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.

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.

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.

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.

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.

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.

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.

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.

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.

Variation in Indole-3-Acetic Acid Production by Wild Saccharomyces cerevisiae and S. paradoxus Strains from Diverse Ecological Sources and Its Effect on Growth.

Phytohormone indole-3-acetic acid (IAA) is the most common naturally occurring and most thoroughly studied plant growth regulator. Microbial synthesis of IAA has long been known. Microbial IAA biosynthesis has been proposed as possibly occurring through multiple pathways, as has been proven in plants. However, the biosynthetic pathways of IAA and the ecological roles of IAA in yeast have not been widely studied. In this study, we investigated the variation in IAA production and its effect on the growth of Saccharomyces cerevisiae and its closest relative Saccharomyces paradoxus yeasts from diverse ecological sources. We found that almost all Saccharomyces yeasts produced IAA when cultured in medium supplemented with the primary precursor of IAA, L-tryptophan (L-Trp). However, when cultured in medium without L-Trp, IAA production was only detected in three strains. Furthermore, exogenous added IAA exerted stimulatory and inhibitory effects on yeast growth. Interestingly, a negative correlation was observed between the amount of IAA production in the yeast cultures and the IAA inhibition ratio of their growth.

The Resistive Switching Characteristics in ZrO2 and Its Filamentary Conduction Behavior.

This study investigated the conduction properties of sputtered ZrO2 exhibiting reversible and stable resistance change. Similar current distributions in on/off conduction and set/reset switching were observed in top electrodes with a diameter of 150, 250, and 350 µm. The size independence of current magnitude implied the presence of an uneven filamentary path over the electrode area. Increased current compliance was imposed on the turn-on process, and the observed increase in on-state current and turn-off threshold was attributed to incremental filament diameter. Variations in current conduction and resistance switching were analyzed by monitoring sweeping bias limits in both positive and negative polarities. These experimental observations were interpreted based on the aspect ratio of channels comprising conductive and oxidized filament portions, thereby elucidating the characteristics of filamentary resistive switching.

Indole-3-acetic acid: A widespread physiological code in interactions of fungi with other organisms.

Plants as well as microorganisms, including bacteria and fungi, produce indole-3-acetic acid (IAA). IAA is the most common plant hormone of the auxin class and it regulates various aspects of plant growth and development. Thus, research is underway globally to exploit the potential for developing IAA-producing fungi for promoting plant growth and protection for sustainable agriculture. Phylogenetic evidence suggests that IAA biosynthesis evolved independently in bacteria, microalgae, fungi, and plants. Present studies show that IAA regulates the physiological response and gene expression in these microorganisms. The convergent evolution of IAA production leads to the hypothesis that natural selection might have favored IAA as a widespread physiological code in these microorganisms and their interactions. We summarize recent studies of IAA biosynthetic pathways and discuss the role of IAA in fungal ecology.

Development of a growth-hormone-conjugated nanodiamond complex for cancer therapy.

It is highly desirable to develop a therapeutic, observable nanoparticle complex for specific targeting in cancer therapy. Growth hormone (GH) and its antagonists have been explored as cancer cell-targeting molecules for both imaging and therapeutic applications. In this study, a low toxicity, biocompatible, therapeutic, and observable GH-nanoparticle complex for specifically targeting growth hormone receptor (GHR) in cancer cells was synthesized by conjugating GH with green fluorescence protein and carboxylated nanodiamond. Moreover, we have shown that this complex can be triggered by laser irradiation to create a "nanoblast" and induce cell death in the A549 non-small-cell lung cancer cell line via the apoptotic pathway. This laser-mediated, cancer-targeting platform can be widely used in cancer therapy.

Synthesis of apolipoprotein B lipoparticles to deliver hydrophobic/amphiphilic materials.

