Nanoengineering of mono (Au, Ag) and bimetallic (Ag-Au) alloy nanoparticles for dye degradation and toxicity assessment.

This research entails the synthesis and catalytic exploration of bimetallic nanoparticles combining silver (Ag) and gold (Au). The Au concentration was systematically varied (20%, 40%, 60%, and 80%), alongside the utilization of CTAB surfactant for nanoparticle stabilization. UV visible spectroscopic analysis confirmed the formation and stability of synthesized Au, Ag and bimetallic (Ag-Au) nanoparticles. FESEM further confirmed the formation of uniform sized Au and Ag nanoparticles. Integration of Au into Ag resulted in bimetallic (Ag-Au) alloy nanoparticles with smaller dimensions as compared to individual Au and Ag nanoparticles. EDX spectra and mapping verified the composition of each synthesized bimetallic nanoparticle variant. The catalytic potential of the synthesized nanoparticles was methodically explored using UV-visible spectroscopy. All the synthesized nanoparticles showcased excellent catalytic efficacy. The synergistic effect of the alloyed bimetallic nanoparticles was found promising. Assessment of dye toxicity pre- and post-degradation was conducted using the ECOSAR program, indicating a reduction in dye toxicity following degradation.

Metabolic signatures of metabolic dysfunction-associated steatotic liver disease in severely obese patients.

BACKROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Still, most patients with MASLD die from cardiovascular diseases indicating metabolic alterations related to both liver and cardiovascular pathology. AIMS AND METHODS: The aim of this study was to assess biologic pathways behind MASLD progression from steatosis to metabolic dysfunction-associated steatohepatitis (MASH) using non-targeted liquid chromatography-mass spectrometry analysis in 106 severely obese individuals (78 women, mean age 47.7 7 ± 9.2 years, body mass index 41.8 ± 4.3 kg/m²) undergoing laparoscopic Roux-en-Y gastric bypass. RESULTS: We identified several metabolites that are associated with MASLD progression. Most importantly, we observed a decrease of lysophosphatidylcholines LPC(18:2), LPC(18:3), and LPC(20:3) and increase of xanthine when comparing those with steatosis to those with MASH. We found that indole propionic acid and threonine were negatively correlated to fibrosis, but not with the metabolic disturbances associated with cardiovascular risk. Xanthine, ketoleucine, and tryptophan were positively correlated to lobular inflammation and ballooning but also with insulin resistance, and dyslipidemia, respectively. The results did not change when taking into account the most important genetic risk factors of MASLD. CONCLUSIONS: Our findings suggest that there are several separate biological pathways, some of them independent of insulin resistance and dyslipidemia, associating with MASLD.

Exome sequencing in four families with neurodevelopmental disorders: genotype-phenotype correlation and identification of novel disease-causing variants in VPS13B and RELN.

Neurodevelopmental disorders (NDDs) are a clinically and genetically heterogeneous group of early-onset pediatric disorders that affect the structure and/or function of the central or peripheral nervous system. Achieving a precise molecular diagnosis for NDDs may be challenging due to the diverse genetic underpinnings and clinical variability. In the current study, we investigated the underlying genetic cause(s) of NDDs in four unrelated Pakistani families. Using exome sequencing (ES) as a diagnostic approach, we identified disease-causing variants in established NDD-associated genes in all families, including one hitherto unreported variant in RELN and three recurrent variants in VPS13B, DEGS1, and SPG11. Overall, our study highlights the potential of ES as a tool for clinical diagnosis.

Identification of metabolites produced by six gut commensal Bacteroidales strains using non-targeted LC-MS/MS metabolite profiling.

