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The impact that ancient Earth surface processes had on long-term thermal regimes remain uncertain despite their potentially important role in fostering craton stabilization and preservation. The distribution and redistribution of heat producing elements (HPEs) during craton development plays a major role in lithospheric cooling and strengthening. Whereas the redistribution of HPEs via erosion has theoretically been suggested to alter the long-term geotherm and contribute to Moho cooling, direct temporal constraints from the field are lacking to adequately assess the role that ancient Earth surface processes may have had on long-term thermal regimes. Here, we used apatite U-Pb thermochronology to assess the thermal evolution of the Archean Bundelkhand craton of central India immediately following its amalgamation and final phase of silicic magmatism at ~2.5 Ga. Apatite from both ~3.4 Ga granitic gneisses and ~2.5 Ga granitoids collected across the ~250 km-wide craton yielded near-uniform apatite U-Pb dates between ~2.4–2.3 Ga, indicating that the craton was broadly exhumed through mid-crustal depths shortly following shallow granitoid emplacement. Unroofing of the craton at this time is further corroborated by the presence of a distinct ~2.5 Ga detrital zircon U-Pb age peak obtained from ~2.2–2.3 Ga sandstones in direct non-conformable contact with Bundelkhand granitoids. We speculate that a two-step redistribution of HPEs largely contributed to the stabilization of the Bundelkhand craton. First, the concentration of HPEs within shallowly emplaced granitoids at ~2.5 Ga reduced the heat production of the lower-most crust. Second, post-emplacement exhumation of HPE-enriched Bundelkhand granitoids further modified the heat source distribution to a thermal regime that promoted cooling of the lower-crust. Although the mechanism driving exhumation through mid-crustal depths remains uncertain, temporal relationships from the Bundelkhand craton suggest that erosional processes may have had a significant role in promoting the craton’s stability and longevity.

siRNA and primer sequences

Supplementary Figures 1-6. Figure S1: UBR5 and MYC interaction assays and WB controls for RNA-seq. experiment. Fig. S2: MYC and NMYC stability regulation by UBR5 and ubiquitin assays in denaturating conditions. Fig. S3: Additional Drosophila phenotype data. Fig. S4: Colony growth and apoptosis assays in UBR5 depleted control and drug-treated cells. Fig. S5: Role of UBR5 in basal-like breast cancer cells and Kaplan-Meier analyses. Fig. S6: IF and IHC analysis of MYC and UBR5 expression in basal-like TNBC.

For maximal oncogenic activity, cellular MYC protein levels need to be tightly controlled so that they do not induce apoptosis. Here, we show how ubiquitin ligase UBR5 functions as a molecular rheostat to prevent excess accumulation of MYC protein. UBR5 ubiquitinates MYC and its effects on MYC protein stability are independent of FBXW7. Silencing of endogenous UBR5 induced MYC protein expression and regulated MYC target genes. Consistent with the tumor suppressor function of UBR5 (HYD) in Drosophila, HYD suppressed dMYC-dependent overgrowth of wing imaginal discs. In contrast, in cancer cells, UBR5 suppressed MYC-dependent priming to therapy-induced apoptosis. Of direct cancer relevance, MYC and UBR5 genes were coamplified in MYC-driven human cancers. Functionally, UBR5 suppressed MYC-mediated apoptosis in p53-mutant breast cancer cells with UBR5/MYC coamplification. Furthermore, single-cell immunofluorescence analysis demonstrated reciprocal expression of UBR5 and MYC in human basal-type breast cancer tissues. In summary, UBR5 is a novel MYC ubiquitin ligase and an endogenous rheostat for MYC activity. In MYC-amplified, and p53-mutant breast cancer cells, UBR5 has an important role in suppressing MYC-mediated apoptosis priming and in protection from drug-induced apoptosis.Significance:These findings identify UBR5 as a novel MYC regulator, the inactivation of which could be very important for understanding of MYC dysregulation on cancer cells.

An assemblage of microfossils of moderate diversity, with the remarkable occurrence of ECAP acritarchs, is reported from the Ediacaran Krol ‘A’ (= the Mahi Formation) succession of Lesser Himalaya, India. Microfossils occur in the chert nodules exposed in Solan district, Himachal Pradesh. Two microfossils, Barogophycus symmetricus n. gen. n. sp. and Botominella lineata are new to the well-established Krol assemblage. The paper concentrates predominantly on fossil eukaryotic filamentous and coccoidal micro-organism of simple morphology. The assemblage is dominated by remains of prokaryotic cyanobacteria and demonstrates the diversity achieved by microorganisms at the beginning of the Ediacaran Period in the aftermath of the Marinoan glaciation. Filamentous and coccoidal microorganisms differ in taxonomic composition from the Mesoproterozoic microbiotas. The Krol microfossils assemblage has biostratigraphic potential and usefulness in broadly demarcating the different levels of the Ediacaran strata. Because of the presence of ECAP acritarchs, along with the appearance of other eukaryotic microorganisms of filamentous and coccoidal morphology, the general level of the Krol ‘A’ assemblage is considered as Ediacaran.

