Interconnection between density-regulation and stability in competitive ecological network.

In natural ecosystems, species can be characterized by the nonlinear density-dependent self-regulation of their growth profile. Species of many taxa show a substantial density-dependent reduction for low population size. Nevertheless, many show the opposite trend; density regulation is minimal for small populations and increases significantly when the population size is near the carrying capacity. The theta-logistic growth equation can portray the intraspecific density regulation in the growth profile, theta being the density regulation parameter. In this study, we examine the role of these different growth profiles on the stability of a competitive ecological community with the help of a mathematical model of competitive species interactions. This manuscript deals with the random matrix theory to understand the stability of the classical theta-logistic models of competitive interactions. Our results suggest that having more species with strong density dependence, which self-regulate at low densities, leads to more stable communities. With this, stability also depends on the complexity of the ecological network. Species network connectance (link density) shows a consistent trend of increasing stability, whereas community size (species richness) shows a context-dependent effect. We also interpret our results from the aspect of two different life history strategies: r and K-selection. Our results show that the stability of a competitive network increases with the fraction of r-selected species in the community. Our result is robust, irrespective of different network architectures.

Extremely oligotrophic and complex-carbon-degrading microaerobic bacteria from Arabian Sea oxygen minimum zone sediments.

Sediments underlying marine hypoxic zones are huge sinks of unreacted complex organic matter, where despite acute O2 limitation, obligately aerobic bacteria thrive, and steady depletion of organic carbon takes place within a few meters below the seafloor. However, little knowledge exists about the sustenance and complex carbon degradation potentials of aerobic chemoorganotrophs in these sulfidic ecosystems. We isolated and characterized a number of aerobic bacterial chemoorganoheterotrophs from across a ~ 3 m sediment horizon underlying the perennial hypoxic zone of the eastern Arabian Sea. High levels of sequence correspondence between the isolates' genomes and the habitat's metagenomes and metatranscriptomes illustrated that the strains were widespread and active across the sediment cores explored. The isolates catabolized several complex organic compounds of marine and terrestrial origins in the presence of high or low, but not zero, O2. Some of them could also grow anaerobically on yeast extract or acetate by reducing nitrate and/or nitrite. Fermentation did not support growth, but enabled all the strains to maintain a fraction of their cell populations over prolonged anoxia. Under extreme oligotrophy, limited growth followed by protracted stationary phase was observed for all the isolates at low cell density, amid high or low, but not zero, O2 concentration. While population control and maintenance could be particularly useful for the strains' survival in the critically carbon-depleted layers below the explored sediment depths (core-bottom organic carbon: 0.5-1.0% w/w), metagenomic data suggested that in situ anoxia could be surmounted via potential supplies of cryptic O2 from previously reported sources such as Nitrosopumilus species.

Revisiting and redefining return rate for determination of the precise growth status of a species.

Growth curve models play an instrumental role in quantifying the growth of biological processes and have immense practical applications across all disciplines. The most popular growth metric to capture the species fitness is the "Relative Growth Rate" in this domain. The different growth laws, such as exponential, logistic, Gompertz, power, and generalized Gompertz or generalized logistic, can be characterized based on the monotonic behavior of the relative growth rate (RGR) to size or time. Thus, in this case, species fitness can be determined truly through RGR. However, in nature, RGR is often non-monotonic and specifically bell-shaped, especially in the situation when a species is adapting to a new environment [1]. In this case, species may experience with the same fitness (RGR) for two different time points. The species precise growth and maturity status cannot be determined from this RGR function. The instantaneous maturity rate (IMR), as proposed by [2], helps to determine the correct maturity status of the species. Nevertheless, the metric IMR suffers from severe drawbacks; (i) IMR is intractable for all non-integer values of a specific parameter. (ii) The measure depends on a model parameter. The mathematical expression of IMR possesses the term "carrying capacity" which is unknown to the experimenter. (iii) Note that for identifying the precise growth status of a species, it is also necessary to understand its response when the populations are deflected from their equilibrium position at carrying capacity. This is an established concept in population biology, popularly known as the return rate. However, IMR does not provide information on the species deflection rate at the steady state. Hence, we propose a new growth measure connected with the species return rate, termed the "reverse of relative of relative growth rate" (henceforth, RRRGR), which is treated as a proxy for the IMR, having similar mathematical properties. Finally, we introduce a stochastic RRRGR model for specifying precise species growth and status of maturity. We illustrate the model through numerical simulations and real fish data. We believe that this study would be helpful for fishery biologists in regulating the favorable conditions of growth so that the species can reach a steady state with optimum effort.

