Genome-wide association studies and transcriptomics reveal mechanisms explaining the diversity of wheat root responses to nutrient availability.

Nutrient availability profoundly influences plant root system architecture, which critically determines crop productivity. While Arabidopsis has provided important insights into the genetic responses to nutrient deficiency, translating this knowledge to crops, particularly wheat, remains a subject of inquiry. Here, examining a diverse wheat population under varying nitrogen (N), phosphorus (P), potassium (K), and iron (Fe) levels, we uncover a spectrum of root responses, spanning from growth inhibition to stimulation, highlighting genotype-specific strategies. Furthermore, we reveal a nuanced interplay between macronutrient deficiency (N, P, and K) and Fe availability, emphasizing the central role of Fe in modulating root architecture. Through genome-wide association mapping, we identify 11 quantitative trait loci underlying root traits under varying nutrient availabilities, including homologous genes previously validated in Arabidopsis, supporting our findings. In addition, utilizing transcriptomics, ROS imaging, and antioxidant treatment, we uncover that wheat root growth inhibition by nutrient deficiency is attributed to ROS accumulation, akin to the role of ROS in governing Arabidopsis root responses to nutrient deficiency. Therefore, our study reveals the conservation of molecular and physiological mechanisms between Arabidopsis and wheat to adjust root growth to nutrient availability, paving the way for targeted crop improvement strategies aimed at increasing nutrient use efficiency.

Long COVID in Pakistan: a cross-sectional analysis of health and psychosocial outcomes.

According to the World Health Organization-led Delphi consensus, long COVID corresponds to the occurrence of symptoms beyond twelve weeks after the onset of acute COVID-19 illness that cannot be explained by alternate diagnosis. This cross-sectional study aimed to analyse the impacts of long COVID on general health and psychosocial well-being. For this study, the participants were interviewed either face to face or via telephone, and their responses were recorded on a questionnaire capturing information on demographics, COVID-19 status, duration of symptoms and long COVID symptoms. The psychosocial impacts of the pandemic were assessed using scales like Short Mood and feeling questionnaire (sMFQ), Warwick-Edinburgh Mental Well-being Scale (WEMWBS), Generalized Anxiety Disorder Assessment (GAD-7) and Perceived Stress Scale (PSS). Regression analysis was conducted to analyse the predictors of long COVID. A total of 300 participants were interviewed, of which 155 (52%) had COVID-19 illness. Of these 54 (35%) had persistent symptoms for a period of more than 12 weeks classified as long COVID. Muscle problems and fatigue were the most frequent (14.7%) symptoms encountered, followed by breathing problems (12.6%) and cognitive issues (12.6%). The symptoms of decrease in appetite and confusion or disorientation during the initial phase of the infection were associated with long COVID. The majority of the participants (83.3%) had moderate level of perceived stress, while moderate to severe levels of stress were observed in 17.3% of the individuals. Moreover, a high level of positive mental well-being was also observed. This study highlights the need for further research into the clinical aspects and implications of long COVID in Pakistan and emphasizes the importance of ongoing support for affected individuals.

Mutation screening of multiple Pakistani MCPH families revealed novel and recurrent protein-truncating mutations of ASPM.

Autosomal primary microcephaly (MCPH) is a heterogenetic disorder that affects brain's cerebral cortex size and leads to a reduction in the cranial vault. Along with the hallmark feature of reduced head circumference, microcephalic patients also exhibit a variable degree of intellectual disability as well. Genetic studies have reported 28 MCPH genes, most of which produce microtubule-associated proteins and are involved in cell division. Herein this study, 14 patients from seven Pashtun origin Pakistani families of primary microcephaly were analyzed. Mutation analysis was performed through targeted Sanger DNA sequencing on the basis of phenotype-linked genetic makeup. Genetic analysis in one family found a novel pathogenic DNA change in the abnormal spindle microtubule assembly (ASPM) gene (NM_018136.4:c.3871dupGA), while the rest of the families revealed recurrent nonsense mutation c.3978G>A (p.Trp1326*) in the same gene. The novel reported frameshift insertion presumably truncates the protein p.(Lys1291Glyfs*14) and deletes the N-terminus domains. Identification of novel ASPM-truncating mutation expands the mutational spectrum of the ASPM gene, while mapping of recurrent mutation c.3978G>A (p.Trp1326*) will aid in establishing its founder effect in the Khyber Pakhtunkhwa (KPK) inhabitant population of Pakistan and should be suggestively screened for premarital counseling of MCPH susceptible families. Most of the recruited families are related to first-degree consanguinity. Hence, all the family elders were counseled to avoid intrafamilial marriages.

