Distinct types of selection and genetic architecture shape molecular variation during the domestication of vegetable crops.

Humans select vegetable crops with desirable traits via a complex evolutionary process called domestication, generating a variety of cultivars worldwide. With advances in sequencing technologies, genomic scans for "signatures of selection" are widely used to identify target loci of selection. In the early phases of domestication, humans tended to favor similar sets of phenotypes in diverse crops, resulting in "domestication syndrome" and parallel evolution in multiple species. Subsequently, adaptation to distinct environments or different consumer preferences have diversified crop cultivars. Here, we review molecular and population genetic studies on genes affecting trait evolution during this complex process. We emphasize that, depending on interactions among different types of selection (directional selection within or divergent selection between groups), the genetic architecture of the target trait (Mendelian or polygenic), and the origin of the causal variant (new mutation or standing variation), the resulting molecular patterns of variation can be highly diverse. Situations in which the typical hard selective sweep model could be applied may be limited. Therefore, it is crucial to obtain a thorough understanding of the target species' historical, environmental, and ecological contexts.

Demographic history and distinct selection signatures of two domestication genes in mungbean.

Domestication is the long and complex process underlying the evolution of crops, in which artificial directional selection transformed wild progenitors into the desired form, affecting genomic variation and leaving traces of selection at targeted loci. However, whether genes controlling important domestication traits follow the same evolutionary pattern expected under the standard selective sweep model remains unclear. With whole-genome resequencing of mungbean (Vigna radiata), we investigated this issue by resolving its global demographic history and targeted dissection of the molecular footprints of genes underlying 2 key traits representing different stages of domestication. Mungbean originated in Asia, and the Southeast Asian wild population migrated to Australia about 50 thousand generations ago. Later in Asia, the cultivated form diverged from the wild progenitor. We identified the gene associated with the pod shattering resistance trait, VrMYB26a, with lower expression across cultivars and reduced polymorphism in the promoter region, reflecting a hard selective sweep. On the other hand, the stem determinacy trait was associated with VrDet1. We found that 2 ancient haplotypes of this gene have lower gene expression and exhibited intermediate frequencies in cultivars, consistent with selection favoring independent haplotypes in a soft selective sweep. In mungbean, contrasting signatures of selection were identified from the detailed dissection of 2 important domestication traits. The results suggest complex genetic architecture underlying the seemingly simple process of directional artificial selection and highlight the limitations of genome-scan methods relying on hard selective sweeps.

Distinct subsets of synovial fibroblasts control cartilage destruction in joint diseases.

Inflammation-induced bone destruction is the main cause of progressive joint damage in rheumatoid arthritis (RA) and osteoarthritis (OA). In addition, depending on the tissue microenvironment stimulators, the synovium transforms into a hyperplastic invasive tissue. The synovium includes two specific subsets of fibroblasts surrounding the joints: lining and sublining synovial fibroblasts (SFs). These SFs grow and interact with immune cells invading the bone and cartilage; specifically, SFs, which are the major mesenchymal cells in the joints, develop an aggressive phenotype, thereby producing cytokines and proteases involved in arthritis pathogeneses. Transcriptomic differences in the heterogeneity of SFs reflect the joint-specific origins of the SFs interacting with immune cells. To understand the subsets of SFs that lead to joint damage in arthritis, clarifying the distinct phenotypes and properties of SFs and understanding how they influence bone cells, such as osteoclasts and chondrocytes, is crucial. This review provides an overview of the advancements in the understanding of SF subsets and features, which may aid in identifying newer therapeutic targets.

Bullying Perpetration and Victimization in Youth: Associations with Irritability and Anxiety.

Prior work on has demonstrated that irritability and anxiety are associated with bullying perpetration and victimization, respectively. Even though symptoms of irritability and anxiety often occur concurrently, few studies have tested their interactive effects on perpetration or victimization. The current study recruited 131 youths from a broader program of research that examines the pathophysiology and treatment of pediatric irritability and anxiety. Two moderation tests were performed to examine concurrent irritability and anxiety symptoms and their relation to perpetration and victimization of bullying. More severe anxiety was associated with greater victimization. However, more severe irritability was associated with, not just greater perpetration, but also greater victimization. An irritability-by-anxiety interaction demonstrated that youths with more severe irritability and lower levels of anxiety engaged in more perpetration. Our findings suggest a more nuanced approach to understanding how the commonly comorbid symptoms of irritability and anxiety interact in relation to peer-directed behavior in youths.

