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Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of genome-wide association studies (GWAS) of blood NfL levels from eleven cohorts of European ancestry, we identify two genome-wide significant loci at 16p12 (UMOD) and 17q24 (SLC39A11). We observe association of three loci at 1q43 (FMN2), 12q14, and 12q21 with blood NfL levels in the meta-analysis of African-American ancestry. In the trans-ethnic meta-analysis, we identify three additional genome-wide significant loci at 1p32 (FGGY), 6q14 (TBX18), and 4q21. In the post-GWAS analyses, we observe the association of higher NfL polygenic risk score with increased plasma levels of total-tau, Aβ-40, Aβ-42, and higher incidence of Alzheimer's disease in the Rotterdam Study. Furthermore, Mendelian randomization analysis results suggest that a lower kidney function could cause higher blood NfL levels. This study uncovers multiple genetic loci of blood NfL levels, highlighting the genes related to molecular mechanism of neurodegeneration. An ancestry-specific and trans-ethnic meta-analysis of Genome-wide Association Study of blood NfL levels identified multiple loci related to neurodegeneration and potential causal association between reduced kidney function and higher blood NfL levels. [ABSTRACT FROM AUTHOR]

Let A be a noncommutative prime ring equipped with an involution '∗', and let Q m s (A) be the maximal symmetric ring of quotients of A . Consider the additive maps H and T : A → Q m s (A) . We prove the following under some inevitable torsion restrictions. (a) If m and n are fixed positive integers such that (m + n) T (a 2) = m T (a) a * + n a T (a) for all a ∈ A and (m + n) H (a 2) = m H (a) a * + n a T (a) for all a ∈ A , then H = 0 . (b) If T (a b a) = a T (b) a * for all a , b ∈ A , then T = 0 . Furthermore, we characterize Jordan left τ-centralizers in semiprime rings admitting an anti-automorphism τ. As applications, we find the structure of generalized Jordan ∗-derivations in prime rings and generalize as well as improve all the results of A. Abbasi, C. Abdioglu, S. Ali, M. R. Mozumder (2022). [ABSTRACT FROM AUTHOR]

Let A be a noncommutative prime ring equipped with an involution ' ∗ '. Let Q ms (A) be the maximal symmetric ring of quotients of A and C be the extended centroid of A . The objective of this manuscript is to characterize the additive map T : A → Q ms (A) satisfying any one of the following conditions. (i) T (a 2) = a T (a) + η T (a) a ∗ for all a ∈ A , where η ∈ C and η ∉ { 0 , 1 } . (ii) T (a) (a ∗) n + a n T (a) = 0 for all a ∈ A , where n is a fixed positive integer. We also study some results concerning generalized derivations in prime rings with involution. Moreover, all the study in the manuscript is carried out in the light of the theory of functional identities. [ABSTRACT FROM AUTHOR]

MYB transcription factors are encoded by a large family of highly conserved genes from plants to vertebrates. There are three members of the MYB gene family in human, namely, MYB, MYBL1, and MYBL2 that encode MYB/c-MYB, MYBL1/A-MYB, and MYBL2/B-MYB, respectively. MYB was the first member to be identified as a cellular homolog of the v-myb oncogene carried by the avian myeloblastosis virus (AMV) causing leukemia in chickens. Under the normal scenario, MYB is predominantly expressed in hematopoietic tissues, colonic crypts, and neural stem cells and plays a role in maintaining the undifferentiated state of the cells. Over the years, aberrant expression of MYB genes has been reported in several malignancies and recent years have witnessed tremendous progress in understanding of their roles in processes associated with cancer development. Here, we review various MYB alterations reported in cancer along with the roles of MYB family proteins in tumor cell plasticity, therapy resistance, and other hallmarks of cancer. We also discuss studies that provide mechanistic insights into the oncogenic functions of MYB transcription factors to identify potential therapeutic vulnerabilities. [ABSTRACT FROM AUTHOR]

