Extracellular Matrix Mimicking Wound Microenvironment Responsive Amyloid-Heparin@TAAgNP Co-Assembled Hydrogel: An Effective Conductive Antibacterial Wound Healing Material.

Bioengineered composite hydrogel platforms made of a supramolecular coassembly have recently garnered significant attention as promising biomaterial-based healthcare therapeutics. The mechanical durability of amyloids, in conjunction with the structured charged framework rendered by biologically abundant key ECM component glycosaminoglycan, enables us to design minimalistic customized biomaterial suited for stimuli responsive therapy. In this study, by harnessing the heparin sulfate-binding aptitude of amyloid fibrils, we have constructed a pH-responsive extracellular matrix (ECM) mimicking hydrogel matrix. This effective biocompatible platform comprising heparin sulfate-amyloid coassembled hydrogel embedded with polyphenol functionalized silver nanoparticles not only provide a native skin ECM-like conductive environment but also provide wound-microenvironment responsive on-demand superior antibacterial efficacy for effective diabetic wound healing. Interestingly, both the cytocompatibility and antibacterial properties of this bioinspired matrix can be fine-tuned by controlling the mutual ratio of heparin sulfate-amyloid and incubated silver nanoparticle components, respectively. The designed biomaterial platform exhibits notable effectiveness in the treatment of chronic hyperglycemic wounds infected with multidrug-resistant bacteria, because of the integration of pH-responsive release characteristics of the incubated functionalized AgNP and the antibacterial amyloid fibrils. In addition to this, the aforementioned assemblage shows exceptional hemocompatibility with significant antibiofilm and antioxidant characteristics. Histological evidence of the incised skin tissue sections indicates that the fabricated composite hydrogel is also effective in controlling pro-inflammatory cytokines such as IL6 and TNFα expressions at the wound vicinity with significant upregulation of angiogenesis markers like CD31 and α-SMA.

Multi-Faceted Antimicrobial Efficacy of a Quinoline-Derived Bidentate Copper(II) Ligand Complex and Its Hydrogel Encapsulated Formulation in Methicillin-Resistant Staphylococcus aureus Inhibition and Wound Management.

The emergence of antimicrobial resistance, exemplified by methicillin-resistant Staphylococcus aureus (MRSA), poses a grave threat to public health globally. Over time, MRSA has evolved resistance to multiple antibiotics, challenging conventional treatment strategies. The relentless adaptability of MRSA underscores the urgent need for innovative and targeted antimicrobial approaches to combat this resilient pathogen. Ancient knowledge and practices, along with scientific evidence, have established that metallic copper, and its organic coordination complexes can act as potential antibacterial substances. In search of a smart and effective antimicrobial against MRSA, we designed, synthesized, and characterized a bidentate copper(II) ligand complex (SG-Cu) utilizing a comprehensive array of analytical techniques, including ESI-MS, elemental analysis, X-ray photoelectron spectroscopy, electron paramagnetic resonance spectroscopy, and others. Antibacterial efficacy and mechanism of action of the complex were assessed through bacterial growth analyses, bacterial membrane perturbation assays, ROS elicitation assays, and field emission scanning electron microscopy. SG-Cu was found to maintain robust biocompatibility against the mammalian cell lines HEK-293, WI-38, and NIH/3T3. Remarkably, SG-Cu demonstrated significant biofilm disruptive tendency evidenced by the retardation of sliding motility, reduction in slime production, reduction in biofilm viability, and enhanced biofilm eradication, both in vitro and in urinary catheters. In vivo studies on murine excisional wounds, with SG-Cu impregnated in a palmitic acid conjugated NAVSIQ hexapeptide (PA-NV) hydrogel, revealed the sustained release of SG-Cu from the gel matrix, facilitating accelerated wound healing and effective wound disinfection. This multifaceted investigation highlights the potential of SG-Cu as a versatile option for combating MRSA infections and promoting wound healing, solidifying its claim to be developed into a viable therapeutic.

Turbulence-induced droplet grouping and augmented rain formation in cumulus clouds.

