Genetic Transmission Research Articles

Clinician’s perspective about risk and protective factors of substance use: a qualitative exploration

ABSTRACT Objective The present study primarily examines the clinician’s perspective on the initiation of substance use among Pakistani adolescents by using bio-psycho-social correlates. Method Qualitative research design was used to explore the risk and protective factors of substance use. For this purpose, twelve clinical experts i.e., clinical psychologists (N = 6 with HEC-recognized MS Clinical Psychology degree) and psychiatrists (N = 6 with valid PMC) were approached for in-depth interviews. The inclusion of experts with at least five years of experience in dealing with Substance Use Disorders (SUD). Their verbatim was transcribed and thematically analyzed by using NVIVO v.12. Results The findings of this study revealed three main themes for risky behavior i.e., temperamental factors (self-esteem-related problems, anxiety sensitivity, experimentation, and assertiveness issue), family-level factors (parenting style, family conflict, and genetic transmission), and environmental risk factors (peer influence, role of media, and easy access of substance). In addition, the protective factor of substance use also emerged i.e., religiosity or spirituality along with the appropriate parenting which can overcome the risk tendencies of substance use in adolescents. Conclusion The study concluded that appropriate parenting can make a bridge between risk factors of substance use.

Large Multicountry Outbreak of Invasive Listeriosis by a Listeria monocytogenes ST394 Clone Linked to Smoked Rainbow Trout, 2020 to 2021.

Whole-genome sequencing (WGS) has revolutionized surveillance of infectious diseases. Disease outbreaks can now be detected with high precision, and correct attribution of infection sources has been improved. Listeriosis, caused by the bacterium Listeria monocytogenes, is a foodborne disease with a high case fatality rate and a large proportion of outbreak-related cases. Timely recognition of listeriosis outbreaks and precise allocation of food sources are important to prevent further infections and to promote public health. We report the WGS-based identification of a large multinational listeriosis outbreak with 55 cases that affected Germany, Austria, Denmark, and Switzerland during 2020 and 2021. Clinical isolates formed a highly clonal cluster (called Ny9) based on core genome multilocus sequence typing (cgMLST). Routine and ad hoc investigations of food samples identified L. monocytogenes isolates from smoked rainbow trout filets from a Danish producer grouping with the Ny9 cluster. Patient interviews confirmed consumption of rainbow trout as the most likely infection source. The Ny9 cluster was caused by a MLST sequence type (ST) ST394 clone belonging to molecular serogroup IIa, forming a distinct clade within molecular serogroup IIa strains. Analysis of the Ny9 genome revealed clpY, dgcB, and recQ inactivating mutations, but phenotypic characterization of several virulence-associated traits of a representative Ny9 isolate showed that the outbreak strain had the same pathogenic potential as other serogroup IIa strains. Our report demonstrates that international food trade can cause multicountry outbreaks that necessitate cross-border outbreak collaboration. It also corroborates the relevance of ready-to-eat smoked fish products as causes for listeriosis. IMPORTANCE Listeriosis is a severe infectious disease in humans and characterized by an exceptionally high case fatality rate. The disease is transmitted through consumption of food contaminated by the bacterium Listeria monocytogenes. Outbreaks of listeriosis often occur but can be recognized and stopped through implementation of whole-genome sequencing-based pathogen surveillance systems. We here describe the detection and management of a large listeriosis outbreak in Germany and three neighboring countries. This outbreak was caused by rainbow trout filet, which was contaminated by a L. monocytogenes clone belonging to sequence type ST394. This work further expands our knowledge on the genetic diversity and transmission routes of an important foodborne pathogen.

