ARTICLE | doi:10.20944/preprints202005.0034.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: the building and the environment; phenotype; genotype
Online: 3 May 2020 (08:10:53 CEST)
Phenotype variation is produced through a complex of interactions between genotype and environment. Phenotype, genotype, and environment are addresses the relationship between architecture and identity. The term genotype biology and phenotype have been adopted into architecture in the late twentieth century. Genotypes are abstract relational models that govern the arrangement of space, and the principle of organizing space and phenotypes is the real realization of genotypes in the physical environment. The genotype is a reflection that is not only about the spatial organization but also the nature of social and cultural patterns. Then this study purpose to an understanding of the connectedness variant phenotype from a genotype and environment. The repetition pattern being stable structure in variation phenotype uses as a database to finding an identity in architecture. The method used in this research was Levi Strauss's structuralism and multi-layer of a biological system. This research samples traditional Malay houses in West Borneo, Indonesia. These houses have a unique site and existing environment. The houses can be found mainly along the river. The results found from the phenotype, genotype, and environment have value and meaning as a traditional Malay house rule in West Borneo which was always handed down from generation to generation.
ARTICLE | doi:10.20944/preprints202103.0210.v1
Online: 8 March 2021 (10:56:37 CET)
Vascular pathogens are the causal agents of main diseases threatening the health and growth of olive crops worldwide. The use of endophytic microorganisms represents a challenging and promising strategy for management of vascular diseases in olive. Although current research has been focused on analyzing the structure and diversity of the endophytic microbial communities inhabiting the olive xylem, the characterization of this ecological niche has been overlooked and to date remain unexplored, despite that the characterization of the xylem sap composition is essential to unravel the nutritional requirements of xylem-limited microorganisms. In this study, branches from plantlets and adult olive trees of cultivars ‘Picual’ and ‘Arbequina' were selected to characterize the chemical composition of olive xylem sap extracted using a Scholander pressure chamber. Metabolome and ionome analyses of xylem sap were performed by proton nuclear magnetic resonance (NMR) spectroscopy-based and by inductively coupled plasma with optical emission spectroscopy (ICP-OES), respectively. Olive xylem sap metabolites included a higher relative percentage of sugars (54.35%), followed by alcohols (28.85%), amino acids (8.01%), organic acids (7.68%) and osmolytes (1.12%). Within each of these groups, the main metabolites in the olive xylem sap were mannitol, ethanol, glutamine, acetate and trigonelline, whereas K and Cl- were the main element and inorganic anion, respectively. Metabolomic profile varied when comparing olive plant age and genotype. The levels of glucose, fructose, sucrose and mannitol, choline, B and PO43 were significantly higher in adult trees than in plantlets for both olive genotypes, whereas NO3- and Rb content showed the opposite behavior. On the other hand, levels of aspartate, phenylalanine and Na were significantly higher in ‘Picual’ than in ‘Arbequina’ whereas Fe showed the opposite behavior but only for adult trees. Non-supervised hierarchical clustering analysis separated xylem sap composition firstly according to the plant age and then by the olive cultivar. Supervised PLS-DA analysis revealed that B, ethanol, Fe, Fructose, glucose, mannitol, sucrose and Sr were the most significative compounds discriminating adult trees from plantlets, whereas asparagine, aspartate, glutamate and phenylalanine or aspartate, arginine, ethanol and Sr were the most contributory compounds in the discrimination of both olive genotypes for adult trees or plantlets, respectively. Knowledge of the chemical composition of xylem sap will lead to a better understanding of the complex nutritional requirements of olive xylem-inhabiting microorganisms, including its vascular pathogens, and would allow the design of artificial growing media to improve culturing the olive microbiome.
REVIEW | doi:10.20944/preprints202101.0549.v1
Subject: Life Sciences, Biochemistry Keywords: Japanese encephalitis virus; birds; genotype shift; JEV genotype I; JEV genotype III
Online: 26 January 2021 (16:47:47 CET)
Japanese encephalitis (JE) is a vaccine preventable disease caused by the Japanese encephalitis virus (JEV), which is primarily prevalent in Asia. JEV is a Flavivirus, classified into a single serotype with five genetically distinct genotypes (I, II, III, IV, and V). JEV genotype III (GIII) had been the most dominant strain and caused numerous out breaks in the JEV endemic countries until 1990. However, recent data shows the emergence of genotype I (GI) as a dominant genotype and it is gradually displacing GIII. The exact mechanism of this genotype displacement is still unclear. The virus can replicate in mosquito vectors and vertebrate hosts to maintain its zoonotic life cycle; pigs and aquatic wading birds act as an amplifying/reservoir hosts, and humans and equines are the dead end hosts. The important role of pigs as an amplifying host for JEV is well known. However, the influence of other domestic animals especially birds that live in high abundance and close proximity to human is not well studied. Here, we strive to briefly highlight the role of birds in JEV zoonotic transmission, discovery of birds as a natural reservoirs and amplifying host for JEV, species of birds susceptible to JEV infection, and the proposed effect of JEV on poultry industry in future perspective which have been neglected for a long times. We also discussed the recent in vitro and in vivo studies which show that the newly emerged GI viruses replicated more efficiently in bird-derived cells and ducklings/chicks than GIII, and an important role of birds in the JEV genotype shift from GIII to GI.
COMMUNICATION | doi:10.20944/preprints202112.0270.v1
Subject: Life Sciences, Virology Keywords: Dengue; Dengue virus; cosmopolitan genotype; Senegal; Mauritania; Molecular characterization; Full genome sequencing
Online: 16 December 2021 (12:06:07 CET)
Globally 390 millions of people are at risk of dengue infection; over the past 50 years the virus incidence increased thirty-fold. In Senegal, an unprecedented occurrence of outbreaks and sporadic cases was noticed since 2017. In October 2018 an outbreak of DENV-2 was reported in Rosso area in the north of Senegal at the border with Mauritania. Out of the 187 blood specimen samples collected, 27 were positives by qRT-PCR and 8 were serologically positive for DENV IgM. Serotyping using qRT-PCR reveals that isolates were positive for DENV-2. A subset of DENV-2 positives samples was selected and subjected to full genome sequencing followed by phylogenetic analysis. Analysis of 06 nearly completed genome sequences (n= 6) revealed that isolates belong to the cosmopolitan genotype and are closely related to the Mauritanian strains detected between 2017 and 2018 and those detected in many West African countries such as Burkina Faso or Cote d’Ivoire. Our results suggest a transboundary circulation of the DENV-2 cosmopolitan genotype between Senegal and Mauritania and call for a need of coordinated surveillance of arboviruses between these two countries. Interestingly, high level of homology between West African isolates highlights endemicity and call for a set-up of sub-regional viral genomic surveillance which will lead to a better understanding of viral dynamic, transmission and spread across Africa.
