Site-specific acetylation of polynucleotide kinase 3'-phosphatase regulates its distinct role in DNA repair pathways.

Mammalian polynucleotide kinase 3'-phosphatase (PNKP), a DNA end-processing enzyme with 3'-phosphatase and 5'-kinase activities, is involved in multiple DNA repair pathways, including base excision (BER), single-strand break (SSBR), and double-strand break repair (DSBR). However, little is known as to how PNKP functions in such diverse repair processes. Here we report that PNKP is acetylated at K142 (AcK142) by p300 constitutively but at K226 (AcK226) by CBP, only after DSB induction. Co-immunoprecipitation analysis using AcK142 or AcK226 PNKP-specific antibodies showed that AcK142-PNKP associates only with BER/SSBR, and AcK226 PNKP with DSBR proteins. Despite the modest effect of acetylation on PNKP's enzymatic activity in vitro, cells expressing non-acetylable PNKP (K142R or K226R) accumulated DNA damage in transcribed genes. Intriguingly, in striatal neuronal cells of a Huntington's Disease (HD)-based mouse model, K142, but not K226, was acetylated. This is consistent with the reported degradation of CBP, but not p300, in HD cells. Moreover, transcribed genomes of HD cells progressively accumulated DSBs. Chromatin-immunoprecipitation analysis demonstrated the association of Ac-PNKP with the transcribed genes, consistent with PNKP's role in transcription-coupled repair. Thus, our findings demonstrate that acetylation at two lysine residues, located in different domains of PNKP, regulates its distinct role in BER/SSBR versus DSBR.

Human DNA polymerase η promotes RNA-templated error-free repair of DNA double-strand breaks.

A growing body of evidence indicates that RNA plays a critical role in orchestrating DNA double-strand break repair (DSBR). Recently, we showed that homologous nascent RNA can be used as a template for error-free repair of double-strand breaks (DSBs) in the transcribed genome and to restore the missing sequence at the break site via the transcription-coupled classical nonhomologous end-joining (TC-NHEJ) pathway. TC-NHEJ is a complex multistep process in which a reverse transcriptase (RT) is essential for synthesizing the DNA strand from template RNA. However, the identity of the RT involved in the TC-NHEJ pathway remained unknown. Here, we report that DNA polymerase eta (Pol η), known to possess RT activity, plays a critical role in TC-NHEJ. We found that Pol η forms a multiprotein complex with RNAP II and other TC-NHEJ factors, while also associating with nascent RNA. Moreover, purified Pol η, along with DSBR proteins PNKP, XRCC4, and Ligase IV can fully repair RNA templated 3'-phosphate-containing gapped DNA substrate. In addition, we demonstrate here that Pol η deficiency leads to accumulation of R-loops and persistent strand breaks in the transcribed genes. Finally, we determined that, in Pol η depleted but not in control cells, TC-NHEJ-mediated repair was severely abrogated when a reporter plasmid containing a DSB with several nucleotide deletion within the E. coli lacZ gene was introduced for repair in lacZ-expressing mammalian cells. Thus, our data strongly suggest that RT activity of Pol η is required in error-free DSBR.

Functional analysis of a conserved site mutation in the DNA end processing enzyme PNKP leading to ataxia with oculomotor apraxia type 4 in humans.

