A microbiome-dependent gut-brain pathway regulates motivation for exercise.

Exercise exerts a wide range of beneficial effects for healthy physiology1. However, the mechanisms regulating an individual's motivation to engage in physical activity remain incompletely understood. An important factor stimulating the engagement in both competitive and recreational exercise is the motivating pleasure derived from prolonged physical activity, which is triggered by exercise-induced neurochemical changes in the brain. Here, we report on the discovery of a gut-brain connection in mice that enhances exercise performance by augmenting dopamine signalling during physical activity. We find that microbiome-dependent production of endocannabinoid metabolites in the gut stimulates the activity of TRPV1-expressing sensory neurons and thereby elevates dopamine levels in the ventral striatum during exercise. Stimulation of this pathway improves running performance, whereas microbiome depletion, peripheral endocannabinoid receptor inhibition, ablation of spinal afferent neurons or dopamine blockade abrogate exercise capacity. These findings indicate that the rewarding properties of exercise are influenced by gut-derived interoceptive circuits and provide a microbiome-dependent explanation for interindividual variability in exercise performance. Our study also suggests that interoceptomimetic molecules that stimulate the transmission of gut-derived signals to the brain may enhance the motivation for exercise.

A genetically encoded protein tag for control and quantitative imaging of CAR T cell therapy.

Chimeric antigen receptor (CAR) T cell therapy has been successful for hematological malignancies. Still, a lack of efficacy and potential toxicities have slowed its application for other indications. Furthermore, CAR T cells undergo dynamic expansion and contraction in vivo that cannot be easily predicted or controlled. Therefore, the safety and utility of such therapies could be enhanced by engineered mechanisms that engender reversible control and quantitative monitoring. Here, we use a genetic tag based on the enzyme Escherichia coli dihydrofolate reductase (eDHFR), and derivatives of trimethoprim (TMP) to modulate and monitor CAR expression and T cell activity. We fused eDHFR to the CAR C terminus, allowing regulation with TMP-based proteolysis-targeting chimeric small molecules (PROTACs). Fusion of eDHFR to the CAR does not interfere with cell signaling or its cytotoxic function, and the addition of TMP-based PROTACs results in a reversible and dose-dependent inhibition of CAR activity via the proteosome. We show the regulation of CAR expression in vivo and demonstrate imaging of the cells with TMP radiotracers. In vitro immunogenicity assays using primary human immune cells and overlapping peptide fragments of eDHFR showed no memory immune repertoire for eDHFR. Overall, this translationally-orientied approach allows for temporal monitoring and image-guided control of cell-based therapies.

Socio-Economic Status Differences in Changing Affordability of Tobacco Products from 2011-2012 to 2018-2019 in India.

INTRODUCTION: We studied the change in affordability of tobacco products, an important determinant of tobacco use, across the different socio-economic status (SES) in India. AIMS AND METHODS: We calculated affordability in the form of relative income price (RIP-cost of tobacco products relative to income) for the years 2011-2012 and 2018-2019 using three different denominators, that is per capita gross domestic product (GDP) and net state domestic product at national and state levels, respectively; monthly per capita consumer expenditure (MPCE); and individual wages. We investigated RIP for cigarettes, bidis, and smokeless tobacco (SLT) across different SES groups (caste groups, type of employment, and education). RESULTS: RIP increased marginally for cigarettes, bidis and remained almost constant for SLT across casual workers. However, when RIP was adjusted with SES variables, there was no significant change (p > .05) in the affordability of products for casual workers in the year 2018-2019 as compared to 2011-2012. For regular workers, cigarettes and bidis became marginally less affordable (ß < 1), whereas affordability remained constant for SLT. All products became more affordable for backward caste groups within regular workers. When RIP was calculated using MPCE all tobacco products became less affordable in the year 2018-2019. However, after adjusting for SES variables SLT reported no change in affordability. There was a marginal increase in affordability for all products when RIP was calculated with GDP. CONCLUSIONS: Although implementation of GST has increased the price of tobacco products, it is still not sufficient to reduce the affordability of tobacco products, particularly SLT and especially for the lower SES group. IMPLICATIONS: Tobacco use and economic disadvantage conditions of the population are intricately linked. Affordability of tobacco products is influenced by socio-economic indicators like age, sex, income, education, etc. The literature measuring the affordability of tobacco products across different SES groups is scant in India. Additionally, existing literature measures affordability of tobacco products based on per capita GDP as a proxy for income. This is the first study in Indian context to report the change in affordability of tobacco products across different SES groups after adjusting for SES indicators, using individual-level income data. We have calculated the change in affordability of tobacco products between the year 2011-2012 and 2018-2019 using GDP, household income, and individual wages as a proxy for income.