As the most abundant gram-negative bacterial order in the gastrointestinal tract, Bacteroidales bacteria have been extensively studied for their contribution to various aspects of gut health. These bacteria are renowned for their involvement in immunomodulation and their remarkable capacity to break down complex carbohydrates and fibers. However, the human gut microbiota is known to produce many metabolites that ultimately mediate important microbe-host and microbe-microbe interactions. To gain further insights into the metabolites produced by the gut commensal strains of this order, we examined the metabolite composition of their bacterial cell cultures in the stationary phase. Based on their abundance in the gastrointestinal tract and their relevance in health and disease, we selected a total of six bacterial strains from the relevant genera Bacteroides, Phocaeicola, Parabacteroides, and Segatella. We grew these strains in modified Gifu anaerobic medium (mGAM) supplemented with mucin, which resembles the gut microbiota's natural environment. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolite profiling revealed 179 annotated metabolites that had significantly differential abundances between the studied bacterial strains and the control growth medium. Most of them belonged to classes such as amino acids and derivatives, organic acids, and nucleot(s)ides. Of particular interest, Segatella copri DSM 18205 (previously referred to as Prevotella copri) produced substantial quantities of the bioactive metabolites phenylethylamine, tyramine, tryptamine, and ornithine. Parabacteroides merdae CL03T12C32 stood out due to its ability to produce cadaverine, histamine, acetylputrescine, and deoxycarnitine. In addition, we found that strains of the genera Bacteroides, Phocaeicola, and Parabacteroides accumulated considerable amounts of proline-hydroxyproline, a collagen-derived bioactive dipeptide. Collectively, these findings offer a more detailed comprehension of the metabolic potential of these Bacteroidales strains, contributing to a better understanding of their role within the human gut microbiome in health and disease.

Botulinum Neurotoxin Induces Neurotoxic Microglia Mediated by Exogenous Inflammatory Responses.

Botulinum neurotoxin serotype A (BoNT/A) is widely used in therapeutics and cosmetics. The effects of multi-dosed BoNT/A treatment are well documented on the peripheral nervous system (PNS), but much less is known on the central nervous system (CNS). Here, the mechanism of multi-dosed BoNT/A leading to CNS neurodegeneration is explored by using the 3D human neuron-glia model. BoNT/A treatment reduces acetylcholine, triggers astrocytic transforming growth factor beta, and upregulates C1q, C3, and C5 expression, inducing microglial proinflammation. The disintegration of the neuronal microtubules is escorted by microglial nitric oxide, interleukin 1ß, tumor necrosis factor α, and interleukin 8. The microglial proinflammation eventually causes synaptic impairment, phosphorylated tau (pTau) aggregation, and the loss of the BoNT/A-treated neurons. Taking a more holistic approach, the model will allow to assess therapeutics for the CNS neurodegeneration under the prolonged use of BoNT/A.

Genetic association of vitamin D receptor gene with female infertility.

BACKGROUND: Infertility is defined as failure to achieve a clinical pregnancy after 12 months of unprotected intercourse. It affects 15% of couples globally and 22% of couples within Pakistan. Female infertility can be caused by numerous genetic or environmental factors including hormone imbalances and exposure to chemicals or radiation. The prevalence of vitamin D deficiency among the adult population was reported to be 14-59% with a higher prevalence in Asian countries. Furthermore, the expression of Vitamin D receptor (VDR) can play a vital role in the reproductive organs of females. Hence, the aim of our present study was to check the association of VDR polymorphisms with infertile females. For this purpose, blood samples were collected for genotyping of four known VDR mutations [FokI (rs2228570), TaqI (rs731236), ApaI (rs7975232), and BsmI (rs1544410)] via PCR-based RFLP assay. RESULTS: Genotyping indicated that FokI, TaqI, and ApaI are associated with infertility (p = 0.004*, p = 0.013*, and p = 0.033*, respectively). However, BsmI did not show any significance. Multinomial regression analysis indicated that FokI heterozygous genotypes increase the risk of infertility by 2.5 times (hetero: OR = 2.5, 95%, p = 0.001*) as compared to wild type. Heterozygous genotypes of TaqI and ApaI were found to play a protective role and reduce the risk of infertility by 58 and 52%, respectively [TaqI: OR = 0.42, 95%, p = 0.004*, ApaI: OR = 0.48, 95%, p = 0.01*, respectively] as compared to wild type. Multinomial logistic regression analysis was also performed for allelic data as well. CONCLUSION: Thus, it could be summarized that among the studied polymorphisms of VDR, FokI SNP greatly increased the risk of infertility, while TaqI and ApaI genotypes protect from infertility. However, BsmI does not influence the risk of infertility in Pakistani females.

