nuclear reactors, or during storage/processing of irradiated nuclear fuel. Contrary to nonionizing radiation, IR significantly affects properties of corrosion system and reactions which proceed inside the system. Therefore, three main areas of research of radiation induced corrosion exist:
ATF3 Regulates the Expression of AChE During Stress

Acetylcholinesterase (AChE) expresses in non-cholinergic cells, but its role(s) there remain unknown. We have previously attributed a pro-apoptotic role for AChE in stressed retinal photoreceptors, though by unknown mechanism. Here, we examined its promoter only to find that it includes a binding sequence for the activating transcription factor 3 (ATF3); a prototypical mediator of apoptosis. This suggests that expression of AChE could be regulated by ATF3 in the retina. Indeed, ATF3 binds the AChE-promoter to down-regulate its expressions in vitro. Strikingly, retinas of “blinded” mice display hallmarks of apoptosis, almost exclusively in the outer nuclear layer (ONL); coinciding with elevated levels of AChE and absence of ATF3. A mirror image is observed in the inner nuclear layer (INL), namely prominent levels of ATF3 and lack of AChE as well as lack of apoptosis. We conclude that segregated patterns of expressions of ATF3 reflect its ability to repress apoptosis in different layers of the retina—a novel mechanism behind apoptosis.
Reassessing Free-Testosterone Calculation by Liquid Chromatography–Tandem Mass Spectrometry Direct Equilibrium Dialysis

Context Assessment of free testosterone (FT) might help evaluate androgen status in patients with borderline total testosterone (T) and/or altered sex hormone-binding globulin (SHBG) levels. However, the validity of different methods to measure FT is debatable. Methods Serum from 183 women and 146 men was analyzed using equilibrium dialysis (ED), with FT directly measured by liquid chromatography-tandem mass spectrometry. FT calculation was re-evaluated for the mass action law-based equation according to Vermeulen (cFT-V), empirical equations according to Ly (cFT-L), and a proposed calculation based on a multistep, dynamic, allosteric model according to Zakharov (cFT-Z). Results FT level analyzed by ED [median,13 pmol/L (1.2% of T) in women; 248 pmol/L (1.5% of T) in men] was strongly inversely correlated to SHBG level, significantly to albumin level in women, and only weakly to SHBG level in men. The median [percentile (p) range, 2.5 to 97.5] ratios of calculated FT (cFT) over ED-FT (from European Male Aging Study samples) were 1.19 (0.9 to 1.47), 1.00 (0.69 to 1.42), and 2.05 (1.26 to 3.26) for cFT-V, cFT-L, and cFT-Z, respectively. The ratio for cFT-V was not significantly affected by SHBG, T, or albumin levels (ρ range, 0.17 to -0.01); ratios for cFT-L and cFT-Z were affected (P < 0.05 and P < 0.001, respectively) and strongly correlated with SHBG levels (ρ = 0.72 and 0.75, respectively). Rank correlations between cFT% and ED-FT% (for men) were 0.62, 0.74, and 0.89 for cFT-Z, cFT-L, and cFT-V, respectively. Conclusion FT results by direct ED confirm prior FT data from indirect ED and ultrafiltration methodologies. Calculations have inherent limitations, with clinically important differences among evaluated equations: cFT-V, although overestimating FT level, appears the most robust approximation, largely independent of SHBG, albumin, and T levels.
Design with constructal theory

Constructal theory is the view that the generation of “designedness” in nature is a universal (physics) phenomenon that can be based on principle (the constructal law): “For a finite-size flow system to persist in time (to live) its configuration must change in time so that it provides greater and greater access to its currents”. This principle predicts natural form across the board, from river basins to animal design, engineering and social dynamics. In this introduction to the theory we show examples of vascular designs at large and small scales and multi-objective flow configurations.
Antibiotic Self-Medication among Non-Medical University Students in Punjab, Pakistan: A Cross-Sectional Survey

