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Marine heatwaves (MHWs) are prolonged warm sea condition events that can have a destructive impact on marine ecosystems. The documentation of MHWs and assessment of their impacts is largely confined to a few regional seas or to global mean studies. The north Indian Ocean received almost no attention in this regard despite the fact that this ocean basin, particularly the Arabian Sea, has been warming at the most rapid pace among the other tropical basins in recent decades. This study shows the characteristics of MHW events for the Arabian Sea during 1982–2019. Our analysis shows that the duration (frequency) of MHWs exhibits a rapidly increasing trend of ∼20 d per decade (1.5–2 events per decade) in the northern Arabian Sea and the southeastern Arabian Sea close to the west coast of India, which is a multifold increase in MHW days (frequency) from the 80s. Notably, since the beginning of the satellite record, the years 2010 and 2016 have exhibited the maximum number of heatwave days when more than 75 % of days of the pre-monsoon and summer monsoon season experience heatwaves. The accelerated trend of the heatwave days is found to be driven by the rapid rise in the mean sea surface temperature (SST) of the Arabian Sea in the recent decade. Moreover, longer heatwave days are also associated with dominant climate modes. Among them, the Indian Ocean Basin Mode via the decaying phase of El Niño is the most influential mode contributing to more than 70 %–80 % of observed heatwave days in this basin. Further analysis of the most prolonged observed heatwave during April–June 2010 indicates that surface heat flux associated with the weaker latent heat loss and the shallow mixed layer was the primary cause of this event. Further, we note that the pre-monsoon cyclonic storms in the Arabian Sea often contribute to the waning of such heatwaves in the basin.

Citrobacter rodentium is an extracellular enteric mouse-specific pathogen used to model infections with human pathogenic Escherichia coli and inflammatory bowel disease. C. rodentium injects type III secretion system effectors into intestinal epithelial cells (IECs) to target inflammatory, metabolic and cell survival pathways and establish infection. While the host responds to infection by activating innate and adaptive immune signalling, required for clearance, the IECs respond by rapidly shifting bioenergetics to aerobic glycolysis, which leads to oxygenation of the epithelium, an instant expansion of mucosal-associated commensal Enterobacteriaceae and a decline of obligate anaerobes. Moreover, infected IECs reprogramme intracellular metabolic pathways, characterized by simultaneous activation of cholesterol biogenesis, import and efflux, leading to increased serum and faecal cholesterol levels. In this Review we summarize recent advances highlighting the intimate relationship between C. rodentium pathogenesis, metabolism and the gut microbiota.

The skin is the body's largest organ and serves as a site of administration for various medications. Transdermal drug delivery systems have several advantages over traditional delivery systems. It has both local and systemic therapeutic properties. Controlled plasma drug levels, reduced dosing frequency, and avoidance of hepatic first-pass metabolism are just a few of these systems' advantages. To achieve maximum efficacy, it is critical to understand the kinetics, physiochemical properties of the drug moiety, and drug transport route. This manuscript focused on the principles of various physical means to facilitate transdermal drug delivery. Some examples are iontophoresis, electrophoresis, photomechanical waves, ultrasound, needleless injections, and microneedles. Mechanical, chemical, magnetic, and electrical energy are all used in physical methods. A major advantage of physical methods is their capability to abbreviate pain, which can be used for effective disease management. Further investigation should be carried out at the clinical level to understand these methods for effective drug delivery.

Diabetes is a chronic metabolic disorder that poses a global burden to healthcare. Increasing incidence of diabetes-related complications in the affected population includes a delay in wound healing that often results in non-traumatic limb amputations. Owing to the intricacies of the healing process and crosstalk between the multitude of participating cells, the identification of hyperglycaemia-induced changes at both cellular and molecular levels poses a challenge. Macrophages are one of the key participants in wound healing and continue to exert functional changes at the wound site since the time of injury. In the present review, we discuss the role of these cells and their aberrant functions in diabetic wounds. We have extensively studied the process of macrophage polarization (MP) and its modulation through epigenetic modifications. Data from both pre-clinical and clinical studies on diabetes have co-related hyperglycaemia induced changes in gene expression to an increased incidence of diabetic complications. Hyperglycaemia and oxidative stress, create an environment prone to changes in the epigenetic code, that is manifested as an altered inflammatory gene expression. Here, we have attempted to understand the different epigenetic modulations that possibly contribute towards dysregulated MP, resulting in delayed wound healing.

Inflammasomes are sensory complexes that alert the immune system to the presence of infection or tissue damage. These complexes assemble NLR (nucleotide binding and oligomerization, leucine-rich repeat) or ALR (absent in melanoma 2-like receptor) proteins to activate caspase-1 cleavage and interleukin (IL)—1β/IL-18 secretion. Here, we identified a non-NLR/ALR human protein that stimulates inflammasome assembly: guanylate binding protein 5 (GBP5). GBP5 promoted selective NLRP3 inflammasome responses to pathogenic bacteria and soluble but not crystalline inflammasome priming agents. Generation of Gbp5 -/- mice revealed pronounced caspase-1 and IL-lβ/IL-18 cleavage defects in vitro and impaired host defense and Nlrp3-dependent inflammatory responses in vivo. Thus, GBP5 serves as a unique rheostat for NLRP3 inflammasome activation and extends our understanding of the inflammasome complex beyond its core machinery.