RAS-mediated human cell transformation requires inhibition of the tumor suppressor protein phosphatase 2A (PP2A). However, the phosphoprotein targets and cellular processes in which RAS and PP2A activities converge in human cancers have not been systematically analyzed. Here, we discover that phosphosites co-regulated by RAS and PP2A are enriched on proteins involved in epigenetic gene regulation. As examples, RAS and PP2A co-regulate the same phosphorylation sites on HDAC1/2, KDM1A, MTA1/2, RNF168, and TP53BP1. We validate RAS- and PP2A-elicited regulation of HDAC1/2 chromatin recruitment, of RNF168-TP53BP1 interaction, and of gene expression. Consistent with their known synergistic effects in cancer, RAS activation and PP2A inhibition resulted in epigenetic reporter derepression and activation of oncogenic transcription. Transcriptional derepression by PP2A inhibition was associated with an increase in euchromatin and a decrease in global DNA methylation. Collectively, the results indicate that epigenetic protein complexes constitute a significant point of convergence for RAS hyperactivity and PP2A inhibition in cancer. Furthermore, the work provides an important resource for future studies focusing on phosphoregulation of epigenetic gene regulation in cancer and in other RAS/PP2A-regulated cellular processes. publishedVersion

Significance of Precambrian and early Cambrian palaeobiological remains recorded over the last few years on the Indian subcontinent are discussed in the present review. The importance of these remains is assessed in the backdrop of new reports from different parts of the world. Archaean, Proterozoic and early Cambrian successions of India have revealed some of the oldest rock fragments of the world, most primitive eukaryotic remains, bizarre Ediacaran forms and typical early Cambrian fossils. For the sake of brevity and easy comprehension, palaeobiological remains are grouped under Archaean, Proterozoic, Ediacaran and early Cambrian time-frames. New evidence of life forms, documented from the sedimentary basins exposed in peninsular and extra-peninsular region of the country, have challenged the various paradigms, viz. evolutionary, biostratigraphic status of different lithounits and age of the encompassing sedimentary successions. Newly published geochronological and geochemical results are also considered in this review to understand the developments in these fields and their significance in the evolution of hydrosphere, biosphere, and moderating processes over the geological timescale. Recent Indian endeavors in the field of Astrobiology and inputs provided in the areas of astrobiological studies are also discussed.

An assemblage of organic walled microfossils (OWM) of 17 taxa belonging to 10 genera is reported from the Neoproterozoic Owk Shale of the Kurnool Group, South India. The assemblage comprises sphaeromorphs, colonial aggregates, filamentous forms, spiral cylindrical filaments belonging to cyanobacteria, problematic acanthomorphic acritarchs, Netromorphic, Sphaeromorphic and Acantomorphic groups. The assemblage includes cyanobacteria: Siphonophycus kestron, S. robustum, S. typicum, S. solidum, Polytrichoides lineatus; Netromorphic acritarch: Arctacellularia tetragonala, Navifusa majensis, Jacutianema solubila; Sphaeromorphic acritarch: Ostiana microcystis, Synsphaeridium spp., Leiosphaeridia minutissima, L. tenuissima, L. crassa, L. jacutica, L. ternate; and Acanthomorphic acritarch: Cavaspina aff. C. acuminata and Variomargosphaeridium aff. V. litoschum. The age conundrum of Kurnool Group (Mesoproterozoic versus Neoproterozoic) is discussed. On the basis of the reported OWM assemblage the age of the Kurnool Group is established as Neoproterozoic.

Discs/discoidal body fossils, an important constituent of Ediacaran biota, are reported from the sandstone unit of the Hotpet Formation of the Bhima Group, South India. Nine specimens preserved as circular to ovate structures are described and attributed to Ediacaran discs and are akin to Fermeuse-style preservation of Ediacaran fossils. These discs, occur as impressions on the bedding planes, are referred as Charniodiscus-like fossils. This is the first report of Ediacaran discs from the Bhima Group, south India.