SHORT NOTE | doi:10.20944/preprints201706.0027.v1
Online: 5 June 2017 (05:43:56 CEST)
This study investigated the presence of human Norovirus (HuNoV) by genotype in 1,486 groundwater samples, collected from 843 groundwater wells suspected of contamination during 2007-2016, in Republic of Korea. We identified and genotyped 186 HuNoV sequences in 178 HuNoV-positive samples using the RIVM-NoroNet norovirus genotyping tool (NGT) and phylogenetic tree analysis based on RIVM-NoroNet reference sequences. HuNoV GII was more prevalent than GI. The major genotypes detected were HuNoV GII.4 (43.0%), GII.22 (15.6%), GI.5 (10.2%) and GI.1 (8.6%); 14 genotypes accounted for < 5.0%. Increasing HuNoV GII.17 has displayed a worldwide trend, including in Europe and Asia since 2010, and it was the dominant HuNoV genotype during 2013-2014 in Korea. However, HuNoV GII.4 was the major genotype detected in groundwater in Korea in 2015-2016, and it is becoming increasingly prevalent similar to HuNoV GII.17.
ARTICLE | doi:10.20944/preprints202111.0505.v1
Subject: Biology, Forestry Keywords: Genotype and environment interaction; Muti-environment test; Genotype selection; BLUP-GGE; Populus euramericana
Online: 26 November 2021 (12:01:42 CET)
Poplar is a globalized commercial tree species that supports humanity's economy, energy, and ecology. To evaluate the twelve hybrid Populus euramericana genotypes developed in China, a total of six locations were selected for the test, comprising four climatic types and three soil kinds. The objective of this study is to characterize the early stages of Populus euramericana growth and test locations; to identify good genotypes for stable and high yield that may be encouraged; and to offer practical experience and technical assistance for further breeding of Populus euramericana. Main research methods include the statistical description of tree heights and diameter at breast heights[DBH], the establishment of a mixed effect model to analyze the genotype and environmental interaction effect [G×E], the use of best linear unbiased prediction[BLUP] values as GGE biplots to achieve visual screening, and the calculation of genetic parameters. Results show that the genotype effect [G], the environmental effect [E], and the G×E is significant; the BLUP value has a strong correspondence with the observed value; the goodness of fit of all biplots can explain more than 85% of the variation; broad-sense heritability of tree height and DBH is 0.13 and 0.3, type-B correlation is 0.36 and 0.65; G5, G7, G4 and G9 are excellent genotypes with high yield and stability; using these four genotypes tree height and DBH can get 3.35% and 0.81% genetic gains.The study concludes as follows: Rank-change interaction and scale-effect interaction were distinctly occurred. The G, E, and G×E all had a significant effect on the growth of poplar trees during their early stage. G4, G5, G7, and G9 genotypes have favorable development characteristics. N146 is a great source of paternal genetics.
ARTICLE | doi:10.20944/preprints202108.0381.v2
Subject: Biology, Agricultural Sciences & Agronomy Keywords: quinoa; genotype; nutritional traits; seed quality
Online: 8 September 2021 (12:37:08 CEST)
Exploiting the relationship between the nutritional properties of seeds and the genetic background, constitutes an essential analysis which contributes to broadening our knowledge regarding the control of the nutritional quality of seeds or any other edible plant structure. This constitutes an important aspect when aiming at improving the nutritional characteristics properties of crops, including those of Chenopodium quinoa Willd (quinoa) which is intended to be one of the main nutrient sources ensuring food security worldwide. Changes in the nutritional properties of quinoa seeds due to the influence exerted by the environment, the genotype, or their interaction, have been already described in previous works, but there is an important limitation in the analyses carried out, including the outcomes that can be translated into agronomical practices by which quality can be improved selecting the most adequate genotype. In the present study, several seed nutritional-related parameters from fifteen quinoa cultivars grown in a particular environmental context were analyzed aiming at targeting compounds that can be determinants of seed quality. Important agronomical and nutritional differences were found among cultivars such as distinct mineral or protein contents and seed viability. More importantly, our analyses revealed key correlations between seed quality-related traits in some cultivars, including those that relate yield and antioxidants or the germination rate. These results highlight the importance of considering the genotypic variation in quinoa when selecting improved quinoa varieties with the best nutritional characteristics for new cultivation environments.
Subject: Biology, Plant Sciences Keywords: callus; genotype-specific recalcitrance; reprogramming; somatic embryogenesis; transcriptomics; upland cotton
Online: 20 July 2021 (15:30:47 CEST)
Somatic embryogenesis-mediated plant regeneration is essential for genetic manipulation of agronomically important traits in upland cotton. Genotype specific recalcitrance to regeneration is a primary challenge in deploying genome editing and incorporating useful transgenes into elite cotton germplasm. In this study, transcriptomes of a semi-recalcitrant cotton (Gossypium hirsutum L.) genotype ‘Coker312’ were analyzed at two critical stages of Somatic Embryogenesis that includes non-embryogenic callus (NEC) and embryogenic callus (EC) cells, and the results compared to a non-recalcitrant genotype ‘Jin668’. We discovered of 305 differentially expressed genes in Coker312, whereas, in Jin668, about 6-fold more genes (2,155) were differentially expressed. A total of 154 differentially expressed genes were common between the two genotypes. Gene enrichment analysis of upregulated genes identified functional categories such as lipid transport, embryo development, regulation of transcription, sugar transport, vitamin biosynthesis, among others. In Coker312 EC cells, five major transcription factors were highly upregulated: LEAFY COTYLEDON 1 (LEC1), WUS-related homeobox 5 (WOX5), ABSCISIC ACID INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and WRKY2. In Jin668, LEC1, BABY BOOM (BBM), FUS3, and AGAMOUS-LIKE15 (AGL15) were highly expressed in EC cells. We also found that gene expression of these embryogenesis genes was typically higher in Jin668 when compared to Coker312. We conclude that significant differences in expression of the above genes between Coker312 and Jin668 may be a critical factor affecting the regenerative ability of these genotypes.
