High performance Pt-anchored MoS2based chemiresistive ascorbic acid sensor.

Ascorbic acid (AA), known as vitamin C, is a vital bioactive compound that plays a crucial role in several metabolic processes, including the synthesis of collagen and neurotransmitters, the removal of harmful free radicals, and the uptake of iron by cells in the human intestines. As a result, there is an absolute need for a highly selective, sensitive, and economically viable sensing platform for AA detection. Herein, we demonstrate a Pt-decorated MoS2for efficient detection of an AA biosensor. MoS2hollow rectangular structures were synthesized using an easy and inexpensive chemical vapor deposition approach to meet the increasing need for a reliable detection platform. The synthesized MoS2hollow rectangular structures are characterized through field effect scanning electron microscopy (FESEM), energy-dispersive spectroscopy elemental mapping, Raman spectroscopy, and x-ray photoelectron spectroscopy. We fabricate a chemiresistive biosensor based on Pt-decorated MoS2that measures AA with great precision and high sensitivity. The experiments were designed to evaluate the response of the Pt-decorated MoS2biosensor in the presence and absence of AA, and selectivity was evaluated for a variety of biomolecules, and it was observed to be very selective towards AA. The Pt-MoS2device had a higher response of 125% against 1 mM concentration of AA biomolecules, when compared to that of all other devices and 2.2 times higher than that of the pristine MoS2device. The outcomes of this study demonstrate the efficacy of Pt-decorated MoS2as a promising material for AA detection. This research contributes to the ongoing efforts to enhance our capabilities in monitoring and detecting AA, fostering advancements in environmental, biomedical, and industrial applications.

Spatio-temporal variation in water quality due to the anthropogenic impact in Rudrasagar Lake, a Ramsar site in India.

Rudrasagar Lake, a vital habitat for diverse flora and fauna, supports over 2000 households to sustain their daily livelihoods. The current study attempts to examine the impact of human activities on spatio-temporal variation in the water quality of the study area. The study integrates extensive field surveys, sample processing, and statistical analysis to assess the recent status of wetland health. Latin Square Matrix (LSM) was employed to select the sampling sites while the Inverse Distance Weighting (IDW) interpolation technique was used for spatial variation mapping. Modified Weighted Arithmetic Water Quality Index (MWAWQI) and Comprehensive Pollution Index (CPI) were utilized for assessing seasonal variation water quality and pollution loads, respectively. The results showed that dissolved oxygen (DO) was strongly influenced by the tributaries, and recreational activities have substantially influenced the highest concentrations of biochemical oxygen demand (BOD), and total suspended solids (TSS). The central portion of the lake is particularly susceptible to pollution from extensive fishing and recreational activities while peripheral sites are strongly influenced by agricultural run-offs, seepages from brick industries, and municipal wastes characterized by high concentrations of pH, total hardness (TH), oxidation-reduction potential (ORP). The findings reveal remarkable spatio-temporal fluctuations and highlight the areas within the lake susceptible to anthropogenic activities. The study proposed a sustainable management model to ameliorate anthropogenic threats. Moreover, the study contributes to the scientific understanding of the challenges and ensures the long-term viability of wetland health as a vital ecological and socio-economic resource.

A Novel HM-HD-RFET Biosensor for Label-Free Biomolecule Detection.

The mortality of people worldwide caused by COVID-19 has enhanced the research interest to design and develop power-efficient, low-cost, and sensitive biosensors to detect a wide range of biomolecules or foreign particles that can cause severe negative impact on humans. A novel Bio-RFET biosensor with hetero-material (HM) for source/channel and drain regions and hetero-dielectric (HD) is proposed, which acts as an n-MOSFET or a p-MOSFET and n-TFET or p-TFET. This HM-HD-RFET biosensor senses the biomolecules by the label-free dielectric modulation (DM) technique. When the biomolecules are present in the nanocavity, the biosensor can detect the biomolecules without labeling costs. It also changes the dielectric polarization within the nanocavities, and causes a drain current variation in the presence of an electric field. In this research article, (SiO2 + TiO2) and an AlGaAs/Ge-based HD-HM-RFET have been analyzed for their use in biosensing. We found that the proposed device exhibits higher sensitivity as compared to a SiO2 + HfO2-HM-RFET and a Si-based SiO2 + TiO2-RFET for varying dielectric constants (K) from K = 20-80 and charge densities in the range - 5 × 1011 to 1 × 1013 C/cm2. Further, it can be noticed that n-SiO2 + TiO2-HM-TFET possesses the highest Id-Vgs sensitivity of 5.09 × 1013, ION/IOFF ratio of 1.23 × 109, lowest SS of 20.3 mV/dec, and Vth of 1.48 V.

