Combining GWAS and comparative genomics to fine map candidate genes for days to flowering in mung bean.

BACKGROUND: Mung bean (Vigna radiata (L.) Wilczek), is an important pulse crop in the global south. Early flowering and maturation are advantageous traits for adaptation to northern and southern latitudes. This study investigates the genetic basis of the Days-to-Flowering trait (DTF) in mung bean, combining genome-wide association studies (GWAS) in mung bean and comparisons with orthologous genes involved with control of DTF responses in soybean (Glycine max (L) Merr) and Arabidopsis (Arabidopsis thaliana). RESULTS: The most significant associations for DTF were on mung bean chromosomes 1, 2, and 4. Only the SNPs on chromosomes 1 and 4 were heavily investigated using downstream analysis. The chromosome 1 DTF association is tightly linked with a cluster of locally duplicated FERONIA (FER) receptor-like protein kinase genes, and the SNP occurs within one of the FERONIA genes. In Arabidopsis, an orthologous FERONIA gene (AT3G51550), has been reported to regulate the expression of the FLOWERING LOCUS C (FLC). For the chromosome 4 DTF locus, the strongest candidates are Vradi04g00002773 and Vradi04g00002778, orthologous to the Arabidopsis PhyA and PIF3 genes, encoding phytochrome A (a photoreceptor protein sensitive to red to far-red light) and phytochrome-interacting factor 3, respectively. The soybean PhyA orthologs include the classical loci E3 and E4 (genes GmPhyA3, Glyma.19G224200, and GmPhyA2, Glyma.20G090000). The mung bean PhyA ortholog has been previously reported as a candidate for DTF in studies conducted in South Korea. CONCLUSION: The top two identified SNPs accounted for a significant proportion (~ 65%) of the phenotypic variability in mung bean DTF by the six significant SNPs (39.61%), with a broad-sense heritability of 0.93. The strong associations of DTF with genes that have orthologs with analogous functions in soybean and Arabidopsis provide strong circumstantial evidence that these genes are causal for this trait. The three reported loci and candidate genes provide useful targets for marker-assisted breeding in mung beans.

Recent Advances in Delivery of Peptide and Protein Therapeutics to the Brain.

The classes of neuropharmaceuticals known as proteins and peptides serve as diagnostic tools and are involved in specific communication in the peripheral and central nervous systems. However, due to tight junctions resembling epithelial cells found in the blood-brain barrier (BBB) in vivo, they are typically excluded from transport from the blood to the brain. The drugs having molecular weight of less than 400 Dalton are able to cross the BBB via lipid-mediated free diffusion. However, large molecule therapeutics are devoid of these characteristics. As an alternative, these substances may be carried via chimeric peptide drug delivery systems, and assist in transcytosis through BBB with the aid of linker strategies. With their recent developments, several forms of nanoparticles, including poly (ethylene glycol)-poly(ε-caprolactone) copolymers, nanogels, liposomes, nanostructured lipid carriers, poly (D, L-lactide-co-glycolide) nanoparticles, chitosan, and solid lipid nanoparticles, have also been considered for their therapeutic applications. Moreover, the necessity for physiologic optimization of current drug delivery methods and their carriers to deliver therapeutic doses of medication into the brain for the treatment of various neurologic illnesses has also been emphasized. Therapeutic use of proteins and peptides has no neuroprotective impact in the absence of all these methods. Each tactic, however, has unique drawbacks and considerations. In this review, we discuss different drug delivery methods for therapeutic distribution of pharmaceuticals, primarily neuroproteins and neuropeptides, through endothelial capillaries via blood-brain barrier. Finally, we have also discussed the challenges and future perspective of protein and peptide therapeutics delivery to the brain. SIGNIFICANCE STATEMENT: Very few reports on the delivery of therapeutic protein and peptide nanoformulations are available in the literature. Herein, we attempted to discuss these nanoformulations of protein and peptide therapeutics used to treat brain diseases.