Changes in liver metabolic pathways demonstrate efficacy of the combined dietary and microbial therapeutic intervention in MASLD mouse model.

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent liver disease globally, yet no therapies are approved. The effects of Escherichia coli Nissle 1917 expressing aldafermin, an engineered analog of the intestinal hormone FGF19, in combination with dietary change were investigated as a potential treatment for MASLD. METHODS: MASLD was induced in C57BL/6J male mice by American lifestyle-induced obesity syndrome diet and then switched to a standard chow diet for seven weeks. In addition to the dietary change, the intervention group received genetically engineered E. coli Nissle expressing aldafermin, while control groups received either E. coli Nissle vehicle or no treatment. MASLD-related plasma biomarkers were measured using an automated clinical chemistry analyzer. The liver steatosis was assessed by histology and bioimaging analysis using Fiji (ImageJ) software. The effects of the intervention in the liver were also evaluated by RNA sequencing and liquid-chromatography-based non-targeted metabolomics analysis. Pathway enrichment studies were conducted by integrating the differentially expressed genes from the transcriptomics findings with the metabolites from the metabolomics results using Ingenuity pathway analysis. RESULTS: After the intervention, E. coli Nissle expressing aldafermin along with dietary changes reduced body weight, liver steatosis, plasma aspartate aminotransferase, and plasma cholesterol levels compared to the two control groups. The integration of transcriptomics with non-targeted metabolomics analysis revealed the downregulation of amino acid metabolism and related receptor signaling pathways potentially implicated in the reduction of hepatic steatosis and insulin resistance. Moreover, the downregulation of pathways linked to lipid metabolism and changes in amino acid-related pathways suggested an overall reduction of oxidative stress in the liver. CONCLUSIONS: These data support the potential for using engineered microbial therapeutics in combination with dietary changes for managing MASLD.

In silico analysis and experimental validation shows negative correlation between miR-1183 and cell cycle progression gene 1 expression in colorectal cancer.

MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by binding to the 3' untranslated regions (UTR) of target genes. Aberrant expression of miRNAs can lead to disease, including cancer. Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Among several factors, differential expression of miRNA can have serious consequences on disease progression. This study was designed to computationally identify and experimentally verify strong miRNA candidates that could influence CRC progression. In silico analysis of publicly available gene expression microarray datasets revealed significant upregulation of miR-1183 in CRC. Comparison of mRNA microarray expression data with predicted miR-1183 targets led to the identification of cell cycle progression gene 1 (CCPG1) as strong, negatively correlated miR-1183 target. Expression analysis by means of quantitative PCR validated the inverse correlation between miR-1183 and CCPG1 in colorectal cancer tissues. CCPG1 indirectly modulates the cell cycle by interacting with the PH/DH domain of Dbs (Rho-specific guanine nucleotide exchange factor). Interestingly, the computational analysis also showed that miR-1183 is upregulated in liver and gastric cancer. This finding is notable as the liver and stomach are the primary metastatic sites for colorectal cancer and hepatocellular carcinoma respectively. This novel finding highlights the broader implications of miR-1183 dysregulation beyond primary CRC, potentially serving as a valuable prognostic marker and a therapeutic target for both primary and metastatic CRC.

Three-dimensional human neural culture on a chip recapitulating neuroinflammation and neurodegeneration.