Gaucher Disease in Internal Medicine and Dentistry

Gaucher disease (GD) is a lysosomal storage pathological condition, characterized by a genetic autosomal recessive transmission. The GD cause is the mutation of GBA1 gene, located on the chromosome 1 (1q21), that induces the deficiency of the lysosomal enzyme glucocerebrosidase with consequent abnormal storage of its substrate (glucosylceramide), in macrophages. The GD incidence in the general population varies from 1:40,000 to 1:60,000 live births, but it is higher in the Ashkenazi Jewish ethnicity (1:800 live births). In the literature, five different types of GD are described: type 1, the most common clinical variant in Europe and USA (90%), affects the viscera; type 2, characterized by visceral damage and severe neurological disorders; type 3, in which the neurological manifestations are variable; cardiovascular type; and, finally, perinatal lethal type. The most affected tissues and organs are the hematopoietic system, liver, bone tissue, nervous system, lungs, cardiovascular system and kidneys. Another aspect of GD is represented by oral and dental manifestations. These can be asymptomatic or cause the spontaneous bleeding, the post oral surgery infections and the bone involvement of both arches through the Gaucher cells infiltration into the maxilla and mandibular regions. The pharmacological treatment of choice is the enzyme replacement therapy, but the new pharmacological frontiers are represented by oral substrate reduction therapy, chaperone therapy, allogeneic hematopoietic stem cell transplantation and gene therapy.

Pathogenicity, transmissibility, and immunogenicity of recombinant H9N2 avian influenza viruses based on representative viruses of Southeast China

H9N2 is currently the main subtype of avian influenza in China. In order to use reverse genetics to rapid preparation of seed strains for vaccine production, and intend to prevent and control the H9N2 subtype epidemic strains of avian influenza virus (AIV). In this study, we successfully rescued 2 H9N2 recombinant viruses based on the representative viruses of Southeast China and confirmed by RT-PCR and sequencing. Genetic stability, pathogenicity, transmissibility, and antigenicity of 2 recombinant viruses were evaluated. Compared to the FZ1, the growth kinetics of H9N2(HA+NA)/PR8 showed no significant difference, H9N2(HA+NA+M+PB1)/PR8 was slightly lower. Our study also confirmed 2 recombinant viruses had good genetic stability after 10 passages but possessed lower pathogenicity than FZ1. Although both recombinant viruses led to seroconversion in all inoculated birds on 14 dpi, they complete loss of viral transmission of the virus to contact birds. In addition, birds were immunized via hypodermic route by inactivated vaccines of H9N2(HA+NA)/PR8, H9N2(HA+NA+M+PB1)/PR8 and wild-type virus with a single dose, and the results showed that the hemagglutination inhibition titers on 21 dpv were 10.5, 9.6, and 10.5 log2, respectively. And recombinant viruses both provided a certain protection against wild-type virus challenge. In conclusion, these data indicated that 2 recombinant viruses will be expected to be used as inactivated vaccines to controlling the spread of H9N2 subtype AIV even have potential application for attenuated viral vaccines, which provides a reference for the prevention and control of influenza virus pandemics.

Characterization of a DRC1 null variant associated with primary ciliary dyskinesia and female infertility

ProposeWe here present a female case with primary ciliary dyskinesia (PCD) and infertility. In this report, we also present the evaluation of the patient family, including her twin sister, also with PCD and infertility.MethodsConfirmation of the PCD clinical diagnosis was performed through assessment of cilia motility, by high-speed video microscopy (HSVM), axoneme ultrastructure, by transmission electron microscopy (TEM), and genetic characterization, by whole-exome sequence (WES). Gene expression studies used qPCR for mRNA expression and immunofluorescence to determine cell protein localization.ResultsWe identified a homozygous nonsense variant in the DRC1 gene (NM 145038.5:c.352C>T (p.Gln118Ter)) in the female patient with PCD and infertility that fit the model of autosomal recessive genetic transmission. This variant eventually results in a dyskinetic ciliary beat with a lower frequency and a partial lack of both dynein arms as revealed by TEM analysis. Moreover, this variant implies a decrease in the expression of DRC1 mRNA and protein. Additionally, expression analysis suggested that DRC1 may interact with other DRC elements.ConclusionsOur findings suggest that the DRC1 null variant leads to PCD associated with infertility, likely caused by defects in axoneme from Fallopian tube cilia. Overall, our outcomes contribute to a better understanding of the genetic factors involved in the pathophysiology of PCD and infertility, and they highlight the interaction of different genes in the patient phenotype, which should be investigated further because it may explain the high heterogeneity observed in PCD patients.

