Acyl carrier protein OsMTACP2 confers rice cold tolerance at the booting stage.

Low temperatures occurring at the booting stage in rice (Oryza sativa L.) often result in yield loss by impeding male reproductive development. However, the underlying mechanisms by which rice responds to cold at this stage remain largely unknown. Here, we identified MITOCHONDRIAL ACYL CARRIER PROTEIN 2 (OsMTACP2), the encoded protein of which mediates lipid metabolism involved in the cold response at the booting stage. Loss of OsMTACP2 function compromised cold tolerance, hindering anther cuticle and pollen wall development, resulting in abnormal anther morphology, lower pollen fertility, and seed setting. OsMTACP2 was highly expressed in tapetal cells and microspores during anther development, with the encoded protein localizing to both mitochondria and the cytoplasm. Comparative transcriptomic analysis revealed differential expression of genes related to lipid metabolism between the wild type and the Osmtacp2-1 mutant in response to cold. Through a lipidomic analysis, we demonstrated that wax esters, which are the primary lipid components of the anther cuticle and pollen walls, function as cold-responsive lipids. Their levels increased dramatically in the wild type but not in Osmtacp2-1 when exposed to cold. Additionally, mutants of two cold-induced genes of wax ester biosynthesis, ECERIFERUM1 and WAX CRYSTAL-SPARSE LEAF2, showed decreased cold tolerance. These results suggest that OsMTACP2-mediated wax ester biosynthesis is essential for cold tolerance in rice at the booting stage.

A prospective observational cohort study of posterior tibial nerve stimulation in patients with multiple sclerosis: design and methods.

BACKGROUND: Posterior tibial nerve stimulation (PTNS) is a promising treatment for lower urinary tract symptoms (LUTS) in patients with MS. However, long term data focusing on PTNS impact on health-related quality of life (HRQOL), bowel and bladder symptoms are lacking. This paper describes a study protocol that examines the extended efficacy of PTNS on MS related bladder and bowel symptoms and resulting HRQOL. METHODS/DESIGN: This is a single-centered, prospective, longitudinal, observational cohort study of patients with MS who suffer from LUTS and are refractory to two prior treatment modalities. Participants who have elected to pursue PTNS therapy for LUTS will be eligible. The primary outcome is the median number of urinary frequency and incontinence episodes on a 3-day voiding diary at 3, 12 and 24 months compared to baseline. Secondary outcome measures will include change in total AUA-SS, M-ISI, NBSS, SF-12, SSS and BCS scores from baseline The Expanded Disability Status Scale and magnetic resonance imaging will be evaluated at baseline and annually throughout the study. DISCUSSION: This research protocol aims to expand on the existing literature regarding outcomes of PTNS in MS. Specifically, it will provide long term follow-up data on bladder, bowel, sexual and HRQOL outcomes. The completion of this study will provide longitudinal efficacy data of the impact of PTNS in MS patients. TRIAL REGISTRATION: NCT04063852.

Characterising 'bounce-back' readmissions after radical cystectomy.

OBJECTIVE: To examine predictors of early readmissions after radical cystectomy (RC). Factors associated with preventable readmissions may be most evident in readmissions that occur within 3 days of discharge, commonly termed 'bounce-back' readmissions, and identifying such factors may inform efforts to reduce surgical readmissions. PATIENTS AND METHODS: We utilised the Healthcare Cost and Utilization Project's State Inpatient Databases to examine 1867 patients undergoing RC in 2009 and 2010, and identified all patients readmitted within 30 days of discharge. We assessed differences between patients experiencing bounce-back readmission compared to those readmitted 8-30 days after discharge using logistic regression models and also calculated abbreviated LACE scores to assess the utility of common readmissions risk stratification algorithms. RESULTS: The 30-day and bounce-back readmission rates were 28.4% and 5.6%, respectively. Although no patient or index hospitalisation characteristics were significantly associated with bounce-back readmissions in adjusted analyses, bounce-back patients did have higher rates of gastrointestinal (14.3% vs 6.7%, P = 0.02) and wound (9.5% vs 3.0%, P < 0.01) diagnoses, as well as increased index and readmission length of stay (5 vs 4 days, P = 0.01). Overall, the median abbreviated LACE score was 7, which fell into the moderate readmission risk category, and no difference was observed between readmitted and non-readmitted patients. CONCLUSION: One in five readmissions after RC occurs within 3 days of initial discharge, probably due to factors present at discharge. However, sociodemographic and clinical factors, as well as traditional readmission risk tools were not predictive of this bounce-back. Effective strategies to reduce bounce-back readmission must identify actionable clinical factors prior to discharge.