Practice makes perfect: familiarity of task determines success in solvable tasks for free-ranging dogs (Canis lupus familiaris).

Domestic dogs' (Canis lupus familiaris) socio-cognitive faculties have made them highly sensitive to human social cues. While dogs often excel at understanding human communicative gestures, they perform comparatively poorly in problem-solving and physical reasoning tasks. This difference in their behaviour could be due to the lifestyle and intense socialization, where problem solving and physical cognition are less important than social cognition. Free-ranging dogs live in human-dominated environments, not under human supervision and are less socialized. Being scavengers, they often encounter challenges where problem solving is required in order to get access to food. We tested Indian street dogs in familiar and unfamiliar independent solvable tasks and quantified their persistence and dependence on a novel human experimenter, in addition to their success in solving a task. Our results indicate that free-ranging dogs succeeded and persisted more in the familiar task as compared to the unfamiliar one. They showed negligible amount of human dependence in the familiar task, but showed prolonged gazing and considerable begging behaviour to the human experimenter in the context of the unfamiliar task. Cognitive abilities of free-ranging dogs thus play a pivotal role in determining task-associated behaviours based on familiarity. In addition to that, these dogs inherently tend to socialize with and depend on humans, even if they are strangers. Our results also illustrate free-ranging dogs' low competence at physical cognitive tasks.

Performance of predictive algorithms in estimating the risk of being a zero-dose child in India, Mali and Nigeria.

INTRODUCTION: Many children in low-income and middle-income countries fail to receive any routine vaccinations. There is little evidence on how to effectively and efficiently identify and target such 'zero-dose' (ZD) children. METHODS: We examined how well predictive algorithms can characterise a child's risk of being ZD based on predictor variables that are available in routine administrative data. We applied supervised learning algorithms with three increasingly rich sets of predictors and multiple years of data from India, Mali and Nigeria. We assessed performance based on specificity, sensitivity and the F1 Score and investigated feature importance. We also examined how performance decays when the model is trained on older data. For data from India in 2015, we further compared the inclusion and exclusion errors of the algorithmic approach with a simple geographical targeting approach based on district full-immunisation coverage. RESULTS: Cost-sensitive Ridge classification correctly classifies most ZD children as being at high risk in most country-years (high specificity). Performance did not meaningfully increase when predictors were added beyond an initial sparse set of seven variables. Region and measures of contact with the health system (antenatal care and birth in a facility) had the highest feature importance. Model performance decreased in the time between the data on which the model was trained and the data to which it was applied (test data). The exclusion error of the algorithmic approach was about 9.1% lower than the exclusion error of the geographical approach. Furthermore, the algorithmic approach was able to detect ZD children across 176 more areas as compared with the geographical rule, for the same number of children targeted. INTERPRETATION: Predictive algorithms applied to existing data can effectively identify ZD children and could be deployed at low cost to target interventions to reduce ZD prevalence and inequities in vaccination coverage.

Role of endoplasmic reticulum stress-related unfolded protein response and its implications in dengue virus infection for biomarker development.