In this study, a reinforced concrete dome biogas plant processing buffalo dung was functioned to investigate the seasonal variations in biogas production, biogas composition, and loss of volatile solid and methane potential of digestate slurry. These analyses were undertaken from January to May 2019. The biogas quality was assessed using gas chromatography and biogas production was measured through the G4 VuGas diaphragm gas meter while methane potential was examined on biochemical methane potential (BMP) assays under mesophilic conditions. In January, when the average digester temperature was 26.1 °C, the minimum biogas production was 0.23 ± 0.004m3/kg VSadded with 67% CH4 and 32.9% CO2. In May, the average digester temperature rose to 36.1 °C and the maximum biogas yield obtained increased to 0.384 ± 0.006m3/kg VSadded, comprising 71% CH4 and 28.8% CO2. In the cold season during January, the percentage losses of biogas production were recorded to be 41% because of lower slurry temperature and accumulation of fatty acids. The average slurry temperatures within the digester during the cold season were 21.3 ∘ C at 6 A.M. and 21.9 ∘ C at 3 P.M., increasing to 36 ∘ C at 6 A.M. and 36.2 ∘ C at 3 P.M. for the warm season. In addition, the methane potential of 115NmL/g VSloss was observed from the digestate slurry through BMP test. The concrete dome biogas plant is favorable for its low cost and was shown to produce adequate amount of biogas to fulfill the domestic requirements during both warm and cold months in Pakistan. [ABSTRACT FROM AUTHOR]

There is a complete lack of highly sensitive and specific biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis, limiting multi-modal therapeutic options. Mitochondrial DNA (mtDNA) is an excellent resource for biomarker discovery because of its high copy number and increased mutational frequency in cancer cells. We examined if mtDNA mutations can be detected in circulating extracellular vesicles (EVs) of PDAC patients and used for discerning between cancer and non-cancer subjects. A greater yield of circulating EVs (~ 1.4 fold; p = 0.002) was obtained in PDAC patients (n = 20) than non-cancer (NC) individuals (n = 10). PDAC-EVs contained a higher quantity of total DNA (~ 5.5 folds; p = 0.0001) than NC-EVs and had greater enrichment of mtDNA (~ 14.02-fold; p = 0.0001). PDAC-EVs also had higher levels of cardiolipin (a mitochondrial inner-membrane phospholipid), suggestive of their mitochondrial origin. All mtDNA mutations in PDAC-EVs were unique and frequency was remarkably higher. Most mtDNA mutations (41.5%) in PDAC-EVs were in the respiratory complex-I (RCI) (ND1-ND6), followed by the RCIII gene (CYTB; 11.2%). Among the non-coding genes, D-Loop and RNR2 exhibited the most mutations (15.2% each). Altogether, our study establishes, for the first time, that mtDNA mutations can be detected in circulating EVs and potentially serve as a tool for reliable PDAC diagnosis. [ABSTRACT FROM AUTHOR]

Background: Aberrant activation of androgen receptor signalling following castration therapy is a common clinical observation in prostate cancer (PCa). Earlier, we demonstrated the role of MYB overexpression in androgen-depletion resistance and PCa aggressiveness. Here, we investigated MYB-androgen receptor (AR) crosstalk and its functional significance.Methods: Interaction and co-localization of MYB and AR were examined by co-immunoprecipitation and immunofluorescence analyses, respectively. Protein levels were measured by immunoblot analysis and enzyme-linked immunosorbent assay. The role of MYB in ligand-independent AR transcriptional activity and combinatorial gene regulation was studied by promoter-reporter and chromatin immunoprecipitation assays. The functional significance of MYB in castration resistance was determined using an orthotopic mouse model.Results: MYB and AR interact and co-localize in the PCa cells. MYB-overexpressing PCa cells retain AR in the nucleus even when cultured under androgen-deprived conditions. AR transcriptional activity is also sustained in MYB-overexpressing cells in the absence of androgens. MYB binds and promotes AR occupancy to the KLK3 promoter. MYB-overexpressing PCa cells exhibit greater tumorigenicity when implanted orthotopically and quickly regain growth following castration leading to shorter mice survival, compared to those carrying low-MYB-expressing prostate tumours.Conclusions: Our findings reveal a novel MYB-AR crosstalk in PCa and establish its role in castration resistance. [ABSTRACT FROM AUTHOR]

