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Parkinson’s disease (PD) is a complex neurodegenerative disorder that is heterogeneous in both its pathophysiology and clinical presentation. Genetic, imaging and biochemical biomarkers not only provide innovative, objective ways to subtype PD but also offer new insights into the underlying pathophysiology, revealing potential therapeutic targets and improving predictions of clinical phenotype, disease progression and treatment response. In this review, we first summarize the phenotypes linked to key PD genes – such as SNCA, LRRK2, GBA and PRKN – highlighting, for instance, that GBA-PD is often associated with prominent nonmotor features. We then explore studies that have defined new robust subtypes with imaging biomarkers, particularly T1-weighted MRI brain atrophy patterns, and their clinical implications. We also review the role of blood, CSF and urine biomarkers for monitoring disease progression and predicting its presentation in various domains (motor, cognitive, autonomic, psychiatric). These findings could have practical implications by guiding clinicians to individualize symptomatic treatment and helping researchers improve clinical trial design and recruitment, thus bringing us closer to the discovery of effective disease-modifying therapies.
Chapter 9 studies the U.S.-China rivalry, which has strengthened since the early 2010s. From an evolutionary perspective, strategy is defined as a phenotype or playbook and strategic rivalry as a contest of different phenotypes in the larger ecological environment. International relations are thus fundamentally defined by competition and selection. Competition may lead to divergence among units, and the mechanism of selection indeed requires different types. The United States and China represent two different types of political systems, although there has also been mutual learning. The U.S.-China rivalry is consequential for East Asia and the world because they are currently the two greatest powers, with the sources of their power constructed and adapted over years. The chapter demonstrates how the United States and China have been in different stages since the founding of the United States in 1776, experiencing ups and downs in their bilateral interactions since 1784.
Edited by
Allan Young, Institute of Psychiatry, King's College London,Marsal Sanches, Baylor College of Medicine, Texas,Jair C. Soares, McGovern Medical School, The University of Texas,Mario Juruena, King's College London
Due to the chronic relapsing nature of mental disorders and increased life expectancy, the societal burden of these non-communicable diseases will increase. Treatments for mental disorders are available, but their effect is limited due to patients’ (genetic) heterogeneity, low treatment compliance and frequent side effects. Today, medication selection in psychiatry relies on a trial-and-error approach based mainly on physicians’ experience. Pharmacogenetic testing can help in this process by determining the person-specific genetic factors that may predict clinical response and side effects associated with genetic variants that impact drug-metabolizing enzymes, drug transporters or drug targets .
Pharmacogenetics is a discipline that investigates genetic factors that affect the absorption, metabolism, and transport of drugs, thereby affecting therapy outcome. These genetic factors can, among other things, lead to differences in the activity of enzymes that metabolize drugs. Recent studies in depressed patients show that genotyping of drug-metabolizing enzymes can increase the effectiveness of treatment, which could benefit millions of patients worldwide.
Grain-cooking traditions in Neolithic China have been characterised as a ‘wet’ cuisine based on the boiling and steaming of sticky varieties of cereal. One of these, broomcorn millet, was one of the earliest Chinese crops to move westward into Central Asia and beyond, into regions where grains were typically prepared by grinding and baking. Here, the authors present the genotypes and reconstructed phenotypes of 13 desiccated broomcorn millet samples from Xinjiang (1700 BC–AD 700). The absence in this area of sticky-starch millet and vessels for boiling and steaming suggests that, as they moved west, East Asian cereal crops were decoupled from traditional cooking practices and were incorporated into local cuisines.
This study aimed to analyse clinical and radiological features (phenotypes) to predict revision risk after functional endoscopic sinus surgery in patients with chronic rhinosinusitis with nasal polyps.
Method
Phenotype characteristics of the patients with chronic rhinosinusitis with nasal polyps who underwent functional endoscopic sinus surgery were analysed retrospectively.
