L-cysteine, a primary building block of mycothiol, plays an essential role in the defense mechanism of Mycobacterium tuberculosis (Mtb). However, it is unclear how Mtb regulates cysteine biosynthesis as no study has reported the cysteine regulatory complex (CRC) in Mtb. Serine acetyltransferase (SAT) and cysteine synthase (CS) interact to form CRC. Although MtCS has been characterized well, minimal information is available on MtSAT, which synthesizes, O-acetylserine (OAS), the precursor of cysteine. This study fills the gap and provides experimental evidence for the presence of MtCRC and a non-canonical multi-oligomeric MtSAT. We employed multiple analytical methods to characterize the oligomeric and kinetic properties of MtSAT and MtCRC. Results show that MtSAT, lacking >75 N-terminal amino acids exists in three different assembly states; trimer, hexamer, and dodecamer, compared to the single hexameric state of SAT of other bacteria. While hexamers display the highest catalytic turnover, the trimer is the least active. The predominance of trimers at low physiologically relevant concentrations suggests that MtSAT displays the lowest catalytic potential known. Further, the catalytic potential of MtSAT is also significantly reduced in CRC state, in contrast to enhanced activity of SAT in CRC of other organisms. Our study provides insights into multi-oligomeric MtSAT with reduced catalytic potential and demonstrates that both MtSAT and MtCS of Mycobacterium interact to form CRC, although with altered catalytic properties. We discuss our results in light of the altered biochemistry of the last step of canonical sulfate-dependent cysteine biosynthesis of Mycobacterium. (c) 2024 Published by Elsevier B.V.

The Government of India has given special emphasis to develop entrepreneurship in the rural population and especially among the marginalised groups in recent times. This article attempts to understand the working of the programme in one of the Blocks of Karnal district in Haryana. This is a qualitative empirical study conducted in the Gharaunda Block of Karnal District, Haryana, in December 2021. The in-depth study is based on a collection of field data and observations documenting the success stories of rural entrepreneurs. Through this article, the authors analysed the functioning, success and challenges of the Start-up Village Entrepreneurship Programme implementation process. The study adopted triangulation data analysis method and recording oral history to document rural entrepreneurs’ stories, including the life story approach, to evaluate the programme. The study was conducted in the four villages of the Gharaunda Block. These rural entrepreneurs are from marginal sections of society, that is, the Scheduled Caste and Other Backward Caste sections. It is worth noting that all the selected entrepreneurs come from marginalised communities and happen to be women. In this article, the authors address the current gap by presenting a policy-relevant framework for conceptualising rural entrepreneurship. The study provides insights into the impact of the programme on rural entrepreneurship and offers input to address the challenges based on the fieldwork.

Background: Tobacco is a major risk factor associaetd with developing oral factor. Recent studies have shown that the age of onset, especially in Asia, is reducing. This study was to determine if tobacco exposure correlated with prognosis in oral squamous cell carcinoms (OSCC) based on age at diagnosis. Methods: Six hundred and forty three patients of OSCC treated in our institution were divided into four groups, younger patients (<= 45 years) with or without tobacco exposure and older patients (>45 years) with or without tobacco exposure, and compared with respect to prognostically relevant variables, disease-free survival (DFS) and overall survival (OS). Survival analysis was performed. Results: The percentage of those with tobacco exposure was comparable in both age groups. Tobacco correlated with known pathological determinants in OSCC; however, perineural invasion, lymphovascular invasion, and extranodal extension were significantly more common in the young. On survival analysis, tobacco exposure impacted OS (P = 0.04) and DFS (P = 0.03) in patients <= 45 years, and not in older patients >45 years. On multivariate analysis, tobacco exposure in the young was significantly associated with recurrence (P = 0.03, hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.07-2.94) but not survival. Conclusion: Younger patients with a history of tobacco use have a significantly higher risk of recurrence and mortality due to OSCC, but this difference could not be attributed to any of the known prognostic determinants in OSCC. Younger patients also had more adverse pathological features. Whether this occurs because of altered disease biology or pathways of carcinogenesis in the young with tobacco exposure is unknown. Younger tobacco users with oral cancer are more likely to have a poor prognosis.

