Genetic Explanation Research Articles

The case against simplistic genetic explanations of evolution.

Humans are curious to understand the causes of traits that distinguish us from other animals and that distinguish vastly different species from one another. We also have a proclivity for simple stories and sometimes tend toward seeking and accepting simple genetic explanations for large evolutionary shifts, even to a single gene. Here, I reveal how a biased expectation of mechanistic simplicity threads through the long history of evolutionary and developmental genetics. I argue, however, that expecting a simple mechanism threatens a deeper understanding of evolution, and I define the limitations for interpreting experimental evidence in evolutionary developmental genetics.

Identification and characterization of NMNAT1 gene mutations in an Iranian patient with Leber congenital amaurosis 9.

The discovery of compound heterozygous NMNAT1 mutations (c.245T>C; p.Val82Ala and c.575A>G; p.Asp192Gly) provides a genetic explanation for Leber congenital amaurosis 9 in an Iranian patient. The proband's symptoms-including severe visual impairment, nystagmus, night blindness, and retinal degeneration-align with Leber congenital amaurosis 9 clinical features. This case underscores the value of exome-sequencing in diagnosing rare genetic disorders and highlights its role in guiding personalized genetic counseling and potential treatments. Leber congenital amaurosis is a severe early-onset inherited retinal dystrophy. This study delves into the genetic basis of Leber congenital amaurosis, pinpointing compound heterozygous mutations in the NMNAT1 gene as significant causative factors. While one mutation validates previous findings (c.245T>C; p.Val82Ala), the second (c.575A>G; p.Asp192Gly) proves novel, expanding the genetic landscape of Leber congenital amaurosis 9. Both mutations, inherited independently from nonconsanguineous parents, contribute to the intricate genetic basis of light on Leber congenital amaurosis 9 in this case. The identified mutations shed light on Leber congenital amaurosis genetics in the Iranian population, showcasing the efficacy of exome-sequencing for molecular diagnoses in hereditary retinal degeneration. These findings provide valuable insights for tailored genetic counseling and potential therapeutic interventions.

Implications of genetic attributions for addiction among addiction professionals

Given increasing emphasis on understanding the role of genes in the etiology of addictive disorders, the present study aimed to investigate the implications of genetic explanations of addiction for attitudes and beliefs about patients among addiction treatment providers. Participants were recruited from addiction-related professional organizations. The sample included professionals with medical backgrounds (n = 153) and with nonmedical backgrounds (n = 232). They viewed a description of a fictitious patient with either alcohol use disorder or gambling disorder, which was experimentally varied to indicate the presence or absence of a genetic cause. They completed measures of their genetic attributions for the patient's symptoms as well as their attitudes and beliefs about the patient. The presence of a genetic explanation increased genetic attribution ratings but did not significantly affect other measured variables. However, participants' genetic attributions for the patient's symptoms were associated with significantly lower ascriptions of blame to the patient and greater belief in the effectiveness of medication, but also with reduced confidence in the effectiveness of psychotherapy and with pessimism about the patient's prognosis. Geneticized, biomedical conceptualizations of addiction may have implications for treatment providers' attitudes toward patients.

Storytelling of Hypertrophic Cardiomyopathy Discovery.