Shigella flexneri, a Gram-negative enteroinvasive pathogen, causes inflammatory destruction of the human intestinal epithelium. Infection by S. flexneri has been well-studied in vitro and is a paradigm for bacterial interactions with the host immune system. Recent work has revealed that components of the cytoskeleton have important functions in innate immunity and inflammation control. Septins, highly conserved cytoskeletal proteins, have emerged as key players in innate immunity to bacterial infection, yet septin function in vivo is poorly understood. Here, we use S. flexneri infection of zebrafish (Danio rerio) larvae to study in vivo the role of septins in inflammation and infection control. We found that depletion of Sept15 or Sept7b, zebrafish orthologs of human SEPT7, significantly increased host susceptibility to bacterial infection. Live-cell imaging of Sept15-depleted larvae revealed increasing bacterial burdens and a failure of neutrophils to control infection. Strikingly, Sept15-depleted larvae present significantly increased activity of Caspase-1 and more cell death upon S. flexneri infection. Dampening of the inflammatory response with anakinra, an antagonist of interleukin-1 receptor (IL-1R), counteracts Sept15 deficiency in vivo by protecting zebrafish from hyper-inflammation and S. flexneri infection. These findings highlight a new role for septins in host defence against bacterial infection, and suggest that septin dysfunction may be an underlying factor in cases of hyper-inflammation.

Storage-class memory (SCM) combines the benefits of a solid-state memory, such as high performance and robustness, with the archival capabilities and low cost of conventional hard-disk magnetic storage. Such a device would require a solid-state nonvolatile memory technology that could be manufactured at an extremely high effective areal density using some combination of sublithographic patterning techniques, multiple bits per cell, and multiple layers of devices. We review the candidate solid-state nonvolatile memory technologies that potentially could be used to construct such an SCM. We discuss evolutionary extensions of conventional flash memory, such as SONOS (silicon-oxide-nitride-oxide-silicon) and nanotraps, as well as a number of revolutionary new memory technologies. We review the capabilities of ferroelectric, magnetic, phase-change, and resistive random-access memories, including perovskites and solid electrolytes, and finally organic and polymeric memory. The potential for practical scaling to ultrahigh effective areal density for each of these candidate technologies is then compared. [PUBLICATION ABSTRACT]

Sensing bacterial products in the cytosol of mammalian cells by NOD-like receptors leads to the activation of caspase-1 inflammasomes, and the production of the pro-inflammatory cytokines interleukin (IL)-18 and IL-1β. In addition, mouse caspase-11 (represented in humans by its orthologs, caspase-4 and caspase-5) detects cytosolic bacterial LPS directly. Activation of caspase-1 and caspase-11 initiates pyroptotic host cell death that releases potentially harmful bacteria from the nutrient-rich host cell cytosol into the extracellular environment. Here we use single cell analysis and time-lapse microscopy to identify a subpopulation of host cells, in which growth of cytosolic Salmonella Typhimurium is inhibited independently or prior to the onset of cell death. The enzymatic activities of caspase-1 and caspase-11 are required for growth inhibition in different cell types. Our results reveal that these proteases have important functions beyond the direct induction of pyroptosis and proinflammatory cytokine secretion in the control of growth and elimination of cytosolic bacteria. Inflammatory caspases restrict microbial growth by inducing cytokine production and pyroptosis, but other caspase-induced mechanisms are thought to contribute. Here the authors use time-lapse microscopy of single cells to show that caspase1/11 has anti-Salmonella functions that occur in advance of cell death induction.

Purpose To evaluate and compare the clinical effectiveness of alkasite with nanofilled resin composite restorations for occlusal caries lesions in permanent molar teeth of children, at one-year follow-up. Methods In this randomized controlled clinical trial with parallel design, 38 children aged 7–13 years with occlusal caries lesions on 59 first permanent molars were randomly allocated into two groups, Group 1: Filtek™ Z350XT (nanocomposite) and Group 2: Cention N ® (alkasite resin composite). The restorations were evaluated at one year using the United States Public Health Service (USPHS) criteria. Data were analyzed using Chi-square or Fisher’s exact test. Results All restorations had either Alpha or Bravo scores at one-year follow-up. In Group 1, all restorations scored Alpha, while one restoration each (3.6%) in Group 2 scored Bravo for fracture and marginal adaptation. All restorations in both groups scored Alpha for retention, secondary caries, and post-operative sensitivity. For anatomic form, all restorations in Group 1 scored Alpha, while three (10.7%) restorations in Group 2 had Bravo scores. For marginal discolouration, three restorations in both groups scored Bravo (11.5% and 10.7%, respectively). For surface roughness, one restoration (3.8%) in Group 1 and three restorations in Group 2 (10.7%) scored Bravo. The comparative results between the two groups for all the variables in the USPHS criteria were not statistically significantly different. Conclusions The performances of the nanofilled composite and alkasite were clinically acceptable and comparable. Alkasite can be an alternative material for the restoration of occlusal caries lesions in permanent molars of children. Clinical trial registration The clinical trial was registered at Clinical Trials Registry—India (CTRI Reg no: CTRI/2020/12/029830 Dated: 15/12/2020).

This Perspective reviews the molecular, cellular and organismal response pathways that nucleic acid nanodevices are likely to interact with when deployed in living systems, and outlines ways to design nanodevices that either evade or react to the host response. DNA is proving to be a powerful scaffold to construct molecularly precise designer DNA devices. Recent trends reveal their ever-increasing deployment within living systems as delivery devices that not only probe but also program and re-program a cell, or even whole organisms. Given that DNA is highly immunogenic, we outline the molecular, cellular and organismal response pathways that designer nucleic acid nanodevices are likely to elicit in living systems. We address safety issues applicable when such designer DNA nanodevices interact with the immune system. In light of this, we discuss possible molecular programming strategies that could be integrated with such designer nucleic acid scaffolds to either evade or stimulate the host response with a view to optimizing and widening their applications in higher organisms.