Inheritance Factors Research Articles

A Review of genetic improvement mechanisms of maize (Zea mays L.) in breeding for nitrogen use efficiency

Maize is the third most prominent crop grown next to wheat and rice globally while extensively affected by stresses; critically abiotic factors like drought and soil acidity are the robust effect. Nitrogen use efficiency (NUE) is an imperative trait in maize to enhance yield with marginal contribution of nitrogen fertilizer. In this review, it has been tried to extant the current progress and the coming projections enlightening the NUE in maize by various mechanisms, especially through conventional breeding and molecular genetics. Of any kind, N fertilizer is amplified the understanding of the appliances prevailing maize N economy is indispensible for refining NUE and plummeting extreme use of fertilizer, whereas retaining an adequate yield and satisfactory income for agrarians. Consuming crops cultivated under managed environments, with various cultivation practices, independently or supplementary principles at minimum and great N inorganic mineral fertilizer expenditure or other organic fertilizer, it is currently conceivable to grow advance the entire maize agronomic and biological revisions. These can be shared with inheritable factor, protein and metabolic sketching to construct a widespread image showing the diverse paces of N acceptance, absorption and recovering to produce either in vegetative biomass or seed protein storage structures. Therefore providing a serious impression in what manner our empathetic of the agro-eco physiological, biological and molecular mechanisms of N adjustment in maize, at different ecological circumstances, has been enhanced. At the movement enduring sustainability is required at maize growing world to limit the application of synthetic N input and avoiding excessive environmental pollution. The knowledge and prospects of the future development and submission for breeding in maize improved at the deprived mineral fertilizer input

Study on anthropometric measurements of head in medical faculty students and their relation with intelligence quotient

Questions about intelligence have always occupied scientists’ minds, and many types of research have been conducted to find answers to these questions. Although inheritance and environmental factors together are influential in the development of intelligence, the belief that intelligent people are biologically and physically different is a common presentation. There are a significant number of studies which aim to find the association between cognitive abilities and anthropometric measurements. The purpose of this study is to research whether there is association between anthropometric measurements taken from the head regions of university students and their IQ values. Our study was conducted with 84 right-handed male students studying at AnA¶nA¼ University Faculty of Medicine. The students were first given R.B. Cattell Culture Free Intelligence Test. After their ages, heights and weights were recorded, and head circumference, bigonial breadth, morphological facial height, head height, head breadth, frontal breadth, maximum head diameter, nose to back of head, distance between gnathion-traction and skull height measurements from the head region were taken. IBM SPSS Statistics 22.0 program was used for the statistical analysis of the results. p

Inheritance pattern of fire blight resistance in pear

Fire blight caused by Erwinia amylovora is a serious disease that directly affects pear agriculture and production around the world. The most effective way to struggle with disease is develop new varieties and rootstocks. In this study, for a better understanding of the genetic base of fire blight such as heritability of disease resistance, breeding values of parents and maternal effect were investigated on F1 hybrid pear population. According to results, disease resistance shows polygenic inheritance and multiple factors were effective in heredity. Resistance to disease is transmitted to next generations by both parents. However, the influence of the female parent on inheritance is much greater than pollinator. ‘Magness’ and ‘Mustafa Bey’ varieties were found more effective for the transmission of disease resistance as female parents to next progenies. Similar results were obtained from ‘Kiefer’ and ‘Limon’ as pollinator. In addition to the importance of the parents exclusively in disease resistance, gene interactions between the parents also had a significant effect on this matter. Heritability of fire blight that was calculated from the non-additive genes was 23%, likewise 32% was calculated from additive genes. Broad-sense heritability of fire blight, representing the sum of this two situations was 55%. Maternal gene effects were greater than the pollinator and maternal effect had a 7% effect on the disease resistance, indicating that the cytoplasmic gene effects had important roles in the resistance. Obtained results will form basis for the development of new varieties that become resistant to fire blight by hybridization.

Genotyping of five Pakistani patients with severe inherited factor X deficiency: identification of two novel mutations.