Neuroinflammation has either beneficial or detrimental effects, depending on risk factors and neuron-glia interactions in neurological disorders. However, studying neuroinflammation has been challenging due to the complexity of cell-cell interactions and lack of physio-pathologically relevant neuroinflammatory models. Here, we describe our three-dimensional microfluidic multicellular human neural culture model, referred to as a 'brain-on-a-chip' (BoC). This elucidates neuron-glia interactions in a controlled manner and recapitulates pathological signatures of the major neurological disorders: dementia, brain tumor and brain edema. This platform includes a chemotaxis module offering a week-long, stable chemo-gradient compared with the few hours in other chemotaxis models. Additionally, compared with conventional brain models cultured with mixed phenotypes of microglia, our BoC can separate the disease-associated microglia out of heterogeneous population and allow selective neuro-glial engagement in three dimensions. This provides benefits of interpreting the neuro-glia interactions while revealing that the prominent activation of innate immune cells is the risk factor leading to synaptic impairment and neuronal loss, validated in our BoC models of disorders. This protocol describes how to fabricate and implement our human BoC, manipulate in real time and perform end-point analyses. It takes 2 d to set up the device and cell preparations, 1-9 weeks to develop brain models under disease conditions and 2-3 d to carry out analyses. This protocol requires at least 1 month training for researchers with basic molecular biology techniques. Taken together, our human BoCs serve as reliable and valuable platforms to investigate pathological mechanisms involving neuroinflammation and to assess therapeutic strategies modulating neuroinflammation in neurological disorders.

Genetic Investigation of Consanguineous Pakistani Families Segregating Rare Spinocerebellar Disorders.

Spinocerebellar disorders are a vast group of rare neurogenetic conditions, generally characterized by overlapping clinical symptoms including progressive cerebellar ataxia, spastic paraparesis, cognitive deficiencies, skeletal/muscular and ocular abnormalities. The objective of the present study is to identify the underlying genetic causes of the rare spinocerebellar disorders in the Pakistani population. Herein, nine consanguineous families presenting different spinocerebellar phenotypes have been investigated using whole exome sequencing. Sanger sequencing was performed for segregation analysis in all the available individuals of each family. The molecular analysis of these families identified six novel pathogenic/likely pathogenic variants; ZFYVE26: c.1093del, SACS: c.1201C>T, BICD2: c.2156A>T, ALS2: c.2171-3T>G, ALS2: c.3145T>A, and B4GALNT1: c.334_335dup, and three already reported pathogenic variants; FA2H: c.159_176del, APTX: c.689T>G, and SETX: c.5308_5311del. The clinical features of all patients in each family are concurrent with the already reported cases. Hence, the current study expands the mutation spectrum of rare spinocerebellar disorders and implies the usefulness of next-generation sequencing in combination with clinical investigation for better diagnosis of these overlapping phenotypes.

Cross-cultural adaptation and validation of the Northwick park neck pain questionnaire to Urdu language.

BACKGROUND: Despite its widespread use for assessing pain and disability in patients suffering from neck pain, the Northwick Park Neck Pain Questionnaire (NPQ) has yet to be translated and validated in Urdu. The purpose of the present study was to translate and cross-culturally adapt the NPQ into Urdu language (NPQ-U), and to investigate the NPQ-U's psychometric properties in patients with non-specific neck pain (NSNP). METHODS: The NPQ was translated and cross-culturally adapted into Urdu in accordance with the previously described guidelines. The study included 150 NSNP patients and 50 healthy participants. The NPQ-U, Urdu version of neck disability index (NDI-U), neck pain and disability scale (NPDS), and numerical pain rating scale (NPRS) were completed by all participants on first visit. After three weeks of physical therapy, the patients completed all of the questionnaires listed above, along with the global rating of change scale. Test-retest reliability was determined on 46 randomly selected patients who completed the NPQ-U again two days after the first response. The NPQ-U was evaluated for internal consistency, content validity, construct (convergent and discriminative) validity, factor analysis, and responsiveness. RESULTS: The NPQ-U demonstrated excellent test-retest reliability (intra-class correlation coefficient = 0.96) and high internal consistency (Cronbach's alpha = 0.89). There were no floor or ceiling effects for the NPQ-U total score, indicating good content validity. A single factor was extracted, which explained 54.56% of the total variance. For convergent validity, the NPQ-U showed a strong correlation with NDI-U (r = 0.89, P < 0.001), NPDS (r = 0.71, P < 0.001), and NPRS (r = 0.73, P < 0.001). The results revealed a significant difference between patients and healthy controls in the NPQ-U total scores (P < 0.001) demonstrating significant discriminative validity. A significant difference in the NPQ-U change scores between the stable and the improved groups (P < 0.001) confirmed its responsiveness. Furthermore, the NPQ-U change score showed a moderate correlation with NPDS change score (r = 0.60, P < 0.001) and NPRS change score (r = 0.68, P < 0.001), but a strong correlation with NDI-U change score (r = 0.75, P < 0.001). CONCLUSION: The NPQ-U is a reliable, valid, and responsive tool for assessing neck pain and disability in Urdu-speaking patients with NSNP.

