Macrophages are key regulators of many organ systems, including innate and adaptive immunity, systemic metabolism, hematopoiesis, vasculogenesis, malignancy, and reproduction. The pleiotropic roles ...of macrophages are mirrored by similarly diverse cellular phenotypes. A simplified schema classifies macrophages as M1, classically activated macrophages, or M2, alternatively activated macrophages. These cells are characterized by their expression of cell surface markers, secreted cytokines and chemokines, and transcription and epigenetic pathways. Transcriptional regulation is central to the differential speciation of macrophages, and several major pathways have been described as essential for subset differentiation. In this review, we discuss the transcriptional regulation of macrophages.
Circadian rhythm evolved to allow organisms to coordinate intrinsic physiological functions in anticipation of recurring environmental changes. The importance of this coordination is exemplified by ...the tight temporal control of cardiac metabolism. Levels of metabolites, metabolic flux, and response to nutrients all oscillate in a time-of-day-dependent fashion. While these rhythms are affected by oscillatory behavior (feeding/fasting, wake/sleep) and neurohormonal changes, recent data have unequivocally demonstrated an intrinsic circadian regulation at the tissue and cellular level. The circadian clock - through a network of a core clock, slave clock, and effectors - exerts intricate temporal control of cardiac metabolism, which is also integrated with environmental cues. The combined anticipation and adaptability that the circadian clock enables provide maximum advantage to cardiac function. Disruption of the circadian rhythm, or dyssynchrony, leads to cardiometabolic disorders seen not only in shift workers but in most individuals in modern society. In this Review, we describe current findings on rhythmic cardiac metabolism and discuss the intricate regulation of circadian rhythm and the consequences of rhythm disruption. An in-depth understanding of the circadian biology in cardiac metabolism is critical in translating preclinical findings from nocturnal-animal models as well as in developing novel chronotherapeutic strategies.
Next generation sequencing (NGS) technologies provide a high-throughput means to generate large amount of sequence data. However, quality control (QC) of sequence data generated from these ...technologies is extremely important for meaningful downstream analysis. Further, highly efficient and fast processing tools are required to handle the large volume of datasets. Here, we have developed an application, NGS QC Toolkit, for quality check and filtering of high-quality data. This toolkit is a standalone and open source application freely available at http://www.nipgr.res.in/ngsqctoolkit.html. All the tools in the application have been implemented in Perl programming language. The toolkit is comprised of user-friendly tools for QC of sequencing data generated using Roche 454 and Illumina platforms, and additional tools to aid QC (sequence format converter and trimming tools) and analysis (statistics tools). A variety of options have been provided to facilitate the QC at user-defined parameters. The toolkit is expected to be very useful for the QC of NGS data to facilitate better downstream analysis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Glutathione S-transferases (GSTs) are multifunctional proteins encoded by large gene family in plants, which play important role in cellular detoxification of several endobiotic and xenobiotic ...compounds. Previously, we suggested the diverse roles of rice GST gene family members in plant development and various stress responses based on their differential expression. In this study, we report the functional characterization of a rice tau class GST gene, OsGSTU4. OsGSTU4 fusion protein was found to be localized in nucleus and cytoplasm. The over-expression of OsGSTU4 in E. coli resulted in better growth and higher GST activity under various stress conditions. Further, we raised over-expression transgenic Arabidopsis plants to reveal its in planta function. These transgenic lines showed reduced sensitivity towards plant hormones, auxin and abscisic acid. Various analyses revealed improved tolerance in transgenic Arabidopsis plants towards salinity and oxidative stresses, which may be attributed to the lower accumulation of reactive oxygen species and enhanced GST activity. In addition, microarray analysis revealed up-regulation of several genes involved in stress responses and cellular detoxification processes in the transgenic plants as compared to wild-type. These results suggest that OsGSTU4 can be used as a good candidate for the generation of stress-tolerant crop plants.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•A network of core clock-slave clock-effectors link the molecular clock to cardiac function.•The core clock machinery BMAL1:CLOCK regulates circadian rhythm through both transcription ...and translation in the heart.•KLF15 is an essential slave clock in the heart that coordinates cardiac catabolism and clearance of the accompanied oxidative stresses in a circadian fashion.•Circadian rhythm in cardiac function is carried out by various circadian effectors including ion channel, metabolic enzyme, metabolite, intracellular signaling, microRNA, as well as other novel mechanisms.•Disruption of intrinsic circadian rhythm is highly associated with cardiovascular disease.
The circadian rhythm has a strong influence on both cardiac physiology and disease in humans. Preclinical studies primarily using tissue-specific transgenic mouse models have contributed to our understanding of the molecular mechanism of the circadian clock in the cardiovascular system. The core clock driven by CLOCK:BMAL1 complex functions as a universal timing machinery that primarily sets the pace in all mammalian cell types. In one specific cell or tissue type, core clock may control a secondary transcriptional oscillator, conceptualized as slave clock, which confers the oscillatory expression of tissue-specific effectors. Here, we discuss a core clock-slave clock-effectors network, which links the molecular clock to cardiac function.