This paper provides the first observational analysis of how droplet separation is impacted by the flinging action of microscale vortices in turbulent clouds over a select radii range and how they vary over cloud cores and along the peripheral edges. It is premised that this mechanism initiates droplet separation within a cloud volume soon after condensational growth, largely in the cloud core, and operates until the cloud droplet radii exceed 20-30 µm when this effect fades rapidly. New observations are presented showing how microscale vortices also impact the settling rates of droplets over a critical size range (6-18 µm) causing them to sediment faster than in still air affecting swept volumes and thereby impacting the rain initiation and formation. Large-scale atmospheric models ignore these microscale effects linked to rapid droplet growth during the early stages of cloud conversion. Previous studies on droplet spatial organization along the cloud edges and inside the deep core have shown that homogeneous Poisson statistics, indicative of the presence of a vigorous in-cloud mixing process at small scales obtained, in contrast to an inhomogeneous distribution along the edges. In this paper, it is established that this marked core region, homogeneity can be linked to microscale vortical activity which flings cloud droplets in the range of 6-18 µm outward. The typical radius of the droplet trajectories or the droplet flung radii around the vortices correlates with the interparticle distance strongly. The correlation starts to diminish as one proceeds from the central core to the cloud fringes because of the added entrainment of cloud-free air. These first results imply that droplet growth in the core is first augmented with this small-scale interaction prior to other more large-scale processes involving entrainment mixing. This first study, combining these amplified velocities are included in a Weather Research and Forecasting- LES case study. Not only are significant differences observed in the cloud morphology when compared to a baseline case, but the 'enhanced' case also shows early commencement of rainfall along with intense precipitation activity compared to the 'standard' baseline case. It is also shown that the modelled equilibrium raindrop spectrum agrees better with observations when the enhanced droplet sedimentation rates mediated by microscale vortices are included in the calculations compared to the case where only still-air terminal velocities are used.

Discovery of Quinazoline and Quinoline-Based Small Molecules as Utrophin Upregulators via AhR Antagonism for the Treatment of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disease caused by the absence of a dystrophin protein. Elevating utrophin, a dystrophin paralogue, offers an alternative therapeutic strategy for treating DMD, irrespective of the mutation type. Herein, we report the design and synthesis of novel quinazoline and quinoline-based small molecules as potent utrophin modulators screened via high throughput In-Cell ELISA in C2C12 cells. Remarkably, lead molecule SG-02, identified from a library of 70 molecules, upregulates utrophin 2.7-fold at 800 nM in a dose-dependent manner, marking the highest upregulation within the nanomolar range. SG-02's efficacy was further validated through DMD patient-derived cells, demonstrating a significant 2.3-fold utrophin expression. Mechanistically, SG-02 functions as an AhR antagonist, with excellent binding affinity (Kd = 41.68 nM). SG-02 also enhances myogenesis, as indicated by an increased MyHC expression. ADME evaluation supports SG-02's oral bioavailability. Overall, SG-02 holds promise for addressing the global DMD population.

Synergistic Augmentation of Beta-Lactams: Exploring Quinoline-Derived Amphipathic Small Molecules as Antimicrobial Potentiators against Methicillin-Resistant Staphylococcus aureus.

The escalation of bacterial resistance against existing therapeutic antimicrobials has reached a critical peak, leading to the rapid emergence of multidrug-resistant strains. Stringent pathways in novel drug discovery hinder our progress in this survival race. A promising approach to combat emerging antibiotic resistance involves enhancing conventional ineffective antimicrobials using low-toxicity small molecule adjuvants. Recent research interest lies in weak membrane-perturbing agents with unique cyclic hydrophobic components, addressing a significant gap in antimicrobial drug exploration. Our study demonstrates that quinoline-based amphipathic small molecules, SG-B-52 and SG-B-22, significantly reduce MICs of selected beta-lactam antibiotics (ampicillin and amoxicillin) against lethal methicillin-resistant Staphylococcus aureus (MRSA). Mechanistically, membrane perturbation, depolarization, and ROS generation drive cellular lysis and death. These molecules display minimal in vitro and in vivo toxicity, showcased through hemolysis assays, cell cytotoxicity analysis, and studies on albino Wistar rats. SG-B-52 exhibits impressive biofilm-clearing abilities against MRSA biofilms, proposing a strategy to enhance beta-lactam antibiosis and encouraging the development of potent antimicrobial potentiators.

Potential Broad-Spectrum Antimicrobial, Wound Healing, and Disinfectant Cationic Peptide Crafted from Snake Venom.