A homozygous founder variant in PDE2A causes paroxysmal dyskinesia with intellectual disability.

Intellectual developmental disorder with paroxysmal dyskinesia or seizures (IDDPADS, OMIM#619150) is an ultra-rare childhood-onset autosomal recessive movement disorder manifesting paroxysmal dyskinesia, global developmental delay, impaired cognition, progressive psychomotor deterioration and/or drug-refractory seizures. We investigated three consanguineous Pakistani families with six affected individuals presenting overlapping phenotypes partially consistent with the reported characteristics of IDDPADS. Whole exome sequencing identified a novel missense variant in Phosphodiesterase 2A (PDE2A): NM_002599.4: c.1514T > C p.(Phe505Ser) that segregated with the disease status of individuals in these families. Retrospectively, we performed haplotype analysis that revealed a 3.16 Mb shared haplotype at 11q13.4 among three families suggesting a founder effect in this region. Moreover, we also observed abnormal mitochondrial morphology in patient fibroblasts compared to controls. Belonging to diverse age groups (13 years-60 years), patients presented paroxysmal dyskinesia, developmental delay, cognitive abnormalities, speech impairment, and drug-refractory seizures with variable onset of disease (as early as 3 months of age to 7 years). Together with the previous reports, we observed that intellectual disability, progressive psychomotor deterioration, and drug-refractory seizures are consistent outcomes of the disease. However, permanent choreodystonia showed variability. We also noticed that the later onset of paroxysmal dyskinesia manifests severe attacks in terms of duration. Being the first report from Pakistan, we add to the clinical and mutation spectrum of PDE2A-related recessive disease raising the total number of patients from six to 12 and variants from five to six. Together, with our findings, the role of PDE2A is strengthened in critical physio-neurological processes.

Translation and validation of the Urdu version of the neck pain and disability scale.

PURPOSE: To translate and cross-culturally adapt the neck pain and disability scale (NPDS) into Urdu language (NPDS-U), and to investigate the NPDS-U's psychometric properties in patients with non-specific neck pain (NSNP). METHODS: The NPDS was translated and cross-culturally adapted into Urdu in accordance with the previously described guidelines. The study included 200 NSNP patients and 50 healthy participants. The NPDS-U, Urdu version of neck disability index (NDI-U), neck Bournemouth questionnaire (NBQ), and numerical pain rating scale (NPRS) were completed by all participants. After three weeks of physiotherapy, the patients completed all of the above-mentioned questionnaires, along with the global rating of change scale. Reliability, factor analysis, validity, and responsiveness were all tested. RESULTS: The NPDS-U demonstrated excellent test-retest reliability (ICC2,1=0.92) and high internal consistency (Cronbach's alpha = 0.96). There were no floor or ceiling effects. A three-factor structure was extracted, which explained 70.42% of the total variance. The NPDS-U showed moderate to strong correlations with NPRS, NDI-U, and NBQ (r = 0.67-0.76, p < 0.001). A significant difference in the NPDS-U change scores between the stable and the improved groups (p < 0.001) confirmed its responsiveness. CONCLUSION: The NPDS-U is a reliable, valid, and responsive scale for assessing neck pain and disability in Urdu-speaking patients with NSNP.