This study introduces a nonlinear wave-wave coupling model to understand the nature of the turbulence generation at the ion scale observed in the interaction of high-intensity laser with plasma. For this nonlinear coupling of waves, the fast magnetosonic wave and the extraordinary mode laser are taken into account, along with the nonlinear ponderomotive force. The model dynamical equations have been developed for the extraordinary mode laser and the fast magnetosonic wave. Laboratory simulations have been employed to solve the obtained model equations utilizing the finite difference and pseudo-spectral methods. The simulation results show the initiation of the nonlinear progression of the laser beam at an early time and its turbulent nature at a later time. The background density perturbation, along with the cavity and hump caused by the ponderomotive force, has also been studied. The simulation results demonstrate that the propagation angle of the fast magnetosonic wave affects the magnitudes of the localization of the laser beam (pump wave) and the perturbed background density. The turbulent power spectra (ensemble-averaged) have also been studied for the different propagation angles of the fast magnetosonic wave. The turbulent spectra demonstrate that the plasma turbulence is MHD-type at small-scale lengths and ion-dominated at larger-scale lengths. This study also observed that the simulation results have some resemblance with the experimental results reported by Chatterjee et al.12 in the intense laser-plasma interaction experiment at a laboratory astrophysical scale.

RFID is a cutting-edge integrated library management system that enables the instantaneous detection and recognition of library materials. RFID applications vary from book monitoring and stock management to security in general and completely automated book classifying at the moment. Shortly, RFID systems will play an important role in data collection, recognition, and analysis required for specific library operations. An RFID-enabled automated library might be a “self-service station” that involves reducing the amount of interference from staff members. Efforts are being made to implement self-service “check-in” and “checkout” to prevent long delays in the delivery of library collection and to improve operational efficiency. Considering the significance of library security, this paper focuses on the use of Radio frequency identification (RFID) in libraries, including its elements, advantages, and the role of the librarian. The researcher collected the data of 50 users from Maharshi Dayanand University library, Rohtak, to find out the status of RFID implementation and the satisfaction level of users with the system. Most of the users are satisfied with the component and its benefits of it.

Protein tertiary structure mimetics are valuable tools to target large protein–protein interaction interfaces. Here, we demonstrate a strategy for designing dimeric helix-hairpin motifs from a previously reported three-helix-bundle miniprotein that targets the receptor-binding domain (RBD) of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Through truncation of the third helix and optimization of the interhelical loop residues of the miniprotein, we developed a thermostable dimeric helix-hairpin. The dimeric four-helix bundle competes with the human angiotensin-converting enzyme 2 (ACE2) in binding to RBD with 2:2 stoichiometry. Cryogenic-electron microscopy revealed the formation of dimeric spike ectodomain trimer by the four-helix bundle, where all the three RBDs from either spike protein are attached head-to-head in an open conformation, revealing a novel mechanism for virus neutralization. The proteomimetic protects hamsters from high dose viral challenge with replicative SARS-CoV-2 viruses, demonstrating the promise of this class of peptides that inhibit protein–protein interaction through target dimerization.

This paper aims to know the level of awareness and attitude towards COVID-19 among students and faculty members of North India Higher Educational Institutes (HEIs). This is seriously concerned as the Government of India has declared the pandemic and to control and curb the same, the lockdown has been implemented and extended according to the requirement which has entered into its fourth phase i.e. Lockdown 4.0 as daily numbers of infected people have been increased in different parts of the country. Therefore, authors feel that only awareness and a positive attitude may help to fight this epidemic situation. Further, for the purpose, to know the level of awareness and attitude, a self-structured questionnaire has distributed among Under Graduate, Post Graduate, M.Phil., Ph.D., and faculty of colleges and universities through Google. Thereby, the authors got responses from 425 respondents from different colleges and universities of North India. The findings of the study say that 96.9% of respondents are aware that an infected person can infect countless people, hence social distancing is mandated. Moreover, 97.2% of respondents agreed that COVID-19 is a deadly virus. 98.8% of respondents are obeying the government instructions which are being issued from time to time. As a considered control mechanism, 87.4% of respondents downloaded the Aarogya-Setu App on their mobile so that in anticipation, they could get the information about the infected person who is in close vicinity of the concerned.

Role of Parthenium hystereophours on population built-up of Meloidogyne incognita on brinjal was studied. The observations recorded revealed that, number of galls soil population, egg population, total root population, total nematode population and multiplication factor of nematode was significantly lower in all the treatment in comparison to treated check. The highest soil population, egg population, total root population, total nematode population, multiplication factor and number of galls was recorded (1938.5), (577.50), (183.75), (78045.25), (15.60) and (173.50) respectively in untreated check with the minimum (536.70), (93.60), (36.25), (9932.75), (1.98) and (25.75) in treated check respectively. Among the Parthenium and compost treatments the most effective treatment for the management of root knot nematode Meloidogyne incognita was Parthenium leaf compost @ 7.5% + compost. It was followed by Parthenium leaf compost @ 5% + compost, Parthenium leaf compost @ 7.5%, Parthenium leaf compost @ 5% + compost, Parthenium leaf compost @ 5%, Parthenium compost @ 5% and compost @ recommended dose in ascending order for the management of root-knot nematode, Meloidogyne incognita. highest multiplication rate 15.60 in untreated check, 11.58, 9.70, 8.86, 8.18, 7.44, 5.95 and 3.98 with the minimum (1.98) in compost @ the recommended dose, Parthenium compost @ 5%, Parthenium leaf compost @ 5%, Parthenium compost @ 5% + compost, Parthenium leaf compost @7.5%, Parthenium leaf compost @ 5% + compost, Parthenium leaf compost @ 7.5% + compost and treated check respectively.