The discovery of hypertrophic cardiomyopathy (HCM) dates back to 1958, when the pathologist Donald Teare of the St. George's Hospital in London performed autopsies in eight cases with asymmetric hypertrophy of the ventricular septum and bizarre disorganization (disarray) at histology, first interpreted as hamartoma. Seven had died suddenly. The cardiac specimens were cut along the long axis, similar to the 2D echo. In the same year, at the National Institute of Health U.S.A., Eugene Braunwald, a hemodynamist, and Andrew Glenn Morrow, a cardiac surgeon, clinically faced a patient with an apparently similar morbid entity, with a systolic murmur and subaortic valve gradient. "Discrete" subaortic stenosis was postulated. However, at surgery, Dr. Morrow observed only hypertrophy and performed myectomy to relieve the obstruction. This first Braunwald-Morrow patient underwent a successful cardiac transplant later at the disease end stage. The same Dr. Morrow was found to be affected by the familial HCM and died suddenly in 1992. The term "functional subaortic stenosis" was used in 1959 and "idiopathic hypertrophic subaortic stenosis" in 1960. Years before, in 1957, Lord Brock, a cardiac surgeon at the Guy's Hospital in London, during alleged aortic valve surgery in extracorporeal circulation, did not find any valvular or discrete subaortic stenoses. In 1980, John F. Goodwin of the Westminster Hospital in London, the head of an international WHO committee, put forward the first classification of heart muscle diseases, introducing the term cardiomyopathy (dilated, hypertrophic, and endomyocardial restrictive). In 1995, the WHO classification was revisited, with the addition of two new entities, namely arrhythmogenic and purely myocardial restrictive, the latter a paradox of a small heart accounting for severe congestive heart failure by ventricular diastolic impairment. A familial occurrence was noticed earlier in HCM and published by Teare and Goodwin in 1960. In 1989-1990, the same family underwent molecular genetics investigation by the Seidman team in Boston, and a missense mutation of the β-cardiac myosin heavy chain in chromosome 14 was found. Thus, 21 years elapsed from HCM gross discovery to molecular discoveries. The same original family was the source of both the gross and genetic explanations of HCM, which is now named sarcomere disease. Restrictive cardiomyopathy, characterized grossly without hypertrophy and histologically by myocardial disarray, was found to also have a sarcomeric genetic mutation, labeled "HCM without hypertrophy". Sarcomere missense mutations have also been reported in dilated cardiomyopathy (DCM) and non-compaction cardiomyopathy. Moreover, sarcomeric gene defects have been detected in some DNA non-coding regions of HCM patients. The same mutation in the family may express different phenotypes (HCM, DCM, and RCM). Large ischemic scars have been reported by pathologists and are nowadays easily detectable in vivo by cardiac magnetic resonance with gadolinium. The ischemic arrhythmic substrate enhances the risk of sudden death.

A genetic explanation for the anhydrite–halite cyclic layers in the Middle Jurassic Louann Salt, U.S. Gulf Coastal Region

ABSTRACT Successions of bipartite layers (couplets) form the bedding fabric of salt stocks of the U.S. Gulf Coastal Region, south-central U.S.A. The cyclic couplets typically have a thickness range of 3–20 cm and a mean of about 10 cm. Each couplet consists of a white band of halite interstratified with a thinner, gray band of halite mixed with anhydrite (generally 3–8 wt % of each couplet). Successions of couplets, which lack siliciclastic beds and significant hiatuses, make up the thick (∼ 1.5 km) Middle Jurassic Louann Salt. Deeply buried (by up to ∼ 18 km), the Louann couplets moved laterally by ductile flow into the base of salt stocks and rose (or appeared to). The Dead Sea is a unique, modern analog of the Louann Salt. The huge lake is a model of how surface evaporation, brine temperature, and double-diffusive salt fingering combined to form the Louann couplets. Halite varves (couplets) presently precipitate from the Dead Sea’s deep (∼ 300 m), marine-like brine. If these modern varves are to be a valid genetic model for the Louann couplets, they too must be annual layers. An explicit similarity of the Louann couplets with two modern and four ancient varve-established evaporitic couplets demonstrates that the Louann anhydrite–halite couplets are truly varves. The Louann varves accumulated at such a rapid rate (∼ 1 m every 10 years) that a deep-water depositional basin must have pre-existed. In the basin, an abrupt destabilized thermocline existed in summer between a surface zone (tens of meters thick) of warm, high-salinity brine and a deep zone (hundreds of meters thick) of cooler, lesser-salinity brine. This disposition resulted in a vertical flux from the thermocline of alternating rising and sinking salt fingers (millimeter wide, centimeter long, and millions per km2). When heat diffused from the warm surface zone into the cooler fingers, their density decreased, they rose, and blended with the ambient brine; and when heat diffused from the warm fingers into the cooler deep zone, their density increased, they sank, and blended with the ambient brine. Salinity also diffused into and from fingers but at a rate ∼ 100 × slower than heat. In summer, the Louann surface zone was NaCl undersaturated because: 1) solar heating caused enhanced NaCl solubility, 2) ascending fingers transferred low-salinity brine into the higher-salinity surface zone, and 3) descending fingers transferred high-salinity brine into the lower salinity deep zone. The Louann surface zone, however, was CaSO4·2H2O supersaturated because of: 1) gypsum’s retrograde solubility and 2) gypsum concentration by evaporation in the surface zone. Gypsum cumulates rained from the surface zone onto the seafloor. As fingers descended from the thermocline into the Louann deep zone, their NaCl salinity state changed from saturated to supersaturated. Cumulate and bottom-growth halite precipitated, and the halite and gypsum accumulated together on the seafloor. With subsequent dehydration of the gypsum, the precipitates formed the thin, gray, anhydrite(halite) summer band of the Louann varves. In the fall, brine above the thermocline began to cool. By mid-winter, energized by wind and convection, the brine column overturned, became significantly cooler, and intensely NaCl-supersaturated. Halite cumulates crystallized throughout and rained onto the seafloor to form the thicker, white, halite winter band of the Louann varves.

