Tracing the Vedic Saraswati River in the Great Rann of Kachchh

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 7 (2017): 5476, doi:10.1038/s41598-017-05745-8.The lost Saraswati River mentioned in the ancient Indian tradition is postulated to have flown independently of the Indus River into the Arabian Sea, perhaps along courses of now defunct rivers such as Ghaggar, Hakra and Nara. The persistence of such a river during the Harappan Bronze Age and the Iron Age Vedic period is strongly debated. We drilled in the Great Rann of Kachchh (Kutch), an infilled gulf of the Arabian Sea, which must have received input from the Saraswati, if active. Nd and Sr isotopic measurements suggest that a distinct source may have been present before 10 ka. Later in Holocene, under a drying climate, sediments from the Thar Desert probably choked the signature of an independent Saraswati-like river. Alternatively, without excluding a Saraswati-like secondary source, the Indus and the Thar were the dominant sources throughout the post-glacial history of the GRK. Indus-derived sediment accelerated the infilling of GRK after ~6 ka when the Indus delta started to grow. Until its complete infilling few centuries ago, freshwater input from the Indus, and perhaps from the Ghaggar-Hakra-Nara, probably sustained a productive marine environment as well as navigability toward old coastal Harappan and historic towns in the region.The drilling effort and subsequent study of the cores was funded by Department of Science and Technology (DST), Government of India sponsored research project to DMM (Project No. SR/S4/ES-21/Kachchh Window/P1) under the science of Shallow Subsurface Programme (SSS). N. Khonde gratefully acknowledges Indo-US Post-doctoral Fellowship sponsored by SERB-IUSSTF for research work at Woods Hole Oceanographic Institution

Proximity-induced ferromagnetism and chemical reactivity in few-layer VSe2 heterostructures

Among transition-metal dichalcogenides, mono and few-layers thick VSe2 has gained much recent attention following claims of intrinsic room-temperature ferromagnetism in this system, which have nonetheless proved controversial. Here, we address the magnetic and chemical properties of Fe/VSe2 heterostructure by combining element sensitive x-ray absorption spectroscopy and photoemission spectroscopy. Our x-ray magnetic circular dichroism results confirm recent findings that both native mono/few-layer and bulk VSe2 do not show intrinsic ferromagnetic ordering. Nonetheless, we find that ferromagnetism can be induced, even at room temperature, after coupling with a Fe thin film layer, with antiparallel alignment of the moment on the V with respect to Fe. We further consider the chemical reactivity at the Fe/VSe2 interface and its relation with interfacial magnetic coupling

A study of the dynamics of magnetic disaccommodation in amorphous ferromagnets. I. Experimental results

Systematic room‐temperature measurements of the aftereffect of the ac magnetic permeability have been performed on a Fe81B13.5 Si3.5C2 amorphous ribbon in order to get detailed information about the nature of the atomic ordering processes responsible for the magnetic relaxation. The magnetic aftereffect related to 180° domain‐wall motion has been measured by means of a specific technique allowing periodic domain‐wall displacements to be induced between two fixed, neighboring equilibrium positions by applying a square‐wave field of proper amplitude and frequency. In this way, the average direction of the magnetization vector is cyclically modified in all points where the studied directional ordering processes may occur. As a consequence, the kinetics of ordering is modified in a characteristic way, giving rise to relevant variations in the intensity of the magnetic aftereffect measured between fixed times (t1=2×10−3 s and t2=10−1 s), and in the value of the magnetic induction at the time t2. All measurements have been performed at constant applied field. The degree of reliability of this experimental technique has been analyzed in detail. The magnetic aftereffect, ΔB=B(t1)−B(t2), and the magnetic induction B(t2) have been measured as functions of the number of domain‐wall cycles, and after removing the square‐wave field for a variable time t∗. The results of many independent measurements are reported and discussed

Clonidine for the Treatment of Agitation After Dexmedetomidine Discontinuation in Pediatric Patients: A Retrospective Cohort Study

OBJECTIVE: Dexmedetomidine has become a widely used drug in PICUs for sedation. We aim to determine the effects of clonidine on pediatric patients after dexmedetomidine use. METHODS: This was a retrospective cohort study that evaluated all pediatric patients admitted to a tertiary PICU who received dexmedetomidine infusion for \u3e48 hours. Outcomes in patients exposed to clonidine (CLON) were compared with those of patients who were not exposed (NoCLON). RESULTS: A total of 216 patients were included in this study (43 CLON and 173 NoCLON). The primary outcome, agitation, was less in the CLON cohort (9.3%) than in the NoCLON cohort (9.3% versus 29.5%, respectively; p \u3c 0.01). Hospital LOS was longer in the CLON group (59 versus 20 days, p \u3c 0.01), as was PICU LOS (37.4 versus 11.1 days, p \u3c 0.01). There was no significant difference in the occurrence of increased heart rate or blood pressure between the 2 cohorts. Patients exposed to concurrent midazolam and opioid infusions had higher incidence of agitation when they did not receive clonidine (CLON 8% versus NoCLON 37%, OR 0.15; 95% CI, 0.05-0.51; p \u3c 0.01). In contrast, there was no difference in the incidence of agitation for the CLON group versus the NoCLON group when dexmedetomidine was administered alone (25% versus 19%, OR 1.4; p = 0.99). CONCLUSIONS: Our study confirms the importance and effectiveness of clonidine to treat agitation after dexmedetomidine discontinuation. A validated withdrawal scoring tool can help better define dexmedetomidine withdrawal in pediatric patients

The Staphylococcus aureus CidA and LrgA Proteins Are Functional Holins Involved in the Transport of By-Products of Carbohydrate Metabolism