: Congenital factor X deficiency is a rare coagulation defect characterized by variable bleeding tendency. The aim of the study was to give a first insight of F10 gene mutations in Pakistani probands. Direct sequencing and/or next-generation sequencing was performed on the coding regions, boundaries and 5' and 3' untranslated regions of the F10 gene in five severe factor X-deficient patients from Pakistan. All patients were born from consanguineous marriages and displayed FX:C levels below 2%. Sequencing revealed five different substitutions, including three previously reported p.Ala15Asp, p.Gly406Ser, and p.Gly420Arg missense variants, and also two novel variants: p.Cys57Arg and p.Gln175*. Though one genotype could not be characterized, we were able to confirm the inherited nature of the defect using familial studies. As the copy number variations were ruled out, we hypothesized the presence of deep intronic mutants that might have escaped detection from sequencing or abnormalities in epigenetic regulation. Three patients presented with severe clinical symptoms, in the early days of life, whereas two presented only with trauma-provoked bleeds and bruises later in life. Those patients with milder forms bore the p.Gly406Ser at the homozygous state and F10 unknown alleles, respectively. F10 mutation spectrum in Pakistan is heterogeneous as seen in other populations. Identification of the F10 mutations is important for genetic counseling and prenatal diagnosis in subsequent pregnancies.

52. Cardiovascular risk factors track from mother to child

Background Cardiovascular risk factors can track from mother to child via several pathways: intra-uterine programming, genetic inheritance and shared environmental risk factors after pregnancy. The degree of tracking and to which extend this is influenced by these pathways is unknown. This study determined the degree of tracking between maternal and offspring micro- and macrovascular cardiovascular risk factors after pregnancy and the extent to which this is influenced by pregnancy complications and shared environmental risk factors. Methods We included 5624 mother-offspring pairs from The Generation R Study; an ongoing prospective population-based birth cohort. Information on pregnancy complications (pre-eclampsia, small for gestational age and preterm birth) was obtained through hospital charts. Mother-offspring associations were assessed six years after pregnancy (central retinal arteriolar and venular calibers, blood pressure, left atrial diameter, aortic root diameter, left ventricular mass, fractional shortening and pulse wave velocity) and nine years after pregnancy (blood pressure). Results We observed a positive association for all mother-offspring parameters six and nine years after pregnancy (P-values Conclusions Six and nine years after pregnancy, an adverse cardiovascular profile in mothers is strongly associated with an adverse cardiovascular profile in their offspring. Results were not attenuated by environmental exposures or a previous pregnancy complication. This supports the hypothesis that cardiovascular risk factors (micro- and macrovascular) track from mother to child, regardless off the course of pregnancy and may aid in cardiovascular risk stratification.

W poszukiwaniu skutecznych metod resocjalizacji sprawców pozbawionych wolności na przykładzie Stanów Zjednoczonych Ameryki