For maximal oncogenic activity, cellular MYC protein levels need to be tightly controlled so that they do not induce apoptosis. Here, we show how ubiquitin ligase UBR5 functions as a molecular rheostat to prevent excess accumulation of MYC protein. UBR5 ubiquitinates MYC and its effects on MYC protein stability are independent of FBXW7. Silencing of endogenous UBR5 induced MYC protein expression and regulated MYC target genes. Consistent with the tumor suppressor function of UBR5 (HYD) in Drosophila, HYD suppressed dMYC-dependent overgrowth of wing imaginal discs. In contrast, in cancer cells, UBR5 suppressed MYC-dependent priming to therapy-induced apoptosis. Of direct cancer relevance, MYC and UBR5 genes were coamplified in MYC-driven human cancers. Functionally, UBR5 suppressed MYC-mediated apoptosis in p53-mutant breast cancer cells with UBR5/MYC coamplification. Furthermore, single-cell immunofluorescence analysis demonstrated reciprocal expression of UBR5 and MYC in human basal-type breast cancer tissues. In summary, UBR5 is a novel MYC ubiquitin ligase and an endogenous rheostat for MYC activity. In MYC-amplified, and p53-mutant breast cancer cells, UBR5 has an important role in suppressing MYC-mediated apoptosis priming and in protection from drug-induced apoptosis. Significance: These findings identify UBR5 as a novel MYC regulator, the inactivation of which could be very important for understanding of MYC dysregulation on cancer cells.

RAS-mediated human cell transformation requires inhibition of the tumor suppressor Protein Phosphatase 2A (PP2A). Both RAS and PP2A mediate their effects by phosphoregulation, but phosphoprotein targets and cellular processes in which RAS and PP2A activities converge in human cancers have not been systematically analyzed. Here, based on mass spectrometry phosphoproteome data we discover that phosphosites co-regulated by RAS and PP2A are enriched on proteins involved in epigenetic gene regulation. As examples, RAS and PP2A co-regulate the same phosphorylation sites on HDAC1/2, KDM1A, MTA1/2, RNF168 and TP53BP1. Mechanistically, we validate co-regulation of NuRD chromatin repressor complex by RAS and PP2A. Consistent with their known synergistic effects in cancer, RAS activation and PP2A inhibition resulted in epigenetic reporter de-repression and activation of oncogenic transcription. Notably, transcriptional de-repression by PP2A inhibition was associated with increased euchromatin and decrease in global DNA methylation. Further, targeting of RAS- and PP2A-regulated epigenetic proteins decreased viability of KRAS-mutant human lung cancer cells. Collectively the results indicate that epigenetic protein complexes involved in oncogenic gene expression constitute a significant point of convergence for RAS hyperactivity and PP2A inhibition in cancer. Further, the results provide a rich source for future understanding of phosphorylation as a previously unappreciated layer of regulation of epigenetic gene regulation in cancer, and in other RAS/PP2A-regulated cellular processes.

RAS-mediated human cell transformation requires inhibition of the tumor suppressor Protein Phosphatase 2A (PP2A). Both RAS and PP2A mediate their effects by phosphoregulation, but phosphoprotein targets in which RAS and PP2A activities converge in human cancers have not been systematically analyzed. Here, based on mass spectrometry phosphoproteome data, we discover that phosphosites co-regulated by RAS and PP2A are enriched on proteins involved in epigenetic gene regulation. As examples, RAS and PP2A co-regulate the same phosphorylation sites on HDAC1/2, KDM1A, MTA1/2, RNF168 and TP53BP1. Mechanistically, we validate co-regulation of NuRD chromatin repressor complex by RAS and PP2A. Consistent with their known synergistic effects in cancer, RAS activation and PP2A inhibition resulted in epigenetic reporter de-repression and activation of oncogenic transcription. Notably, transcriptional de-repression by PP2A inhibition was associated with increased euchromatin and decrease in global DNA methylation. In RAS-driven cancers, PP2A activity is inhibited by nuclear PP2A inhibitor proteins PME-1 and SET. We further demonstrate that these PP2A inhibitors drive oncogenic transcription, but that their transcriptional targets are highly diversified. Whereas PME-1 controls RAS and MYC-driven transcription, SET controls TP53 targets and G2/M checkpoint genes. We further provide evidence that these nuclear PP2A inhibitors significantly differ in their roles in regulating DNA methylation. Collectively the results indicate that epigenetic protein complexes involved in oncogenic gene expression constitute a significant point of convergence for RAS hyperactivity and PP2A inhibition in cancer. Further, the results provide a rich source for future understanding of phosphorylation as a previously unappreciated layer of regulation of epigenetic gene regulation in cancer, and in other RAS/PP2A-regulated cellular processes. Citation Format: Mukund Sharma, Anna Aakula, Francesco Tabaro, Henrik Honkanen, Jesse Kamila, Matthieu Schapira, Cheryl Arrowsmith, Matti Nykter, Jukka K. Westermarck. RAS and PP2A activities converge on phosphoregulation of epigenetic complexes in cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4727.

