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The Ayeyawady delta is the last Asian megadelta whose evolution has remained essentially unexplored so far. Unlike most other deltas across the world, the Ayeyawady has not yet been affected by dam construction, providing a unique view on largely natural deltaic processes benefiting from abundant sediment loads affected by tectonics and monsoon hydroclimate. To alleviate the information gap and provide a baseline for future work, here we provide a first model for the Holocene development of this megadelta based on drill core sediments collected in 2016 and 2017, dated with radiocarbon and optically stimulated luminescence, together with a reevaluation of published maps, charts and scientific literature. Altogether, these data indicate that Ayeyawady is a mud-dominated delta with tidal and wave influences. The sediment-rich Ayeyawady River built meander belt alluvial ridges with avulsive characters. A more advanced coast in the western half of the delta (i.e., the Pathein lobe) was probably favored by the more western location of the early course of the river. Radiogenic isotopic fingerprinting of the sediment suggests that the Pathein lobe coast does not receive significant sediment from neighboring rivers. However, the eastern region of the delta (i.e., Yangon lobe) is offset inland and extends east into the mudflats of the Sittaung estuary. Wave-built beach ridge construction during the late Holocene, similar to several other deltas across the Indian monsoon domain, suggests a common climatic control on monsoonal delta morphodynamics through variability in discharge, changes in wave climate or both. Correlation of the delta morphological and stratigraphic architecture information on land with the shelf bathymetry, as well as its tectonic, sedimentary and hydrodynamic characteristics, provides insight on the peculiar growth style of the Ayeyawady delta. The offset between the western Pathein lobe and the eastern deltaic coast appears to be driven by tectonic-hydrodynamic feedbacks as the extensionally lowered shelf block of the Gulf of Mottama amplifies tidal currents relative to the western part of the shelf. This situation probably activates a perennial shear front between the two regions that acts as a leaky energy fence. Just as importantly, the strong currents in the Gulf of Mottama act as an offshore-directed tidal pump that helps build the deep mid-shelf Mottama clinoform with mixed sediments from the Ayeyawady, Sittaung and Thanlwin rivers. The highly energetic tidal, wind and wave regime of the northern Andaman Sea thus exports most sediment offshore despite the large load of the Ayeyawady River. [ABSTRACT FROM AUTHOR]

Abstract: The TRIB1 locus (8q24.13) is a novel locus identified and replicated by several genome-wide association studies for associations with plasma triglycerides, apolipoprotein B and coronary artery disease. The TRIB1 protein product, tribbles-like protein 1 (Trib1), regulates MAPK activity. MAP kinases transduce a large variety of external signals, leading to a wide range of cellular responses, including growth, differentiation, inflammation and apoptosis. Importantly, Trib1 has been shown to regulate hepatic lipogenesis and very low density lipoprotein production. Despite the relevance of hepatocyte Trib1 to lipid metabolism and atherosclerosis, little is known about the mechanisms regulating Trib1 itself. Here, we identify the mitochondria axis as a regulator of Trib1. Treatment of HepG2 cells with a short pulse of a low oligomycin concentration led to a potent and prolonged increase in the Trib1 mRNA, an effect that was shared with other mitochondria stressors. HuH7 cells as well murine hepatocytes were also responsive albeit to a weaker extent. The upregulation appeared largely independent of reactive oxygen species generation or metabolic stress and was mainly under transcriptional control, with ERK1/2 playing an important regulating role in the process. While the presence of the Trib1 protein could be inferred, attempts to correlate the increased mRNA to changes in protein level were unsuccessful due to the lack of recognizable Trib1 signal. Our data enrich the current paradigm of Trib1 as an activator of the MAPK pathway by uncovering a role for MAPK in regulating Trib1. [Copyright &y& Elsevier]