CFAP47 is implicated in X-linked polycystic kidney disease

IntroductionAutosomal dominant polycystic kidney disease (ADPKD) is a well-described condition in which ∼80% of all cases have a genetic explanation, and among sporadic cases without a family history, the genetic bases remains unclear in ∼30% of cases. This study aimed to identify genes associated with polycystic kidney disease (PKD) in patients with sporadic cystic kidney disease in which a clear genetic change was not identified in established genes. MethodsA next-generation sequencing panel analyzed known genes related to kidney cysts in 118 sporadic cases, followed by whole-genome sequencing on 47 unrelated individuals without identified candidate variants. Immunohistological examination was then conducted on both human kidney tissue and kidneys from Cfap47-/Y mice. ResultsThree male patients were found to have rare missense variants in the X-linked gene Cilia And Flagella Associated Protein 47 (CFAP47), none of whom had a family history of the condition. CFAP47 was expressed in primary cilia of human kidney tubules, and knockout mice exhibited vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation. ConclusionThis discovery of CFAP47 as a newly identified gene associated with PKD, displaying X-linked inheritance, emphasizes the need for further cases to understand the role of CFAP47 in PKD.

Fruit resources shape sexual selection processes in a lek mating system.

The degree to which within-population variation in sexual trait expression relates to resource heterogeneity remains poorly explored. This is particularly true in lek-mating species, where genetic explanations for male phenotypic variance and mating success are dominant. Here, we demonstrate a link between fine-scale fruit resource availability and indices of male mating success in the white-bearded manakin (Manacus manacus), a lek-mating frugivorous bird that produces energetically costly courtship displays. We used motion-activated camera traps to monitor male display behaviour and female visitation at male courts while concurrently conducting twice-monthly fruit surveys around courts. We observed significant variability in ripe fruit biomass among display courts and leks, and mean fruit biomass at courts significantly predicted male display rates. In turn, male display rate was the strongest predictor of female visitation to courts. Causal modelling supported the hypothesis that hyper-local fruit availability indirectly affects female visitation via its direct effects on male display rate. The demonstration that resource availability at fine spatial scales predicts display rate in a lekking organism-for which resource-related variables are typically not considered to play important roles in shaping male reproductive variance-has implications for the expression, honesty and maintenance of sexually selected traits under fluctuating ecological conditions.

Disparate and parallel craniofacial climatic adaptations in native populations of Asia, North America, and South America.

Understanding the impact that climate had in shaping cranial variation is critical for inferring the evolutionary mechanisms that played a role in human diversification. Here, we provide a comprehensive study aiming to analyze the association between climate and cranial variation of high latitude populations living in temperate to cold environments of Asia, North America, and South America. For this, we compiled a large morphometric dataset (N = 2633), which was combined with climatic and genomic data. We tested the influence of climate on the facial skeleton, nasal protrusion, and cranial vault and through multiple statistical tests at two geographical scales: intracontinental and intercontinental. We show that populations living in cold areas share a morphological pattern characterized by an increase in nasal height, facial and orbital heights and widths, a decrease in facial protrusion, and larger, longer, and lower cranial vaults. There are also distinctive features; populations from north Asia present the tallest noses, largest faces, and cranial vaults of the whole sample. Nasal breadth dimensions show small values in Asians, large values in South Americans, and non-significant changes in arctic North America. The morphological pattern in populations living at high latitude may be the result of parallel adaptation, as supported by physiological, morphometric, ecological, and genetic explanations, while the differences in magnitude and phenotypic expression could be due to the diverse population histories, severity of climate, and cultural strategies. Overall, our study shows that climate is a relevant factor shaping modern human morphology and it should be considered when studying modern human evolution and diversification.