Polynucleotide kinase 3'-phosphatase (PNKP), an essential DNA end-processing enzyme in mammals with 3'-phosphatase and 5'-kinase activities, plays a pivotal role in multiple DNA repair pathways. Its functional deficiency has been etiologically linked to various neurological disorders. Recent reports have shown that mutation at a conserved glutamine (Gln) in PNKP leads to late-onset ataxia with oculomotor apraxia type 4 (AOA4) in humans and embryonic lethality in pigs. However, the molecular mechanism underlying such phenotypes remains elusive. Here, we report that the enzymatic activities of the mutant versus WT PNKP are comparable; however, cells expressing mutant PNKP and peripheral blood mononuclear cells (PBMCs) of AOA4 patients showed a significant amount of DNA double-strand break accumulation and consequent activation of the DNA damage response. Further investigation revealed that the nuclear localization of mutant PNKP is severely abrogated, and the mutant proteins remain primarily in the cytoplasm. Western blot analysis of AOA4 patient-derived PBMCs also revealed the presence of mutated PNKP predominantly in the cytoplasm. To understand the molecular determinants, we identified that mutation at a conserved Gln residue impedes the interaction of PNKP with importin alpha but not with importin beta, two highly conserved proteins that mediate the import of proteins from the cytoplasm into the nucleus. Collectively, our data suggest that the absence of PNKP in the nucleus leads to constant activation of the DNA damage response due to persistent accumulation of double-strand breaks in the mutant cells, triggering death of vulnerable brain cells-a potential cause of neurodegeneration in AOA4 patients.

Nei-like DNA glycosylase 2 selectively antagonizes interferon-ß expression upon respiratory syncytial virus infection.

As part of the antiviral response, cells activate the expressions of type I interferons (IFNs) and proinflammatory mediators to control viral spreading. Viral infections can impact DNA integrity; however, how DNA damage repair coordinates antiviral response remains elusive. Here we report Nei-like DNA glycosylase 2 (NEIL2), a transcription-coupled DNA repair protein, actively recognizes the oxidative DNA substrates induced by respiratory syncytial virus (RSV) infection to set the threshold of IFN-ß expression. Our results show that NEIL2 antagonizes nuclear factor κB (NF-κB) acting on the IFN-ß promoter early after infection, thus limiting gene expression amplified by type I IFNs. Mice lacking Neil2 are far more susceptible to RSV-induced illness with an exuberant expression of proinflammatory genes and tissue damage, and the administration of NEIL2 protein into the airway corrected these defects. These results suggest a safeguarding function of NEIL2 in controlling IFN-ß levels against RSV infection. Due to the short- and long-term side effects of type I IFNs applied in antiviral therapy, NEIL2 may provide an alternative not only for ensuring genome fidelity but also for controlling immune responses.

A Hybrid Power-Rate Management Strategy in Distributed Congestion Control for 5G-NR-V2X Sidelink Communications.

The accelerated growth of 5G technology has facilitated substantial progress in the realm of vehicle-to-everything (V2X) communications. Consequently, achieving optimal network performance and addressing congestion-related challenges have become paramount. This research proposes a unique hybrid power and rate control management strategy for distributed congestion control (HPR-DCC) focusing on 5G-NR-V2X sidelink communications. The primary objective of this strategy is to enhance network performance while simultaneously preventing congestion. By implementing the HPR-DCC strategy, a more fine-grained and adaptive control over the transmit power and transmission rate can be achieved. This enables efficient control by dynamically adjusting transmission parameters based on the network conditions. This study outlines the system model and methodology used to develop the HPR-DCC algorithm and investigates its characteristics of stability and convergence. Simulation results indicate that the proposed method effectively controls the maximum CBR value at 64% during high congestion scenarios, which leads to a 6% performance improvement over the conventional DCC approach. Furthermore, this approach enhances the signal reception range by 20 m, while maintaining the 90% packet reception ratio (PRR). The proposed HPR-DCC contributes to optimizing the quality and reliability of 5G-NR-V2X sidelink communication and holds great promise for advancing V2X applications in intelligent transportation systems.

Participation in Everyday Occupations Among Rohingya Refugees in Bangladeshi Refugee Camps.

