Molecular Aspects Research Articles

Genetics of sorghum: grain quality, molecular aspects, and drought responses.

Sorghum kernel composition is a crucial characteristic that determines its functional qualities. The total protein content of sorghum grain increases under drought stress, but starch, protein digestibility, and micronutrient contents decrease. Sorghum (Sorghum bicolor L.) is a staple source of starch, protein, and micronutrients in Ethiopia, where it is a key ingredient in local foods like injera and traditional beverages such as tela and areke. It has adapted remarkably to the diverse climatic conditions and soils of both highland and lowland regions. However, grain quality is influenced by climate change, drought stress, and genotype-environment interactions. Under drought conditions, sorghum shows reduced starch content, protein digestibility, and micronutrient levels, as well as increased kernel hardness and total protein content. The genetic and geographic diversity of sorghum makes it an adaptable crop, essential for breeding and diversity studies. Genome-wide association studies (GWAS) have emerged as essential tools for identifying candidate genes linked to key traits, thereby advancing genetic improvement initiatives, particularly for Ethiopian sorghum landraces. Advances in genotyping techniques, particularly genotyping-by-sequencing (GBS) and association mapping, have facilitated the identification of quantitative trait loci (QTL) associated with grain quality, enhancing breeding efficiency and the development of resilient, high-quality sorghum varieties. This review explored the genetic and phenotypic diversity of sorghum, focusing on grain quality traits, molecular mechanisms, and responses to drought stress.

Amoebas: the omnipotent organism and silent assassin.

Amoebas are characterized by their unique ability to exist both as free-living organisms and, occasionally, as parasites within host tissues, earning them the designation 'amphizoic amoebae'. While amoebic infections are less prevalent, their health impact can be tremendous, leading to several diseases. In low-income countries, poor sanitation and socioeconomic conditions significantly increase the risk of amoebic infections, particularly E. histolytica, which affects up to 50 million people and causes over 100,000 deaths each year. Diagnostic methods, including microscopy, serological tests, polymerase chain reaction, and the loop-mediated isothermal amplification assay, have improved the accuracy and timeliness of amoeba diagnosis. However, these methodologies are often cost-prohibitive for developing countries. Conversely, current treatments involve aggressive protocols using antibiotics, antifungals, and anticancer agents. However, the prognosis for severe infections such as Primary Amoebic Meningoencephalitis and Granulomatous Amebic Encephalitis remains poor. Despite advancements, effective treatments, and new low-cost therapeutic options are still being researched. Thus, the current review sought to provide a description of molecular aspects such as amoeba virulence factors and invasion processes, focusing on recent advances in the detection, identification, and treatment of associated diseases.

Analysis of the public art value of Huizhou three carvings from the perspectives of biomechanics and biology: Digitization, inheritance, and their impact on the development of museum city

This paper explores the three carvings in Huizhou from a novel perspective integrating cell molecular biomechanics. Taking the stone carving, wood carving, and pottery carving of the Ming Dynasty as examples, after gathering relevant literature via the network and classification, microscopic and scanning techniques were employed. The granite used in stone carving, at a cell molecular level, consists of silicate minerals with strong covalent bonds. These bonds endow the stone with hardness and resistance to deformation. The cells and molecules within the granite are arranged in a crystalline lattice, which dictates its mechanical properties. Mahogany in wood carving has cellulose and lignin molecules. The lignin provides rigidity and hydrophobicity, protecting the wood cells from moisture and external mechanical stresses. In pottery carving, the clay particles are sintered together during firing, creating a new molecular structure. The formation of a grease protective film and oxide on the brick carving is a result of molecular interactions at the surface. This layer can be seen as a self-assembled molecular barrier, similar to how cell membranes protect cells. The axisymmetric modeling and downward center of gravity influence the stress distribution at a molecular scale. A streamlined shape may reduce air or fluid resistance, minimizing mechanical forces acting on the carving's surface molecules. The delicate material with small particles implies a specific microstructure that affects its mechanical behavior. Understanding these cell molecular biomechanical aspects not only reveals the hidden scientific secrets of Huizhou carvings but also aids in their conservation and restoration. It enriches our comprehension of their durability and aesthetic qualities from a microscopic and molecular vantage point, further enhancing their cultural and digital significance in the context of the museum city's development.