Exploring the role of vitamin D-VDR pathway in pemphigus foliaceous: a novel perspective on disease pathogenesis.

Several auto-immune diseases have been linked to vitamin D deficiency as a contributing environmental factor. Its pleiotropic effects on the immune system, especially its essential role in maintaining immune tolerance, make the vitamin D pathway of great interest. In this study, we focused on Pemphigus foliaceous (PF) in Tunisian population. we aimed to quantify the Serum 25[OH]D levels using chemiluminescence assay and to analyze the differential expression of the VDR, CYP27B1 and CYP24A1 genes in the circulating blood cells and lesional skin tissue of PF patients using Q-PCR. A genetic explanation was then sought to explore any direct relationship between tag polymorphisms and the inherited features of PF. Results confirmed a vitamin D hypovitaminosis in Tunisian PF patients. Interestingly, a differential gene expression correlated to the disease stratification was noted. Indeed, at the systemic level, an upregulation of VDR and CYP27B1 genes was observed in healthy controls compared to PF patients. Notably, in lesional skin tissue, the clinical and serological remission phase was correlated with high transcriptional levels of the VDR gene and conversely a drop in expression of the CYP24A1 gene. Genetic analysis indicated the involvement of the most appealing polymorphisms, rs2228570 and poly (A) microsatellite, in PF etiopathogenesis. Indeed, CAC13 haplotype was associated with a higher risk of PF development. Our findings suggest that alterations in the vitamin D-VDR pathway may influence PF physiopathology, making this pathway a potential target for pharmacological modulation, especially for cortico-resistant PF patients.

P-115 GATAD2B is required for pre-implantation embryo development by delaying zygotic genome activation

Abstract Study question Major zygotic genome activation (ZGA) involving the activation of thousands of genes occurs at the late-2cell stage, but the regulatory mechanisms governing ZGA remain unclear. Summary answer Our results demonstrate that GATAD2B is essential for early embryonic development, in part through facilitating zygotic genome activation (ZGA). What is known already Acetylation modifications of histone tails promote transcriptional activation, and the maternal deletion of H4K16ac leads to failure in ZGA. GATAD2B is one of the core subunits of the Nucleosome remodeling and histone deacetylation complex(NuRD). Study design, size, duration Using mouse embryos as the research model, the study was conducted over a period of approximately two years to ensure a relatively small-scale investigation. Participants/materials, setting, methods We examined the dynamic expression of NURD complex components, including GATAD2B, during pre-implantation embryonic stages. GATAD2B expression was specifically reduced via microinjection of GATAD2B-siRNA during the zygote stage, revealing its impact on early embryonic development in mice. Zygotic genome activation (ZGA), morula compaction, and blastocyst lineage differentiation were investigated using immunofluorescence, western blot, and other techniques. Additionally, we employed RNA-seq, protein immunoprecipitation, and mass spectrometry to uncover underlying molecular mechanisms. Main results and the role of chance Our research has shown that GATAD2B exhibits specific nucleus localization and high protein expression from the late-2-cell to 8-cell. This intriguing phenomenon prompted us to investigate the relationship between GATAD2B and the ZGA. We discovered a distinctive pattern of GATAD2B, starting from the late 2-cell stage with nuclear localization. GATAD2B depletion resulted in defective embryonic development, including increased DNA damage at morula, decreased blastocyst formation rate and abnormal differentiation of ICM/TE lineages. Consistent with the delay during the cleavage stage, the transcriptome analysis of the 2-cell revealed inhibition of the cell cycle G2/M phase transition pathway. Furthermore, the GATAD2B proteomics data provided clear evidence of a certain association between GATAD2B and molecules involved in the cell cycle pathway. As hypothesized, GATAD2B-deficient 2-cell embryos exhibited abnormalities in ZGA during the maternal-to-embryonic transition, with lower expression of the major ZGA mark MERVL. Limitations, reasons for caution Given the limitations of antibody effectiveness and specificity required for the experiments, the exploration of molecular mechanisms is still ongoing. Wider implications of the findings Our findings have elucidated the impact of GATAD2B on early embryonic development through the regulation of zygotic genome activation (ZGA), providing a novel genetic explanation for clinical defects in early embryonic development. Trial registration number not applicable

Clinical Association of Lupus Erythematosus with Patients of Vitiligo: A Case Control Study