Enhanced Room-Temperature Thermoelectric Performance of 2D-SnSe Alloys via Electric-Current-Assisted Sintering.

Single-crystalline tin-selenide (SnSe) has emerged as a high-performance and eco-friendly alternative to the lead-chalcogens often used in mid-temperature thermoelectric (TE) generators. At high temperature >800 K, the phase transition from Pnma to Cmcm causes a significant rise in the TE figure-of-merit (zT) curve. Conversely, the SnSe TE requires a booster at low temperatures, which allows broader applicability from a device perspective. Herein, a synergy of Cu alloy and Ag-coating is realized through a sequential multi-step synthesis, designed to combine different metal deposition effects. Single-crystalline (Cu2Se)x(SnSe)1−x alloys grown by the Bridgman method were then coated with a thin Ag layer by radio frequency (RF) sputtering, and the interlayer epitaxial film was observed via electric-current assisted sintering (ECAS). Consequently, the thin Ag-coating improves the electrical conductivity (σ) and reduces the thermal conductivity (κ) for (Cu2Se)0.005(SnSe)0.995+Ag alloy, increasing the zT curve at close to room temperature (373 K). The incorporation of multistep addition by ECAS enables tuning of the overall solubility of the alloy, which opens a new avenue to optimize TE performance in anisotropic 2D materials.

Environment as a limiting factor of the historical global spread of mungbean.

While the domestication process has been investigated in many crops, the detailed route of cultivation range expansion and factors governing this process received relatively little attention. Here, using mungbean (Vigna radiata var. radiata) as a test case, we investigated the genomes of more than 1000 accessions to illustrate climatic adaptation's role in dictating the unique routes of cultivation range expansion. Despite the geographical proximity between South and Central Asia, genetic evidence suggests mungbean cultivation first spread from South Asia to Southeast, East and finally reached Central Asia. Combining evidence from demographic inference, climatic niche modeling, plant morphology, and records from ancient Chinese sources, we showed that the specific route was shaped by the unique combinations of climatic constraints and farmer practices across Asia, which imposed divergent selection favoring higher yield in the south but short-season and more drought-tolerant accessions in the north. Our results suggest that mungbean did not radiate from the domestication center as expected purely under human activity, but instead, the spread of mungbean cultivation is highly constrained by climatic adaptation, echoing the idea that human commensals are more difficult to spread through the south-north axis of continents.

Mungbean, also known as green gram, is an important crop plant in China, India, the Philippines and many other countries across Asia. Archaeological evidence suggests that humans first cultivated mungbeans from wild relatives in India over 4,000 years ago. However, it remains unclear how cultivation has spread to other countries and whether human activity alone dictated the route of the cultivated mungbean's expansion across Asia, or whether environmental factors, such as climate, also had an impact. To understand how a species of plant has evolved, researchers may collect specimens from the wild or from cultivated areas. Each group of plants of the same species they collect in a given location at a single point in time is known collectively as an accession. Ong et al. used a combination of genome sequencing, computational modelling and plant biology approaches to study more than 1,000 accessions of cultivated mungbean and trace the route of the crop's expansion across Asia. The data support the archaeological evidence that mungbean cultivation first spread from South Asia to Southeast Asia, then spread northwards to East Asia and afterwards to Central Asia. Computational modelling of local climates and the physical characteristics of different mungbean accessions suggest that the availability of water in the local area likely influenced the route. Specifically, accessions from arid Central Asia were better adapted to drought conditions than accessions from wetter South Asia. However, these drought adaptations decreased the yield of the plants, which may explain why the more drought tolerant accessions have not been widely grown in wetter parts of Asia. This study shows that human activity has not solely dictated where mungbean has been cultivated. Instead, both human activity and the various adaptations accessions evolved in response to their local environments shaped the route the crop took across Asia. In the future these findings may help plant breeders to identify varieties of mungbean and other crops with drought tolerance and other potentially useful traits for agriculture.