Four first-order (Hadean, Archean, Proterozoic and Phanerozoic eon) and nine second-order (Paleoarchean, Mesoarchean, Neoarchean, Paleoproterozoic, Mesoproterozoic, Neoproterozoic, Paleozoic, Mesozoic and Cenozoic era) units continue to provide intuitive subdivision of geological time. Major transitions in Earth’s tectonic, biological and environmental history occurred at approximately 2.5-2.3, 1.8-1.6, 1.0-0.8 and 0.7-0.5 Ga, and so future rock-based subdivision of pre-Cryogenian time, eventually by use of global stratotypes (GSSPs), will likely require only modest deviation from current chronometric boundaries (GSSAs) at 2.5, 1.6 and 1.0 Ga, respectively. Here we argue that removal of GSSAs could be expedited by establishing event-based concepts and provisional, approximate ages for eon-, era- and period-level subdivisions as soon as practicable, in line with ratification of an Ediacaran GSSP in 2004 and chronostratigraphic definition of the Cryogenian Period at c. 720 Ma in 2012. We also outline the geological basis behind current chronometric divisions, explore how they might differ in any future rock-based scheme, identify where major issues might arise during the transition, and outline where some immediate changes to the present scheme could be easily updated/formalised, as a framework for future GSSP development. In line with these aims, we note that the currently recommended four-fold Archean subdivision has not been formally ratified and agree with previous workers that it could be simplified to an informal three-fold subdivision, pending more detailed analysis. Although the ages of period boundaries would inevitably change in a more closely rock-based or chronostratigraphic scheme, we support retention of all currently ratified period names. Existing period names, borrowed from the Greek, were chosen to delimit natural phenomena of global reach. Any new global nomenclature ought to follow this lead for consistency, and so we discourage the use of supercontinent names (e.g. Rodinian, Columbian) and regional phenomena, however exceptional. In this regard, we tentatively suggest that a new period (e.g. the ‘Kratian’), could precede the Tonian as the first period of the Neoproterozoic Era and we concur with previous authors that the existing Siderian Period (named for banded iron formations) would fit better as a chronostratigraphically defined period of the terminal Archean. Indeed, all pre-Cryogenian subdivisions will need more conceptual grounding in any future chronostratigraphic scheme. We conclude that improved rock-based division of the Proterozoic Eon would likely comprise a three-fold, period-level subdivision of the Paleoproterozoic Era (Oxygenian Rhyacian, Orosirian), a four-fold subdivision of the Mesoproterozoic Era (Statherian, Calymmian, Ectasian, Stenian) and potentially four-fold subdivision of the Neoproterozoic Era (pre-Tonian ‘Kratian’, Tonian, Cryogenian and Ediacaran). Future refinements towards an improved rock-based pre-Cryogenian geological time scale could be propoosed by new international bodies to cover the 1) pre-Ediacaran Neoproterozoic, 2) Mesoproterozoic, 3) Paleoproterozoic and 4) Archean (and Hadean) as few experts and disciplines can speak to the entire pre-Cryogenian rock record.

Boron is associated with several Archean stromatolite deposits, including the tourmaline-rich Barberton stromatolites in South Africa and tourmaline-bearing pyritic laminae associated with stromatolites of the 3.48 Ga Dresser Formation in the Pilbara Craton, Australia. Boron is also a critical element in prebiotic organic chemistry, including in the formation of ribose, a crucial component in RNA. As geological evidence and advances in prebiotic chemistry are now suggesting that hot spring activity may be associated with the origins of life, an understanding of boron and its mobility and isotopic fractionation in geothermal settings may provide important insights into the setting for the origin of life. Here, we report on the boron isotopic compositions and elemental concentrations in a range of fluid, sediment, and mineral samples from the active, boron-rich Puga geothermal system in the Himalayas, India. This includes one of the lowest boron isotope values ever recorded in modern settings: diatom-rich sediments (δ