Background: Vitiligo is an idiopathic acquired depigmentary skin/ mucous membrane disorder. Lupus erythematosus and vitiligo are diseases of autoimmune origin. A genetic explanation for the association between lupus erythematosus and vitiligo has recently been attempted. Objective: To find out the association of lupus Erythematosus in patients of vitiligo. Methods: This case control study was carried out in the department of Dermatology & Venereology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka during the period of January 2023 to December 2023. A total of 180 patients with and without vitiligo from both genders and different ages for case and control groups were included in the study based on inclusion and exclusion criteria. Patients were divided into two groups, 90 patients with vitiligo as cases and 90 patients without vitiligo (healthy subjects) as controls. Wood’s lamp examination was performed for diagnosis of vitiligo. LE was diagnosed based on ACR criteria and laboratory test including Complete blood count, Urinalysis, ANA, anti-ds DNA, VDRL and Skin biopsy. Patients with lupus erythematosus and patients without lupus erythematosus were considered as group I and group II respectively. Results: In this study, the mean age was found 41.7±12.8 years in case group (Vitiligo) and 42.1±13.6 years in control group (Healthy subjects).More than half (51.1%) of the patients were female in case group and 41(45.6%) in control group. There was no significant difference was found regarding age, sex, anemia, leucopenia, thrombocytopenia, proteinuria, ANA and anti ds-DNA. Family history of vitiligo was significantly higher in vitiligo patients than healthy patients (26.7% vs 12.2%). The majority 45(50.0%) presented with generalize followed by 21(23.3) acrofacial, 13(14.4%) focal, 10(11.1%) segmental and 1(1.1%) mucosal of vitiligo. Lupus erythematosus was higher in vitiligo patients than healthy patients (4.4% vs 1.1%) but the difference was not statistically significant between the two groups (p=0.184). Conclusions: This study concluded that family history of vitiligo was significantly higher in vitiligo patients than healthy patients. Lupus erythematosus was higher in vitiligo patients than healthy patients, but not statistically significant. J Rang Med Col. March 2024; Vol. 9, No. 1: 33-38

Mechanistic complement of autosomal dominant polycystic kidney disease: the role of aquaporins.

Autosomal dominant polycystic kidney disease is a genetic kidney disease caused by mutations in the genes PKD1 or PKD2. Its course is characterized by the formation of progressively enlarged cysts in the renal tubules bilaterally. The basic genetic explanation for autosomal dominant polycystic kidney disease is the double-hit theory, and many of its mechanistic issues can be explained by the cilia doctrine. However, the precise molecular mechanisms underpinning this condition's occurrence are still not completely understood. Experimental evidence suggests that aquaporins, a class of transmembrane channel proteins, including aquaporin-1, aquaporin-2, aquaporin-3, and aquaporin-11, are involved in the mechanism of autosomal dominant polycystic kidney disease. Aquaporins are either a potential new target for the treatment of autosomal dominant polycystic kidney disease, and further study into the physiopathological role of aquaporins in autosomal dominant polycystic kidney disease will assist to clarify the disease's pathophysiology and increase the pool of potential treatment options. We primarily cover pertinent findings on aquaporins in autosomal dominant polycystic kidney disease in this review.

The effects of BDNF rs6265 and FGF21 rs11665896 polymorphisms on alcohol use disorder-related impulsivity in Han Chinese adults.

Patients with alcohol use disorder (AUD) often experience repeated withdrawal. Impulsivity is the most relevant factor influencing successful withdrawal. Brain-derived neurotrophic factor (BNDF) and fibroblast growth factor 21 (FGF21) are associated with impulsivity. Previous studies on the differential effects of BDNF or FGF21 on impulsivity have focused on single-gene effects and have inconsistent results. We aim to investigate the effects of BDNF rs6265 and FGF21 rs11665896, individually and together, on impulsivity during alcohol withdrawal in patients with AUD. We recruited 482 adult Han Chinese males with AUD and assessed their impulsivity using the Barratt Impulsivity Scale. Genomic DNA was extracted and genotyped from peripheral blood samples. Statistical analysis was conducted on the data. The T-test and 2 × 2 analysis of variance were used to investigate the effects of the genes on impulsivity. There was a significant BDNF × FGF21 interaction on no-planning impulsiveness (F = 9.15, p = 0.003, η2p = 0.03). Simple main effects analyses and planned comparisons showed that BDNF rs6265 A allele × FGF21 rs11665896 T allele was associated with higher no-planning impulsiveness. Finally, hierarchical regression analyses revealed that only the interaction of BDNF and FGF21 accounted for a significant portion of the variance in no-planning impulsiveness. The combination of BDNF rs6265 A allele and FGF21 rs11665896 T allele may increase impulsivity and discourage alcohol withdrawal. Our study provides a possible genetic explanation for the effects of associated impulsivity in patients with AUD from the perspective of gene-gene interactions.