Coenzyme Q10 ameliorates chemotherapy-induced cognitive impairment in mice: a preclinical study.

BACKGROUND: Among the three most used anticancer drugs, cyclophosphamide, Adriamycin, and 5-Fluorouracil (CAF), the most significant outcome is chemobrain, caused by increased oxidative stress, inflammatory insult, and mitochondrial dysfunction. OBJECTIVE: In this study, endogenous antioxidant coenzyme Q10 (CoQ10) was evaluated for its neuroprotective effects in CICI. MATERIALS AND METHODS: The chemobrain was induced in Swiss albino female mice by administering CAF (40 + 4 + 25 mg/kg) intraperitoneal (i.p.) in three cycles (single injection per week) followed by treatment with CoQ10 (40 mg/kg; p.o.) for up to 3 weeks followed by behavioral, biochemical, molecular and histopathological analysis. RESULTS: Treatment with CoQ10 significantly improved cognition by improving exploring time in novel objects recognition test followed by increasing the time spent in the target quadrant in MWM test as compared to CAF-treated animals. Moreover, CoQ10 demonstrated antioxidant properties by reducing the expression of LPO while increasing levels of GSH, SOD, and catalase as compared to CAF-treated animals. While the levels of AChEs were significantly reduced after CoQ10 treatment in CAF-treated animals. In terms of its mechanism, it effectively counteracted the pro-inflammatory substances (TNF-α and IL-1ß) triggered by CAF while also enhancing the levels of anti-inflammatory markers (IL-10 and Nrf2). Moreover, CoQ10 showed mitochondrial enhancers and it improved the level of Complex (I, II, and IV). Besides that, mitochondrial morphological analysis was done by TEM, and neuronal morphology along with quantification analysis was performed by H&E staining using Image J software to confirm the neuroprotective effect of CoQ10 over CAF-induced cognitive impairment. CONCLUSION: This study suggests CoQ10 can protect the mitochondria by imposing antioxidant, and anti-inflammatory properties, which could be a potential therapy for CICI.

Association of nature of work and work-related characteristics with cognitive functioning, life satisfaction and depression among Indian ageing adults.

BACKGROUND: Most individuals spend a significant amount of their time at work, and the dynamics at work can potentially influence their overall life, especially health and mental health. The present study tried to understand the association of the nature of work categorized as physically demanding, psychologically demanding, and environmentally hazardous on life satisfaction, cognitive functioning, and depressive symptoms among working middle-aged and older adults in India. METHOD: We used data from the Longitudinal Ageing Study in India (LASI), Wave 1, collected between 2017 and 2018. The study sample consists of 28,653 working adults aged between 45 and 70. The study measures were assessed using standard tools. Linear regression analysis was employed. RESULTS: The results indicate that individuals working in less physically demanding (ß = 0.06, 99% CI = 0.02-0.09) and not hazardous environments (ß = 0.15, 99% CI = 0.09-0.20) had better life satisfaction. Also, not being involved in hazardous work environments increased the likelihood of good cognitive functioning and reduced depressive symptoms (ß= -0.17, 99% CI= -0.20- -0.15). However, samples involved in works requiring less psychological demand had an increased likelihood of reduced life satisfaction and increased depressive symptoms. CONCLUSION: This study's results highlight the importance of creating a conducive working environment for the ageing adults.

First Report of Stem Blight of Mungbean (Vigna radiata) Caused by Diaporthe longicolla in the United States.