A rare occurrence of a microspherule has been found in the infratrappean sediments, encountered below 338 m thick Deccan volcanic cover in KLR-1 scientific borehole, drilled in the epicentral zone of the 1993 Killari earthquake (Maharashtra, India). Palynological studies of the sediments indicate their age as Early Permian (Asselian, 298–295 Ma) for deposition. Transmission electron microscope studies reveal that the spherule from the infratrappeans, is having a similar composition to that of the Neoarchean amphibolite to granulite facies mid crustal basement. The spherule is non-spherical in nature, containing mostly FeO (10.70 ± 0.20 wt.%), CaO (13.8 ± 0.5 wt.%), Al2O3 (7.78 ± 0.30 wt.%), MgO (6.47 ± 0.3 wt.%), SiO2 (47.46 ± 0.50 wt.%), TiO2 (2.47 ± 0.3 wt.%), K2O (1.89 ± 0.20 wt.%), and Cl (0.33 ± 0.05 wt.%). Since the Fe composition of the spherule is almost same as the basement rock (10.5 wt.%), and the chlorine content is also in the same range as the basement (0.04–0.24 wt.%), it would suggest possibility of an extraterrestrial impact over the Indian terrain during the erstwhile Gondwana sedimentation period that may be associated with the Permian–Triassic mass extinction, the most severe one in the Earth's history. Keywords: Deccan trap, Killari borehole, Microspherules, Gondwana sediments, Tectonics, P-T impact

In the present paper, well-preserved specimens of taxonomically distinctive Proterozoic eukaryotic fossil Tappania Yin are recorded for the first time from the rocks of the Saraipali Formation of the Singhora Group, Chhattisgarh Supergroup, India. In the global context, among the various species of this genus, Tappania plana is widely distributed in the latest Palaeoproterozoic (Statherian) to the early Mesoproterozoic (Calymmian) organic-walled microfossil assemblages. Tappania plana of the Saraipali is subjected to transmitted light microscopy, confocal laser scanning microscopy and laser Raman spectroscopy and these results are presented. Collectively, the occurrence of remarkable microfossil Tappania and other associated microfossils in the Saraipalli Formation of rocks demonstrate the Calymmian age for the lower sediments of the Chhattisgarh Supergroup.

The geological timescale before 720 Ma uses rounded absolute ages rather than specific events recorded in rocks to subdivide time. This has led increasingly to mismatches between subdivisions and the features for which they were named. Here we review the formal processes that led to the current timescale, outline rock-based concepts that could be used to subdivide pre-Cryogenian time and propose revisions. An appraisal of the Precambrian rock record confirms that purely chronostratigraphic subdivision would require only modest deviation from current chronometric boundaries, removal of which could be expedited by establishing event-based concepts and provisional, approximate ages for eon-, era- and period-level subdivisions. Our review leads to the following conclusions: (1) the current informal four-fold Archean subdivision should be simplified to a tripartite scheme, pending more detailed analysis, and (2) an improved rock-based Proterozoic Eon might comprise a Paleoproterozoic Era with three periods (early Paleoproterozoic or Skourian, Rhyacian, Orosirian), Mesoproterozoic Era with four periods (Statherian, Calymmian, Ectasian, Stenian) and a Neoproterozoic Era with four periods (pre-Tonian or Kleisian, Tonian, Cryogenian and Ediacaran). These proposals stem from a wide community and could be used to guide future development of the pre-Cryogenian timescale by international bodies. Publisher PDF

Protein phosphatase 2A (PP2A) is a tumor suppressor while RAS proteins are potent oncogenes in different cancer types. It is well established that RAS-mediated oncogenic transformation requires simultaneous inhibition of PP2A, but the molecular basis of their interaction is poorly understood. To address the target mechanisms co-regulated by RAS and PP2A we performed a phosphoproteomics screen upon RAS or PP2A manipulation. Overall the results indicated that RAS and PP2A regulate overlapping cellular processes, and that their activities might in particular converge at epigenetic machineries. To study the RAS and PP2A synergy on transcriptional and epigenome regulation we performed multi-omics analysis of cancer cells in which RAS and PP2A activities were modulated. PP2A inhibition resulted in global gene activation while RAS inhibition lead predominantly to gene repression. Use of GFP reporter indicative of epigenetic silencing further confirmed the role of PP2A as a transcriptional repressor and RAS as a transcriptional activator. To investigate the DNA methylation changes and chromatin remodeling effects upon PP2A modulation we used RRBS (Reduced representation bisulfite sequencing) & ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) respectively. PP2A inhibition resulted in global DNA hypomethylation and an open state of chromatin confirming its role as a global repressor of epigenetic processes. To delineate the molecular mechanism behind the transcriptional regulation by RAS and PP2A we monitored the chromatin recruitment of transcriptional repressors upon PP2A or RAS manipulation. Either pharmacological or siRNA mediated PP2A or RAS modulation significantly affected gene repressor complex recruitment to the chromatin. Role of phosphorylation as a critical switch for chromatin repressor complex recruitment was demonstrated by CRISPR/Cas9-mediated mutagenesis of PP2A target phosphorylation site, which also led to a clear phenotype in in vivo tumorigenesis and oncogenic transcription. Collectively these results identify a novel phosphorylation switch on chromatin repressor complex as a converge point of KRAS and PP2A activities in lung cancer. Generally the results provide first indications to global importance of PP2A-mediated phosphorylation regulation in epigenetic gene regulation in cancer. Citation Format: Mukund Sharma, Anna Aakula, Francesco Tabaro, Karolina Pavic, Riikka Huhtaniemi, Matti Nykter, Jukka Westermarck. Chromatin repressor complex as a converge point of RAS and PP2A activities in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2958.