Flash-induced chlorophyll fluorescence relaxation is a powerful tool to monitor the reoxidation reactions of the reduced primary quinone acceptor, QA− by QB and the plastoquinone (PQ) pool, as well as the charge recombination reactions between the donor and acceptor side components of Photosystem II (PSII). Under certain conditions, when the PQ pool is highly reduced (e.g. in microaerobic conditions), a wave phenomenon appears in the fluorescence relaxation kinetics, which reflects the transient reoxidation and re-reduction of QA− by various electron transfer processes, which in cyanobacteria is mediated by NAD(P)H dehydrogenase (NDH-1). The wave phenomenon was also observed and assigned to the operation of type 2 NAD(P)H dehydrogenase (NDH-2) in the green alga Chlamydomonas reinhardtii under hydrogen-producing conditions, which required a long incubation of algae under sulphur deprivation (Krishna et al. J Exp Bot 70 (21):6321–6336, 2019). However, the conditions that induce the wave remained largely uncharacterized so far in microalgae. In this work, we investigated the wave phenomenon in Chlamydomonas reinhardtii under conditions that lead to a decrease of PSII activity by applying hydroxylamine treatment, which impacts the donor side of PSII in combination with a strongly reducing environment of the PQ pool (microaerobic conditions). A similar wave phenomenon could be induced by photoinhibitory conditions (illumination with strong light in the presence of the protein synthesis inhibitor lincomycin). These results indicate that the fluorescence wave phenomenon is activated in green algae when the PSII activity decreases relative to Photosystem I (PS I) activity and the PQ pool is strongly reduced. Therefore, the fluorescence wave could be used as a sensitive indicator of altered intersystem electron transfer processes, e.g. under stress conditions. [ABSTRACT FROM AUTHOR]

Land use and land cover modifications have been undergoing at a hasty pace across the world. The dynamics of growth and change in land use in Peshawar City during the period 1991–2014 was studied utilizing GIS and remote sensing technologies. Using Landsat TM imageries, this study examined land use alterations in urban and peri-urban Peshawar and their impact on ground water. Beside this, the study used temporal and spatial dataset of water table for the year 1991 and 2014 that were gathered from Water and Works Department Peshawar, Pakistan. This study also used Cellular Automata–Markov (CA–Markov model) to predict the future change in built up area up to 2044 on the basis of past trend (1991–2014) and its impact on the encroachment or loss of agricultural land as well as the level of ground water. The past trend of fluctuation of groundwater (in feet) with the expansion in size of built-uses was also used to predict future trend in ground water depletion. The most severe impact in terms of groundwater depletion will take place in the southern parts of the city. The sharp decrease of groundwater table was observed in the central parts of the city compared to the peripheries. If this declining trend of groundwater level continues that might put an amplified stress on underground aquifers and may trigger to land subsidence or other environmental hazards. [ABSTRACT FROM AUTHOR]

The large yellow croaker (Larimichthys crocea) is an important mariculture fish in China. Farmed large yellow croaker undergo periods of fasting to adapt to the environment or to improve meat quality. To better understand the physiological responses of their muscle tissues to fasting stresses, we analyzed the transcriptomes and proteomes of both normally-fed and fasting fish groups and identified 7 578 differentially expressed genes (DEGs) and 297 differentially expressed proteins (DEPs) among them. Gene ontology and KEGG analysis showed that the enriched biological pathways were mainly involved in various synthetic and catabolic pathways, especially the protein metabolism. Based on the omics data, nine DEGs related to muscle composition (CAN3, MYL3, and TNNC2), growth (MSTN and MYF5), autophagy (TSC2 and ULK1), and the ubiquitin proteasome pathway (PRS6B and UCHL3) were examined using qPCR. In response to fasting stress, MYL3 and TNNC2 were significantly downregulated, while genes associated with autophagy and the ubiquitin proteasome pathway were significantly upregulated. In response to fasting stress, MYL3, TNNC2, and MYF5 positively correlated with muscle growth were significantly downregulated, while inhibiting growth MSTN and genes associated with autophagy and the ubiquitin proteasome pathways were significantly upregulated. These results clarify the effects of fasting on metabolic changes in their muscle components and growth at the molecular level. [ABSTRACT FROM AUTHOR]

