Genome-wide identification and in-silico expression analysis of CCO gene family in sunflower (Helianthus annnus) against abiotic stress.

Carotenoid cleavage oxygenases (CCOs) enzymes play an important role in plant growth and development by producing a wide array of apocarotenoids and their derivatives. These compounds are vital for colouring flowers and fruits and synthesizing plant hormones such as abscisic acid and strigolactones. Despite their importance, the gene family responsible for CCO enzymes in sunflowers has not been identified. In this study, we identify the CCO genes of the sunflower plant to fill this knowledge gap. Phylogenetic and synteny analysis indicated that the Helianthus annnus CCO (HaCCO) genes were conserved in different plant species and they could be divided into three subgroups based on their conserved domains. Analysis using MEME tool and multiple sequence alignment identified conserved motifs in the HaCCO gene sequence. Cis-regulatory elements (CREs) analysis of the HaCCO genes indicated the presence of various responsive elements related to plant hormones, development, and responses to both biotic and abiotic stresses. This implies that these genes may respond to plant hormones, developmental cues, and drought stress, offering potential applications in the development of more resistant crops. Genes belonging to the 9-cis-epoxy carotenoid dioxygenases (NCED) subgroups predominantly exhibited chloroplast localization, whereas the genes found in other groups are primarily localized in the cytoplasm. These 21 identified HaCCOs were regulated by 60 miRNAs, indicating the crucial role of microRNAs in gene regulation in sunflowers. Gene expression analysis under drought stress revealed significant up-regulation of HaNCED16 and HaNCED19, genes that are pivotal in ABA hormone biosynthesis. During organ-specific gene expression analysis, HaCCD12 and HaCCD20 genes exhibit higher activity in leaves, indicating a potential role in leaf pigmentation. This study provides a foundation for future research on the regulation and functions of the CCO gene family in sunflower and beyond. There is potential for developing molecular markers that could be employed in breeding programs to create new sunflower lines resistant to biotic and abiotic stresses.

Enabling High Reversibility of Zn anode via Interfacial Engineering Induced by Amino acid Electrolyte Additive.

Despite possessing substantial benefits of enhanced safety and cost-effectiveness, the aqueous zinc ion batteries (AZIBs) still suffers with the critical challenges induced by inherent instability of Zn metal in aqueous electrolytes. Zn dendrites, surface passivation, and corrosion are some of the key challenges governed by water-driven side reactions in Zn anodes. Herein, a highly reversible Zn anode is demonstrated via interfacial engineering of Zn/electrolyte driven by amino acid D-Phenylalanine (DPA) additions. The preferential adsorption of DPA and the development of compact SEI on the Zn anode suppressed the side reactions, leading to controlled and uniform Zn deposition. As a result, DPA added aqueous electrolyte stabilized Zn anode under severe test environments of 20.0 mA cm-2 and 10.0 mAh cm-2 along with an average plating/stripping Coulombic efficiency of 99.37%. Under multiple testing conditions, the DPA-incorporated electrolyte outperforms the control group electrolyte, revealing the critical additive impact on Zn anode stability. This study advances interfacial engineering through versatile electrolyte additive(s) toward development of stable Zn anode, which may lead to its practical implementation in aqueous rechargeable zinc batteries.

Clinical and genetic investigation of 14 families with various forms of short stature syndromes.

Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology. Homozygosity mapping, whole exome sequencing, and Sanger sequencing were used to search for the disease-causing gene variants. In total, we have identified 13 sequence variants in 10 different genes. The variants in the HSPG2 and XRCC4 genes were not reported previously in the Pakistani population. This study will expand the mutation spectrum of the identified genes and will help in improved diagnosis of the syndromic form of short stature in the local population.

Phytoremediation through microstructural and functional alterations in alkali weed (Cressa cretica L.) in the hyperarid saline desert.