Mungbean (Vigna radiata) is primarily grown in Asia and directly consumed by humans. U.S. consumers embraced mungbean as a plant-based protein in vegan eggs and meat substitutes. New cultivars are being developed for American farmers because of the crop's tolerance to heat and drought, and its adaptability to current farming infrastructure. Mungbean's short season complements various cropping systems such as intercropping, alternative cropping, and green manure. With rotations and inclusion with soybean systems, there is a concern about the overlap of common pathogens for soybean and mungbean. During August 2022 when mungbeans reached full maturity (growth stage R6), reddish-brown and necrotic stem lesions with linear rows of black pycnidia were observed on Berken and OK2000 cultivars at fields located in Hancock County, IA and Story County, IA in the United States. Pycnidia measured 0.5-0.6mm in length. Disease incidence was approximately 10% of plants in Hancock County, IA and less than 3% of plants in Story County, IA. Pycnidia from 16 plants were excised and immersed in a 0.5% NaOCl solution for 1 min, rinsed with autoclaved distilled water, and placed onto potato dextrose agar (PDA). Eighteen isolates were hyphal tipped and grown on PDA and were stored at 25°C. Isolates were then visually identified by culture and conidia morphology (Hobbs et al. 1985, Santos et al. 2011). Colonies were cream to white, dense, and floccose. Large black stromata were formed in a concentric pattern or scattered; alpha conidia were ellipsoidal. Template DNA for PCR amplification of the internal transcribed spacer region of the nuclear ribosomal DNA operon (ITS) and the beta-tubulin gene (TUB) was extracted from 18 isolates by scraping mycelia with a sterile pipette tip and transferring it into 50 ul of PrepMan Ultra Sample Reagent (Applied Biosystems, Foster City, California, USA). Fungal primers were ITS1 and ITS4 (White et al. 1990) and Bt-2F/Bt-2R (Udayanga et al. 2014). Sequences of isolates obtained from fields in both counties were identical, providing no species diversity. GenBank accession numbers for the ITS region were PP105598 and PP105599; PP108254 and PP108255 for TUB sequences. BLAST results showed the ITS 550/550 base pairs with type specimen D. longicolla ATCC 60326 GB NR_144924 and the TUB 446/446 base pairs with type specimen D. longicolla ATCC 60325 GB KJ610883. Thus, the isolates were identified as Diaporthe longicolla (Hobbs) J.M. Santos, Vrandecic & A.J.L. Phillips based on morphology and molecular characters (Santo et al 2011; Udayanga et al. 2014). To confirm the pathogenicity of the D. longicolla isolates, twenty mungbean plants (cv. Berken and OK2000) were grown in the greenhouse at 85% RH and 16hr light for 20 days. Inoculum was prepared by placing sterile toothpicks on 1/3 PDA with a single representative isolate from each field location for 21 days (Ghimire et al. 2019). Mungbean plants were grown in a 10cm-by-10cm pot containing a greenhouse professional growing mix (Sungrow, Agawam, Massachusetts, USA) and grown for 30 days post emergence. After 12 days of growing, a 3mm segment of the infested toothpick was inserted into a stem wound below the first trifoliate and sealed with parafilm. A sterile toothpick was inserted into the control plants. After 14 days, red lesions extended downward 1 to 3 cm from the inoculation site, and white mycelial was present in the wound. At 21 days red lesions spanned 3 to 9 cm upward and downward from the inoculation site. Pycnidia were present on collapsed stem tissue, and leaves became chlorotic. Damage was limited to 2mm from the mock-inoculation site, with no discoloration in the control plants. Symptomatic tissues were plated and compared to the original isolates. Alpha conidia were ellipsoidal with the base end rounded. To our knowledge, this is the first report of Diaporthe longicolla causing disease on mungbean within the U.S. and worldwide. The presence of this disease in two locations suggests the potential for Diaporthe longicolla to be a serious disease of mungbean in the future.

Understanding zebrafish sleep and wakefulness physiology as an experimental model for biomedical research.

Sleep is a globally observable fact, or period of reversible distracted rest, that can be distinguished from arousal by various behavioral criteria. Although the function of sleep is an evolutionarily conserved behavior, its mechanism is not yet clear. The zebrafish (Danio rerio) has become a valuable model for neurobehavioral studies such as studying learning, memory, anxiety, and depression. It is characterized by a sleep-like state and circadian rhythm, making it comparable to mammals. Zebrafish are a good model for behavioral studies because they share genetic similarities with humans. A number of neurotransmitters are involved in sleep and wakefulness. There is a binding between melatonin and the hypocretin system present in zebrafish. The full understanding of sleep and wakefulness physiology in zebrafish is still unclear among researchers. Therefore, to make a clear understanding of the sleep/wake cycle in zebrafish, this article covers the mechanism involved behind it, and the role of the neuromodulator system followed by the mechanism of the HPA axis.