Enhancers represent noncoding regulatory regions of the genome located distantly from their target genes. They regulate gene expression programs in a context‐specific manner via interacting with ...promoters of one or more target genes and are generally associated with transcription factor binding sites and epi(genomic)/chromatin features, such as regions of chromatin accessibility and histone modifications. The enhancers are difficult to identify due to the modularity of their associated features. Although enhancers have been studied extensively in human and animals, only a handful of them has been identified in few plant species till date due to nonavailability of plant‐specific experimental and computational approaches for their discovery. Being an important regulatory component of the genome, enhancers represent potential targets for engineering agronomic traits, including salinity stress tolerance in plants. Here, we provide a review of the available experimental and computational approaches along with the associated sequence and chromatin/epigenetic features for the discovery of enhancers in plants. In addition, we provide insights into the challenges and future prospects of enhancer research in plant biology with emphasis on potential applications in engineering salinity stress tolerance in crop plants.
Auxin influences growth and development in plants by altering gene expression. Many auxin‐responsive genes have been characterized in Arabidopsis in detail, but not in crop plants. Earlier, we ...reported the identification and characterization of the members of the GH3, Aux/IAA and SAUR gene families in rice. In this study, whole genome microarray analysis of auxin‐responsive genes in rice was performed, with the aim of gaining some insight into the mechanism of auxin action. A comparison of expression profiles of untreated and auxin‐treated rice seedlings identified 315 probe sets representing 298 (225 upregulated and 73 downregulated) unique genes as auxin‐responsive. Functional categorization revealed that genes involved in various biological processes, including metabolism, transcription, signal transduction, and transport, are regulated by auxin. The expression profiles of auxin‐responsive genes identified in this study and those of the members of the GH3, Aux/IAA, SAUR and ARF gene families were analyzed during various stages of vegetative and reproductive (panicle and seed) development by employing microarray analysis. Many of these genes are, indeed, expressed in a tissue‐specific or developmental stage‐specific manner, and the expression profiles of some of the representative genes were confirmed by real‐time PCR. The differential expression of auxin‐responsive genes during various stages of panicle and seed development implies their involvement in diverse developmental processes. Moreover, several auxin‐responsive genes were differentially expressed under various abiotic stress conditions, indicating crosstalk between auxin and abiotic stress signaling.
Chronic inflammation is a key feature of vascular disease states such as atherosclerosis. Multiple clinical studies have shown that a class of medications termed statins lower cardiovascular ...morbidity and mortality. Originally developed to lower serum cholesterol, increasing evidence suggests that these medications have potent anti-inflammatory effects that contribute to their beneficial effects in patients. Here, we discuss the clinical and experimental evidence underlying the anti-inflammatory effects of these agents.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Magnesium alloy sheets usually has to be processed by warm forming, and change of strain path and evolution of microstructure can significantly influence their warm formability. Forming limit test ...for an AZ31B alloy sheet under strain path changes was configured and implemented, and the effects of strain paths and microstructure evolution on the forming limit diagram are investigated. The sheet was pre-strained under in-plane uniaxial, plane strain and biaxial tension loading paths at 150 °C, 200 °C and 300 °C, followed by hemispherical punch stretching experiments at the three temperatures using specimens extracted from the pre-strained samples. A crystal plasticity model that incorporates dynamic recrystallization (DRX) and annealing recovery was combined with the Marciniak-Kuczyński (M-K) approach to calculate the FLDs. The evolution of dislocation density during annealing in the pre-strained FLD test at 200 °C was evaluated, through which the predictions of pre-strained FLDs were considerably improved. The present work provides experimental as well as crystal plasticity based methods for evaluating warm formability of magnesium alloys influenced by temperature, pre-straining, DRX and recovery.
BACKGROUND—Although metabolic reprogramming is critical in the pathogenesis of heart failure, studies to date have focused principally on fatty acid and glucose metabolism. Contribution of amino acid ...metabolic regulation in the disease remains understudied.
METHODS AND RESULTS—Transcriptomic and metabolomic analyses were performed in mouse failing heart induced by pressure overload. Suppression of branched-chain amino acid (BCAA) catabolic gene expression along with concomitant tissue accumulation of branched-chain α-keto acids was identified as a significant signature of metabolic reprogramming in mouse failing hearts and validated to be shared in human cardiomyopathy hearts. Molecular and genetic evidence identified the transcription factor Krüppel-like factor 15 as a key upstream regulator of the BCAA catabolic regulation in the heart. Studies using a genetic mouse model revealed that BCAA catabolic defect promoted heart failure associated with induced oxidative stress and metabolic disturbance in response to mechanical overload. Mechanistically, elevated branched-chain α-keto acids directly suppressed respiration and induced superoxide production in isolated mitochondria. Finally, pharmacological enhancement of branched-chain α-keto acid dehydrogenase activity significantly blunted cardiac dysfunction after pressure overload.
CONCLUSIONS—BCAA catabolic defect is a metabolic hallmark of failing heart resulting from Krüppel-like factor 15–mediated transcriptional reprogramming. BCAA catabolic defect imposes a previously unappreciated significant contribution to heart failure.
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