Background: Antibiotic resistance is a global threat. Scarce knowledge about safe and appropriate antibiotic use is coupled with frequent self-administration, e.g., in China. This repeated self-medication poses potential risk in terms of antibiotic resistance. Low-resource countries are facing an elevated burden of antibiotic self-medication as compared to developed ones. Thus, this study focused on evaluating the pervasiveness of antibiotic self-medication in 3 universities of Southern Punjab, Pakistan. Methods: We conducted a descriptive cross-sectional survey in three government sector universities of Southern Punjab, Pakistan. The study was carried out with self-administered paper-based questionnaires. Data was analyzed using SPSS version 18.0 (IBM, Chicago, IL, USA). Results: Seven hundred twenty-seven students out of 750 (response rate 97%) with a mean age ± SD of 23.0 ± 3.4 years agreed to participate in the study. The proportion of females was slightly greater (52%) compared with males (48%), and almost one-third of the respondents (36%) were in their 2nd year of university. Out of the total, 58.3% practiced self-medication in the preceding six months, and 326 (45%) confirmed the use of antibiotics. Metronidazole was the most frequently self-medicated antibiotic (48%). Out of the total, 72% demonstrated awareness regarding the side effects of antibiotics. Diarrhea was the well-known adverse effect (38%). Forty-three percent affirmed having antibiotic resistance knowledge, and 30% knew that the irregular use of antibiotics would lead to increased antibiotic resistance. Conclusion: Despite having ample awareness of the adverse antibiotic reactions, self-medication among the university students was high and antibiotic resistance was a fairly unknown term.
Infection of Female Primary Lower Genital Tract Epithelial Cells after Natural Pseudotyping of HIV-1: Possible Implications for Sexual Transmission of HIV-1

The global AIDS pandemic continues to expand and in some regions of the world, such as southern Africa, the prevalence of HIV-1 infection exceeds 20%. The devastating spread of the virus in young women in these countries appears disproportional to overall risk of infection. Regions with high prevalence of HIV-1 are often also highly endemic for other pathogenic viruses including HSV, CMV and HTLV. We propose that acquisition by HIV-1 of the envelope glycoproteins of other viruses, in a process we call “natural pseudotyping,” expands the cellular tropism of HIV-1, enabling it to infect female genital epithelial cells directly and thereby dramatically increasing risk of infection during sexual intercourse. In this proof-of-concept study, we demonstrate that when HIV-1 co-infects T cells along with the gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV), progeny HIV-1 particles are produced capable of infecting primary vaginal, ectocervical and endocervical epithelial cells. These cell types are normally resistant to HIV-1 infection. Infection of primary genital cells was neutralized by antisera against the XMRV glycoprotein, confirming that infection was mediated by the XMRV glycoprotein acquired through pseudotyping of HIV. Inhibition by AZT showed that active replication of HIV-1 occurred in these cells and ruled out non-specific endocytic uptake of the virus. These results demonstrate that natural pseudotyping can expand the tropism of HIV-1 to include genital epithelial cells and have potential implications for sexual transmission of the virus.
Individual Differences Influencing Immediate Effects of Internal and External Focus Instructions on Children’s Motor Performance

ABSTRACT Purpose: A large pool of evidence supports the beneficial effect of an external focus of attention on motor skill performance in adults. In children, this effect has been studied less and results are inconclusive. Importantly, individual differences are often not taken into account. We investigated the role of working memory, conscious motor control, and task-specific focus preferences on performance with an internal and external focus of attention in children. Methods: Twenty-five children practiced a golf putting task in both an internal focus condition and external focus condition. Performance was defined as the average distance toward the hole in 3 blocks of 10 trials. Task-specific focus preference was determined by asking how much effort it took to apply the instruction in each condition. In addition, working memory capacity and conscious motor control were assessed. Results: Children improved performance in both the internal focus condition and external focus condition (ŋp2 = .47), with no difference between conditions (ŋp2 = .01). Task-specific focus preference was the only factor moderately related to the difference between performance with an internal focus and performance with an external focus (r = .56), indicating better performance for the preferred instruction in Block 3. Conclusion: Children can benefit from instruction with both an internal and external focus of attention to improve short-term motor performance. Individual, task-specific focus preference influenced the effect of the instructions, with children performing better with their preferred focus. The results highlight that individual differences are a key factor in the effectiveness in children’s motor performance. The precise mechanisms underpinning this effect warrant further research.
The biodiversity cost of carbon sequestration in tropical savanna

Forest expansion into Brazilian savanna due to fire suppression causes precipitous species loss. Tropical savannas have been increasingly viewed as an opportunity for carbon sequestration through fire suppression and afforestation, but insufficient attention has been given to the consequences for biodiversity. To evaluate the biodiversity costs of increasing carbon sequestration, we quantified changes in ecosystem carbon stocks and the associated changes in communities of plants and ants resulting from fire suppression in savannas of the Brazilian Cerrado, a global biodiversity hotspot. Fire suppression resulted in increased carbon stocks of 1.2 Mg ha−1 year−1 since 1986 but was associated with acute species loss. In sites fully encroached by forest, plant species richness declined by 27%, and ant richness declined by 35%. Richness of savanna specialists, the species most at risk of local extinction due to forest encroachment, declined by 67% for plants and 86% for ants. This loss highlights the important role of fire in maintaining biodiversity in tropical savannas, a role that is not reflected in current policies of fire suppression throughout the Brazilian Cerrado. In tropical grasslands and savannas throughout the tropics, carbon mitigation programs that promote forest cover cannot be assumed to provide net benefits for conservation.