Changes in tobacco depictions after implementation of tobacco-free film and TV rules in Bollywood films in India: a trend analysis.

BACKGROUND: India's tobacco-free film and TV rules were implemented from 2012. To assess the effect of the rules, we studied tobacco depictions in top-grossing Bollywood films released between 2006 and 2017 and rule compliance after 2012. METHODS: Tobacco incidents and brand appearances were coded in 240 top-grossing Bollywood films (2006-2017) using the Breathe California method. Trends in number of tobacco incidents per film per year were studied before and after implementation of the rules using Poisson regression analysis. Compliance with rules over the years was studied using Pearson product-moment correlations. RESULTS: Forty-five films were U-rated (all ages), 162 were UA-rated (below age 12 years must be adult-accompanied), and 33 were A-rated (age 18+ years only). Before implementation of the rules, the number of tobacco incidents per film was increasing by a factor of 1.1/year (95% CI 1.0 to 1.2, p=0.002). However, beginning year 2013, the number of incidents per film started falling significantly by a factor of 0.7/year (95% CI 0.6 to 0.9; p=0.012) compared with the previous increasing trend. The percentage of youth-rated (U and UA) films with any tobacco incidents also declined from a peak of 76% in 2012 to 35% in 2017. The percentage of films complying with the rules (audio-visual disclaimers, health spots, static warnings) did not change significantly from 2012 to 2017. CONCLUSION: India's 2012 rules were followed by a reduction in tobacco depictions in Bollywood films. Enhanced monitoring of compliance is needed to ensure the continued effectiveness of the rules.

Assessment of air pollution tolerance potential of selected dicot tree species for urban forestry.

Air pollution is one of the killers of our age especially for the urban areas. Urban forestry which involves planting more trees has been considered as one of the prominent strategies to mitigate air pollution. Identification of trees tolerant to air pollution is important for plantation drives being organized across the country. The present study aimed to compare the air pollution tolerance potential of 46 tree species growing in Guru Nanak Dev University (GNDU) campus, Amritsar, using two indices, viz., Air Pollution Tolerance Index (APTI) and Anticipated Performance Index (API). APTI is based on four biochemical parameters, viz., relative water content, leaf extract pH, total chlorophyll, and ascorbic acid contents of leaf samples, whereas API takes into consideration morphological and socioeconomic values of plant species along with their APTI. Based on APTI values calculated for 46 tree species, only 2 tree species, viz., Psidium guajava (46.26) and Cassia fistula (41.83), were found to be tolerant to air pollution, while 25 species showed intermediate tolerance. API scores revealed one tree species, namely, P. guajava, as an excellent performer, 8 species as very good performers, and 28 species as moderate to good performers against air pollution. In conclusion, tree species like Alstonia scholaris, C. fistula, Ficus tsjakela, Grevillea robusta, Kigelia africana, Mangifera indica, Melia azedarach, P. guajava, Pongamia pinnata, Pterospermum acerifolium, Putranjiva roxburghii, Syzygium cumini, Terminalia arjuna, and Toona ciliata can be considered as most desirable for plantations in areas around GNDU campus.

Progress and challenges in the biofoundry of immunosuppressants: From process to practice.