In its introduction, the article characterises - in a most comprehensible way - themain objectives of criminal sanctions and their role in preventing crime, according tothe most commonly expressed opinions on the subject from American scholars. It isfollowed by a brief history of assessing the risk of committing an offence in the UnitedStates in recent decades. The risk assessment process was developed before World WarII as a tool to predict possible recidivism in the case of inmates released on parole, butit has been in more common use since 1980s. While the “What works?” movementinitially emerged in the United States, one needs to remember the publication of Robert Martinso’s report that created the “Nothing works” (concerning prison rehabilitation)doctrine. It aided the justification of severe changes in punitive prison policies inthe 1970s that continued well into the 1990s, with the slogans “tough on crime, toughon the causes of crime” being more prominent. It took more than a decade to reestablishsome hope in prison rehabilitation programmes and allow the paradigm shiftsto happen – from the retribution “being tough on offenders” policy to more creativeapproaches towards offenders. By constructive approaches to working with offenders,one means the use of effective methods and techniques to alter criminal behaviourof inmates to prevent their possible relapse into crime (crime prevention).The main goal of the article is to present the most fundamental system in the UScriminal justice system that is most commonly applied nowadays: the Risk-Need-Responsivity (RNR) model and its principles to offender assessment. The aforementionedprinciples were laid down by Canadian scholars, Donald Arthur Andrews andJames Bonta. In that model, “risk” means the identification of specific factors thatare associated with recidivism (in general, depending on a specific crime, e.g. sexualoffenders or offenders who committed violent crimes). Andrews and Bonta argue thata number of factors need to be considered in any comprehensive theory of criminalbehaviour, including biological or neurological issues, inheritance, temperamentand social and cultural factors, while also noting that criminal behaviour is a multifactorialissue. “Need” assesses criminogenic needs and targets them in prison treatmentprogrammes for elimination, while “responsivity” intends to maximise the offender’sability to learn how to combat possible recidivism through rehabilitative intervention,providing cognitive behavioural treatment – with the said intervention being tailoredto the learning style, motivation, abilities and strengths of the offender.Risk assessment is applied during different stages of the criminal procedure: beforesentencing and during the period of time when the criminal sanction is executed, i.e.while serving a custodial sentence. It must be noted that, in the US justice system, judgesare not the only people obliged to assess the potential risk of an offender relapsinginto crime in the future. Prison officers are also tasked with such assessment. Throughthe application of the RNR model, it is possible for the prison staff to divide inmatesinto specific groups, depending on security levels and adequate treatment programmes.In that case, the assessment tools based on the RNR model not only allow a predictionof a possible relapse into crime, but also a proper allocation of convicts to rehabilitationprogrammes provided within prisons. A convict undergoes an evaluation before andafter the treatment. Such evaluations are imposed on most prisoners, so performingthem does have an impact on the financial and human resources of a given penitentiaryunit.The most important question, “What works in prison?” is answered by the majorityof scholars through propositions of providing cognitive and behavioural skill programmesto the convicts. They have clear criteria to ensure that objectives, methods andapplication of rehabilitation programmes correspond with the needs of criminaloffenders. The conclusion of the research is meant to prove that providing offenders with such treatment (based upon the RNR model) may have a positive effect on re -ducing the risk of relapse into crime in the future. However, the appropriate methodsof treatment are based not only on psychotherapy (or, sometimes, on pharmacologicaltreatment), but also on education, vocational training, personal development, strengtheningself-control mechanisms and improving interpersonal skills.

Interaction of heat shock protein 70 (HSP70) polymorphisms and occupational hazards increases the risk of hypertension in coke oven workers

ObjectivesThe interaction between genetic, epigenetic inheritance and environmental factors determines susceptibility to hypertension. Previous epidemiology studies have shown that coke oven workers who are frequently exposed to various occupational hazards...

Factor VII deficiency – an enigma; clinicohematological profile in 12 cases

ABSTRACTObjective: Factor VII deficiency is the commonest of the rare bleeding disorders with limited knowledge on clinical profile. The objective of this study was to study the prevalence and clinico-hematological profile of factor VII-deficient patients.Methods: It is a retrospective observational study of probable inherited factor VII deficiency covering 18 months. Their clinical profile, family history, investigation and treatment records were studied in detail.Results: The study group comprised of total 12 factor VII deficiency cases with mean age of 17.5 years of onset of symptoms. The commonest symptom was menorrhagia (41.6%) followed by epistaxis (25%) and easy bruisability (16.6%). These 12 patients when categorized according to bleeding severity: severe bleeding – 2, moderate bleeding – 3, mild bleeding – 6 and asymptomatic – 1. All cases had prolonged prothrombin time (PT) with mean PT of 35.4 seconds (range 18–50 seconds) and mean prolongation of PT from upper limit of normal – 19.4 seconds (range 2–34 seconds). Factor VII levels ranged from < 1–40% in these patients. Clinical symptoms were not in concordance with factor levels. Of 12 patients, required treatment other than local measures.Discussion and Conclusion: Inherited factor VII deficiency is the commonest autosomally inherited factor deficiency with marked variation in the age of presentation and clinical symptoms. The laboratory results in form of PT and factor VII levels do not correlate with the severity of clinical presentation. A comprehensive evaluation to exclude acquired causes of factor VII deficiency, e.g. obesity, liver diseases, vitamin K deficiency and acquired inhibitors is required before labeling it as inherited in the absence of family history and molecular studies.

Muscle health and performance in monozygotic twins with 30 years of discordant exercise habits.

