Selective refueling of CAR T cells using ADA1 and CD26 boosts antitumor immunity.

Chimeric antigen receptor (CAR) T cell therapy is hindered in solid tumor treatment due to the immunosuppressive tumor microenvironment and suboptimal T cell persistence. Current strategies do not address nutrient competition in the microenvironment. Hence, we present a metabolic refueling approach using inosine as an alternative fuel. CAR T cells were engineered to express membrane-bound CD26 and cytoplasmic adenosine deaminase 1 (ADA1), converting adenosine to inosine. Autocrine secretion of ADA1 upon CD3/CD26 stimulation activates CAR T cells, improving migration and resistance to transforming growth factor ß1 suppression. Fusion of ADA1 with anti-CD3 scFv further boosts inosine production and minimizes tumor cell feeding. In mouse models of hepatocellular carcinoma and non-small cell lung cancer, metabolically refueled CAR T cells exhibit superior tumor reduction compared to unmodified CAR T cells. Overall, our study highlights the potential of selective inosine refueling to enhance CAR T therapy efficacy against solid tumors.

Comprehensive Assessment of Artificial Intelligence Tools for Driver Monitoring and Analyzing Safety Critical Events in Vehicles.

Human factors are a primary cause of vehicle accidents. Driver monitoring systems, utilizing a range of sensors and techniques, offer an effective method to monitor and alert drivers to minimize driver error and reduce risky driving behaviors, thus helping to avoid Safety Critical Events (SCEs) and enhance overall driving safety. Artificial Intelligence (AI) tools, in particular, have been widely investigated to improve the efficiency and accuracy of driver monitoring or analysis of SCEs. To better understand the state-of-the-art practices and potential directions for AI tools in this domain, this work is an inaugural attempt to consolidate AI-related tools from academic and industry perspectives. We include an extensive review of AI models and sensors used in driver gaze analysis, driver state monitoring, and analyzing SCEs. Furthermore, researchers identified essential AI tools, both in academia and industry, utilized for camera-based driver monitoring and SCE analysis, in the market. Recommendations for future research directions are presented based on the identified tools and the discrepancies between academia and industry in previous studies. This effort provides a valuable resource for researchers and practitioners seeking a deeper understanding of leveraging AI tools to minimize driver errors, avoid SCEs, and increase driving safety.

Horizontal magnetic tweezers and its applications in single molecule micromanipulation experiments.

Magnetic tweezers (MTs) have become indispensable tools for gaining mechanistic insights into the behavior of DNA-processing enzymes and acquiring detailed, high-resolution data on the mechanical properties of DNA. Currently, MTs have two distinct designs: vertical and horizontal (or transverse) configurations. While the vertical design and its applications have been extensively documented, there is a noticeable gap in comprehensive information pertaining to the design details, experimental procedures, and types of studies conducted with horizontal MTs. This article aims to address this gap by providing a concise overview of the fundamental principles underlying transverse MTs. It will explore the multifaceted applications of this technique as an exceptional instrument for scrutinizing DNA and its interactions with DNA-binding proteins at the single-molecule level.

Video-microscopy-based automated trajectory determination.

We present a method for tracking densely clustered, high-velocity, indistinguishable objects being spawned at a high rate and moving in a directed force field using only object centroids as inputs and no other image information. The algorithm places minimal restrictions on the velocities or accelerations of the objects being tracked and uses a methodology based on a scoring function and a backtracking refinement process. This combination leads to successful tracking of hundreds of particles in challenging environments even when the displacement of the individual objects at successive times approaches the separation between neighboring objects in any one frame. We note that these cases can be particularly difficult to handle by existing methods. The performance of the algorithm is methodically examined by comparison to simulated trajectories, which vary the temporal and spatial densities, velocities, and accelerations of the objects in motion, as well as the signal/noise ratio. Also, we demonstrate its capability by analyzing data from experiments with superparamagnetic microspheres moving in an inhomogeneous magnetic field in aqueous buffer at room temperature. Our method should be widely applicable since trajectory determination problems are ubiquitous in video microscopy applications in biology, materials science, physics, and engineering.

Food waste-based bio-fertilizers production by bio-based fermenters and their potential impact on the environment.