The Role of Mitophagy in Various Neurological Diseases as a Therapeutic Approach.

Mitochondria are critical to multiple cellular processes, from the production of adenosine triphosphate (ATP), maintenance of calcium homeostasis, synthesis of key metabolites, and production of reactive oxygen species (ROS) to maintain necrosis, apoptosis, and autophagy. Therefore, proper clearance and regulation are essential to maintain various physiological processes carried out by the cellular mechanism, including mitophagy and autophagy, by breaking down the damaged intracellular connections under the influence of various genes and proteins and protecting against various neurodegenerative diseases such as Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), and Huntington disease (HD). In this review, we will discuss the role of autophagy, selective macroautophagy, or mitophagy, and its role in neurodegenerative diseases along with normal physiology. In addition, this review will provide a better understanding of the pathways involved in neuron autophagy and mitophagy and how mutations affect these pathways in the various genes involved in neurodegenerative diseases. Various new findings indicate that the pathways that remove dysfunctional mitochondria are impaired in these diseases, leading to the deposition of damaged mitochondria. Apart from that, we have also discussed the therapeutic strategies targeting autophagy and mitophagy in neurodegenerative diseases. The mitophagy cycle results in the degradation of damaged mitochondria and the biogenesis of new healthy mitochondria, also highlighting different stages at which a particular neurodegenerative disease could occur.

Non-cigarette tobacco use and stroke among West Africans: evidence from the SIREN study.

INTRODUCTION: Non-cigarette tobacco (NCT) represents a form of tobacco use with a misperceived significance in chronic disease events. Whether NCT use is sufficient to promote stroke events, especially among Africans, is yet to be understood. This study assessed the relationship between NCT use and stroke among indigenous Africans. METHODS: A total of 7,617 respondents (NCT users: 41 vs. non-NCT: 7576) from the Stroke Investigation Research and Educational Network study were included in the current analysis. NCT use was defined as self-reported use of smoked (cigars or piper) or smokeless (snuff or chewed) tobacco in the past year preceding stroke events. Stroke was defined based on clinical presentation and confirmed with a cranial CT/MRI. Multivariable-adjusted logistic regression was applied to estimate the odds ratio (OR) and 95% confidence interval (CI) for the relationship between NCT and stroke at p<0.05. RESULTS: Out of the 41 (0.54%) who reported NCT use, 27 (65.9%) reported using smokeless NCT. NCT users were older than non-smokers (62.8±15.7 vs 57.7±14.8 years). Overall, NCT use was associated with first-ever stroke (OR: 2.08; 95%CI: 1.02, 4.23) in the entire sample. Notably, smokeless NCT use was independently associated with higher odds of stroke (OR: 2.74; 95%CI: 1.15, 6.54), but smoked NCT use (OR: 0.16; 95%CI: 0.02, 1.63) presented a statistically insignificant association after adjusting for hypertension and other covariates. CONCLUSIONS: NCT use was associated with higher odds of stroke, and public health interventions targeting NCT use might be promising in reducing the burden of stroke among indigenous Africans. IMPLICATIONS: A detailed understanding of the relationship between NCT use and stroke will likely inform well-articulated policy guidance to promote evidence-based recommendations for public health prevention and management of stroke on the African continent.

Are there differences in perceptions, preferences and attitudes towards disclosure of genetic testing for Stroke? A qualitative study among stroke-free SIREN-SIBS genomics study participants.