Salt excretory halophytes are the major sources of phytoremediation of salt-affected soils. Cressa cretica is a widely distributed halophyte in hypersaline lands in the Cholistan Desert. Therefore, identification of key physio-anatomical traits related to phytoremediation in differently adapted C. cretica populations was focused on. Four naturally adapted ecotypes of non-succulent halophyte Cressa cretica L. form hyper-arid and saline desert Cholistan. The selected ecotypes were: Derawar Fort (DWF, ECe 20.8 dS m-1) from least saline site, Traway Wala Toba (TWT, ECe 33.2 dS m-1) and Bailah Wala Dahar (BWD, ECe 45.4 dS m-1) ecotypes were from moderately saline sites, and Pati Sir (PAS, ECe 52.4 dS m-1) was collected from the highly saline site. The natural population of this species was collected and carefully brought to the laboratory for different structural and functional traits. As a result of high salinity, Na+, Cl-, K+, and Ca2+ content significantly increased at root and shoot level. At root level, some distinctive modifications such as increased sclerification in vascular bundles, enlarged vascular bundles, metaxylem vessels, phloem region, and storage parenchyma (cortex) are pivotal for water storage under extreme arid and osmotic condition. At the stem level, enhanced sclerification in outer cortex and vascular bundles, stem cellular area, cortical proportion, metaxylem and phloem area, and at the leaf level, very prominent structural adaptations were thicker and smaller leaves with increased density of salt glands and trichomes at surface, few and large stomata, reduced cortical and mesophyll parenchyma, and narrow xylem vessels and phloem area represent their non-succulent nature. The ecotype collected from hypersaline environments was better adapted regarding growth traits, ion uptake and excretion, succulence, and phytoremediation traits. More importantly, structural and functional traits such as root length and biomass, accumulation of toxic ions along with K+ in root and shoot, accumulation of Ca2+ in shoot and Mg2+ in root, excretion of toxic ions were the highest in this ecotype. In conclusion, all these alterations strongly favor water conservation, which certainly contributes to ecotypes survival under salt-induced physiological drought.

Naturally adapted salt tolerant plants provide exceptional material for exploring adaptive mechanisms they use to confront high salt concentrations. Cressa cretica is a hypersaline hyperarid desert colonizer, which was previously underexplored. In the present study, we focused on the new insight on relationship among anatomical modifications, salt accumulation and excretion and phytoremediation potential of this rare species.

Genetic overview of postaxial polydactyly: Updated classification.

Polydactyly or polydactylism, also known as a hyperdactyly, is a congenital limb defect with various morphologic phenotypes. Apart from physical and functional impairments, the presence of polydactyly is an indication of an underlying syndrome in the newborn. Usually, it follows as an autosomal dominant/recessive inheritance pattern with defects in the limb development's anteroposterior patterning. Although mutations in several genes have been associated with polydactyly; however, the exact underlying cause, pathways, and disease mechanisms are still unexplored, thus making it of multi-factorial origin. Polydactyly is divided into three subtypes; radial, ulnar, and central polydactyly. So far, 11 loci (PAPA1-PAPA11) and seven human genes have been reported to cause non-syndromic postaxial polydactyly in humans, including the ZNF141, GLI3, IQCE, GLI1, FAM92A1, KIAA0825, and DACH1. In this review, we discuss emerging evidences of clinical and molecular characterization of polydactyly types in term of the involvement of newly associated genes and loci for non-syndromic postaxial polydactyly, and how these might impact our understanding of the genetic mechanisms and molecular etiology involved in the cause of polydactyly.

Structural determinants of phytoremediation capacity in saltmarsh halophyte Diplachne fusca (L.) P. Beauv. ex Roem. & Schult. subsp. fusca.

Micro and macro-morphological features contribute to plants' tolerance to a variety of environmental pollutants. The contribution of such structural modifications in the phytoremediation potential of Diplachne fusca populations collected from five saline habitats were explored when treated with 100 to 400 mM NaCl for 75 days along with control. Structural modifications in the populations from the highest salinity included development of aerenchyma in stem instead of chlorenchyma, absence of excretory hairs in stem, and exceptionally large trichomes on the leaf surface to help excretion of excess salt. Large parenchyma cells provided more space for water and solute storage, while broad metaxylem vessels were linked to better conduction water and nutrients, which ultimately excreted via glandular hairs, microhairs, and vesicular hairs. Broad metaxylem vessels and exceptionally long hairs observed in the populations collected from 52 dS m-1. In conclusion, large stem aerenchyma, exceptionally large trichomes on the leaf surface, and tightly packed outer cortical region in roots with intensive sclerification just inside the epidermis accompanied with salt excretion via glandular hairs, microhairs, and vesicular hairs were the main anatomical modifications involved in the phytoremediation potential of D. fusca in hyper-saline environments.