Physical health and function depend upon both genetic inheritance and environmental factors (e.g., exercise training). To enhance the understanding of heritability/adaptability, we explored the skeletal muscle health and physiological performance of monozygotic (MZ) twins with > 30 years of chronic endurance training vs. no specific/consistent exercise. One pair of male MZ twins (age = 52 years; Trained Twin, TT; Untrained Twin, UT) underwent analyses of: (1) anthropometric characteristics and blood profiles, (2) markers of cardiovascular and pulmonary health, and (3) skeletal muscle size, strength, and power and molecular markers of muscle health. This case study represents the most comprehensive physiological comparison of MZ twins with this length and magnitude of differing exercise history. TT exhibited: (1) lower body mass, body fat%, resting heart rate, blood pressure, cholesterol, triglycerides, and plasma glucose, (2) greater relative cycling power, anaerobic endurance, and aerobic capacity (VO2max), but lower muscle size/strength and poorer muscle quality, (3) more MHC I (slow-twitch) and fewer MHC IIa (fast-twitch) fibers, (4) greater AMPK protein expression, and (5) greater PAX7, IGF1Ec, IGF1Ea, and FN14 mRNA expression than UT. Several measured differences are the largest reported between MZ twins (TT expressed 55% more MHC I fibers, 12.4ml/kg/min greater VO2max, and 8.6% lower body fat% vs. UT). These data collectively (a) support utilizing chronic endurance training to improve body composition and cardiovascular health and (b) suggest the cardiovascular and skeletal muscle systems exhibit greater plasticity than previously thought, further highlighting the importance of studying MZ twins with large (long-term) differences in exposomes.

Plasticity of Meiotic Recombination Rates in Response to Temperature in Arabidopsis.

Meiotic recombination shuffles genetic information from sexual species into gametes to create novel combinations in offspring. Thus, recombination is an important factor in inheritance, adaptation, and responses to selection. However, recombination is not a static parameter; meiotic recombination rate is sensitive to variation in the environment, especially temperature. That recombination rates change in response to both increases and decreases in temperature was reported in Drosophila a century ago, and since then in several other species. But it is still unclear what the underlying mechanism is, and whether low- and high-temperature effects are mechanistically equivalent. Here, we show that, as in Drosophila, both high and low temperatures increase meiotic crossovers in Arabidopsis thaliana We show that, from a nadir at 18°, both lower and higher temperatures increase recombination through additional class I (interfering) crossovers. However, the increase in crossovers at high and low temperatures appears to be mechanistically at least somewhat distinct, as they differ in their association with the DNA repair protein MLH1. We also find that, in contrast to what has been reported in barley, synaptonemal complex length is negatively correlated with temperature; thus, an increase in chromosome axis length may account for increased crossovers at low temperature in A. thaliana, but cannot explain the increased crossovers observed at high temperature. The plasticity of recombination has important implications for evolution and breeding, and also for the interpretation of observations of recombination rate variation among natural populations.

The current state of research on psychiatric genetics in Poland and the world: A report covering recent years

The aim of this article was to review the results of research carried out in recent years in relation to genetic studies in psychiatry. The authors’ focus is on the selected disorders, with particular emphasis on the reports from Poland. For this purpose, the most often mentioned studies describing genes and biomarkers involved in psychiatry were selected. Genetic polymorphisms were described in relation to schizophrenia, alcoholism, addiction to psychoactive substances, autistic spectrum, unipolar depression and bipolar disorder, eating disorders and other psychiatric disorders. Characterizing the impact of inheritance factors on the processes in the central nervous system, it can be observed that some biological mechanisms forms associations with tested genetic variants and this combination is linked with the risk of mental disorders. To understand the role of psychiatric genetics, surveys which join genotype and phenotype associations (endophenotype) are essential. It seems important to study and search for associations of genes polymorphisms and biomarkers with mental and psychiatric disorders in order to better understanding the biological basis of the disease and more effective treatment of patients. In many cases, the variability analysis of selected genes sheds new light on understanding the etiology of diseases and mental disorders. Genetics is a powerful technique which allows us to study the impact of the inherited variance on changes in mental state, even without having prior knowledge about biological changes.