The Urdu version of Neck Pain and Disability Scale (NPDS-U) is a reliable and valid tool for assessing neck pain and disability in Urdu-speaking patients with non-specific neck pain (NSNP).The NPDS-U can be used to distinguish between people who have neck pain and disability and those who do not.NPDS-U exhibited a 3-factor structure.The NPDS-U is a responsive instrument that can be used to assess treatment efficacy in NSNP patients.The NPDS-U is a simple and easy to use in clinical and research settings.

Associations of altered hepatic gene expression in American lifestyle-induced obesity syndrome diet-fed mice with metabolic changes during NAFLD development and progression.

Non-alcoholic fatty liver disease (NAFLD) pathogenesis remains poorly understood due to the complex metabolic and inflammatory changes in the liver. This study aimed to elucidate hepatic events related to inflammation and lipid metabolism and their linkage with metabolic alterations during NAFLD in American lifestyle-induced obesity syndrome (ALIOS) diet-fed mice. Forty-eight C57BL/6J male mice were fed with ALIOS diet (n=24) or control chow diet (n=24) for 8, 12, and 16 weeks. At the end of each timepoint, eight mice were sacrificed where plasma and liver were collected. Hepatic fat accumulation was followed using magnetic resonance imaging and confirmed with histology. Further, targeted gene expression and non-targeted metabolomics analysis were conducted. Our results showed higher hepatic steatosis, body weight, energy consumption, and liver mass in ALIOS diet-fed mice compared to control mice. ALIOS diet altered expression of genes related to inflammation (Tnfa and IL-6) and lipid metabolism (Cd36, Fasn, Scd1, Cpt1a, and Ppara). Metabolomics analysis indicated decrease of lipids containing polyunsaturated fatty acids such as LPE(20:5) and LPC(20:5) with increase of other lipid species such as LPI(16:0) and LPC(16:2) and peptides such as alanyl-phenylalanine and glutamyl-arginine. We further observed novel correlations between different metabolites including sphingolipid, lysophospholipids, peptides, and bile acid with inflammation, lipid uptake and synthesis. Together with the reduction of antioxidant metabolites and gut microbiota-derived metabolites contribute to NAFLD development and progression. The combination of non-targeted metabolomics with gene expression in future studies can further identify key metabolic routes during NAFLD which could be the targets of potential novel therapeutics.

Critical analysis in the advancement of cell-based assays for botulinum neurotoxin.

The study on botulinum neurotoxins (BoNTs) has rapidly evolved for their structure and functions as opposed to them being poisons or cures. Since their discoveries, the scientific community has come a long way in understanding BoNTs' structure and biological activity. Given its current application as a tool for understanding neurocellular activity and as a drug against over 800 neurological disorders, relevant and sensitive assays have become critical for biochemical, physiological, and pharmacological studies. The natural entry of the toxin being ingestion, it has also become important to examine its mechanism while crossing the epithelial cell barrier. Several techniques and methodologies have been developed, for its entry, pharmacokinetics, and biological activity for identification, and drug efficacy both in vivo and in vitro conditions. However, each of them presents its own challenges. The cell-based assay is a platform that exceeds the sensitivity of mouse bioassay while encompassing all the steps of intoxication including cell binding, transcytosis, endocytosis, translocation and proteolytic activity. In this article we review in detail both the neuronal and nonneuronal based cellular interaction of BoNT involving its transportation, and interaction with the targeted cells, and intracellular activities.