Dengue virus (DENV) causes debilitating disease in humans, which varies at different rates in host cells, such as monocytes, macrophages, dendritic cells, Langerhans cells, and other cell types. Such heterogeneity in DENV infection in cells could be attributed to a range of factors, including host cell immune response, anti-viral cellular proteins, and virus mediated cellular autophagy. This review delineates an important feature of every cell, the unfolded protein response (UPR) that is attributed to the accumulation of several viral and unfolded/misfolded proteins, such as in DENV infection. UPR is a normal process to counteract endoplasmic reticulum (ER) stress that leads to cell autophagy; though the phenomenon is markedly upregulated during DENV infection. This could be attributed to the uncontrolled activation of the key UPR signaling pathways: inositol-requiring transmembrane kinase/endoribonuclease 1 (IRE1), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), and activating transcription factor-6 (ATF6), which promote cell autophagy under normal and diseased conditions through the downstream regulation of apoptosis promoting factors such as X-box binding protein (XBP1), GADD34, and ATF-6. Because DENV can modulate these signaling cascades, by promoting dysregulated cell autophagy, the ER stress mediated UPR pathways and the inherent agents could play an important role in delineating the severity of dengue infection with a potential for developing DENV targeted therapeutics.

Protein-stabilized silver nanoparticles encapsulating gentamycin for the therapy of bacterial biofilm infections.

Aim: An antibiotic-conjugated protein-stabilized nanoparticle hybrid system was developed to combat the challenges faced during the treatment of drug-resistant bacterial biofilm-associated infections. Materials & methods: Biocompatible silver nanoparticles were synthesized using intracellular protein and gentamycin was attached. The resulting nanohybrid was characterized and its antibacterial efficiency was assessed against Gram-positive, Gram-negative and drug-resistant bacteria. Results: Spectroscopic and electron microscopic analysis revealed that the nanoparticles were spherical with a diameter of 2-6 nm. Red-shifting of the surface plasmon peak and an increase in hydrodynamic diameter confirmed attachment of gentamycin. The nanohybrid exhibited antibacterial efficiency against a range of bacteria with the ability to inhibit and disrupt bacterial biofilm. Conclusion: A unique nanohybrid was designed that has potential to be used to control drug-resistant bacterial infections in the future.

Loss of MyoD and Myf5 in Skeletal Muscle Stem Cells Results in Altered Myogenic Programming and Failed Regeneration.

MyoD and Myf5 are fundamental regulators of skeletal muscle lineage determination in the embryo, and their expression is induced in satellite cells following muscle injury. MyoD and Myf5 are also expressed by satellite cell precursors developmentally, although the relative contribution of historical and injury-induced expression to satellite cell function is unknown. We show that satellite cells lacking both MyoD and Myf5 (double knockout [dKO]) are maintained with aging in uninjured muscle. However, injured muscle fails to regenerate and dKO satellite cell progeny accumulate in damaged muscle but do not undergo muscle differentiation. dKO satellite cell progeny continue to express markers of myoblast identity, although their myogenic programming is labile, as demonstrated by dramatic morphological changes and increased propensity for non-myogenic differentiation. These data demonstrate an absolute requirement for either MyoD or Myf5 in muscle regeneration and indicate that their expression after injury stabilizes myogenic identity and confers the capacity for muscle differentiation.

Activin-dependent signaling in fibro/adipogenic progenitors causes fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal-dominant disorder characterized by progressive and profoundly disabling heterotopic ossification (HO). Here we show that fibro/adipogenic progenitors (FAPs) are a major cell-of-origin of HO in an accurate genetic mouse model of FOP (Acvr1 tnR206H ). Targeted expression of the disease-causing type I bone morphogenetic protein (BMP) receptor, ACVR1(R206H), to FAPs recapitulates the full spectrum of HO observed in FOP patients. ACVR1(R206H)-expressing FAPs, but not wild-type FAPs, activate osteogenic signaling in response to activin ligands. Conditional loss of the wild-type Acvr1 allele dramatically exacerbates FAP-directed HO, suggesting that mutant and wild-type ACVR1 receptor complexes compete for activin ligands or type II BMP receptor binding partners. Finally, systemic inhibition of activin A completely blocks HO and restores wild-type-like behavior to transplanted Acvr1 R206H/+ FAPs. Understanding the cells that drive HO may facilitate the development of cell-specific therapeutic approaches to inhibit catastrophic bone formation in FOP.

