Open Access Pub publishes peer-reviewed, free-to-read open-access articles. Showing
articles matching Phenotype — open any to read the full text,
or download the PDF or XML.
Dec 2023 DOI 10.14302/issn.3070-1937.ijbt-23-4714
M. Gaji AhmedCorresponding author
Background and Objectives Duffy (FY) blood group system is implicated in transfusion incompatibilities and haemolytic disease of the foetus and newborn (HDFN). The primary objective was to determine the Duffy phenotype among indigenous pregnant women in Gombe, Gombe State, Nigeria. Materials and Methods This was a Cross sectional study where simple random sampling was employed on consented participants. Two hundred and fifty nine pregnant women attending antenatal clinic at Federal Teaching Hospital Gombe were randomly recruited into the study. About 3mls of blood was taken, and Duffy antigen typed by standard tube technique (LORNE LABORATORY UK). Results Among the Indigenous tribe, the percentage of Fy(a+b+) was seen in 2.2% of Fulani and 3.4% of Tangale, Fy(a+b-) phenotype was seen in 4.3% of Tangale, 6.8% of Fulani,9.5% of Tera, 10.3% of Hausa and 10.5% of Waja. Fy(a-b+) phenotype was seen in 5.3% of Waja, 7.6% of Fulani,8.7% of Tangale, 9.5% of Tera and 12.5% of Bolawa. Fy(a-b-) phenotype was seen in 2.4% of Tula,6.4% of Bolawa,7.3% of Waja, 7.8% of Tera, 17.8% of Tangale, 11.8% of Hausa and 46.5% of Fulani. About 84.6% of the study population had the null Duffy phenotype. Conclusion The research showed the phenotypic distribution of Duffy blood group among the study participants with relatively high percentage of null Duffy phenotype hence possible risk of alloimmunisation.
Jul 2020 DOI 10.14302/issn.2379-7835.ijn-20-3463
Lemogoum DanielCorresponding author
Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
Background Evidence suggests that low birth weight (LBW) is associated with increased cardiovascular and metabolic risk in adulthood, including increased arterial stiffness, a marker of early vascular aging (EVA) assessable by pulse wave velocity (PWV), obesity and glucose homeostasis abnormalities. The present study aimed to explore the late impact of LBW on PWV and cardiometabolic phenotypes among young adult Cameroonians. Methods The study evaluated 120 subjects (mean age: 26 ± 5 years; 54% male sex) at the Cameroon Heart Institute, Douala, Cameroon, between January and June 2018. Birth weight (BW) and gestational age, sociodemographic, anthropometrics and fasting capillary blood glucose were recorded in all participants. Blood pressure (BP) and PWV were measured using an automatic oscillometric device (Mobil-O-Graph®). Multiple-adjusted linear regression was used to determine predictive factors for PWV. For assessment of potential impact of BW on EVA, PWV was adjusted for age, sex, body mass index (BMI) and mean arterial pressure (MAP). Results 28 participants (23.3%) of the study sample had LBW (<3000g). There was no gender difference between LBW or normal birth weight patients (NBW; controls). Age- and MAP-adjusted PWV (aPWV) were higher in women with LBW compared to NBW (5.6 m/s and 5.3 m/s respectively, P = 0.038). In men, aPWV was similar in LBW and NBW. In this study population, aPWV was higher (on average +15 cm/s) in LBW than in controls, although the difference was not statistically significant (P=0.083). Multivariate regression analysis showed age, male sex, BMI and MAP were independent determinants of PWV, but not LBW. Compared to NBW controls, the prevalence of overweight/obesity, impaired glucose homeostasis and diabetes was higher in LBW: 42.9% vs 37%; 10.7% vs 3.3%, and 3.6 % vs 1.1%, respectively. Moreover, compared with controls, LBW individuals who were overweight/obese in adulthood had a much higher mean fasting capillary glucose (1.54 ±0.17 g/l vs 0.87 ±0.11 g/l in NBW, p=0.003). Conclusion This study suggests that although LBW is associated with increased aortic stiffness in young adulthood, mainly in women, the association was predominantly driven by aging, MAP, BMI and male sex. In adulthood, LBW subjects exhibited higher obesity indices and altered glucose homeostasis.
