Miracle-dz/UniFAR-FTUs huggingface dataset:
More than just activity control: phosphorylation may control all aspects of a protein's properties

Protein phosphorylation is a major post‐translational modification of proteins. Due to the introduction of a very large, strongly charged group, phosphorylation often has a dramatic effect on the characteristics of the protein, including alterations in activity or interaction properties. In this issue of Molecular Microbiology, Jers et al. have addressed the effect of protein tyrosine phosphorylation in Bacillus subtilis. They demonstrate that tyrosine phosphorylation stimulates the activity of several but not all targets. In addition, the subcellular localization of several proteins was shown to depend on tyrosine phosphorylation that is catalysed by the BY kinase PtkA. This is the first report showing that phosphorylation controls protein localization in bacteria and adds another important function to this post‐translational modification.
Nanopore modifications with lipid bilayer membranes for optical tweezers DNA force measurements

Driving small molecules, such as DNA, electrophoretically through a nanometre-sized pore provides single-molecule sensitivity and analytical properties (e.g. sequencing) without prior molecular amplification and necessity for labeling. Theoretical and experimental investigations indicate that the forces, which contribute to this translocation process, depend on an interplay of ionic screening and hydrodynamics. Therefore, it is of essential importance to study and characterize these threading forces to gain a deeper understanding of the underlying mechanisms. Utilizing optical tweezers, the experimental results presented here have expanded the force measurements in solid-state nanopores to include a surface modification by a lipid bilayer coating. It was demonstrated that the DNA threading forces increased by 80 % compared to an uncoated nanopore of the same size. Thus, these findings led to a more comprehensive theoretical description of polyelectrolyte dynamics in the highly confined environment of a nanopore. In addition, a fundament of preparation techniques was explored and established, to demonstrate that it is possible to produce nanopore-spanning and thus, freestanding lipid bilayer membranes. It was shown that these lipid bilayers were stable for hours and suitable for the incorporation of α-hemolysin (a pore-forming protein). Furthermore, free translocation experiments with DNA-oligomers through this biological pore were conducted successfully. Based on this technological fundament, it will be feasible to conduct optical tweezers threading force measurements on these bio-logical pores, in order to provide prospective influential insights, as well as additional contributions to an unambiguous theoretical model.
Histological Changes Related to Symptomatic Improvement of Spontaneous Keloids Treated with a Low-Dosage Regimen of UVA-1 Phototherapy

Keloids are a difficult-to-treat disease characterized by an imbalance in mechanisms of tissue reparation. We present the case of a middle-aged woman with spontaneous keloids which histologically and clinically improved after UVA-1 phototherapy treatment. There are few reported cases of keloids treated with high doses of UVA-1 phototherapy. We used a low-dosage regimen with a good response in only one cycle, which could diminish the risk of skin cancer development.
Photoelectrocatalytic materials for environmental applications

This feature article summarizes recent research on and development of semiconductor-based photocatalyst materials that are applicable to environmental remediation and/or chemical synthesis purposes. A wide variety of TiO2 particles and/or films have been studied during the past 30 years because they are the most stable and powerful photocatalysts leading to the degradation of various organic pollutants. The photocatalytic performance of other semiconductor materials such as ZnO, SnO2, WO3, Fe2O3 and CdS has also been intensively investigated. A general limitation in the efficiency of any photocatalytic process is the recombination of the photogenerated charge carriers, i.e., of electrons and holes, following bandgap illumination. Considerable efforts have been made to suppress this recombination and hence to enhance the charge carrier separation and the overall efficiency by means of coupling of different semiconductors with desirable matching of their electronic band structures, or incorporation of noble metal nanoclusters onto the surface of semiconductor photocatalyst particles. Modification of the physicochemical properties, such as particle size, surface area, porosity and/or crystallinity of the semiconductor materials, and optimization of the experimental conditions, such as pH, illumination conditions and/or catalyst loading, during photocatalytic reactions have also been carefully addressed to achieve high reaction rates or yields. To utilize solar energy more efficiently, i.e., to extend the optical absorption of the mostly UV-sensitive photocatalysts into the visible light range, numerous research groups have contributed to the development of novel visible light active photocatalysts. With the application of semiconductors with narrower bandgaps such as CdS, Fe2O3 and WO3 being straightforward choices, doping of wide bandgap semiconductors like TiO2 has been the most popular technique to enhance the catalysts' optical absorption abilities. Research on mixed-oxide-based semiconductor photocatalysts with deliberately modulated band structures has also attracted tremendous attention in the past decade, concentrating on, for example, the generation of H2 and/or O2 from H2O splitting, and the degradation of organic pollutants under visible light irradiation. Both theoretical calculations and experimental results have convincingly shown that the developed materials can serve as highly efficient photocatalysts that are both environmentally and economically significant.
A structural model of anti‐anti‐σ inhibition by a two‐component receiver domain: the PhyR stress response regulator

