bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic analysis of DAF-18/PTEN missense mutants for the ability to maintain quiescence of the somatic gonad and germ line in Caenorhabditis elegans dauer larvae
Authors: Wittes Julia , Greenwald Iva 
Published: April 2022

Abstract
The mammalian tumor suppressor PTEN has well-established lipid phosphatase and protein phosphatase activities. DAF-18, the Caenorhabditis elegans ortholog of PTEN, has a high degree of conservation in the catalytic domain, and human PTEN complements a null allele of daf-18, suggesting conserved protein function. Insights gleaned from studies of mammalian PTEN have been applied to studies of DAF-18 in C. elegans, including predicted enzymatic properties of mutants. Here, we characterize DAF-18 missense mutants previously treated as selectively disrupting either protein or lipid phosphatase activity in genetic assays to connect distinct phenotypes to specific enzymatic activities of DAF-18/PTEN. We analyze the ability of these mutants to maintain quiescence of the somatic gonad and germ line in dauer larvae, a state of diapause during which development is suspended. We show that transgenes expressing either the putative lipid phosphatase-deficient or putative protein phosphatase-deficient form fail to complement a daf-18 null allele, and that the corresponding homozygous endogenous missense mutant alleles fail to maintain developmental quiescence. We also show that the endogenous daf-18 missense alleles fail to complement each other, suggesting that one or both of the missense forms are not activity-selective. Furthermore, homozygous daf-18 missense mutants have a more severe phenotype than a daf-18 null mutant, suggesting the presence of functionally compromised mutant DAF-18 is more deleterious than the absence of DAF-18. We discuss how these genetic properties complicate the interpretation of genetic assays to associate specific enzymatic activities with specific phenotypes.
High-throughput characterization, correlation, and mapping of leaf photosynthetic and functional traits in the soybean (Glycine max) nested association mapping population
Authors: Montes Christopher M , Fox Carolyn , Sanz-Sáez Álvaro , Serbin Shawn P , Kumagai Etsushi , Krause Matheus D , Xavier Alencar , Specht James E , Beavis William D , Bernacchi Carl J , Diers Brian W , Ainsworth Elizabeth A 
Published: April 2022

AbstractPhotosynthesis is a key target to improve crop production in many species including soybean [Glycine max (L.) Merr.]. A challenge is that phenotyping photosynthetic traits by traditional approaches is slow and destructive. There is proof-of-concept for leaf hyperspectral reflectance as a rapid method to model photosynthetic traits. However, the crucial step of demonstrating that hyperspectral approaches can be used to advance understanding of the genetic architecture of photosynthetic traits is untested. To address this challenge, we used full-range (500–2,400 nm) leaf reflectance spectroscopy to build partial least squares regression models to estimate leaf traits, including the rate-limiting processes of photosynthesis, maximum Rubisco carboxylation rate, and maximum electron transport. In total, 11 models were produced from a diverse population of soybean sampled over multiple field seasons to estimate photosynthetic parameters, chlorophyll content, leaf carbon and leaf nitrogen percentage, and specific leaf area (with R2 from 0.56 to 0.96 and root mean square error approximately &lt;10% of the range of calibration data). We explore the utility of these models by applying them to the soybean nested association mapping population, which showed variability in photosynthetic and leaf traits. Genetic mapping provided insights into the underlying genetic architecture of photosynthetic traits and potential improvement in soybean. Notably, the maximum Rubisco carboxylation rate mapped to a region of chromosome 19 containing genes encoding multiple small subunits of Rubisco. We also mapped the maximum electron transport rate to a region of chromosome 10 containing a fructose 1,6-bisphosphatase gene, encoding an important enzyme in the regeneration of ribulose 1,5-bisphosphate and the sucrose biosynthetic pathway. The estimated rate-limiting steps of photosynthesis were low or negatively correlated with yield suggesting that these traits are not influenced by the same genetic mechanisms and are not limiting yield in the soybean NAM population. Leaf carbon percentage, leaf nitrogen percentage, and specific leaf area showed strong correlations with yield and may be of interest in breeding programs as a proxy for yield. This work is among the first to use hyperspectral reflectance to model and map the genetic architecture of the rate-limiting steps of photosynthesis.
Critical metabolic pathways and SAD/FADs, WRI1s, and DGATs cooperate for high-oleic acid oil production in developing oil tea (Camellia oleifera) seeds
Authors: Yang Jihong , Chen Beibei , Manan Sehrish , Li Penghui , Liu Chun , She Guangbiao , Zhao Shancen , Zhao Jian 
Published: April 2022