Spatial characterization and quantification of CD40 expression across cancer types.

BACKGROUND: CD40, a TNF receptor family member, is expressed by a variety of immune cells and is involved in the activation of both adaptive and innate immune responses. Here, we used quantitative immunofluorescence (QIF) to evaluate CD40 expression on the tumor epithelium of solid tumors in large patient cohorts of lung, ovarian, and pancreatic cancers. METHODS: Tissue samples from nine different solid tumors (bladder, breast, colon, gastric, head and neck, non-small cell lung cancer (NSCLC), ovarian, pancreatic and renal cell carcinoma), constructed in tissue microarray format, were initially assessed for CD40 expression by QIF. CD40 expression was then evaluated on the large available patient cohorts for three of the tumor types demonstrating high CD40 positivity rate; NSCLC, ovarian and pancreatic cancer. The prognostic impact of CD40 expression on tumor cells was also investigated. RESULTS: CD40 expression on tumor cells was found to be common, with 80% of the NSCLC population, 40% of the ovarian cancer population, and 68% of the pancreatic adenocarcinoma population displaying some degree of CD40 expression on cancer cells. All of three of these cancer types displayed considerable intra-tumoral heterogeneity of CD40 expression, as well as partial correlation between expression of CD40 on tumor cells and on surrounding stromal cells. CD40 was not found to be prognostic for overall survival in NSCLC, ovarian cancer, or pancreatic adenocarcinoma. CONCLUSIONS: The high percentage of tumor cells expressing CD40 in each of these solid tumors should be considered in the development of therapeutic agents designed to target CD40.

Probiotic Characterization of Arsenic-resistant Lactic Acid Bacteria for Possible Application as Arsenic Bioremediation Tool in Fish for Safe Fish Food Production.

Arsenic (As) contamination of water and food is a global problem posing a severe threat to environmental and human health; therefore, fish as an aquatic animal is immensely affected by the hazardous impacts of As. The present study aimed to explore the As-resistant probiotic bacteria and characterize their potential for applying as an As bioremediation tool in fish. As-resistant lactic acid bacteria (LAB) were isolated from sludge samples of an old stabilization pond/lagoon of wastewater treatment plant using spared plate techniques. The potential probiotic was selected by assessing the sequential probiotic characterization, As resistance and removal properties. The selected probiotic was identified by PCR-based molecular method using 16S rDNA. A total of 51 As-resistant LAB were isolated from sludge samples. Potential six As-resistant LAB strains (As4, 11, 20, 21, 41 and 48) were selected from 51 isolates through sequential probiotic characterizations using mimic fish gastrointestinal conditions. The selected probiotics displayed relatively elevated As (> 1000 mg L-1), cadmium (20-100 mg L-1) and lead (> 2000 mg L-1)-resistant patterns and excellent As-removal efficiencies (0.0012-0.0044 mg As mg cell-1 h-1) from water along with favourable various associative probiotic properties. The 16S rDNA sequence-based molecular identification and phylogenetic analysis revealed that the strains As4, 11, 20, 21, 41 and 48 belong to Limosilactobacillus fermentum (Lactobacillus fermentum according to old taxonomy). The As removal and survival in mimic gastrointestinal conditions of fish indicated that new Limosilactobacillus fermentum strains could be employed as the novel and potential probiotic tools for possible bioremediation of As and other pollutants in the fish to prevent the bioaccumulation and toxicity impacts of As in fish for cleaner and safe fish food production.