Genomic Epidemiology and Transmission Dynamics of Global Coxsackievirus B4.

The aim of this study was to determine the global genetic diversity and transmission dynamics of coxsackievirus B4 (CVB4) and to propose future directions for disease surveillance. Next-generation sequencing was performed to obtain the complete genome sequence of CVB4, and the genetic diversity and transmission dynamics of CVB4 worldwide were analyzed using bioinformatics methods such as phylogenetic analysis, evolutionary dynamics, and phylogeographic analysis. Forty complete genomes of CVB4 were identified from asymptomatic infected individuals and hand, foot, and mouth disease (HFMD) patients. Frequent recombination between CVB4 and EV-B multiple serotypes in the 3Dpol region was found and formed 12 recombinant patterns (A-L). Among these, the CVB4 isolated from asymptomatic infected persons and HFMD patients belonged to lineages H and I, respectively. Transmission dynamics analysis based on the VP1 region revealed that CVB4 epidemics in countries outside China were dominated by the D genotype, whereas the E genotype was dominant in China, and both genotypes evolved at a rate of > 6.50 × 10-3 substitutions/site/year. CVB4 spreads through the population unseen, with the risk of disease outbreaks persisting as susceptible individuals accumulate. Our findings add to publicly available CVB4 genomic sequence data and deepen our understanding of CVB4 molecular epidemiology.

The genetic diversity, replication, and transmission of 2009 pandemic H1N1 viruses in China.

The 2009 pandemic H1N1 influenza A virus (pdm09) continue to evolve, and few studies have systemically analyzed the evolution, replication, and transmission of pmd09 viruses in China. To better understand the evolution and pathogenicity of pdm09 viruses, we systematically analyzed viruses that were confirmed in 2009-2020 in China and characterized their replication and transmission ability. We extensively analyzed the evolution characteristics of pdm/09 in China over the past decades. The replication ability of 6B.1 and 6B.2 lineages on Madin-Darby canine kidney (MDCK) and human lung adenocarcinoma epithelial (A549) cells and their pathogenicity and transmission in guinea pigs were also compared. In total, 3,038 pdm09 viruses belonged to clade 6B.1 (62% of all pdm09 viruses) and clade 6B.2 (4%). Clade 6B.1 pdm09 viruses are the predominant clade, with proportions of 54.1%, 78.9%, 57.2%, 58.6%, 61.7%, 76.3%, and 66.6% in the North, Northeast, East, Central, South, Southwest, and Northeast regions in China, respectively. The isolation proportion of clade 6B.1 pdm/09 viruses was 57.1%, 74.3%, 96.1%, 98.2%, 86.7%, and 78.5% in 2015-2020, respectively. A clear differentiation time point appeared in 2015 before which the evolution trend of pdm09 viruses in China was similar to that in North America but then showed a different trend after that point. To characterize pdm09 viruses in China after 2015, we further analyzed 33 pdm09 viruses isolated in Guangdong in 2016-2017, among which A/ Guangdong/33/2016 and A/Guangdong/184/2016 (184/2016) belonged to clade 6B.2, and the other 31 strains belonged to clade 6B.1. A/Guangdong/887/2017 (887/2017) and A/Guangdong/752/2017 (752/2017) (clade 6B.1), 184/2016 (clade 6B.2) and A/California/04/2009 (CA04) replicated efficiently in MDCK cells and A549 cells, as well as the turbinates of guinea pigs. 184/2016 and CA04 could transmit among guinea pigs through physical contact. Our findings provide novel insights into the evolution, pathogenicity, and transmission of pdm09 virus. The results show that enhancing surveillance of pdm09 viruses and timely evaluation of their virulence are essential.