Abstract
Oil tea trees produce high-quality edible oils with desirably high oleic acid (18:1) and low linoleic (18:2) and linolenic (18:3) fatty acid (FA) levels, but limited understanding of tea oil biosynthesis and regulation has become a significant obstacle for the breeding of high-yield and -quality oil tea varieties. By integrating metabolite and transcriptome analyses of developing oil tea seeds, we dissected the critical metabolic pathways, including glycolysis, fatty acid, and triacylglycerol (TAG) biosynthesis, as well as genes essential for tea seed oil production. Two plastidic stearoyl-acyl carrier protein desaturases (CoSAD1 and 2) and two endoplasmic reticulum-localized FA desaturases (CoFAD2 and 3) were functionally characterized as responsible for high 18:1 and low 18:2 and 18:3 proportions in tea oils. Two diacylglycerol O-acyltransferases (CoDGAT1 and 2) that may prefer to synthesize 18:1-TAG were functionally characterized and might be also important for high 18:1-TAG production. The highly expressed CoWRI1a and b were identified and characterized as activators of glycolysis and regulators of directing source carbon flux into FA biosynthesis in developing oil tea seeds. The upregulated CoSADs with downregulated CoFAD2 and CoFAD3 at the late seed developmental stages mainly accounted for high 18:1 levels. Two CoDGATs might be responsible for assembling TAGs with oleoyl acyl chains, whilst two CoWRI1s regulated carbons from parental sources, partitioning into oil production in oil tea embryo sinks. This study provides a deep understanding of the biosynthesis of tea seed oils and information on genes that may be used as molecular markers to breed oil tea varieties with higher oil yield and quality.
Introducing melatonin to the horticultural industry: physiological roles, potential applications, and challenges
Authors: Gao Tengteng , Liu Xiaomin , Tan Kexin , Zhang Danni , Zhu Bolin , Ma Fengwang , Li Chao 
Published: April 2022

Abstract
Melatonin (N-acetyl-5-methoxytryptamine) is an emerging biomolecule that influences horticultural crop growth, flowering, fruit ripening, postharvest preservation, and stress protection. It functions as a plant growth regulator, preservative and antimicrobial agent to promote seed germination, regulate root system architecture, influence flowering and pollen germination, promote fruit production, ensure postharvest preservation, and increase resistance to abiotic and biotic stresses. Here, we highlight the potential applications of melatonin in multiple aspects of horticulture, including molecular breeding, vegetative reproduction, production of virus-free plants, food safety, and horticultural crop processing. We also discuss its effects on parthenocarpy, autophagy, and arbuscular mycorrhizal symbiosis. Together, these many features contribute to the promise of melatonin for improving horticultural crop production and food safety. Effective translation of melatonin to the horticultural industry requires an understanding of the challenges associated with its uses, including the development of economically viable sources.
Comparative methylomics and chromatin accessibility analysis in
Osmanthus fragrans
uncovers regulation of genic transcription and mechanisms of key floral scent production
Authors: Han Yuanji , Lu Miaomiao , Yue Shumin , Li Ke , Dong Meifang , Liu Luxian , Wang Hongyun , Shang Fude 
Published: April 2022

Abstract
Linalool and ionone are two important aromatic components in sweet osmanthus petals, and the regulatory mechanisms that produce these two components remain unclear. In this study, we employed whole-genome methylation sequencing and ATAC-seq technology to analyze the genomic DNA methylation status and chromatin accessibility of the sweet osmanthus cultivars ‘Zaohuang’ and ‘Chenghong Dangui’. Results showed that the promoter region of TPS2, a key gene in the linalool synthesis pathway, was less methylated in ‘Chenghong Dangui’ than in ‘Zaohuang’. The chromatin was more accessible in ‘Chenghong Dangui’ than in ‘Zaohuang’, which resulted in a much stronger expression of this gene in ‘Chenghong Dangui’ than in ‘Zaohuang’. This eventually led to a high quantity of linalool and its oxides in the petals of ‘Chenghong Dangui’, but there were lower levels present in the petals of ‘Zaohuang’. These results suggest that DNA methylation and chromatin accessibility play major roles in linalool synthesis in sweet osmanthus. The methylation level of the promoter region of CCD4, a key gene for ionone synthesis, was higher in ‘Zaohuang’ than in ‘Chenghong Dangui’. The chromatin accessibility was lower in ‘Zaohuang’ than in ‘Chenghong Dangui’, although the expression of this gene was significantly higher in ‘Zaohuang’ than in ‘Chenghong Dangui’. ChIP-seq analysis and a series of experiments showed that the differential expression of CCD4 and CCD1 in the two cultivars may predominantly be the result of regulation by ERF2 and other transcription factors. However, a 183-bp deletion involving the CCD4 promoter region in ‘Chenghong Dangui’ may be the main reason for the low expression of this gene in its petals. This study provides an important theoretical basis for improving selective breeding of key floral fragrance components in sweet osmanthus.
Functional analysis of the dihydroflavonol 4-reductase family of Camellia sinensis: exploiting key amino acids to reconstruct reduction activity
Authors: Ruan Haixiang , Shi Xingxing , Gao Liping , Rashid Arif , Li Yan , Lei Ting , Dai Xinlong , Xia Tao , Wang Yunsheng 
Published: April 2022