Results
The rates of asthma, aspirin sensitivity, smoking and a positive prick test result were significantly higher in revision functional endoscopic sinus surgery cases (p < 0.001, 0.001, < 0.001 and < 0.001, respectively). Multivariate analysis demonstrated that only gender, pre-operative nasal steroid use, pre-operative systemic steroid use, intra-operative systemic steroid use and smoking were significant risk factors for revision functional endoscopic sinus surgery (p = 0.034, 0.001, 0.010, 0.007 and 0.001, respectively). In addition, only eosinophilia and aspirin sensitivity were significant risk factors for multiple revision functional endoscopic sinus surgery procedures (p = 0.043 and 0.005, odds ratio = 2.4 and 5.2).
Conclusion
Beyond the endotype of chronic rhinosinusitis with nasal polyps, defining clinical and radiological factors enables a valid prediction of patients at high risk of revision functional endoscopic sinus surgery.
For cooperation to be beneficial, cooperators should be able to differentiate individuals who are willing to cooperate from free-riders. In the absence of kin or of familiar individuals, phenotypic similarity (e.g. in terms of language) can be used as a cue of how likely two or more individuals are to behave similarly (whether they will cooperate or free-ride). Thus, phenotypic similarity could affect cooperation. However, it is unclear whether humans respond to any type of phenotypic similarity or whether only salient phenotypic traits guide cooperation. We tested whether within-group, non-salient phenotypic similarity affects cooperation in 280, 3 to 10 year old children and in 76 young adults (mean 19.8 years old) in the UK. We experimentally manipulated the degree of phenotypic similarity in three computer-based experiments. We found no evidence of a preference for, or greater cooperation with, phenotypically similar individuals in children, even though children displayed ingroup preference. Conversely, young adults cooperated more with phenotypically similar than with phenotypically diverse individuals to themselves. Our results suggest that response to non-salient phenotypic similarity varies with age and that young adults may pay more attention to non-salient cues of diversity then children.
I am broadly sympathetic to D. C. Matthew's analysis. However, in what follows, I restrict my remarks to a few areas where I think he either lacks empirical precision, or overstates his case.
If available for use on snap bean, pyroxasulfone would provide valuable preemergence control of troublesome weed species that currently contaminate the crop postharvest. The extent to which snap bean tolerates pyroxasulfone is poorly documented. The objective of this research was to quantify the extent to which pyroxasulfone tolerance exists in a large collection of snap bean cultivars. A snap bean diversity panel of 277 entries was screened for tolerance to sulfentrazone at a rate of 420 g ai ha−1 in a field trial in 2019 and 2020 near Urbana, IL. Snap bean cultivars exhibited variation in tolerance to pyroxasulfone. While a handful of cultivars were tolerant across variable environments, most cultivars were sensitive in the year that had 30% more water supply (rainfall plus sprinkler irrigation) within 3 wk of planting. Low estimates of broad-sense heritability reflect a large influence of the environment on seedling emergence and growth. With a few exceptions, currently, the margin of crop safety across diverse germplasm is insufficient for registration of pyroxasulfone use on snap bean crops.
Forensic samples are among the most complex encountered. Blood is best known, but other biological matrices also carry genetic information. Cheek swabs (buccal swabs) collect cells from the inside of the mouth and have the advantage of being a non-invasive sample collection compared to a blood draw. Hair, depending on the presence of the root, is amenable to DNA typing. Semen, vaginal fluids, and vaginal swabs are collected in sexual assault cases. Any surface on which biological fluids (blood, oral fluid, vaginal fluid, etc.) are deposited becomes a potential DNA source.
The initial deposition (called the primary transfer) occurs from a person to a surface. It is the deposition of blood, saliva, semen, or other biological substance directly from the body onto a surface. This process could be a victim’s blood dripping onto an assailant’s clothing, saliva on a cigarette, or seminal fluid on a bedsheet.