Thermal Endurance by a Hot-Spring-Dwelling Phylogenetic Relative of the Mesophilic Paracoccus.

High temperature growth/survival was revealed in a phylogenetic relative (SMMA_5) of the mesophilic Paracoccus isolated from the 78 to 85°C water of a Trans-Himalayan sulfur-borax spring. After 12 h at 50°C, or 45 min at 70°C, in mineral salts thiosulfate (MST) medium, SMMA_5 retained ~2% colony forming units (CFUs), whereas comparator Paracoccus had 1.5% and 0% CFU left at 50°C and 70°C, respectively. After 12 h at 50°C, the thermally conditioned sibling SMMA_5_TC exhibited an ~1.5 time increase in CFU count; after 45 min at 70°C, SMMA_5_TC had 7% of the initial CFU count. 1,000-times diluted Reasoner's 2A medium, and MST supplemented with lithium, boron, or glycine-betaine, supported higher CFU-retention/CFU-growth than MST. Furthermore, with or without lithium/boron/glycine-betaine, a higher percentage of cells always remained metabolically active, compared with what percentage formed single colonies. SMMA_5, compared with other Paracoccus, contained 335 unique genes: of these, 186 encoded hypothetical proteins, and 83 belonged to orthology groups, which again corresponded mostly to DNA replication/recombination/repair, transcription, secondary metabolism, and inorganic ion transport/metabolism. The SMMA_5 genome was relatively enriched in cell wall/membrane/envelope biogenesis, and amino acid metabolism. SMMA_5 and SMMA_5_TC mutually possessed 43 nucleotide polymorphisms, of which 18 were in protein-coding genes with 13 nonsynonymous and seven radical amino acid replacements. Such biochemical and biophysical mechanisms could be involved in thermal stress mitigation which streamline the cells' energy and resources toward system-maintenance and macromolecule-stabilization, thereby relinquishing cell-division for cell-viability. Thermal conditioning apparently helped inherit those potential metabolic states which are crucial for cell-system maintenance, while environmental solutes augmented the indigenous stability-conferring mechanisms. IMPORTANCE For a holistic understanding of microbial life's high-temperature adaptation, it is imperative to explore the biology of the phylogenetic relatives of mesophilic bacteria which get stochastically introduced to geographically and geologically diverse hot spring systems by local geodynamic forces. Here, in vitro endurance of high heat up to the extent of growth under special (habitat-inspired) conditions was discovered in a hot-spring-dwelling phylogenetic relative of the mesophilic Paracoccus species. Thermal conditioning, extreme oligotrophy, metabolic deceleration, presence of certain habitat-specific inorganic/organic solutes, and potential genomic specializations were found to be the major enablers of this conditional (acquired) thermophilicity. Feasibility of such phenomena across the taxonomic spectrum can well be paradigm changing for the established scopes of microbial adaptation to the physicochemical extremes. Applications of conditional thermophilicity in microbial process biotechnology may be far reaching and multifaceted.

Contrasting Distribution of SARS-CoV-2 Lineages across Multiple Rounds of Pandemic Waves in West Bengal, the Gateway of East and North-East States of India.