The Staphylococcus aureus cidABC and lrgAB operons encode members of a well-conserved family of proteins thought to be involved in programmed cell death (PCD). Based on the structural similarities that CidA and LrgA share with bacteriophage holins, we have hypothesized that these proteins function by forming pores within the cytoplasmic membrane. To test this, we utilized a lysis cassette system that demonstrated the abilities of the cidA and lrgA genes to support bacteriophage endolysin-induced cell lysis. Typical of holins, CidA- and LrgA-induced lysis was dependent on the coexpression of endolysin, consistent with the proposed holin-like functions of these proteins. In addition, the CidA and LrgA proteins were shown to localize to the surface of membrane vesicles and cause leakage of small molecules, providing direct evidence of their hole-forming potential. Consistent with recent reports demonstrating a role for the lrgAB homologues in other bacterial and plant species in the transport of by-products of carbohydrate metabolism, we also show that lrgAB is important for S. aureus to utilize pyruvate during microaerobic and anaerobic growth, by promoting the uptake of pyruvate under these conditions. Combined, these data reveal that the CidA and LrgA membrane proteins possess holin-like properties that play an important role in the transport of small by-products of carbohydrate metabolism. IMPORTANCE The Staphylococcus aureus cidABC and lrgAB operons represent the founding members of a large, highly conserved family of genes that span multiple kingdoms of life. Despite the fact that they have been shown to be involved in bacterial PCD, very little is known about the molecular/biochemical functions of the proteins they encode. The results presented in this study reveal that the cidA and lrgA genes encode proteins with bacteriophage holin-like functions, consistent with their roles in cell death. However, these studies also demonstrate that these operons are involved in the transport of small metabolic by-products of carbohydrate metabolism, suggesting an intriguing link between these two seemingly disparate processes

Staphylococcus aureus ATP Synthase Promotes Biofilm Persistence by Influencing Innate Immunity

ABSTRACT Staphylococcus aureus is a major cause of prosthetic joint infection (PJI), which is characterized by biofilm formation. S. aureus biofilm skews the host immune response toward an anti-inflammatory profile by the increased recruitment of myeloid-derived suppressor cells (MDSCs) that attenuate macrophage proinflammatory activity, leading to chronic infection. A screen of the Nebraska Transposon Mutant Library identified several hits in the ATP synthase operon that elicited a heightened inflammatory response in macrophages and MDSCs, including atpA, which encodes the alpha subunit of ATP synthase. An atpA transposon mutant (ΔatpA) had altered growth kinetics under both planktonic and biofilm conditions, along with a diffuse biofilm architecture that was permissive for leukocyte infiltration, as observed by confocal laser scanning microscopy. Coculture of MDSCs and macrophages with ΔatpA biofilm elicited significant increases in the proinflammatory cytokines interleukin 12p70 (IL-12p70), tumor necrosis factor alpha (TNF-α), and IL-6. This was attributed to increased leukocyte survival resulting from less toxin and protease production by ΔatpA biofilm as determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The enhanced inflammatory response elicited by ΔatpA biofilm was cell lysis-dependent since it was negated by polyanethole sodium sulfanate treatment or deletion of the major autolysin, Atl. In a mouse model of PJI, ΔatpA-infected mice had decreased MDSCs concomitant with increased monocyte/macrophage infiltrates and proinflammatory cytokine production, which resulted in biofilm clearance. These studies identify S. aureus ATP synthase as an important factor in influencing the immune response during biofilm-associated infection and bacterial persistence. IMPORTANCE Medical device-associated biofilm infections are a therapeutic challenge based on their antibiotic tolerance and ability to evade immune-mediated clearance. The virulence determinants responsible for bacterial biofilm to induce a maladaptive immune response remain largely unknown. This study identified a critical role for S. aureus ATP synthase in influencing the host immune response to biofilm infection. An S. aureus ATP synthase alpha subunit mutant (ΔatpA) elicited heightened proinflammatory cytokine production by leukocytes in vitro and in vivo, which coincided with improved biofilm clearance in a mouse model of prosthetic joint infection. The ability of S. aureus ΔatpA to augment host proinflammatory responses was cell lysis-dependent, as inhibition of bacterial lysis by polyanethole sodium sulfanate or a ΔatpAΔatl biofilm did not elicit heightened cytokine production. These studies reveal a critical role for AtpA in shaping the host immune response to S. aureus biofilm

A central role for carbon-overflow pathways in the modulation of bacterial cell death.

Similar to developmental programs in eukaryotes, the death of a subpopulation of cells is thought to benefit bacterial biofilm development. However mechanisms that mediate a tight control over cell death are not clearly understood at the population level. Here we reveal that CidR dependent pyruvate oxidase (CidC) and α-acetolactate synthase/decarboxylase (AlsSD) overflow metabolic pathways, which are active during staphylococcal biofilm development, modulate cell death to achieve optimal biofilm biomass. Whereas acetate derived from CidC activity potentiates cell death in cells by a mechanism dependent on intracellular acidification and respiratory inhibition, AlsSD activity effectively counters CidC action by diverting carbon flux towards neutral rather than acidic byproducts and consuming intracellular protons in the process. Furthermore, the physiological features that accompany metabolic activation of cell death bears remarkable similarities to hallmarks of eukaryotic programmed cell death, including the generation of reactive oxygen species and DNA damage. Finally, we demonstrate that the metabolic modulation of cell death not only affects biofilm development but also biofilm-dependent disease outcomes. Given the ubiquity of such carbon overflow pathways in diverse bacterial species, we propose that the metabolic control of cell death may be a fundamental feature of prokaryotic development