Aug 2018
Sh. Badawy M.Corresponding author
Chest Department, Qena Faculty of medicine, South Valley University, Egypt
Background: Co-morbidities are associated with increasing risk of mortality, hospitalizations and costs of treatment in Chronic Obstructive Pulmonary Disease patients. Identification of Co- morbidities related to COPD phenotypes may guide individualized therapies and achieve better prognosis. Methods: A prospective study of one hundred ten patients of confirmed COPD diagnosis were carried out and divided into five different phenotypes with related co-morbidities. History taking, clinical examination, Chest X-ray, Computed chest Tomography, laboratory investigations, arterial blood gas, Echocardiography and Electrocardiography were done for all patients. St. George’s Respiratory Questionnaire, COPD assessment test (CAT score) and BODEx (BMI, FEV1, dyspnea and exacerbations) were used for assessment of disease impact on quality of life, severity, and exacerbation respectively. Results: Emphysema group were 31% among all cases with mean age 61.8±9.1, frequent exacerbator group and Chronic bronchitis phenotype were 18% with mean age 64.4±11.3, and 48.8±9 respectively. COPD with bronchiectasis group were 19% with mean age 60.3±6 and Asthma COPD Overlap Syndrome (ACOS) were 12% with mean age 62.8±15.8. There was significant difference as regards age between different group of phenotypes P- value <0.001. There was significance difference in BODEx index and in (CAT) score among different COPD phenotypes P-value 0.020, 0.001 respectively. There was significant difference in all items of SGRQ among different COPD phenotypes P–value 0.001. Diabetes was commonly presented in 50 % ACOS cases, Ischemic heart disease was present more in Emphysema 22.9%, Osteoporosis was more in COPD with bronchiectasis 28.6%, Cor-pulmonale was more present in frequent excerbator 65%, and Anemia more common in COPD with bronchiectasis 23.8%. Depression was more common in frequent excerbator phenotype (45.0 %). Gastro-esophageal reflux was the most common co-morbidities (58 %) then cor-pulmonale 41.8%, systemic hypertension 40 % and pulmonary hypertension 28%. Conclusion: The presence of significant co-morbidities is important modifying risk factors for severity in COPD. They contribute to the overall severity in individual patients, have a major impact on quality of life, and major causes of hospitalization. Co-morbidities can be associated with any clinical phenotype.
Dec 2017 DOI 10.14302/issn.2576-6694.jbbs-17-1869
de Cassia Stocco RitaCorresponding author
Genetics Laboratory, Butantan Institute, São Paulo-SP, Brazil
Introduction Bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, infectious and neoplastic disease, characterized by the presence of multiple papillomas that can regress spontaneously or to persist and progress to malignancies when in association with environmental cofactors. Although recognized that the BPV can induce DNA damages, the viral role following cancer initiation remains unresolved. Based on this, we stablished cell lines derived from cutaneous papilloma, fibropapilloma and esophageal carcinoma to study the BPV action on epithelial-mesenchymal transition (EMT). Our results showed strong evidences that the virus action can contribute to EMT and, therefore, metastasis. Aim In this study, we analyzed the expression levels of the EMT markers (cytokeratin 10, STAT3 Y705, Oct-3/4 and vimentin) in paraffin-embed samples, using the same tissues that originated the cell lines previous studied, aiming to validate the results observed using cell lines. Material and Methods Expression levels of these markers was analyzed by immunohistochemistry and the collagen composision by Picrosirius red staining. Results We verified an overexpression of these markers in fibroblastoid cells present into the epidermis and ketarinocyte-like cells into the dermis present in dermo-epidermal junction. These data reinforce our previous results using cell cultures, validating both systems (cell culture and paraffin-embed tissues) as useful models to study the natural history of BPV-infected lesions. Conclusion Altogether, the results from these systems indicate that the BPV promote the cancer progression and metastasis through the transdifferentiation of an epithelial to mesenchymal cells (EMT).
Jun 2015 DOI 10.14302/issn.2379-7835.ijn-14-591
Negri RossellaCorresponding author
Department of Translational Medicine, Pediatrics, European Laboratory for Food Induced Diseases, University of Naples Federico II, Italy.
Objectives Taste sensitivity is an important determinant of food choice and differs between children and adults. This difference is probably due to several factors that constitute an individual’s phenotype. The aim of this study was to explore taste perception in relation to the TAS2R38 and CAVI (gustin) genotypes in age classes from infancy to adulthood in a Mediterranean population. Methods In this cross-sectional study we evaluated the TAS2R38 and gustin genotypes and administered a standardized PROP taste test in 705 individuals (435 adults, 270 children); the sample included 224 mother-child dyads. We also explored the acceptance and consumption of bitter and non-bitter vegetables. Results Sensitivity to bitterness was strongly related to the TAS2R38 haplotype, and we observed an intriguing relationship with age. In fact, children were more sensitive than adults with the same TAS2R38 haplotype also within mother-child dyads. The mother-child tasting differences decreased with age and became minimal when children reached adolescence. Variations in the gustin gene did not contribute significantly to the overall taste phenotype, but helped to differentiate among non-tasters. Conclusions The genetic profile of the bitter-taste receptor TAS2R38 explains most of the variance in bitter taste perception, but the related phenotype is also strongly influenced by age, also in mother-child dyads that share the same genotype. This finding is likely to have a significant impact on the complex feeding relationship between mother and child.