Abstract
Anthocyanins and proanthocyanidins (PAs) are important types of flavonoids, plant secondary metabolites with a wide range of industrial and pharmaceutical applications. DFR (dihydroflavonol 4-reductase) is a pivotal enzyme that plays an important role in the flavonoid pathway. Here, four CsDFR genes were isolated from Camellia sinensis, and their overexpression was analyzed in vitro and in vivo. Based on transcription and metabolic analyses, CsDFR expression was closely consistent with catechins and PAs accumulation. Moreover, enzyme activity analyses revealed that the two recombinant proteins CsDFRa and CsDFRc exhibited DFR activity, converting dihydroflavonols into leucoanthocyanins in vitro, but CsDFRb1 and CsDFRb3 did not. CsDFRa and CsDFRc overexpression in AtDFR mutants (tt3) revealed that CsDFRs are involved in the biosynthesis of anthocyanins and PAs, as CsDFRa and CsDFRc restored not only the purple petiole phenotype but also the seed coat color. Site-directed mutagenesis revealed that the two amino acid residues S117 and T123 of CsDFRa play a prominent role in controlling DFR reductase activity. Enzymatic assays indicated that CsDFRa and CsDFRc exhibited a higher affinity for DHQ and DHK, respectively, whereas CsDFRb1N120S and CsDFRb1C126T exhibited a higher affinity for DHM. Our findings comprehensively characterize the DFRs from C. sinensis and shed light on their critical role in metabolic engineering.
Current Venous Thromboembolism Chemoprophylaxis Practices After Surgery for Inflammatory Bowel Diseases
Authors: Bickston Stephen J , Patrone Michael V 
Published: April 2022

Lay Summary
Recent events shed light on the high risk of venous thromboembolism (VTE) in patients with inflammatory bowel disease and the importance of prophylaxis in such patients. Protocols within the electronic medical record help improve compliance with VTE prophylaxis.
Molecular biomarker-defined brain tumors: Epidemiology, validity, and completeness in the United States
Authors: Iorgulescu J Bryan , Sun Chuxuan , Neff Corey , Cioffi Gino , Gutierrez Catherine , Kruchko Carol , Ruhl Jennifer , Waite Kristin A , Negoita Serban , Hofferkamp Jim , Tihan Tarik , McLendon Roger , Brat Daniel J , Ostrom Quinn T , Barnholtz-Sloan Jill S 
Published: April 2022