Morpho-anatomical characteristics of the differently adapted populations of Diplachne fusca has never been reported. In particular, structural variation in their mechanism of adaptation for salinity tolerance was investigated for the first time in current study.

Aridity-driven changes in structural and physiological characteristics of Buffel grass (Cenchrus ciliaris L.) from different ecozones of Punjab Pakistan.

Cenchrus ciliaris L. is a perennial grass that can grow in a diverse range of habitats including challenging deserts. The purpose of the study was to investigate the impact of aridity on morpho-anatomical and physiological traits in C. ciliaris populations collected from arid and semi-arid areas of Punjab, Pakistan. The populations growing in extremely arid conditions displayed a range of structural and physiological adaptations. Under extremely dry conditions, root epidermal thickness (90.29 µm), cortical cell area (7677.78 µm2), and metaxylem cell area (11,884.79 µm2) increased while root pith cell area (2681.96 µm2) decreased in tolerant populations. The populations under extremely aridity maximized leaf lamina (184.21 µm) and midrib thickness (316.46 µm). Additionally, highly tolerant populations were characterized by the accumulation of organic osmolytes such as glycinebetaine (132.60 µmol g-1 FW) was increased in QN poulations, proline (118.01 µmol g-1 F.W) was maximum in DF populations, and total amino acids (69.90 mg g-1 FW) under extreme water deficit conditions. In arid conditions, abaxial stomatal density (2630.21 µm) and stomatal area (8 per mm2) were also reduced in DF populations to check water loss through transpiration. These findings suggest that various parameters are crucial for the survival of C. ciliaris in arid environments. The main strategies used by C. ciliaris was intensive sclerification, effective retention of ions, and osmotic adjustment through proline and glycinebetaine under arid conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01351-3.

Loss of Function Variants in the XPC Causes Severe Xeroderma Pigmentosum in Three Large Consanguineous Families.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare recessively inherited disorder that presents clinical and genetic heterogeneity. Mutations in eight genes, of which seven are involved in nucleotide excision repair (NER) pathway have been reported to cause the XP. METHODS AND RESULTS: Three large consanguineous families of Pakistani origin displaying typical clinical hallmarks of XP were evaluated at clinical and molecular level. Homozygosity mapping using microsatellite markers established linkage of the families to XPC gene on chromosome 3p25.1. Sanger sequencing of the XPC gene identified a novel homozygous single bp deletion [NM_004628.5; c.1934del; p.(Pro645Leufs*5)] and two previously reported mutations that included a nonsense [c.1243 C>T; p.(Arg415*)] and a splice acceptor site (c.2251-1 G>C), all segregating with the disease phenotypes in the families. CONCLUSION: This report has extended the spectrum of mutations in the XPC gene and will also facilitate in diagnosis of XP and counselling of families inheriting it, which is the only inevitable tool for preventing the disease occurrence in future generations.

On fractal-fractional Covid-19 mathematical model.

In this article, we are studying a Covid-19 mathematical model in the fractal-fractional sense of operators for the existence of solution, Hyers-Ulam (HU) stability and computational results. For the qualitative analysis, we convert the model to an equivalent integral form and investigate its qualitative analysis with the help of iterative convergent sequence and fixed point approach. For the computational aspect, we take help from the Lagrange's interpolation and produce a numerical scheme for the fractal-fractional waterborne model. The scheme is then tested for a case study and we obtain interesting results.

Biallelic variant in DACH1, encoding Dachshund Homolog 1, defines a novel candidate locus for recessive postaxial polydactyly type A.