Molecular aspects of cell-penetrating peptides: key amino acids, membrane partners, and non-covalent interactions

Molecular aspects of cell-penetrating peptides: key amino acids, membrane partners, and non-covalent interactions

The Importance of Edible Medicinal Mushrooms and Their Potential Use as Therapeutic Agents Against Insulin Resistance.

In addition to conventional treatments, there is growing interest in preventive and complementary therapies. Proper nutrition can prevent the manifestation of several chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer, and can attenuate the severity of these diseases. Edible mushrooms have been used as nutrition and medicine for thousands of years. The spectrum and quantity of their medicinal compounds made them a widely investigated target both in basic research and clinical trials. The most abundant and medically important components are polysaccharides, terpenoids, phenols, and heterocyclic amines, but bioactive proteins, vitamins, including vitamin D, polyunsaturated fatty acids, and essential minerals are also important ingredients with noteworthy health benefits. Mushroom extracts have anti-diabetic, anti-hyperlipidemic, anti-inflammatory, antioxidant, cardioprotective, anti-osteoporotic, and anti-tumor effects and are well tolerated, even by cancer patients. In our previous review we detailed the molecular aspects of the development of type 2 diabetes, discussing the role of physical activity and diet, but we did not detail the role of medicinal mushrooms as part of nutrition. In this review, we aimed to summarize the most important medical mushrooms, along with their natural habitats, growing conditions, and components, that are presumably sufficient for the prevention and treatment of insulin resistance.

Mouse models for metabolic health research: molecular mechanism of exercise effects on health improvement through adipose tissue remodelling.

Exercise provides health benefits to multiple metabolic tissues through complex biological pathways and interactions between organs. However, investigating these complex mechanisms in humans is still limited, making mouse models extremely useful for exploring exercise-induced changes in whole-body metabolism and health. In this review, we focus on gaining a broader understanding of the metabolic phenotypes and molecular mechanisms induced by exercise in mouse models. We first discuss the differences in adaptations induced by aerobic and resistance exercise, and compare voluntary wheel running and forced treadmill exercise, the two main methods of aerobic exercise research in mice, to show the similarities and differences between the same aerobic exercise but different methods, and their impact on experimental outcomes. The effects of exercise on metabolic phenotypes, including alleviation of obesity and metabolic disorders, and the mechanisms involved in adipose tissue remodelling and browning are explored, as well as the role of the gut microbiota in mediating the physiological responses and metabolic effects of exercise. Understanding these molecular mechanisms and methodological aspects of exercise experiments in mouse models can serve as a valuable template for the design of future basic research in exercise physiology and will provide a strong scientific evidence base for optimizing the design of exercise intervention programmes for metabolic health.

High Nutritional Conditions Influence Feeding Plasticity in Pristionchus pacificus and Render Worms Non-Predatory.

Developmental plasticity, the ability of a genotype to produce different phenotypes in response to environmental conditions, has been subject to intense studies in the last four decades. The self-fertilising nematode Pristionchus pacificus has been developed as a genetic model system for studying developmental plasticity due to its mouth-form polyphenism that results in alternative feeding strategies with a facultative predatory and non-predatory mouth form. Many studies linked molecular aspects of the regulation of mouth-form polyphenism with investigations of its evolutionary and ecological significance. Also, several environmental factors influencing P. pacificus feeding structure expression were identified including temperature, culture condition and population density. However, the nutritional plasticity of the mouth form has never been properly investigated although polyphenisms are known to be influenced by changes in nutritional conditions. For instance, studies in eusocial insects and scarab beetles have provided significant mechanistic insights into the nutritional regulation of polyphenisms but also other forms of plasticity. Here, we study the influence of nutrition on mouth-form polyphenism in P. pacificus through experiments with monosaccharide and fatty acid supplementation. We show that in particular glucose supplementation renders worms non-predatory. Subsequent transcriptomic and mutant analyses indicate that de novo fatty acid synthesis and peroxisomal beta-oxidation pathways play an important role in the mediation of this plastic response. Finally, the analysis of fitness consequences through fecundity counts suggests that non-predatory animals have an advantage over predatory animals grown in the glucose-supplemented condition.