The evolution of viral variants and their impact on viral transmission have been an area of considerable importance in this pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed the viral variants in different phases of the pandemic in West Bengal, a state in India that is important geographically, and compared the variants with other states like Delhi, Maharashtra, and Karnataka, located in other regions of the country. We have identified 57 pango-lineages in 3,198 SARS-CoV-2 genomes, alteration in their distribution, as well as contrasting profiles of amino acid mutational dynamics across different waves in different states. The evolving characteristics of Delta (B.1.617.2) sublineages and alterations in hydrophobicity profiles of the viral proteins caused by these mutations were also studied. Additionally, implications of predictive host miRNA binding/unbinding to emerging spike or nucleocapsid mutations were highlighted. Our results throw considerable light on interesting aspects of the viral genomic variation and provide valuable information for improved understanding of wave-defining mutations in unfolding the pandemic. IMPORTANCE Multiple waves of infection were observed in many states in India during the coronavirus disease 2019 (COVID19) pandemic. Fine-scale evolution of major SARS-CoV-2 lineages and sublineages during four wave-window categories: Pre-Wave 1, Wave 1, Pre-Wave 2, and Wave 2 in four major states of India: Delhi (North), Maharashtra (West), Karnataka (South), and West Bengal (East) was studied using large-scale virus genome sequencing data. Our comprehensive analysis reveals contrasting molecular profiles of the wave-defining mutations and their implications in host miRNA binding/unbinding of the lineages in the major states of India.

Instantaneous maturity rate: a novel and compact characterization of biological growth curve models.

Modeling and analysis of biological growth curves are an age-old study area in which much effort has been dedicated to developing new growth equations. Recent efforts focus on identifying the correct model from a large number of equations. The relative growth rate (RGR), developed by Fisher (1921), has largely been used in the statistical inference of biological growth curve models. It is convenient to express growth equations using RGR, where RGR can be expressed as functions of size or time. Even though RGR is model invariant, it has limitations when it comes to identifying actual growth patterns. By proposing interval-specific rate parameters (ISRPs), Pal et al. (2018) appeared to solve this problem. The ISRP is based on the mathematical structure of the growth equations. Therefore, it is not model invariant. The current effort is to develop a measure of growth that is model invariant like RGR and shares the advantages of ISRP. We propose a new measure of growth, which we call instantaneous maturity rate (IMR). IMR is model invariant, which allows it to distinguish growth patterns more clearly than RGR. IMR is also scale-invariant and can take several forms including increasing, decreasing, constant, sigmoidal, bell-shaped, and bathtub. A wide range of possible IMR shapes makes it possible to identify different growth curves. The estimation procedure of IMR under a stochastic setup has been developed. Statistical properties of empirical IMR estimators have also been investigated in detail. In addition to extensive simulation studies, real data sets have been analyzed to prove the utility of IMR.

A noble extended stochastic logistic model for cell proliferation with density-dependent parameters.

Cell proliferation often experiences a density-dependent intrinsic proliferation rate (IPR) and negative feedback from growth-inhibiting molecules in culture media. The lack of flexible models with explanatory parameters fails to capture such a proliferation mechanism. We propose an extended logistic growth law with the density-dependent IPR and additional negative feedback. The extended parameters of the proposed model can be interpreted as density-dependent cell-cell cooperation and negative feedback on cell proliferation. Moreover, we incorporate further density regulation for flexibility in the model through environmental resistance on cells. The proposed growth law has similarities with the strong Allee model and harvesting phenomenon. We also develop the stochastic analog of the deterministic model by representing possible heterogeneity in growth-inhibiting molecules and environmental perturbation of the culture setup as correlated multiplicative and additive noises. The model provides a conditional maximum sustainable stable cell density (MSSCD) and a new fitness measure for proliferative cells. The proposed model shows superiority to the logistic law after fitting to real cell culture datasets. We illustrate both conditional MSSCD and the new cell fitness for a range of parameters. The cell density distributions reveal the chance of overproliferation, underproliferation, or decay for different parameter sets under the deterministic and stochastic setups.

Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-mediated Antitumor Responses In Vivo.