Polydactyly or hexadactyly is characterized by an extra digit/toe with or without a bone. Currently, variants in ten genes have been implicated in the non-syndromic form of polydactyly. DNA from a single affected individual having bilateral postaxial polydactyly was subjected to whole exome sequencing (WES), followed by Sanger sequencing. Homology modeling was performed for the identified variant and advance microscopy imaging approaches were used to reveal the localization of the DACH1 protein at the base of primary cilia. A disease-causing biallelic missense variant (c.563G > A; p.Cys188Tyr; NM_080760.5) was identified in the DACH1 gene segregating perfectly within the family. Structural analysis using homology modeling of the DACH1 protein revealed secondary structure change that might result in loss of function or influence downstream interactions. Moreover, siRNA-mediated depletion of DACH1 showed a key role of DACH1 in ciliogenesis and cilia function. This study provides the first evidence of involvement of the DACH1 gene in digits development in humans and its role in primary cilia. This signifies the importance and yet unexplored role of DACH1.

Melatonin In Acute Mania Investigation (MIAMI-UK). A randomized controlled trial of add-on melatonin in bipolar disorder.

OBJECTIVES: Current options for treating emergent episodes of hypomania and mania in bipolar disorder are limited. Our objective was to compare the effectiveness and safety of add-on melatonin in hypomania or mania over 3 weeks as a well-tolerated therapy. METHODS: A randomized, double-blind, parallel-group, 3-week comparison of modified release melatonin (n = 21) vs placebo (n = 20) in adult bipolar patients aged 18-65 years. Permuted block randomization was used with participants and investigators masked to treatment allocation. Trial registration is ISRCTN28988273 and EUdraCT2008-000281-23. Approved by the South Central National Research Ethics Service (Oxford REC A) ref: 09/H0604/63. RESULTS: The trial was negative as there was no significant difference between melatonin and placebo on the primary outcome-mean Young Mania Rating Scale (YMRS) score at Day 21: (mean difference [MD] -1.77 ([95% CI: -6.39 to 2.85]; P = .447). Significantly fewer patients on melatonin scored 10 or more on the Altman Self Rating Mania Scale: (odds ratio [OR] 0.164 [95% CI: 0.0260-1.0002]; P = .05). Quick Inventory of Depression Symptomatology Clinician Version-16 (QIDS-C16) scores were not significantly different. (OR 1.77 [95% CI: 0.43-7.29]; P = .430). The proportion of patients scoring less than or equal to 5 on the self-report QIDS-SR16 at end-point was greater for the melatonin group (OR 8.35 [95% CI: 1.04-67.23]; P = .046). CONCLUSIONS: In this small trial, melatonin did not effectively treat emerging hypomania or mania as there was no significant difference on the primary outcome. The sample size limitation and secondary outcomes suggest further investigation of melatonin treatment in mood episodes is indicated.

Identification of a novel biallelic missense variant in the KIAA0825 underlies postaxial polydactyly type A.

Postaxial polydactyly (PAP) is characterized by development of extra digits, which mostly segregates in autosomal recessive pattern. The underlying genetic cause of recessive non-syndromic PAP type A has been associated with sequence variants in five different genes (ZNF141, IQCE, GLI1, FAM92A, KIAA0825). The present study was aimed to investigate clinical and genetic causes of PAPA in a consanguineous family of Pakistani origin. Microsatellite-based linkage analysis was used to search for the disease-causing gene. Linkage in the family was established at chromosome 5q15 harbouring a candidate gene KIAA0825. Subsequently, Sanger sequencing revealed a novel homozygous missense variant [c.50T>C; p. (Leu17Ser)] in the gene, which co-segregated with the disease within the family. Protein structural analysis predicted a substantial change in the secondary structure of the mutant protein affecting its function. This is the third disease causing variant identified in the KIAA0825. This has not only expanded spectrum of the mutations in the gene but also further substantiated its role in the limb development in human.

Respiratory syncytial virus F and G protein core fragments fused to HBsAg-binding protein (SBP) induce a Th1-dominant immune response without vaccine-enhanced disease.