Intervening with Opioid-Exposed Newborns:: Modifying an Evidence-Based Parenting Intervention.

Background: Prenatal opioid exposure predisposes infants to adverse development of regulatory systems and jeopardizes their long-term health outcomes. While sensitive caregiving promotes healthy development of emotional and physiological regulation and may remediate risks associated with prenatal opioid exposure, mothers with opioid use disorder often experience unique challenges that make providing sensitive care difficult. Rationale: Empirically tested early interventions, such as the Attachment and Biobehavioral Catch-up (ABC) intervention, can positively impact children's development following adversity through promoting sensitive caregiving. ABC intervention targets correspond to those parenting behaviors that may be challenging for mothers with opioid use disorder (i.e., nurturing infants who may be difficult to soothe, responding sensitively to infants by following the child's lead with delight, and avoiding intrusive/frightening behavior), and have positive impacts on child development and regulation. However, given the unique challenges for infants and mothers impacted by opioid use, some adaptations may strategically address those vulnerabilities and thereby maximize the potential benefits for this population. Methods: The present paper describes modifications made to the ABC intervention for use with pregnant mothers in treatment for opioid use disorder. This modified intervention is currently being examined via a large scale randomized clinical trial (RCT) at the University of Delaware, and a case study is presented here to highlight considerations for working with mothers and infants impacted by opioid use and to exemplify ways that modified ABC addresses the needs of this population.

Structural Connectivity Between Rostral Anterior Cingulate Cortex and Amygdala Predicts First Onset of Depressive Disorders in Adolescence.

BACKGROUND: Adolescent-onset depressive disorders (DDs) are associated with deficits in the regulation of negative affect across modalities (self-report, behavioral paradigms, and neuroimaging), which may manifest prior to first-onset DDs. Whether the neurocircuitry governing emotional regulation predates DDs is unclear. This study tested whether a critical pathway for emotion regulation (rostral anterior cingulate cortex-amygdala structural connectivity) predicts first-onset DDs in adolescent females. METHODS: Diffusion tensor imaging data were acquired on adolescent females (n = 212) without a history of DDs and the cohort was reassessed for first-onset DDs over the next 27 months. RESULTS: A total of 26 girls developed first onsets of DDs in the 27 months after imaging. Multivariate logistic regression showed that lower weighted average fractional anisotropy of uncinate fasciculus tracts between the rostral anterior cingulate cortex and amygdala prospectively predicted first onset of DDs (adjusted odds ratio = 0.44, p = .005), above and beyond established risk factors including baseline depression symptom severity, history of anxiety disorders, parental history of depression, parental education, and age. CONCLUSIONS: This study provides evidence for the first time showing that aberrant structural connectivity between the rostral anterior cingulate cortex and amygdala prospectively predates first onset of DDs in adolescent females. These results highlight the importance of a well-established neural circuit implicated in the regulation of negative affect as a likely etiological factor and a promising target for intervention and prevention of DDs.

Propofol increases bone morphogenetic protein-7 and decreases oxidative stress in sepsis-induced acute kidney injury.

BACKGROUND: Pro-inflammatory cytokines and free radicals damage renal tissue leading to acute kidney injury (AKI) during sepsis. Bone morphogenetic protein-7 (BMP-7) represses tumour necrosis factor (TNF)-α-induced inflammatory responses and protects kidney from injury. The sedative agent, propofol, has immunomodulatory and antioxidative properties. The present study investigated whether propofol could reduce AKI in caecal ligation and puncture (CLP) mice and the possible mechanism behind this. METHODS: Mice were treated with propofol or saline immediately and 12 h after CLP surgery. Kidney injury, survival and cytokine expressions of CLP mice were observed 24 h after CLP surgery. In vitro, lipopolysaccharide (LPS)-stimulated rat mesangial cells (RMCs) or hydrogen peroxide (H(2)O(2))-exposed murine kidney epithelial cells (M1) were treated with propofol. The expression of BMP-7, TNF-α and monocyte chemotactic protein (MCP)-1 in CLP mice kidney, RMCs or M1 cells was determined by RT-PCR. Free radical generation and cell death of RMCs and M1 cells were analysed. Nuclear factor (NF)-κB and peroxisome proliferator-activated receptor (PPAR)-γ expressions in LPS-stimulated RMCs were determined by western blotting. RESULTS: Propofol increased survival and ameliorated AKI in CLP mice. Propofol increased BMP-7 expression but decreased TNF-α and MCP-1 expressions in the kidney of CLP mice and LPS-stimulated RMCs. Propofol also inhibited free radical generation and cell death in LPS-stimulated RMCs and decreased the TNF-α expression and cell death in H(2)O(2)-exposed M1 cells. Moreover, propofol decreased NF-κB but increased PPAR-γ expression in LPS-stimulated RMCs. CONCLUSIONS: Propofol treatment could protect kidney from sepsis-induced AKI by increasing BMP-7 expression, decreasing inflammatory cytokines and inhibiting oxidative stress.