Feb 2026 DOI 10.14302/issn.2689-4602.jes-25-5926
Easttom ChuckCorresponding author
The impact of ionizing radiation on genetic change is well established, yet the extent to which naturally occurring radiation fields have influenced evolutionary trajectories remains incompletely understood. This study examined correlations between microbial evolution and the radiation and geochemical environments associated with natural fission reactors, with emphasis on the Oklo–Bangombé system in present-day Gabon, Africa. The current paper compares plausible doserate regimes adjacent to reactor zones with published observations of radiationinduced phenotypes, geneexpression changes, and repair strategies in model organisms and complex biotas. This study further considers indirect mechanisms (e.g., water radiolysis, redox restructuring, tracemetal mobilization) by which natural reactors could have modulated ecological selection pressures over long timescales. The synthesis supports the plausibility of three interacting pathways: (i) increased mutation supply under low, chronic dose rates; (ii) selection in oxidantrich, redoxstratified niches; and (iii) metabolic subsidies (e.g., H₂) from radiolysis that support chemotrophic guilds. Although temporal–spatial associations exist between reactor activity and biological innovations preserved in Paleoproterozoic strata of Gabon, current evidence remains correlational rather than demonstrably causal. The study further outlines testable predictions and experimental designs capable of discriminating among these mechanisms.
Sep 2024 DOI 10.14302/issn.2690-4721.ijcm-24-5195
Mutile Kavai SusanCorresponding author
The persistence of multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) is a challenge especially in regions where typhoid is endemic. Surveillance of circulating genotypes of MDR S. Typhi is crucial in typhoid acute cases and carriers. This study aimed to investigate genotypic diversity of S. Typhi from symptomatic and asymptomatic children in endemic settings in Nairobi, Kenya. Symptomatic and asymptomatic individuals’ ≤ 16 years were recruited at four health facilities and tested for typhoid through stool cultures. The S. Typhi isolates were subjected to antibiotic susceptibility testing to investigate multidrug resistance. The MDR S. Typhi isolates’ DNA was extracted and illumina sequenced. Raw reads were de novo assembled and analyzed by pathogen-watch. From the 90 sequenced isolates, 60 (67%) were confirmed to be S. Typhi (sequence Type 1 and genotype 4.3.1). Out of the 60 S. Typhi strains; 39 (65%) had plasmids, from these 38 (97%) had IncHI1 plasmids alone. Out of the 60, 59 (98%) S. Typhi isolates had blaTEM-1D. Point mutations conferring reduced susceptibility to quinolones were detected in 42 (70%) of S. Typhi isolates, from these; 14 (33%) had gyrA S83Y , and 28 (67%) gyrB S464F genes, respectively. This study reports 4.3.1 (H58) as the most dominant S. Typhi genotype responsible for spread of MDR phenotypes carried on IncHI1 plasmids. Presence of MDR S. Typhi with resistance genes such as blaTEM-1Dand reduced susceptibility to ciprofloxacin especially among asymptomatic individuals, reiterates the need for use of typhoid conjugate vaccine among vulnerable children as a control and prevention measure against typhoid.
Sep 2023 DOI 10.14302/issn.2574-4496.jtc-23-4722
J. Conway PatrickCorresponding author
Background Patients with distant metastatic Medullary Thyroid Carcinoma (MTC) have an estimated 40% ten-year survival rate. Gain of function mutations in the REarranged during Transfection or RET gene in MTC can result in an aggressive phenotype resistant to traditional therapy. In this case report, we describe the treatment of an MTC patient with a unique RET kinase deletion mutation. Case presentation Since diagnosis, 21 years ago, this patient has had chronically elevated calcitonin levels (>40,000 pg/mL) that was unable to be controlled by conventual therapy and clinical trials. As result of uncontrolled MTC, metastatic disease was found in the spine, liver, and lungs. Circulating tumor DNA (ctDNA) analysis identified a RET 898-901Del mutation, reported as a variant of unknown significance. The treating physician identified that the deletion was in the activation loop of RET kinase and considered that the mutation was constitutively activating RET kinase. The patient was prescribed Pralsetinib, a small molecule inhibitor targeting the ATP binding site of RET. Pralsetinib treatment achieved a durable response and was able to significantly decrease serum calcitonin levels (<200 pg/mL) and tumor size. Conclusion This RET deletion mutation is a pathogenic mutation with comparable enzymatic activity to the more common RET M918T mutation. The case report highlights the versatility of structural biologic approaches to guide therapeutic decisions.