Microorganisms are known to produce pharmaceutically important secondary metabolites that are used as drug moieties in the treatment of various disorders. Discovery of one such class of drugs called immunosuppressants led the way for new and improved treatment regimens for the cases of organ rejections as well as for autoimmune diseases. Uncovering the role of these secondary metabolites as immunomodulators had increased their demand in the global drug market. However, this was soon overshadowed by the low amount of product obtained after fermentation and tedious downstream processing for the recovery of product. Hence, continuous efforts are being made to enhance their production by unveiling the basic biosynthetic pathways involved in their synthesis. From unearthing these immunosuppressants to their rapid development towards commercialization, these drugs have gained a significant place in the world market. Hence, the present review is focused on the progress and challenges in the production and downstream processing of different immunosuppressants (tacrolimus, cyclosporine, rapamycin, and mycophenolic acid). This is the first review report on how the market demand of immunosuppressants could be fulfilled by exploring biofoundry approaches to achieve the goal.

A qualitative study regarding menstrual hygiene in a rural community of Haryana, India.

INTRODUCTION: Adolescent girls face challenges in menstrual hygiene in routine patterns which impacts their education and health. A qualitative study was undertaken to assess the knowledge and practices regarding menstruation in a rural community of Haryana and to identify the barriers to menstrual hygiene. METHODOLOGY: The study was conducted in the month of September 2019 among various stakeholders i.e. adolescent females, adolescent males, Accredited Social Health Activist (ASHA) workers, Anganwadi workers, school teachers and Medical Officers. The stakeholders were mapped with the help of a Multi-Purpose Health Worker and ASHA of the village. Interview guides for focus group discussion (FGD) and in-depth interview (IDI) were prepared from previous literature to understand menstrual health management among the stakeholders. RESULTS: After IDI and FGD, we found that there is a barrier to accessibility of regular sanitary pads, a lack of education on menstrual hygiene among adolescent girls. School absenteeism was a concern due to the unavailability of mechanisms for the disposal of sanitary pads in school and poor maintenance of toilets. CONCLUSION: Proper implementation of the Adolescent Reproductive Sexual Health program and Menstrual health education can improve the use and reduce stigma and ignorance. Free uninterrupted supply of sanitary pads through school and Anganwadi will help improving accessibility and separate toilets for girls would lead to a reduction in absenteeism.

Effects of Intermittent Fasting on Weight Loss in Asian Indian Adults with Obesity.

BACKGROUND: Worldwide, obesity has nearly tripled since 1975 and has become a major healthcare challenge today. Intermittent fasting (IF) is gaining popularity as a weight loss strategy in recent times. This study aimed to study the role of IF as a modern-day weight-loss strategy in obese adults through a real-world pilot experiment conducted at a nutrition clinic in Mumbai. METHODOLOGY: To understand the effects of IF on weight loss, 32 overweight/obese [body mass index (BMI) ≥23 kg/m2] adults from a nutrition clinic in Mumbai, were assigned consecutively to an IF plan and followed up for 3 months. Their demographic, anthropometric, and dietary assessments were done pre- and post-intervention. Qualitative interviews were done at the end of the study to record the participants' overall well-being, experience, and sustainability of IF. RESULTS: 56% of study participants were males and their mean age was 35.6 ± 8.9 years. 65.6% of participants were able to maintain 14-16 hours of fasting and 53% managed all 7 days of IF. Analysis of post-intervention data showed a significant reduction in mean body weight (88.5 ± 19 to 83.8 ± 17.6 kg), waist circumference (M: 108.2 ± 11.3 to 103.6 ± 4.4 cm, F: 98.9 ± 8.8 to 93.3 ± 3.3 cm), BMI (31.4 ± 5.3 to 29.6 ± 5.1 kg/m2), daily calories (1782 ± 237 to 1388 ± 243 kcal/day), carbohydrate intake (267 ± 18.4 to 164 ± 4.0 g/day), and an increase in protein intake (39 ± 11 to 55 ± 11 g/day). Participants reported positive experiences of practicing IF such as improved fitness, sleep cycle, and adoption of healthy eating habits. CONCLUSION: The study demonstrates that IF could aid in weight loss and adoption of a healthier lifestyle.

A place for everything and everything in its place: spatial organization of individuals on nests of the primitively eusocial wasp Ropalidia marginata.