Late diagnosis, unreliable prognostic assessment, and poorly-guided therapeutic planning result in dismal survival of ovarian cancer (OC) patients. Therefore, identifying novel functional biomarker(s) is highly desired for improved clinical management. MYB is an oncogenic transcription factor with emerging functional significance in OC. Here we examined its clinicopathologic significance by immunohistochemistry and TCGA/GTex data analyses. Aberrant MYB expression was detected in 94% of OC cases (n = 373), but not in the normal ovarian tissues (n = 23). MYB was overexpressed in all major epithelial OC histological subtypes exhibiting the highest incidence (~ 97%) and overall expression in serous and mucinous carcinomas. MYB expression correlated positively with tumor grades and stages. Moreover, MYB exhibited race-specific prognostic association. Moderate-to-high MYB levels were significantly associated with both poor overall- (p = 0.02) and progression-free (p = 0.02) survival in African American (AA), but not in the Caucasian American (CA) patients. Consistent with immunohistochemistry data, we observed significantly higher MYB transcripts in OC cases (n = 426) than normal ovary (n = 88). MYB transcripts were significantly higher in all epithelial OC subtypes, compared to normal, and its greater levels predicted poor survival in AA OC, but not CA OC, patients. Thus, MYB appears to be a useful clinical biomarker for prognostication, especially in AA patients. [ABSTRACT FROM AUTHOR]

In the present paper, we investigate the commutativity of 3-prime near-rings satisfying certain conditions involving left generalized multiplicative derivations on semigroup ideals. Moreover, examples have been provided to justify the necessity of 3-primeness condition in the hypotheses of various results. [ABSTRACT FROM AUTHOR]

We report simultaneous photoinitiated polymerization and stimulated Raman scattering (SRS) from polymers of methacrylate monomers using a Q-switched Nd: YAG laser (second harmonic radiation at 532 nm). The monomers used were n-butyl methacrylate and n-octadecyl methacrylate together with benzoyl peroxide as initiator, dissolved in ethanol. During the interaction of focused laser pulses with the mixtures of monomers, a strong signal in the forward direction at 630.4 nm was recorded that corresponds to SRS signal originating from Raman active vibrational stretching modes of νs(C-H) of -OCH3 with νs(C-H) of α-CH3 and νa(CH2) groups at 2957cm-1 in the polymethacrylate. In addition, another SRS signal at 773.2 nm corresponding to the first overtone of the referred Raman mode was also recorded. Results are presented where different compositional mixtures of the polymerizing monomers, and different laser energies were used mainly for the strongest SRS intensities that could possibly be an index of the rate and extent of polymerization. [ABSTRACT FROM AUTHOR]