In this unashamed polemic I argue that most extant plant species currently represented by a Linnean binomial exist only at the most basic level of a primary hypothesis that has not yet been subjected to the crucial test of circumscription. Rigorous circumscription requires sampling of numerous populations across the full range of a putative species and its supposed close relatives for several properties, including analytical morphology and genetics, preferably supported by gene exchange experiments and autecological observations. In the absence of genuine, demonstrable discontinuities in at least one biologically meaningful property, perceived species boundaries remain entirely arbitrary, thereby hindering rather than assisting every kind of biological investigation. The term 'cryptic species' has many implied definitions, but in my opinion it simply boils down to the many situations where limited morphological and molecular differentiation leave the analyst unsure whether credible species boundaries exist among the representative individuals analysed. The lack of obvious discontinuities typically reflects ongoing gene-flow and/or low levels of extinction of intermediate lineages. At present, the status of a putative species is rarely subjected to critical appraisal through the lens of any specified species concept or evolutionary mechanism, despite the widely accepted primacy of species in systematic biology.
Mood disorders, including depressive and bipolar disorders, represent a multidimensional and prevalent group of psychiatric illnesses characterized by disturbances in emotion, cognition and metabolism. Maladaptive eating behaviors in mood disorders are diverse and warrant characterization in order to increase the precision of diagnostic criteria, identify subtypes and improve treatment strategies. The current narrative review synthesizes evidence for Eating Behavioral Phenotypes (EBP) in mood disorders as well as advancements in pathophysiological conceptual frameworks relevant to each phenotype. Phenotypes include maladaptive eating behaviors related to appetite, emotion, reward, impulsivity, diet style and circadian rhythm disruption. Potential treatment strategies for each phenotype are also discussed, including psychotherapeutic, pharmacological and nutritional interventions. Maladaptive eating behaviors related to mood disorders are relevant from both clinical and research perspectives, yet have been somewhat overlooked thus far. A better understanding of this aspect of mood disorders holds promise to improve clinical care in this patient group and contribute to the subtyping of these currently subjectively diagnosed and treated disorders.
Edited by
James Law, University of Newcastle upon Tyne,Sheena Reilly, Griffith University, Queensland,Cristina McKean, University of Newcastle upon Tyne
Developmental language disorder (DLD) is estimated to affect 8 per cent of primary school-aged children, and has lasting impacts on academic achievement and social-emotional and behavioural outcomes. DLD is classified as a severe and persistent impairment in the acquisition, understanding, production or use of language, occurring in the absence of comorbid neurodevelopmental disorder. The phenotype of DLD is well established, yet there is relatively limited understanding of its aetiology. A complex interaction of genetic variants and environmental factors is thought to be the cause. To date, linkage and association analyses have implicated a handful of genes in DLD populations, including CMIP and ATP2C2. While many of these variants are common in DLD, they are not consistently associated with severe language impairment, and many overlap with chromosome regions commonly associated with neurodevelopmental disorders such as intellectual disability. The effects of alternate genetic models such as copy number and rare variants may provide a gateway to understanding the complex genetic pathways of this disorder. Pleiotropy and generalisation are also important considerations in understanding the genetic architecture of DLD. Here we outline the phenotype of DLD and provide an overview of recently identified gene pathways implicated in this disorder.
Human beings are one of the innumerable products of the process of evolution by natural selection. As such, understanding our psychological makeup requires an appreciation of the mechanism of natural selection itself. When a population of reproducing entities has (1) variation in traits, (2) inheritance of variation, and (3) nonrandom differential reproduction, entities with traits that are good at making themselves more numerous will, by definition, tend to be better represented in future generations. Organisms that are best able to interact with their environment in a way that promotes their own reproduction are favored automatically. Under consistent environmental conditions, small changes in inherited traits can add up to complex adaptations by adding incremental improvements to the organisms’ fit with the environment. The relationship between variation and inheritance is complex in organisms because variation is manifest in the phenotype, but inheritance occurs between genotypes. The relationship between these two aspects of organisms is complex because genes must act through interaction with the environment. Further complications arise due to the blindness of natural selection to changes in future environments and available variation. Despite these intricacies, natural selection has crafted vastly complex and diverse organisms over the course of billions of years, with no foresight or thought.
