Underlying plant trait strategies for understanding the carbon sequestration in Banj oak Forest of Himalaya.

Plant functional attributes are subjected to environmental adjustments, which lead to modulations in forest processes under environmental changes. However, a comprehensive assessment of the relationships between plant traits and carbon stock remains subtle. The present study attempted to accomplish the gap of knowledge by examining the linkages between forest carbon with plant traits within the Banj Oak forest in the Garhwal Himalaya. Twelve individuals from three major species in the Banj Oak forest were randomly selected for trait measurements, and soil samples were collected randomly across the area for evaluation of soil nutrients and carbon. Forest biomass and soil carbon were estimated following standard protocols. A Structural Equation Model (SEM) was applied to establish the relationship between above ground carbon (AGC) and soil organic carbon (SOC) with leaf and stem traits, and soil nutrients. Stem traits were tree height and tree diameter; whereas leaf morphological traits were leaf area, specific leaf area, leaf dry matter content; leaf physiological traits were photosynthesis rate, stomatal conductance, and transpiration rate; and leaf biochemical traits were leaf carbon concentration, leaf nitrogen concentration, and leaf phosphorus concentration. Soil nutrients were available nitrogen, available phosphorus, and exchangeable potassium. Based on SEM results, AGC of the forest was positively correlated with stem traits and leaf physiological traits, while negatively correlated with leaf morphological traits. SOC was positively correlated with soil nutrients and leaf biochemical traits, whereas negatively correlated with stem traits. These findings may support for precise quantification of forest carbon and modeling of forest carbon stocks besides providing inputs to forest managers for devising effective forest management strategies.

An iron rheostat controls hematopoietic stem cell fate.

Mechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response to limited iron-particularly during mitosis. To study the functional and molecular consequences of iron restriction, we developed models allowing for transient iron bioavailability limitation and combined single-molecule RNA quantification, metabolomics, and single-cell transcriptomic analyses with functional studies. Our data reveal that the activation of the limited iron response triggers coordinated metabolic and epigenetic events, establishing stemness-conferring gene regulation. Notably, we find that aging-associated cytoplasmic iron loading reversibly attenuates iron-dependent cell fate control, explicating intervention strategies for dysfunctional aged stem cells.

Synthesis of oligosaccharides to identify an immunologically active epitope against Candida auris infection.

Candida auris (C. auris) is an emerging multidrug-resistant fungal pathogen that represents a significant public health challenge as it can spread rapidly and result in high mortality rates. The mannans on the C. auris cell surface are potent immunogens and attractive targets for developing a glycoconjugate vaccine. We synthesized the oligosaccharides resembling cell surface mannans of C. auris and printed them onto microarray slides that were used to screen plasma from mice infected with C. auris. IgM antibodies in mouse plasma recognize the ß-1,2 linkage present in C. auris surface mannans. Disaccharide 19 emerged from glycan array screening as a lead for developing a vaccine against C. auris, as the majority of patient plasma samples showed antibodies against this glycan. The synthetic oligosaccharides can be used for the early detection of C. auris infections.

When a calorie is not just a calorie: Diet quality and timing as mediators of metabolism and healthy aging.

An epidemic of obesity has affected large portions of the world, increasing the risk of developing many different age-associated diseases, including cancer, cardiovascular disease, and diabetes. In contrast with the prevailing notion that "a calorie is just a calorie," there are clear differences, within and between individuals, in the metabolic response to different macronutrient sources. Recent findings challenge this oversimplification; calories from different macronutrient sources or consumed at different times of day have metabolic effects beyond their value as fuel. Here, we summarize discussions conducted at a recent NIH workshop that brought together experts in calorie restriction, macronutrient composition, and time-restricted feeding to discuss how dietary composition and feeding schedule impact whole-body metabolism, longevity, and healthspan. These discussions may provide insights into the long-sought molecular mechanisms engaged by calorie restriction to extend lifespan, lead to novel therapies, and potentially inform the development of a personalized food-as-medicine approach to healthy aging.

mTORC2-NDRG1-CDC42 axis couples fasting to mitochondrial fission.