Antimicrobial cationic peptides are intriguing and propitious antibiotics for the future, even against multidrug-resistant superbugs. Venoms serve as a source of cutting-edge therapeutics and innovative, unexplored medicines. In this study, a novel cationic peptide library consisting of seven sequences was designed and synthesized from the snake venom cathelicidin, batroxicidin (BatxC), with the inclusion of the FLPII motif at the N-terminus. SP1V3_1 demonstrated exceptional antibacterial effectiveness against Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Klebsiella pneumoniae and destroyed the bacteria by depolarizing, rupturing, and permeabilizing their membranes, as evident from fluorescence assays, atomic force microscopy, and scanning electron microscopy. SP1V3_1 was observed to modulate the immune response in LPS-elicited U937 cells and exhibited good antibiofilm activity against MRSA and K. pneumoniae. The peptide promoted wound healing and disinfection in the murine model. The study demonstrated that SP1V3_1 is an exciting peptide lead and may be explored further for the development of better therapeutic peptides.

The impact of short-duration precipitation events over the historic Cauvery basin: a study on altered water resource patterns and associated threats.

The Cauvery Delta, the 'Rice Bowl' of India follows a time-tested cultivation pattern over several irrigation zones. However, in this era of the Anthropocene, it is now well-established that short-duration, intense precipitation episodes will batter the flood plains year after year. The purpose of this first study is thus to quantify the impacts that such episodes may have on the floodplains of the Cauvery Delta and the concomitant threats to the historic Kallanai Dam. Precipitation events during the North-East monsoon period are driven not just by warm rain microphysics but also by large frozen hydrometeors falling from deep clouds causing undesirable flooding over the region to the extent of 66%. Additionally, from an assessment of the velocity heads and the floodwater depths, this study projects a heightened vulnerability. The total extent of submergence along riverbanks and other flow paths was estimated to be 145.98 [Formula: see text] out of which 65.14% of the submerged area is agricultural land. The most important conceptual advance established in this paper is that sub-zones in major watersheds that are currently safe will get inundated in the RCP8.5 warming scenario in 2050.

Amyloid-Inspired Engineered Multidomain Amphiphilic Injectable Peptide Hydrogel─An Excellent Antibacterial, Angiogenic, and Biocompatible Wound Healing Material.

The ingrained mechanical robustness of amyloids in association with their fine-tunable physicochemical properties results in the rational design and synthesis of tailor-made biomaterials for specific applications. However, the incredible antimicrobial efficacy of these ensembles has largely been overlooked. This research work provides an insight into the interplay between self-assembly and antimicrobial activity of amyloid-derived peptide amphiphiles and thereby establishes a newfangled design principle toward the development of potent antimicrobial materials with superior wound healing efficacy. Apart from the relationship with many neurodegenerative diseases, amyloids are now considered as an important cornerstone of our innate immune response against pathogenic microbes. Impelled by this observation, a class of amphiphilic antimicrobial peptide-based biomaterial has been designed by taking Aß42 as a template. The designed AMP due to its amphipathic nature undergoes rapid self-assembly to form a biocompatible supramolecular hydrogel network having significant antibacterial as well as wound healing effectivity on both Gram-negative P. aeruginosa and MRSA-infected diabetic wounds via reduced inflammatory response and enhanced angiogenesis. Results suggest that disease-forming amyloids can be used as a blueprint for the fabrication of biomaterial-based antimicrobial therapeutics by fine-tuning both the hydrophobicity of the ß-aggregation prone zone as well as membrane interacting cationic residues.

Improvement of CNR in low-count PET scans using tissue-scattered data as initial estimate in non-TOF MLEM reconstruction.

We have proposed a method to improve contrast-to-noise ratios (CNRs) of lesions in low-count PET scans using the rejected single scattered (inside tissue) data. Indeed, with the advent of high-quality detectors regarding their energy and time resolution, and list mode data acquisition, adding single scattered events by estimating their original line of response has become more and more feasible. The low-count PET scan data were simulated using GATE software considering Jaszczak type object, and images were reconstructed using STIR. A deconvolution based method to create images from rejected single scatter data has been proposed. These scatter images were, in turn, used as an initial estimate in non-TOF MLEM reconstruction. Three types of human-sized PET scanners-ideal, state-of-art, and future generation-with different timing and energy resolutions were considered. We found a significant improvement in trade-off between the contrast recovery coefficient (CRC) and coefficient of variation (CoV) for the non-TOF MLEM reconstructed images while comparing with other less computational ways of creating initial estimates. CNR improvements were found for all lesions. The present work demonstrated the beneficial use of tissue-scattered TOF PET events which constitutes a high percentage of data in PET imaging, and rejected in general. Our approach has a potential and scope for further study.