The quality of life on the Earth is linked inextricably to the overall quality of the environment. Unfortunately the progress in science and technology has led to generation of large amount of waste ranging from raw sewage to nuclear waste, thereby posing a serious problem for survival of mankind itself on earth. Research efforts have been devoted to the development of new, low-cost, low-technology, eco-friendly treatments capable of reducing and even eliminating pollution in the atmosphere, the hydrosphere, and soil environments. The use of microorganisms (bioremediation) and plants (phytoremediation) to remediate polluted environments is a promising and growing area of environmental biotechnology. Many bacterial, fungal, and plant enzymes explicate a degradative function and have been reported to be involved in the biodegradation of toxic organic pollutants. The use of extracellular and/or cell-free enzymes has been also proposed as an innovative remediation technique and uses purified or partially purified enzymes to catalyze contaminant detoxification. The application of these enzymes can offer advantages over the use of whole cells and would contribute toward developing advanced bioprocess technology to reduce the toxicity of the pollutants.

Endosulfan is a broadly applied cyclodiene insecticide which has been in use across 80 countries since last 5 decades. Owing to its recalcitrant nature, endosulfan residues have been reported from air, water and soil causing toxicity to various non-target organisms. Microbial decontamination of endosulfan has been reported previously by several authors. In the current study, we have evaluated the pathways of endosulfan degradation and its hazardous impact on other living beings including insects, humans, plants, aquatic life and environment by in-silico methods. For establishment of the endosulfan metabolism in different ecosystems, cell designer was employed. The established model was thereafter assessed and simulated to understand the biochemical and physiological metabolism of the endosulfan in various systems of the network. Topological investigation analysis of the endosulfan metabolism validated the presence of 207 nodes and 274 edges in the network. We have concluded that biomagnification of the endosulfan generally occurs in the various elements of the ecosystem. Dynamics study of endosulfan degrading enzymes suggested the important role of monooxygenase I, II and hydrolase in endosulfan bioremediation. Endosulfan shows toxicity in human beings, fishes and plants, however it is biodegraded by the microbes. To date, there are no reports of in- silico analysis of bioremediation of endosulfan and its hazardous effects on the environment. Thus, this report can be important in terms of modelling and simulation of biodegradation network of endosulfan and similar compounds and their impact on several other systems. Communicated by Ramaswamy H. Sarma

The increased global linkages give an investor opportunity to invest in equities across the global markets. This linkage can be the reason for spill over of the volatility from one market to the other. This paper makes an attempt to understand the effect of global linkages on the volatility of the stock market. For the purpose of study, stock index data of selected developed and emerging markets were collected and tested to see if there is variation across time, and if yes, uniformity of variation was also tested. It was found from the analysis that the variation across the countries was found to be uniform and most of the pairs of countries had a positive integration between them. It was found from examination that there is no significant difference in the extent of volatility across the countries.

Results of a robust high-resolution carbon and oxygen stable isotope studies conducted on the Ediacaran Bilara carbonate sequence of the Marwar Supergroup, Rajasthan, India are presented. The δ13C-carb and δ18O-carb in the Bilara Group vary from −9.0 to 4.1‰ and from −10.7 to 8.3‰ respectively. Overall, 457 analyzed samples have δ18O-carb significantly above −10‰, below which carbonates are considered diagenetically altered. The results are compared with well-dated established high amplitude negative carbon isotope excursions sites in other parts of the world recorded from the Ediacaran successions. The Bilara δ13C-carb pattern is closely similar to that of the Yangtze Gorges platform, South China, where the Ediacaran δ13C-carb variation profile revealed four negatives (EN1, EN2, EN3, EN4) and three positive excursions (EP1, EP2, EP3). Similarities of δ13C-carb pattern demonstrate that carbonate succession of the Bilara Group is likely time equivalent to Yangtze Gorges succession.

