NMR studies on truncated sequences of human telomeric DNA: observation of a novel A-tetrad

The structure of the telomeric DNA has been a subject of extensive investigation in recent years due to the realization that it has important functional roles to play in vivo and the observations that truncated telomeric sequences exhibit a great variety of 3D structures in aqueous solutions. In this context, we describe here NMR structural studies on two truncated human telomeric DNA sequences, d-AG3T and d-TAG3T in solutions containing K+ ions. The G3 stretches in both the oligonucleotides were seen to form parallel-stranded quadruplexes. However, the AG3 segment as a whole, had different structural characteristics. The structure of d-AG3T revealed the formation of a novel A-tetrad, which was not seen in d-TAG3T. The A's in the tetrad had syn glycosidic conformation as opposed to the anti conformation of the G's in the G-tetrads. The A-tetrad stacked well over the adjacent G-tetrad and the twist angle at this step was smaller in d-AG3T than in d-TAG3T. These observations are expected to be significant from the point of view of structural diversity and recognition in telomeres

Multipolymer microsphere delivery of SARS-CoV-2 antigens

Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective responses against viral exposures. To improve severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen delivery, a controlled biodegradable, stable, biocompatible, and nontoxic polymeric microsphere system was developed for chemically inactivated viral proteins. SARS-CoV-2 proteins encapsulated in polymeric microspheres induced robust antiviral immunity. The viral antigen-loaded microsphere system can preclude the need for repeat administrations, highlighting its potential as an effective vaccine. Statement of significance Successful SARS-CoV-2 vaccines were developed and quickly approved by the US Food and Drug Administration (FDA). However, each of the vaccines requires boosting as new variants arise. We posit that injectable biodegradable polymers represent a means for the sustained release of emerging viral antigens. The approach offers a means to reduce immunization frequency by predicting viral genomic variability. This strategy could lead to longer-lasting antiviral protective immunity. The current proof-of-concept multipolymer study for SARS-CoV-2 achieve these metrics. [PDF also includes a graphical abstract that can not be displayed here.

Multipolymer microsphere delivery of SARS-CoV-2 antigens

Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective re- sponses against viral exposures. To improve severe acute respiratory syndrome coronavirus-2 (SARS-CoV- 2) antigen delivery, a controlled biodegradable, stable, biocompatible, and nontoxic polymeric micro- sphere system was developed for chemically inactivated viral proteins. SARS-CoV-2 proteins encapsulated in polymeric microspheres induced robust antiviral immunity. The viral antigen-loaded microsphere sys- tem can preclude the need for repeat administrations, highlighting its potential as an effective vaccine

Post-traumatic stress disorder in children and adolescents one year after a super-cyclone in Orissa, India: exploring cross-cultural validity and vulnerability factors

BACKGROUND: It has been asserted that psychological responses to disasters in children and adolescents vary widely across cultures, but this has rarely been investigated. The objectives of the study were to clinically evaluate the construct of traumatic stress symptoms and disorder in children and adolescents after a super-cyclone in Orissa, India; to find out the prevalence at one year; compare the effect in high and low exposure areas and study the factors associated with it. METHODS: Clinical examination of children and adolescents (n = 447) was done, supplemented by a symptoms checklist based on International Classification of Mental and Behavioural Disorders, Diagnostic Criteria for Research and a semi-structured questionnaire for disaster related experiences. RESULTS: A majority of children had post-traumatic symptoms. Post-traumatic stress disorder (PTSD) was present in 30.6% (95% confidence interval: 26.4 to 34.9), and an additional 13.6% had sub-syndromal PTSD. Parents or teachers reported mental health concerns in 7.2% subjects, who were a minor proportion (12.8%) of subjects with any syndromal diagnosis (n = 196). Significantly more (43.7%) children in high exposure areas had PTSD than that (11.2%) in low exposure areas (p < 0.001). Depression was significantly associated with PTSD. Binary logistic regression analysis indicated that high exposure, lower educational level and middle socioeconomic status significantly predicted the outcome of PTSD. Extreme fear and perceived threat to life during the disaster, death in family, damage to home, or staying in shelters were not significantly associated with PTSD. CONCLUSION: Following natural disaster PTSD is a valid clinical construct in children and adolescents in Indian set up; and though highly prevalent it may be missed without clinical screening. Its manifestation and associated factors resembled those in other cultures

Human resource management in the age of generative artificial intelligence::Perspectives and research directions on ChatGPT

ChatGPT and its variants that use generative artificial intelligence (AI) models have rapidly become a focal point in academic and media discussions about their potential benefits and drawbacks across various sectors of the economy, democracy, society, and environment. It remains unclear whether these technologies result in job displacement or creation, or if they merely shift human labour by generating new, potentially trivial or practically irrelevant, information and decisions. According to the CEO of ChatGPT, the potential impact of this new family of AI technology could be as big as “the printing press”, with significant implications for employment, stakeholder relationships, business models, and academic research, and its full consequences are largely undiscovered and uncertain. The introduction of more advanced and potent generative AI tools in the AI market, following the launch of ChatGPT, has ramped up the “AI arms race”, creating continuing uncertainty for workers, expanding their business applications, while heightening risks related to well‐being, bias, misinformation, context insensitivity, privacy issues, ethical dilemmas, and security. Given these developments, this perspectives editorial offers a collection of perspectives and research pathways to extend HRM scholarship in the realm of generative AI. In doing so, the discussion synthesizes the literature on AI and generative AI, connecting it to various aspects of HRM processes, practices, relationships, and outcomes, thereby contributing to shaping the future of HRM research