Free-ranging dogs show age related plasticity in their ability to follow human pointing.

Differences in pet dogs' and captive wolves' ability to follow human communicative intents have led to the proposition of several hypotheses regarding the possession and development of social cognitive skills in dogs. It is possible that the social cognitive abilities of pet dogs are induced by indirect conditioning through living with humans, and studying free-ranging dogs can provide deeper insights into differentiating between innate abilities and conditioning in dogs. Free-ranging dogs are mostly scavengers, indirectly depending on humans for their sustenance. Humans can act both as food providers and as threats to these dogs, and thus understanding human gestures can be a survival need for the free-ranging dogs. We tested the responsiveness of such dogs in urban areas toward simple human pointing cues using dynamic proximal points. Our experiment showed that pups readily follow proximal pointing and exhibit weaker avoidance to humans, but stop doing so at the later stages of development. While juveniles showed frequent and prolonged gaze alternations, only adults adjusted their behaviour based on the reliability of the human experimenter after being rewarded. Thus free-ranging dogs show a tendency to respond to human pointing gestures, with a certain level of behavioural plasticity that allows learning from ontogenic experience.

FACS Fractionation and Differentiation of Skeletal-Muscle Resident Multipotent Tie2+ Progenitors.

The skeletal muscle niche is complex and heterogeneous. Over the past few decades, various groups have reported the existence of multiple adult stem cell populations within this environment. Techniques commonly used to identify and assess the differentiation capacities of these cellular fractions, oftentimes rare populations, include the use of lineage tracers, immunofluorescence and histochemistry, flow cytometry, gene expression assays, and phenotypic analysis in culture or in vivo. In 2012, our lab identified and characterized a skeletal-muscle resident Tie2+ progenitor that exhibits adipogenic, chondrogenic, and osteogenic differentiation potentials (Wosczyna et al., J Bone Miner Res 27:1004-1017, 2012). This Tie2+ progenitor also expresses the markers PDGFRα and Sca-1 which in turn label a population of muscle-resident fibro/adipogenic progenitors (FAPs) (Joe et al., Nat Cell Biol 12:153-163, 2010; Uezumi et al., Nat Cell Biol 12:143-152, 2010), suggesting similar identities or overlap in the two mesenchymal progenitor populations. Our study demonstrated that these Tie2-expressing mesenchymal progenitors contribute robustly to BMP-induced heterotopic ossification (HO) in mice, and therefore could represent a key cellular target for therapeutic intervention in HO treatment (Wosczyna et al., J Bone Miner Res 27:1004-1017, 2012). In this chapter, we provide a detailed description of our updated fluorescence-activated cell sorting (FACS) strategy and describe cell culture methods for differentiation of Tie2+ progenitors to adipogenic and osteogenic fates. This strategy is easily adaptable for the prospective isolation of other rare subpopulations resident in skeletal muscle.

Multipotent progenitors resident in the skeletal muscle interstitium exhibit robust BMP-dependent osteogenic activity and mediate heterotopic ossification.

Heterotopic ossification is a debilitating condition that can result from traumatic injury, surgery, or genetic disease. We investigated the cellular origins of heterotopic skeletogenesis in the mouse using lineage tracing and bioassays of heterotopic ossification based on intramuscular transplantation. We identified, characterized, and purified a tissue-resident stem/progenitor cell population that exhibits robust osteogenic potential and represents a major cell-of-origin for heterotopic ossification. These progenitors reside in the interstitium of skeletal muscle and other tissues, and are distinct from the endothelium, which does not exhibit osteogenic activity in response to bone morphogenetic protein 2 (BMP2) stimulation. Intramuscular transplantation, together with clonal analysis in culture, revealed that these progenitors are multipotent, exhibiting the capacity for both BMP-dependent skeletogenic differentiation and spontaneous adipogenic differentiation. Identifying the cells-of-origin responsible for heterotopic ossification provides a potential therapeutic target to treat, mitigate, or prevent this disabling condition.