The Siberian pine growth dynamics in Altai Mountains, China

Abstract Climatic factors play an essential role in the growth of tree ring width. In this study, we aimed to evaluate the correlation between climatic variables and tree-ring growth characteristics of Pinus sibirica in Altai mountains, northwestern China. This study being is first of its kind on climate growth analysis of Pinus sibirica in northwestern China. The study showed great potential to understand the species growing under the specific climatic conditions. Total of 70 tree cores collected from three sites in the sampling area, out of which 63 tree cores considered for this study. The effect of climatic variables which was studied include precipitation, temperature and PDSI. Our results showed that Tree Ring Width chronology has a significantly positive correlation with the late winter (March) temperature and significant negative correlation with the July temperatures. A significant correlation was observed with the late summer precipitation whereas no significant relation found with the Palmer Drought Severity Index. These significant correlations with temperature and precipitation suggested that this tree species had the potential for the reconstruction of the past climate in the area.

RESUMO Fatores climáticos desempenham papel essencial no crescimento da largura dos anéis das árvores. Neste estudo, objetivou-se avaliar a correlação entre variáveis climáticas e características de crescimento de anéis de árvores de Pinus sibirica nas montanhas de Altai, noroeste da China. Este estudo é o primeiro desse tipo na análise do crescimento climático de Pinus sibirica no noroeste da China. O estudo mostrou grande potencial para entender as espécies que crescem sob as condições climáticas específicas. Total de 70 testemunhos coletados em três locais na área de amostragem, dos quais 63 testemunhos considerados para este estudo. O efeito das variáveis climáticas estudadas incluem precipitação, temperatura e PDSI. Nossos resultados mostraram que a cronologia da Largura do Anel da Árvore tem uma correlação significativamente positiva com a temperatura do final do inverno (março) e uma correlação negativa significativa com as temperaturas de julho. Uma correlação significativa foi observada com a precipitação do final do verão, enquanto nenhuma relação significativa foi encontrada com o Índice de Severidade de Seca de Palmer. Essas correlações significativas com a temperatura e precipitação sugeriram que esta espécie de árvore tinha o potencial para a reconstrução do clima passado na área.

The Siberian pine growth dynamics in Altai Mountains, China / A dinâmica de crescimento do pinheiro siberiano nas montanhas de Altai, China

Climatic factors play an essential role in the growth of tree ring width. In this study, we aimed to evaluate the correlation between climatic variables and tree-ring growth characteristics of Pinus sibirica in Altai mountains, northwestern China. This study being is first of its kind on climate growth analysis of Pinus sibirica in northwestern China. The study showed great potential to understand the species growing under the specific climatic conditions. Total of 70 tree cores collected from three sites in the sampling area, out of which 63 tree cores considered for this study. The effect of climatic variables which was studied include precipitation, temperature and PDSI. Our results showed that Tree Ring Width chronology has a significantly positive correlation with the late winter (March) temperature and significant negative correlation with the July temperatures. A significant correlation was observed with the late summer precipitation whereas no significant relation found with the Palmer Drought Severity Index. These significant correlations with temperature and precipitation suggested that this tree species had the potential for the reconstruction of the past climate in the area.

Fatores climáticos desempenham papel essencial no crescimento da largura dos anéis das árvores. Neste estudo, objetivou-se avaliar a correlação entre variáveis climáticas e características de crescimento de anéis de árvores de Pinus sibirica nas montanhas de Altai, noroeste da China. Este estudo é o primeiro desse tipo na análise do crescimento climático de Pinus sibirica no noroeste da China. O estudo mostrou grande potencial para entender as espécies que crescem sob as condições climáticas específicas. Total de 70 testemunhos coletados em três locais na área de amostragem, dos quais 63 testemunhos considerados para este estudo. O efeito das variáveis climáticas estudadas incluem precipitação, temperatura e PDSI. Nossos resultados mostraram que a cronologia da Largura do Anel da Árvore tem uma correlação significativamente positiva com a temperatura do final do inverno (março) e uma correlação negativa significativa com as temperaturas de julho. Uma correlação significativa foi observada com a precipitação do final do verão, enquanto nenhuma relação significativa foi encontrada com o Índice de Severidade de Seca de Palmer. Essas correlações significativas com a temperatura e precipitação sugeriram que esta espécie de árvore tinha o potencial para a reconstrução do clima passado na área.