IMPORTANCE: Bangladesh hosts a large number of Rohingya refugees from Myanmar. Living in refugee camps, the Rohingya refugees face challenges in everyday occupations because of violence, limited opportunities, and corporal punishment by the community. OBJECTIVE: To explore how Rohingya refugees experience participation in everyday occupations while living in temporary refugee camps in Bangladesh. DESIGN: Phenomenological study to describe, understand, and interpret the meanings of life experiences in particularly adverse conditions. SETTING: Rohingya refugee camps in Bangladesh. PARTICIPANTS: Fifteen purposively selected participants from the camps. OUTCOMES AND MEASURES: In-depth semistructured interview, as well as participant and environmental observations. Researchers used line-by-line data analysis to capture quotations and patterns using interpretive phenomenological analysis, which included establishment of initial codes, interpretation, determining selected codes, and categorization. RESULTS: The research identified four major themes-(1) mental stress, sleep disturbances, and daily occupations; (2) adjustment to inconsistent daily activities; (3) complex relationships and limited social roles that decreased occupational engagement; and (4) involvement in precarious occupations that exacerbated severe health risks-and four subthemes-(1) fragmented family relationships, (2) formation of new relationships to perform social roles, (3) inconvenient and inaccessible living conditions, and (4) continuation of unlawful work to survive. CONCLUSIONS AND RELEVANCE: Rohingya refugees should receive comprehensive health and rehabilitative care because of their perilous mental health conditions, precarious occupations, and lack of trustworthy relationships with family and neighbors. What This Article Adds: Rohingya refugees experience imbalanced, deprived, and maladapted occupations in refugee camps. Suggestions to improve their lived experience with further peer support programs may help them participate in occupation-based rehabilitation services to facilitate their social integration.

Living-in-history effect in the dating of important autobiographical memories.

The tendency of a person to frequently use public (i.e., historical) events as temporal landmarks when dating personal memories is termed the living-in-history (LiH) effect. We investigated the LiH effect in autobiographical memories of Bangladeshi older adults who lived through the 1960s Bengali nationalist movement and the 1971 Bangladesh War of Independence. 476 participants (mean age = 67.16 years; SD = 5.96 years), including 62 independence war veterans, retrieved and dated three important memories from their life and completed two scales: (a) a transitional impact-of-war scale and (b) a generational identity scale. Results showed that nearly one-third of the total memories (32%) were dated using public event references, demonstrating a LiH effect. However, this effect was twice as strong among veterans (58%) than among nonveterans (28%). The memory content analysis revealed that public event references were mostly used to date public memories (e.g., war and political struggle) and the memories with negative valence. Multivariate analyses showed that veteran identity, material changes due to war and participants' age significantly predicted the use of public event references to date one, two or three memories relative to no use of those references. The public memories that were personally significant and the extent participants experienced the material changes due to war mainly caused the LiH effect. We discuss the results considering current theories of autobiographical memory.

Medicinal Plants and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Treatment of Arthritis: A Literature Review.

Context: Arthritis is an inflammatory disease of diarthrodial joints and is associated with swollen inflamed joints, disruption of joints, and loss of integrity of articular cartilage and synovial joints. Objective: The current review intended to examine the data on the epidemiology, causes, clinical diagnosis, and prevention and control of different types of arthritis and on the use of medicinal plants in gouty arthritis. Design: The research team performed a literature review, searching relevant literature databases, including bioRxiv, medRxiv, Google Scholar, Embase, PsychINFO, and PubMed. The search terms were arthritis, diarthodial joints, use of medicinal plants in gouty arthritis, and synovial joints. Setting: The study took place in the main library of the University of Sargodha in Sargodha, Pakistan. Results: The research team identified 135 studies, and eventually 92 unique academic publications were included in the analysis. Arthritis can develop and progress in any musculoskeletal joint, and most commonly occurs in knees, hips, shoulders, and hands. Major risk factors for arthritis include age, obesity, trauma, other diseases, and smoking. Arthritis is classified into various types, including rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis, septic arthritis, and psoriatic arthritis (PsA). RA and OA are the most common types worldwide. RA is an autoimmune disease in which the body's immune cells attack the joints. OA develops due to damage of cartilage, tissues, and joints due to age, obesity, or stress on joints. Gouty arthritis develops due to hyperuricemia; deposits of monosodium urate crystals can lead to gouty arthritis. Septic arthritis occurs due to a microbial infection in synovial joints because in synovial joints the basement membrane is absent. PsA develops due to the psoriasis-skin disease. Conclusions: The current review showed that different types of arthritis has different causes and pathogeneses. Pain in joints is a major and common symptom in all types of arthritis. Arthritis is managed pharmacologically and nonpharmacologically. Treatment is different for each class of arthritis according to its cause and symptoms.

