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Regions of genomic DNA can become single-stranded in the course of normal replication and transcription as well as during DNA repair. Abnormal repair and replication intermediates can contain large stretches of persistent single-stranded DNA, which is extremely vulnerable to DNA damaging agents and hypermutation. Since such single-stranded DNA spans only a fraction of the genome at a given instance, hypermutation in these regions leads to tightly-spaced mutation clusters. This phenomenon of hypermutation in single-stranded DNA has been documented in several experimental models as well as in cancer genomes. Recently, hypermutated single-stranded RNA viral genomes also have been documented. Moreover, indications of hypermutation in single-stranded DNA may also be found in the human germline. This review will summarize key current knowledge and the recent developments in understanding the diverse mechanisms and sources of ssDNA hypermutation.Since the 1970s, the biological role of vanadium compounds has been discussed as insulin-mimetic or insulin-enhancer agents. The action of vanadium compounds has been investigated to determine how they influence the insulin signaling pathway. Khan and coworkers proposed key proteins for the insulin pathway study, introducing the concept "critical nodes". In this review, we also considered critical kinases and phosphatases that participate in this pathway, which will permit a better comprehension of a critical node, where vanadium can act a) insulin receptor, insulin receptor substrates, and protein tyrosine phosphatases; b) phosphatidylinositol 3'-kinase, 3-phosphoinositide-dependent protein kinase and mammalian target of rapamycin complex, protein kinase B, and phosphatase and tensin homolog; and c) insulin receptor substrates and mitogen-activated protein kinases, each node having specific negative modulators. Additionally, leptin signaling was considered because together with insulin, it modulates glucose and lipid homeostasis. Even in recent literature, the possibility of vanadium acting against metabolic diseases or cancer is confirmed although the mechanisms of action are not well understood because these critical nodes have not been systematically investigated. Through this review, we establish that vanadium compounds mainly act as phosphatase inhibitors and hypothesize on their capacity to affect kinases, which are critical to other hormones that also act on common parts of the insulin pathway.Two new Schiff base ligands (TE and TF) were prepared from conjugation of testosterone with 4-(4-ethylphenyl)-3-thiosemicarbazide and 4-(4-fluorophenyl)-3-thiosemicarbazide, respectively. Their nickel (NE and NF) and zinc (ZE and ZF) complexes were reported. X-ray crystallography revealed a distorted square planar geometry was adopted by NE. The compounds demonstrated excellent selectivity towards the colorectal carcinoma cell line HCT 116 despite their weak preferences towards the prostate cancer cell lines (PC-3 and LNCaP). Against HCT 116, all these compounds were able to arrest cell cycle at G0/G1 phase and induce apoptosis via mitochondria-dependent (TE, NE, and TF) and extrinsic apoptotic pathway (ZE, NF, and ZF). Moreover, only ZE was able to act as topoisomease I poison and halt its enzymatic reactions although all compounds presented excellent affinity towards DNA.Weight discrimination is a well-established risk factor for disordered eating cognitions and behaviors. However, little is known about what may account for this association. Recent research suggests that anticipated weight stigma may explain the relationship between weight discrimination and non-eating disorder related health outcomes; the present study seeks to replicate this premise and extend it to the disordered eating realm. In a non-clinical sample of adults in the United States (N = 297) we test the hypothesis that weight discrimination has an indirect association with eating disorder symptomatology through anticipated stigma. At a single timepoint, participants recruited from the online data collection platform SocialSci completed self-report, online surveys of weight discrimination in day-to-day life, anticipated weight stigma, eating disorder symptoms, and demographic information. As hypothesized, weight discrimination was indirectly associated with greater disordered eating symptoms via its association with anticipated weight stigma. This pattern of results held when controlling for gender, body mass index, and self-perceived weight status. KRAS G12C inhibitor 19 in vitro These findings suggest that anticipated stigma is relevant in the association between weight discrimination and greater disordered eating. This premise deserves additional attention using methodological approaches that can facilitate stronger causal claims. We discuss the potential for this line of research to inform clinical interventions.Background Arthroscopic partial meniscectomy may cause knee osteoarthritis, which may be related to altered joint loading. Previous research has failed to demonstrate that exercise can reduce medial compartment knee loads following meniscectomy but has not considered muscular loading in their estimates. Research question What is the effect of exercise compared to no intervention on peak medial tibiofemoral joint contact force during walking using an electromyogram-driven neuromusculoskeletal model, following medial arthroscopic partial meniscectomy? Methods This is a secondary analysis of a randomized controlled trial (RCT). 