Fasting triggers diverse physiological adaptations including increases in circulating fatty acids and mitochondrial respiration to facilitate organismal survival. The mechanisms driving mitochondrial adaptations and respiratory sufficiency during fasting remain incompletely understood. Here we show that fasting or lipid availability stimulates mTORC2 activity. Activation of mTORC2 and phosphorylation of its downstream target NDRG1 at serine 336 sustains mitochondrial fission and respiratory sufficiency. Time-lapse imaging shows that NDRG1, but not the phosphorylation-deficient NDRG1Ser336Ala mutant, engages with mitochondria to facilitate fission in control cells, as well as in those lacking DRP1. Using proteomics, a small interfering RNA screen, and epistasis experiments, we show that mTORC2-phosphorylated NDRG1 cooperates with small GTPase CDC42 and effectors and regulators of CDC42 to orchestrate fission. Accordingly, RictorKO, NDRG1Ser336Ala mutants and Cdc42-deficient cells each display mitochondrial phenotypes reminiscent of fission failure. During nutrient surplus, mTOR complexes perform anabolic functions; however, paradoxical reactivation of mTORC2 during fasting unexpectedly drives mitochondrial fission and respiration.

Phenological variations in relation to climatic variables of moist temperate forest tree species of western Himalaya, India.

Phenology, an important ecological attribute, deals with the development of vegetative and reproductive parts of trees called "phenophases", which are important determinants of primary productivity and sensitive to climate change. The present study recorded various phenophases of major tree species (i.e., Quercus leucotrichophora, Rhododendron arboreum, and Myrica esculenta) as per the two-digit numerical system of Biologische Bundesanstalt, Bundessortenamt, Chemische Industrie (BBCH) scale. A total of 72 individual trees, twenty-four from each species, distributed between 1400 and 1980 m. a.s.l elevations were tagged and measured fortnightly for two consecutive years (2019-2021) in the moist temperate forest of Western Himalaya and compared with earlier existing records. Various phenophases were correlated with climatic factors along with duration and thermal time for each phenological growth stage. We found 24 growth stages for Q. leucotrichophora and M. esculenta and 28 for R. arboreum distributed across seven principal growth stages (e.g. bud development, 0; leaf development, 1; shoot development, 3; inflorescence development, 5; flower development, 6; fruit development, 7; and fruit maturation, 8) of trees as per BBCH scale. Maximum growing degree was 748.87 and 627.95 days recorded for R. arboreum and M. esculenta during leaf development, and 796.17 days for Q. leucotrichophora during fruit development. Flower emergence was observed pre, during, and post-emergence of new leaves for R. arboreum, M. esculenta, and Q. leucotrichophora, respectively, which varied at spatial scale with previous findings. Longevity of fruit development to ripening took 17, 4, and 2 months, respectively in Q. leucotrichophora, R. arboreum and M. esculenta. Duration of leaf initiation and flowering was positively correlated with climatic variables, whereas, the reverse was observed for fruiting in the studied tree species. The study concludes that the variations in phenophases of the three species were strongly influenced by climatic variations, especially minimum temperature. The result of the present study would be important in enabling us to formulate efficient forest management strategies by understanding the short-term adaptation of the climate-sensitive important tree species in the western Himalaya.

Epidural stimulation restores muscle synergies by modulating neural drives in participants with sensorimotor complete spinal cord injuries.