OBJECTIVE: This study explored perceptions, preferences and attitudes towards disclosure of genetic testing results for stroke among stroke-free controls (and their family members) in the SIREN-SIBS Genomics Study, healthcare providers and policymakers. MATERIALS AND METHODS: We conducted a qualitative thematic analysis of key informant interviews with 61 participants recruited from community advisory boards (30) and health care providers (31) across seven sites in Nigeria and Ghana. RESULTS: Major findings illustrate differences in the knowledge of genetic testing with superior knowledge among health care professionals. Relatives and religious leaders were opined as the best to receive the disclosure as they would be able to break the news to the patient in a culturally sensitive manner to reduce the likely resultant emotional outburst. Poor level of awareness of national guidelines for disclosing genetic results exist. Key facilitating factors for disclosure are education, enabling environment, involvement of religious and community leaders, campaigns, and possible treatment options. Disclosure inhibitors include inadequate information, fear of marital break-up or family displacement, fear of stigmatization, fear of isolation, religious beliefs, health worker attitude, and lack of preparedness to accept results. CONCLUSIONS: These necessitate culturally sensitive interventions for continuing education, increased awareness and sustained engagement to equip all stakeholders in genetic testing disclosure process.

Crosstalk between phytochemicals and inflammatory signaling pathways.

Novel bioactive constituents from natural sources are actively being investigated. The phytochemicals in these phenolic compounds are believed to have a variety of beneficial effects on human health. Several phenolic compounds have been found in plants. The antioxidant potential of phenols has been discussed in numerous studies along with their anti-inflammatory effects on pro-inflammatory cytokine, inducible cyclooxygenase-2, and nitric oxide synthase. Through current study, an attempt is made to outline and highlight a wide variety of inflammation-associated signaling pathways that have been modified by several natural compounds. These signaling pathways include nuclear factor-kappa B (NF-кB), activator protein (AP)-1, protein tyrosine kinases (PTKs), mitogen-activated protein kinases (MAPKs), nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factors, tyrosine phosphatidylinositol 3-kinase (PI3K)/AKT, and the ubiquitin-proteasome system. In light of the influence of natural substances on signaling pathways, their impact on the production of inflammatory mediator is highlighted in this review.

Phenolic and flavonoid contents and antioxidant activity of an endophytic fungus Nigrospora sphaerica (EHL2), inhabiting the medicinal plant Euphorbia hirta (dudhi) L.

Since endophytic fungi are pivotal sources of various bioactive natural compounds, the present study is aimed to investigate the antioxidant compounds of the endophytic fungus Nigrospora sphaerica isolated from a pantropical weed, Euphorbia hirta L. The fungus was fermented in four different media and each filtered broth was sequentially extracted in various solvents. Crude extracts collected from different solvents were subjected to phytochemical analysis and antioxidant activity. The total phenolic content (TPC) and total flavonoid content (TFC) were maximal in ethyl acetate crude extract (EtOAcE) of endophyte fermented in potato dextrose broth (PDB) medium (77.74 ± 0.046mgGAE/g and 230.59 ± 2.0 mgRE/g) with the highest 96.80% antioxidant activity. However, TPC and TFC were absent in hexane extract of Czapek Dox broth (CDB) medium exhibiting the lowest 4.63 ± 2.75% activity. The EtOAcE (PDB) showed a positive correlation between TFC and antiradical activity (R2 = 0.762; P < 0.05), whereas a high positive correlation was noticed between TPC and antioxidant activity (R2 = 0.989; P < 0.05). Furthermore, to determine the antioxidant activity, EtOAcE (PDB) was subjected to TLC bioautography-based partial purification, while GC/MS analysis of the partial purified extract was done to confirm the presence of phenolics along with antioxidant compounds that resulted in the detection of 2,4-Di-tert-butylphenol (13.83%), a phenolic compound accountable for the antioxidant potential. Conclusively, N. sphaerica is a potential candidate for natural antioxidant.

Drug-herb combination therapy in cancer management.