The rising demand for powerful oncolytic virotherapy agents has led to the identification of Maraba virus, one of the most potent oncolytic viruses from Rhabdoviridae family which displays high selectivity for killing malignant cells and low cytotoxicity in normal cells. Although the virus is readied to be used for clinical trials, the interactions between the virus and the host cells is still unclear. Using a newly developed interferon-sensitive mutant Maraba virus (MG1), we have identified two key regulators of global translation (4E-BP1 and eIF2α) as being involved in the regulation of protein synthesis in the infected cells. Despite the translational arrest upon viral stress, we showed an up-regulation of anti-apoptotic Bcl-xL protein that provides a survival benefit for the host cell, yet facilitates effective viral propagation. Given the fact that eIF5B canonically regulates 60S ribosome subunit end joining and is able to replace the role of eIF2 in delivering initiator tRNA to the 40S ribosome subunit upon the phosphorylation of eIF2α we have tested whether eIF5B mediates the translation of target mRNAs during MG1 infection. Our results show that the inhibition of eIF5B significantly down-regulates the level of Bcl-xL steady-state mRNA, thus indirectly attenuates viral propagation. [ABSTRACT FROM AUTHOR]

Vegetated mid‐channel islands play an important though poorly understood role in the sediment dynamics and morphology of tide‐dominated deltas. Meinmahla Island is a mangrove‐forest preserve at the mouth of the Bogale distributary channel, in the Ayeyarwady Delta, Myanmar. In this relatively unaltered mid‐channel island, sediment dynamics can be directly connected to morphology. Field measurements from 2017 to 2019 provide insight into the pathways for sediment transport and resulting morphological evolution. Water depth, salinity and turbidity were monitored semi‐continuously, and velocity profilers with turbidity and salinity sensors were deployed seasonally in single‐entrance (dead‐end/blind) and multi‐entrance tidal channels of the island. The morphological evolution was evaluated using grain size, 210Pb geochronology, remote sensing and channel surveys. The data show that ebb‐dominant, single‐entrance channels along the island exterior import sediment year‐round to the land surface. However, these exterior channels do not deliver enough sediment to maintain the observed ca 0.8 cm/yr accretion rate, and most of the sediment import occurs via interior, multi‐entrance channels. Interior channels retain water masses that are physically distinct from the water in the Bogale distributary, and estuarine processes at the tidal‐channel mouths import sediment into the island. Sediment is sourced to the island from upriver in the wet season and from the Gulf of Mottoma in the dry season, as the location of the estuary shifts seasonally within the Bogale distributary. The salinity and biogeochemistry of the distributary water are affected by interactions with sediment and groundwater in the island interior. The largest interior channels have remained remarkably stable while the island has aggraded and prograded over decadal timescales. However, the studied multi‐entrance channel is responding to a drainage‐network change by narrowing and shoaling. Overall, mid‐channel islands trap sediment and associated nutrients at the river–ocean interface, and these resilient landscape features evolve in response to changes in drainage‐network connectivity. [ABSTRACT FROM AUTHOR]

Genome-wide association studies for plasma triglycerides and hepatic steatosis identified a risk locus on chromosome 8q24 close to the TRIB1 gene, encoding Tribbles Pseudokinase 1 (TRIB1). In previous studies conducted in murine models, hepatic over-expression of Trib1 was shown to increase fatty acid oxidation and decrease triglyceride synthesis whereas Trib1 knockdown mice exhibited hypertriglyceridemia. Here we have examined the impact of TRIB1 suppression in human and mouse hepatocytes. Examination of a panel of lipid regulator transcripts revealed species-specific effects, prompting us to focus on human models for the remainder of the study. Acute knockdown of TRIB1 in human primary hepatocytes resulted in decreased expression of MTTP and APOB , required for very low density lipoprotein (VLDL) assembly although particle secretion was not significantly affected. A parallel analysis performed in HepG2 revealed reduced MTTP, but not APOB, protein as a result of TRIB1 suppression. Global gene expression changes of human primary hepatocytes upon TRIB1 suppression were analyzed by clustering algorithms and found to be consistent with dysregulation of several pathways fundamental to liver function, including altered CEBPA and B transcript levels and impaired glucose handling. Indeed, TRIB1 expression in HepG2 cells was found to be inversely proportional to glucose concentration. Lastly TRIB1 downregulation in primary hepatocytes was associated with suppression of the HNF4A axis. In HepG2 cells, TRIB1 suppression resulted in reduced HNF4A protein levels while HNF4A suppression increased TRIB1 expression. Taken together these studies reveal an important role for TRIB1 in human hepatocyte biology. [ABSTRACT FROM AUTHOR]