B-cell maturation antigen (BCMA) is an attractive therapeutic target highly expressed on differentiated plasma cells in multiple myeloma and other B-cell malignancies. GSK2857916 (belantamab mafodotin, BLENREP) is a BCMA-targeting antibody-drug conjugate approved for the treatment of relapsed/refractory multiple myeloma. We report that GSK2857916 induces immunogenic cell death in BCMA-expressing cancer cells and promotes dendritic cell activation in vitro and in vivo GSK2857916 treatment enhances intratumor immune cell infiltration and activation, delays tumor growth, and promotes durable complete regressions in immune-competent mice bearing EL4 lymphoma tumors expressing human BCMA (EL4-hBCMA). Responding mice are immune to rechallenge with EL4 parental and EL4-hBCMA cells, suggesting engagement of an adaptive immune response, immunologic memory, and tumor antigen spreading, which are abrogated upon depletion of endogenous CD8+ T cells. Combinations with OX40/OX86, an immune agonist antibody, significantly enhance antitumor activity and increase durable complete responses, providing a strong rationale for clinical evaluation of GSK2857916 combinations with immunotherapies targeting adaptive immune responses, including T-cell-directed checkpoint modulators.

34S enrichment as a signature of thiosulfate oxidation in the "Proteobacteria".

Kinetics of thiosulfate oxidation, product and intermediate formation, and 34S fractionation, were studied for the members of Alphaproteobacteria Paracoccus sp. SMMA5 and Mesorhizobium thiogangeticum SJTT, the Betaproteobacteria member Pusillimonas ginsengisoli SBO3, and the Acidithiobacillia member Thermithiobacillus sp. SMMA2, during chemolithoautotrophic growth in minimal salts media supplemented with 20 mM thiosulfate. The two Alphaproteobacteria oxidized thiosulfate directly to sulfate, progressively enriching the end-product with 34S; Δ34Sthiosulfate-sulfate values recorded at the end of the two processes (when no thiosulfate was oxidized any further) were -2.9‰ and -3.5‰, respectively. Pusillimonas ginsengisoli SBO3 and Thermithiobacillus sp. SMMA2, on the other hand, oxidized thiosulfate to sulfate via tetrathionate intermediate formation, with progressive 34S enrichment in the end-product sulfate throughout the incubation period; Δ34Sthiosulfate-sulfate, at the end of the two processes (when no further oxidation took place), reached -3.5‰ and -3.8‰, respectively. Based on similar 34S fractionation patterns recorded previously during thiosulfate oxidation by strains of Paracoccus pantotrophus, Advenella kashmirensis and Hydrogenovibrio crunogenus, it was concluded that progressive reverse fractionation, enriching the end-product sulfate with 34S, could be a characteristic signature of bacterial thiosulfate oxidation.

COVID-19 pandemic models revisited with a new proposal: Plenty of epidemiological models outcast the simple population dynamics solution.

We have put an effort to estimate the number of publications related to the modelling aspect of the corona pandemic through the web search with the corona associated keywords. The survey reveals that plenty of epidemiological models outcast the simple population dynamics solution. Most of the future predictions based on these epidemiological models are highly unreliable because of the complexity of the dynamical equations and the poor knowledge of realistic values of the model parameters. The incidence time series of top ten corona infected countries are erratic and sparse. But in comparison, the incidence and disease fitness relationships are uniform and concave upward in nature. These simple profiles with the acceleration curves have fundamental implications in understanding the instinctive dynamics of the corona pandemic. We propose a simple population dynamics solution based on the incidence-fitness relationship in predicting that a plateau or steady state of SARS-CoV-2 will be reached using the basic concept of geometry.

Aerobic microbial communities in the sediments of a marine oxygen minimum zone.