Multiple studies have corroborated the restoration of volitional motor control after motor-complete spinal cord injury (SCI) through the use of epidural spinal cord stimulation (eSCS), but rigorous quantitative descriptions of muscle coordination have been lacking. Six participants with chronic, motor and sensory complete SCI underwent a brain motor control assessment (BMCA) consisting of a set of structured motor tasks with and without eSCS. We investigated how muscle activity complexity and muscle synergies changed with and without stimulation. We performed this analysis to better characterize the impact of stimulation on neuromuscular control. We also recorded data from nine healthy participants as controls. Competition exists between the task origin and neural origin hypotheses underlying muscle synergies. The ability to restore motor control with eSCS in participants with motor and sensory complete SCI allows us to test whether changes in muscle synergies reflect a neural basis in the same task. Muscle activity complexity was computed with Higuchi Fractal Dimensional (HFD) analysis, and muscle synergies were estimated using non-negative matrix factorization (NNMF) in six participants with American Spinal Injury Association (ASIA) Impairment Score (AIS) A. We found that the complexity of muscle activity was immediately reduced by eSCS in the SCI participants. We also found that over the follow-up sessions, the muscle synergy structure of the SCI participants became more defined, and the number of synergies decreased over time, indicating improved coordination between muscle groups. Lastly, we found that the muscle synergies were restored with eSCS, supporting the neural hypothesis of muscle synergies. We conclude that eSCS restores muscle movements and muscle synergies that are distinct from those of healthy, able-bodied controls.

Numerical Analysis of Coronavirus Detection Using Photonic Crystal Fibre-Based SPR Sensor.

Coronavirus disease (COVID-19) is a worldwide health emergency caused by the coronavirus 2 (severe acute respiratory illness) (SARS-CoV-2). COVID-19 has a wide range of symptoms, making a definitive diagnosis difficult. The shortage of equipment for testing technology COVID-19 has resulted in long queues for COVID-19 testing, which is a major problem. COVID-19 testing is currently performed using sluggish and costly technology like single-photon emission computed tomography (SPECT), computed tomography (CT), positron emission tomography (PET), and enzyme-linked immunosorbent assay (ELISA). The gold standard test for diagnosing COVID-19 is real-time reverse transcriptase-polymerase chain reaction (RT-PCR), which necessitates highly skilled workers and has a lengthy turnaround time. However, rapid and affordable immunodiagnostic techniques (antigen or antibody tests) are also available with some trade off accuracy. Optical sensors are frequently employed in a variety of applications, because of their increased sensitivity, strong selectivity, rapid reaction times, and outstanding resolution. The use of photonic crystal fibre (PCF) is advantageous for the quick detection of the new coronavirus and is suggested with the use of a PCF-based (Au/BaTiO3/graphene) multilayered surface plasmon resonance (SPR) biosensor. The proposed sensor can quickly detect the COVID-19 virus in two different ligand-analyte environments: (i) the virus spike receptor-binding domain (RBD) as an analyte and monoclonal antibodies (mAbs) as a probe ligand, and (ii) monoclonal antibodies (IgG or IgM) as an analyte and the virus spike RBD as a probe ligand. The finite element method (FEM) is used to quantitatively examine the performance of the PCF-based multilayered SPR sensor.

Increased adipose catecholamine levels and protection from obesity with loss of Allograft Inflammatory Factor-1.

Recent studies implicate macrophages in regulation of thermogenic, sympathetic neuron-mediated norepinephrine (NE) signaling in adipose tissues, but understanding of such non-classical macrophage activities is incomplete. Here we show that male mice lacking the allograft inflammatory factor-1 (AIF1) protein resist high fat diet (HFD)-induced obesity and hyperglycemia. We link this phenotype to higher adipose NE levels that stem from decreased monoamine oxidase A (MAOA) expression and NE clearance by AIF1-deficient macrophages, and find through reciprocal bone marrow transplantation that donor Aif1-/- vs WT genotype confers the obesity phenotype in mice. Interestingly, human sequence variants near the AIF1 locus associate with obesity and diabetes; in adipose samples from participants with obesity, we observe direct correlation of AIF1 and MAOA transcript levels. These findings identify AIF1 as a regulator of MAOA expression in macrophages and catecholamine activity in adipose tissues - limiting energy expenditure and promoting energy storage - and suggest how it might contribute to human obesity.

Congenital Segmental Dilatation of Ascending Colon with Distal Microcolon: A Diagnostic Dilemma.

A 5-day-old male presented with bilious vomiting, a grossly distended abdomen, and passage of a small amount of stool. The anal opening was at a normal position. X-ray abdomen showed a large bowel loop with a single air-fluid level occupying more than half of the abdominal width. On laparotomy, the ascending colon was dilated to form a pouch-like structure, and the ileum and appendix were opening into it. Colon distal to pouch was present as microcolon. Histopathology of the dilated segment was suggestive of congenital segmental dilatation (CSD). In CSD, the distal bowel is of normal caliber. This is a rare case of CSD of ascending colon with distal microcolon.