Unravelling the maternal evolutionary history of the African leopard (Panthera pardus pardus).

The African leopard (Panthera pardus pardus) has lost a significant proportion of its historical range, notably in north-western Africa and South Africa. Recent studies have explored the genetic diversity and population structure of African leopards across the continent. A notable genetic observation is the presence of two divergent mitochondrial lineages, PAR-I and PAR-II. Both lineages appeared to be distributed widely, with PAR-II frequently found in southern Africa. Until now, no study has attempted to date the emergence of either lineage, assess haplotype distribution, or explore their evolutionary histories in any detail. To investigate these underappreciated questions, we compiled the largest and most geographically representative leopard data set of the mitochondrial NADH-5 gene to date. We combined samples (n = 33) collected in an altitudinal transect across the Mpumalanga province of South Africa, where two populations of leopard are known to be in genetic contact, with previously published sequences of African leopard (n = 211). We estimate that the maternal PAR-I and PAR-II lineages diverged approximately 0.7051 (0.4477-0.9632) million years ago (Ma). Through spatial and demographic analyses, we show that while PAR-I underwent a mid-Pleistocene population expansion resulting in several closely related haplotypes with little geographic structure across much of its range, PAR-II remained at constant size and may even have declined slightly in the last 0.1 Ma. The higher genetic drift experienced within PAR-II drove a greater degree of structure with little haplotype sharing and unique haplotypes in central Africa, the Cape, KwaZulu-Natal and the South African Highveld. The phylogeographic structure of PAR-II, with its increasing frequency southward and its exclusive occurrence in south-eastern South Africa, suggests that this lineage may have been isolated in South Africa during the mid-Pleistocene. This hypothesis is supported by historical changes in paleoclimate that promoted intense aridification around the Limpopo Basin between 1.0-0.6 Ma, potentially reducing gene flow and promoting genetic drift. Interestingly, we ascertained that the two nuclear DNA populations identified by a previous study as East and West Mpumalanga correspond to PAR-I and PAR-II, respectively, and that they have come into secondary contact in the Lowveld region of South Africa. Our results suggest a subdivision of African leopard mtDNA into two clades, with one occurring almost exclusively in South Africa, and we identify the potential environmental drivers of this observed structure. We caution that our results are based on a single mtDNA locus, but it nevertheless provides a hypothesis that can be further tested with a dense sample of nuclear DNA data, preferably whole genomes. If our interpretation holds true, it would provide the first genetic explanation for the smaller observed size of leopards at the southernmost end of their range in Africa.

Sleep Disorder and its Treatment: From Nature to Laboratory

Sleep is the natural cellular repair mechanism to improve and restore central neural mechanism, memory, hormonal imbalance, and finally, cell rejuvenation. Sleep disorder is characterized by insomnia, circadian rhythm disorder (CRD), sleep apnea, narcolepsy, parasomnia, and restless leg syndrome (RLS) or periodic limb movement disorder (PLMD). Both oversleeping and less sleeping are associated with sleep disorders (SD). Anxiety, schizophrenia, weight loss/gain, hypothyroidism, and oxidative stress are the most common outcomes of SD. There is also a genetic explanation behind circadian rhythmicity, circadian disorder, narcolepsy-cataplexy syndrome, fatal familial insomnia, and somnambulism. Excessive work pressure, stress, and consumption of caffeine and alcohol collectively push a person toward sleep deprivation. Anxiety, schizophrenia, weight loss/gain, hypothyroidism, and oxidative stress are the most common outcomes of SD. Adenosine, melatonin, dopamine, serotonin, gamma amino butyric acid (GABA), orexin, and histamine regulate SDs by various pathways. Among natural sources, Centella asiatica, Bacopa monnieri, Acorus calamus, Withania somnifera, Nardostachys jatamansi, Poria cocos is, Valeriana officinalis, Matricaria chamomilla, Lavandula angustifolia, Nelumbo nucifera, Melissa officinalis, Convolvulus pluricaulis, Camellia sinensis, Ziziphus jujube, Datura stramonium, Zhizhipus jujube, Passiflora incarnata, and Moringa oleifera showed remarkable effects on different forms of SDs through GABAA, serotonin, and melatonin receptors. Pramipexole, ropinirole, rotigotine, clonazepam, lorazepam, estazolam, zolpidem, lemborexant, daridorexant, and suvorexant showed its activity in the treatment of SDs as a dopamine agonist, inhibitor of GABAA receptor, dual orexin receptor antagonist, respectively. This article focused on the types of SDs, the effects of SDs on mental health, receptors involved in the sleep cycle, and the impact of natural molecules and synthetic molecules in the management of SDs.

