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Podocyte or endothelial cell VEGF-A knockout causes thrombotic microangiopathy in adult mice. To study the mechanism involved in acute and local injury caused by low podocyte VEGF-A we developed an inducible, podocyte-specific VEGF-A knockdown mouse, and we generated an immortalized podocyte cell line (VEGF(KD)) that downregulates VEGF-A upon doxycycline exposure. Tet-O-siVEGF:podocin-rtTA mice express VEGF shRNA in podocytes in a doxycycline-regulated manner, decreasing VEGF-A mRNA and VEGF-A protein levels in isolated glomeruli to ~20% of non-induced controls and urine VEGF-A to ~30% of control values a week after doxycycline induction. Induced tet-O-siVEGF:podocin-rtTA mice developed acute renal failure and proteinuria, associated with mesangiolysis and microaneurisms. Glomerular ultrastructure revealed endothelial cell swelling, GBM lamination and podocyte effacement. VEGF knockdown decreased podocyte fibronectin and glomerular endothelial alpha(V)beta(3) integrin in vivo. VEGF receptor-2 (VEGFR2) interacts with beta(3) integrin and neuropilin-1 in the kidney in vivo and in VEGF(KD) podocytes. Podocyte VEGF knockdown disrupts alpha(V)beta(3) integrin activation in glomeruli, detected by WOW1-Fab. VEGF silencing in cultured VEGF(KD) podocytes downregulates fibronectin and disrupts alpha(V)beta(3) integrin activation cell-autonomously. Collectively, these studies indicate that podocyte VEGF-A regulates alpha(V)beta(3) integrin signaling in the glomerulus, and that podocyte VEGF knockdown disrupts alpha(V)beta(3) integrin activity via decreased VEGFR2 signaling, thereby damaging the three layers of the glomerular filtration barrier, causing proteinuria and acute renal failure.

Background Aging is associated with complex molecular alterations at the cellular level. Bone marrow exhibits distinct phenotypic, genetic and epigenetic alterations with aging. Metabolic changes in the bone marrow related to aging have not been studied. Methods In this study, we characterized the metabolome and transcriptome of aging murine bone marrow and compared it with bone marrow from young healthy mice and chemotherapy treated mice; chemotherapy treatment is known to induce age-related changes in hematopoiesis. Results The metabolome of the aging bone marrow exhibited a signature of suppressed fatty-acid oxidation: accumulation of free fatty acids, reduced acyl-carnitines and low β-hydroxy butyric acid. The aged bone marrow also exhibited a significant reduction in amino acid and nucleic acid pool. The transcriptome of the aging bone marrow revealed a signature of oxidative stress, known to be associated with mitochondrial dysfunction. Lastly, the metabolic and transcriptomic profiles of the bone marrow of chemotherapy treated mice did not show broad age-related changes but rather mostly resembled young healthy mice, suggestive of a lack of ‘metabolic aging’ with chemotherapy exposure. Conclusion Our results revealed broad changes in lipids, amino acids, and nucleotides in aging marrow tissue. Together, these data provide a rich resource for the study of metabolic changes associated with aging in bone marrow.