Perceptions about Sickle Cell Disease among Adults in Al Baha Region : A Cross-Sectional Study

Background: Sickle-cell disease (SCD) is a group of genetic disorders characterized by abnormally shaped red blood cells (RBCs), which are destroyed at increased rates, leading to anemia. Recently, Saudi Arabia has been reported to have an increased prevalence of SCD. Objective: The aim of the present study was to assess perceptions about SCD among the general population in Albaha region, Saudi Arabia, and the possible relationship between their levels of knowledge and socio-demographic characteristics. Methods: The study was carried out on 218 Saudi subjects who completed the self-administered questionnaires during the study period. Results: This study demonstrated that more than two-thirds of the respondents (68.80%) had good knowledge about basics of sickle cell disease. Those with poor knowledge (31.20%) were mainly younger males and works as businessmen and housewives, and all of them had no previous experience with SCD child. Despite the recorded favorable level of knowledge, certain gaps in knowledge were identified; most of them falsely believed that some foods like fava beans, lentils, falafel made with fava beans, vigna and /or nuts could precipitate sickle-cell crisis.Moreover, in depth information of our study population about pattern of inheritance of SCD and its complications were not sufficient. Conclusion: In our study, a good level of awareness regarding SCD was found. Some of the respondents were confused about the nature of inheritance, complications and dietary factors related to the disease. So, community health education meetings and/or media programs to increase the public awareness are recommended.

The arrangement of the coronary artery trunks is subject to inheritance factors: A study in Syrian hamsters.

The concept that anatomical variations in the coronary artery tree might be influenced by genes is relatively old. However, empirical evidence on the effect of genotype on the coronary morphology is still scarce. In the Syrian hamster, there is a septal coronary artery which arises from the left or from the right coronary artery and supplies most of the interventricular septum. The aim was to decide whether the anatomical origin of the septal artery is subject to inheritance factors. Overall, 483 internal casts of the heart and coronary arteries were examined. All the hamsters included in this study had normal coronary arteries. The results of 74 crosses were compared statistically to seek for any significant difference between the phenotypes of the offspring and the phenotypes of the parents. The left septal artery was over-represented in the offspring of crosses between parents having both a left septal artery (p<.01), while the right septal artery was over-represented in the offspring of crosses between parents, one with a right and the other with a left septal artery (p<.001), and, more markedly, in the offspring of crosses between parents both with a right septal artery (p<.001). These results are the first to reveal that the coronary artery pattern is influenced by genetic factors, at least in its proximal portion with regard to the aorta.

Cakutome, a high-throughput tool for molecular diagnosis and identification of novel causative genes for CAKUT patients

Introduction Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of renal failure in children. CAKUT are phenotypically and genetically heterogeneous and more than 50 genes have been reported as mutated in patients. The most frequently mutated genes are those encoding transcription factors HNF1B, PAX2, EYA1 and SIX1. Most of the other genes are only mutated in a few patients and their implication is sometimes elusive. Methods We developped a targeted exome sequencing strategy («CAKUTOME», sureselect Agilent) focusing on 330 genes, including known validated or likely causative CAKUT genes, as well as candidate genes. A total of 215 unrelated patients were analysed, including 50 who had previously been tested for HNF1B, PAX2, EYA1 and/or SIX1 mutations by Sanger sequencing. Results/discussion/conclusion This approach proved to be an efficient and cost-effective strategy to identify pathogenic mutations and copy number variations in known CAKUT genes. The 25/165 rate of mutation we identified in HNF1B, PAX2, EYA1 or SIX1 is similar to the one obtained by Sanger sequencing. In addition, we identified heterozygous mutations in ANOS1 (Kallmann syndrome), GATA3 (hypoparathyroidism, deafness and kidney disease), or CHD7 (Charge syndrome), and biallelic mutation in KIF14 in 2, 3, 1 and 2 cases, respectively. Our data also led to the identification of a novel CAKUT gene, the mutation/deletion of which affected 5 unrelated cases in the cohort. Moreover, we identified variants in several other genes never reported as mutated in CAKUT patients, whose pathogenicity is being tested. Finally, no relevant variant was identified in 40 % of our series. Although mutations in gene(s), non-coding regions or microRNAs not targeted in our CAKUTOME could be involved in some of these cases, complex inheritance, somatic events, and/or environmental factors or epigenetic mechanisms likely explain this large fraction of cases.