The volcanic emplacement and subsequent weathering of the Deccan Traps of India is believed to have had a significant influence in driving global climatic shifts from the Late Cretaceous and through the Cenozoic. The magnitude of the Deccan Traps' impact on Earth's surface environment is largely dependent on the speculated original footprint of the large igneous province. To test established estimates for the pre-erosive northern extent of the Deccan Traps, we applied low-temperature apatite (U-Th)/He thermochronology (AHe) on rocks from the Bundelkhand craton and overlying Proterozoic Vindhyan successions of central India ∼150–200 km northeast of the northernmost preservation of Deccan basalts. New AHe data reveal young ∼5–85 Ma AHe dates with low effective uranium concentrations (eU) between 5–22 ppm, with a steep positive date-eU correlation that plateaus at ∼350 Ma in grains with eU values >50 ppm. Inverse thermal history modeling—utilizing AHe diffusion parameters of the Radiation Damage Accumulation and Annealing Model (RDAAM)—indicate that observed AHe date-eU correlations are most consistent with thermal histories that require the craton and Vindhyan strata to be at or near surface temperatures by ∼66 Ma, followed by a discrete reheating event associated with Deccan volcanism. These results establish new minimal areal constraints for the northern extent of Deccan volcanism which thermally perturbed much of the Vindhyan succession. Thermal alteration of organic rich Vindhyan sediment may have provided an additional source of volatile emissions that facilitated late Maastrichtian warming at the onset of Deccan volcanism. New minimal northern constraints on Deccan volcanism additionally confirm that large volumes of Deccan basalts have been stripped away since the time of their emplacement, which poses considerable implications for unraveling their role in Cenozoic cooling.

As a major growth factor transducer, Ras is an upstream activator of mTORC1, which further integrates nutrient and energy inputs. To ensure a contextual coupling of cell division via Ras/MAPK-signalling and growth via mTORC1-signalling, feedback loops from one pathway back to the other are required. Here we describe a novel feedback from mTORC1, which oppositely affects oncogenic H-ras- and K-ras-signalling output, and as a consequence stemness properties of tumourigenic cells. Amino acid stimulation of mTORC1 increases the processed form of SREBP1, a major lipidome regulator. We show that modulation of the SREBP1 levels downstream of S6K1 has opposite effects on oncogenic H-ras and K-ras nanoscale membrane organisation, ensuing signalling output and promotion of mammospheres expressing these oncogenes. Our data suggest that modulation of phosphatidic acid, a major target of SREBP1 controlled lipid metabolism, is sufficient to affect H-ras and K-ras oppositely in the membrane. Thus mTORC1 activation increases H-ras-, but decreases K-ras-signalling output in cells transformed with the respective oncogene. Given the different impact of these two Ras isoforms on stemness, our results could have implications for stem cell biology and inhibition of cancer stem cells.

Extreme environments are considered the biodiversity hotspots especially in terms of microorganisms. Microbiomes of the extreme environment impart important information about the critical limits for survival and adaptability of microorganism. Hill and mountain agroecosystems demand distinct microflora which can endure in these extreme environments and simultaneously perpetuate their plant growth promontory properties. Microorganism native of the cold environment is widely distributed in the agroecosystem and has physiologically, metabolically, and biologically well adapted to such environments. Thus, microbial inoculants from these extreme conditions possessing PGP attributes can be efficiently utilized for promoting growth and yield of high altitude crops. Numerous plant growth-promoting rhizobacteria (PGPR) from high altitude soils containing vital enzymes involved in plant growth enhancement have been reported. These organisms can thus be employed as biofertilizers, biocontrol agents, and bioremediation for enhancing agricultural productivity.