Gout: an independent risk factor for all-cause and cardiovascular mortality.

OBJECTIVE: The relation of gout and hyperuricaemia to cardiovascular diseases has been well documented. This study investigates the survival impact of both gout and hyperuricaemia. METHODS: The subjects of this study comprised participants of a health screening programme conducted by the Chang Gung Memorial Hospital in Taiwan from 2000 to 2006. The status and causes of death were ascertained by the Taiwan National Death Registry 2000-07. Cox proportional hazard model was performed to examine the association. RESULTS: Among 61 527 subjects, 1383 deaths (198 cardiovascular deaths) were identified, corresponding to a crude mortality rate of 4.86 deaths per 1000 person-years. Crude mortality rates were 4.50, 5.61 and 10.46 deaths per 1000 person-years for subjects with normouricaemia, hyperuricaemia and gout, respectively. Compared with subjects with normouricaemia, the hazard ratios (HRs) of all-cause mortality were 1.46 (95% CI 1.12, 1.91) for individuals with gout and 1.07 (95% CI 0.94, 1.22) for those with hyperuricaemia, respectively, after adjustments were made for age, sex, component number of metabolic syndrome and proteinuria. The adjusted HRs of cardiovascular mortality were 1.97 (95% CI 1.08, 3.59) for individuals with gout and 1.08 (95% CI 0.78, 1.51) for those with hyperuricaemia. Moreover, the risk of all-cause or cardiovascular mortality for gout remained unchanged when limiting the data to those with an estimated glomerular filtration of >60 ml/min/1.73 m(2). CONCLUSION: This study demonstrates a link of gout, not hyperuricaemia, with a higher risk of death from all causes and cardiovascular diseases.

Role of uric acid in the link between arterial stiffness and cardiac hypertrophy: a cross-sectional study.

OBJECTIVES: Hyperuricaemia has been linked to atherosclerosis; however, there is limited evidence about its association with arterial stiffness and cardiac hypertrophy, which are associated with adverse cardiovascular outcomes. We studied the association of hyperuricaemia with an increased risk of arterial stiffness and cardiac hypertrophy in a population participating in a health-screening programme. METHODS: In subjects who underwent health screening from 2005 to 2007, arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV), whereas cardiac hypertrophy was determined by plain chest radiography and electrocardiography. Polychotomous logistic regression was used to identify associations of hyperuricaemia with arterial stiffness and cardiac hypertrophy, after adjusting for the presence of metabolic syndrome. RESULTS: Of the total 9375 subjects enrolled, 1324 (14.5%) had hyperuricaemia. Subjects with hyperuricaemia had a significantly higher baPWV [1618.8 (379.3) cm/s] than those without it [1501.8 (334.9) cm/s]. Cardiac hypertropy was observed in 1047 (11.2%) subjects. Hyperuricaemia was associated with cardiac hypertrophy with an odds ratio (OR) of 1.53 (95% CI 1.32, 1.77). Polychotomous logistic regression showed that hyperuricaemia was associated with ORs (95% CI) for coexisting abnormal baPWV and cardiac hypertrophy of 1.75 (95% CI 1.24, 2.47) and 1.41 (95% CI 1.04, 1.91) in men and women, respectively, after adjusting for age, proteinuria, high high-sensitive CRP, abnormal ankle-brachial index or a number of metabolic syndrome components present. CONCLUSION: Hyperuricaemia was associated with arterial stiffness and cardiac hypertrophy. Hyperuricaemia, along with other risk factors related to atherosclerosis, could play a role in the development of cardiac hypertrophy by increasing arterial stiffness.