Aug 2023
Almabadi BayanCorresponding author
DADA2 (deficiency of adenosine deaminase type 2) is an autoinflammatory autosomal recessive disease resulting from biallelic loss of function mutations in ADA2 gene. Clinical presentation and age of onset vary widely even among related patients, and variability of symptoms and severity manifestations include bone marrow failure, autoinflammation, immunodeficiency and vasculitis. Here, we report a case of young male with adult onset DADA2, who presented with fever, lower limbs skin rash, joint pain, and anemia resembling systemic lupus erythematous (SLE). DADA2 has an extremely variable clinical phenotype. It was described into three categories: inflammatory/vascular, immune dysregulation, and hematologic. However, the data is scant in describing autoimmunity phenotype in DADA2 and further studies are required to investigate the clinical correlation and presence of autoantibodies. We recommend genetic testing in cases with lupus-like disease especially if there is consanguinity between parents and family history of vasculitis.
Sep 2022 DOI 10.14302/issn.2641-4538.jphi-22-4238
Bavbek SevimCorresponding author
Department of Chest Disease, Division of Allergy and Clinical Immunology, Ankara University, School of Medicine, Ankara, Turkey
The safety of cyclooxygenase (COX)-2 inhibitors has been tested in patients who had cross-reactive hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs). However, these studies have been mainly done before the current classification of NSAID hypersensitivity and cross-reaction between COX-2 inhibitors has been rarely reported.We aimed to assess tolerability of COX-2 inhibitors and to evaluate the cross-reactivity between them in cross-reactive phenotype of NSAID hypersensitivity. The diagnosis was based on clinical features, reliable history of HSRs to at least two chemically different NSAIDs, and/or positive provocation tests with implicated NSAIDs in 151 patients. Single-blind, oral challenges with 1/4 and 3/4 divided doses of placebo, nimesulide, meloxicam, and celecoxib, as COX-2 inhibitors, were performed. The most common cross-reactive phenotype was NSAID-induced urticaria/angioedema (56.3%). Positive reactions to meloxicam, nimesulide, and celecoxib challenges were observed in 23/140 (16.4%), 7/33 (21.2%), and none of six patients, respectively. Overall, 24 patients were tested with two, one was tested with three COX-2 inhibitors. Six (31.6%) of 19 patients with meloxicam intolerance reacted to nimesulide provocation. Nimesulide, meloxicam, and celecoxib appeared safe alternatives in cross-reactive phenotypes of NSAID hypersensitivity. Although celecoxib has the most favorable tolerability, cross-reactivity among COX-2 inhibitors seems to be possible.
Oct 2021 DOI 10.14302/issn.2639-3166.jar-21-3952
Narain PremCorresponding author
Professor and Independent Researcher, 29278 Glen Oaks Blvd. West, Farmington Hills, USA.
This methods‑focused review addresses missing heritability and co‑heritability in genomic studies, considering polygenicity, rare variants, gene–gene and gene–environment interactions, and phenotype definition. It surveys analytical strategies—from improved GWAS modeling to partitioning heritability and family‑based designs—to better capture shared genetic architecture. Recommendations emphasize data integration and robust inference to close current explanatory gaps.
Aug 2021 DOI 10.14302/issn.2641-5518.jcci-21-3914
Yang LiCorresponding author
Department of Endocrinology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan 410000, China.
A patient with Carney complex is reported with a previously undescribed PRKAR1A mutation. The article situates the variant within PKA pathway biology and clinical phenotype, underscoring the value of genetic testing for diagnosis, counseling, and surveillance.
Jul 2020 DOI 10.14302/issn.2576-6694.jbbs-20-3450
M. Mahmoud MagdyCorresponding author
Faculty of Science, Ain Shams University, Cairo Egypt.
Background Hyperphenylalaninemia (HPA) combined with neurological signs due to impaired catecholamine, dopamine and serotonin synthesis. Symptoms may appears in first week of life but most seen in age of 4 months. Atypical PKU disease caused mainly by deficiency in 6-pyruvoyltetrahydropterin synthase (PTPS) involved in synthesis of BH4. Clinical symptoms may include poor sucking, impaired tone, ataxia, and seizures. The purpose of this study was to analyze the genotype-phenotype relation among BH4 deficient patients because of PTPS mutations in different state of Egypt. Methods Suspected PKU patients loaded with phenylalanine/Kuvan, and the level of phe and phe/tyrosine ratio determined using tandem mass spectrometry by dried blood spots. Blood samples of 13 unrelated Egyptian patients were collected for total RNA extraction, amplification of PTPS gene by PCR followed with sequencing by Sanger method and finally mutations were recorded for genetic analysis. Results The mean value of phe in 13 patients decreased after loaded of phenylalanine from 482.5μmol/L to 270.63 μmol/L as well as phe/tyrosine ratio was decreased from 13.4 to 6.36 after 24hour of treatment with Kuvan. Sanger sequencing of PTPS gene of those patient showed 21 SNPs and Indels mutations. The most repeated mutation is a novel 23 base pair homozygous deletion in 12/13; c.200C>T in four patients, a novel c.86A>T in two patients and three different mutations located once in three different patients (novel c.22C>T; novel c.273G>A and 405T>C) among patients. On amino acid predicted sequences 4 different types of mutations on protein level were presented, 1 deletion mutation in seven amino acid and 3 different missense mutations in addition to 2 silent mutations among 13 patients. Conclusion Patients were the first case of clinical diagnosis as hyperphenylalaninemia (HPA) undergoing genetic diagnosis for PTPS deficiency in Egypt. The sever HPA patients with severe nervous system damage mainly accompanied with deletion mutations and should pay more attention to the BH4 deficiency. While mild HPA is associated with base substitution mutations with mainly transition mutations (7/9; 78%). Next-generation sequencing technique can increase the mutation detection rate when the hereditary diseases are highly suspected in clinic.