Podocyte or endothelial cell VEGF-A knockout causes thrombotic microangiopathy in adult mice. To study the mechanism involved in acute and local injury caused by low podocyte VEGF-A we developed an inducible, podocyte-specific VEGF-A knockdown mouse, and we generated an immortalized podocyte cell line (VEGF.sup.KD) that downregulates VEGF-A upon doxycycline exposure. Tet-O-siVEGF:podocin-rtTA mice express VEGF shRNA in podocytes in a doxycycline-regulated manner, decreasing VEGF-A mRNA and VEGF-A protein levels in isolated glomeruli to ~20% of non-induced controls and urine VEGF-A to ~30% of control values a week after doxycycline induction. Induced tet-O-siVEGF:podocin-rtTA mice developed acute renal failure and proteinuria, associated with mesangiolysis and microaneurisms. Glomerular ultrastructure revealed endothelial cell swelling, GBM lamination and podocyte effacement. VEGF knockdown decreased podocyte fibronectin and glomerular endothelial alpha.sub.V beta.sub.3 integrin in vivo. VEGF receptor-2 (VEGFR2) interacts with beta.sub.3 integrin and neuropilin-1 in the kidney in vivo and in VEGF.sup.KD podocytes. Podocyte VEGF knockdown disrupts alpha.sub.V beta.sub.3 integrin activation in glomeruli, detected by WOW1-Fab. VEGF silencing in cultured VEGF.sup.KD podocytes downregulates fibronectin and disrupts alpha.sub.V beta.sub.3 integrin activation cell-autonomously. Collectively, these studies indicate that podocyte VEGF-A regulates alpha.sub.V beta.sub.3 integrin signaling in the glomerulus, and that podocyte VEGF knockdown disrupts alpha.sub.V beta.sub.3 integrin activity via decreased VEGFR2 signaling, thereby damaging the three layers of the glomerular filtration barrier, causing proteinuria and acute renal failure.

Podocyte or endothelial cell VEGF-A knockout causes thrombotic microangiopathy in adult mice. To study the mechanism involved in acute and local injury caused by low podocyte VEGF-A we developed an inducible, podocyte-specific VEGF-A knockdown mouse, and we generated an immortalized podocyte cell line (VEGF.sup.KD) that downregulates VEGF-A upon doxycycline exposure. Tet-O-siVEGF:podocin-rtTA mice express VEGF shRNA in podocytes in a doxycycline-regulated manner, decreasing VEGF-A mRNA and VEGF-A protein levels in isolated glomeruli to ~20% of non-induced controls and urine VEGF-A to ~30% of control values a week after doxycycline induction. Induced tet-O-siVEGF:podocin-rtTA mice developed acute renal failure and proteinuria, associated with mesangiolysis and microaneurisms. Glomerular ultrastructure revealed endothelial cell swelling, GBM lamination and podocyte effacement. VEGF knockdown decreased podocyte fibronectin and glomerular endothelial alpha.sub.V beta.sub.3 integrin in vivo. VEGF receptor-2 (VEGFR2) interacts with beta.sub.3 integrin and neuropilin-1 in the kidney in vivo and in VEGF.sup.KD podocytes. Podocyte VEGF knockdown disrupts alpha.sub.V beta.sub.3 integrin activation in glomeruli, detected by WOW1-Fab. VEGF silencing in cultured VEGF.sup.KD podocytes downregulates fibronectin and disrupts alpha.sub.V beta.sub.3 integrin activation cell-autonomously. Collectively, these studies indicate that podocyte VEGF-A regulates alpha.sub.V beta.sub.3 integrin signaling in the glomerulus, and that podocyte VEGF knockdown disrupts alpha.sub.V beta.sub.3 integrin activity via decreased VEGFR2 signaling, thereby damaging the three layers of the glomerular filtration barrier, causing proteinuria and acute renal failure.