41 participants aged between 30-50 years with medial arthroscopic partial meniscectomy within the past 3-12 months, were randomly allocated to either a 12-week, home-based, physiotherapist-guided exercise program or to no exercise (control group). Three-dimensional lower-body motion, ground reaction forces, and surface electromyograms from eight lower-limb muscles were acquired during selexercise intervention in a RCT. While our results suggest that a 12-week exercise program does not alter peak medial knee loads after meniscectomy, within-participant variability suggests individual-specific muscle activation patterns that warrant further investigation.Background The differences in anatomical structure between men and women are widely known. Unfortunately, the influence of gender on the biomechanics of a healthy knee joint during gait is still poorly understood. Research question The aim of the presented study was to determine loads acting in the knee joint during gait, based on the observation of a large group of healthy young adults, in particular to determine the influence of gender on values of forces and moments and their time characteristics during gait cycle. Methods Time-spatial gait parameters and ground reaction force were registered for 86 persons (43 females and 43 males) using a motion capture system and force plates. The numerical simulation with the AnyBody system was used to estimate loadings acting in the knee joint. Differences between women and men were tested using the unpaired Student's t-test with a Bonferroni correction. Results The maximum values of loadings acting in the knee joint were 411.1 %BW (body weight) for resultant force, 390.6 %BW for proximo-distal force, 110.8 %BW for antero-posterior force, 77.0 %BW for medio-lateral force, 2.63 %BWh (body weight times height) for flexion/extension moment, 0.97 %BWh for internal/external rotation moment and 5.7 %BWh for abduction/adduction moment. In general, the normalised forces were greater in the male group, while the normalised external moments acting on the knee were greater in the female group. Local extrema of forces during the stance phase were observed earlier for women. Significance Knowledge about gender differences in loadings acting in the knee joint can be of great importance in the case of detecting the early stages of gait abnormalities and treatment planning.Background Osteoarthritis of the knee is characterized by progressive cartilage deterioration causing pain and function loss. Symptoms develop late with limited disease-modifying opportunities. Osteoarthritis is a major cause of immobility, with a higher prevalence above 60 years. This age-related increase in prevalence is further amplified by the female gender. Imaging and biochemical analyses for detection of osteoarthritis of the knee are expensive and labor-intensive. Continuous movement tracking could aid in detecting onset and/or worsening of symptoms. Methods We used portable technology to investigate kinematic differences in female patients with knee osteoarthritis, weight-matched healthy female volunteers and obese female patients with osteoarthritis of the knee. Knee osteoarthritis was established radiographically and corroborated using magnetic resonance imaging. Findings The total amount, type and level of activity did not differ significantly between groups. The temporal activity pattern during the day was however significantly different with a bimodal signature in healthy volunteers only. Sequence analyses revealed more time to recuperate after dynamic activity in both patient groups. Analysis of walking bouts revealed significant differences in stride interval dynamics, indicative of gait naturalness, only in healthy volunteers. Temporal activity, sequence and walking patterns were independent of body weight. Interpretation We thus provide for the first-time evidence of temporal specific kinematic signatures in amount and quality of movement also in stride interval dynamics between people with and without osteoarthritis of the knee independent of body weight. These findings could allow early and non-intrusive diagnosis of osteoarthritis enabling concordant treatment.Cold-pressed rapeseed meal with high protein content (38.76% protein dry weight basis) was used to prepare rapeseed protein isolates (RPIs) by alkaline extraction (pH 8.0, 9.0, 10.0, 11.0, 12.0 and 13.0) and acid precipitation (pH 3.0, 3.5, 4.0, 4.5, 5.0 and 5.5). The protein with an intact structure and the highest yield (65.08%) was obtained at extraction pH 9.0 and precipitation pH 4.5, accompanied by the lowest D-amino acid content, the lightest colour and the lowest contents of glucosinolates (2.85 mmol/kg), phytic acid (1.05 mg/g) and sinapine (0.68 mg/g). Additionally, water/oil absorption, foaming and emulsifying capacities decreased with decreasing precipitation pH, while the solubility showed the reverse trend. During gastric simulation digestion, the α-polypeptide of cruciferin and napin in the RPIs showed digestive resistance. Overall, pH regulation might be an effective method to isolate high quality RPIs for use in the food processing industry.Wheat is one of the main dietary sources for mycotoxins that can cause adverse health effects in humans. Here we report results of a 3-year survey which compared the effects of flour type (whole-grain vs white), wheat species (common vs spelt), and farming system (organic vs conventional) on mycotoxin concentrations in UK and German wheat flour brands. Wholegrain, conventional and organic flour contained 124, 31 and 9% higher concentrations of T-2/HT-2, DON and ZEA respectively, but concentrations of the three Fusarium mycotoxins assessed were ~10 times lower than the EC-maximum contamination levels (MCL). Thirty one percent of flour samples had Ochratoxin A (OTA) concentrations above the MCL (3 µg/kg), but OTA levels were no affected by wheat species, farming system and flour type. Results suggest that both organic and conventional primary production methods and postharvest quality assurance systems are effective for maintaining Fusarium mycotoxins, but not OTA concentrations, below the MCL.
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