Increasing food waste is creating a global waste (and management) crisis. Globally, ∼1.6 billion tons of food is wasted annually, worth ∼$1.2 trillion. By reducing this waste or by turning it into valuable products, numerous economic advantages can be realized, including improved food security, lower production costs, biodegradable products, environmental sustainability, and cleaner solutions to the growing world's waste and garbage management. The appropriate handling of these detrimental materials can significantly reduce the risks to human health. Food waste is available in biodegradable forms and, with the potential to speed up microbial metabolism effectively, has immense potential in improving bio-based fertilizer generation. Synthetic inorganic fertilizers severely affect human health, the environment, and soil fertility, thus requiring immediate consideration. To address these problems, agricultural farming is moving towards manufacturing bio-based fertilizers via utilizing natural bioresources. Food waste-based bio-fertilizers could help increase yields, nutrients, and organic matter and mitigate synthetic fertilizers' adverse effects. These are presented and discussed in the review.

The cellular consequences of particulate matter pollutants in plants: Safeguarding the harmonious integration of structure and function.

Particulate matter (PM) pollution is one of the pressing environmental concerns confronting human civilization in the face of the Anthropocene era. Plants are continuously exposed to an accelerating PM, threatening their growth and productivity. Although plants and plant-based infrastructures can potentially reduce ambient air pollutants, PM still affects them morphologically, anatomically, and physiologically. This review comprehensively summarizes an up-to-date review of plant-PM interaction among different functional plant groups, PM deposition and penetration through aboveground and belowground plant parts, and plants' cellular strategies. Upon exposure, PM represses lipid desaturases, eventually leading to modification of cell wall and membrane and altering cell fluidity; consequently, plants can sense the pollutants and, thus, adapt different cellular strategies. The PM also causes a reduction in the photosynthetically active radiation. The study demonstrated that plants reduce stomatal density to avoid PM uptake and increase stomatal index to compensate for decreased gaseous exchange efficiency and transpiration rates. Furthermore, genes and gene sets associated with photosynthesis, glycolysis, gluconeogenesis, and the TCA cycle were dramatically lowered by PM stress. Several transcription factors, including MYB, C2H2, C3H, G2-like, and WRKY were induced, and metabolites such as proline and soluble sugar were accumulated to increase resistance against stressors. In addition, enzymatic and non-enzymatic antioxidants were also accumulated to scavenge the PM-induced reactive oxygen species (ROS). Taken together, this review provides an insight into plants' underlying cellular mechanisms and gene regulatory networks in response to the PM to determine strategies to preserve their structural and functional blend in the face of particulate pollution. The study concludes by recommending that future research should precisely focus on plants' response to short- and long-term PM exposure.

Towards inoculant development for Bambara groundnut (Vigna subterranean (L.) Verdc) pulse crop production in Namibia.

Introduction: The globally expanding population, together with climate change, poses a risk to the availability of food for humankind. Bambara groundnut (BGN) (Vigna subterranea (L.) Verdc) is a neglected, relatively drought-tolerant native legume of Sub-Saharan Africa that has the potential to become a successful food crop because of its nutritional quality and climate-smart features. Nitrogen fixation from root nodule symbiosis with climate-adapted rhizobial symbionts can contribute nitrogen and organic material in nutrient-poor soil and improve yields. However, high soil temperature and drought often reduce the abundance of native rhizobia in such soil. Therefore, the formulation of climate-smart biofertilizers has the potential to improve the farming of BGN at a low cost in a sustainable manner. Method: The effect of seven Bradyrhizobium spp. strains native to Namibia, including B. vignae and B. subterraneum, were tested on three Namibian BGN varieties (red, brown, cream) in greenhouse pot experiments in Namibia, using soil from the target region of Kavango. Each variety was treated with a mixed inoculant consisting of seven preselected strains ("MK") as well as with one promising single inoculant strain. Results: The results revealed that in all three varieties, the two inoculants (mixed or single) outperformed the non-inoculated cultivars in terms of shoot dry weight by up to 70%; the mixed inoculant treatment performed significantly better (p < 0.05) in all cases compared to the single inoculant used. To test whether the inoculant strains were established in root nodules, they were identified by sequence analysis. In many cases, the indigenous strains of Kavango soil outcompeted the inoculant strains of the mix for nodule occupancy, depending on the BGN variety. As a further preselection, each of the individual strains of the mix was used to inoculate the three varieties under sterile conditions in a phytotron. The agronomic trait and root nodulation response of the host plant inoculations strongly differed with the BGN variety. Even competitiveness in nodule occupancy without involving any indigenous strains from soil differed and depended strictly on the variety. Discussion: Severe differences in symbiont-plant interactions appear to occur in BGN depending on the plant variety, demanding for coupling of breeding efforts with selecting efficient inoculant strains.