Natural Clay Minerals as Potential Arsenic Sorbents from Contaminated Groundwater: Equilibrium and Kinetic Studies.

Arsenic (As) contaminated groundwater is a worldwide concern due to its chronic effects on human health. The objectives of the study were to evaluate natural inexpensive raw laterite (RL) and kaolinite (RK) for their potential use as As sorbents and to understand the As sorption on laterite and kaolinite by employing sorption and kinetic models. Raw laterite and RK were tested for EC, pH, XRF and CEC as basic parameters. Batch sorption and kinetic experiments data were fitted in the sorption (Langmuir and Freundlich) model and kinetic (pseudo-first and pseudo-second order) reaction equations, respectively. Morphological and structural changes were observed in RL and RK samples before and after As saturation by employing FTIR and SEM. The major constituent in RL was Fe and Al oxides while in RK major oxides were silica and Al. The Freundlich sorption model well explained the experimental data, indicating a greater sorption capacity of RL on a hetero-layered surface compared to RK. The kinetic reaction equations showed that equilibrium was achieved after a contact time of 240 min and the adsorption was chemisorption in nature. The RL and RK were found to be effective sorbents for As removal, however, RL showed maximum As adsorption and thus superior in comparison with RK. Structural and morphological characterization reveals the role of Fe and Al oxides in the case of RL, and Al oxides in the case of RK, in the adsorption of As. Hence this study concludes that these naturally occurring inexpensive resources can be used as sorbent agents for As-contaminated drinking water treatment.

ZEB2 haploinsufficient Mowat-Wilson syndrome induced pluripotent stem cells show disrupted GABAergic transcriptional regulation and function.

Mowat-Wilson syndrome (MWS) is a severe neurodevelopmental disorder caused by heterozygous variants in the gene encoding transcription factor ZEB2. Affected individuals present with structural brain abnormalities, speech delay and epilepsy. In mice, conditional loss of Zeb2 causes hippocampal degeneration, altered migration and differentiation of GABAergic interneurons, a heterogeneous population of mainly inhibitory neurons of importance for maintaining normal excitability. To get insights into GABAergic development and function in MWS we investigated ZEB2 haploinsufficient induced pluripotent stem cells (iPSC) of MWS subjects together with iPSC of healthy donors. Analysis of RNA-sequencing data at two time points of GABAergic development revealed an attenuated interneuronal identity in MWS subject derived iPSC with enrichment of differentially expressed genes required for transcriptional regulation, cell fate transition and forebrain patterning. The ZEB2 haploinsufficient neural stem cells (NSCs) showed downregulation of genes required for ventral telencephalon specification, such as FOXG1, accompanied by an impaired migratory capacity. Further differentiation into GABAergic interneuronal cells uncovered upregulation of transcription factors promoting pallial and excitatory neurons whereas cortical markers were downregulated. The differentially expressed genes formed a neural protein-protein network with extensive connections to well-established epilepsy genes. Analysis of electrophysiological properties in ZEB2 haploinsufficient GABAergic cells revealed overt perturbations manifested as impaired firing of repeated action potentials. Our iPSC model of ZEB2 haploinsufficient GABAergic development thus uncovers a dysregulated gene network leading to immature interneurons with mixed identity and altered electrophysiological properties, suggesting mechanisms contributing to the neuropathogenesis and seizures in MWS.

Toxic Leadership and Project Success: Underpinning the Role of Cronyism.

Project success is the backbone of competitiveness and sustainability. The study aims to examine the role of cronyism in the relationship between toxic leadership and project success while taking information technology projects as the study context. Cross-sectional data (n = 240) was collected through closed-ended survey questionnaires to record the responses of IT project employees. The structural equation modeling (SEM) technique was used for analyzing the collected data. Results revealed a negative relationship between toxic leadership and project success, while cronyism positively and significantly mediated the relationship and converted the negative relationship between TL and PS to a positive relationship.