A potent estrogen receptor and microtubule specific purine-benzothiazole-based fluorescent molecular probe induces apoptotic death of breast cancer cells.

Breast cancer is the most common malignancy in women and is a heterogeneous disease at molecular level. Early detection and specificity are the key prerequisite for the treatment of this deadly cancer. To address these issues attention on the breast cancer specific receptor protein(s) is the most realistic option. Herein estrogen (E) and progesterone (Pg) receptors(R) were considered to design fluorescent molecular probes with possible therapeutic option. We adopted QSAR technique to design a library of benzothiazole-purine hybrid molecules. Molecular docking offers us three screened molecules as most potential. Among these molecules one abbreviated as "CPIB" showed blue fluorescence and detected ER positive cancer cells at 1 nM concentration. At elevated concentration, CPIB induces apoptotic deaths of same cancer cells through targeting intracellular microtubules without affecting normal cells or ER negative cells. CPIB is one of its kind with two-in-one potential of "Detection and Destroy" ability targeting ER positive breast cancer cells.

Exosome: The "Off-the-Shelf" Cellular Nanocomponent as a Potential Pathogenic Agent, a Disease Biomarker, and Neurotherapeutics.

Exosomes are nanosized "off-the-shelf" lipid vesicles released by almost all cell types and play a significant role in cell-cell communication. Exosomes have already been proven to carry cell-specific cargos of proteins, lipids, miRNA, and noncoding RNA (ribonucleic acid). These vesicles can be selectively taken up by the neighboring cell and can regulate cellular functions. Herein, we have discussed three different roles of exosomes in neuroscience. First, we have discussed how exosomes play the role of a pathogenic agent as a part of cell-cell communication and transmit pathogens such as amyloid-beta (Aß), further helping in the propagation of neurodegenerative and other neurological diseases. In the next section, the review talks about the role of exosomes in biomarker discovery in neurological disorders. Toward the end, we have reviewed how exosomes can be harnessed and engineered for therapeutic purposes in different brain diseases. This review is based on the current knowledge generated in this field and our comprehension of this domain.

Facile Method of Tubulin Purification from Goat Brain for Reconstitution of Microtubule-Associated Intracellular Function.

Tubulin/microtubule plays crucial role in eukaryotic cell division. Polymerization of αß-tubulin heterodimers forms the microtubules, which is essential for the segregation of chromosomes during cell division and organelle positioning. Our method of tubulin purification from the goat brain includes isolation of goat brain, multiple cycles of polymerization (warming at 37 °C)-depolymerization (cooling at 4 °C) followed by centrifugation process. The purified tubulin from goat brain is highly functional and successfully used in different applications including reconstitution of cell like environments and understanding molecular mechanisms. Toward the end of the chapter, we have discussed, how this purified tubulin can be used for reconstitution of intracellular microtubule-associated events or function. To enable our reconstitution approach, we have developed various micropatterned-based platform and their fabrication methodology with single ligand and dual-ligand functionalizations, which are also demonstrated. These chemically functionalized micropatterned platforms are extremely useful for immobilization of tubulin/microtubule onto the localized defined area, which will be helpful in mimicking cellular phenomena like kinesin-driven transport, microtubule dynamics, etc.

Designed hybrid anticancer nuclear-localized peptide inhibits aggressive cancer cell proliferation.

Cell proliferation is a crucial step that might promote cancer if deregulated. Therefore, this vital segment is critically controlled by a complicated cell-cycle process in normal cells that is regulated by some regulatory proteins. It has been observed that p16 protein, playing a crucial role in cell-cycle progression/regulation, remains inactivated in different cancer cells. This inactivity of p16 protein leads to the enhancement of cancer cell proliferation by allowing uncontrolled cancer cell division. Hence, the activity of p16 protein needs to be restored using new viral vectors, small molecules as well as peptides to control/suppress this type of abnormal cell proliferation. In this work, we have taken an interesting approach to increase the efficiency and bio-availability of p16 peptide (functional part of p16 protein) to be an aggressive anti-leukemia therapeutic agent by conjugating a nuclear-localized signal (NLS) sequence and a short peptide (AVPI) with it. Moreover, this newly designed NLS attached hybrid peptide greatly affects XIAP expressing but p16 lower expressing human chronic myelogenous leukemia (CML) cell proliferation by targeting both nuclear (CDK4/cyclin D) and cellular factors (XIAP) and promoting the caspase-3 dependent apoptosis pathway.