Common intronic SNPs in the human fat mass and obesity associated (FTO) gene are strongly associated with body mass index (BMI). In mouse models, inactivation of the Fto gene results in a lean phenotype, whereas overexpression of Fto leads to increased food intake and obesity. The latter finding suggests that copy number variants at the FTO locus might be associated with extremes of adiposity. To address this question, we searched for rare, private or de novo copy number variation in a cohort of 985 obese and 869 lean subjects of European ancestry drawn from the extremes of the BMI distribution, genotyped on Affymetrix 6.0 arrays. A ∼680 kb duplication, confirmed by real-time PCR and G-to-FISH analyses, was observed between ∼rs11859825 and rs9932411 in a 68-year-old male with severe obesity. The duplicated region on chromosome 16 spans the entire genome-wide association studies risk locus for obesity, and further encompasses RBL2, AKTIP, RPGRIP1L and all but the last exon of the FTO gene. Affected family members exhibit a unique obesity phenotype, characterized by increased fat distribution in the shoulders and neck with a significantly increased neck circumference. This phenotype was accompanied by increased peripheral blood expression of RBL2 with no alteration in expression of FTO or other genes in the region. No other duplications or deletions in this region were identified in the cohort of obese and lean individuals or in a further survey of 4778 individuals, suggesting that large rare copy number variants surrounding the FTO gene are not a frequent cause of obesity. [ABSTRACT FROM AUTHOR]

Purpose. To identify systemic factors that may influence the response to anti-VEGF therapy in patients with diabetic macular edema (DME). Methods. 35 patients undergoing anti-VEGF injections for centre-involving DME were studied in this prospective observational study. The primary outcome was change in macular thickness one month after treatment, measured using spectral-domain optical coherence tomography (OCT). At baseline, information on various systemic factors was collected including glycosylated hemoglobin (HbA1c), serum VEGF levels, lipid profile and markers of renal function, and blood pressure. Thirty-three of the 35 patients were included in this study. Nonparametric statistical tests were used for the analysis of the data in view of the nonnormal distribution of the outcome variables. Multivariate analysis was performed using logistic regression. Stata 12.1 software was used for the analysis. Main Outcome Measures. Reduction in macular central subfield thickness (on spectral-domain OCT) and change in logMAR visual acuity at one month after injection. Results. Lower HbA1c levels (7% or less) were significantly associated with greater reduction in central macular subfield thickness at one month after injection of bevacizumab or ranibizumab on both univariate analysis (p = 0.012) and multivariate analysis (p = 0.042). Conclusions. Better glycemic control is associated with a greater reduction in central macular thickness after the first injection of bevacizumab or ranibizumab in diabetic macular edema. Patients with high levels of HbA1c and poor response to anti-VEGF may benefit from strict control of their blood glucose. [ABSTRACT FROM AUTHOR]

Heavy metal and metalloid contaminations are among the most concerning types of pollutant in the environment. Consequently, it is important to investigate the molecular mechanisms of cellular responses and detoxification pathways for these compounds in living organisms. To date, a number of genes have been linked to the detoxification process. The expression of these genes can be controlled at both transcriptional and translational levels. In baker’s yeast, Saccharomyces cerevisiae, resistance to a wide range of toxic metals is regulated by glutathione S-transferases. Yeast URE2 encodes for a protein that has glutathione peroxidase activity and is homologous to mammalian glutathione S-transferases. The URE2 expression is critical to cell survival under heavy metal stress. Here, we report on the finding of two genes, ITT1, an inhibitor of translation termination, and RPS1A, a small ribosomal protein, that when deleted yeast cells exhibit similar metal sensitivity phenotypes to gene deletion strain for URE2. Neither of these genes were previously linked to metal toxicity. Our gene expression analysis illustrates that these two genes affect URE2 mRNA expression at the level of translation. [ABSTRACT FROM AUTHOR]

The Arakan forest turtle ( Heosemys depressa) is a critically endangered, poorly known chelonian endemic to western Myanmar. Previously known only from the Rakhine ( = Arakan) Hills, we here report a significant northward range extension into the southern Chin Hills, verify the occurrence of H. depressa in Kyauk Pan Taung Wildlife Sanctuary, and present new information on elevational limits, natural history, and folk taxonomy of this enigmatic species. [ABSTRACT FROM AUTHOR]