Genomic Characterization of a Vancomycin-Resistant Strain of Enterococcus faecium Harboring a rep2 Plasmid.

In China, vancomycin-resistant enterococci (VRE) was not a common occurrence, and research on the genetic context and transmission mechanism of vanA-plasmid was scarce. The aim of this study was to molecularly characterise a vancomycin-resistant Enterococcus faecium isolate from a bloodstream infection and determine the genetic environment and delivery pattern of the plasmid carrying vancomycin-resistant gene. In May 2022, a vancomycin-resistant strain of Enterococci was identified during routine screening for VRE bacteria at the First Affiliated Hospital, Zhejiang University School of Medicine. Utilizing matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), the isolate was accurately identified. Antimicrobial susceptibility and whole-genome sequencing (WGS) were employed to perform phenotypic and genomic analysis, respectively. Further bioinformatics analyses was carried out to characterize the vanA-bearing plasmid. The antimicrobial susceptibility test showed that SJ2 strain was resistant to multiple antimicrobials, including ampicillin, benzylpenicillin, ciprofloxacin, erythromycin, levofloxacin, streptomycin, and vancomycin. Whole-genome analysis revealed that SJ2 strain carries several antimicrobial resistance genes and virulence determinants. MLST analysis found that SJ2 strain belongs to an unknown ST type. Plasmid analysis confirmed that the vanA gene was located on a variant of ~50 kb rep2 plasmid. Our study found that vanA-bearing rep2 plasmid is a potential source of dissemination and outbreak, and continuous surveillance is necessary to control its spread in Hangzhou, China.

Genetic and Cultural Transmission of Alcohol Use Disorder in Swedish Twin Pedigrees.

Using Swedish nationwide registry data, we investigated the contribution of genetic and environmental risk factors to the etiology of alcohol use disorder (AUD) by extended twin pedigree modeling. AUD was defined using public inpatient, outpatient, prescription, and criminal records. Three-generational pedigrees were selected for index individuals born between 1980 and 1990, obtained from the national twin and genealogical registers, whose parents were twins. Relatives of the twins included in the pedigrees were their parents, siblings, spouses, and children. Genetic structural equation modeling was applied to the population-based data on AUD, using OpenMx, with age used as a covariate. Analyses including up to 162,469 individuals in 18,971 pedigrees estimated AUD prevalence at 5%-12% in men and 2%-5% in women. Results indicated substantial heritability (about 50%-60%), of which a portion upwards of 5% was attributable to the consequences of assortative mating. Contributions of shared environmental factors to AUD, which represent a mix of within- and cross-generational effects, appeared to be moderate (about 10%-20%). Unique environment accounted for the remaining variance (about 20%-30%). Sex differences in the magnitude of the variance components suggested higher heritability in men and correspondingly higher shared environmental contributions in women. Using objective registry data, we found that AUD is highly heritable. Furthermore, shared environmental factors contributed significantly to the liability of AUD in both men and women.

Neurogenomics in Africa: current state, challenges, opportunities, and recommendation.

Neurological diseases are becoming more common in Africa. Current estimates indicate that Africa has a significant burden of neurological illnesses, though it is unclear what fraction of the burden may be linked to genetic transmission. In recent years, there has been a significant expansion in the knowledge of the genetic basis of neurological illnesses. This has been made possible mainly by the positional cloning research paradigm, which uses linkage studies to pinpoint specific genes on chromosomes and targeted screening of Mendelian neurological illnesses to identify the causative genes. However, there is currently very little and unequal geographic knowledge about neurogenetics in African people. The lack of collaboration between academics studying neurogenomics and bioinformatics contributes to the scarcity of large-scale neurogenomic investigations in Africa. The primary cause is a shortage of funding from the African government for clinical researchers; this has resulted in heterogeneity in research collaboration in the region as African researchers work more closely with researchers outside the region due to pulling factors of standardized laboratory resources and adequate funding. Therefore, adequate funding is required to elevate researchers' morale and give them the resources they need for their neurogenomic and bioinformatics studies. For Africa to fully benefit from this significant research area, substantial and sustainable financial investments in the training of scientists and clinicians will be required.