Probing the self-defining period in memories of the Bangladesh independence war generation.

This study investigated the self-defining periods (SPs) in private and public memories of Bangladeshi older adults (N = 476; mean age = 67.16 years) who, during adolescence and early adulthood, witnessed the 1960s Bengali nationalist movement and the 1971 Bangladesh War of Independence. Each participant retrieved three private and three public memories they considered to be highly significant. The lifespan distributions for private and public memories were identical; in both cases, participants recalled more than half of their memories from 10 to 29 years of age. The calendar-year distributions revealed that nearly one-fourth of private and one-third of public memories were recalled from the year of the War of Independence. The memory content analysis showed that participants sampled more negative than positive memories: 55% versus 45% for private memory and 66% versus 34% for public memory. The enhanced recollection of private and public memories from 10 to 29 years of age was predominantly shaped by memories of the independence struggle-a period that was self-defining for the entire Bangladeshi society.

The Potentially Recommended Pharmacotherapy for COVID-19.

CONTEXT: A completely unique coronavirus (2019-nCoV), formally referred to as severe acute respiratory syndrome (SARS-CoV-2), appeared in China. SARS-CoV-2 is an etiological mediator of coronavirus 2 (COVID-19), characterized by pneumonic contagion in human beings. In spite of forceful suppression, this virus has spread worldwide. No specific drugs have been approved by the FDA for treating COVID-19 patients. OBJECTIVE: The study intended to examine the data from studies on clinical management of COVID-19. DESIGN: The research team performed a literature review, searching relevant literature databases. The sources of data included bioRxiv, medRxiv, Google Scholar, Embase, PsychINFO, WanFang Data, and PubMed. The search terms were treatment of the novel coronavirus, management of nCoV-19, chloroquine, and hydroxychloroquine. SETTING: The study took place in the main library of the University of Sargodha in Sargodha, Pakistan. RESULTS: The study identified 42 unique studies that had reported and confirmed over 1500 cases of nCoV-19 by April 21, 2020. The studies found that clinical management, for patients who presented with symptoms, included supportive care and control measures that comprised mechanical ventilator support and supplementary oxygen. CONCLUSIONS: There have been intensive attempts to explore drug therapy for the prophylaxis and treatment of SARS-CoV-2 infection during this COVID-19 pandemic. Several drugs have been identified which including remdesivir, two antimalarials (chloroquine and hydroxychloroquine) and immunosuppressive agents. The effects of most drug interventions are currently highly uncertain and several drugs and vaccines are under trail for the effective treatment of COVID-19 virus, until an effective treatment will discover social distancing and physical hygiene should be practiced strictly.

Biochemical Dynamics and Clinical Features of Novel Corona Virus (2019-nCoV).

CONTEXT: The novel Corona Virus (nCoV-19) was initially reported in Wuhan, China during December 2019, and later people with nCoV-19 were identified in different parts of the world. Infected people had shown symptoms resembling pneumonia, but about 50% of patients were asymptomatic. OBJECTIVE: The study intended to examine the data from studies on nCoV-19. DESIGN: The research team performed a literature review, searching relevant literature databases. The sources of data included bioRxiv, medRxiv, Google Scholar, Embase, PsychINFO, WanFang Data and PubMed. The search terms were novel Corona Virus, and nCoV-19 structure. SETTING: The study took place in the main library of the University of Sargodha, Sargodha, Pakistan. RESULTS: The study identified 22 studies that had reported and confirmed over 2000 cases of nCoV-19 by January 26, 2020. The studies found that the virus was transmitted through respiratory droplets. The virus has two serotypes, OC43 and 229E. CONCLUSIONS: No specific curative therapy is available for CoVid-19. However, certain precautionary measures may potentially reduce the transmission, including washing hands, using sanitizers frequently, avoiding public gatherings, and quarantining or isolating patients. This virus has spread globally and immunocompromised individuals, and especially older individuals, are at significant risk. Community and healthcare professionals have a positive role to play in controlling the spread of the disease.