ARTICLE | doi:10.20944/preprints202107.0568.v1
Subject: Life Sciences, Biochemistry Keywords: pattern mining; digenic traits; genotype pattern; diplotype
Online: 26 July 2021 (11:14:06 CEST)
Some genetic diseases (“digenic traits”) are due to the interaction between two DNA variants, which presumably reflects biochemical interactions. For example, certain forms of Retinitis Pigmentosa, a type of blindness, occur in the presence of two mutant variants, one each in the ROM1 and RDS genes, while occurrence of only one such variant results in a normal phenotype. Detecting variant pairs underlying digenic traits by standard genetic methods is difficult and is downright impossible when individual variants alone have minimal effects. Frequent Pattern Mining (FPM) methods are known to detect patterns of items. We make use of FPM approaches to find pairs of genotypes (from different variants) that can discriminate between cases and controls. Our method is based on genotype patterns of length two, and permutation testing allows assigning p-values to genotype patterns, where the null hypothesis refers to equal pattern frequencies in cases and controls. We compare different interaction search approaches and their properties on the basis of published datasets. Our implementation of FPM to case-control studies is freely available.
REVIEW | doi:10.20944/preprints202010.0118.v1
Online: 6 October 2020 (10:53:17 CEST)
Here we review and describe a set of research priorities to meet present and future challenges posed to farmed animal production that build on progress, successes and resources from the Functional Annotation of ANimal Genomes (FAANG) project.
REVIEW | doi:10.20944/preprints201807.0089.v1
Subject: Medicine & Pharmacology, Other Keywords: multidisciplinary; Gaucher; genotype/phenotype correlation; genetic counselling
Online: 5 July 2018 (08:51:35 CEST)
Managing the multisystemic symptoms of type I Gaucher Disease (GD) requires a multidisciplinary team approach that includes disease-specific treatments, as well as supportive care. This involves a range of medical specialists, general practitioners, supportive care providers, and patients. Phenotype classification and the setting of treatment goals are important for optimizing the management of type I GD, and providing personalized care. The ability to classify disease severity using validated measurement tools allows the standardization of patient monitoring, and the measurement of disease progression and treatment response. Defining treatment goals is useful to provide a benchmark for assessing treatment response, and managing the expectations of patients and their families. Although treatment goals will vary depending on disease severity, they include the stabilization, improvement or reversal (if possible) of clinical manifestations. Enzyme replacement therapy (ERT) is the standard care for patients with type I GD, but a novel substrate reduction therapy (SRT), Eliglustat has demonstrated safety and efficacy in selected patients. To ensure that treatment goals are being achieved, regular, comprehensive follow up is necessary.
ARTICLE | doi:10.20944/preprints202207.0267.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: Dioscorea; yield stability; environments; genotype; dry matter; disease resistance; Uganda
Online: 18 July 2022 (10:56:10 CEST)
Often yam varieties grown in different agro-ecologies show differential responses across production environments, a term known as genotype-by-environment interaction. Genotype-by-environment interaction makes selecting the best genotypes under varied production environments more complex. This study tested twenty yam genotypes evaluated in six test environments to assess genotype, environment, and the interaction between genotypes and environmental effect for tuber yield, yam mosaic virus, and dry matter content. The experiments were conducted in two seasons across three locations in Uganda using a randomized complete block design with three replications. The results showed a significant effect (p ≤ 0.001) for genotype (G), environment (E), and genotype by environment interaction for all the traits. Serere 2021 and Namulonge 2021 were identified as the most discriminating and representative environments for testing the yam mosaic virus, respectively. Serere 2021 was recognized as the most discriminating environment, whereas Arua 2021 was identified as the closest to an ideal environment for assessing yam tuber yields. The tested genotypes also exhibited high resistance to yam mosaic virus disease, high tuber yields, and high dry matter content. Genotypes UGY16020, UGY16034, UGY16042, and UGY16080 demonstrated great resistance to yam mosaic virus disease, high yielding, and considerable dry matter content and are thus potential parents for yam improvement. Further evaluation of the four genotypes should be done under farmers' production systems for selection, improvement, and release as new yam varieties for Uganda
ARTICLE | doi:10.20944/preprints202211.0057.v1
Subject: Medicine & Pharmacology, Other Keywords: hepatitis; HCV; epidemiology; genotype; subgenotype; recombinant; RF1_2k/1b; direct-acting antivirals
Online: 2 November 2022 (11:08:11 CET)
Hepatitis C virus (HCV) causes both acute and chronic disease of the liver that can lead to liver cirrhosis, cancer and liver failure. HCV is characterized by high genetic diversity and substantial variations in prevalence of specific HCV genotypes in different countries of the world. Many effective regimens of direct-acting antivirals (DAAs), including pan-genotypic, can successfully treat HCV infection. However, genotype-specific treatments for HCV are being actively employed in the national plans for elimination of HCV infection around the world. Evaluation of HCV genotype prevalence in a country is mandatory for successful implementation of the national plans for elimination of HCV infection and allocation of financial resources to DAAs most effecting for specific HCV genotypes prevalent in a country. Here, we analyzed HCV genotypes, subgenotypes and recombinants in 10,107 serum samples from patients with chronic HCV infection from all Federal districts of Russia collected in 2015-2017. This is the first, largest evaluation of HCV genotypes performed on samples from all territories of Russia, from its Central Federal district to the Far East. Moreover, we have updated retrospective epidemiological analysis of chronic and acute HCV infection in Russia in 2001-2021. We demonstrate that the incidence of acute HCV infection in Russia reduced from 16.7 cases per 100,000 population in 2001 to 0.6 cases per 100,000 population in 2021. The number of cases of chronic HCV infection decreased from 29.5 to 16.4 per 100,000 population during this period. HCV genotype analysis indicated that HCV genotype 1 dominates in Russia (53.6%). Genotypes 3 and 2 were detected in 35.4% and 7.8% of patients respectively. These proportions are virtually identical in all regions of Russia except for Far East, where HCV genotype 2 amounts only to 1%. HCV genotypes 1 and 2 are more widespread in women, while HCV genotype 3 in men. The highest frequency of identification of genotype 3 was found in the age group of 31-40 years old (44.9%, respectively), and genotype 1 was more prevalent in a group of over 70 years old (72.2%). The proportion of HCV genotype 2 is predominant among HCV-infected persons older than 40 years. Discriminating HCV genotype 2 and recombinant RF1_2k/1b, which are frequently misclassified, is important for successful antiviral treatment of such patients. For the first time, we demonstrate the countrywide prevalence of HCV RF1_2k/1b in different regions of Russia. HCV RF1_2k/1b amounts to 3.2% in the structure of HCV genotypes, reaching 30% among samples classified as genotype 2 by some commercial genotyping tests. The highest proportion of HCV RF1_2k/1b was detected in the north-west (60%), southern (41.6%) and central (31.6%) federal district. Its frequency in Far Eastern and North Caucasus Districts was ~ 14.3%. HCV RF1_2k/1b was not detected in the Volga, Ural and Siberian districts. To conclude, this is the first and most complete evaluation of HCV epidemiology and genotype/subgenotype distribution in Russia.