Whole-genome sequencing to characterize the genetic structure and transmission risk of Mycobacterium tuberculosis in Yichang city of China.

The burden of both general and drug-resistant tuberculosis in rural areas is higher than that in urban areas in China. To characterize the genetic structure and transmission risk of Mycobacterium tuberculosis in rural China, we used whole genome sequencing to analyze clinical strains collected from patients in two counties of Yichang for three consecutive years. From 2018 to 2020, sputum samples were collected for cultures from patients with suspected tuberculosis in Yidu and Zigui county, and DNA was extracted from the positive strains for genome sequencing. The online SAM-TB platform was used to identify the genotypes and drug resistance-related mutations of each strain, establish a phylogenetic tree, and calculated the genetic distances between pairwise strains. Twelve single nucleotide polymorphisms (SNPs) were used as thresholds to identify transmission clusters. The risk of related factors was estimated by univariable and multivariable logistic regression. A total of 161 out of the collected 231 positive strains were enrolled for analysis, excluding non-tuberculous mycobacterium and duplicate strains from the same patient. These strains belonged to Lineage 2 (92, 57.1%) and Lineage 4 (69, 42.9%), respectively. A total of 49 (30.4%) strains were detected with known drug resistance-related mutations, including 6 (3.7%) multidrug-resistant-TB (MDR-TB) strains and 11 (6.8%) RIF-resistant INH-susceptible TB (Rr-TB) strains. Six of the MDR/Rr-TB (35.3%) were also resistant to fluoroquinolones, which made them pre-extensively drug-resistant TB (pre-XDR-TB). There were another seven strains with mono-resistance to fluoroquinolones and one strain with resistance to both INH and fluoroquinolones, making the overall rate of fluoroquinolones resistance 8.7% (14/161). A total of 50 strains (31.1%) were identified as transmission clusters. Patients under 45 years old (adjusted odds ratio 3.46 [95% confidential intervals 1.28-9.35]), treatment-naive patients (6.14 [1.39-27.07]) and patients infected by lineage 4 strains (2.22 [1.00-4.91]) had a higher risk of transmission. The drug resistance of tuberculosis in rural China, especially to the second-line drug fluoroquinolones, is relatively serious. The standardized treatment for patients and the clinical use of fluoroquinolones warrant attention. At the same time, the recent transmission risk of tuberculosis is high, and rapid diagnosis and treatment management at the primary care needs to be strengthened.

First detection of Blastocystis sp. in migratory whooper swans (Cygnus cygnus) in China

Blastocystis is a usual intestinal protist that always found in humans and various animals. Currently, the prevalence of Blastocystis in the migratory whooper swan (Cygnus cygnus) is unknown. In our research, we aimed to determine the occurrence, prevalence, subtype distribution and dynamic transmission mechanisms of Blastocystis in the migratory whooper swan in China. We also assessed the zoonotic potential of Blastocystis isolates, as well as possible routes of transmission and impact of this organism on One Health perspective. Fecal samples (n = 770) were collected from whooper swans inhabiting the Sanmenxia Swan Lake National Urban Wetland Park, China. The overall prevalence of Blastocystis was 11.6% (89/770). We identified 9 subtypes of Blastocystis sp., including 5 zoonotic subtypes [ST1 (Cakir et al., 2019 (8)), ST4 (Selma and Karanis, 2011 (4)), ST5 (Stensvold et al., 2009 (1)), ST6 (Fare et al., 2019 (5)) and ST7(58)] and 3 host-specific subtypes [ST10 (Zhao et al., 2018 (7)), ST14 (Tan et al., 2010 (2)), ST23 (Wang et al., 2018 (3)), and ST25 (Stensvold et al., 2009 (1))]. Subtypes ST4, ST5, ST6, ST10, ST14, ST23, and ST25 were first identified in the whooper swan. Among these subtypes, ST23 and ST25 were identified in birds for the first time, indicating that these subtypes are expanding their host range. So far, this is the first research reporting on the prevalence and subtypes distribution of Blastocystis in the migratory whooper swan in China. The findings obtained in this study will provide new insights into the genetic diversity and transmission routes of Blastocystis, and the possible public health concerns posed by this organism.