Treatment of infected predators under the influence of fear-induced refuge.

In this research, we delve into the dynamics of an infected predator-prey system in the presence of fear and refuge, presenting a novel inclusion of treatment for infected individuals in this type of model. Through our analytical efforts, we establish a significant reproduction number that holds a pivotal role in determining disease extinction or persistence within the system. A noteworthy threshold value for this reproduction number delineates a boundary below which the infected population cannot endure in the system. It's important to note that a range of reproduction numbers leads to both disease-free and endemic scenarios, yet the stability of these situations is contingent upon the initial population sizes. Furthermore, our investigation extends to the exploration of various types of bifurcation-namely, Backward, Saddle-node, and Hopf bifurcations. These findings unravel the intricate and diverse dynamics of the system. Of particular significance is the derivation of an optimal control policy for treatment, augmenting the practical utility of our work. The robustness of our analytical findings is fortified through meticulous verification via numerical simulations. These simulations not only bolster the credibility of our analytical results but also enhance their accessibility. Our study unveils that fear, refuge, and treatment possess individual capabilities to eradicate the disease from the system. Notably, increasing levels of fear and refuge exert a passive influence on the elimination of the infected population, whereas treatment wields an active influence-a crucial insight that bolsters the foundation of our model. Furthermore, our investigation uncovers a spectrum of system dynamics including bistability, one-period, two-period, and multi-period/chaotic behavior. These discoveries contribute to a profound enrichment of the system's dynamic landscape.

Scalable computational algorithms for geospatial COVID-19 spread using high performance computing.

A nonlinear partial differential equation (PDE) based compartmental model of COVID-19 provides a continuous trace of infection over space and time. Finer resolutions in the spatial discretization, the inclusion of additional model compartments and model stratifications based on clinically relevant categories contribute to an increase in the number of unknowns to the order of millions. We adopt a parallel scalable solver that permits faster solutions for these high fidelity models. The solver combines domain decomposition and algebraic multigrid preconditioners at multiple levels to achieve the desired strong and weak scalabilities. As a numerical illustration of this general methodology, a five-compartment susceptible-exposed-infected-recovered-deceased (SEIRD) model of COVID-19 is used to demonstrate the scalability and effectiveness of the proposed solver for a large geographical domain (Southern Ontario). It is possible to predict the infections for a period of three months for a system size of 186 million (using 3200 processes) within 12 hours saving months of computational effort needed for the conventional solvers.

Recent advances in microbial engineering approaches for wastewater treatment: a review.

In the present era of global climate change, the scarcity of potable water is increasing both due to natural and anthropogenic causes. Water is the elixir of life, and its usage has risen significantly due to escalating economic activities, widespread urbanization, and industrialization. The increasing water scarcity and rising contamination have compelled, scientists and researchers, to adopt feasible and sustainable wastewater treatment methods in meeting the growing demand for freshwater. Presently, various waste treatment technologies are adopted across the globe, such as physical, chemical, and biological treatment processes. There is a need to replace these technologies with sustainable and green technology that encourages the use of microorganisms since they have proven to be more effective in water treatment processes. The present review article is focused on demonstrating how effectively various microbes can be used in wastewater treatment to achieve environmental sustainability and economic feasibility. The microbial consortium used for water treatment offers many advantages over pure culture. There is an urgent need to develop hybrid treatment technology for the effective remediation of various organic and inorganic pollutants from wastewater.

Microbial engineering approaches for wastewater treatment.Current and emerging sources of water pollution are discussed.Various treatment technologies for wastewater treatment.Biological methods and microbes are used for degradation.Parameters responsible for the degradations processes of wastewater.

Exploring the benefits of inoculated cowpeas under different climatic conditions in Namibia.