PhyR is a hybrid stress regulator conserved in α‐proteobacteria that contains an N‐terminal σ‐like (SL) domain and a C‐terminal receiver domain. Phosphorylation of the receiver domain is known to promote binding of the SL domain to an anti‐σ factor. PhyR thus functions as an anti‐anti‐σ factor in its phosphorylated state. We present genetic evidence that Caulobacter crescentus PhyR is a phosphorylation‐dependent stress regulator that functions in the same pathway as σT and its anti‐σ factor, NepR. Additionally, we report the X‐ray crystal structure of PhyR at 1.25 Å resolution, which provides insight into the mechanism of anti‐anti‐σ regulation. Direct intramolecular contact between the PhyR receiver and SL domains spans regions σ2 and σ4, likely serving to stabilize the SL domain in a closed conformation. The molecular surface of the receiver domain contacting the SL domain is the structural equivalent of α4‐β5‐α5, which is known to undergo dynamic conformational change upon phosphorylation in a diverse range of receiver proteins. We propose a structural model of PhyR regulation in which receiver phosphorylation destabilizes the intramolecular interaction between SL and receiver domains, thereby permitting regions σ2 and σ4 in the SL domain to open about a flexible connector loop and bind anti‐σ factor.
Classification of Fatigue Phases in Healthy and Diabetic Adults Using Wearable Sensor

Fatigue is defined as “a loss of force-generating capacity” in a muscle that can intensify tremor. Tremor quantification can facilitate early detection of fatigue onset so that preventative or corrective controls can be taken to minimize work-related injuries and improve the performance of tasks that require high-levels of accuracy. We focused on developing a system that recognizes and classifies voluntary effort and detects phases of fatigue. The experiment was designed to extract and evaluate hand-tremor data during the performance of both rest and effort tasks. The data were collected from the wrist and finger of the participant’s dominant hand. To investigate tremor, time, frequency domain features were extracted from the accelerometer signal for segments of 45 and 90 samples/window. Analysis using advanced signal processing and machine-learning techniques such as decision tree, k-nearest neighbor, support vector machine, and ensemble classifiers were applied to discover models to classify rest and effort tasks and the phases of fatigue. Evaluation of the classifier’s performance was assessed based on various metrics using 5-fold cross-validation. The recognition of rest and effort tasks using an ensemble classifier based on the random subspace and window length of 45 samples was deemed to be the most accurate (96.1%). The highest accuracy (~98%) that distinguished between early and late fatigue phases was achieved using the same classifier and window length.
Training Multilayer Perceptron with Genetic Algorithms and Particle Swarm Optimization for Modeling Stock Price Index Prediction