REVIEW | doi:10.20944/preprints202105.0301.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Hepatitis E virus; Genotype; Epidemic hepatitis; Sporadic hepatitis; Pregnancy; Foetus; Neonate; Vaccine
Online: 13 May 2021 (13:52:29 CEST)
The adverse relationship between viral hepatitis and pregnancy in developing countries was seen as a reflection of retrospective biased hospital-based data collection by the West. However, the discovery of HEV from an epidemic of non-A, non-B hepatitis in Kashmir and documenting increased incidence and severity of hepatitis E in pregnancy from a house-to-house survey unmasked the unholy alliance. Among the family of HEV’s, genotype (gt)-1, with a unique ORF4-encoded protein enhancing viral polymerase activity and viral replication, is the sole HEV that shows this adverse relationship. The epidemics caused by HEV-gt1 and not by HEV-gt2 show adverse relationship with pregnancy. The pathogenesis of the unholy alliance is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the mother including: infection, replication and damage to the maternal-foetal interface by HEV-gt1; vertical transmission of HEV to foetus causing severe foetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the mother promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of ALF. Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.
ARTICLE | doi:10.20944/preprints202212.0483.v1
Subject: Life Sciences, Genetics Keywords: genotype imputation; population genetics; rare-variants; reference panel; admixture
Online: 26 December 2022 (09:52:08 CET)
Genotype imputation is widely used to enrich genetic datasets. The operation relies of panels of known reference haplotypes with typically whole-genome sequencing data. How to choose a reference panel has been widely studied and it is essential to have a panel that is well matched to the individuals who require imputation of missing genotypes. However, it is broadly accepted that such an imputation panel will have an enhanced performance with the inclusion of diversity; haplotypes from many different populations. We investigate this observation in this work by examining in fine detail exactly which reference haplotypes are contributing at different regions of the genome. This is achieved using a novel method of inserting synthetic genetic variation into the reference panel in order to track the performance of leading imputation algorithms. We show that while diversity may globally improve imputation accuracy, there can be occasions where incorrect genotypes are imputed following the inclusion of more diverse haplotypes in the reference panel. We however demonstrate a technique for retaining and benefitting from the diversity in the reference panel whilst avoiding the occasional adverse effects on imputation accuracy. What is more, our results elucidate more clearly the role of the diversity in a reference panel than has been shown in previous studies.
ARTICLE | doi:10.20944/preprints201909.0198.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: flowering time; genotype × environment interaction; grain yield; sorghum; tillering capacity; water stress
Online: 18 September 2019 (05:23:50 CEST)
Sorghum in Australia is grown in water-limited environments of varying extent, generating substantial genotype × environment interaction (GEI). Much of the yield variation and GEI results from variations in flowering time and tillering through their effects on canopy development. The confounding effects of flowering and tillering complicate the interpretation of breeding trials. In this study, we evaluated the impacts of both flowering time (DTF) and tillering capacity (FTN) on yield of 1741 unique test hybrids derived from three common female testers in 21 yield testing trials (48 tester/trial combinations) across the major sorghum production regions in Australia in three seasons. Contributions of DTF and FTN to genetic variation in grain yield were significant in 14 and 12 tester/trial combinations, respectively. The proportion of genetic variance in grain yield explained by DTF and FTN ranged from 0.2% to 61.0% and from 1.4% to 56.9%, respectively, depending on trials and genetic background of female testers. The relationship of DTF or FTN with grain yield of hybrids was frequently positive, but varied across the genetic background of testers. Accounting for the effects of DTF and FTN using linear models did not substantially increase the between trial genetic correlations for grain yield. The results suggested that other factors affecting canopy development dynamics and grain yield might contribute GEI and/or the linear approach to account for DTF and FTN on grain yield did not capture the complex non-linear interactions.
BRIEF REPORT | doi:10.20944/preprints202201.0057.v1
Subject: Life Sciences, Virology Keywords: Dengue virus; complete genome; Cosmopolitan genotype; Senegal; 2018; Regional diversification
Online: 6 January 2022 (09:56:19 CET)
To assess the genetic diversity of circulating dengue virus 2 in Senegal in 2018 we performed molecular characterization by complete genome sequencing and performing phylogenetic analysis. Sequenced strains belong to Cosmopolitan genotype of DENV-2 we observed intra-genotype variability leading to a divergence in two clades with differential geographic distribution. We report two variants namely; the “Northern variant” harbouring three nonsynonymous mutations (V1183M, R1405K, P2266T) located respectively on NS2A, NS2B and NS4A and the “Western variant” with two nonsynonymous mutations (V1185E, V3214E) located respectively in the NS2A gene and the NS5 gene. Findings calls for in depth in vitro and functional study to elucidate the impact of observed mutations on viral fitness, spread, epidemiology and disease outcome.
ARTICLE | doi:10.20944/preprints201903.0038.v1
Subject: Chemistry, Other Keywords: biomass; chemometrics, genotype; HSQC NMR; lignin; Miscanthus X giganteus; monolignol ratio; principal component analysis
Online: 4 March 2019 (10:30:04 CET)
As a renewable industrial crop, Miscanthus offers numerous advantages, namely high photosynthesis activity (as a C4 plant) and exceptional CO2 fixation rate. These properties make Miscanthus very attractive for industrial exploitation, such as lignin generation. Here, we present a systematic study analyzing the correlation of the lignin structure with Miscanthus genotype and plant portion (stem versus leaf). Specifically, the ratio of the three monolignols and corresponding building blocks as well as the linkages formed between the units have been studied. Depending on the Miscanthus genotype and plant component (leaf versus stem), correlations between chemical structure and properties of the lignins have been determined, i.e. correlations in molecular weight, polydispersity and decomposition temperature. Lignin isolation was performed using non-catalyzed organosolv pulping and the structure analysis includes NREL, FTIR, UV-Vis, HSQC-NMR, TGA, pyrolysis GC/MS. Structural differences were found for stem and leaf-derived lignins. Compared to beech wood lignins, Miscanthus lignins possess lower molecular weight and narrow polydispersities (< 1.5 Miscanthus vs. > 2.5 beech) corresponding to improved homogeneity. In addition to conventional univariate analysis of FTIR spectra, multivariate chemometrics revealed distinct differences for aromatic in-plane deformations of stem versus leaf-derived lignins. These results emphasize the potential of Miscanthus as low-input resource and Miscanthus-derived lignin as promising agricultural feedstock.
