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Our study replicated some well-characterized targets for positive selection in East Asia and sub-Saharan Africa, and proposes new candidates for follow-up in South Asia (SLC39A5) and Africa (SLC39A7). Finally, we identified candidate variants for adaptation in ZTGs that could contribute to different disease susceptibilities and zinc-related human health traits.Myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) are reported in up to 20% patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), where a shared clonal origin is shown in individual case studies. In this study, we performed targeted next generating sequencing on multiple bone marrow (BM), skin or sorted cells from 51 BPDCN patients (68.7 years,14.4-84.7), and detected mutations in BM hematopoietic cells in 65% (30/46) and BPDCN in 100% (27/27), both components showing similar high frequencies of TET2 (60% versus 58%) and ASXL1 (33% versus 40%). Of 24 patients with paired mutation data, 13(54%) had shared mutations, with TET2(77%), ASXL1(37%) and ZRSR2(22%) the most commonly shared, and NRAS the most gained mutation in BPDCN(9/24, 38%). Karyotypic abnormalities were detected in 19/29(66%) BPDCN but only in 1/49 BM hematopoietic cells, providing additional evidence of clonal evolution. BM clonal hematopoiesis (CH) was associated with an older age (p  less then  0.001), being confounding factors in multivariate analysis; whereas less then 10% BM BPDCN infiltrate and stem cell transplant were associated with favorable outcomes. This study is the first to report a high prevalence of BM CH in BPDCN patients beyond an associated diagnosis of MDS/CMML, and demonstrates a frequent clonal relationship in elderly, findings contributing to the understanding of BPDCN clonal origin.Professional societies, guideline writing committees, and other interested parties emphasize the importance of accurate measurement of blood pressure for clinical and public health decisions related to prevention, treatment, and follow-up of high blood pressure. Use of a clinically validated instrument to measure blood pressure is a central component of measurement accuracy and precision. Despite this, most regulatory authorities do not specify validation requirements that manufacturers must meet to sell their blood pressure measurement devices. Likewise, device validity is not a major area of focus for most consumers and healthcare providers, perhaps because they assume it is a pre-requisite for market approval. This has led to a global proliferation of non-validated blood pressure measurement devices, with only a small minority of blood pressure measurement devices having passed internationally accepted validation protocols. The clinical consequences are likely to be significant because non-validated devices are more likely to provide inaccurate estimates of blood pressure compared with validated devices. Even small inaccuracies in blood pressure measurement can result in substantial misdiagnosis and mistreatment of hypertension. There is an urgent need for clinical validation of blood pressure measurement devices prior to marketing them to consumers. There is also need for simplification of the process for consumers and healthcare providers to determine whether a blood pressure measurement device has successfully met an internationally accepted test of validity.Pomegranate breeding to improve the marketability requires the production of large and high quality fruits. Gamma radiation on pomegranate can be used to generate genetic diversity that allows the breeder to screen the mutants for superior quality and quantity. For this purpose, dormant buds on 1-year-old shoots of pomegranate cultivar "Malase Saveh" were subjected to 36 Gy (Gy) of gamma irradiation from a cobalt (60CO) source. Shoot cuttings were taken from the mutated shoots and generate M1V2. The number of 11 mutants were selected from M1V2 plants based on their winter survival and disease resistance. After a period of 3-4 years, leaf and fruit samples were harvested from the M1V5. Results showed that physiological and biochemical parameters of leaves were altered unevenly, some clones showed no alterations from the control, while others revealed considerable differences. Irradiation altered various aspects related to fruit, such as the number and weight of ripe and unripe fruits, number of cracked, sunburn, worm-eaten fruits, and fruit size. In general, mutant clones 5, 8, and 10 had higher fruit sizes and weight of ripe fruits and less number and weight of unripe fruits. The stability of the detected mutants will be evaluated and new commercial field trials using selected materials will be established.In plants, the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8) perceives UV-B and induces UV-B responses. UVR8 absorbs a range of UV-B (260-335 nm). However, the responsiveness of plants to each UV-B wavelength has not been intensively studied so far. Here, we performed transcriptome and metabolome analyses of Arabidopsis using UV light emitting diodes (LEDs) with peak wavelengths of 280 and 310 nm to investigate the differences in the wavelength-specific UV-B responses. Irradiation with both UV-LEDs induced gene expression of the transcription factor ELONGATED HYPOCOTYL 5 (HY5), which has a central role in the UVR8 signaling pathway. However, the overall transcriptomic and metabolic responses to 280 and 310 nm UV-LED irradiation were different. Most of the known UV-B-responsive genes, such as defense-related genes, responded only to 280 nm UV-LED irradiation. Lipids, polyamines and organic acids were the metabolites most affected by 280 nm UV-LED irradiation, whereas the effect of 310 nm UV-LED irradiation on the metabolome was considerably less. Enzymatic genes involved in the phenylpropanoid pathway upstream in anthocyanin biosynthesis were up-regulated only by 280 nm UV-LED irradiation. These results revealed that the responsivenesses of