Mitochondrial dysfunction contributes to the cytotoxicity of some 3,5-bis(benzylidene)-4-piperidone derivatives in colon HCT-116 cells.

The objectives of this study are to investigate the possible ways by which the curcumin analogs 2a and 2b exert their antiproliferative properties. The analogs 2a and 2b have submicromolar IC(50) values towards human HCT-116 colon cancer cells but are far less toxic to human non-malignant CRL-1790 colon cells. Both compounds affected a number of mitochondrial functions in HCT-116 cells namely increasing the intracellular concentrations of reactive oxygen species, inhibiting oxygen consumption and decreasing the mitochondrial membrane potential. These molecules also produced swelling of isolated rat liver mitochondria, supporting a mitochondrial mechanism of cytotoxicity. Both compounds reacted with glutathione in the presence of glutathione S-transferase π and hence they may be classified as thiol alkylators.

Modifiable and nonmodifiable factors associated with anxiety, depression, and stress after one year of the COVID-19 pandemic.

BACKGROUND: People worldwide have experienced various mental health issues during the COVID-19 pandemic. This study investigates the modifiable and nonmodifiable predictors of anxiety, depression, and stress among Bangladeshi participants after one year of the pandemic. METHOD: A large group of adult participants (N = 1897), recruited from eight administrative divisions in Bangladesh, completed an online survey in May and June 2021 when the Movement Control Order was in place. We used the Beck Anxiety Inventory, Patient Health Questionnaire-9, and Perceived Stress Scale-4 to assess the participants' anxiety, depression, and stress. We also gave the Mindful Attention Awareness Scale and Life-Orientation Test-Revised to assess mindfulness and optimism. RESULTS: The results revealed that the prevalence rates for anxiety and depression were 62.5% and 45.3%, respectively. Multivariate analyses showed that several nonmodifiable factors, such as those who were students, unmarried and females, and those living in the Northern region (Rajshahi and Mymensingh division) and dwelling in the rural areas, suffered from worse mental health (accounted for 5%-23% of the variances in the mental health outcome scores). Modifiable factors accounted for an additional 10%-25% of the variances in the same outcome variables. Adults with higher mindfulness and optimism, living in the country's Southern region (Chattogram division) and those who took both vaccine doses and had no history of mental illness reported better mental health. CONCLUSION: Anxiety, depression, and stress remained high in Bangladeshi adults after one year of the pandemic. The community-based interventions should aim to increase the mindfulness and optimism levels among the sufferers. More accelerated vaccination programs across the country could protect people from suffering from overall mental distress.

The Role of Pro-Inflammatory Mediator Interleukin-32 in Osteoclast Differentiation.

The recently explained cytokine, which is produced after the stimulation of interferon (IFN)-c, interleukin (IL)-2, and IL-18 is IL-32, has pro-inflammatory IFN-c, IL-2 and IL-18 are IL-32 mediator's properties that are generally entailed in many diseases, including infections, cancer, and chronic inflammation. After the initial statement in 2005, it promoted the osteoclast precursor's differentiation into TRAcP plus VNR plus multinucleated cells that express explicit osteoclast indicators. Furthermore, the loss of bone resorption might be accredited because of the collapse of the multinucleated cells, which are produced of the reaction to IL-32 to direct factoring that is ultimately essential for attaching the cells for bone resorption. Thus, in conclusion, IL-32, the pro-inflammatory mediator, has an important and indirect role in regulating osteoclast differentiation. In bone disorder's pathophysiology, critical role of IL-32 needs more scientific evidence to develop a rational treatment protocol. IL-32 can become a potent mediator of active osteoclast generation in the presence of receptor activator of NF-κB ligand (RANKL). This novel cytokine can introduce more favorable conditions for osteoclastogenesis in the rheumatic arthritis by increasing the RANKL and osteoprotegerin ratio in fibroblast-like synoviocytes.