Evolutionary lineage-specific genomic imprinting at the ZNF791 locus.

Genomic imprinting is an epigenetic process that results in parent-of-origin effects on mammalian development and growth. Research on genomic imprinting in domesticated animals has lagged due to a primary focus on orthologs of mouse and human imprinted genes. This emphasis has limited the discovery of imprinted genes specific to livestock. To identify genomic imprinting in pigs, we generated parthenogenetic porcine embryos alongside biparental normal embryos, and then performed whole-genome bisulfite sequencing and RNA sequencing on these samples. In our analyses, we discovered a maternally methylated differentially methylated region within the orthologous ZNF791 locus in pigs. Additionally, we identified both a major imprinted isoform of the ZNF791-like gene and an unannotated antisense transcript that has not been previously annotated. Importantly, our comparative analyses of the orthologous ZNF791 gene in various eutherian mammals, including humans, non-human primates, rodents, artiodactyls, and dogs, revealed that this gene is subjected to genomic imprinting exclusively in domesticated animals, thereby highlighting lineage-specific imprinting. Furthermore, we explored the potential mechanisms behind the establishment of maternal DNA methylation imprints in porcine and bovine oocytes, supporting the notion that integration of transposable elements, active transcription, and histone modification may collectively contribute to the methylation of embedded intragenic CpG island promoters. Our findings convey fundamental insights into molecular and evolutionary aspects of livestock species-specific genomic imprinting and provide critical agricultural implications.

Whole genome sequencing, assembly and annotation of the Southern Ground Hornbill – Bucorvus leadbeateri

The Southern Ground Hornbill (SGH – Bucorvus leadbeateri) is one of the largest hornbill species worldwide, known for its complex social structures and breeding behaviours. This bird has been of great interest due to its declining population and disappearance from historic ranges in southern Africa. Despite being the focus of numerous conservation efforts, with research forming an integral part of these initiatives, there is still a substantial lack of knowledge regarding the molecular biology aspects of this bird species. In this study, whole genome sequencing of the SGH was achieved using Illumina short-read (NovaSeq 6000) and Pacific Biosciences long-read technologies. A hybrid de novo genome assembly followed by reference-based refinement produced a 1.16 Gb high-quality draft genome assembly of the SGH comprised of 1,672 contigs (N50 value of 40.45 Mb). The availability of this genome will aid in improving our current understanding of this bird at a genomic level and provide a pivotal foundation for comparative genomic analysis with other hornbill species.

Celiac Disease: A Transitional Point of View.

Celiac disease (CeD) is a chronic, lifelong, multifactorial, polygenic, and autoimmune disorder, characteristically triggered by exposure to the exogenous factor "gluten" in genetically predisposed individuals, with resulting duodenal inflammation and enteropathy, as well as heterogeneous multisystemic and extraintestinal manifestations. The immunopathogenesis of CeD is complex, favored by a peculiar human leukocyte antigen (HLA) genetic predisposition, leading to gluten presentation by antigen-presenting cells to CD4+ T helper (Th) cells, T cell-B cell interactions, and production of specific antibodies, resulting in the immune-mediated killing of enterocytes and, macroscopically, in duodenal inflammation. Here, the most relevant correlations between cellular and molecular aspects and clinical manifestations of this complex disease are reviewed, with final considerations on nutritional aspects for disease management.

Generation and Characterization of a Knockout Mouse of an Enhancer of EBF3.