Spit for Science and the Limits of Applied Psychiatric Genetics

The research program Spit For Science was launched at Virginia Commonwealth University (VCU) in 2011. Since then, more than 10,000 freshmen have been enrolled in the program, filling out extensive questionnaires about their drinking, general substance use, and related behaviors, and also contributing saliva for genotyping. The goals of the program, as initially stated by the investigators, were to find the genes underlying the heritability of alcohol use and related behaviors, and in addition to put genetic knowledge to work in ways that might aid university administrators and mental health professionals in the prevention and treatment of substance abuse. We review every empirical paper involving genetic data that has emerged from the program, and reach a surprising conclusion: the study has never identified a single genetic effect of more than trivial magnitude. Although the quantitative results of the studies were reported transparently, the theoretical ramifications of the negligible results have never been acknowledged. To the contrary, most of the papers ignore the tiny effects, reaching optimistic conclusions about the prospects for future genetic explanations of alcohol use. We explore the implications of these results for the broader prospects of applied psychiatric genetics.

Comparative proteomic analysis of seed germination between allotetraploid cotton Gossypium hirsutum and Gossypium barbadense

Seed germination, a key initial event in the plant life cycle, directly affects cotton yield and quality. Gossypium barbadense and Gossypium hirsutum gradually evolved through polyploidization, resulting in different characteristics, and this interspecific variation lacks genetic and molecular explanation. This work aimed to compare the proteomes between G. barbadense and G. hirsutum during seed germination. Here, we identified 2740 proteins for G. barbadense and 3758 for G. hirsutum. In the initial state, proteins in two cotton involved similar bioprocess, such as sugar metabolism, DNA repairing, and ABA signaling pathway. However, in the post-germination stage, G. hirsutum expressed more protein related to redox homeostasis, peroxidase activity, and pathogen interactions. Analyzing the different expression patterns of 915 single-copy orthogroups between the two kinds of cotton indicated that most of the differentially expressed proteins in G. barbadense were related to carbon metabolism. In contrast, most proteins in G. hirsutum were associated with stress response. Besides that, by proteogenomic analysis, we found 349 putative non-canonical peptides, which may be involved in plant development. These results will help to understand the different characteristics of these two kinds of cotton, such as fiber quality, yield, and adaptability. Significance statementCotton is the predominant natural fiber crop worldwide; Gossypium barbadense and Gossypium hirsutum have evolved through polyploidization to produce differing traits. However, given their specific features, the divergence of mechanisms underlying seed germination between G. hirsutum and G. barbadense has not been discussed. Here, we explore what protein contributes to interspecific differences between G. barbadense and G. hirsutum during the seed germination period. This study helps to elucidate the evolution and domestication history of cotton polyploids and may allow breeders to understand their domestication history better and improve fiber quality and adaptability.

Refleksje o podręczniku metodologii historii (Wprowadzenie do metodologii historii, red. nauk. Ewa Domańska, Jan Pomorski, Wydawnictwo Naukowe PWN, Warszawa 2022, ss. 572)