Cancer is the second leading cause of fatality all over the world. Various unwanted side effects are being reported with the use of conventional chemotherapy. The plant derived bioactive compounds are the prominent alternative medicinal approach for reduction of chemotherapy associated side effects. The data is collected from Pubmed, Sci-hub, Google scholar, and Research gate were systematically searched up to year 2020. Several herbal drugs have been investigated and found with grateful anti-cancer potentials hence, it can be used in combination with chemotherapy for the depletion of associated side-effects. Herbal drugs and their extracts contain a mixture of active ingredients, which show interactions within themselves and along with chemotherapeutic agents to show either synergistic or antagonistic therapeutic effects. Therefore, it is necessary to develop alternative treatment to control chemotherapy associated side-effects. In this review, we discussed some of the significant chemical compounds, which could be efficient against cancer. This review focuses on the different herbal drugs that play an important role in the treatment of cancer and its associated side-effects. This study aimed to evaluate the efficacy of herbal treatment in combination with chemotherapy for cancer treatment.

Quercetin ameliorates lipopolysaccharide-induced neuroinflammation and oxidative stress in adult zebrafish.

BACKGROUND: Quercetin is a natural flavonoid that is known to have numerous pharmacological activities such as antioxidative, anti-inflammatory, and neuroprotective effects against various neurological disorders. Lipopolysaccharide (LPS) is a potent endotoxin, reported causing several neurological disorders. AIM: The present study was designed to investigate the possibility that quercetin ameliorates LPS induced oxidative stress and neuroinflammation in adult zebrafish. MATERIALS AND METHODS: Zebrafish (weighing 470-530 mg) were treated with a single injection of LPS (1 mg/kg) intraperitoneally (i.p.) followed by post-treatment with quercetin (50 and 100 mg/kg; i.p.) for 7 days. After sacrificing brain was harvested and subjected for biochemical, molecular, and histological analyses. RESULTS: Results revealed post-treatment with quercetin was able to ameliorate the behavioral abnormalities as in novel tank diving test- time spent in the top zone (TSTZ), and the number of entries in the top zone was significantly (p < 0.01) more as compared to time spent in the bottom zone (TSBZ). In the light-dark chamber test- time spent in the light zone (TSLZ), and the number of entries in the light zone were significantly (p < 0.01) more as compared to time spent in the dark compartment (TSDC). Additionally, results of histopathology (H & E stain) studies showed less disruption in neuronal cells as compared to the LPS treated group. Moreover, the results of the molecular analysis revealed that quercetin treatment significantly (p < 0.01) decrease TNF-α and IL-1ß levels as compared to LPS treated animals. Further, results of the biochemical analysis reveal that quercetin significantly (p < 0.01) reduces the level of LPO, nitrite, AChEs and increases anti-oxidant GSH. CONCLUSION: Quercetin treatment helps to prevent oxidative damage and neuroinflammation in LPS treated adult zebrafish.

Legal Implications of Stroke Biobanking and Genomics Research in Sub-Saharan Africa.

Stroke is a major cause of death in Sub-Saharan Africa (SSA) and genetic factors appear to play a part. This has led to stroke biobanking and genomics research in SSA. Existing stroke studies have focused on causes, incidence rates, fatalities and effects. However, scant attention has been paid to the legal issues in stroke biobanking and genomics research in the sub-region. Therefore, this article examines the legal implications of stroke biobanking and genomics research in SSA. The article adopts a textual analysis of primary and secondary sources in law. It reports that there are laws from the perspectives of human right, the common law, and intellectual property. However, there are gaps to be filled. The article therefore argues for legislative intervention. It concludes that pending the time the statute will be enacted, genomics researchers in Africa should adopt the ethical guidelines prepared by Human Heredity and Health in Africa (H3 Africa).

Bioactive potential evaluation and purification of compounds from an endophytic fungus Diaporthe longicolla, a resident of Saraca asoca (Roxb.) Willd.