Cowpeas (Vigna uniculata L. Walp) are grown by many smallholder farmers in sub-Saharan Africa for food and their ability to fix nitrogen even under stress. Their performance depends on the indigenous rhizobial strains that live in symbiotic association with the roots; it can be enhanced if the seeds are inoculated with more effective ones. Data of the effectiveness of the technique under a variety of climatic conditions is rare. Here, we thus use a model to upscale two field experiments conducted in Namibia to include different climate change scenarios. The simulations show that non-inoculated cowpeas have mean yields of 0.5 t/ha and inoculated cowpeas 1 t/ha. If climatic conditions are favorable (cool and wet), estimated yield differences increase to over 1 t/ha. In dry years (< 200 mm), the average yield difference is only 0.1 t/ha. In the far future (2080-2100), instances of dry and hot years will increase. Using inoculated cowpea seeds instead of non-inoculated ones thus does not benefit farmers as much then as in the near future (2030-2050). In conclusion, using cowpea seeds inoculated with an efficient rhizobial strain can significantly increase yields under varying climatic conditions, but yield advantages decrease markedly in very dry and hot years.

Interactive relations between plants, the phyllosphere microbial community, and particulate matter pollution.

Particulate matter (PM) pollution poses a significant risk to many ecosystems; as sessile organisms, plants are at particular risk from PM pollution since they cannot move away from it. Microorganisms are essential components of ecosystems that can help macro-organisms to cope with pollutants (such as PM). In the phyllosphere (the aerial/above-ground parts of plants colonized by microbial communities), plant-microbe associations have been found to promote plant development while also increasing host resilience to biotic and abiotic stressors. This review discusses how plant-microbe symbiosis in the phyllosphere potentially affects host survivability and efficiency in the face of pollution and factors such as climate change. Evidence is presented that plant-microbe associations can be beneficial, such as by degrading pollutants, yet also bring disadvantages, such as causing the loss of symbiotic organisms and/or inducing disease. It is suggested that plant genetics is a fundamental driver of the phyllosphere microbiome assembly, connecting phyllosphere microbiota to plant health management in adverse conditions. Finally, potential ways that essential community ecological processes might influence plant-microbe partnerships in the face of Anthropocene-linked changes and what this might mean for environmental management are discussed.

Regulation of ethylene metabolism in tomato under salinity stress involving linkages with important physiological signaling pathways.

The tomato is well-known for its anti-oxidative and anti-cancer properties, and with a wide range of health benefits is an important cash crop for human well-being. However, environmental stresses (especially abiotic) are having a deleterious effect on plant growth and productivity, including tomato. In this review, authors describe how salinity stress imposes risk consequences on growth and developmental processes of tomato through toxicity by ethylene (ET) and cyanide (HCN), and ionic, oxidative, and osmotic stresses. Recent research has clarified how salinity stress induced-ACS and - ß-CAS expressions stimulate the accumulation of ET and HCN, wherein the action of salicylic acid (SA),compatible solutes (CSs), polyamines (PAs) and ET inhibitors (ETIs) regulate ET and HCN metabolism. Here we emphasize how ET, SA and PA cooperates with mitochondrial alternating oxidase (AOX), salt overly sensitive (SOS) pathways and the antioxidants (ANTOX) system to better understand the salinity stress resistance mechanism. The current literature evaluated in this paper provides an overview of salinity stress resistance mechanism involving synchronized routes of ET metabolism by SA and PAs, connecting regulated network of central physiological processes governing through the action of AOX, ß-CAS, SOS and ANTOX pathways, which might be crucial for the development of tomato.

Breathing Fresh Air in the City: Implementing Avenue Trees as a Sustainable Solution to Reduce Particulate Pollution in Urban Agglomerations.

The issue of air pollution from particulate matter (PM) is getting worse as more and more people move into urban areas around the globe. Due to the complexity and diversity of pollution sources, it has long been hard to rely on source control techniques to manage this issue. Due to the fact that urban trees may provide a variety of ecosystem services, there is an urgent need to investigate alternative strategies for dramatically improving air quality. PM has always been a significant concern due to its adverse effects on humans and the entire ecosystem. The severity of this issue has risen in the current global environmental context. Numerous studies on respiratory and other human disorders have revealed a statistical relationship between human exposure to outdoor levels of particles or dust and harmful health effects. These risks are undeniably close to industrial areas where these airborne, inhalable particles are produced. The combined and individual effects of the particle and gaseous contaminants on plants' general physiology can be detrimental. According to research, plant leaves, the primary receptors of PM pollution, can function as biological filters to remove significant amounts of particles from the atmosphere of urban areas. This study showed that vegetation could provide a promising green infrastructure (GI) for better air quality through the canopy and leaf-level processes, going beyond its traditional role as a passive target and sink for air pollutants. Opportunities exist for urban GI as a natural remedy for urban pollution caused by PMs.