Reflections on a methodology of history textbook (Wprowadzenie do metodologii historii, ed. Ewa Domańska, Jan Pomorski, Wydawnictwo Naukowe PWN, Warsaw 2022, 572pp) The article is a critical analysis of selected issues examined in Wprowadzenie do metodologii historii (Introduction to the Methodology of History), edited by Ewa Domańska and Jan Pomorski, Warsaw 2022. The reviewer focuses on general methodological and epistemological issues, believing that the authors of the various chapters pay too little attention, for the most part, to the relation between the methodology of history and general methodology. The discussion concerns the history of historiography, the role of history in the emergence of the humanities, the dispute over the status of history in the nineteenth century, particularly nomothetism and idiographism in the light of Auguste Comte’s classification of sciences compiled in France and their division as seen by Wilhelm Windelband and Heinrich Rickert, proposed in Germany, as well as explanation in historiography. With regard to that last point, deductive-nomological and genetic explanations are considered. Attention is drawn to the problematic nature of the application of the classic pattern of deductive-nomological explanation in connection with the problem of universal laws and historical theories (more generally – concerning the social sciences), as well as to the differences in the understanding of causality in historiography and theoretical natural sciences, which is relevant to the analysis of the genetic explanation. In the final section of the article the author points to the link between the approach to historical cognition and general problems of epistemology.

Current Perception of Nature vs.Nurture Debate among Students at the University of Medicine of Tirana

Introduction: One topic still debated in the scientific community and beyond is the influence of genetic or environmental factors on an individual's behavior. The essence of this debate lies in discussing the role and impact of genetic and environmental factors on an individual's behavior, known otherwise as the nature-nurture debate.
 In a survey-type study, we sought to assess perceptions of the nature-nurture argument among first-year technical medical sciences students at the University of Tirana, Albania.
 Materials and Methods: A cross-sectional study was conducted using a survey-type questionnaire on a sample of 100 first-year medical university students at the Faculty of Medical Technical Sciences, University of Medicine in Tirana, in April 2023. The questionnaire was based on six specific questions underlying the potential impact of genetic (nature) and environmental factors (nurture) influencing certain types of behavior, such as personality, sexual orientation, and intelligence—or psycho-emotional stress.
 Results: According to the analysis of the data collected on our sample of students, 84.9% of them perceive that acquired factors (nurture) influence more than innate factors (nature) in forming personality traits, whereas 15.1% perceive the opposite. After adjusting for potential confounders, environmental factors remained statistically significant compared with genetic factors (odds ratio 1.42, 95% CI 0.65 to 0.97). 
 Conclusion: Genetic and sociological research has shown that genetics, life experiences, and environmental factors influence the expression of key traits in shaping behavior. In this study, we confirm the perception of this interaction among medical students. For some aspects of behavior, students are less likely to believe in genetic explanations and more likely to believe in environmental causes.

Multiple Allergic Rhinitis Single Nucleotide Polymorphism Variants are Associated with Sleep-Breathing Parameters in Men with Obstructive Sleep Apnea: A Large-Scale Study.

Sleep-disordered breathing is more prevalent in individuals with allergic rhinitis (AR) than in those without AR. In addition to increased risk for sleep-disordered breathing, AR is associated with greater severity of obstructive sleep apnea (OSA) symptoms. The aim of this research study was to evaluate the association of multiple single nucleotide polymorphism (SNP) variations in AR with sleep- and breathing-related parameters in men with OSA. Men who had complained of snoring were consecutively enrolled in the Shanghai Sleep Health Study of Shanghai Sixth People's Hospital from 2007 to 2018. After rigorous screening, 5322 men were included in the analysis. Anthropometric, fasting biochemical, and polysomnographic parameters, along with 27 AR-associated SNPs were analyzed. The associations between AR-related genetic polymorphisms and OSA were determined via linear, binary, and multinomial logistic regression analyses. Rs12509403 had significantly positive associations with most sleep-breathing parameters. While the risk for OSA was increased by rs12509403, it was decreased by rs7717955 [odds ratio (OR) = 1.341, 95% confidence interval [CI] = 1.039-1.732, P = 0.024; OR = 0.829, 95% CI = 0.715-0.961, P = 0.013, respectively]. A graded increase in the risk of being in the highest quartile (Q4) vs the reference category (Q1) for sleep breathing indicators, especially REM-AHI and NREM-AHI, was identified by rs12509403 (OR = 1.496, 95% CI = 1.175-1.904, P = 0.001; OR = 1.471, 95% CI = 1.151-1.879, P < 0.001, respectively). The association of multiple AR SNPs with OSA-related hypoxia and sleep indices provides a genetic explanation for the higher AR susceptibility of OSA patients. Understanding the AR-related genetic underpinnings of OSA may lead to more personalized treatment approaches.