Predicting stock market (SM) trends is an issue of great interest among researchers, investors and traders since the successful prediction of SMs’ direction may promise various benefits. Because of the fairly nonlinear nature of the historical data, accurate estimation of the SM direction is a rather challenging issue. The aim of this study is to present a novel machine learning (ML) model to forecast the movement of the Borsa Istanbul (BIST) 100 index. Modeling was performed by multilayer perceptron–genetic algorithms (MLP–GA) and multilayer perceptron–particle swarm optimization (MLP–PSO) in two scenarios considering Tanh (x) and the default Gaussian function as the output function. The historical financial time series data utilized in this research is from 1996 to 2020, consisting of nine technical indicators. Results are assessed using Root Mean Square Error (RMSE), Mean Absolute Percentage Error (MAPE) and correlation coefficient values to compare the accuracy and performance of the developed models. Based on the results, the involvement of the Tanh (x) as the output function, improved the accuracy of models compared with the default Gaussian function, significantly. MLP–PSO with population size 125, followed by MLP–GA with population size 50, provided higher accuracy for testing, reporting RMSE of 0.732583 and 0.733063, MAPE of 28.16%, 29.09% and correlation coefficient of 0.694 and 0.695, respectively. According to the results, using the hybrid ML method could successfully improve the prediction accuracy.
Nanopore sequencing sheds a light on the FLT3 gene mutations complexity in acute promyelocytic leukemia

Abstract Acute promyelocytic leukemia (APL) patients carry in 27% of cases an activating mutation of the fms-like tyrosine kinase-3 (FLT3) gene: internal tandem duplication (ITD) or tyrosine kinase domain (TKD) point mutation. The simultaneous presence of both types of mutations, so-called FLT3 dual mutations, has been reported in 2% of APL, but this circumstance has never been studied. We studied a cohort of 74 APL cases, performing an in-depth analysis of three FLT3 dual mutant cases. Nanopore sequencing (NS) allowed us to characterize their complex mutational profile, showing the occurrence of multiple activating FLT3 mutations on different alleles in the leukemic promyelocytes and suggesting a cumulative impact of these events on the constitutive activation of the FLT3 pathway in APL cells. NS approach not only sheds light on the FLT3 mutational complexity in APL, but may also be useful to better clarify the FLT3 mutations landscape in acute myeloid leukemia.
Five-Year Outcomes in Bariatric Surgery Patients

Background and objectives: Obesity presents as a multifactorial, pandemic disease that arises as a consequence of unequal energy intake and energy consumption. Obesity adversely affects the quality of life, leading not only to disability, but also to various other disorders. Bariatric surgery is the most effective method for achieving significant and sustained weight loss in individuals with extreme obesity. The aim of this study was to examine how well surgically induced weight loss is maintained after five years of follow-up and its effects on cardiovascular risk factors and outcome. Materials and Methods: This is a retrospective cross-sectional study of 66 patients with morbid obesity, with body mass index (BMI) ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 and obesity-related health conditions, aged 20 to 61 years, mostly women (77.3%) who underwent laparoscopic Roux-en-Y gastric bypass surgery. Results: Average follow-up was 6.42 years (95% CI 6.30–6.54 years) after surgery, with survival rate of 97% in operated individuals. There was a statistically significant reduction of weight and body mass index 6 months and 5 years after surgery in comparison to the initial values (p < 0.001). Of 62 patients who presented weight loss at the end of the follow-up period, 38 were able to maintain the amount of weight loss that was attained 6 months after surgery, while 24 patients regained weight compared to their postoperative weight at 6 months. Two patients reported no weight loss after treatment. Significant weight reduction was associated with better control of diabetes and increased self-reported physical activity at 6 months and 5 years after surgery, as well as with a reduction of the use of anti-diabetic and anti-hypertensive medications. Conclusions: Our research demonstrates a positive long-term impact of bariatric surgery on patients’ health conditions, significant and sustained weight loss, and decrease in BMI, which were associated with a reduction of co-morbidities and risk factors for cardiovascular diseases.
Medium‐ and long‐term clinical benefits of periodontal regenerative/reconstructive procedures in intrabony defects: Systematic review and network meta‐analysis of randomized controlled clinical studies