Investigating the interference of single nucleotide polymorphisms with miRNA mediated gene regulation in pancreatic ductal adenocarcinoma: An in silico approach.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a strong genetic component and single nucleotide polymorphisms (SNPs) in key genes have been found to modulate the susceptibility of the individuals to the disease. SNPs in 3'-UTR of the target genes or in miRNA seed region has gained much importance as this may lead to impairment of miRNA-mRNA interaction. Not much information about this phenomenon is available with respect to PDAC and we wanted to predict such SNPs which could affect miRNA function in the disease using bioinformatics tools. METHODS: After identifying the deregulated miRNAs and genes in PDAC, we determined how many of those altered genes are among experimentally validated targets of those miRNAs. Subsequently, SNPs which could alter these miRNA-mRNA interactions were detected using multiple webtools following high stringent conditions. Disease relevance of the SNPs were also evaluated. RESULTS: We identified a total of 2492 experimentally validated target genes for 303 miRNAs deregulated in PDAC. Our meta-analysis from 363 PDAC patients and 162 control individuals resulted in a set of differentially expressed genes in pancreatic cancer, which was further compared with the miRNA target genes to get targets differentially expressed in pancreatic cancer. We further detected SNPs either in 'seed' region of miRNAs or 'seed-match' sequence of mRNAs either having disruption or creation of miRNA binding site, correlated the expression for each miRNA-SNP-mRNA interaction. Selected SNPs were found to be in LD with important GWAS identified SNPs. CONCLUSION: Our study, hereby, explores the probable effects of SNPs on miRNA-target mRNA interactions. Through stringent analytical methods, we have identified 3 common variants and 13other rare variants possibly interfering with miRNA mediated gene regulation in PDAC.

Engineered bioclimatic responses in ancient settlements: a case study.

The Mandya district of Karnataka, India, houses a unique Jain settlement constructed about 1000 years ago. Recent excavations by the Archaeological Survey of India (ASI) indicate a high degree of engineering skills among the builders of this settlement. Adapting to heat-stresses in a region where the Monsoons often failed was and is still a matter of concern. Ingenious methods were adopted to modulate bioclimatic responses to maintain thermal comfort indices. The Aretippurians used composite building fabrics which modulated heat transfer to the interiors. Indeed, the thermal transmittances for these composite fabrics were low to moderate for both the temple complexes as well as the dormitories; these were 0.27 Wm-1K-1 and 0.23 Wm-1K-1, respectively. A site visit revealed that a unique and engineered micro-climate was also made to prevail on this hilltop settlement housing several hundred Jain settlers. A granite skirted reservoir was indeed the pièce-de-résistance promoting hydraulic air-conditioning for eight months of the year around the premises with copious winds blowing over a large and exposed rain-fed reservoir. This fanned chilled air across the open plan temples, courtyards, and lived-in areas. This paper explores bioclimatic responses for around 120 residents to the prevailing indoor settings modulated by an engineered microclimate. This was possible because of the staggered layout, unique building forms, use of mixed building fabric, and carefully chosen glazing ratios which yielded salubrious settings. Clearly, this entailed a complex interplay between the intercepted solar insolation, structure-driven turbulence, and the transfer of heat across the original composite walls within and around the complex, requiring a systematic experimental as well as modelling study. The experimental part of the project involved the calculation of the thermal transmittivity across the walls made up of fired bricks, granite, and limestone, and the theoretical part involved the use of appropriate software to reconstruct air flow and heat distribution across floors, walls, and ceilings to proxy the original flow pattern yielding the comfortable PMV (predicted mean vote) and PET (physiological equivalent temperature) values within these premises. This exercise may well lead to further explorations on indoor comfort adaptations in tropical settings with the use of many edifying vernacular idioms in ancient settlements which prevail even in modern layouts.

Cell-Derived Exosome Therapy: A Novel Approach to Treat Post-traumatic Brain Injury Mediated Neural Injury.

Traumatic brain injury (TBI) causes serious neuronal injury that often leads to death. To date there is no clinically successful treatment strategy that has been reported which offers repair of the brain injury or neural injury. Significant attempts have been made to develop effective therapies for TBI, and one of the most promising approaches is a stem cell based therapeutic approach with mesenchymal stem cells (MSCs). This approach is regarded as having the most potential in regenerative medicine. Toward this venture, the generation and release of exosomes can be attributed to the therapeutic effects of MSCs. Exosomes are nanosized vesicles, carry proteins, lipids, mRNA, and miRNA, and assist in cell-cell communication. Exosomes can interact with brain parenchyma cells and with the neurogenic niche, which can help in neurogenesis and brain remodeling. Exosomes derived from MSCs and human-induced pluripotent stem cells (hiPSCs) can be a promising approach in neuronal injury healing. In this Viewpoint, we discussed the most recent knowledge for exosome therapies for neural injuries and highlighted the major advantages of this therapy.