The induction of a dominant Th2-type response is the main cause of harmful inflammation in respiratory syncytial virus (RSV) vaccine trials. A balanced Th1 versus Th2 immune response is needed for a safe and effective RSV vaccine. In this study, we evaluated the potential of a recombinant protein SBP-FG as a vaccine candidate with the main focus on shifting the harmful Th2 response to a Th1 response. SBP-FG consists of epitopes from RSV fusion (F) and attachment (G) proteins conjugated to the N-terminus of HBsAg-binding protein (SBP). SBP-FG induced significantly stronger immune responses assessed at the level of total IgG, IgA and neutralizing antibodies as compared with formalin-inactivated RSV (FI-RSV) and live RSV. Analysis of IgG isotypes, lung cytokines and T helper cells showed that SBP-FG induced a dominant Th1-type response. Further, SBP-FG immunized mice showed significantly reduced lung eosinophilia, reduced viral multiplication in lungs after challenge infection and provided protection against RSV infection. These results suggest that SBP-FG can be developed into a safe and effective vaccine against RSV. However, more studies are required to further evaluate SBP-FG as a potent vaccine candidate against RSV.

Graphene/graphitic carbon nitride decorated with AgBr to boost photoelectrochemical performance with enhanced catalytic ability.

A novel graphene nanoplatelets (GNP) bridge between two semiconductors (AgBr and graphitic carbon nitride) was created to boost photoelectrochemical performance. The heterojunction created makes the whole system a Z-scheme catalyst. For the construction of this catalyst, the syringe pump methodology was adopted and different analytical techniques were used for the confirmation of structure and morphology. High angle annular dark field (HAADF), dark field (DF), DF-4 and DF-2 techniques, using Z-contrast phenomena, confirmed the heterostructure (ABGCN) and its composition. The constructed structure showed an enhanced photoelectrochemical and catalytic property against 'acute toxicity category-III (MM)' and 'category-IV (tetracycline hydrochloride (TH))' organic pollutants. The constructed catalyst degraded the MM in 57 min and the TH in 35 min with degradation rates of 0.01489 min-1 and 0.02387 min-1, respectively, due to the accumulation of photogenerated electrons on the conduction band (CB) of g-C3N4 and photogenerated holes on the valence band (VB) of AgBr by the transformation of charges through the graphene bridge. An ion trapping study also revealed that ·O2 and h+ were the active species which actively participated in the photocatalytic reaction.

Whole-exome sequencing revealed a nonsense mutation in STKLD1 causing non-syndromic pre-axial polydactyly type A affecting only upper limb.

Pre-axial polydactyly (PPD) is characterized by well-developed non-functional 1st digit (thumb) duplication in hands and/or feet. It is mostly inherited in autosomal dominant manner. In the present study, two families of Pakistani origin, demonstrating unilateral PPD type A, have been characterized at clinical and genetic levels. Whole-exome sequencing (WES) revealed a nonsense mutation (c.84C > A, p.Tyr28*) in the STKLD1, located on chromosome 9q34.2, in affected individuals of both the families. Our findings report the first direct involvement of the STKLD1 in the digit development and highlight the importance of inclusion of this gene for screening individuals presenting non-syndromic recessive PPD.

Predictors of therapeutic failure among patients with acute brucellosis treated by dual therapy with doxycycline-rifampin.

OBJECTIVE: To determine the frequency of therapeutic failure among patients with acute and subacute brucellosis and to explore the predictors of failure. METHODS: The study included 213 consecutive, naïve patients with acute and subacute brucellosis. All participants underwent clinical evaluation, chest radiography, stool microscopic examination and interferon-gamma release assay. Patients received the WHO-recommended therapy of doxycycline 200 mg/day and rifampin 900 mg/day, for 6 weeks. RESULTS: Mean age of the study population was 39.8 ± 12.2 years; 64.8% of them were males. The therapeutic failure rate was 16.4%. Adverse effects were reported by 13.1%. Multivariate analysis of factors associated with therapeutic failure revealed latent tuberculosis infection (LTBI) (OR 3.1, 95% CI, 1.9-24.6, P: 0.009), ascariasis (OR 2.6, 95% CI 1.5-17.9, P: 0.012), and the use of acid suppressive therapy (OR 2.1, 95% CI 1.2-19.5, P: 0.037) as the predictors of therapeutic failure. CONCLUSIONS: The prevalence of therapeutic failure among the Egyptian patients with acute/subacute brucellosis is increasing. Predictors of therapeutic failure are LTBI, ascariasis, and the use of acid suppressive therapy.