This paper highlights unique sites in Ladakh, India, investigated during our 2016 multidisciplinary pathfinding expedition to the region. We summarize our scientific findings and the site's potential to support science exploration, testing of new technologies and science protocols within the framework of astrobiology research. Ladakh has several accessible, diverse, pristine and extreme environments at very high altitudes (3000-5700 m above sea level). These sites include glacial passes, sand dunes, hot springs and saline lake shorelines with periglacial features. We report geological observations and environmental characteristics (of astrobiological significance) along with the development of regolith-landform maps for cold high passes. The effects of the diurnal water cycle on salt deliquescence were studied using the ExoMars Mission instrument mockup: HabitAbility: Brines, Irradiance and Temperature (HABIT). It recorded the existence of an interaction between the diurnal water cycle in the atmosphere and salts in the soil (which can serve as habitable liquid water reservoirs). Life detection assays were also tested to establish the best protocols for biomass measurements in brines, periglacial ice-mud and permafrost melt water environments in the Tso-Kar region. This campaign helped confirm the relevance of clays and brines as interest targets of research on Mars for biomarker preservation and life detection., The team would like to express its gratitude to BirbalSahni Institute of Palaeosciences, Department of Science and Technology,Office of Chief Wildlife Warden of Ladakh, Government of India for helpingarrange the requisite clearances and permits for the conducted work. Projectmentoring and guidance provided by Spaceward Bound members at NASAAmes Research Center. Financial and logistics support provided by TataMotors Ltd, Inspired Journeys Co, Pearl Travels Ltd and NationalGeographic Traveller India. Website and IT support provided by the BlueMarble Space Institute of Science. Audio-video documentation support pro-vided by Astroproject India and The Hi

Integrated detrital zircon U–Pb and Lu–Hf isotope analyses were conducted on three siliciclastic sedimentary rock samples from the Vindhyan Supergroup in the Son Valley section of central India. These display two prominent 2.7–2.4 Ga and 1.9–1.5 Ga age groupings along with minor Paleoarchean-Mesoarchean (3.5–2.9 Ga) and late Mesoproterozoic (1.3–1.0 Ga) zircons. These 3.5–1.5 Ga detrital zircons match well with the exposed magmatic and metamorphic rock components within the Bundelkhand and Aravalli cratons of the Northern India Block. Zircon grains of >2.0 Ga mainly produce negative eHf(t) values suggestive of episodic recycling and reworking of old crust components in Northern India Block, whereas zircon grains in the age range of 2.0–1.4 Ga commonly produce positive eHf(t) values, indicating dominant juvenile crust growth in response to assembly and breakup of Columbia supercontinent. Contemporaneous mafic dykes (2.15–2.0 Ga and ca. 1.98 Ga) intruded into the Bundelkhand Igneous Complex present direct lithological evidence for juvenile crustal growth. Similar basement rock compositions and detrital zircon age distributions provide robust evidence that the Bundelkhand craton has possibly been combined with the Aravalli-Banded Gneiss Complex (ABGC) since Paleoproterozoic. 1.3–1.0 Ga old detrital zircons could have sourced from South China or the Central Indian Tectonic Zone or the Eastern Ghats or a pre-existing hidden terrane in India; their dominant negative eHf(t) values suggest reworking of old crustal components in Northern India Block in response to the assembly of Rodinia supercontinent.

Proterozoic carbonaceous macrofossils are key to understand the evolution of early eukaryotes and how they acquired macroscopic sizes. However, phylogenetic interpretation of these macrofossils is challenging because most of them are morphologically simple and lack phylogenetically diagnostic features. Among Proterozoic carbonaceous macrofossils, the tomaculate fossil Tawuia is relatively rich in characters and is common in Proterozoic successions. However, its phylogenetic interpretation is uncertain and Tawuia has been variously interpreted as a bacterium or an alga (photosynthetic eukaryote), in part because certain aspects of its morphologies have not been consistently documented, hampering their functional interpretations. Here we report exceptionally preserved Tawuia specimens from the Tonian Liulaobei and Shiwangzhuang formations in North China. These fossils show that Tawuia is a tomaculate organism, sometimes with an axial stripe, terminal discoidal structures, and transverse constrictions, features that were previously documented but variously interpreted. We infer that Tawuia was a coenocytic organism with recalcitrant cell walls, asexual reproduction through asymmetric constrictions, and possible abscission structures. These features indicate that Tawuia is probably a coenocytic eukaryote, and possibly a macroalga, although more evidence is needed to confirm these interpretations, particularly the photosynthetic nature of Tawuia. A literature review reveals that the key features described here occur not only in many Tonian Tawuia specimens, but also in some possible Mesoproterozoic Tawuia fossils as much as ca. 1.6 Ga old. The new data and interpretations of Tawuia presented here provide important constraints on the origin and early evolution of coenocytic eukaryotes, primary plastids, and macroalgae, particularly if the Mesoproterozoic Tawuia fossils are confirmed as macroalgae.