Abstract Background Systematic reviews have established the short‐term improvements of periodontal regenerative/reconstructive procedures compared to conventional surgical treatment in intrabony defects. However, a hierarchy of periodontal regenerative/reconstructive procedures regarding the medium‐ to long‐term results of treatment does not exist. Aim To systematically assess the literature to answer the focused question “In periodontitis patients with intrabony defects, what are the medium‐ and long‐term benefits of periodontal regenerative/reconstructive procedures compared with open flap debridement (OFD), in terms of clinical and/or radiographic outcome parameters and tooth retention? ”. Material & Methods Randomized controlled clinical trials (RCTs), reporting on clinical and/or radiographic outcome parameters of periodontal regenerative/reconstructive procedures ≥3 years post‐operatively, were systematically assessed. Clinical [residual probing pocket depth (PD) and clinical attachment level (CAL) gain, tooth loss] and radiographic [residual defect depth (RDD), bone gain (RBL)] outcome parameters were assessed. Descriptive statistics were calculated, and Bayesian random‐effects network meta‐analyses (NMA) were performed where possible. Results Thirty RCTs, presenting data 3 to 20 years after treatment with grafting, GTR, EMD, as monotherapies, combinations thereof, and/or adjunctive use of blood‐derived growth factor constructs or with OFD only, were included. NMA based on 21 RCTs showed that OFD was clearly the least efficacious treatment; regenerative/reconstructive treatments resulted in significantly shallower residual PD in 4 out 8 comparisons [range of mean differences (MD): −2.37 to −0.60 mm] and larger CAL gain in 6 out 8 comparisons (range of MD: 1.26 to 2.66 mm), and combination approaches appeared as the most efficacious. Tooth loss after regenerative/reconstructive treatment was less frequent (0.4%) compared to OFD (2.8%), but the evidence was sparse. There were only sparse radiographic data not allowing any relevant comparisons. Conclusion Periodontal regenerative/reconstructive therapy in intrabony defects results, in general, in shallower residual PD and larger CAL gain compared with OFD, translating in high rates of tooth survival, on a medium (3–5 years) to long‐term basis (5–20 years). Combination approaches appear, in general, more efficacious compared to monotherapy in terms of shallower residual PD and larger CAL gain. A clear hierarchy could, however, not be established due to limited evidence.
The diagnostic value of golgi protien-73 and DICKKOPF-1 in hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Early detection of HCC is essential for improved prognosis and long-term survival. Golgi protein-73 (GP73) and Dickkopf-1 (DKK1), can be used as noninvasive biomarkers for early diagnosis of HCC. Aim of the work: measure and assess the clinical utility of Golgi protein-73 and Dickkopf-1 as noninvasive biomarkers for early diagnosis of HCC. This study included 60 patients: 30 patients with HCC, 30 patients with cirrhosis together with 30 healthy controls. There was a highly significant difference in GP73 and DKK1 between all the studied groups. There was a highly significant positive correlation between GP73 and DKK1 and a significant negative correlation between (GP73 and albumin) and (DKK1 and ALT) in group I. GP73, DKK-1 correlated with the number, overall size, and lymph node metastasis. GP73 and DKK1 can serve as diagnostic serologic markers for early HCC as they had high sensitivity and specificity, correlated with the aggressiveness of the tumor superior to AFP. The combined use of GP73, DKK-1, and AFP increased the sensitivity and specificity for the diagnosis of HCC than each one alone.
Non‐Equilibrium Large‐Scale Membrane Transformations Driven by MinDE Biochemical Reaction Cycles

Abstract The MinDE proteins from E. coli have received great attention as a paradigmatic biological pattern‐forming system. Recently, it has surfaced that these proteins do not only generate oscillating concentration gradients driven by ATP hydrolysis, but that they can reversibly deform giant vesicles. In order to explore the potential of Min proteins to actually perform mechanical work, we introduce a new model membrane system, flat vesicle stacks on top of a supported lipid bilayer. MinDE oscillations can repeatedly deform these flat vesicles into tubules and promote progressive membrane spreading through membrane adhesion. Dependent on membrane and buffer compositions, Min oscillations further induce robust bud formation. Altogether, we demonstrate that under specific conditions, MinDE self‐organization can result in work performed on biomimetic systems and achieve a straightforward mechanochemical coupling between the MinDE biochemical reaction cycle and membrane transformation.
Fetal germ cell development in the rat testis and the impact of di (n-Butyl) phthalate exposure