The ecology of aerobic microorganisms is never explored in marine oxygen minimum zone (OMZ) sediments. Here we reveal aerobic bacterial communities along ∼3 m sediment-horizons of the eastern Arabian Sea OMZ. Sulfide-containing sediment-cores retrieved from 530 mbsl (meters beneath the sea-level) and 580 mbsl were explored at 15-30 cm intervals, using metagenomics, pure-culture-isolation, genomics and metatranscriptomics. Genes for aerobic respiration, and oxidation of methane/ammonia/alcohols/thiosulfate/sulfite/organosulfur-compounds, were detected in the metagenomes from all 25 sediment-samples explored. Most probable numbers for aerobic chemolithoautotrophs and chemoorganoheterotrophs at individual sample-sites were up to 1.1 × 107 (g sediment)-1. The sediment-sample collected from 275 cmbsf (centimeters beneath the seafloor) of the 530-mbsl-core yielded many such obligately aerobic isolates belonging to Cereibacter, Guyparkeria, Halomonas, Methylophaga, Pseudomonas and Sulfitobacter which died upon anaerobic incubation, despite being provided with all possible electron acceptors and fermentative substrates. High percentages of metatranscriptomic reads from the 275 cmbsf sediment-sample, and metagenomic reads from all 25 sediment-samples, matched the isolates' genomic sequences including those for aerobic metabolisms, genetic/environmental information processing and cell division, thereby illustrating the bacteria's in-situ activity, and ubiquity across the sediment-horizons, respectively. The findings hold critical implications for organic carbon sequestration/remineralization, and inorganic compounds oxidation, within the sediment realm of global marine OMZs.

An extended stochastic Allee model with harvesting and the risk of extinction of the herring population.

Overexploitation of commercially beneficial fish is a serious ecological problem around the world. The growth profiles of most of the species are likely to follow density regulated theta-logistic model irrespective of any taxonomy group [Sibly et al., Science, 2005]. Rapid depletion of population size may cause reduced fitness, and the species is exposed to Allee phenomena. Here sustainability is addressed by modelling the herring population as a stochastic process and computing the probability of extinction and expected time to extinction. The models incorporate an Allee effect, crowding effect which reduce birth and death rates at large populations, and two possible choices of harvesting models viz. linear harvesting and nonlinear harvesting. A seminal attempt is made by Saha [Saha et al., Ecol. Model, 2013] for this economically beneficial fish, but ignored the vital phenomena of harvesting. Moreover, in this model, the demographic stochasticity is introduced through the white-noise term, which has certain limitations when harvesting is introduced into the system. White noise is appropriate for such a system where immigration and emigration are allowed, but a harvesting model is rational for a closed system. The demographic stochasticity is introduced by replacing an ordinary differential equation model with a stochastic differential equation model, where the instantaneous variance in the SDE is derived directly from the birth and death rates of a birth-death process. The modelling parameters are fit to data of the herring populations collected from Global Population Dynamics Database (GPDD), and the risk of extinction of each population is computed under different harvesting protocols. A threshold for handling times is computed beneath which the risk of extinction is high. This is proposed as a recommendation to management for sustainable harvesting.

Microbiome and ecology of a hot spring-microbialite system on the Trans-Himalayan Plateau.

Little is known about life in the boron-rich hot springs of Trans-Himalayas. Here, we explore the geomicrobiology of a 4438-m-high spring which emanates ~70 °C-water from a boratic microbialite called Shivlinga. Due to low atmospheric pressure, the vent-water is close to boiling point so can entropically destabilize biomacromolecular systems. Starting from the vent, Shivlinga's geomicrobiology was revealed along the thermal gradients of an outflow-channel and a progressively-drying mineral matrix that has no running water; ecosystem constraints were then considered in relation to those of entropically comparable environments. The spring-water chemistry and sinter mineralogy were dominated by borates, sodium, thiosulfate, sulfate, sulfite, sulfide, bicarbonate, and other macromolecule-stabilizing (kosmotropic) substances. Microbial diversity was high along both of the hydrothermal gradients. Bacteria, Eukarya and Archaea constituted >98%, ~1% and <1% of Shivlinga's microbiome, respectively. Temperature constrained the biodiversity at ~50 °C and ~60 °C, but not below 46 °C. Along each thermal gradient, in the vent-to-apron trajectory, communities were dominated by Aquificae/Deinococcus-Thermus, then Chlorobi/Chloroflexi/Cyanobacteria, and finally Bacteroidetes/Proteobacteria/Firmicutes. Interestingly, sites of >45 °C were inhabited by phylogenetic relatives of taxa for which laboratory growth is not known at >45 °C. Shivlinga's geomicrobiology highlights the possibility that the system's kosmotrope-dominated chemistry mitigates against the biomacromolecule-disordering effects of its thermal water.