ARTICLE | doi:10.20944/preprints202204.0233.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: chronic kidney disease; gene polymorphism; angiotensin-converting enzyme; cardiovascular disease; cardiovascular mortality risk; genotype
Online: 26 April 2022 (10:05:25 CEST)
The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.
ARTICLE | doi:10.20944/preprints202002.0187.v1
Subject: Biology, Plant Sciences Keywords: dioecious; DNA quality; flower type; sample preservation method; sex genotype; sex phenotype; visual assay
Online: 14 February 2020 (04:22:20 CET)
Methods for high-quality DNA extraction and knowledge of sex expression and flowering time are essential for applying genomic-assisted breeding and improve the success with hybridization in Guinea yam. A dioecious or monoecious pattern of flowering and sometimes non-flowering is a common phenomenon within and between the Dioscorea species. The flowering in yam plants raised from botanical seeds often takes an extended period, mostly till the first clonal generation after propagation from the tubers. The prolonged process of testing required to identify plant sex and flowering intensity in yam breeding often poses a challenge to realize reduced breeding cycle and apply genomic selection. This study assessed sample preservation methods for DNA quality during extraction and potential of DNA marker to diagnose plant sex at the early seedling stage in white Guinea yam. The predicted sex at the seedling stage was further validated with the visual score for the sex phenotype at the flowering stage. DNA extracted from leaf samples preserved in liquid nitrogen, silica gel, dry ice, and oven drying methods was similar in quality with a high molecular weight than samples stored in ethanol solution. Yam plant sex diagnosis with the DNA marker (sp16) identified a higher proportion of ZW genotypes (female or monoecious phenotypes) than the ZZ genotypes (male phenotype) in the studied materials with 74% prediction accuracy. The results from this study provided valuable insights on suitable sample preservation methods for quality DNA extraction and the potential of DNA marker sp16 to predict sex in white Guinea yam.
ARTICLE | doi:10.20944/preprints202201.0350.v1
Subject: Life Sciences, Genetics Keywords: genetics; DNA; polymorphism; genotype; muscle protein synthesis; anabolism; hypertrophy; endurance; athletes
Online: 24 January 2022 (11:49:22 CET)
Branched-chain amino acid (BCAA) levels are associated with skeletal muscle cross-sectional area (CSA). Serum BCAA levels are enhanced by whey protein supplementation (WPS), and evidence in clinical populations suggests an association of single nucleotide polymorphisms (SNPs) with BCAA metabolite levels. It is not known whether the same SNPs are associated with the ability to catabolise BCAAs from exogenous sources, such as WPS. The present study investigated whether possessing a higher number of alleles associated with increased BCAA metabolites correlates with muscle fiber CSA of m. vastus lateralis in physically active participants, and whether any relationship is enhanced by WPS. Endurance-trained participants (n=75) were grouped by self-reported habitual WPS consumption and genotyped for 5 SNPs (PPM1K rss1440580, APOA5 rs2072560, CBLN1 rs1420601, DDX19B rs12325419, TRMT61A rs58101275). Body mass, BMI and fat percentage were significantly lower and muscle mass higher in the WPS group (n=22) compared to Non-WPS (n=53). The number of BCAA-increasing alleles was correlated with fiber CSA in the WPS group (r=0.75, p<0.0001) and was stronger for fast-twitch fibers (p=0.001) than slow-twitch fibers (p=0.048). Similar results remained when corrected for multiple covariates (age, physical activity, meat and dairy intake). No correlation was found in the Non-WPS group. This study presents novel evidence of a positive relationship between BCAA-increasing alleles and muscle fiber CSA in athletes habitually consuming WPS. We suggest that a high number of BCAA-increasing alleles improves the efficiency of WPS by stimulation of muscle protein synthesis, and contributes to greater fiber CSA.
ARTICLE | doi:10.20944/preprints202301.0033.v2
Subject: Life Sciences, Microbiology Keywords: Staphylococcus aureus; clinical mastitis; antibiotic resistance (AR) prevalence; AR phenotype; AR genotype; recent trend
Online: 22 January 2023 (06:50:19 CET)
This study was aimed to examine the recent trends of antibiotic resistance (AR) prevalence in Staphylococcus aureus isolated from milk of animals with clinical mastitis in areas of the Abruzzo and Molise regions in central Italy. Fifty-four S. aureus isolates could be obtained from routine testing for clinical mastitis agents carried out in the author institution in years 2021 and 2022. These were analyzed for phenotypic resistance to eight antibiotics recommended for testing by European norms and belonging to the antibiotic classes used for mastitis treatment in milk producing animals. Moreover, the presence of 14 transferable genetic determinants encoding resistance to the same antibiotics was analyzed by qPCR tests developed in this study. Phenotypic resistance to non-β-lactams was infrequent, with only one 2022 isolate resistant to clindamycin. However, low level resistance to the β-lactam cefoxitin was observed in 59.2% isolates in both years making these isolates classifiable as methicillin resistant. The AR genotypes detected were blaZ gene (50% 2021 isolates and 44.4% 2022 isolates), ermC/T- aphA3-blaZ (one 2021 isolate), ant6-ermC/T-aphA3-blaZ (one 2021 isolate), ermB-blaZ (one 2022 isolate) and mecA-mph (one 2022 isolate). An interview to the veterinarians who conferred the samples, regarding antimicrobials prescribed for mastitis treatment and criteria of usage, indicated a possible causal relation with the AR test results. The low prevalence of AR genotypes, not increasing in time, most probably reflecting the reported management of antibiotic therapies in farms. However, the frequently observed cefoxitin resistance needs to be explained genotypically, further monitored and limited by modifying antibiotic usage practices. The identification of a mecA positive isolate in 2022 suggests to investigate further if this genotype is emerging locally.