An endophytic fungus (L3), isolated from the leaf tissues of Saraca asoca was identified as D. longicolla by microscopic and molecular methods. The crude extracts of D. longicolla revealed to harbor seven compounds in GC-MS analysis which was subjected to a thin layer chromatography (TLC) for purification and separation of bioactive ingredients. The partially purified fraction from TLC displayed the presence of 2-tridecene (Z) (RT-14.50), 5-tridecene (E) (RT-16.65) and 2,4-di-tert-butylphenol (RT-13.92) in GC-MS. High-performance liquid chromatography (HPLC) was performed to further purify the constituents which led to the collection of 2,4-di-tert-butyl phenol (RT-2.34) with excellent antioxidant activity and antibacterial activity against methicillin resistance Staphylococcus aureus (MRSA).

Antibacterial potential of selected phytomolecules: An experimental study.

Antibiotic resistance is a snowballing international threat. Some of the antibiotics have lost their effectiveness due to overuse and underuse. Thus, there is an urgent need to tackle this global challenge, either by inhibiting the resistance mechanisms or by the development of new chemical entities. Thus, in the current study, the antibacterial activity of selected phytomolecules was investigated against bacterial strains, alone and in combination, with standard drugs. The antibacterial potential of these phytomolecules was explored using in vitro assays (microtiter assay, bacterial growth kinetics, percentage retardation of growth, and antimicrobial synergy study) and in vivo studies (zebrafish infection model). In vitro and in vivo studies have shown promising antibacterial effects against, both, Gram-positive and Gram-negative bacteria. Moreover, a cell viability assay also indicated the cytoprotective effect of these phytomolecules in combination with standard antibiotics (SABX). Thus, these phytomolecules could be a promising broad-spectrum antibacterial agent in combination with standard antibiotics.

Zebrafish an experimental model of Huntington's disease: molecular aspects, therapeutic targets and current challenges.

Huntington disease (HD) is a lethal autosomal dominant neurodegenerative disease whose exact causative mechanism is still unknown. It can transform from one generation to another generation. The CAG triplet expansion on polyglutamine (PolyQ) tract on Huntingtin protein primarily contributes in HD pathogenesis. Apart from this some another molecular mechanisms are also involved in HD pathology such as loss of Brain derived neurotrophic factor in medium spiny neurons, mitochondrial dysfunction, and alterations in synaptic plasticity are briefly discussed in this review. However, several chemicals (3-nitropropionic acid, and Quinolinic acid) and genetic (mHTT-ΔN17-97Q over expression) experimental models are used to explore the exact pathogenic mechanism and finding of new drug targets for the development of novel therapeutic approaches. The zebrafish (Danio rerio) is widely used in in-vivo screening of several central nervous system (CNS) diseases such as HD, Alzheimer's disease (AD), Parkinson's disease (PD), and in memory deficits. Thus, this makes zebrafish as an excellent animal model for the development of new therapeutic strategies against various CNS disorders. We had reviewed several publications utilizing zebrafish and rodents to explore the disease pathology. Studies suggested that zebrafish genes and their human homologues have conserved functions. Zebrafish advantages and their characteristics over the other experimental animals make it an excellent tool for the disease study. This review explains the possible pathogenic mechanism of HD and also discusses about possible treatment therapies, apart from this we also discussed about possible potential therapeutic targets which will helps in designing of novel therapeutic approaches to overcome the disease progression.  Diagrammatic depiction shows prevention of HD pathogenesis through attenuation of various biochemical alterations.

An explainable deep machine vision framework for plant stress phenotyping.