The deposits of large Asian rivers with unique drainage geometries have attracted considerable attention due to their explanatory power concerning tectonism, surface uplift and upstream drainage evolution. This study presents the first petrographic, heavy mineral, Nd and Sr isotope geochemistry, and detrital zircon geochronology results from the Holocene Irrawaddy megadelta alongside modern and ancient sedimentary provenance datasets to assess the late Neogene evolution of the Irrawaddy River. Contrary to models advocating a steady post-middle Miocene river, we reveal an evolution of the Irrawaddy River more compatible with regional evidence for kinematic reorganization in Myanmar during late-stage India-Asia collision. Quaternary sediments are remarkably consistent in terms of provenance but highlight significant decoupling amongst fine and coarse fraction 87Sr/86Sr and ε Nd due to hydraulic sorting. Only well after the late Miocene do petrographic, heavy mineral, isotope geochemistry, and detrital zircon U–Pb results from the trunk Irrawaddy and its tributaries achieve modern-day signatures. The primary driver giving rise to the geometry and provenance signature of the modern Irrawaddy River was regional late Miocene (≤10 Ma) basin inversion coupled with uplift and cumulative displacement along the Sagaing Fault. Middle to late Miocene provenance signatures cannot be reconciled with modern river geometries, and thus require significant loss of headwaters feeding the Chindwin subbasin after ∼14 Ma and the northern Shwebo subbasin after ∼11 Ma. Large-scale reworking after ∼7 Ma is evidenced by modern Irrawaddy River provenance, by entrenchment of the nascent drainage through Plio-Pleistocene inversion structures, and in the transfer of significant sediment volumes to the Andaman Sea. • Main trunk and tributary provenance not stable until after late Miocene. • Hydraulic sorting drives fine and coarse sediment 87Sr/86Sr and ε Nd decoupling. • Sagaing Fault beheaded tributaries after 14 Ma in west and 11 Ma in east. • Quaternary provenance reflects post-10 Ma inversion and entrenchment. [ABSTRACT FROM AUTHOR]

The Great Slaty Woodpecker (Mulleripicus pulverulentus) of South and Southeast Asia, the third largest woodpecker species in the world, is currently in the IUCN Red List category of Least Concern. This woodpecker appears associated with old-growth forests, and the rapid reductions in forest cover and old-growth area in Southeast Asia urged examination of its global population trends. We assessed population densities, tree diameter use by the woodpecker, and logging disturbance at 21 transects in four regions across the range of the species: west Borneo, Lingga Island (Riau Archipelago, Indonesia), Tenasserim (Myanmar), and west-central Myanmar. Transect survey effort was 937km. We assessed rates of deforestation and loss of old-growth forest in the range of the species from expert review reports. By combining population density and forest cover data sets we calculated the global population trend of the species. We found a preference for large diameter trees by foraging and nesting Great Slaty Woodpeckers, and a reduction of the frequency of such trees in logged forests. Across the four study regions, between old-growth forests and logged forests, densities of Great Slaty Woodpeckers were reduced by 80–94%. Although Great Slaty Woodpeckers occur in 15 countries, ca. 70% of the global population occurs in just four countries (Myanmar, Indonesia, Cambodia, and Malaysia), three of which have high annual rates of deforestation and loss of old-growth forest. Our population calculations show that over the past century at least 90% of the global population of the Great Slaty Woodpecker has been lost. At present 26,000–550,000 individuals remain. The current global decline rate of ca. 59%±SD 17% in three generations justifies IUCN Vulnerable or Endangered status. Contributing factors to the steep decline rate of the species are a long generation time of 5.9–8.2 years and an association with old-growth, lower elevation forests. The Great Slaty... [Copyright &y& Elsevier]