ARTICLE | doi:10.20944/preprints201905.0207.v1
Subject: Biology, Horticulture Keywords: bacterial wilt; Ralstonia solanacearum; genotype-by-sequencing; disease resistance; quantitative trait loci; Solanum lycopersicum
Online: 16 May 2019 (10:35:18 CEST)
Bacterial wilt (BW), caused by Ralstonia solanacearum is one of the major biotic factors limiting tomato production in the humid tropics. Pyramiding of resistance genes through marker-assisted selection is an efficient way to develop durable BW resistant cultivars. Tomato line ‘Hawaii 7996’ (H7996) is a stable and robust resistance source against various R. solanacearum strains. Major BW resistance quantitative trait loci (QTLs) Bwr-12 and Bwr-6, and several minor or strain specific QTLs have been coarse-mapped in this line, but none has been fine-mapped and validated. The objective of the current study was to construct a high density genetic map using single-nucleotide polymorphism (SNP) markers derived from genotyping-by-sequencing, fine-map Bwr-12 and Bwr-6 and determine the effects of these QTLs using a near isogenic line (NIL) population. A high density genetic map using 1,604 SNP markers with an average distance of 0.82 cM was developed for 188 F9 recombinant inbred lines derived from the cross H7996 × WVa700. A total of seven QTLs associated with BW resistance to race 1-phylotype I or/and race 3-phylotype II strains were located on chromosomes 6 (Bwr-6.1, 6.2, 6.3 and 6.4) and 12 (Bwr-12.1, Bwr-12.2 and Bwr-12.3) with logarithm of odds (LOD) scores of 6.2-15.6 and 6.2-31.1, explaining 14.2-33.4% and 15.9-53.9% of the total phenotypic variation contributed from H7996, respectively. To validate the genetic effects of the two QTL regions, a set of 80 BC3F3 NILs containing different sections of Bwr-6 with or without Bwr-12 was phenotyped for disease severity after challenge with either race 1-phylotype I Pss4 or race 3-phylotype II Pss1632 BW strains over two seasons. Bwr-6.1 specific to Pss4 and Bwr-6.3 specific to Pss1632 were mapped to an interval of 5.0 cM (P < 0.05) between 6_33,444,000_SLM6-47 and 6_33,868,000_SLM6-124 SNP marker, and to 2.7 cM (P < 0.01) between positions 6_35,949,000 _SLM6-107 to 6_36,750,000_SLM6-82 marker, respectively. In addition, the specific effect of Bwr-12 for resistance to Pss4 (LOD score of 5.8-16.1, P < 0.01) was confirmed and markers for this QTL have already been made available previously.
CASE REPORT | doi:10.20944/preprints201805.0146.v2
Subject: Medicine & Pharmacology, Behavioral Neuroscience Keywords: Growth Hormone; cognition; recent memory; PET-SCAN; hippocampus; amygdala; parahippocampus; ApoE genotype.
Online: 5 June 2018 (15:18:11 CEST)
1) Background: We analyzed, by PET-SCAN, how growth hormone (GH) could act on the brain of an older woman, not GH-deficient, which was beginning to show some cognitive deficiencies and presented an ApoE genotype 4/3; 2) Methods: After performing a first psychometric study (TAVEC verbal learning test), the metabolic activity of brain structures related to knowledge, memory, and behavior was analyzed using 18-F Fluorodeoxyglucose PET-SCAN. The patient was then treated with GH (0.4 mg/day) for three weeks and on the last day under this treatment, a new PET-SCAN was performed. One month after beginning treatment with GH, a new TAVEC test was performed; 3) Results: GH administration normalized the cognitive deficits observed in the first psychometric test and increased significantly (P < 0.025) the metabolic activity in practically all brain cortical areas, specifically in the left hippocampus and left amygdala, although not in the left parahippocampus; and 4) Conclusions: This is the first study in which the positive effects of GH on cerebral metabolism have been visualized in a human patient. Our data confirm the positive effects of this hormone on cognition, memory and behavior in patients affected by mild cognitive impairments.
ARTICLE | doi:10.20944/preprints202108.0368.v1
Subject: Life Sciences, Genetics Keywords: pancreatic cancer; cancer subtype identification; somatic point mutations; genotype and phenotype characterization; therapeutic targets; personalized medicine
Online: 17 August 2021 (22:24:57 CEST)
It has now known that at least 10% of samples with pancreatic cancers (PC) contain a causative mutation in the known susceptibility genes, suggesting the importance of identifying cancer-associated genes that carry the causative mutations in high-risk individuals for early detection of PC. In this study, we develop a statistical pipeline using a new concept, called gene-motif, that utilizes both mutated genes and mutational processes to identify 4,211 3-nucleotide PC-associated gene-motifs within 203 significantly mutated genes in PC. Using these gene-motifs as distinguishable features for pancreatic cancer subtyping results in identifying five PC subtypes with distinguishable phenotypes and genotypes. Our comprehensive biological characterization reveals that these PC subtypes are associated with different molecular mechanisms including unique cancer related signaling pathways, in which for most of the subtypes targeted treatment options are currently available. Some of the pathways we identified in all five PC subtypes, including cell cycle and the Axon guidance pathway are frequently seen and mutated in cancer. We also identified Protein kinase C, EGFR (epidermal growth factor receptor) signaling pathway and P53 signaling pathways as potential targets for treatment of the PC subtypes. Altogether, our results uncover the importance of considering both the mutation type and mutated genes in the identification of cancer subtypes and biomarkers.
ARTICLE | doi:10.20944/preprints201808.0187.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: Porcine rotavirus H; Porcine rotavirus C; Full genome; Classification; Genotype; Non-structural protein 3; Gene rearrangement
Online: 9 August 2018 (11:38:44 CEST)
Rotavirus species H (RVH) has been detected in pigs, humans and bats. Moreover, porcine RVHs have been recently identified in several swine-producing countries. Despite their zoonotic impact, genome information of RVHs is still limited. This study aimed to establish a tentative complete genome-based genotyping system for RVHs, by appending genomic sequences from 12 porcine RVHs identified in Japan between 2013 and 2015 to those from human and other porcine RVHs reported in previous studies. Phylogenetic analysis of 11 RNA segments indicated that porcine RVHs could be classified into multiple genotypes. Consequently, the genotype classification for RVHs revealed the existence of genotypes 10G, 6P, 6I, 3R, 4C, 7M, 6A, 2N, 4T, 6E, 3H for the genes VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Surprisingly, two distinctive types in NSP1 and NSP3 genes were identified from among the twelve porcine RVHs. Our data suggest a potentially novel gene rearrangement event between porcine RVH and rotavirus species C in the NSP3 gene. These findings would provide a new insight in understanding for evolution of RV.