May 2020 DOI 10.14302/issn.2692-1537.ijcv-20-3357
Klepikov IgorCorresponding author
MD, Professor, Retired
This perspective calls for cross‑disciplinary brainstorming on novel COVID‑19 pneumonia phenotypes. It discusses hypotheses on immune dysregulation, microvascular injury, and tailored respiratory strategies.
Dec 2019 DOI 10.14302/issn.2639-3166.jar-19-3116
Masoero GiorgioCorresponding author
Accademia di Agricoltura di Torino, Italy
Foliar pH is a specific multifaceted parameter that is sensitive to a deficit in soil water and to temperature variations. It also represents a tool that can be used to rapidly phenotype the symbiosis induced in several crops by bio-fertilizers containing Arbuscular Mycorrhizal Fungi. Yearly decreases in foliar pH, which dropped from 3.73 in 2015 to 3.15 in 2017 and then stabilized at around 3.13, have been observed in an experimental vineyard near Torino (Italy) in six grapevine cultivars. In this paper, these curious, original results have been paired with the average sunspots of the 24th sun cycle, proximal to its endpoint. The paired values were highly correlated (r 0.95 P< 0.01), with close parabolic patterns. A lowering in foliar pH has been correlated with a modification of the leaf composition, as characterized by the higher hydration and reinforced wall. An increase in the circulating acidity of the plants has been hypothesized to interfere in a diminution in the general predisposition to block parasite attacks. From this perspective, the retrieval of several historic outbreaks and the long-term systematic monitoring of mud and Erwinia amylovora frequencies have suggested that the hypothesis that links the solar minima with dysfunctions of the plant-pest relationships cannot always be rejected. Cosmic influences pertaining to UV variations are poorly understood in plant physiopathology. Foliar pH appears to be a rapid and simple tool to unveil high-level mechanisms. It is this simple parameter that physiologists and geneticists, but also agronomists, are asked to consider.
Nov 2019 DOI 10.14302/issn.2639-3166.jar-19-3089
Masoero GiorgioCorresponding author
Accademia di Agricoltura di Torino, Italy
The agronomic management of symbiotic (S) inoculations, by means of bio-fertilizers (BF), is aimed at inducing modifications of the plant rhizosphere and thereafter of the phenotype and yield of the crop. It is here shown that the yield response of maize to a symbiotic treatment may be correlated to six easy-to-calculate indicator variables on the basis of the raw foliar pH, NIR-Spectroscopy of leaves, and the NIRS of hay litter-bags from soils. It has been confirmed, in a set of thirteen pairwise comparisons of Symbiotic (S) soil inoculated by BF vs. Control (non-inoculated soil; C), that the inoculation on average acidified the leaves by -3.7% pH units (P<0.0001). The responses in yield ranged from +25.2% to -9.2% (av.ge +3.5%; P = 0.03), but with average null responses in two centers and a significant response (+11%) in a third center. NIR-Tomoscopy scans (No. 574) were also performed on the leaves, and in addition, hay-litter-bags that had previously been buried in fields were dug up after two months, and 431 NIR- scans were acquired. The effect-size on the yield was expressed as the logarithm of the response ratio, i.e. the mean of the inoculated Symbiotic treatment divided by the mean of the non-inoculated Control for each pairwise comparison. A multiple regression model was developed to predict the symbiotic response to the treatment using six independent variables, including the squared litter-bag fingerprints, and an R2adj. level of 0.78 (P=0.01) was reached, with a standard error of ±4%. Validation in one external maize field, with a positive response to bio-fertilizers, demonstrates the juxtaposition of the estimated and accomplished yield. In a second experiment, with 40 pairwise comparisons, the two tested maize varieties did not respond to five types of bio-fertilizer, and the negative results were predicted at 84% (P 0.0012). The soil biota is a key factor for the application of appropriate microbial inoculants in the field, but the genotype/genotype interactions between the microbial strain (s) and the crop cultivar (s) require prior screening to obtain the desired results.