As the Ayeyarwady River approaches the Andaman Sea, it splits into numerous delta distributary channels, which together discharge >108 t/y of sediment to the coastal ocean. This study aims to understand: 1) sediment retention and geomorphic variability through the lower tidally influenced distributaries, 2) deltaic growth along mangrove shorelines, and 3) sediment export through this relatively natural, but rapidly changing deltaic system. We focus on three of the distributary channels that have differing fluvial discharge and marine tidal forcing. There is an order-of-magnitude difference between the discharge carried by the largest of the distributaries, the Yangon River, and the smallest studied, the Bogale River. From east to west, the tidal range at the distributary mouths decreases from ~6 m at the eastern Yangon River, to 3.5 m at central Bogale River, to 3.2 m at the western Pathein River. Seasonal variations are associated with tropical monsoons, and our studies occurred during both high- and low-discharge conditions. During high-discharge conditions, suspended-sediment concentrations (SSC) and sediment dynamics are similar across all three distributary channels. They all carry sediment with a median grain size of 3-4 microns in suspension. During low-discharge, salinity intrusion extends many tens of kilometers upstream of the river mouths, shifting the dynamics within the distributaries from those of a tidal river to an estuary. In this regime, SSC values are observed to decrease in the Pathein River (10s mg/L), while in the Yangon River, SSC increases to >5 g/L. In addition to in-situ data collected during the two seasonal conditions, surface SSC derived from calibrated multispectral remote-sensing products provide a synoptic view of turbidity across the delta, and resolve long-term trends in surface SSC for the distributaries of the Ayeyarwady River. Landsat images suggest greater turbidity toward the apex of the Gulf of Mottama, and in all three distributaries, surface SSC is generally greater near the mouths, and decreases upstream, consistent with our observations. Relating suspended sediment transport in the distributaries to local morphology, we find that channel-bed sediment is primarily muddy sand, but mud deposits can be found in regions of the estuarine turbidity maximum. On the adjacent mangrove-forested intertidal surfaces, morphodynamic studies document sediment-accumulation rates of ~1 cm/yr in the aggrading mangrove forest and prograding subaqueous shoal. Natural networks of dendritic tidal channels within the forest efficiently deliver sediment to intertidal land surfaces distal to the main channels. The mangrove forests of the Ayeyarwady Delta, while diminishing in size due to human factors, are an important sediment sink upstream of the coastal ocean. Due to its large sediment discharge, dynamic seasonal and tidal conditions, and intact mangrove forests, the Ayeyarwady Delta is an important and understudied component of global source-to-sink systems. [ABSTRACT FROM AUTHOR]

The Irrawaddy (Ayeyawady) delta of Myanmar is one of the last unexplored megadeltas,delivering one of the highest fluxes of sediment in the world to the Andaman Sea. Two drillcores from Ta Loke Htaw and Kyonmangay provide new Sr and Nd isotope geochemistry(<2μm and >2 μm size fractions) and detrital zircon U-Pb geochronology that are used toconstrain fluvial sediment provenance variability recorded within the Irrawaddy delta sincethe Last Glacial Maximum. These data are synthesized together with published bulk andsingle-grain sediment provenance datasets from the modern river, delta, and source bedrock,and integrated with geomorphic, neotectonic, and paleoenvironmental datasets to provideinitial constraints on tectonic and surface process controls on Quaternary sediment delivery tothe Andaman offshore. Initial data show a limited range in 87Sr/86Sr isotope values between 0.714045 and0.717467 (±0.000062, 2σ) and epsilon Nd values of -6.95 to -5.85 (±0.13, 2σ) for clay-sizedmaterial. Coarser material (>2 μm) show slightly less radiogenic87Sr/86Sr signatures(0.711441–0.716361) and a ∼2 epsilon offset to less radiogenic values (-8.97 to -7.94) thanfiner fractions. Nd isotope signatures are overall more radiogenic than previously observed inthe modern river (-11 to -8). The consistent ∼2 epsilon Nd value offset between grain-sizefractions indicates hydrodynamic sorting has allocated different phases between the <2μmand >2 μm fractions and/or phase(s) sourced from bedrock terranes with differinghistories. Detrital zircon samples yield U-Pb ages ranging from early Miocene to late Archean, with31–42% of ages between 20–75 Ma, 16–36% between 75–180 Ma, with smaller and variablepeaks at ∼500–600 Ma, ∼850–1200 Ma, and 2300–2600 Ma. Delta samples indicate strongcontributions from the Myittha-Chindwin tributaries and uppermost Irrawaddy since the LastGlacial Maximum and up to 10–9 ka. After 9 ka and until at least 5 ka, delta sediments atKyonmangay show a shift to greater contributions from the southern Indo-BurmanRange/Arakan Yoma and the Shan Plateau/Sibumasu terrane. By 1.5–1.0 ka, moderatelymore material is sourced again from the uppermost Irrawaddy and northeast Chindwin, withgreater incorporation of southern Indo-Burman Range materials after 1.0 ka to present-day. [ABSTRACT FROM AUTHOR]