Genomic studies of autism and other neurodevelopmental disorders have identified several relevant protein-coding and noncoding variants. One gene with an excess of protein-coding de novo variants is EBF3 that also is the gene underlying the Hypotonia, Ataxia, and Delayed Development Syndrome (HADDS). In previous work, we have identified noncoding de novo variants in an enhancer of EBF3 called hs737 and further showed that there was an enrichment of deletions of this enhancer in individuals with neurodevelopmental disorders. In this present study, we generated a novel mouse line that deletes the highly conserved, orthologous mouse region of hs737 within the Rr169617 regulatory region, and characterized the molecular and phenotypic aspects of this mouse model. This line contains a 1,160 bp deletion within Rr169617 and through heterozygous crosses we found a deviation from Mendelian expectation (p = 0.02) with a significant depletion of the deletion allele (p = 5.8 × 10 -4 ). Rr169617 +/- mice had a reduction of Ebf3 expression by 10% and Rr169617 -/- mice had a reduction of Ebf3 expression by 20%. Differential expression analyses in E12.5 forebrain, midbrain, and hindbrain in Rr169617 +/+ versus Rr169617 -/- mice identified dysregulated genes including histone genes ( i.e., Hist1h1e , Hist1h2bk , Hist1h3i , Hist1h2ao) and other brain development related genes (e.g., Chd5 , Ntng1 ). A priori phenotyping analysis (open field, hole board and light/dark transition) identified sex-specific differences in behavioral traits when comparing Rr169617 -/- males versus females; whereby, males were observed to be less mobile, move slower, and spend more time in the dark. Furthermore, both sexes when homozygous for the enhancer deletion displayed body composition differences when compared to wild-type mice. Overall, we show that deletion within Rr169617 reduces the expression of Ebf3 and results in phenotypic outcomes consistent with potential sex specific behavioral differences. This enhancer deletion line provides a valuable resource for others interested in noncoding regions in neurodevelopmental disorders and/or those interested in the gene regulatory network downstream of Ebf3 .

The Rise of Fentanyl: Molecular Aspects and Forensic Investigations.

Fentanyl is a synthetic opioid widely used for its potent analgesic effects in chronic pain management and intraoperative anesthesia. However, its high potency, low cost, and accessibility have also made it a significant drug of abuse, contributing to the global opioid epidemic. This review aims to provide an in-depth analysis of fentanyl's medical applications, pharmacokinetics, metabolism, and pharmacogenetics while examining its adverse effects and forensic implications. Special attention is given to its misuse, polydrug interactions, and the challenges in determining the cause of death in fentanyl-related fatalities. Fentanyl misuse has escalated dramatically, driven by its substitution for heroin and its availability through online platforms, including the dark web. Polydrug use, where fentanyl is combined with substances like xylazine, alcohol, benzodiazepines, or cocaine, exacerbates its toxicity and increases the risk of fatal outcomes. Fentanyl undergoes rapid distribution, metabolism by CYP3A4 into inactive metabolites, and renal excretion. Genetic polymorphisms in CYP3A4, OPRM1, and ABCB1 significantly influence individual responses to fentanyl, affecting its efficacy and potential for toxicity. Fentanyl's side effects include respiratory depression, cardiac arrhythmias, gastrointestinal dysfunction, and neurocognitive impairments. Chronic misuse disrupts brain function, contributes to mental health disorders, and poses risks for younger and older populations alike. Fentanyl-related deaths require comprehensive forensic investigations, including judicial inspections, autopsies, and toxicological analyses. Additionally, the co-administration of xylazine presents distinct challenges for the scientific community. Histological and immunohistochemical studies are essential for understanding organ-specific damage, while pharmacogenetic testing can identify individual susceptibilities. The growing prevalence of fentanyl abuse highlights the need for robust forensic protocols, advanced research into its pharmacogenetic variability, and strategies to mitigate its misuse. International collaboration, public education, and harm reduction measures are critical for addressing the fentanyl crisis effectively.

Sex hormones and allergies: exploring the gender differences in immune responses.