Frailty is an important geriatric syndrome that is common and commonly missed, and affects more than a third of people over age 85. Frailty is characterized by diminished physiologic reserves and function, leading to decreased capacity to withstand stressors. Frail adults are at a higher risk of dependency, institutionalization, and death. Multiple interventions have been attempted, including physical activity, improving nutrition, and hormonal therapy, but there are no curative interventions for frailty and it is not clear if frailty can be reversed. Several issues have limited the advancement of frailty research and translation into practice, including the lack of consensus regarding the definition of frailty, the proliferation of assessment tools, and the gaps in validated best practice guidance for frail patients. The recognition of frailty, especially in its early stages, offers the possibility of preventing or mitigating adverse clinical outcomes. Older adults who are frail may benefit most from a comprehensive geriatric evaluation to help elucidate a plan of care that is consistent with patient's goals, values, and preferences.
The IUCN now recognizes the savannah Loxodonta africana and forest Loxodonta cyclotis elephants to be separate species. Despite ecological, behavioural and morphological differences, and different habitat ranges, genetic studies confirm that the two species and hybrids coexist in forest–savannah ecotones. However, the hybrid phenotypes have not yet been described. In this survey we examined whether the phenotypes of the two species and of hybrids can be distinguished. In the first step, we used a machine learning algorithm (K-nearest neighbours) to compare 296 reference images of African elephants from five forest areas and six savannah areas where hybrids have not been recorded, confirming that six morphological criteria can be used to distinguish the species with more than 90% confidence. In the second step, we analysed 1,408 videos of elephants from 14 camera traps in Sebitoli, in Kibale National Park, Uganda, part of the main hybridization area. We used a multiple correspondence analysis and a species assignment key, highlighting the presence of three categories of phenotypes. Compared to the savannah and forest phenotypes (36.8 and 12.1%, respectively), the intermediate phenotypes, which could include hybrids, were more frequent (51.1%). Further studies combining morphology and genetics of the same individuals will be necessary to refine this species assignment key to characterize phenotypes confidently. This non-invasive, fast and inexpensive phenotypical-based method could be a valuable tool for conservation programmes.
This chapter will set the table for your personal decisions when considering taking a leadership position and what should go into your thinking as you’re weighing your options. It covers what goes into understanding the position itself and how to find out the crucial details and duties it requires. It then discusses the leadership “phenotype” – what personal skills you bring to the role and whether the role will be a good “fit” for you. It probes what motivates you to be a leader and why, and whether that will give you a durable effect. Finally, it helps you to look at the career move in the context of your overall career, and whether the position will bridge you to something greater in the long run, or whether it’s a dead end. This chapter sets the stage for what comes next, an understanding of your personality as a leader.
Vanishing white matter disease (VWMD) due to eIF2B mutations is a common leukodystrophy characterised by childhood onset, autosomal recessive inheritance, and progressive clinical course with episodic worsening. There are no reports of genetically confirmed adult patients from India. We describe the phenotype of two adults with genetically confirmed VWMD and typical radiological findings. Both had spastic ataxia and cognitive and behavioural disturbances. Other neurological features included myoclonic jerks and parkinsonism. At the last follow-up (duration: 2–9 years), one patient was wheelchair-bound. VWMD is rare in adults but should be suspected based on radiological findings and confirmed by eIF2B mutation.
15q11.2-q13.3 region is prone to genomic rearrangements leading to both deletions and duplications. A wide spectrum of neuropsychiatric conditions, such as developmental delay/intellectual disability (DD/ID), autism, attention-deficit hyperactivity disorder, schizophrenia, epilepsy was reported in association with genomic imbalances of this region.
Objectives
In this paper we report on 9 children carrying 15q11.2-q13.3 duplications.
Methods
Seven boys and two girls, aged 15 months to 15 years, were included in the study. Genomic investigations were carried out by array-based comparative genomic hybridization (Agilent Technologies). In all patients the psychomotor development, dysmorphic features, neuroimaging and EEG anomalies were assessed. Psychologic and psychiatric evaluation was performed with specific tests.