REVIEW | doi:10.20944/preprints201905.0330.v1
Subject: Biology, Other Keywords: gene expression; gene regulation; evolution; allele specific expression; eQTL; RNAseq; ChIPseq; chromatin; ATACseq; genotype-phenotype map
Online: 28 May 2019 (10:29:26 CEST)
Research in various fields of evolutionary biology has shown that divergence in gene expression is a key driver for phenotypic variation. An exceptional contribution of cis-regulatory evolution has for instance been found to contribute to morphological diversification. In the light of these findings, the analysis of genome-wide expression data has become one of the central tools to link genotype and phenotype information on a more mechanistic level. However, in many studies, especially if general conclusions are drawn from such data, a key feature of gene regulation is often neglected. With our article, we want to raise awareness that gene regulation and thus gene expression is highly context dependent. Genes show tissue- and developmental stage-specific expression. We argue that the regulatory context must be considered when studying evolution of gene expression.
REVIEW | doi:10.20944/preprints202212.0422.v1
Subject: Medicine & Pharmacology, Other Keywords: Infections; Human Adenovirus; Social Determinants of Health; Adenovirus Vaccine; Genotype; Molecular Diagnostic Testing
Online: 22 December 2022 (07:05:34 CET)
Human adenoviruses are one of the most important pathogens detected in acute respiratory diseases in pediatrics and immunocompromised patients. In 1953, Wallace Rowe described it for the first time in oropharyngeal lymphatic tissue. To date, more than 85 types of HAdV have been described, with different cellular tropisms. They can cause respiratory and gastrointestinal symptoms, even urinary tract inflammation, although most infections are asymptomatic. However, there is a population at risk that can develop serious and even lethal conditions. These viruses have a double-stranded DNA genome, 25-48 kbp, 90 nm in diameter, without a mantle, stable in the environment, and resistant to fat-soluble detergents. Currently the diagnosis is made with lateral flow immunochromatography or molecular biology through a polymerase chain reaction. The objective of this review is to recognize the variability of HAdV, the pandemic potential that a recombinant could present between HAdV-3 and 7 viral types, known to produce aggressive outbreaks in health facilities. The review determined the characteristics of HAdV, from the infection to treatment, vaccine development and the evaluation of the social determinants of health associated with HAdV, guiding the necessary measures for future sanitary control, and preventing disasters such as the SARS-CoV-2 pandemic.
ARTICLE | doi:10.20944/preprints202212.0065.v1
Subject: Life Sciences, Genetics Keywords: pulmonary tuberculosis; lymph node tuberculosis; extra-pulmonary tuberculosis; single nucleotide polymorphisms; cytokine; innate immunity; genetic association; genotype; serum
Online: 5 December 2022 (08:00:15 CET)
Background: Tuberculosis (TB) manifests itself primarily in the lungs as pulmonary disease (PTB) and sometimes disseminates to other organs to cause extra-pulmonary TB, such as lymph node TB (LNTB). This study aimed to investigate the role of host genetic polymorphism in immunity related genes to find a genetic basis for such differences. Methods: Sixty-three, Single nucleotide polymorphisms (SNPs) in twenty-three, TB-immunity related genes including eleven innate immunity (SLCA11, VDR, TLR2, TLR4, TLR8, IRGM, P2RX7, LTA4H, SP110, DCSIGN and NOS2A) and twelve cytokine (TNFA, IFNG, IL2, Il12, IL18, IL1B, IL10, IL6, IL4, IL1RA, IL8 and TNFB) genes were investigated to find genetic associations in both PTB and LNTB as compared to healthy community controls. The serum cytokine levels were correlated for association with the genotypes. Results: PTB and LNTB showed differential genetic associations. The genetic variants in the cytokine genes (IFNG, IL12, IL4, TNFB and IL1RA and TLR2,4 associated with PTB susceptibility and cytokine levels but not LNTB (p < 0.05). Similarly, genetic variants in LTA4H, P2RX7, DCSIGN and SP110 showed susceptibility to LNTB and not PTB. Pathway analysis showed abundance of cytokine related variants for PTB and apoptosis related variants for LNTB. Conclusions: PTB and LNTB outcomes of TB infection have a genetic component and should be considered for any future susceptibility and functional studies.
ARTICLE | doi:10.20944/preprints202005.0407.v1
Subject: Life Sciences, Virology Keywords: SARS-CoV-2; spike protein; D614G mutation; genotype distribution; furin cleavage site; secondary structure; sequence analysis; homology modeling
Online: 24 May 2020 (20:31:16 CEST)
We analyzed the SARS-CoV-2 spike (S) protein amino acid sequence extracted from 11,542 viral genomic sequences submitted to the Global Initiative on Sharing All Influenza Data (GISAID) database through April 27, 2020. Consistent with prior reports, we found a major S protein mutation, D614 to G614, that was represented in 56% of all the analyzed sequences. All other mutations combined were less than 10%. After parsing the data geographically, we found most of the Chinese patient samples showed D614 (97%). By contrast, most patient samples in many European countries showed G614 (51 to 88%). In the United States, the genotypic distribution in California and Washington was similar to Asian countries, while the distribution in other US states was comparable to Europe. We observed a dramatic increase in the frequency of G614 over time in multiple regions, surpassing D614 when both were present, suggesting G614 S protein virus outcompetes D614 S protein virus. To gain insight into the consequences of the D614G mutation, homology modeling using a multi-template threading mechanism with ab initio structural refinement was performed for a region of the S protein (S591 to N710) spanning the D614G mutation and the S1 furin cleavage site. Molecular models of this region containing D614 or G614 revealed a major difference in secondary structure at the furin domain (RRARS, R682 to S686). The D614 model predicted a random coil structure in the furin domain whereas the G614 model predicted an alpha helix. Critical residues in the cleavage domain of G614 model were found to better align with the PDB structure of a furin inhibitor. Thus, homology modeling studies suggest a potential mechanism whereby the D614G mutation may confer a competitive advantage at the furin binding domain that may contribute to the rise of the D614G SARS-CoV-2 mutant.