Chaperone-mediated autophagy regulates adipocyte differentiation.

Adipogenesis is a tightly orchestrated multistep process wherein preadipocytes differentiate into adipocytes. The most studied aspect of adipogenesis is its transcriptional regulation through timely expression and silencing of a vast number of genes. However, whether turnover of key regulatory proteins per se controls adipogenesis remains largely understudied. Chaperone-mediated autophagy (CMA) is a selective form of lysosomal protein degradation that, in response to diverse cues, remodels the proteome for regulatory purposes. We report here the activation of CMA during adipocyte differentiation and show that CMA regulates adipogenesis at different steps through timely degradation of key regulatory signaling proteins and transcription factors that dictate proliferation, energetic adaptation, and signaling changes required for adipogenesis.

Biopolymeric nanoparticles based effective delivery of bioactive compounds toward the sustainable development of anticancerous therapeutics.

Nowadays, effective cancer therapy is a global concern, and recent advances in nanomedicine are crucial. Cancer is one of the major fatal diseases and a leading cause of death globally. Nanotechnology provides rapidly evolving delivery systems in science for treating diseases in a site-specific manner using natural bioactive compounds, which are gaining widespread attention. Nanotechnology combined with bioactives is a very appealing and relatively new area in cancer treatment. Natural bioactive compounds have the potential to be employed as a chemotherapeutic agent in the treatment of cancer, in addition to their nutritional benefits. Alginate, pullulan, cellulose, polylactic acid, chitosan, and other biopolymers have been effectively used in the delivery of therapeutics to a specific site. Because of their biodegradability, biopolymeric nanoparticles (BNPs) have received a lot of attention in the development of new anticancer drug delivery systems. Biopolymer-based nanoparticle systems can be made in a variety of ways. These systems have developed as a cost-effective and environmentally friendly solution to boost treatment efficacy. Effective drug delivery systems with improved availability, increased selectivity, and lower toxicity are needed. Recent research findings and current knowledge on the use of BNPs in the administration of bioactive chemicals in cancer therapy are summarized in this review.

Process Optimization for Development of Guar Gum-Based Biodegradable Hydrogel Film Using Response Surface Methodology.

In the current study, a guar-gum-based biodegradable hydrogel film was prepared using an initiator (potassium persulfate), crosslinker (N-N methyl bis acrylamide), and plasticizer (glycerol) for packaging of fruits and vegetables. The effect of independent variables (initiator, crosslinker, and plasticizer) on the biodegradation (% wt. loss), color difference (ΔE), hardness (N), swelling index (%), and transparency (%) of the film was studied using Box-Behnken design, random surface methodology (RSM). The results showed significant effects on all the abovementioned parameters, and it was observed that the developed model was accurate, with a prediction error of only -3.19 to 2.99%. The optimized formulation for the preparation of hydrogel film was 0.15% initiator, 0.02% crosslinker, and 2.88% plasticizer exhibiting satisfactory biodegradability, color difference, hardness, swelling index, and transparency. Results showed that a guar-gum-based biodegradable hydrogel film has adequate physical, optical, and biodegradable properties and can be successfully utilized in the food packaging industry.

Biochemical, dielectric and surface characteristics of freeze-dried bovine colostrum whey powder.

Colostrum samples of recently registered cow breed "Himachali Pahari" were assorted from high altitude zone (901-2200 m). Prepared bovine colostrum whey powder (BCWP) was analysed for chemical composition, amino acids, minerals, surface morphology (SEM-EDS), FTIR and dielectric properties. Results showed that freeze-dried BCWP contained a considerable amount of nutritional parameters viz IgG (18.55 g/100 g), protein (71.72 g/100 g) and total amino acids (69.64 g/100 g). Additionally, the concentration of essential minerals was found to be adequate, and there was no presence of heavy metals. The BCWP exhibits good dielectric properties (resistance ∼57 M-Ω). SEM-EDS showed the broken up-wards layer structure with the uniform distribution of minerals on the surface. The FTIR spectra confirmed the presence of a higher proportion of ß-sheets and ß-turn structures in BCWP. Thus, on account of good functional and nutritive properties, BCWP could be foreseen as the future of functional food.