Mechanism of high-frequent horizontal gene transfer in Gram positive bacterial pathogens

Horizontal gene transfer through transconjugation and natural transformation plays a major role in the spread of antimicrobial resistance. Although the phenomenon of genetic element transmission has long been known, the rapid increase in the number of antimicrobial resistant bacteria in recent years and the accompanying accumulation of genomic information have revealed that horizontal gene transfer contributes to genome plasticity in various ways. The author reported the molecular mechanism of the antimicrobial activity of the accessory factor bacteriocin encoded by the junctional transfer plasmid of Enterococcus faecalis, a representative Gram-positive opportunistic pathogen that is concerned as highly antimicrobial resistant, and found diversity in the selfimmune system based on epidemiological studies. In addition, the author established a technique to visualize and quantify genomic recombination by natural transformation in Streptococcus pneumoniae which is also one of the most concerns for antimicrobial resistance and vaccine escape, at single cells level resolution in real time. Focuses on outcome from these research, this paper introduces the molecular mechanisms that promote horizontal gene transmission and the prospects for their technological application.

ПРОГНОСТИЧНА КОМПЕТЕНТНІСТЬ УЧИТЕЛЯ: СУТЬ І МІСЦЕ У ПРОФЕСІЙНОМУ СТАНДАРТІ

Background. The article presents the analysis of prognostic competence of teacher. Authors support the point of view of Jerome B. Gardner, that a prognostic competence is an ability to understand the necessities of students and envisage the possible ways of their development, that include ability to observe students, analyse their behavior and give timely and corresponding support to them. Results. The prognostic competence of teacher not only envisages future results but also the ability to adapt oneself to the changes and create effective educational strategies. A prognostic competence can be examined as an ability of teacher to understand the necessities of students and envisage the possible ways of their development; it consists not only in the foresight of future results but also in ability to adapt oneself to the changes, to create effective educational strategies As the conducted analysis shows, a prognostic competence is important for teachers, as it allows to them to identify students that have difficulties in studies, and to render necessary support to them, to work out the individualized programs of studies, that deal with the necessities of students, plan lessons and activity, that are interesting for students, to create positive and supportive educational environment, where student can successfully study. Conclusions. The comparative analysis of structure of prognostic competence is conducted in the professional standards of teacher in Ukraine and Japan. In Japan in particular, the prognostic competence of teacher includes ability to take into account the necessities of certain generation, genetic transmission of experience, that it is related to that in the Japanese culture a large value is spared to traditions and domestic values. It is considered that experience that a person gets from the ancestors influences their personality and determines their way in life. Japanese teachers take into account influence of generation and genetic transmission of experience on development of the students. The prognostic competence of teacher in Japan is based on the general values of Japanese education, such as mutual respect, responsibility, harmony and independence. A teacher must take into account these values at planning, prognostication and realization of on-line tutorials.