During gonad development and fetal life, the germ cells (GC) undergo a range of different developmental processes necessary for correct postnatal gametogenesis and the production of the next generation. If these fetal events are disrupted by genetic or environmental factors, there could be severe consequences that may not present until adulthood. This is of particular importance in relation to human testicular GC tumours (TGCT), the most common cancer of young men, as TGCT is thought to arise from fetal GCs that have failed to differentiate normally during development and thus persist into adulthood, eventually becoming tumourigenic. TGCT is one of several related disorders of male reproductive health thought to comprise a Testicular Dysgenesis Syndrome (TDS), in which faulty testis development in fetal life may predispose to the development of cryptorchidism, hypospadias, reduced sperm count and TGCT. Currently there is no accepted animal model for TGCT, but some insight into human TDS has been gained through the use of a rat model using in utero Di (n-Butyl) Phthalate (DBP) exposure to induce cryptorchidism, hypospadias, low sperm count and reduced fertility (but not TGCT). However, a previous study suggested that DBP exposure can disrupt GC differentiation, resulting in significantly reduced GC number prior to birth and postnatal consequences. This thesis has been directed at investigating the normal process of GC development in the fetal rat and how this is altered by DBP exposure; such understanding may give insights into the origins of human TGCT by showing how and when disruption of normal fetal GC differentiation can occur. The first objective was to characterise GC development in both the rat testis and ovary to understand the normal events that occur between embryonic day (e)13.5 and e21.5, as most data in the literature is based on the mouse. Analysis by immunohistochemical, stereological and mRNA expression indentified that during this time period, a GC will undergo a dynamic sequence of changes involving migration, proliferation followed by differentiation (manifested by loss of specific
Effect of water immersion restraint stress on gastric mucosa in rats with removed salivary glands.

OBJECTIVE To explore the effect of salivary gland removal on water immersion restraint stress (WIRS)-induced gastric mucosal injury (GMI) in rats. METHODS Eighty male WISTAR rats were allocated into sham operation (sham) group, sham + WIRS group, salivary gland removal group, and salivary gland removal + WIRS group, with 20 rats in each group. In the sham group, skin and subcutaneous tissues were cut to expose glands. The rats in other three groups were subjected to a total salivary gland resection, and all their submandibular glands and sublingual glands and part of the parotid glands were removed, and the parotid duct was ligated. Afterwards, rats were exposed to WIRS for one and a half months and sacrificed. The severity of GMI was scored, and any histologic and ultrastructural changes were monitored. RESULTS There were differences in the Guth index (GMI evaluation) scores among the four groups (P=0.000), which were higher in salivary gland removal + WIRS group than those in the other three groups (all P<0.001), and were higher in the sham + WIRS group and salivary gland removal group than those in the sham group (all P=0.000). Compared with other groups, the gastric mucosa was severely injured in the salivary gland removal + WIRS group, with obvious congestion, edema, inflammatory cell infiltrate, mucosal shedding, bleeding ulcers, enlarged intercellular spaces, and damaged organelles. CONCLUSION Salivary gland removal aggravates WIRS-induced GMI to a certain extent.
The Emerging Role of Microbiota and Microbiome in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumors due to the absence of biomarkers for early-stage detection and poor response to therapy. Since mounting evidence supports the role of microbiota composition in tumorigenesis and cancer treatment, the link between microbiome and PDAC has been described. In this review, we summarize the current knowledge regarding the impact of the gut and oral microbiome on the risk of PDAC development. Microenvironment-driven therapy and immune system interactions are also discussed. More importantly, we provide an overview of the clinical trials evaluating the microbiota role in the risk, prognosis, and treatment of patients suffering from PDAC and solid tumors. According to the research findings, immune tolerance might result from the microbiota-derived remodeling of pancreatic tumor microenvironment. Thus, microbiome profiling and targeting represent the potential trend to enhance antitumor immunity and improve the efficacy of PDAC treatment.