The immune checkpoint B7-H3 (CD276) regulates adipocyte progenitor metabolism and obesity development.

The immune checkpoint B7-H3 (CD276) is a member of the B7 family that has been studied in the tumor microenvironment and immunotherapy, but its potential role in metabolism remains largely unknown. Here, we show that B7-H3 is highly expressed in mouse and human adipose tissue at steady state, with the highest levels in adipocyte progenitor cells. B7-H3 is rapidly down-regulated upon the initiation of adipocyte differentiation. Combined RNA sequencing and metabolic studies reveal that B7-H3 stimulates glycolytic and mitochondrial activity of adipocyte progenitors. Loss of B7-H3 in progenitors results in impaired oxidative metabolism program and increased lipid accumulation in derived adipocytes. Consistent with these observations, mice knocked out for B7-H3 develop spontaneous obesity, metabolic dysfunction, and adipose tissue inflammation. Our results reveal an unexpected metabolic role for B7-H3 in adipose tissue and open potential new avenues for the treatment of metabolic diseases by targeting the B7-H3 pathway.

Protective role of chaperone-mediated autophagy against atherosclerosis.

Chaperone-mediated autophagy (CMA) contributes to regulation of energy homeostasis by timely degradation of enzymes involved in glucose and lipid metabolism. Here, we report reduced CMA activity in vascular smooth muscle cells and macrophages in murine and human arteries in response to atherosclerotic challenges. We show that in vivo genetic blockage of CMA worsens atherosclerotic pathology through both systemic and cell-autonomous changes in vascular smooth muscle cells and macrophages, the two main cell types involved in atherogenesis. CMA deficiency promotes dedifferentiation of vascular smooth muscle cells and a proinflammatory state in macrophages. Conversely, a genetic mouse model with up-regulated CMA shows lower vulnerability to proatherosclerotic challenges. We propose that CMA could be an attractive therapeutic target against cardiovascular diseases.

Synthesis of Oligosaccharides Resembling the Streptococcus suis Serotype 18 Capsular Polysaccharide as a Basis for Glycoconjugate Vaccine Development.

Here we report the first total synthesis of several oligosaccharides resembling the capsular polysaccharide of swine pathogen S. suis serotype 18 repeating unit [→3)-d-GalNAc(α1-3)[d-Glc(ß1-2)]-d-GalA4OAc(ß1-3)-d-GalNAc(α1-3)-d-BacNAc4NAc(α1→]n. Access to the pentasaccharide repeating unit antigen proved to be very challenging due to the poor reactivity in the context of the trisaccharide. The challenge was overcome by the creation of a galacturonic acid in a late stage of the synthesis.

Redox signaling by glutathione peroxidase 2 links vascular modulation to metabolic plasticity of breast cancer.

In search of redox mechanisms in breast cancer, we uncovered a striking role for glutathione peroxidase 2 (GPx2) in oncogenic signaling and patient survival. GPx2 loss stimulates malignant progression due to reactive oxygen species/hypoxia inducible factor-α (HIF1α)/VEGFA (vascular endothelial growth factor A) signaling, causing poor perfusion and hypoxia, which were reversed by GPx2 reexpression or HIF1α inhibition. Ingenuity Pathway Analysis revealed a link between GPx2 loss, tumor angiogenesis, metabolic modulation, and HIF1α signaling. Single-cell RNA analysis and bioenergetic profiling revealed that GPx2 loss stimulated the Warburg effect in most tumor cell subpopulations, except for one cluster, which was capable of oxidative phosphorylation and glycolysis, as confirmed by coexpression of phosphorylated-AMPK and GLUT1. These findings underscore a unique role for redox signaling by GPx2 dysregulation in breast cancer, underlying tumor heterogeneity, leading to metabolic plasticity and malignant progression.