Micromechanical Study of Hyperacetylated Nucleosomes Using Single Molecule Transverse Magnetic Tweezers.

Nucleosomes are stable complexes of DNA and histone proteins that are essential for the proper functioning of the genome. These structures must be unwrapped and disassembled for processes such as gene expression, replication, and repair. Histone post-translational modifications (PTMs) are known to play a significant role in regulating the structural changes of nucleosomes. However, the underlying mechanisms by which these modifications function remain unclear. In this study, we report the results of single molecule micromanipulation experiments on DNA-protein complexes composed of hyperacetylated histone proteins using transverse magnetic tweezers. The experiments were conducted by pre-extending λ-DNA with a force less than 4 pN before introducing hyperacetylated histones into the sample chamber. The DNA shortened as the histones formed complexes with it and the nucleosome arrays were then exposed to increasing tension, resulting in quantized changes in the DNA's extension with step sizes of (integral multiples of) ~50 nm. We also compared results of experiments using PTM histones and native histones with data collected for both types of histones for the same force ranges (2-80 pN) and loading rates. Our data show that hyperacetylated nucleosomes require an unbinding force of around ~2.5 pN, which is similar to that required for native histones. Moreover, we identified clear differences between the step-size distributions of native and hyperacetylated histones and found that in contrast to tethers reconstituted with native histones, the majority of nucleosomes in tethers compacted with hyperacetylated histones underwent disassembly at forces significantly lower than 6 pN.

Identifying polymorphic cis-regulatory variants as risk markers for lung carcinogenesis and chemotherapy responses in tobacco smokers from eastern India.

Aberrant expression of xenobiotic metabolism and DNA repair genes is critical to lung cancer pathogenesis. This study aims to identify the cis-regulatory variants of the genes modulating lung cancer risk among tobacco smokers and altering their chemotherapy responses. From a list of 2984 SNVs, prioritization and functional annotation revealed 22 cis-eQTLs of 14 genes within the gene expression-correlated DNase I hypersensitive sites using lung tissue-specific ENCODE, GTEx, Roadmap Epigenomics, and TCGA datasets. The 22 cis-regulatory variants predictably alter the binding of 44 transcription factors (TFs) expressed in lung tissue. Interestingly, 6 reported lung cancer-associated variants were found in linkage disequilibrium (LD) with 5 prioritized cis-eQTLs from our study. A case-control study with 3 promoter cis-eQTLs (p < 0.01) on 101 lung cancer patients and 401 healthy controls from eastern India with confirmed smoking history revealed an association of rs3764821 (ALDH3B1) (OR = 2.53, 95% CI = 1.57-4.07, p = 0.00014) and rs3748523 (RAD52) (OR = 1.69, 95% CI = 1.17-2.47, p = 0.006) with lung cancer risk. The effect of different chemotherapy regimens on the overall survival of lung cancer patients to the associated variants showed that the risk alleles of both variants significantly decreased (p < 0.05) patient survival.

No association of the common Asian mitochondrial DNA haplogroups with lung cancer in East Indian population.

OBJECTIVES: Mitochondrial dysfunction has long been associated with the pathogenesis of lung cancer (LC). Mitochondrial DNA (mtDNA) haplogroups have been reported to modify the risk of LC in a few different populations; however, no study has been done among the Indians. Here, we explore the relationship between mtDNA haplogroups and LC in a representative eastern Indian sample set. METHODS: Different combinations of six mtDNA SNPs, which define the major Asian mtDNA haplogroups M and N, and their sub-haplogroups D, G, M7, R, and F were genotyped via polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) - sequencing approach in 94 smoker LC patients and 100 healthy smoker controls from an eastern Indian cohort. RESULTS: The distribution of 7 mtDNA haplogroups did not show any significant differences between patients and controls (p<0.05). We did not find sub-haplogroup M7 in our study population. CONCLUSIONS: Our study is the first to indicate that the major Asian mtDNA haplogroups have no significant (p<0.05) association with LC in East Indian population.