Non-random space use is common among animals across taxa and habitats. Social insects often use space non-randomly, outside as well as inside their nests. While such non-random space use outside the nest may improve foraging efficiency, inside the nest, it is often associated with the efficient division of labour. Non-random space use by adults on their nests has been hypothesized to result from dyadic dominance interactions, non-random distribution of tasks, differential activity levels, workers avoiding their queens or prophylactic avoidance of disease spread. These hypotheses are generally derived from species in which the tasks of the workers are themselves non-randomly distributed on the nest. Here, we study the primitively eusocial wasp Ropalidia marginata, in which tasks are not distributed non-randomly, and show that 62.4% ± 16.2% of the adults nevertheless use space on their nest non-randomly. In this species, we find that non-random space use may help optimizing nutritional exchange between individuals while prophylactically minimizing disease spread among nest-mates. We did not find evidence for the roles of dominance interactions, activity levels or location of larvae in non-random space use. Spatial organization appears to be a mechanism of minimizing the costs and maximizing the benefits of social life.

Tocilizumab for the management of immune mediated adverse events secondary to PD-1 blockade.

BACKGROUND: Immune checkpoint inhibitors are poised to revolutionize the management of a growing number of malignancies. Unfortunately, the management of steroid-refractory immune mediated adverse events is based on a paucity of randomized data and limited to single center experiences. Our initial experience with the IL-6 receptor antagonist tocilizumab showed clinical improvement in a wide variety of irAEs. As a result, we adopted the use of tocilizumab for the management of steroid refractory irAEs. METHODS: The character and clinical course of irAEs were abstracted from the medical record and analyzed. The dose of tocilizumab was 4 mg/kg given IV over one hour. C-reactive protein was drawn at first nivolumab infusion and at q two weeks (and with irAEs) thereafter. Clinical improvement was defined as either: documentation of resolution of symptoms or hospital discharge within seven days. RESULTS: Of the initial 87 patients that were treated with nivolumab, 34 required tocilizumab (39.1%). All patients were on corticosteroids. The majority (88.2%) were lung cancer patients. The index grade 3/4 irAE was pneumonitis in 35.3%, serum sickness/SIRS in 35.3%, cerebritis in 14.7% and one case each of hypophysitis, colitis, pancreatitis, hepatitis and immune mediated coagulopathy. Median time between first nivolumab and initiation of tocilizumab was 76 days (range 1-429). There was a statistically significant increase in C-reactive protein from a median of 23 mg/L (range 0.1-238.5) at baseline to 109.3 mg/L (21.5-350.4) at the time of index irAE, followed by a decrease to 19.2 mg/L (0.25-149) after tocilizumab ( p < 0.00001). Clinical improvement was noted in 27/34 patients (79.4%). Some patients (52.9%) required a single dose, while 38.2% required two, 8.8% required three and 1 patient required four doses. Twenty-seven doses were given in the inpatient setting (49.1%). Median time to discharge was four days (range 1-27). Seventy-four percent of patients were discharged home. For the 53 doses of tocilizumab that were delivered when infliximab was an option, there was a cost savings of $141,048.72 (WAC) during the 18 month study period. CONCLUSIONS: Tocilizumab may be a therapeutic option for the management of steroid refractory irAEs secondary to immune checkpoint blockade. However, randomized trials are needed to better elucidate the relative efficacy and safety of these agents.

Experimental and theoretical investigations of regioselective functionalization of 3-hydroxy bisindoles with thiols.

An instant and efficient p-TSA·H2O-catalyzed sulfenylation reaction of 3-hydroxy bisindole derivatives is reported. This highly regioselective approach afforded C-3 functionalized products in excellent yield, and this methodology was found to be compatible with both aromatic and aliphatic thiols having electronic and steric divergence as well as diverse functional groups. The sulfenylation reaction was performed at room temperature with a green solvent with minimal catalyst loading and proceeded with the involvement of a quasi-antiaromatic-2H-indol-2-one ring intermediate. Moreover, the experimental results obtained for the sulfenylation reaction of 3-hydroxy bisindoles were supported by theoretical calculations in order to comprehend the regioselectivity and chemical reactivity observed in the thiolation reaction of 3-hydroxy bisindoles. The protocol involved the SN1 pathway, as also demonstrated by theoretical calculations.