A decentralized framework for cultivating research lifecycle transparency.

Research transparency has been advocated as a key means of addressing the current crisis of reproducibility. This article proposes an enhanced form of research transparency, termed lifecycle transparency. Over the entire lifecycle of a research effort, this approach captures the syntactical contexts of artifacts and stakeholders, such as timestamps, agreements, and/or dependency requirements for completing each research phase. For example, such contexts might include when, where, and from whom patients' consent and institutional review board approvals were received before a clinical trial was carried out. However, as existing open-science tools are often dedicated to certain research phases or disciplines, and thus insufficient to support lifecycle transparency, we propose a novel decentralized framework to serve as a common medium for interaction among open-science tools, and produces irrefutable and immutable proofs of progress that can be verified automatically.

Psychometric evaluation of the WHOQOL-BREF in community-dwelling older people in Taiwan using Rasch analysis.

OBJECTIVE: To examine the psychometric characteristics of the brief version of the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire in rural-community-dwelling older people in Taiwan using Rasch analysis. METHODS: This is a cross-sectional study. A total of 1200 subjects aged >or=65 years were recruited to complete the 26-item WHOQOL-BREF. Scale dimensionality, item difficulty, scale reliability and separation, item targeting, item-person map, and differential item functioning (DIF) were examined. RESULTS: The four WHOQOL-BREF scales (physical capacity, psychological well-being, social relationships, and environment) were found to be unidimensional and reliable. The item-person map for each domain indicated that the spread of the item thresholds sufficiently covered the latent trait continuum being measured. However, gaps in content coverage were identified in the social domain. Analyses of the DIF revealed that one psychological item (body image) exhibited DIF across the two age groups (old-old vs. young-old) and that two social items (sexual activity and friends' support) displayed DIF across genders and the two age groups. CONCLUSIONS: Rasch analysis is a comprehensive method of psychometric evaluation of the WHOQOL-BREF and identifies areas for improvements. Three items displaying age-related DIF (body image, sexual activity, and friends' support) may potentially cause biased health-related QOL assessments, and their impacts on scores should be carefully examined.

Splenic infarction and abscess complicating infective endocarditis.

Acute abdominal pain is one of the most common conditions confronted in the emergency department. Clues related to splenic infarction may be obscured, and the diagnosis is quite challenging even for experienced physicians or surgeons. For every patient diagnosed with splenic infarction, a scrutiny on the possible source of emboli should be carried out. In addition, splenic abscess must be suspected in patients of splenic infarction, especially if the infectious signs persist despite appropriate treatment. Rapid diagnosis and treatment are essential as its course can prove fatal. Infective endocarditis is the most common condition predisposing a patient to splenic abscess. Indeed, splenic abscess or infarction may be a disease entity at different stages in patients of infective endocarditis due to septic emboli of the spleen. The treatment of choice has been antibiotics, splenectomy, and valve replacement surgery. Herein, we report a case of splenic abscess and infective endocarditis cured by antibiotic treatment without the aid of drainage or surgery.

Synthesis, DNA binding, and cytotoxicity of 1,4-bis(2-amino-ethylamino)anthraquinone-amino acid conjugates.

Two series of 1,4-bis(2-amino-ethylamino)anthraquinone-amino acid conjugates (BACs), ametantrone (AT)-amino acid conjugates (AACs) and mitoxantrone (MX)-amino acid conjugates (MACs), were designed and synthesized. The DNA binding of BACs was evaluated by DNA thermal denaturation experiment. In the series, the methionine-substituted BACs had the weakest DNA binding, while the lysine-substituted BACs had the highest T(m) values. The abilities of BACs to inhibit the growth of MCF-7, NCI-H460, SF-268, and PC-3 cell lines were determined. l-Met-MAC 16 and l-Lys-MAC 20 were the most potent growth inhibitors. MAC 16 was more cytotoxic than MX, whereas the T(m) of MAC 16 was much lower than that of MX. In contrast to MAC 16, l-Lys-MAC 20 demonstrated higher T(m) than MX. These data suggested that Met-BACs possessed a different pharmacological profile, in which the ability to stabilize DNA is not parallel to the ability to kill cancer cells, from that of AT and MX. The primary mechanism of cytotoxicity for MAC 16 was most likely through TOP2 poisoning. Therefore, MAC 16 may provide a lead for the development of novel generations of anthraquinone-type antitumor agents.