Unravelling the Complexity of Irregular Shiftwork, Fatigue and Sleep Health for Commercial Drivers and the Associated Implications for Roadway Safety.

Fatigue can be a significant problem for commercial motor vehicle (CMV) drivers. The lifestyle of a long-haul CMV driver may include long and irregular work hours, inconsistent sleep schedules, poor eating and exercise habits, and mental and physical stress, all contributors to fatigue. Shiftwork is associated with lacking, restricted, and poor-quality sleep and variations in circadian rhythms, all shown to negatively affect driving performance through impaired in judgment and coordination, longer reaction times, and cognitive impairment. Overweight and obesity may be as high as 90% in CMV drivers, and are associated with prevalent comorbidities, including obstructive sleep apnea, hypertension, and cardiovascular and metabolic disorders. As cognitive and motor processing declines with fatigue, driver performance decreases, and the risk of errors, near crashes, and crashes increases. Tools and assessments to determine and quantify the nature, severity, and impact of fatigue and sleep disorders across a variety of environments and populations have been developed and should be critically examined before being employed with CMV drivers. Strategies to mitigate fatigue in CMV operations include addressing the numerous personal, health, and work factors contributing to fatigue and sleepiness. Further research is needed across these areas to better understand implications for roadway safety.

Effect of seasonally forced noisy environment on aquatic prey-predator model with water level fluctuations.

In this paper, the impact of environmental noise on prey-predator interactions with seasonal fluctuations in water levels has been studied. Both intensity of noise and water level variations together play a significant role in the dynamics of an aquatic prey-predator system. Analytically, we have shown the existence of a positive solution and its uniqueness, the ultimate bound of the system's solutions, and the global attractivity of the solution. Moreover, parametric conditions for which model species either persist (strongly or weakly) in the system or go into extinction are derived and their biological significance is also discussed. The sufficient condition of stochastic permanence is also analyzed. To justify the analytical results, we have performed numerical simulations of both deterministic and stochastic systems and observed some significant dynamics in the considered system.

Recycling of silicon-rich agro-wastes by their combined application with phosphate solubilizing microbe to solubilize the native soil phosphorus in a sub-tropical Alfisol.

It is imperative to find suitable strategies to utilize the native soil phosphorus (P), as natural rock phosphate deposits are at a verge of depletion. We explored two such cost-effective and eco-friendly strategies for native soil P solubilization: silicon (Si)-rich agro-wastes (as Si source) and phosphate solubilizing microorganism (PSM). An incubation study was conducted in a sub-tropical Alfisol for 90 days at 25 °C under field capacity moisture. A factorial completely randomized design with 3 factors, namely: Si sources (three levels: sugarcane bagasse ash, rice husk ash, and corn cob ash), PSM (two levels: without PSM, and with PSM); and Si doses [three levels: no Si (Si0), 125 (Si125) and 250 (Si250) mg Si kg-1 soil] was followed. The PSM increased solution P and soluble Si level by ∼22.2 and 1.88%, respectively, over no PSM; whereas, Si125 and Si250 increased solution P by ∼60.4 and 77.1%, as well as soluble Si by ∼41.5 and 55.5%, respectively, over Si0. Also, interaction of PSM × Si doses was found significant (P<0.05). Activities of soil enzymes (dehydrogenase, acid phosphatase) and microbial biomass P also increased significantly both with PSM and Si application. Overall, PSM solubilized ∼4.18 mg kg-1 of inorganic P and mineralized ∼5.92 mg kg-1 of organic P; whereas, Si125 and Si250 solubilized ∼3.85 and 5.72 mg kg-1 of inorganic P, and mineralized ∼4.15 and 5.37 mg kg-1 of organic P, respectively. Path analysis revealed that inorganic P majorly contributed to total P solubilization; whereas, soluble and loosely bound, iron bound and aluminium bound P significantly influenced the inorganic P solubilization. Thus, utilization of such wastes as Si sources will not only complement the costly P fertilizers, but also address the waste disposal issue in a sustainable manner.