AbstractBackgroundSelected molecular biomarkers were incorporated into the US cancer registry reporting for patients with brain tumors beginning in 2018. We investigated the completeness and validity of these variables and described the epidemiology of molecularly defined brain tumor types.MethodsBrain tumor patients with histopathologically confirmed diagnosis in 2018 were identified within the Central Brain Tumor Registry of the United States and NCI’s Surveillance, Epidemiology, and End Results Incidence databases. The brain molecular markers (BMM) site-specific data item was assessed for coding completeness and validity. 1p/19q status, MGMT promoter methylation, WHO grade data items, and new ICD-O-3 codes were additionally evaluated. These data were used to profile the characteristics and age-adjusted incidence rates per 100 000 population of molecularly defined brain tumors with 95% confidence intervals (95% CI).ResultsBMM completeness across the applicable tumor types was 75%-92% and demonstrated favorable coding validity. IDH-wildtype glioblastomas’ incidence rate was 1.74 (95% CI: 1.69-1.78), as compared to 0.14 for WHO grade 2 (95% CI: 0.12-0.15), 0.15 for grade 3 (95% CI: 0.14-0.16), and 0.07 for grade 4 (95% CI: 0.06-0.08) IDH-mutant astrocytomas. Irrespective of WHO grade, IDH mutation prevalence was highest in adolescent and young adult patients, and IDH-mutant astrocytomas were more frequently MGMT promoter methylated. Among pediatric-type tumors, the incidence rate was 0.06 for H3K27M-mutant diffuse midline gliomas (95% CI: 0.05-0.07), 0.03 for SHH-activated/TP53-wildtype medulloblastomas (95% CI: 0.02-0.03), and &lt;0.01 for both C19MC-altered embryonal tumor with multilayered rosettes and RELA-fusion ependymomas.ConclusionsOur findings illustrate the success of developing a dedicated, integrated diagnosis variable, which provides critical molecular information about brain tumors related to accurate diagnosis.
Salvage brachytherapy for multiply recurrent metastatic brain tumors: A matched case analysis
Authors: Wu Kyle C , Cantalino Jonathan M , Dee Edward C , Hsu Liangge , Harris Thomas C , Rawal Bhupendra , Juvekar Parikshit R , Mooney Michael A , Dunn Ian F , Aizer Ayal A , Devlin Phillip M , Bi Wenya Linda 
Published: April 2022

Abstract

Background
Patients with recurrent brain metastases who have exhausted external radiation options pose a treatment challenge in the setting of advances in systemic disease control which have improved quality of life and survival. Brachytherapy holds promise as salvage therapy given its ability to enforce surgical cytoreduction and minimize regional toxicity. This study investigates the role of salvage brachytherapy in maintaining local control for recurrent metastatic lesions.

Methods
We retrospectively reviewed our institution’s experience with brachytherapy in patients with multiply recurrent cerebral metastases who have exhausted external radiation treatment options (14 cases). The primary outcome of the study was freedom from local recurrence (FFLR). To capture the nuances of tumor biology, we compared FFLR achieved by brachytherapy to the preceding treatment for each patient. We further compared the response to brachytherapy in patients with lung cancer (8 cases) against a matched cohort of maximally radiated lung brain metastases (10 cases).

Results
Brachytherapy treatment conferred significantly longer FFLR compared to prior treatments (median 7.39 vs 5.51 months, P = .011) for multiply recurrent brain metastases. Compared to an independent matched cohort, brachytherapy demonstrated superior FFLR (median 8.49 vs 1.61 months, P = .004) and longer median overall survival (11.07 vs 5.93 months, P = .055), with comparable side effects.

Conclusion
Brachytherapy used as salvage treatment for select patients with a multiply recurrent oligometastatic brain metastasis in the setting of well-controlled systemic disease holds promise for improving local control in this challenging patient population.
Heterogeneity of Potassium Channels in Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium
Authors: Korkka Iina , Skottman Heli , Nymark Soile 
Published: April 2022

AbstractHuman pluripotent stem cell (hPSC)-derived retinal pigment epithelium (RPE) is extensively used in RPE research, disease modeling, and transplantation therapies. For successful outcomes, a thorough evaluation of their physiological authenticity is a necessity. Essential determinants of this are the different ion channels of the RPE, yet studies evaluating this machinery in hPSC-RPE are scarce. We examined the functionality and localization of potassium (K+) channels in the human embryonic stem cell (hESC)-derived RPE. We observed a heterogeneous pattern of voltage-gated K+ (KV) and inwardly rectifying K+ (Kir) channels. Delayed rectifier currents were recorded from most of the cells, and immunostainings showed the presence of KV1.3 channel. Sustained M-currents were also present in the hESC-RPE, and based on immunostaining, these currents were carried by KCNQ1-KCNQ5 channel types. Some cells expressed transient A-type currents characteristic of native human fetal RPE (hfRPE) and cultured primary RPE and carried by KV1.4 and KV4.2 channels. Of the highly important Kir channels, we found that Kir7.1 is present both at the apical and basolateral membranes of the hESC- and fresh native mouse RPE. Kir currents, however, were recorded only from 14% of the hESC-RPE cells with relatively low amplitudes. Compared to previous studies, our data suggest that in the hESC-RPE, the characteristics of the delayed rectifier and M-currents resemble native adult RPE, while A-type and Kir currents resemble native hfRPE or cultured primary RPE. Overall, the channelome of the RPE is a sensitive indicator of maturity and functionality affecting its therapeutic utility.
Effects of Serum and Compound Preparation Methods on Delayed Repolarization Evaluation With Human iPSC-CMs
Authors: Wei Feng , Pence Lisa , Woodling Kellie , Bagam Prathyusha , Beger Richard , Gamboa da Costa Goncalo , Pang Li 
Published: April 2022