Molecular mechanism of sulfur chemolithotrophy in the betaproteobacterium Pusillimonas ginsengisoli SBSA.

Chemolithotrophic sulfur oxidation represents a significant part of the biogeochemical cycling of this element. Due to its long evolutionary history, this ancient metabolism is well known for its extensive mechanistic and phylogenetic diversification across a diverse taxonomic spectrum. Here we carried out whole-genome sequencing and analysis of a new betaproteobacterial isolate, Pusillimonas ginsengisoli SBSA, which is found to oxidize thiosulfate via the formation of tetrathionate as an intermediate. The 4.7 Mb SBSA genome was found to encompass a soxCDYZAXOB operon, plus single thiosulfate dehydrogenase (tsdA) and sulfite : acceptor oxidoreductase (sorAB) genes. Recombination-based knockout of tsdA revealed that the entire thiosulfate is first converted to tetrathionate by the activity of thiosulfate dehydrogenase (TsdA) and the Sox pathway is not functional in this bacterium despite the presence of all necessary sox genes. The ∆soxYZ and ∆soxXA knockout mutants exhibited a wild-type-like phenotype for thiosulfate/tetrathionate oxidation, whereas ∆soxB, ∆soxCD and soxO::KanR mutants only oxidized thiosulfate up to tetrathionate intermediate and had complete impairment in tetrathionate oxidation. The substrate-dependent O2 consumption rate of whole cells and the sulfur-oxidizing enzyme activities of cell-free extracts, measured in the presence/absence of thiol inhibitors/glutathione, indicated that glutathione plays a key role in SBSA tetrathionate oxidation. The present findings collectively indicate that the potential glutathione : tetrathionate coupling in P. ginsengisoli involves a novel enzymatic component, which is different from the dual-functional thiol dehydrotransferase (ThdT), while subsequent oxidation of the sulfur intermediates produced (e.g. glutathione : sulfodisulfane molecules) may proceed via the iterative action of soxBCD .

Draft Genome Sequences of Two Boron-Tolerant, Arsenic-Resistant, Gram-Positive Bacterial Strains, Lysinibacillus sp. OL1 and Enterococcus sp. OL5, Isolated from Boron-Fortified Cauliflower-Growing Field Soils of Northern West Bengal, India.

Two novel boron-tolerant, arsenic-resistant, Gram-positive bacterial strains, Lysinibacillus sp. OL1 and Enterococcus sp. OL5, were isolated from boron fertilizer-amended cauliflower plantation field soils in India. Here, we report the draft genome sequences of OL1 (4.87 Mb) and OL5 (3.93 Mb) to explore the intricacies of boron tolerance in bacteria.

Two pathways for thiosulfate oxidation in the alphaproteobacterial chemolithotroph Paracoccus thiocyanatus SST.