Background: The programmed cell death-1 (PD-1) receptor and its ligands PD-L1 and PD-L2 are immune checkpoints that suppress anti-cancer immunity. Typically, cancer cells express the PD-Ls that bind PD-1 on immune cells, inhibiting their activity. Recently, PD-1 expression has also been found in cancer cells. Here, we analysed expression and functions of PD-1 in thyroid cancer (TC). Methods: PD-1 expression was evaluated by immunohistochemistry on human TC samples and by RT-PCR; western blot and FACS on TC cell lines. Proliferation and migration of TC cells in culture were assessed by BrdU incorporation and Boyden chamber assays. Biochemical studies were performed by western blot, immunoprecipitation, pull-down and phosphatase assays. TC cell tumorigenicity was assessed by xenotransplants in nude mice. Results: Human TC specimens (47%), but not normal thyroids, displayed PD-1 expression in epithelial cells, which significantly correlated with tumour stage and lymph-node metastasis. PD-1 was also constitutively expressed on TC cell lines. PD-1 overexpression/stimulation promoted TC cell proliferation and migration. Accordingly, PD-1 genetic/pharmacologic inhibition caused the opposite effects. Mechanistically, PD-1 recruited the SHP2 phosphatase to the plasma membrane and potentiated its phosphatase activity. SHP2 enhanced Ras activation by dephosphorylating its inhibitory tyrosine 32, thus triggering the MAPK cascade. SHP2, BRAF and MEK were necessary for PD-1-mediated biologic functions. PD-1 inhibition decreased, while PD-1 enforced expression facilitated, TC cell xenograft growth in mice by affecting tumour cell proliferation. Conclusions: PD-1 circuit blockade in TC, besides restoring anti-cancer immunity, could also directly impair TC cell growth by inhibiting the SHP2/Ras/MAPK signalling pathway.

Transient abnormal myelopoiesis is a transient myeloproliferative disorder seen in ∼15% to 20% of infants with Down syndrome. These infants are usually asymptomatic, requiring only monitoring, but they can have variable severity of symptoms up to multisystemic dysfunction requiring chemotherapy. GATA-1 somatic mutations acquired in utero are pathognomic of this entity and present nearly in all cases. Herein, we present a case of Down syndrome in a neonate who presented within her first week of life with life-threatening features of transient abnormal myelopoiesis requiring chemotherapy support. In addition, next-generation sequencing revealed a small mutant clone (8%) positive for a novel frameshift GATA-1 mutation.

Present study was conducted in Haryana state to see the adoption of beekeeping and constraints there in. Data was collected from six hundred people imparted training by SNIATTE, CCS HAU, Hisar during the year 2014-18. Study revealed that beekeeping is a male dominating enterprise carried out by young age people having low level of education, landless to small land holding and low income. Adoption of beekeeping as an enterprise was low, might be due to various constraints like priority to other activities, lack of land and resources, finance, marketing of honey and lack of quality equipments etc. At the same time, some factors like low initial investment, less labor intensive, less technical and good return favored the adoption of beekeeping. To support adoption of beekeeping, increase in awareness, provision of loan facilities and improvement in marketing structure of bee products are the major steps necessary to be taken by the government and other organizations.

This chapter looks at some of Dr Ambedkar's major ideas and contributions, including the Hindu social order, as he started his academic journey from critically analysing caste and its manifestation in different forms. His passion for democracy, equal rights to women, nation and nationalism, constitution-making, etc. are discussed in this chapter as well as his concern for minority rights and fraternity between majority and minority. The chapter argues that he was much ahead of his times and that is why he became so popular.

The management of the disease can be done through fungicides, bio-agents and plant extract but Integrated Disease Management (IDM) strategy has proved better as compare to other strategies. IDM practice also significantly increased the shoot and root length of linseed plant than untreated treatment (check). The maximum shoot (62.48 cm) and root (14.25 cm) length, seed yield (1370.70 kg/ha) and minimum disease severity (19.19% on leaves and 14.78% on buds) were recorded in treatment T4 treatment (ST with T. harzianum + two foliar sprays Propiconazole). The maximum cost: benefit ratio 1:5.26 was calculated in treatment T7,followed by 1:4.21 in T3 treatment.