Sep 2019 DOI 10.14302/issn.2572-5424.jgm-19-3024
Hayat Khan SikandarCorresponding author
PNS HAFEEZ Hospital
Background The objective of this review is to unify the various genetic defects along with elaborating metabolic pathways in Familial Combined Hyperlipidemia(FCHL) and also to differentiate the phenotype of FCHL from metabolic syndrome. Methods PubMed and Cochrane’s library was searched for keyword “Familial combined hyperlipidemia” and latter with “Familial combined hyperlipidemia genes” to finally shortlist 23 articles. Further search with key words “molecular pathogenesis of familial combined hyperlipidemia” and “metabolic syndrome and familial combined hyperlipidemia” was carried out for finding molecular defects in FCHL, non-molecular findings distinguishing FCHL from metabolic syndrome and overlapping features between FCHL and metabolic syndrome. Results Major culprit regions identified included Chromosome-1q21-q24(USF1 and FOXA2) , Ch-11q (APOA5), Ch-16q24, Ch-20q12-q13.1, Ch.4q32.3 (rs6829588), and Ch-19q13.32 containing PVRL-2 gene (Also known as Nectin-2). The genetic and metabolic pathways linked to FCHL may involve: 1-Defective clearance of Apo-B containing lipoproteins, 2-Overproduction of Apo-B containing lipoprotein i.e., VLDL and 3-Adipose tissue dysfunction. FCHL phenotype showed close resemblance with metabolic syndrome clinical and biochemical features with slight differences. Conclusion The reviewed data suggested that FCHL phenotype is the resultant end outcome from multiple molecular defects and thus underlying genetic defect identification in the index case is important for personalized medicine and incoming gene therapy. Further research is warranted to explore specific genetic defects.
May 2019 DOI 10.14302/issn.2639-3166.jar-19-2780
Masoero GiorgioCorresponding author
Accademia di Agricoltura di Torino, Italy
The inoculation of soil with a bio-fertilizer (BF), with arbuscular mycorrhiza fungi, characterizes a Symbiotic (S) agriculture mode, aimed at promoting the yield and health of crops through modifications in the rhizosphere as well as in the plant phenotype. The main objective of this study was to reduce the incidence of Olive Quick Decline Syndrome (OQDS, involving Xylella fastidiosasubsp.pauca) that afflicts the olive groves in Apulia (Italy). Non-inoculated control (C) plants were compared with Symbiotic (S) plants inoculated with 20 kg ha-1 of Micosat F ®, through a 15 cm deep scarification, in the groves of seven farms covering an area of 27 ha. In addition to a visual observation of 484 plants, to obtain a gradation of the disease severity, some objective rapid type methods were utilized to survey the plants and soil , namely leaf pH, NIR tomoscopy of the leaves, hay-litter-bag probes coupled with NIR spectroscopy and the prediction of soil induced respiration. The fingerprinting of the S and C types of leaves and litter-bags was ascertained by means of the use of a random forest algorithm in the classification matrices. The results on the symptoms appeared variable: they were significantly mitigated in two groves out of six, but they were aggravated in one. All the rapid measurements became essentials in a “holistic” model which was able to explain over 95% of the average mitigation / null / aggravation response to BF inoculation. The holistic model gathers differential and compositional analyses of the leaf (pH, crude protein, water) and of the soil (respiration), but depends mainly on the fingerprinting of the C and S leaves and litter-bags. Two keys were identified for a successful inoculation: a high degree of variability of the soil conditions permitting hospitality for the BF with enhancement of the microbial activity in the S soil (lowering the fingerprint of the control litter-bags) and homogeneity of the leaves (with increases in the fingerprint of the S leaves treated with BF). In short, the inoculation of diseased plants with one BF consortium is far from being the ultimate remedy to mitigate OQDS in all situations. Further studies are needed, at a field level, to clarify the soil hosting capacity and to define the mycorrhizal and / or endophytic * plant * pathogen interactions, even using rapid methods.
Jan 2019 DOI 10.14302/issn.2641-5526.jmid-18-2529
Luis Fernández-Martínez JuanCorresponding author
Group of Inverse Problems, Optimization and Machine Learning. Department of Mathematics. C/ Federico García Lorca, 18. 33007 Oviedo. University of Oviedo. Spain
Discrimination of case-control status based on gene expression differences has potential to identify novel pathways relevant to neurodegenerative diseases including Parkinson’s disease (PD). In this paper we applied two different novel algorithms to predict dysregulated pathways of gene expression across several different regions of the brain in PD and controls. The Fisher’s ratio sampler uses the Fisher’s ratio of the most discriminatory genes as prior probability distribution to sample the genetic networks and their likelihood (accuracy) was established via Leave-One-Out-Cross Validation (LOOCV). The holdout sampler finds the minimum-scale signatures corresponding to different random holdouts, establishing their likelihood using the validation dataset in each holdout. Phenotype prediction problems have by genesis a very high underdetermined character. We used both approaches to sample different lists of genes that optimally discriminate PD from controls and subsequently used gene ontology to identify pathways affected by disease. Both algorithms identified common pathways of Insulin signaling, FOXA1 Transcription Factor Network, HIF-1 Signaling, p53 Signaling and Chromatin Regulation/Acetylation. This analysis provides new therapeutic targets to treat PD.