Iodine-Catalyzed Regioselective Synthesis of Multisubstiuted Pyrrole Polyheterocycles Free from Rotamers and Keto-Enol Tautomers.

A highly regioselective iodine-mediated cascade reaction for the synthesis of multifunctional polyheterocyclic systems is developed by employing 3-(2-oxo-2-arylethylidene)oxindoles and 1,4-benzoxazinone as starting materials. The polyheterocycles are skillfully embraced with oxindole, pyrrole, and coumarin scaffolds, which are well-known for their enriched biological activity. The current approach worked under mild reaction conditions. The reaction afforded a single product, and no rotameric and keto-enol isomeric products are formed. The method is environmentally benign and atom-economical, and the only side product of this reaction is water. This protocol obviates the purification techniques such as column chromatography for the isolation of the products. The products were isolated by decantation of the solvent or by recrystallization. The reaction proceeds through inter- and intramolecular C-C and C-N bond formation.

BF3·OEt2 Mediated Regioselective Reaction of Electron-Rich Arenes with 3-Ylidene Oxindoles.

A BF3·OEt2 mediated novel and regioselective protocol for the construction of a C-C bond between 3-ylidene oxindoles and electron-rich arenes has been successfully accomplished. The reaction was compatible with a wide variety of electron-rich arenes. A cascade reaction of 3-ylidene oxindoles with phenols and ß-naphthol resulted in 2,3-difunctionalized benzofuran and lactone bearing indoline-2-one scaffolds under same conditions.

Development of metasurface based hyperthermia lens applicator for heating of cancerous tissues.

Numerous designs and methods have been examined to improve penetration depth (PD), but there is a need for research to explore the potential increase in PD through uniform heating, a compact applicator, and low input power. This paper presents metasurface based hyperthermia lens applicator with water bolus for uniform heating of cancerous tissues. The proposed applicator consists of a stacked spiral antenna and a spiral-shaped frequency selective surface as a superstrate. The spiral antenna and superstrate are optimized on a low cost FR4 substrate having a size of 32 × 32 × 3.27mm3 and 10 × 10 × 1.6mm3 (size of the unit cell), respectively. The proposed applicator is simulated with heterogeneous phantom (skin, fat, and muscle layers) and with the Gustav voxel model with and without a water bolus layer. The number of unit cells in the superstrate is optimized to direct the maximum energy toward the tumor location. The performance study of the applicator is carried out in terms of specific absorption rate, PD, and effective field size. Further, thermal analysis is carried out with 1.9 W of input power at the antenna port, and the highest 44.7 °C temperature rise is obtained. The cancerous tissue's (tumor) surrounding temperature is between 41 and 45 °C, which is adequate for efficient hyperthermia treatment. Finally, the proposed metasurface hyperthermia lens applicator is fabricated and experimentally validated in a mimicked phantom's presence. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00300-z.

Option or necessity: Role of environmental education as transformative change agent.

There is a consensus around the importance of environmental education in mitigating the ill effects of environmental problems and preserving the natural environment and promoting green behaviours. The present paper studies the role of environmental education based on transformative learning theory. It intends to present and test a model proposal using sequential mediation analysis of several constructs as the Environmental Education Support (EES) and Volunteer Attitude (VA). A quantitative study was carried out by using data obtained through online questionnaires from several Indian and Brazilian Higher Education Institutions. A multivariate statistical method was employed to analyse the data by using partial least squares structural equation modelling. The results demonstrated that environmental education positively influences students' environmental concern, willingness to be environmentally friendly, and volunteer attitude. As a novelty, it reports that environmental education beliefs, concern for the environment and willingness to be environmentally friendly sequentially mediate the relationship between environmental education support and volunteering attitude.

Social situations differ in their contribution to population-level social structure in griffon vultures.