How to standardize 3 finger positions of examiner for palpating radial pulses at wrist in traditional Chinese medicine.

This study was to provide a standardized definition of the positioning method of finger placement on the radial artery for pulse diagnosis in traditional Chinese medicine (TCM); that is, to define the locations of Cun, Guan and Chi in TCM. A total of 200 subjects (100 males and 100 females, 18-40 years of age) were recruited from the general population. According to ancient TCM records, the "6% of the elbow length" (ELx6%) is used as the standard method of establishing the length of Cun. We hypothesized that the highest point of "prominent bone" (PB) is the lower limit of Cun, so "the distance between the distal wrist crease and the highest point of the PB" (DWP) is considered the length of Cun. If this hypothesis holds, then we can define the locations of Cun, Guan and Chi by using the ratio 6:6:7 from the ancient TCM records. The distribution of relative bias and paired t-test were used to verify the findings. The mean value of relative bias of DWP compared with ELx6% was close to 0% (males = 2.1%, SD = 12.2%; females = 0.2%, SD = 12.6%). The paired t-test confirmed that there was no significant difference (p > 0.05) between the mean values of the DWP and ELx6%. Therefore, it is reasonable to assume that the length of the Cun is equal to the length of the DWP. Our findings confirm that the location of Cun is from the distal wrist crease to the highest point of PB.

Development of Liquid Bait With Unique Bait Station for Control of Dolichoderus thoracicus (Hymenoptera: Formicidae).

The Dolichoderus thoracicus (Smith) has seriously infested urban, village, and agricultural environments in Taiwan. To develop optimal bait for the effective control of D. thoracicus, we investigated the feeding preferences of this ant at different sugar and amino acid concentrations in a laboratory setting. The number of feeding workers was significantly higher for 20% sucrose compared with that for other sugars at 10% and 20% concentrations. Furthermore, among all tested concentrations of monosodium glutamate (MSG; 1%, 3%, 5%, and 10%), the highest number of ants were attracted by 1% MSG with 20% sucrose. The consumption of each bait solution was also measured, and the results were similar to those for ant number. Regarding toxicants, the toxicity and repellency of 3% boric acid and borax bait were evaluated individually. Both 3% boric acid and borax demonstrated no repellency against D. thoracicus workers. The LT50 of the 3% boric acid bait was 4.87 d, whereas that of 3% borax bait was only 1.56 d. Thus, 3% boric acid showed further delayed action, facilitating workers spreading the toxicant to their nestmates through trophallaxis. In combination with our unique bait station, we propose an optimal bait formulation comprising 20% sucrose, 1% MSG, and 3% boric acid as a promising candidate for controlling D. thoracicus.

Fast and Facile Synthesis of 4-Nitrophenyl 2-Azidoethylcarbamate Derivatives from N-Fmoc-Protected α-Amino Acids as Activated Building Blocks for Urea Moiety-Containing Compound Library.

A fast and facile synthesis of a series of 4-nitrophenyl 2-azidoethylcarbamate derivatives as activated urea building blocks was developed. The N-Fmoc-protected 2-aminoethyl mesylates derived from various commercially available N-Fmoc-protected α-amino acids, including those having functionalized side chains with acid-labile protective groups, were directly transformed into 4-nitrophenyl 2-azidoethylcarbamate derivatives in 1 h via a one-pot two-step reaction. These urea building blocks were utilized for the preparation of a series of urea moiety-containing mitoxantrone-amino acid conjugates in 75-92% yields and parallel solution-phase synthesis of a urea compound library consisted of 30 members in 38-70% total yields.