Aug 2018 DOI 10.14302/issn.2639-3166.jar-18-2264
Masoero GiorgioCorresponding author
Accademia di Agricoltura di Torino, Torino, Italy
The management of symbiotic Microbial Biota (MB) in the soil as agents that promote the yield and health of crops, is aimed at inducing modifications of the phenotype of plants, both over and under the ground. It is here shown, in Sorghumsudanensis plants, that: i) a simple response to MB inoculation is the result of the fall out of the raw pH; ii) the simple NIR scans of leaves can be considered to rapidly classify the outcomes; iii) the raw pH can be considered a key-variable of leaf modifications. An experiment was carried out on Sorghumsudanensis. The plants were seeded in pots and grown for 66 d, and then a control non-inoculated group (C) was compared with thirteen Arbuscular Mycorrhizae (AM) Glomus inoculated groups and with two commercial MB products. A total of 374 raw pH measurements conducted on the leaves showed that the 5.18 pH units in the C group were scaled by -1.9% (P<0.0336) in the MB group and by -3.4% in the AM group (P<0.0001), with a relevant diversity between groups. Direct discrimination of these three groups, by means of smart NIR-SCIO, showed a % reclassification of the C, MB and AM groups of 74%, 59% and 96% in the fresh leaves and of 65%, 51% and 94% in the dried ground leaves, respectively. The composition of the dried leaves, based on a set of 14 variables predicted via NIRS models, plus the total foliar dry weight and percentage, showed a typical increase in protein, ash and hemicellulose, and a typical decrease in the cellulose, dry matter, crude fiber and crop maturity index. These variables were related to the foliar pH, as a key-variable, by means of a PLS standard model (R2 0.81) in which a low pH steadily favored the dry mass weight and, to a lesser extent, the hemicellulose and the digestible NDF contents; on the other hand, a high pH increased the dry matter percentage and the cellulose content of the leaves. As expected, the leaves of the inoculated plants showed a more juvenile ontogenic status. The epigean botanical modifications can be considered harmonic expressions of a luxuriant symbiosis, as testified by the homologous NIR categorization. The outlook for a symbiotic agriculture, with mycorrhizal plants, should consider the raw pH as a multifaceted variable.
May 2018
Alatsathianos IoannisCorresponding author
Laboratory of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Genetics alone cannot thoroughly expound the environmental impact on the molecular complexity of the endocrine system. Epigenetic-induced alteration in gene expression has emerged as a way in which environmental compounds may exert endocrine effects. The environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to, on a daily basis. Epigenetic mechanisms, mainly the methylation of DNA and the modification of histones, lead to differentiated activation and deactivation of genome domains creating phenotype plasticity and divergent endocrine function among populations and individuals, as well. The issues examined in the present review are related to environmental epigenetics, and more precisely, the epigenetic-mediated modulation and relevance of endocrine disrupting chemicals, focusing on three broad aspects: 1) persistence of EDs, 2) their major hormonal effects and 3) the potential of compounds previously considered as endocrine disruptors to induce epigenetic effects. Evidence suggests that environmental exposures notably impact expression of endocrine-related genes and, thus, affect clinical endocrine outcomes.
Nov 2017 DOI 10.14302/issn.2576-6694.jbbs-17-1748
Nair AjayCorresponding author
Oklahoma Medical Research Foundation, Arthritis and Clinical Immunology Research Program, Oklahoma City, Oklahoma 73104, USA
Neo-Darwinian natural selection theory indicates that sudden, drastic changes in the environment place selective pressure on genetic variants in a population. As time progresses, this pressure sculpts individuals to better fit this new environment. Waddington’s classic experiment was repeated using white-eyed (the w1118strains) flies which produced the crossveinless (cve; disturbed wing crossveins) trait from the parent generation. The F1 generation was split into two selection lines: an Upward Selection Line, that produced more cve in successive generations, and a Downward Selection Line that responded with a consistent but non-linear decline in the percentage of crossveinless. This article will introduce and enlarge observations made on flies with cve; especially the manner in which the Waddington experiment impacts the population. It seems that Waddington evaluated crossveinless just by what it is good for, but not by the price of using it. That is to say, there is an inevitable cost that needs to be paid in order to acquire crossveinless-ness (cve and the associated phenotypes).