Arabidopsis to 280 and 310 nm UV-B were significantly different, suggesting that UV-B signaling is mediated by more complex pathways than the current model.Humanity is facing an increasing health threat caused by a variety of multidrug resistant bacteria. Within this scenario, Staphylococcus aureus, in particular methicillin resistant S. aureus (MRSA), is responsible for a number of hospital-acquired bacterial infections. The emergence of microbial antibiotic resistance urgently requires the identification of new and innovative strategies to treat antibiotic resistant microorganisms. In this context, structure and function analysis of potential drug targets in metabolic pathways vital for bacteria endurance, such as the vitamin K2 synthesis pathway, becomes interesting. We have solved and refined the crystal structure of the S. aureus DHNA thioesterase (SaDHNA), a key enzyme in the vitamin K2 pathway. The crystallographic structure in combination with small angle X-ray solution scattering data revealed a functional tetramer of SaDHNA. Complementary activity assays of SaDHNA indicated a preference for hydrolysing long acyl chains. Site-directed mutagenesis of SaDHNA confirmed the functional importance of Asp16 and Glu31 for thioesterase activity and substrate binding at the putative active site, respectively. Docking studies were performed and rational designed peptides were synthesized and tested for SaDHNA inhibition activity. The high-resolution structure of SaDHNA and complementary information about substrate binding will support future drug discovery and design investigations to inhibit the vitamin K2 synthesis pathway.Pro-apoptotic BAK and BAX are activated by BH3-only proteins to permeabilise the outer mitochondrial membrane. The antibody 7D10 also activates BAK on mitochondria and its epitope has previously been mapped to BAK residues in the loop connecting helices α1 and α2 of BAK. A crystal structure of the complex between the Fv fragment of 7D10 and the BAK mutant L100A suggests a possible mechanism of activation involving the α1-α2 loop residue M60. M60 mutants of BAK have reduced stability and elevated sensitivity to activation by BID, illustrating that M60, through its contacts with residues in helices α1, α5 and α6, is a linchpin stabilising the inert, monomeric structure of BAK. Our data demonstrate that BAK's α1-α2 loop is not a passive covalent connector between secondary structure elements, but a direct restraint on BAK's activation.Understanding how marine food webs are affected by anthropogenic stressors is an important steppingstone toward the improved management of natural resources. Stable isotope analysis of historical and modern samples spanning a century indicated that the niche width of an exploited fish community increased after the expansion of New Zealand fisheries. Since the 2000s most species increased their reliance on food webs supported by pelagic production, compared to coastal production supported by macroalgae, and shifted to a higher trophic level. Overall changes were coincident with ocean warming, climate oscillations, prey abundance and fishing intensity, but their effects were specific to each fish assemblage analyzed. Etomoxir Data derived from historical samples revealed how anthropogenic stressors can drive long-term shifts in the trophic structure of an exploited fish community.Midpalatal suture was analysed with cone beam computed tomography to identify its maturation with respect to age and maxillary-complex growth in 72 patients 9- to 21-year-old. Maxillary-complex was divided in premaxillary, maxillary, and palatine segment. Interdigitation and ossification of midpalatal suture, its density relative to hard tissues and soft tissues, and midpalatal suture density ratio were measured for each segment. Correlation of each parameter with age and maxillary-complex length was analysed, and classification trees were developed for staging parameters. Midpalatal suture maturation stages (MPSMS, from A to E) were applied to assess relationship with age and maxillary-complex length. Regarding age, ossification increased in maxillary segment of males (rS = 0.39, p = 0.032), while suture density relative to soft tissues increased in maxillary (rS = 0.37, p = 0.042) and palatine segments (rS = 0.41, p = 0.027) of males and in palatine segment of females (rS = 0.32, p = 0.041). In males, suture density relative to soft tissues discriminated two age-stages (p = 0.024), and the same parameter (p = 0.023) paired with ossification (p = 0.027) discriminated two length-stages. MPSMS identified length-differences between stage A and B in females (p = 0.001). Midpalatal-suture ossification and its density relative to soft tissues showed some relationship with age and maxillary-complex length, especially in males. However, challenging staging and limitations in the imaging method may limit clinical applications.Maximum power point tracking (MPPT) is an effective method to improve the power generation efficiency and power supply quality of a proton exchange membrane fuel cell (PEMFC). Due to the inherent nonlinear characteristics of PEMFC, conventional MPPT methods are often difficult to achieve a satisfactory control effect. Considering this, artificial bee colony algorithm combining fuzzy control (ABC-fuzzy) was proposed to construct a MPPT control scheme for PEMFC. The global optimization ability of ABC algorithm was used to approach the maximum power point of PEMFC and solve the problem of falling into local optimization, and fuzzy control was used to eliminate the problems of large overshoot and slow convergence speed of ABC algorithm. The testing results show that compared with perturb & observe algorithm, conductance increment and ABC methods, ABC-fuzzy method can make PEMFC obtain greater output power, faster regulation speed, smaller steady-state error, less oscillation and stronger anti-interference ability.
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