Allergies are closely associated with sex-related hormonal variations that influence immune function, leading to distinct symptom profiles. Similar sex-based differences are observed in other immune disorders, such as autoimmune diseases. In allergies, women exhibit a higher prevalence of atopic conditions, such as allergic asthma and eczema, in comparison to men. However, age-related changes play a significant role because men have a higher incidence of allergies until puberty, and then comes a switch ratio of prevalence and severity in women. Investigations into the mechanisms of how the hormones influence the development of these diseases are crucial to understanding the molecular, cellular, and pathological aspects. Sex hormones control the reproductive system and have several immuno-modulatory effects affecting immune cells, including T and B cell development, antibody production, lymphoid organ size, and lymphocyte death. Moreover, studies have suggested that female sex hormones amplify memory immune responses, which may lead to an excessive immune response impacting the pathogenesis, airway hyperresponsiveness, inflammation of airways, and mucus production of allergic diseases. The evidence suggests that estrogens enhance immune humoral responses, autoimmunity, mast cell reactivity, and delayed IV allergic reactions, while androgens, progesterone, and glucocorticoids suppress them. This review explores the relationship between sex hormones and allergies, including epidemiological data, experimental findings, and insights from animal models. We discuss the general properties of these hormones, their effects on allergic processes, and clinical observations and therapeutic results. Finally, we describe hypersensitivity reactions to these hormones.

Antioxidant Properties of Albumin and Diseases Related to Obstetrics and Gynecology.

Albumin, the most abundant protein, contributes significantly to various physiological processes, indicating its multifunctional properties. It has drawn the attention of scientists and physicians because of its primary role in maintaining osmotic pressure and involvement in transporting numerous small molecules, including hormones, fatty acids, and drugs. A growing body of evidence has recently illustrated an additional aspect of albumin's antioxidant properties. Therefore, based on recent research findings, this review article delves into the molecular and biochemical aspects of albumin's antioxidative capabilities. We highlight the multifaceted significance of proteins in oxidative stress and their relation to pathologies in obstetrics and gynecology. In particular, we focused on preeclampsia, in which oxidative stress is closely involved in the pathogenesis, and renal dysfunction leads to increased albumin excretion into the urine, resulting in hypoalbuminemia. In addition, we discussed the role of albumin in preeclampsia pathogenesis, diagnosis, and patient prognosis. Understanding the antioxidant properties of albumin opens new avenues for therapeutic intervention and sheds light on novel strategies for combating preeclampsia associated with oxidative damage. In this study, we employed the PubMed database to search for articles that assessed the antioxidant properties of albumin, with a specific focus on obstetric diseases, particularly preeclampsia. The last update of the search was conducted in November 2024.

Malian field isolates provide insight into Plasmodium malariae intra-erythrocytic development and invasion.

Plasmodium malariae is the third most prevalent human malaria parasite species and contributes significantly to morbidity. Nevertheless, our comprehension of this parasite's biology remains limited, primarily due to its frequent co-infections with other species and the lack of a continuous in vitro culture system. To effectively combat and eliminate this overlooked parasite, it is imperative to acquire a better understanding of this species. In this study, we embarked on an investigation of P. malariae, including exploring its clinical disease characteristics, molecular aspects of red blood cell (RBC) invasion, and host-cell preferences. We conducted our research using parasites collected from infected individuals in Mali. Our findings revealed anaemia in most of P. malariae infected participants presented, in both symptomatic and asymptomatic cases. Regarding RBC invasion, quantified by an adapted flow cytometry based method, our study indicated that none of the seven antibodies tested, against receptors known for their role in P. falciparum invasion, had any impact on the ability of P. malariae to penetrate the host cells. However, when RBCs were pre-treated with various enzymes (neuraminidase, trypsin, and chymotrypsin), we observed a significant reduction in P. malariae invasion, albeit not a complete blockade. Furthermore, in a subset of P. malariae samples, we observed the parasite's capability to invade reticulocytes. These results suggest that P. malariae employs alternative pathways to enter RBCs of different maturities, which may differ from those used by P. falciparum.

Canine mammary tumors as a promising adjunct preclinical model for human breast cancer research: similarities, opportunities, and challenges.