Social relationships among animals emerge from interactions in multiple ecological and social situations. However, we seldom ask how each situation contributes to the global structure of a population, and whether different situations contribute different information about social relationships and the position of individuals within the social fabric. Griffon vultures (Gyps fulvus) interact socially in multiple situations, including communal roosting, joint flights, and co-feeding. These social interactions can influence population-level outcomes, such as disease transmission and information sharing that determine survival and response to changes. We examined the unique contribution of each social and ecological situation to the social structure of the population and individuals' positions within the overall social network using high-resolution GPS tracking. We found that the number of individuals each vulture interacted with (degree) was best predicted by diurnal interactions-both during flights and on the ground (such as when feeding). However, the strength of social bonds, that is, the number of interactions an individual had (strength), was best predicted by interactions on the ground-both during the day (e.g., while feeding) and at night (e.g., while roosting) but not by interactions while flying. Thus, social situations differ in their impact on the relationships that individuals form. By incorporating the ecological situations in which social interactions occur we gain a more complete view of how social relationships are formed and which situations are important for different types of interactions.

Multi-Object Tracking in Heterogeneous environments (MOTHe) for animal video recordings.

Aerial imagery and video recordings of animals are used for many areas of research such as animal behaviour, behavioural neuroscience and field biology. Many automated methods are being developed to extract data from such high-resolution videos. Most of the available tools are developed for videos taken under idealised laboratory conditions. Therefore, the task of animal detection and tracking for videos taken in natural settings remains challenging due to heterogeneous environments. Methods that are useful for field conditions are often difficult to implement and thus remain inaccessible to empirical researchers. To address this gap, we present an open-source package called Multi-Object Tracking in Heterogeneous environments (MOTHe), a Python-based application that uses a basic convolutional neural network for object detection. MOTHe offers a graphical interface to automate the various steps related to animal tracking such as training data generation, animal detection in complex backgrounds and visually tracking animals in the videos. Users can also generate training data and train a new model which can be used for object detection tasks for a completely new dataset. MOTHe doesn't require any sophisticated infrastructure and can be run on basic desktop computing units. We demonstrate MOTHe on six video clips in varying background conditions. These videos are from two species in their natural habitat-wasp colonies on their nests (up to 12 individuals per colony) and antelope herds in four different habitats (up to 156 individuals in a herd). Using MOTHe, we are able to detect and track individuals in all these videos. MOTHe is available as an open-source GitHub repository with a detailed user guide and demonstrations at: https://github.com/tee-lab/MOTHe-GUI.

In-vitro anti-sickling potential of baicalin and naringenin isolated from Oroxylum indicum and Citrus aurantium on human sickle red blood cells.

Sickle cell disease (SCD) is a rare inherited disorder in which red blood cells (RBCs) under oxidative stress have altered sickle shape resulting in clinical complications. In this study, a library of pure natural products were screened to see their effectiveness in preventing sickling induced in blood samples of SCA patients, ex-vivo. The results indicated that baicalin (1) and naringenin (2), reduced sickling by 46.03 and 37.48 percent, respectively, compared to positive control, 4-hydroxybenzoic acid (4-HBA), which inhibited RBC sickling by 56.87 percent. As a result of this screening, two compounds, baicalin (1) and naringenin (2), have been identified as potent sickling inhibitors. Study has clearly shown promising role of flavonoids for the management of SCD crisis for that not effective therapy is available. These phytochemicals or plant extracts can be explored further as an alternative anti-sickling remedy, owing to their high efficacy in the management of SCD crisis.

Behavioural ecology at the spatial-social interface.

Spatial and social behaviour are fundamental aspects of an animal's biology, and their social and spatial environments are indelibly linked through mutual causes and shared consequences. We define the 'spatial-social interface' as intersection of social and spatial aspects of individuals' phenotypes and environments. Behavioural variation at the spatial-social interface has implications for ecological and evolutionary processes including pathogen transmission, population dynamics, and the evolution of social systems. We link spatial and social processes through a foundation of shared theory, vocabulary, and methods. We provide examples and future directions for the integration of spatial and social behaviour and environments. We introduce key concepts and approaches that either implicitly or explicitly integrate social and spatial processes, for example, graph theory, density-dependent habitat selection, and niche specialization. Finally, we discuss how movement ecology helps link the spatial-social interface. Our review integrates social and spatial behavioural ecology and identifies testable hypotheses at the spatial-social interface.