Current approaches for accurate identification, classification, and quantification of biotic and abiotic stresses in crop research and production are predominantly visual and require specialized training. However, such techniques are hindered by subjectivity resulting from inter- and intrarater cognitive variability. This translates to erroneous decisions and a significant waste of resources. Here, we demonstrate a machine learning framework's ability to identify and classify a diverse set of foliar stresses in soybean [Glycine max (L.) Merr.] with remarkable accuracy. We also present an explanation mechanism, using the top-K high-resolution feature maps that isolate the visual symptoms used to make predictions. This unsupervised identification of visual symptoms provides a quantitative measure of stress severity, allowing for identification (type of foliar stress), classification (low, medium, or high stress), and quantification (stress severity) in a single framework without detailed symptom annotation by experts. We reliably identified and classified several biotic (bacterial and fungal diseases) and abiotic (chemical injury and nutrient deficiency) stresses by learning from over 25,000 images. The learned model is robust to input image perturbations, demonstrating viability for high-throughput deployment. We also noticed that the learned model appears to be agnostic to species, seemingly demonstrating an ability of transfer learning. The availability of an explainable model that can consistently, rapidly, and accurately identify and quantify foliar stresses would have significant implications in scientific research, plant breeding, and crop production. The trained model could be deployed in mobile platforms (e.g., unmanned air vehicles and automated ground scouts) for rapid, large-scale scouting or as a mobile application for real-time detection of stress by farmers and researchers.

A study on the motivation of Indian patients to consult complementary and alternative medicine practitioners to treat coronary artery disease.

BACKGROUND: In India, the use of traditional medicine for health problems is a part of the cultural discourse on treatment, but the introduction of Western medicines has adversely affected their popularity. However, with the rapid spread of chronic diseases like coronary artery disease (CAD), many Indians are reverting to complementary and alternative medicine (CAM) treatments. Although previous literature has identified several motivational factors underlying CAM usage, we know little from the perspective of its practitioners. AIM: The aim of the present study was to investigate the motivations behind the use of CAM treatments among Indian patients with CAD. METHOD: Using semi-structured interviews, we collected data from 15 CAM practitioners and 14 CAD patients utilising CAM treatments alongside conventional biomedical (BM) treatment. We used the Clarke and Braun (2006) method of thematic analysis. RESULT AND CONCLUSION: Our findings suggest that the use of CAM treatments depends on various factors working at multiple levels viz., personal factors, disease' characteristics, perceived treatment characteristics (positive attributes of CAM and negative attributes of BM) and external facilitators. Furthermore, our analysis also identifies the role of two underlining forces-push and pull-in motivating CAD patients to choose CAM treatments. The push force comprises factors that participants found to have a repelling nature, whereas pull forces were regarded as advantageous for CAM usage. Although some reasons behind the usage of CAM treatments according to patients and practitioners were overlapping, both groups also provided many distinct insights into the studied health behaviour.

Phone-Based Intervention under Nurse Guidance after Stroke (PINGS II) Study: Protocol for a Phase III Randomized Clinical Trial.

OBJECTIVES: The Sub-Saharan African (SSA) region now has the highest estimated effect size of hypertension for stroke causation worldwide. An urgent priority for countries in SSA is to develop and test self-management interventions to control hypertension among those at highest risk of adverse outcomes. Thus the overall objective of the Phone-based Intervention under Nurse Guidance after Stroke II study (PINGS-2) is to deploy a hybrid study design to assess the efficacy of a theoretical-model-based, mHealth technology-centered, nurse-led, multi-level integrated approach to improve longer term blood pressure (BP) control among stroke survivors. MATERIALS AND METHODS: A phase III randomized controlled trial involving 500 recent stroke survivors to be enrolled across 10 Ghanaian hospitals. Using a computer-generated sequence, patients will be randomly assigned 1:1 into the intervention or usual care arms. The intervention comprises of (i) home BP monitoring at least once weekly with nurse navigation for high domiciliary BP readings; (2) medication reminders using mobile phone alerts and (3) education on hypertension and stroke delivered once weekly via audio messages in preferred local dialects. The intervention will last for 12 months. The control group will receive usual care as determined by local guidelines. The primary outcome is the proportion of patients with systolic BP <140 mm Hg at 12 months. Secondary outcomes will include medication adherence, self-management of hypertension, major adverse cardiovascular events, health related quality of life and implementation outcomes. CONCLUSION: An effective PINGS intervention can potentially be scaled up and disseminated across healthcare systems in low-and-middle income countries challenged with resource constraints to reduce poor outcomes among stroke survivors.