Study of seminal fluid parameters and fertility of male sickle-cell disease patients and potential impact of hydroxyurea treatment

Context: Male sickle-cell disease (SCD) patients often have moderate to severe hypogonadism resulting in abnormal seminal fluid parameters. Hydroxyurea (HU) used in SCD patients has been found to further aggravate the testicular dysfunction. Aims: To study the seminal fluid parameters and fertility of male SCD patients and to evaluate the potential impact of HU treatment on the above factors. Settings and Design: This was a prospective study of 100 male SCD patients of age group 18 to 45 years. Materials and Methods: Seminal fluid analysis was done before starting low dose of HU (10 mg/kg/day) and every 3 months after initiation of HU. Patients with abnormal seminal parameters before HU therapy were not given HU therapy. In SCD patients with HU therapy, who developed abnormal seminal fluid parameters, HU was stopped for 3 months and seminal fluid parameters were re-evaluated. Results: Among SCD patients without HU therapy, nine (18%) patients developed oligospermia and two (4%) developed azoospermia. Among SCD patients with HU therapy, 10 (20%) patients developed oligospermia and five (10%) developed azoospermia. Seminal fluid parameters reverted to normal after stoppage of HU for 3 months in 73% of patients. Conclusions: Alteration of sperm parameters is seen in a significant number of SCD patients. Also, alterations of seminal fluid parameters are exacerbated by HU treatment even with low dose

Distinctive features in the structure and dynamics of the DNA repeat sequence GGCGGG

G-rich DNA has been known to form a variety of folded and multistranded structures, with even single base modifications causing important structural changes. But, very little is known about the dynamic characteristics of the structures, which may play crucial roles in facilitating the structural transitions. In this background, we report here NMR investigations on the structure and dynamics of a DNA repeat sequence GGCGGG in aqueous solution containing Na+ ions at neutral pH. The chosen sequence d-TGGCGGGT forms a parallel quadruplex with a C-tetrad in the middle, formed by symmetrical pairing of four Cs in a plane via NH2-O2 H-bonds. 13C relaxation measurements at natural abundance for C1' sugar carbons provided valuable insight into the sequence specific dynamism of G and C-tetrads in the quadruplex. The C4 tetrad seems to introduce high conformational dynamism at milli- to micro-second time scale in the quadruplex. Concomitantly, there is a decrease in the pico-second time scale dynamics. Interestingly, these effects are seen more prominently at the G-tetrads on the 3' end of C-tetrad than on its 5' end. These observations would have important implications for the roles the tetrads may play in many biological functions

Comparative study of clinical presentation and hematological indices in hospitalized sickle cell patients with severe Plasmodium falciparum malaria

Background: Sickle-cell-gene has a high frequency in malaria endemic regions. In India, though the prevalence of both sickle-cell-gene and malaria are high, no study has been carried out. This study aims to find out the possible differences in hematological and clinical parameters in severe falciparum malaria with respect to sickle cell genotypes. Methods: Five hundred fourteen adults with severe falciparum malaria hospitalized in Department of Medicine, Veer Surendra Sai Institute of Medical Sciences and Research, Burla, between August, 2010 to December, 2014 were included and categorized on the basis of sickle cell genotypes. The hematological parameters were compared by one-way-analysis-of-variance and incidence of sub-phenotypes of severe malaria was compared by χ2 test across the groups. Results: Patients with sickle cell anemia (HbSS) and severe falciparum malaria had lower hemoglobin level compared to patients with normal β-globin genotype (HbAA) and sickle cell trait (HbAS). Most of the hematological parameters were homogeneous in patients with HbAA and HbAS and different from patients with HbSS. Incidence of acute renal failure was low (χ2, 9.91; p, 0.002) and jaundice was high (χ2, 5.20; p, 0.022) in patients with HbSS. No clinical difference was observed in patients with HbAA and HbAS. The mortality was low (χ2, 4.33; p, 0.037) and high (χ2, 10.48; p, 0.001) in patients with HbAS and HbSS respectively compared to patients with HbAA. Conclusion: Though sickle-cell-gene protects against falciparum infections, the hematological parameters and sub-phenotypes of severe malaria remain unchanged when the infection progresses to a severe form in patients with HbAA and HbAS. Presence of hemolytic anemia in patients with HbSS shows diverse hematological and clinical phenotypes as compared to others. High mortality in patients with HbSS emphasizes the need for a better preventive approach to save valuable lives. Keywords: Plasmodium falciparum, Severe malaria, Sickle cell gene, Anemia, Mortalit