Despite significant progress in the field of human breast cancer research and treatment, there is a consistent increase in the incidence rate of 0.5 percent annually, posing challenges in the development of effective novel therapeutic strategies. The failure rate of drugs in clinical trials stands at approximately 95%, primarily attributed to the limitations and lack of reliability of existing preclinical models, such as mice, which do not mimic human tumor biology. This article examines the potential utility of canine mammary tumors as an adjunct preclinical model for investigating human breast cancer. Given the numerous similarities between canine and human breast cancer, canines present a promising alternative model. The discussion delves into the intricate molecular and clinical aspects of human breast cancer and canine mammary tumors, shedding light on the tumors' molecular profiles, identifying specific molecular markers, and the application of radiological imaging modalities. Furthermore, the manuscript addresses the current constraints of preclinical cancer studies, the benefits of using canines as models, and the obstacles linked to the canine mammary tumors model. By concentrating on these elements, this review aims to highlight the viability of canine models in enhancing our understanding and management of human breast cancer.

Identification and structure-guided development of triazole urea-based selective antagonists of Arabidopsis karrikin signaling

The smoke-derived butenolides, karrikins (KARs), regulate many aspects of plant growth and development. However, KARs and a plant hormone, strigolactones (SLs), have high resemblance in signal perception and transduction, making it hard to delineate KARs response due to the shortage of chemical-genetic tools. Here, we identify a triazole urea KK181N1 as an inhibitor of the KARs receptor KAI2. KK181N1 selectively depress the KAR-induced phenotypes in Arabidopsis. We further elucidate the antagonistic, KAI2 binding mechanism of KK181N1, showing that KK181N1 binds to the catalytic pockets of KAI2 in a non-covalent binding manner. Our experiments also demonstrate the binding affinity of triazole urea compounds are regulated by the structured water molecule networks. By fine-tuning this network, we successfully develop a more potent derivative of KK181N1. We anticipate that these chemicals will be applicable to the elucidation of KARs biology, especially for discriminating the molecular and physiological aspects of KARs and SL signaling.

Omics approaches: Role in acute myeloid leukemia biomarker discovery and therapy.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults and has the highest fatality rate. Patients aged 65 and above exhibit the poorest prognosis, with a mere 30 % survival rate within one year. One important issue in optimizing outcomes for AML patients is their limited ability to predict responses to specific therapies, response duration, and likelihood of relapse. Despite rigorous therapeutic interventions, a significant proportion of patients experience relapse. Consequently, there is a pressing need to introduce new targets for therapy. Sequencing and biotechnology have come a long way in the last ten years. This has made it easier for many omics technologies, like genomics, transcriptomics, proteomics, and metabolomics, to study molecular mechanisms of AML. An integrative approach is necessary to understand a complex biological process fully and offers an important opportunity to understand the information underlying diseases. In this review, we studied papers published between 2010 and 2024 employing omics approaches encompassing diagnosis, prognosis, and risk stratification of AML. Finally, we discuss prospects and challenges in applying -omics technologies to the discovery of novel biomarkers and therapy targets. Our review may be helpful for omics researchers who want to study AML from different molecular aspects.

Molecular diagnosis and epidemiological aspects of cutaneous Leishmaniasis in Aleppo: Current status

Molecular diagnosis and epidemiological aspects of cutaneous Leishmaniasis in Aleppo: Current status

EMSPLA for accurate feature molecular extraction from protein-ligand interactions

Protein-ligand interactions are fundamental in various biological and medical fields, influencing drug discovery and therapeutic development. In recent years, deep learning (DL) has revolutionized the study of these interactions, but significant challenges remain in accurately representing molecular structures for DL models. Traditional featurization techniques often depend on handcrafted features, requiring expert knowledge and potentially missing crucial molecular aspects. This work addresses these challenges by developing and evaluating a novel protein-ligand feature extraction system using an enhanced molecular similarity protein-ligand aligner (EMSPLA). The primary objective is to leverage EMSPLA for similarity matching in protein-ligand interactions, improving predictive model accuracy. The methodology combines convolutional neural networks (CNN) for local feature extraction with an attention module to capture long-distance dependencies, enhancing binding site predictions. Using the PDBbind v.2020 dataset, the EMSPLA model demonstrated superior performance with a root mean square error (RMSE) of 0.67, surpassing current state-of-the-art models. These findings highlight the system’s potential for efficient deployment and scalability, positioning it as a powerful tool in computational biology and drug discovery, ultimately advancing our understanding of protein-ligand interactions.