Targeting Chondroitin Sulfate Proteoglycans: An Emerging Therapeutic Strategy to Treat CNS Injury.

Chondroitin sulfate proteoglycans (CSPGs) are the most abundant components of glial scar formed after severe traumatic brain injury as well as spinal cord injury and play a crucial inhibitory role in axonal regeneration by selective contraction of filopodia of the growth cone of sprouting neurites. Healing of central nervous system (CNS) injury requires degradation of the glycosamine glycan backbone of CSPGs in order to reduce the inhibitory effect of the CSPG layer. The key focus of this Viewpoint is to address a few important regenerative approaches useful for overcoming the inhibitory barrier caused by chondroitin sulfate proteoglycans.

An overview of key potential therapeutic strategies for combat in the COVID-19 battle.

The sudden ravaging outbreak of a novel coronavirus, or SARS-CoV-2, in terms of virulence, severity, and casualties has already overtaken previous versions of coronaviruses, like SARS CoV and MERS CoV. Originating from its epicenter in Wuhan, China, this mutated version of the influenza virus with its associated pandemic effects has engulfed the whole world with awful speed. In the midst of this bewildering situation, medical and scientific communities are on their toes to produce the potential vaccine-mediated eradication of this virus. Though the chances are really high, to date no such panacea has been reported. The time requirements for the onerous procedures of human trials for the successful clinical translation of any vaccine or potential therapeutics are also a major concern. In order to build some resistance against this massive pandemic, the repurposing of some earlier antiviral drugs has been done, along with the refurbishment of some immune-responsive alternative avenues, like monoclonal antibody mediated neutralization, interferon treatment, and plasma therapy. New drugs developed from the RBD domain of the virus spike protein and drugs targeting viral proteases are also undergoing further research and have shown potential from preliminary results. The sole purpose of this review article is to provide a brief collective overview of the recent status of therapeutics advances and approaches, and their current state of implementation for the management of COVID-19.

Three-Dimensional Microfluidic Platform with Neural Organoids: Model System for Unraveling Synapses.

Unraveling the large number of various signals in the brain under the influence of physical and chemical cues that govern the formation of individual neurons, axons, dendrites, and their functional synapses during the development of neural network is a challenging task. To understand this task, microfluidic devices equipped with microchannels for reconstitution of cell/tissue-culture environments have been studied. Microfluidic devices are emerging as powerful tools in neurobiology, since they are capable of controlling and manipulating the microenvironment of the brain in a precise manner. They can enhance the physiological relevance of three-dimensional (3D) cell culture by allowing spatial control over fluids in micrometer-sized channels. Recent technological advancement in designing microfluidic platforms for studying neural communication, disease progression, and detection of neurotransmitters enhance our fundamental knowledge and understanding. However, more such advanced and innovative interventions are required. This Viewpoint focuses on highlighting a few of them with future scope of further advancement in this field.

High-Dimensional Posterior Consistency in Bayesian Vector Autoregressive Models.

Vector autoregressive (VAR) models aim to capture linear temporal interdependencies amongst multiple time series. They have been widely used in macroeconomics and financial econometrics and more recently have found novel applications in functional genomics and neuroscience. These applications have also accentuated the need to investigate the behavior of the VAR model in a high-dimensional regime, which provides novel insights into the role of temporal dependence for regularized estimates of the model's parameters. However, hardly anything is known regarding properties of the posterior distribution for Bayesian VAR models in such regimes. In this work, we consider a VAR model with two prior choices for the autoregressive coefficient matrix: a non-hierarchical matrix-normal prior and a hierarchical prior, which corresponds to an arbitrary scale mixture of normals. We establish posterior consistency for both these priors under standard regularity assumptions, when the dimension p of the VAR model grows with the sample size n (but still remains smaller than n). A special case corresponds to a shrinkage prior that introduces (group) sparsity in the columns of the model coefficient matrices. The performance of the model estimates are illustrated on synthetic and real macroeconomic data sets.