Indirect calculation of LDL using thirteen equations in Pakistani population.

BACKGROUND: Owing to the atherogenic properties, low density lipoprotein cholesterol (LDL-C) is the primary target for treatment and diagnosis of cardiovascular diseases (CVDs), hence accurate measurement of LDL-C is critical. Despite the availability of direct measurement assays for LDL-C, it is routinely calculated by Friedewald equation in clinical settings in Pakistan mostly due to financial constraints. However, the validity of this equation is impacted by several factors, therefore several other equations have been developed for the calculation of LDL-C. MATERIALS AND METHODS: LDL-C of 39,385 individuals measured directly by homogenous assays (dLDL) was compared with LDL-C calculated by thirteen equations (cLDL-C). Stratifications based on different lipids i.e., triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL) were made to check the validity of these equations across all ranges of lipid profile. The correlation and median difference between dLDL and cLDL-C was statistically analyzed. RESULTS: Overall Teerakanchana equation displayed a strong positive correlation (ρ = 0.967) and least median difference (-8.81) with dLDL, followed by Martin equation (ρ = 0.967). For higher TG ranges (>500 mg/dL), Teerakanchana equation had the least median difference (1.31) and a strong correlation (ρ = 0.800). CONCLUSION: Our data suggest that Teerakanchana equation may be employed as an alternative to Friedewald equation for Pakistani population.

Immune-related therapeutics: an update on antiviral drugs and vaccines to tackle the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic rapidly spread globally. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is a positive-sense single-stranded RNA virus with a reported fatality rate ranging from 1% to 7%, and people with immune-compromised conditions, children, and older adults are particularly vulnerable. Respiratory failure and cytokine storm-induced multiple organ failure are the major causes of death. This article highlights the innate and adaptive immune mechanisms of host cells activated in response to SARS-CoV-2 infection and possible therapeutic approaches against COVID-19. Some potential drugs proven to be effective for other viral diseases are under clinical trials now for use against COVID-19. Examples include inhibitors of RNA-dependent RNA polymerase (remdesivir, favipiravir, ribavirin), viral protein synthesis (ivermectin, lopinavir/ ritonavir), and fusion of the viral membrane with host cells (chloroquine, hydroxychloroquine, nitazoxanide, and umifenovir). This article also presents the intellectual groundwork for the ongoing development of vaccines in preclinical and clinical trials, explaining potential candidates (live attenuated-whole virus vaccines, inactivated vaccines, subunit vaccines, DNAbased vaccines, protein-based vaccines, nanoparticle-based vaccines, virus-like particles and mRNA-based vaccines). Designing and developing an effective vaccine (both prophylactic and therapeutic) would be a long-term solution and the most effective way to eliminate the COVID-19 pandemic.

Adenovirus vector system: construction, history and therapeutic applications.

Since the isolation of adenovirus (AdV) in 1953, AdVs have been used as vectors for various therapeutic purposes, such as gene therapy in cancers and other malignancies, vaccine development and delivery of CRISPR-Cas9 machinery. Over the years, several AdV vector modifications have been introduced, including fiber switching, incorporation of ligands in the viral capsid and hexon modification of the fiber, to improve the efficiency of AdV as a vector. CRISPR-Cas9 has recently been used for these modifications and is also used in other adeno-associated viruses. These modifications further allow the production of AdV libraries that display random peptides for the production of cancer-targeting AdV vectors. This review focuses on the common methods of AdV construction, changes in AdV tropism for the improvement of therapeutic efficiency and the role of AdV vectors in gene therapy, vaccine development and CRISPR-Cas9 delivery.