CT/MRI-Guided Synergistic Radiotherapy and X-ray Inducible Photodynamic Therapy Using Tb-Doped Gd-W-Nanoscintillators.

The use of X-rays instead of UV/Vis light to trigger photodynamic therapy, named X-ray inducible photodynamic therapy, holds tremendous promise due to a high penetration capacity in tissues and is worthy of in-depth study. In this study, a novel multifunctional nanoagent based on Merocyanine 540-coupled Gd2 (WO4 )3 :Tb nanoscintillators and the vitalization of its abilities for dual-modal computed tomography and the magnetic-resonance-imaging-guided synergistic radio-/X-ray inducible photodynamic therapy of tumors is reported. Synergistic therapies show a higher tumor growth inhibition efficiency at a lower X-ray dose than radiotherapy alone. Through this proof-of-concept work, a way to tactfully understand and utilize nanoscintillators for cancer theranostics is shown.

A novel homozygous missense variant in NECTIN4 (PVRL4) causing ectodermal dysplasia cutaneous syndactyly syndrome.

Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare form of ectodermal dysplasia including anomalies of hair, nails, and teeth along with bilateral cutaneous syndactyly of hands and feet. In the present report, we performed a clinical and genetic characterization of a consanguineous Pakistani family with four individuals affected by EDSS1. We performed exome sequencing using DNA of one affected individual. Exome data analysis identified a novel homozygous missense variant (c.242T>C; p.(Leu81Pro)) in NECTIN4 (PVRL4). Sanger sequencing validated this variant and confirmed its cosegregation with the disease phenotype in the family members. Thus, our report adds a novel variant to the NECTIN4 mutation spectrum and contributes to the NECTIN4-related clinical characterization.

Homozygous sequence variants in the WNT10B gene underlie split hand/foot malformation.

Split-hand/split-foot malformation (SHFM), also known as ectrodactyly is a rare genetic disorder. It is a clinically and genetically heterogeneous group of limb malformations characterized by absence/hypoplasia and/or median cleft of hands and/or feet. To date, seven genes underlying SHFM have been identified. This study described four consanguineous families (A-D) segregating SHFM in an autosomal recessive manner. Linkage in the families was established to chromosome 12p11.1-q13.13 harboring WNT10B gene. Sequence analysis identified a novel homozygous nonsense variant (p.Gln154*) in exon 4 of the WNT10B gene in two families (A and B). In the other two families (C and D), a previously reported variant (c.300_306dupAGGGCGG; p.Leu103Argfs*53) was detected. This study further expands the spectrum of the sequence variants reported in the WNT10B gene, which result in the split hand/foot malformation.

Oxidative Stress Response Induced by Butachlor in Zebrafish Embryo/Larvae: The Protective Effect of Vitamin C.

The widespread contamination and persistence of the herbicide butachlor in the environment resulted in the exposure of non-target organisms. The present study investigated the toxicity effect of butachlor (1-15 µmol/L) and the protective effect of vitamin C (VC) against butachlor-induced toxicity in zebrafish. It was found that butachlor significantly increased the mortality and malformation rates in a dose-dependent manner, which caused elevation in reactive oxygen species (ROS) and malondialdehyde (MDA) after 72 h exposure. Compared with butachlor treatment group, the protective effect of VC against butachlor-induced toxicity were observed after adding 40, 80 mg/L VC respectively. VC significantly decreased the mortality, malformation rates, ROS, MDA, and normalized antioxidant enzymes activities of zebrafish after 72 h exposure. The result shows VC has mitigative effect on butachlor-induced toxicity and it can be used as an effective antioxidant in aquaculture.