Maize is one of the most versatile and commercially produced crops used for food, feed, fodder, ethanol, oil, and industrial raw materials. Maize is affected by various diseases, but among these, maydis leaf blight (MLB) is one of the most serious diseases. The disease is caused by Cochliobolus heterostrophus and is responsible for yield losses up to 40%. When developing cultivars for a specific ecology, days to flowering and maturity are important breeding traits to consider. Thus, understanding the genetic basis of MLB resistance, specifically the “O” race of the pathogen, and maturity-related traits is crucial to develop climate-resilient maize hybrids. This study aimed to determine the gene actions and their interactions for MLB resistance and maturity-related traits using a six-parameter model (P 1 , P 2 , F 1 , BC 1 P 1 , BC 1 P 2 , and F 2 ). Five experimental crosses were attended using resistant (R) ( CML269-1 and P72c1Xbrasil1177-2 ) and susceptible (S) ( HKIPC4B and ESM113 ) lines in R×S (1), S×R (2), R×R (1), and S×S (1) combinations. The susceptible lines belonged to the early ( HKIPC4B ) and medium ( ESM113 ) maturity groups, while the resistant lines belonged to the medium ( CML269-1 ) and late ( P72c1Xbrasil1177-2 ) maturity groups. These six genetic populations were screened under artificially created epiphytotic conditions at a hot-spot site. In the analysis, MLB resistance showed a dominance genetic effect with significant ( P <0.01) additive × additive interactions. Maturity-related traits showed significant dominance genetic effects (P< 0.01), with dominance × dominance interactions, suggesting the suitability of hybrid breeding for these traits. The estimated genes responsible for MLB resistance ranged from 0.002 to 5.78 per cross. In MLB resistance, broad and narrow-sense heritability were found to be 91.9% and 84.3%, respectively, which indicated the possibility of genetic improvement through selection. Disease response and maturity-related traits were negatively correlated, suggesting that long-duration genotypes are more resistant to disease than short-duration. The detailed understating of gene actions can aid in designing breeding strategies to develop resistant cultivars with the required duration for various stress-prone ecologies.

PurposeThis study examines how domestic honeymoon destination quality contributes to achieving honeymooners' fantasy experience and how fantasy experience impacts honeymooners' revisit intention.Design/methodology/approachUsing the convenience sampling technique, 202 self-administrated survey questionnaires were collected (184 considered useable) from domestic honeymooners who had experienced honeymoon trip. The analysis was performed by employing partial least squares structural equation modeling (PLS-SEM) using SmartPLS 4.0.FindingsThe findings indicate that honeymoon destination image strongly and significantly influenced honeymooners' fantasy experience, followed by honeymooners' privileges, service providers, social aspects and accommodation. At the same time, the dining experience and honeymoon expenses had no significant impact on the honeymooners' fantasy experience. Notably, honeymooners' fantasy experience also had a strong and significant effect on their revisit intention to honeymoon destination in the future.Originality/valueThis study has an important theoretical contribution, being the first to explore the post-consumption behavior, that is, fantasy experience and revisit intention of domestic honeymooners in tourism literature. The study also has important implications for tourism industry stakeholders, that is, government, tourism department and officials, honeymoon tour planners and hotel managers, to make honeymoon destinations more attractive and fascinating, especially among newlywed couples and the young generation of tourists.

PurposeThe present study aims to examine the households’ attitudes and intentions to adopt an indoor air purifier against the smog crisis in India by using a comprehensive theoretical framework based on the combination of the Protective Action Decision Model (PADM) and the Theory of Planned Behavior (TPB). The United Nations Sustainable Development Goals (SDGs) 2030 also emphasized ensuring a healthy and safe life, especially by achieving SDG-3, SDG-11 and SDG-13.Design/methodology/approachUsing purposive sampling, the data were collected through a survey questionnaire distributed to 382 households, and study hypotheses were assessed by using partial least squares structural equation modeling employing SmartPLS.FindingsThe results revealed that mental health risk perception (MHRP) was the most influential determinant of households’ attitudes toward adopting air purifiers, followed by smog knowledge, physical health risk perception (PHRP), information seeking and product knowledge. Notably, results revealed that households’ attitude is a leading determinant of their adoption intention toward the air purifier compared to subjective norms (SN) and perceived behavioral control (PBC).Originality/valueTo the best of the authors’ knowledge, the present study is the first to provide new insights into an individual’s protective behavior response toward ecological hazards by examining the households’ adoption intention toward the air purifier against the smog crisis using PADM and TPB model inclusively. In addition, the present study analyzes the impact of both PHRP and MHRP on individuals’ protective behavior separately. Also, this study provides theoretical contributions and important practical implications for the government, manufacturers and air purifier sellers.