Mitochondrial tRNAThr 15909A>G mutation associated with hypertension in a Chinese Han pedigree

Mitochondrial DNA mutations are one of the molecular genetic bases of hypertension. Here, we performed clinical, genetic and mutational evaluation, molecular characterization as well as biochemical analysis of a Chinese Han family with maternally inherited hypertension. The m.15909A > G variant in tRNAThr was identified. This mutation abolished a highly conserved base pairing (11U-24A) in the D-stem of tRNAThr and affected the structure and function of mitochondrial tRNAThr. As a result, the overall levels of mitochondrial translation products was decreased. The reduced mitochondrial protein synthesis resulted in the decrease in the activity of complex, and in turn, the production of ATP decreased and the generation of ROS increased. The m.15909A > G mutation maybe an inherited factor leading to the development of hypertension in this Chinese Han pedigree.

A Third Type of Resistance to Cydia pomonella Granulovirus in Codling Moths Shows a Mixed Z-Linked and Autosomal Inheritance Pattern.

Different isolates of Cydia pomonella granulovirus (CpGV) are used worldwide to control codling moth larvae (Cydia pomonella) in pome fruit production. Two types of dominantly inherited field resistance of C. pomonella to CpGV have been recently identified: Z-chromosomal type I resistance and autosomal type II resistance. In the present study, a CpGV-resistant C. pomonella field population (termed SA-GO) from northeastern Germany was investigated. SA-GO individuals showed cross-resistance to CpGV isolates of genome group A (CpGV-M) and genome group E (CpGV-S), whereas genome group B (CpGV-E2) was still infective. Crossing experiments between individuals of SA-GO and the susceptible C. pomonella strain CpS indicated the presence of a dominant autosomal inheritance factor. By single-pair inbreeding of SA-GO individuals for two generations, the genetically more homogenous strain CpRGO was generated. Resistance testing of CpRGO neonates with different CpGV isolates revealed that isolate CpGV-E2 and isolates CpGV-I07 and -I12 were resistance breaking. When progeny of hybrid crosses and backcrosses between individuals of resistant strain CpRGO and susceptible strain CpS were infected with CpGV-M and CpGV-S, resistance to CpGV-S appeared to be autosomal and dominant for larval survivorship but recessive when success of pupation of the hybrids was considered. Inheritance of resistance to CpGV-M, however, is proposed to be both autosomal and Z linked, since Z linkage of resistance was needed for pupation. Hence, we propose a further type III resistance to CpGV in C. pomonella, which differs from type I and type II resistance in its mode of inheritance and response to CpGV isolates from different genome groups.IMPORTANCE The baculovirus Cydia pomonella granulovirus (CpGV) is registered and applied as a biocontrol agent in nearly all pome fruit-growing countries worldwide to control codling moth caterpillars in an environmentally friendly manner. It is therefore the most widely used commercial baculovirus biocontrol agent. Since 2005, field resistance of codling moth to CpGV products has been observed in more than 40 field plantations in Europe, threatening organic and integrated apple production. Knowledge of the inheritance and mechanism(s) of resistance is indispensable for the understanding of host response to baculovirus infection on the population level and the coevolutionary arms race between virus and host, as well as for the development of appropriate resistance management strategies. Here, we report a codling moth field population with a new type of resistance, which appears to follow a highly complex inheritance in regard to different CpGV isolates.

High mobility group box 1 in diabetic nephropathy.

Type 2 diabetes (T2D) is a complex disorder caused by the combined effects of genetic inheritance and environmental factors. The abnormal secretion of albumin via urine is the characteristic feature of a diabetic nephropathy (DN) patient. Moreover, the detection of this observable characteristic feature of DN is quite late. As a result the time, at which DN is observable, large extent of kidney damage has already occurred. Thus, this late observation significantly decreases the chances of efficient management of DN and associated outcomes. The current biomarker used to detect DN is microalbuminuria, the presence of albumin in the urine. However, the current biomarkers often lead to false negative results. The high mobility group box (HMGB)1 is an upcoming molecule being explored for its application in the management of DN. The present review enlightens the current status of HMGB1 in DN.

The RNAi Inheritance Machinery of Caenorhabditis elegans.