Jun 2017 DOI 10.14302/issn.2474-7785.jarh-17-1578
Wilson DaisyCorresponding author
Institute of Ageing and Inflammation, University of Birmingham, Edgbaston, Birmingham, UK, B15 2GW
Frailty describes a medical syndrome that confers increased vulnerability to disproportionate changes in health status following minor stressors. With loss of homeostatic reserve in multiple physiological systems, frailty conveys an increased risk of adverse health outcomes. Despite the lack of a clear universal definition, the utilisation of two landmark operational models has allowed a rapid expansion in frailty-centred research. The pathophysiology of frailty is yet to be elucidated in the literature, but a critical role for a heightened inflammatory state is hypothesised. Raised levels of pro-inflammatory cytokines are associated with frailty, with emerging evidence relating their biochemical action with development of the frailty phenotype. Dysregulation of both the innate and adaptive immune system are key components of the frailty syndrome. Remodelling of the T cell compartment and upregulated inflammatory pathways are theorised to propagate the heightened inflammatory state critical in the frailty syndrome. Increased neutrophil counts, in conjunction with ineffective neutrophil migration associated with age, is theorised to produce tissue damage and secondary inflammation conducive of the inflammatory picture in frailty. Beyond the gold standard of the comprehensive geriatric assessment, management of frailty is a fast-evolving area of research. Exercise interventions have shown promising results, improving functional ability and showing beneficial immunomodulation. Vitamin D supplementation, with proposed anti-inflammatory effects, nutritional support and pharmacological treatments all provide promising areas for future therapeutic intervention.
Jun 2016 DOI 10.14302/issn.2470-5020.jnrt-16-993
Jurkat-Rott KarinCorresponding author
Division of Neurophysiology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany
Autosomal dominant inherited hypokalemic periodic paralysis (HypoPP) is caused by S4 voltage sensor mutations in skeletal muscle CaV1.1 calcium or NaV1.4 sodium channels. In the present study, a small German family with the known CaV1.1-R528G is described. The phenotype consists of short and infrequent episodes of limb weakness with ictal respiratory and cardiac involvement. There is incomplete penetrance in women, and acetazolamide is beneficial in two patients also taking daily potassium. Expression of the mutation in the GLT mouse muscle cell line revealed accelerated kinetics of inactivation by twofold, a left-shift of the steady-state inactivation curve by 13mV and a reduced recovery from fast inactivation by up to 39%. These changes suggest a stabilization of the inactivated state. Additional significant slowing of activation may support a second open state with differing ion selectivity or decreased activation of calcium-activated potassium channels and thereby contribute to weakness similar to other CaV1.1 mutations. Also, as documented for other HypoPP mutants, we found a hyperpolarization-induced inward guanidinium current of 22nS/nF which can be interpreted as an omega current along the voltage sensor gating pore that leads to a gain- of- function at potentials near the resting membrane potential. This finding can explain the long-lasting depolarizations that are known to lead to paralysis. The omega current is large enough so that a relatively mild hypokalemic trigger of 2.4mM already produces episodes of weakness in vivo.
Jul 2013 DOI 10.14302/issn.2326-0793.jpgr-13-207
Floros JoannaCorresponding author
Center for Host defense, Inflammation, and Lung Disease (CHILD) Research and Departments of Pediatrics
Surfactant protein A (SP-A) plays a number of roles in lung host defense and innate immunity. There are two human genes, SFTPA1 and SFTPA2, and evidence indicates that the function of SP-A1 and SP-A2 proteins differ in several respects. To investigate the impact of SP-A1 and SP-A2 on the alveolar macrophage (AM) phenotype, we generated humanized transgenic (hTG) mice on the SP-A knockout (KO) background, each expressing human SP-A1 or SP-A2. Using two-dimensional difference gel electrophoresis (2D-DIGE) we studied the AM cellular proteome. We compared mouse lines expressing high levels of SP-A1, high levels of SP-A2, low levels of SP-A1, and low levels of SP-A2, with wild type (WT) and SP-A KO mice. AM from mice expressing high levels of SP-A2 were the most similar to WT mice, particularly for proteins related to actin and the cytoskeleton, as well as proteins regulated by Nrf2. The expression patterns from mouse lines expressing higher levels of the transgenes were almost the inverse of one another – the most highly expressed proteins in SP-A2 exhibited the lowest levels in the SP-A1 mice and vice versa. The mouse lines where each expressed low levels of SP-A1 or SP-A2 transgene had very similar protein expression patterns suggesting that responses to low levels of SP-A are independent of SP-A genotype, whereas the responses to higher amounts of SP-A are genotype-dependent. Together these observations indicate that in vivo exposure to SP-A1 or SP-A2 differentially affects the proteomic expression of AMs, with SP-A2 being more similar to WT.