In this study, we have analyzed the metagenomic DNA from the pooled sediment sample of the river Ganges to explore the abundance and diversity of phages, microbial community, and antibiotic resistance genes (ARGs). Utilizing data from Illumina platform, 4,174 (∼0.0013%) reads were classified for the 285 different DNA viruses largely dominated by the group of 260 distinctive phages (3,602 reads, ∼86.3%). Among all, Microcystis (782 hits), Haemophilus (403), Synechococcus (386), Pseudomonas (279), Enterococcus (232), Bacillus (196), Rhodococcus (166), Caulobacter (163), Salmonella (146), Enterobacteria (143), Mycobacterium and (128) phages show the highest abundance and account for ∼90% of the total identified phages. In addition, we have also identified corresponding host pertaining to these phages. Mainly, Proteobacteria (∼69.3%) dominates the microbial population structure. Primarily, orders such as Caulobacterales (∼28%), Burkholderiales (∼13.9%), Actinomycetales (∼13.7%), and Pseudomonadales (∼7.5%) signify the core section. Furthermore, 21,869 (∼0.00695%) reads were classified in 20 ARG types (classes) and 240 ARGs (subtypes), among which 4 ARG types, namely multidrug resistance (12,041 reads, ∼55%), bacitracin (3,202 reads, ∼15%), macrolide-lincosamide-streptogramin (1,744 reads, ∼7.98%), and fosmidomycin (990 reads, ∼4.53%), have the highest abundance. Simultaneously, six resistance mechanisms were also recognized with the dominance of antibiotic efflux (72.8%, 15,919 reads). The results unveil the distribution of (pro)-phages; microbial community; and various ARGs in the Ganges river sediments.

Medical applications of charged particle beams require a full online characterisation of the beam to ensure patient safety, treatment efficacy, and facility efficiency. In-vivo dosimetry, measurement of delivered dose during treatment, is a significant part of this characterisation. Current methods offer limited information or are invasive to the beam, meaning measurements must be done offline. This contribution presents the development of a non-invasive gas jet in-vivo dosimeter for treatment facilities. The technique is based on the interaction between a particle beam and a supersonic gas jet curtain, which was originally developed for the high luminosity upgrade of the large hadron collider (HL-LHC). To demonstrate the medical application of this technique, an existing HL-LHC test system with minor modifications will be installed at the University of Birmingham’s 35 MeV proton cyclotron, which has properties comparable to that of a treatment beam. This contribution presents the design and development of this test setup, plans for initial benchmarking measurements, and plans for a future optimised medical accelerator gas jet in-vivo dosimeter.

A quantum gas jet scanner-based beam profile monitor is under development at the Cockcroft Institute (CI), UK for beam diagnostics based on the principle of ionization detection induced in a quantum gas jet interacting with an ionizing primary beam that shall be characterized. It promises superior position resolution and high signal intensity resulting from a strongly focused quantum gas jet. In order to achieve the gas jet with a diameter of less than 100 μm, a novel focusing method exploiting the quantum wave function of the neutral gas atoms, generate an interference pattern with a single maximum acting as ultra-thin gas jet. An ‘atom sieve’ has been designed for generating the interference pattern, applying the principle of a photon sieve. It will be analogous to a mechanical wire scanner though with minimal interception. The idea of moving a quantum gas jet through the beam is proposed for transverse profiling. This contribution provides a general overview of the design, working principle, the results obtained from initial measurements carried out at CI and University of Bergen (Norway), for designing the same and possible methods for optimizing the scanner’s design.

The programmed cell death-1 (PD-1) and its ligands PD-L1 and PD-L2 are immune checkpoints. Typically, cancer cells express the PD-Ls that bind PD-1 on immune cells, inhibiting their anti-cancer activity. Recently, PD-1 expression has been found in cancer cells. We analysed expression and functions of PD-1 in thyroid cancer (TC). Human TC specimens (47%), but not normal thyroids, displayed PD-1 expression in epithelial cells, which significantly correlated with tumour stage and lymph-node metastasis. PD-1 overexpression/stimulation promoted TC cell proliferation and migration in culture. PD-1 recruited the SHP2 phosphatase, potentiated its phosphatase activity thus enhancing Ras activation by dephosphorylation of inhibitory tyrosine 32 and triggering the MAPK cascade. PD-1 inhibition decreased, while PD-1 overexpression facilitated, TC cell xenograft growth by affecting cell proliferation. PD-1 circuit blockade in TC, besides restoring anti-cancer immunity, could also directly impair TC cell growth by inhibiting the Ras/MAPK pathway. ### Competing Interest Statement The authors have declared no competing interest.