To develop a drug delivery system (DDS), it is critical to address challenging tasks such as the delivery of hydrophobic and amphiphilic compounds, cell uptake, and the metabolic fate of the drug delivery carrier. Low-density lipoprotein (LDL) has been acknowledged as the human serum transporter of natively abundant lipoparticles such as cholesterol, triacylglycerides, and lipids. Apolipoprotein B (apo B) is the only protein contained in LDL, and possesses a binding moiety for the LDL receptor that can be internalized and degraded naturally by the cell. Therefore, synthetic/reconstituting apoB lipoparticle (rABL) could be an excellent delivery carrier for hydrophobic or amphiphilic materials. Here, we synthesized rABL in vitro, using full-length apoB through a five-step solvent exchange method, and addressed its potential as a DDS. Our rABL exhibited good biocompatibility when evaluated with cytotoxicity and cell metabolic response assays, and was stable during storage in phosphate-buffered saline at 4 °C for several months. Furthermore, hydrophobic superparamagnetic iron oxide nanoparticles (SPIONPs) and the anticancer drug M4N (tetra-O-methyl nordihydroguaiaretic acid), used as an imaging enhancer and lipophilic drug model, respectively, were incorporated into the rABL, leading to the formation of SPIONPs- and M4N- containing rABL (SPIO@rABL and M4N@rABL, respectively). Fourier transform infrared spectroscopy suggested that rABL has a similar composition to that of LDL, and successfully incorporated SPIONPs or M4N. SPIO@rABL presented significant hepatic contrast enhancement in T2-weighted magnetic resonance imaging in BALB/c mice, suggesting its potential application as a medical imaging contrast agent. M4N@rABL could reduce the viability of the cancer cell line A549. Interestingly, we developed solution-phase high-resolution transmission electron microscopy to observe both LDL and SPIO@rABL in the liquid state. In summary, our LDL-based DDS, rABL, has significant potential as a novel DDS for hydrophobic and amphiphilic materials, with good cell internalization properties and metabolicity.

Biological treatment of TMAH (tetra-methyl ammonium hydroxide) in a full-scale TFT-LCD wastewater treatment plant.

This study evaluated biological treatment of TMAH in a full-scale methanogenic up-flow anaerobic sludge blanket (UASB) followed by an aerobic bioreactor. In general, the UASB was able to perform a satisfactory TMAH degradation efficiency, but the effluent COD of the aerobic bioreactor seemed to increase with an increased TMAH in the influent wastewater. The batch test results confirmed that the UASB sludge under methanogenic conditions would be favored over the aerobic ones for TMAH treatment due to its superb ability of handling high strength of TMAH-containing wastewaters. Based on batch experiments, inhibitory chemicals present in TFT-LCD wastewater like surfactants and sulfate should be avoided to secure a stable methanogenic TMAH degradation. Finally, molecular monitoring of Methanomethylovorans hollandica and Methanosarcina mazei in the full-scale plant, the dominant methanogens in the UASB responsible for TMAH degradation, may be beneficial for a stable TMAH treatment performance.

Anthracenedione-methionine conjugates are novel topoisomerase II-targeting anticancer agents with favorable drug resistance profiles.

Structure-associated drug resistance and DNA-unwinding abilities have greatly limited the clinical usage of anthracenediones, including mitoxantrone (MX) and ametantrone (AT), which intercalate into DNA and induce topoisomerase II (TOP2)-mediated DNA break. We studied a series of 1,4-bis(2-amino-ethylamino) MX- and AT-amino acid conjugates (M/AACs) and showed that abilities in cancer cell killing correlate with the amounts of chromosomal DNA breaks induced by M/AACs. Notably, the 1,4-bis-L/l-methionine-conjugated MAC (L/LMet-MAC) exhibits DNA-breaking, cancer cell-killing and anti-tumor activities rivaling those of MX. Interestingly, l- and d-form Met-M/AACs unwind DNA poorly compared to MX and AT. The roles of the two human TOP2 isozymes (hTOP2α and 2ß) in the L/LMet-MAC-induced DNA breakage and cancer cell-killing were suggested by the following observations: (i) M/AAC-induced DNA breakage, cytotoxicity and apoptosis are greatly reduced in various TOP2-deficient conditions; (ii) DNA breaks induced by MACs are highly reversible and effectively antagonized by the TOP2 catalytic inhibitors; (iii) MACs induced differential TOP2-mediated DNA cleavage in vitro using recombinant hTOP2α proteins and the formation of hTOP2α/ßcc in the cell culture system. Interestingly, d-aa-conjugated MACs often caused a lower level in hTOP2-mediated DNA breaks and cell-killing than the corresponding l-form ones indicating a steric-specific effect of MACs. Together, our results suggest that both enzyme- and DNA-drug interactions might contribute to TOP2-targeting by M/AACs. Furthermore, Met-MACs are poor substrates for the MDR1 transporter. Therefore, L/LMet-MAC represents a promising class of TOP2-targeting drugs with favorable drug resistance profiles.