Role of Post-Acute Care on Hospital Readmission After High-Risk Surgery.

BACKGROUND: Payment models, including the Hospital Readmissions Reduction Program and bundled payments, place pressures on hospitals to limit readmissions. Against this backdrop, we sought to investigate the association of post-acute care after major surgery and readmission rates. METHODS: We identified patients undergoing high-risk surgery (abdominal aortic aneurysm repair, coronary bypass grafting, aortic valve replacement, carotid endarterectomy, esophagectomy, pancreatectomy, lung resection, and cystectomy) from 2005 to 2010 using the Healthcare Cost and Utilization Project's State Inpatient Database. The primary outcome was readmission rates after major surgery. Secondary outcome was readmission length of stay. RESULTS: We identified 135,523 patients of whom 56,720 (42%) received post-acute care. Patients receiving post-acute care had higher readmission rates than those who were discharged home (16% versus 10%, respectively; P < 0.001). The risk-adjusted readmission length of stay was greatest for patients who received care from a skilled nursing facility, followed by those who received home care, and lowest for those who did not receive post-acute care (7.1 versus 5.4 versus 4.8 d, respectively; P < 0.001). CONCLUSIONS: The use of post-acute care was associated with higher readmission rates and higher readmission lengths of stay. Improving the support of patients in post-acute care settings may help reduce readmissions and readmission intensity.

Predictors of low urinary quality of life in spinal cord injury patients on clean intermittent catheterization.

OBJECTIVE: Clean intermittent catheterization (CIC) is a preferred method of bladder management for many patients with spinal cord injury (SCI), but long-term adherence is low. The aim of this study is to identify factors associated with low urinary quality of life (QoL) in SCI adults performing CIC. METHODS: Over 1.5 years, 1479 adults with SCI were prospectively enrolled through the Neurogenic Bladder Research Group registry, and 753 on CIC with no prior surgeries were included. Injury characteristics, complications, hand function, and Neurogenic Bladder Symptom Score (NBSS) were analyzed. The NBSS QoL question (overall satisfaction with urinary function) was dichotomized to generate comparative groups (dissatisfied vs neutral/satisfied). RESULTS: The cohort was 32.9% female with a median age of 43.2 (18-86) years, time since the injury of 9.8 (0-48.2) years, and 69.0% had an injury at T1 or below. Overall 36.1% were dissatisfied with urinary QoL. On multivariable analysis, female gender (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.15-2.31; P = 0.016), earlier injury (OR, 0.95 per year; 95% CI, 0.93-0.97; P < 0.001), ≥4 urinary tract infections (UTIs) per year (OR, 2.36; 95% CI, 1.47-3.81; P = 0.001), and severe bowel dysfunction (OR, 1.42; 95% CI, 1.02-1.98; P = 0.035) predicted dissatisfaction. Level of injury, fine motor hand function, and caregiver dependence for CIC were not associated with dissatisfaction. CONCLUSIONS: In a mature SCI cohort, physical disability does not predict dissatisfaction with urinary QoL but severe bowel dysfunction and recurrent UTIs have a significant negative impact. With time the rates of dissatisfaction decline but women continue to be highly dissatisfied on CIC and may benefit from early intervention to minimize the burden of CIC on urinary QoL.

SLC34A2 regulates miR-25-Gsk3ß signaling pathway to affect tumor progression in gastric cancer stem cell-like cells.