Site-specific acetylation of polynucleotide kinase 3'-phosphatase (PNKP) regulates its distinct role in DNA repair pathways.

Mammalian polynucleotide kinase 3'-phosphatase (PNKP) is a dual-function DNA end-processing enzyme with 3'-phosphatase and 5'-kinase activities, which generate 3'-OH and 5'-phosphate termini respectively, as substrates for DNA polymerase and DNA ligase to complete DNA repair. PNKP is thus involved in multiple DNA repair pathways, including base excision (BER), single-strand break (SSBR), and double-strand break repair (DSBR). However, little is known as to how PNKP functions in such diverse repair processes, which involve distinct sets of proteins. In this study, we report that PNKP is acetylated at two lysine (K142 and K226) residues. While K142 (AcK142) is constitutively acetylated by p300, CBP acetylates K226 (AcK226) only after DSB induction. Co-immunoprecipitation analysis using antibodies specific for PNKP peptides containing AcK142 or AcK226 of PNKP showed that AcK142-PNKP associates only with BER/SSBR, and AcK226 PNKP only with DSBR proteins. Although acetylation at these residues did not significantly affect the enzymatic activity of PNKP in vitro, cells expressing nonacetylable PNKP (K142R or K226R) accumulated DNA damage, specifically in transcribed genes. Intriguingly, in striatal neuronal cells of a Huntington's Disease (HD)-based mouse model, K142, but not K226, was acetylated. This observation is consistent with the reported degradation of CBP but not p300 in HD cells. Moreover, genomes of HD cells progressively accumulated DSBs specifically in the transcribed genes. Chromatin-immunoprecipitation analysis using anti-AcK142 or anti-AcK226 antibodies demonstrated an association of Ac-PNKP with the transcribed genes, consistent with PNKP's role in transcription-coupled repair. Thus, our findings collectively demonstrate that acetylation at two lysine residues located in different domains of PNKP regulates its functionally distinct role in BER/SSBR vs. DSBR.

The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection.

SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant NEIL2 in A549-ACE2 cells shows decreased expression of proinflammatory genes and viral E-gene, as well as lowers the yield of viral progeny compared to mock-treated cells. Mechanistically, NEIL2 cooperatively binds to the 5'-UTR of SARS-CoV-2 genomic RNA to block viral protein synthesis. Collectively, these data strongly suggest that the maintenance of basal NEIL2 levels is critical for the protective response of hosts to viral infection and disease.

Is there a gradient in the association between internet addiction and health?

BACKGROUND: Internet Addiction (IA) is often shown to be associated with health issues, but no study explicitly examined a possible gradient in the association between different levels of IA and health. This study aimed to examine if the levels of IA had a graded relationship with poor sleep quality, psychological distress, and self-rated health among university students in Bangladesh. METHODS: In this cross-sectional study, a sample of 625 students from six universities/colleges responded to an online survey that contained measures of internet addiction test (IAT), general health questionnaire (GHQ-12), sleep quality, and self-rated health. Modified Poisson regression models were fitted to estimate the adjusted risk ratios (RR) and confidence intervals (CI) of the associations between IA and health outcomes. RESULTS: The IA levels were associated with each of the three health outcomes in a linear fashion. Compared to the lowest IA quintile, the highest quintile remained associated with an increased risk of poor-quality sleeping (RR: 1.77; 95% CI: 1.26, 2.48), psychological distress (RR: 2.09; 95% CI: 1.55, 2.82), and worse self-rated health (RR: 1.46; 95% CI: 1.09, 1.96) after adjusting for socio-demographic covariates. There were also dose-response associations between IAT z-scores and health outcomes. The association between IAT z-scores and psychological distress was significantly stronger in males compared to females (p-value for interaction<0.05). CONCLUSIONS: The study found strong gradients between levels of addiction to internet and health outcomes, suggesting that increased health risks may exist even at lower levels of internet addiction. The findings highlight the need for departure of current research from a focus on the classic dichotomy of problematic versus not problematic internet use and a move toward recognizing the potential hierarchical effects of IA on health.