Maize is a highly versatile crop holding significant importance in global food, feed and nutritional security. Grain yield is a complex trait and difficult to improve without targeting the improvement of grain yield attributing traits, which are relatively less complex in nature. Hence, considering the erosion in genetic diversity, there is an urgent need to use wild relatives for genetic diversification and unravel the genomic regions for grain yield attributing traits in maize. Thus, the current study aimed to identify quantitative trait loci (QTLs) linked with grain yield and yield attributing traits. Two BC2F2 populations developed from the cross of LM13 with Zea parviglumis (population 1) and LM14 with Zea parviglumis (population 2) were genotyped and phenotyped in field conditions in the kharif season. BC2F2:3 lines in both populations were phenotyped again for grain yield and attributing traits in the spring season. In total, three QTLs each for ear height (EH), two QTLs for flag leaf length (FLL) and one QTL each for ear diameter (ED), plant height, flag leaf length (FLL), flag leaf width and 100 kernel-weight were identified in population 1. In population 2, two QTLs for kernel row per ear (KRPE) and one QTL for FLL were detected in. QTLs for EH, FLL and KPRE showed consistency across seasons. Among the identified QTLs, six QTLs were found to be co-localized near identified genomic regions in previous studies, validating their potential in contributing to trait expression. The identified QTLs can be utilized for marker assisted selection, transferring favorable alleles from wild relatives in modern maize.

Maydis leaf blight (MLB) is a prevalent disease, caused by the necrotrophic plant pathogen Bipolaris maydis (Nisikado and Miyake), affecting maize worldwide. Depending on environmental conditions, MLB can lead to yield losses of up to 40% or more. The existing management approach of chemical disease control is expensive and unsustainable. Hence the need to evaluate an integrated approach of chemical and biocontrol/botanical agents for its sustainable management. This study aimed to assess the efficacy of three management modules namely organic, chemical, and integrated disease management (IDM) against this disease in maize. The effectiveness of three modules was tested at three hot spot locations (Ludhiana, Karnal, and Delhi), during 2019 and 2020. The chemical module was most effective in controlling the disease followed by the IDM module, with control rates of 54.16% and 45.87% in Ludhiana and 52.92% and 44.69% in Karnal, respectively. Conversely, the organic module showed the lowest effectiveness. Notably, at the Delhi location, the standard control (foliar spray with Mancozeb 75WP@ 2.5 g/l water) proved most effective, achieving a disease control percentage of 64.29%, followed by the IDM module at 50.00%. The chemical module exhibited the highest increase in yield at Ludhiana (86.47%) and Karnal (52.92%), compared to other treatments. Overall, based on location-wise averages, the chemical module gave the highest mean percent disease control at 52.36% and mean percent yield increase at 49.18%. This study emphasizes the benefits of integrated disease management and underscores the enhanced efficacy of chemicals when compared to the positive control.

Advances in sequencing technologies and bioinformatics tools have fueled a renewed interest in whole genome sequencing efforts in many organisms. The growing availability of multiple genome sequences has advanced our understanding of the within-species diversity, in the form of a pangenome. Pangenomics has opened new avenues for future research such as allowing dissection of complex molecular mechanisms and increased confidence in genome mapping. To comprehensively capture the genetic diversity for improving plant performance, the pangenome concept is further extended from species to genus level by the inclusion of wild species, constituting a super-pangenome. Characterization of pangenome has implications for both basic and applied research. The concept of pangenome has transformed the way biological questions are addressed. From understanding evolution and adaptation to elucidating host–pathogen interactions, finding novel genes or breeding targets to aid crop improvement to design effective vaccines for human prophylaxis, the increasing availability of the pangenome has revolutionized several aspects of biological research. The future availability of high-resolution pangenomes based on reference-level near-complete genome assemblies would greatly improve our ability to address complex biological problems.