PS-C14-10: THE INFLUENCE OF ARTERIAL HYPERTENSION ON THE PROGRESSION OF OBSTRUCTION IN HYPERTROPHIC CARDIOMYOPATHY

The nature of hypertrophic cardiomyopathy remains unexplored to date, but there is a very reasonable opinion about the genetic transmission of the disease. Given the presence of arterial hypertension in 88% of patients with hypertrophic cardiomyopathy, the issue remains relevant. To date, there is no clear understanding of hypertrophy in hypertrophic cardiomyopathy and hypertensive heart. Objective: To evaluate the effect of arterial hypertension on obstruction in hypertrophic cardiomyopathy. Material and Methods: From 2017 to 2022, 70 patients diagnosed with hypertrophic cardiomyopathy were under observation. Given the obstructive form of hypertrophic cardiomyopathy, 40 patients were operated on, Morrow operation, 30 patients diagnosed with hypertrophic cardiomyopathy without obstructive lesions are under observation, this group will take part in the study. All patients underwent genetic testing. The age of the patients ranged from 18.3 to 80.4 years, the median was 57.3 years; in most cases, pathology occurs in females, 67%, while in men it is 2 times less, 33%. Exclusion criteria for patients with aortic stenosis and “athletic” heart. Complaints were shortness of breath, headaches, dizziness, syncope. Results as a result of studies in 56% of patients test for genetic mutations is positive. Arterial hypertension was detected in 88% of patients. The duration of the disease in patients varied significantly from 1 to 35 years, the interquartile range was from 5.3 to 15.1 years, the median was 10 years. Systolic blood pressure in patients ranged from 92 to 260 mm Hg, the median was 180.5 mm Hg. Diastolic blood pressure in patients ranged from 61 to 130 mm Hg, the median was 90 mm Hg. In patients with a negative genetic analysis, 44%, a long history of arterial hypertension was revealed. Most of the patients were not adherent to therapy, despite the 3rd degree of arterial hypertension, only 13% were constantly taking antihypertensive drugs. Considering these data, we identified relevant data on echocardiography. In patients with a long history of hypertension, an increase in the left atrium, a concentric variant of hypertrophy, can be noted. There is thickening of both the aorta and the aortic valve cusps. Conclusions: The mechanism of development of hypertrophic cardiomyopathy is not completely clear; therefore, the genetic diagnosis of this disease is an integral part. Timely identified and initiated treatment of hypertension can prevent the risks of developing hypertrophy in the future.

The sleep homeostatic response to sleep deprivation in humans is heritable.

Following sleep deprivation, increases in delta power have historically been used to index increases in sleep pressure. Research in mice has demonstrated that the homeostatic delta power response to sleep deprivation is heritable. Whether this is true in humans is unknown. In the present study, we used delta power and ORP, a novel measure of sleep depth, to investigate the effects of acute sleep deprivation on sleep depth and to assess the heritability of sleep homeostasis in humans. ORP and delta power were examined during baseline and recovery sleep following 38 h of sleep deprivation in 57 monozygotic and 38 dizygotic same-sex twin pairs. Two complementary methods were used to estimate the trait heritability of sleep homeostasis. During recovery sleep, ORP was lower and delta power was higher than at baseline, indicating deeper sleep. However, at the end of the recovery night, delta power reached baseline levels but ORP demonstrated incomplete recovery. Both ORP and delta power showed a broad sense heritability of sleep homeostasis following sleep deprivation. The classical approach demonstrated an h2 estimate of 0.43 for ORP and 0.73 for delta power. Mixed-effect multilevel models showed that the proportion of variance attributable to additive genetic transmission was 0.499 (95% CI = 0.316-0.682; p < .0001) for ORP and 0.565 (95% CI = 0.403-0.726; p < .0001 for delta power. These results demonstrate that the homeostatic response to sleep deprivation is a heritable trait in humans and confirm ORP as a robust measure of sleep depth.

Advances in amyotrophic lateral sclerosis research in 2022

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, and patients and their family members are often concerned about possible genetic transmission. About 10% of patients with ALS have a family history of the disease. Furthermore, approximately 30 genes have been implicated in ALS. Advances in genetics research in 2022 led to improvements in the understanding of ALS pathogenesis, which will be important for the development of disease-modifying therapies in the future.