Results
The size of the duplications ranged from 9.65 Mb to 0.38 Mb. All patients presented speech delay. Autistic behavior and muscular hypotonia were detected in 8 out of 9 patients, DD/ID in 6. Two children presented epileptic seizures, in addition 4 other children had EEG anomalies. Facial dysmorphic features were observed in 5 patients. Neuroimaging studies showed anomalies in 4 children. The smallest region of overlap in our patient group harbors CHRNA7 gene, a candidate for the behavioral abnormalities.
Conclusions
15q duplications encompassing CHRNA7 gene were associated with different neuropsychiatric features in our patients. Our results further support the association of 15q duplications with neuropsychiatric phenotypes, with clinical heterogeneity and variable severity, which is yet to be explained. Acknowledgment: The research leading to these results has received funding from the EEA RO NO Grant 2014-2021, the project contract No 6/2019.
Pharmacogenetics (PGx) studies genetic variance and related differences in drug outcomes. PGx guidelines for psychotropic drugs are available (PGx drugs). By executing PGx testing in a prospective or pre-emptive setting, dose adjustments or even change of treatment type can be applied prior to start of therapy to patients who carry a specific geno- or phenotype (i.e. actionable geno- or phenotypes). By doing so, increased efficacy of therapy or reduced risk of adverse events of treatment can be accomplished. In Denmark, broad implementation of PGx is currently still low.
Objectives
The aim of this study is to classify the PGx profiles of Danish individuals with and without severe mental disorders (SMD), to be used in follow-up studies investigating PGx and drug outcomes.
Methods
This study made use of imputed genotyping data of the Danish iPSYCH sample, which includes 77,639 young individuals born between 1981-2005, with or without a diagnosis of one or more of five selected SMD (i.e. depression, attention-deficit/hyperactivity disorder, autism, bipolar disorder and schizophrenia). We investigated a panel of 48 genetic variants with known PGx applications (part of the U-PGx consortium, a Horizon2020 funded project on clinical relevant PGx in the EU).
Results
Imputed data contains over 11 million SNPs of 77,639 individuals.
Conclusions
We expect results in the end of 2020.
Disclosure
We thank the iPSYCH consortium, in specific the iPSYCH PI’s (Merete Nordentoft, Anders Børglum, Preben B. Mortensen, Ole Mors, Thomas Werge and David M. Hougaard). The iPSYCH project is funded by the Lundbeck Foundation Denmark and the universities and un
This study aims to investigate the pathogenic gene variant in a family with hypertrophic cardiomyopathy by using whole-exome sequencing and to explore the relationship between the gene variant and clinical phenotype.
Methods:
Peripheral blood was collected from a family with hypertrophic cardiomyopathy, and deoxyribonucleic acid was extracted. The possible pathogenic genes were detected by whole-exome sequencing, and the variant was verified by Sanger sequencing. Functional change in the variant was predicted by bioinformatics software. Clinical data of the family members are analysed simultaneously.
Results:
The proband carries a novel heterozygous nonsense variant of MYBPC3:c.2731G > T (p.E911X). The analysis of amino acid conservation suggests that the variation is highly conserved. The three-dimensional protein structure shows that the variant in MYBPC3 results in the incompleteness of the fibronectintype-III2 (p872–967) domain and deletion of Ig-like C2-type 6 (p971–1065) and fibronectin type-III 3 and Ig-like C2-type 7 (p1181–1274) domains, in which p1253–1268 is predicted to have a transmembrane helix structure. Clinical data indicate that the phenotypes of variant carriers with hypertrophic cardiomyopathy are diverse, suggesting the functional damages to the protein of MYBPC3.
Conclusion:
The phenotypes of variant carriers with hypertrophic cardiomyopathy caused by the novel variant in MYBPC3: c.2731G > T (p.E911X) exhibit variable severity and clinical manifestations. Whole-exome sequencing can be used to comprehensive screen hypertrophic cardiomyopathy genes and provide a strong basis for early screening and accurate diagnosis and treatment of hypertrophic cardiomyopathy in children.