Gene silencing mediated by dsRNA (RNAi) can persist for multiple generations in Caenorhabditis elegans (termed RNAi inheritance). Here we describe the results of a forward genetic screen in C. elegans that has identified six factors required for RNAi inheritance: GLH-1/VASA, PUP-1/CDE-1, MORC-1, SET-32, and two novel nematode-specific factors that we term here (heritable RNAi defective) HRDE-2 and HRDE-4 The new RNAi inheritance factors exhibit mortal germline (Mrt) phenotypes, which we show is likely caused by epigenetic deregulation in germ cells. We also show that HRDE-2 contributes to RNAi inheritance by facilitating the binding of small RNAs to the inheritance Argonaute (Ago) HRDE-1 Together, our results identify additional components of the RNAi inheritance machinery whose conservation provides insights into the molecular mechanism of RNAi inheritance, further our understanding of how the RNAi inheritance machinery promotes germline immortality, and show that HRDE-2 couples the inheritance Ago HRDE-1 with the small RNAs it needs to direct RNAi inheritance and germline immortality.

Purinergic signaling during intestinal inflammation

Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer. Aberrant purinergic signaling pathways have been implicated in disordered thromboregulation and immune dysregulation, as noted in the pathogenesis of IBD and other gastrointestinal/hepatic autoimmune diseases. Expression of CD39 on endothelial or immune cells allows for homeostatic integration of hemostasis and immunity, which are disrupted in IBD. Our focus in this review is on novel aspects of the functions of CD39 and related NTPDases in IBD. Regulated CD39 activity allows for scavenging of extracellular nucleotides, the maintenance of P2-receptor integrity and coordination of adenosinergic signaling responses. CD39 together with CD73, serves as an integral component of the immunosuppressive machinery of dendritic cells, myeloid cells, T and B cells. Genetic inheritance and environental factors closely regulate the levels of expression and phosphohydrolytic activity of CD39, both on immune cells and released microparticles. Purinergic mechanisms associated with T regulatory and supressor T helper type 17 cells modulate disease activity in IBD, as can be modeled in experimental colitis. As a recent example, upregulation of CD39 is dependent upon ligation of the aryl hydrocarbon receptor (AHR), as with natural ligands such as bilirubin and 2-(1' H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Decreased expression of CD39 and/or dysfunctional AHR signaling, however, abrogates the protective effects of immunosuppressive AHR ligands. These factors could also serve as biomarkers of disease activity in IBD. Heightened thrombosis, inflammation, and immune disturbances as seen in IBD appear to be associated with aberrant purinergic signaling. Ongoing development of therapeutic strategies augmenting CD39 ectonucleotidase bioactivity via cytokines or AHR ligands offers promise for management of thrombophilia, disordered inflammation, and aberrant immune reactivity in IBD.

Age-Dependent Association of TNFSF15/TNFSF8 Variants and Leprosy Type 1 Reaction.

A current major challenge in leprosy control is the prevention of permanent disabilities. Host pathological inflammatory responses termed type 1 reaction (T1R) are a leading cause of nerve damage for leprosy patients. The environmental or inherited factors that predispose leprosy cases to undergo T1R are not known. However, studies have shown an important contribution of host genetics for susceptibility to T1R. We have previously identified variants encompassing the TNFSF15/TNFSF8 genes as T1R risk factors in a Vietnamese sample and replicated this association in a Brazilian sample. However, we failed to validate in Brazilian patients the strong association of TNFSF15/TNFSF8 markers rs6478108 and rs7863183 with T1R that we had observed in Vietnamese patients. Here, we investigated if the lack of validation of these variants was due to age-dependent effects on association using four independent population samples, two from Brazil and two from Vietnam. In the combined analysis across the four samples, we observed a strong association of the TNFSF15/TNFSF8 variants rs6478108, rs7863183, and rs3181348 with T1R (pcombined = 1.5E−05, pcombined = 1.8E−05, and pcombined = 6.5E−06, respectively). However, the association of rs6478108 with T1R was more pronounced in leprosy cases under 30 years of age compared to the global sample [odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.54–2.46, pcombined = 2.5E−08 versus OR = 1.46, 95% CI = 1.23–1.73, pcombined = 1.5E−05]. A multivariable analysis indicated that the association of rs6478108 with T1R was independent of either rs7863183 or rs3181348. These three variants are known regulators of the TNFSF8 gene transcription level in multiple tissues. The age dependency of association of rs6478108 and T1R suggests that the genetic control of gene expression varies across the human life span.