Diyalektikten Tedrici İlerlemeye Gelişme Fikrinin Dönüşümü: Herbert Spencer'in Bilgi Anlayışı ve Evrim Düşüncesi

Genel olarak canlılar arasındaki benzerlikler, farklılıklar, ortak atadan gelme, genetik aktarım, doğal seçilim ve güçlü olanın hayatta kalması gibi ilke ve önermeler üzerine inşa olan evrim düşüncesi, her ne kadar zirve noktasına ondokuzuncu yüzyılda Darwin ile birlikte ulaşsa da, tarihsel olarak çok daha gerilere uzanmaktadır. Canlıların ya da sosyal yapıların basit olandan karmaşığa, belirli ilkeler doğrultusunda ve zamana yayılan bir biçimde değiştiği/evrildiği fikri düşünce tarihinin ilk dönemlerinden itibaren birçok düşünür tarafından ele alından bir konu olmuştur. Ancak tarih içerisinde, canlıların bir takım ilkeler doğrultusunda var oldukları ve varlıklarını sürdürdükleri düşüncesi, mevcut bilimsel verilerin sınırlılığından dolayı bilimsel bir açıklama niteliği kazanamamış, canlılar arasındaki benzerlik, akrabalık, çeşitlenme, doğal ayıklanma ya da en iyi olanın hayatta kalması gibi süreçler bilimsel bulgular ışığında tam olarak açıklanamamıştır. Bu çerçevede, modern anlamda evrimci düşüncenin bilimsel tarihi çok daha yenidir. Bu makale, modern anlamda evrimci düşüncenin ondozuncu yüzyıldaki en önemli temsilcilerinden olan Herbert Spencer’in İlk Prensipler adlı çalışmasında tartışmaya açtığı din ve bilim arasındaki sınırların yeniden inşa çabasını ve bu sınırlar çerçevesinde düşünür tarafından geliştirilen bilimsel bilgi ve evrim hakkındaki düşünceleri konu edinmektedir.

Genetic nurture versus genetic transmission of risk for ADHD traits in the Norwegian Mother, Father and Child Cohort Study

Identifying mechanisms underlying the intergenerational transmission of risk for attention-deficit/hyperactivity disorder (ADHD) traits can inform interventions and provide insights into the role of parents in shaping their children’s outcomes. We investigated whether genetic transmission and genetic nurture (environmentally mediated effects) underlie associations between polygenic scores indexing parental risk and protective factors and their offspring’s ADHD traits. This birth cohort study included 19,506 genotyped mother-father-offspring trios from the Norwegian Mother, Father and Child Cohort Study. Polygenic scores were calculated for parental factors previously associated with ADHD, including psychopathology, substance use, neuroticism, educational attainment, and cognitive performance. Mothers reported on their 8-year-old children’s ADHD traits (n = 9,454 children) using the Parent/Teacher Rating Scale for Disruptive Behaviour Disorders. We found that associations between ADHD maternal and paternal polygenic scores and child ADHD traits decreased significantly when adjusting for the child polygenic score (pΔβ = 9.95 × 10−17 for maternal and pΔβ = 1.48 × 10−14 for paternal estimates), suggesting genetic transmission of ADHD risk. Similar patterns suggesting genetic transmission of risk were observed for smoking, educational attainment, and cognition. The maternal polygenic score for neuroticism remained associated with children’s ADHD ratings even after adjusting for the child polygenic score, indicating genetic nurture. There was no robust evidence of genetic nurture for other parental factors. Our findings indicate that the intergenerational transmission of risk for ADHD traits is largely explained by the transmission of genetic variants from parents to offspring rather than by genetic nurture. Observational associations between parental factors and childhood ADHD outcomes should not be interpreted as evidence for predominantly environmentally mediated effects.

Annual Research Review: Towards a deeper understanding of nature and nurture: combining family-based quasi-experimental methods with genomic data.

Distinguishing between the effects of nature and nurture constitutes a major research goal for those interested in understanding human development. It is known, for example, that many parent traits predict mental health outcomes in children, but the causal processes underlying such associations are often unclear. Family-based quasi-experimental designs such as sibling comparison, adoption and extended family studies have been used for decades to distinguish the genetic transmission of risk from the environmental effects family members potentially have on one another. Recently, these designs have been combined with genomic data, and this combination is fuelling a range of exciting methodological advances. In this review we explore these advances - highlighting the ways in which they have been applied to date and considering what they are likely to teach us in the coming years about the aetiology and intergenerational transmission of psychopathology.