Abstract
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used in the Comprehensive in vitro Proarrhythmia Assay (CiPA). The notable difference of the electrophysiological (EP) responses of hiPSC-CMs in serum and serum-free media (SFM) is puzzling and may impact regulatory decision-making on the cardiac safety of candidate drugs in inducing QT prolongation and torsade de pointes (TdP). In this study, we compared the EP responses of hiPSC-CMs to 10 CiPA compounds and moxifloxacin in serum and SFM; explained the potential reason behind the different EP responses—abiotic compound loss to plastic tubes/plates of hydrophobic compounds prepared in SFM; and investigated the impact of compound preparation methods on drug bioavailability in exposure media, which affects the TdP risk prediction of drugs tested in serum-containing and SFM. For assays to be conducted in SFM, awareness of abiotic compound loss of hydrophobic compounds in serum-free preparations is critical for delay repolarization evaluation and data extrapolation from in vitro to in vivo.
Cutaneous Perforators and Their Clinical Implications on Intrinsic Hand Flaps: A Systematic Review
Authors: Prasetyono Theddeus Octavianus Hari , Menna Clara 
Published: April 2022

Background:
Most hand flaps are local intrinsic flaps because hand perforators are small and fragile. The purpose of this review was to gather anatomical data on cutaneous perforators of the hand and their implications on intrinsic hand flaps.

Methods:
An electronic search was performed through PubMed, Scopus, ScienceDirect, ProQuest, and CINAHL in April 2021. The search terms included “hand,” “palm,” “manus,” “cutaneous artery,” “angiosome,” and “perforasome.” Studies were filtered according to the PRISMA flow chart, and critically appraised using the Quality Appraisal for Cadaveric Studies (QUAC) and Appraisal Tool for Cross-sectional Studies (AXIS).

Results:
A total of 33 studies were included, of which 20 were pure anatomical studies, 10 combined anatomical and clinical studies, and three imaging-based clinical studies. A total of 643 hands and 406 fingers were included. The dorsal aspect of the hand, the dorsal digits, hypothenar, midpalm, thenar, and dorsal wrist consistently have adequate, closely distributed perforators of small diameters and short pedicle lengths. A series of clinical studies proved the success of elevating local perforator flaps on each of these areas.

Conclusions:
The hand contained densely interlinked cutaneous perforators of varying sizes and pedicle lengths. Although some areas of the hand are still unexplored, knowledge on cutaneous perforators of the hand allows the creation of a variety of possibilities for intrinsic hand flap designs.
Expanding the Classic Facial Canons: Quantifying Intercanthal Distance in a Diverse Patient Population
Authors: Bouhadana Gabriel , Gornitsky Jordan , Saleh Eli , Oliveira Trabelsi Nadia , Borsuk Daniel E. 
Published: April 2022

Background:
The intercanthal distance (ICD) is central to our perception of facial proportions, and it varies according to gender and ethnicity. Current standardized reference values do not reflect the diversity among patients. Therefore, the authors sought to provide an evidence-based and gender/ethnicity-specific reference when evaluating patients’ ICD.

Methods:
As per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search of PubMed, Medline, and Embase was carried out for studies reporting on the ICD. Demographics, study characteristics, and ICDs were extracted from included studies. ICD values were then pooled for each ethnicity and stratified by gender. The difference between men and women, and that across ethnicities and measurement types were compared by means of independent sample t-test and one-way ANOVA (SPSS v.24).

Results:
A total of 67 studies accounting for 22,638 patients and 118 ethnic cohorts were included in this pooled analysis. The most reported ethnicities were Middle Eastern (n = 6629) and Asian (n = 5473). ICD values (mm) in decreasing order were: African 38.5 ± 3.2, Asian 36.4 ± 1.6, Southeast Asian 32.8 ± 2.0, Hispanic 32.3 ± 2.0, White 31.4 ± 2.5, and Middle Eastern 31.2 ± 1.5. A statistically significant difference (P < 0.05) existed between all ethnic cohorts, between genders among most cohorts, and between most values stratified by measurement type.

Conclusions:
Our standards of craniofacial anthropometry must evolve from the neoclassical canons using White values as references. The values provided in this review can aid surgeons in appreciating the gender- and ethnic-specific differences in the ICD of their patients.