Chemolithotrophic bacteria oxidize various sulfur species for energy and electrons, thereby operationalizing biogeochemical sulfur cycles in nature. The best-studied pathway of bacterial sulfur-chemolithotrophy involves direct oxidation of thiosulfate (S2O32-) to sulfate (SO42-) without any free intermediate. This pathway mediated by SoxXAYZBCD is apparently the exclusive mechanism of thiosulfate oxidation in facultatively chemolithotrophic alphaproteobacteria. Here we explore the molecular mechanisms of sulfur oxidation in the thiosulfate- and tetrathionate(S4O62-)-oxidizing alphaproteobacterium Paracoccus thiocyanatus SST, and compare them with the prototypical Sox process of Paracoccus pantotrophus. Our results reveal a unique case where an alphaproteobacterium has Sox as its secondary pathway of thiosulfate oxidation converting ∼10% of the thiosulfate supplied, whilst ∼90% of the substrate is oxidized via a pathway that produces tetrathionate as an intermediate. Sulfur oxidation kinetics of a deletion mutant showed that thiosulfate-to-tetrathionate conversion, in SST, is catalyzed by a thiosulfate dehydrogenase (TsdA) homolog that has far-higher substrate-affinity than the Sox system of this bacterium, which in turn is also less efficient than the P. pantotrophus Sox. Deletion of soxB abolished sulfate-formation from thiosulfate/tetrathionate, while thiosulfate-to-tetrathionate conversion remained unperturbed. Physiological studies revealed the involvement of glutathione in SST tetrathionate oxidation. However, zero impact of the insertional mutation of a thiol dehydrotransferase (thdT) homolog, together with the absence of sulfite as an intermediate, indicated that SST tetrathionate oxidation is mechanistically novel, and distinct from its betaproteobacterial counterpart mediated by glutathione, ThdT, SoxBCD and sulfite:acceptor oxidoreductase. The present findings highlight extensive functional diversification of sulfur-oxidizing enzymes across phylogenetically close, as well as distant, bacteria.

A Novel Unification Method to Characterize a Broad Class of Growth Curve Models Using Relative Growth Rate.

Growth curve models serve as the mathematical framework for the quantitative studies of growth in many areas of applied science. The evolution of novel growth curves can be categorized in two notable directions, namely generalization and unification. In case of generalization, a modeler starts with a simple mathematical form to describe the behavior of the data and increases the complexity of the equation by incorporating more parameters to obtain a more flexible shape. The unification refers to the process of obtaining a compact representation of a large number of growth equations. An enormous number of growth equations are made available in the literature by means of the generalization of existing growth laws. However, the unification of growth equations has received relatively less attention from the researchers. Two significant unification functions are available in the literature, namely the Box-Cox transformation by Garcia (For Biometry Model Inf Sci 1:63-68, 2005) and generalized logarithmic and exponential functions by Martinez et al. (Phys A 387:5679-5687, 2008; Phys A 388:2922-2930, 2009). Existing unification approaches are found to have limited applications if the growth equation is characterized by the relative growth rate (RGR). RGR has immense practical value in biological growth curve analysis, which has been amplified by the construction of size and time covariate models, in which; RGR is represented either as a function of size or time or both. The present study offers a unification function for the RGR growth curves. The proposed function combines a broad class of the growth curves and possesses a greater generality than the existing unification functions. We also propose the notion of generalized RGR, which is capable of making interrelations among the unifying functions. Our proposed method is expected to enhance the generality of software and may aid in choosing an optimal model from a set of competitor growth equations.

An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles.

Tumor-derived extracellular vesicles (TEV) "educate" healthy cells to promote metastases. We found that melanoma TEV downregulated type I interferon (IFN) receptor and expression of IFN-inducible cholesterol 25-hydroxylase (CH25H). CH25H produces 25-hydroxycholesterol, which inhibited TEV uptake. Low CH25H levels in leukocytes from melanoma patients correlated with poor prognosis. Mice incapable of downregulating the IFN receptor and Ch25h were resistant to TEV uptake, TEV-induced pre-metastatic niche, and melanoma lung metastases; however, ablation of Ch25h reversed these phenotypes. An anti-hypertensive drug, reserpine, suppressed TEV uptake and disrupted TEV-induced formation of the pre-metastatic niche and melanoma lung metastases. These results suggest the importance of CH25H in defense against education of normal cells by TEV and argue for the use of reserpine in adjuvant melanoma therapy.