The DNA glycosylase NEIL2 plays a vital role in combating SARS-CoV-2 infection.

Compromised DNA repair capacity of individuals could play a critical role in the severity of SARS-CoV-2 infection-induced COVID-19. We therefore analyzed the expression of DNA repair genes in publicly available transcriptomic datasets of COVID-19 patients and found that the level of NEIL2, an oxidized base specific mammalian DNA glycosylase, is particularly low in the lungs of COVID-19 patients displaying severe symptoms. Downregulation of pulmonary NEIL2 in CoV-2-permissive animals and postmortem COVID-19 patients validated these results. To investigate the potential roles of NEIL2 in CoV-2 pathogenesis, we infected Neil2-null (Neil2-/-) mice with a mouse-adapted CoV-2 strain and found that Neil2-/- mice suffered more severe viral infection concomitant with increased expression of proinflammatory genes, which resulted in an enhanced mortality rate of 80%, up from 20% for the age matched Neil2+/+ cohorts. We also found that infected animals accumulated a significant amount of damage in their lung DNA. Surprisingly, recombinant NEIL2 delivered into permissive A549-ACE2 cells significantly decreased viral replication. Toward better understanding the mechanistic basis of how NEIL2 plays such a protective role against CoV-2 infection, we determined that NEIL2 specifically binds to the 5'-UTR of SARS-CoV-2 genomic RNA and blocks protein synthesis. Together, our data suggest that NEIL2 plays a previously unidentified role in regulating CoV-2-induced pathogenesis, via inhibiting viral replication and preventing exacerbated proinflammatory responses, and also via its well-established role of repairing host genome damage.

Construction and Validation of a Generational Identity Scale on Bangladeshi Older Adults.

There is a lack of a psychometric tool for generational identity. We have conducted two studies involving Bangladeshi older adults who have witnessed the Bangladesh liberation war in 1971 to develop a new generational identity scale (GIS). The first study (N = 300) prepared an initial pool of 31 items and got them vetted by expert judges, which retained 21 items to form the provisional GIS (GIS-21). An exploratory factor analysis on GIS-21 excluded eight items and offered a two-factor solution: (i) identification with the generation and (ii) awareness of the generational importance. The second study (N = 176) ran a confirmatory factor analysis on the resulting GIS-13 and dropped another item to achieve a better model fit (SRMR =0.058, GFI = 0.986, AGFI = 0.980, and NFI = 0.980). The remaining 12-item GIS (GIS-12) showed excellent reliability (Mc Donald's omega = 0.898) and satisfactory temporal stability (ICC = 0.59, 95% CI = 0.27-0.77) over a 4-week interval. The scale's moderate correlation with another measure for generational identification demonstrates its convergent validity. Participants' transitional experience caused by the Bangladesh independence war in 1971 was also moderately correlated with the GIS-12 supporting further theoretical convergence of this scale. We recommend that researchers could use this scale on different populations and age groups upon appropriate validation.

Plant Cell Wall Hydration and Plant Physiology: An Exploration of the Consequences of Direct Effects of Water Deficit on the Plant Cell Wall.

The extensibility of synthetic polymers is routinely modulated by the addition of lower molecular weight spacing molecules known as plasticizers, and there is some evidence that water may have similar effects on plant cell walls. Furthermore, it appears that changes in wall hydration could affect wall behavior to a degree that seems likely to have physiological consequences at water potentials that many plants would experience under field conditions. Osmotica large enough to be excluded from plant cell walls and bacterial cellulose composites with other cell wall polysaccharides were used to alter their water content and to demonstrate that the relationship between water potential and degree of hydration of these materials is affected by their composition. Additionally, it was found that expansins facilitate rehydration of bacterial cellulose and cellulose composites and cause swelling of plant cell wall fragments in suspension and that these responses are also affected by polysaccharide composition. Given these observations, it seems probable that plant environmental responses include measures to regulate cell wall water content or mitigate the consequences of changes in wall hydration and that it may be possible to exploit such mechanisms to improve crop resilience.