ARTICLE | doi:10.20944/preprints201912.0035.v1
Subject: Mathematics & Computer Science, Applied Mathematics Keywords: virus density distribution; genotype; virus infection; immune response; resistance to treatment; nonlocal interaction; quasispecies diversification
Online: 4 December 2019 (03:59:20 CET)
The work is devoted to the investigation of virus quasispecies evolution and diversification due to mutations, competition for host cells, and cross-reactive immune responses. The model consists of a nonlocal reaction-diffusion equation for the virus density depending on the genotype considered as a continuous variable and on time. This equation contains two integral terms corresponding to the nonlocal effects of virus interaction with host cells and with immune cells. In the model, a virus strain is represented by a localized solution concentrated around some given genotype. Emergence of new strains corresponds to a periodic wave propagating in the space of genotypes. The conditions of appearance of such waves and their dynamics are described.
ARTICLE | doi:10.20944/preprints202210.0412.v1
Subject: Life Sciences, Microbiology Keywords: biolog phenotypic technology; Candida; energy-dispersive X-ray spectroscopy; genotype; multilocus DNA sequencing; one new taxon; yeast
Online: 26 October 2022 (10:15:55 CEST)
The majority of Candida species are known as non-pathogenic yeasts and rarely involved in human diseases. However, recently case reports of human infections caused by non-albicans Candida species have increased, mostly in immunocompromised hosts. Our study aimed to describe and caracterise as thoroughly as possible, a new species of the Candida genus, named here Candida massiliensis (PMML0037), isolated from a clinical sample of human sputum. We compared genetic data based on the sequences of four genetic regions: "Internal Transcribed Spacers" of rRNA, D1/D2 domains (28S large subunit rRNA) and part of the genes encoding Translation Elongation Factor 1-α and β-tubulin2, to morphological characters, from scanning electron microscopy (TM 4000 Plus, SU5000), physiological, including the results of oxidation and assimilation tests of different carbon sources by the Biolog system, and chemical mapping by Energy-Dispersive X-ray Spectroscopy. Lastly, the in vitro antifungal susceptibility profile was performed using the E-testTM exponential gradient method. The multilocus analysis supported the genetic position of Candida massiliensis (PMML0037) as a new species of the genus Candida, and the phenotypic analysis highlighted its unique morphological and chemical profile when compared to other Candida species included in the study.
CONCEPT PAPER | doi:10.20944/preprints202008.0574.v2
Subject: Life Sciences, Biotechnology Keywords: evolution; evotype; engineering theory; genotype-phenotype maps; directed evolution; selection; synthetic biology; bioengineering; evolvability; self-adaptive systems
Online: 9 December 2020 (10:51:51 CET)
Biological technologies are fundamentally unlike any other because biology evolves. Bioengineering therefore requires novel design methodologies with evolution at their core. Knowledge about evolution is currently applied to the design of biosystems ad hoc. Unless we have a unified engineering theory of evolution, we will neither be able to meet evolution’s potential as a design tool, nor understand or limit its unintended consequences on our designs. Our concept of the evotype offers a conceptual framework for engineering the evolutionary potential of biosystems. We show how a biosystem’s evolutionary properties might be rationally designed by engineering aspects of genetic variation, designed function, and natural selection. This idea could apply to all biosystems – from individual proteins to communities of whole-cells or even entire ecosystems – whether the goal is to direct evolution in the design process, or to limit its impacts during application. These principles could even be used beyond the realm of bioengineering to design entirely synthetic evolving auto-adaptive technologies.
ARTICLE | doi:10.20944/preprints201810.0314.v1
Subject: Life Sciences, Other Keywords: hepatitis B virus (HBV); cccDNA; basal core promoter; X promoter; single nucleotide polymorphisms; logo analyses; genotype alignments
Online: 15 October 2018 (13:03:06 CEST)
Over 250 million people are infected chronically with hepatitis B virus (HBV), the leading cause of liver cancer worldwide. HBV persists due in part to its compact, stable minichromosome, the covalently-closed, circular DNA (cccDNA), which resides in the hepatocytes’ nuclei. Current therapies target downstream replication products, however, a true virological cure will require targeting the cccDNA. Finding targets on such a small, compact genome is challenging. For HBV, to remain replication-competent, it needs to maintain nucleotide fidelity in key regions, such as the promoter regions, to ensure that it can continue to utilize the necessary host proteins. HBVdb (HBV database) is a repository of HBV sequences spanning all genotypes (A-H) amplified from clinical samples, and hence implying an extensive collection of replication-competent viruses. Here, we analyzed the HBV sequences from HBVdb using bioinformatics tools to comprehensively assess the HBV core and X promoter regions amongst the nearly 70,000 HBV sequences for highly-conserved nucleotides and variant frequencies. Notably, there is a high degree of nucleotide conservation within specific segments of these promoter regions highlighting their importance in potential host protein-viral interactions and thus the virus’ viability. Such findings may have key implications for designing antivirals to target these areas.
ARTICLE | doi:10.20944/preprints202208.0324.v1
Subject: Life Sciences, Immunology Keywords: T cytotoxic cells; Leukocyte-associated Immunoglobulin-like Receptor-1; LAIR-1; Hepatitis C virus genotype 4; HCV G4; hepatocellular carcinoma; cirrhosis; immune inhibitory checkpoints; inflammation; prognosis; insulin resistance
Online: 17 August 2022 (11:38:10 CEST)
Background and Aim. Since virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, post-hepatitis C virus (HCV) infection would be a cause for liver cirrhosis that would progress to HCC. Cytotoxic T cells (Tc) are known to be involved in post-HCV complications and HCC pathogenesis. The inhibitory checkpoint Leukocyte-Associated Immunoglobulin-like Receptor-1 (LAIR-1) is expressed on Tc. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression post-HCV and moreover, to evaluate LAIR-1 expression as a non-invasive biomarker for HCC progression in the context of liver cirrhosis post-HCV genotype 4 (G4) in Egyptian patients’ peripheral venous blood liquid biopsy. We studied LAIR-1 expression on Tc related to the progression of liver cirrhosis in a case-controlled study enrolled 64 patients with post-HCV G4-HCC and 37 patients with post-HCV G4-liver cirrhosis. Methods: LAIR-1 expression was analyzed by flow cytometry. Results: LAIR-1 expression on Tc and the percentage of Tc positive for LAIR-1 (LAIR-1+Tc %) were significantly higher in the post-HCV G4-HCC group compared to the post-HCV G4-liver cirrhosis