Background: Chemoresistance is a significant clinical problem in pancreatic cancer (PC) and underlying molecular mechanisms still remain to be completely understood. Here we report a novel exosome-mediated mechanism of drug-induced acquired chemoresistance in PC cells.Methods: Differential ultracentrifugation was performed to isolate extracellular vesicles (EVs) based on their size from vehicle- or gemcitabine-treated PC cells. Extracellular vesicles size and subtypes were determined by dynamic light scattering and marker profiling, respectively. Gene expression was examined by qRT-PCR and/or immunoblot analyses, and direct targeting of DCK by miR-155 was confirmed by dual-luciferase 3'-UTR reporter assay. Flow cytometry was performed to examine the apoptosis indices and reactive oxygen species (ROS) levels in PC cells using specific dyes. Cell viability was determined using the WST-1 assay.Results: Conditioned media (CM) from gemcitabine-treated PC cells (Gem-CM) provided significant chemoprotection to subsequent gemcitabine toxicity and most of the chemoresistance conferred by Gem-CM resulted from its EVs fraction. Sub-fractionation grouped EVs into distinct subtypes based on size distribution and marker profiles, and exosome (Gem-Exo) was the only sub-fraction that imparted chemoresistance. Gene expression analyses demonstrated upregulation of SOD2 and CAT (ROS-detoxifying genes), and downregulation of DCK (gemcitabine-metabolising gene) in Gem-Exo-treated cells. SOD/CAT upregulation resulted, at least in part, from exosome-mediated transfer of their transcripts and they suppressed basal and gemcitabine-induced ROS production, and partly promoted chemoresistance. DCK downregulation occurred through exosome-delivered miR-155 and either the functional suppression of miR-155 or restoration of DCK led to marked abrogation of Gem-Exo-mediated chemoresistance.Conclusions: Together, these findings establish a novel role of exosomes in mediating the acquired chemoresistance of PC. [ABSTRACT FROM AUTHOR]

Climate change is expected to have adverse impact on Pakistan. This is ironical for a country, which ranks 135th in the world in terms of global green house gases (GHG) emissions per capita, but ranks 16th in terms of vulnerability to climate change. Climate change poses a major threat to all dimensions of sustainable development and has widespread impacts across various sectors and ecosystems such as food, water and energy; forests and biodiversity; coastal and marine environment; as well as on the occurrence and intensity of climate related hazards such as floods and drought. It also carries potential for internal and external conflicts. The paper examines the present and potential impact of climate change in Pakistan, and reviews national policies and plans to examine the extent to which climate-related issues have been integrated within these. The paper also discusses adaptation and mitigation measures and identifies the key elements that need to be included in the Climate Change Action Plan of Pakistan and stresses their mainstreaming into the national development policies and plans. [ABSTRACT FROM AUTHOR]

We demonstrate that low-pressure glow discharges in He–O2 gas mixture are effective in removing carbonaceous surface layers from coked catalysts. These discharges contain a number of reactive species including O, O3, and O2*, and all these could contribute in the decoking process. However, an evolving understanding is that the O atoms in the discharge have a predominant role in this. A working hypothesis is that the O atoms react with the coke to form CO, CO2 and other carbon complexes. Online measurements using emission spectra from O, H, and CO in the discharges are compared for the cases of He–O2 and Ar–O2 gas mixtures. Under the reported experimental conditions the estimated reactivity of the He–O2 discharges is considerably higher compared with discharges in the Ar–O2 gas mixture. Raman spectroscopy is used to confirm the removal of the coke from the surface of Pt/Alumina catalyst. [ABSTRACT FROM AUTHOR]

Exosomes have received significant attention for their role in pathobiological processes and are being explored as a tool for disease diagnosis and management. Consequently, various isolation methods based on different principles have been developed for exosome isolation. Here we compared the efficacy of four kits from Invitrogen, 101Bio, Wako and iZON along with conventional ultracentrifugation-based method for exosome yield, purity and quality. Cell culture supernatant was used as an abundant source of exosomes, and exosome quantity, size-distribution, zeta-potential, marker-expression and RNA/protein quality were determined. The Invitrogen kit gave the highest yield but the preparation showed broader size-distribution likely due to microvesicle co-precipitation and had the least dispersion stability. Other preparations showed <150 nm size range and good stability. Preparation from iZON column; however, had a broader size-distribution in the lower size range suggestive of some impurities of non-vesicular aggregates. RNA quality from all preparations was comparable; however, proteins from Invitrogen method-based exosomal preparation showed polyethylene glycol (PEG) contamination in mass spectrometry. Chemical impurities from the precipitant could also be the cause of toxicity of Invitrogen method-based exosomal preparation in biological growth measurement assay. Together, these findings should serve as a guide to choose and further optimize exosome isolation methods for their desired downstream applications. [ABSTRACT FROM AUTHOR]