A novel paradigm in tumor biology suggests that gastric cancer progression is driven by gastric cancer stem cell-like cells (GCSCs), but molecular mechanisms regulating tumorigenic and self-renewal potential of GCSCs are still unclear. Here, we aim to investigate biological function of SLC34A2 in regulating sphere formation and tumorigenicity (both are the hallmark of CSCs) of GCSCs and its underlying mechanisms. Our findings testified that CD44+ cells which were derived from fresh primary gastric cancer samples and cell lines displayed stem cell-like features. Significantly, SLC34A2 is increased in CD44+ GCSCs compared with those in adherent counterpart from CD44+ GCSCs. On clinic, SLC34A2 is overexpressed in primary tumor tissues compared with adjacent counterparts. We showed that SLC34A2 regulated sphere formation and self-renewal properties of CD44+ GCSCs in vitro and in vivo. Mechanistic investigations revealed that Gsk3ß was the most strikingly up-regulated gene in response to SLC34A2 knockdown in GCSCs and Wnt/ß-cantenin signaling was required for SLC34A2-mediated sphere formation. Furthermore, SLC34A2 directly binds specific sites in the miR-25 promoter region and that the promoter activity is decreased after the mutation of putative SLC34A2-binding sites, indicating that SLC34A2 is required for the transcriptional induction of miR-25. Meanwhile, luciferase assays showed that miR-25 directly targeted Gsk3ß in CD44+ GCSCs. Overall, our findings define a SLC34A2-miR-25-Gsk3ß pathway in the regulation of GCSCs features and gastric cancer progression, with potential therapeutic applications in blocking their progression.

Does Post-Void Residual Volume Predict Worsening Urological Symptoms in Patients with Multiple Sclerosis?

PURPOSE: Our goal was to examine how post-void residual urine volume relates to urinary symptoms in patients with multiple sclerosis. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with multiple sclerosis who had lower urinary tract symptoms and presented to a tertiary neurourology clinic. Patients for whom post-void residual volume was recorded at the initial urological assessment were included in our analysis. Results of the AUA (American Urological Association) SI (Symptom Index) and the M-ISI (Michigan Incontinence Symptom Index) completed at this visit were analyzed to assess the severity of lower urinary tract symptoms and incontinence. A chart review was performed to obtain information on demographics and documented urinary tract infections. RESULTS: Between 2014 and 2017, 110 patients diagnosed with multiple sclerosis underwent post-void residual volume measurement at our clinic. Average post-void residual volume was 123.4 cc (range 0 to 650 cc). The mean AUA symptom score was 19.1 with an average bother score of 4.1. Analysis of post-void residual volume as a continuous variable did not show an association between increasing post-void residual volume and an increasing AUA SI or bother score (p = 0.53 and 0.44, respectively). When evaluated by post-void residual volume tertile, no relationship was found between post-void residual volume, and the AUA SI and the M-ISI (p = 0.54 and 0.57, respectively). No correlation was also found between increasing post-void residual volume and a recent history of recurrent urinary tract infections (p = 0.27). CONCLUSIONS: Post-void residual volume was not associated with worsening obstructive lower urinary tract symptoms as assessed by the AUA SI, worsening incontinence as measured by the M-ISI score or an increased risk of recurrent urinary tract infections in select patients with multiple sclerosis and lower urinary tract symptoms.

The effects of cystoscopy and hydrodistention on symptoms and bladder capacity in interstitial cystitis/bladder pain syndrome.

AIMS: The use of cystoscopy and hydrodistention in the management of interstitial cystitis/bladder pain syndrome (IC/BPS) varies widely between providers. Current evidence regarding the risks and benefits of hydrodistention, as well as the long term effects of repeated hydrodistention are not well established. We sought to characterize the effects of hydrodistention on IC/BPS symptoms as well as bladder capacity. METHODS: We retrospectively queried our institutional records for patients with non-ulcerative IC/BPS who underwent hydrodistention over an 11-year period to obtain demographic and clinical factors at the time of diagnosis and treatment. Symptom relief and bladder capacity changes were assessed, and multivariable models were used to predict response to treatment. RESULTS: There were 328 patients who underwent hydrodistention during the study period, of whom 36% received the procedure multiple times, and overall median follow-up was 38.6 months. Patients with repeated hydrodistentions were more likely to be female, have more comorbid pain disorders, and have trialed anticholinergic medications and intravesical instillations. No decrease in mean bladder capacity was observed over time (P = 0.40). Significant decreases in symptom scores were observed following the procedure on multiple questionnaires. CONCLUSIONS: Hydrodistention does not decrease bladder capacity even with multiple procedures, and measurably improves symptoms in some patients with IC/BPS. Continuing efforts to better identify those patients most likely to benefit from this procedure are justified.

Predictors and Cost of Readmission in Total Knee Arthroplasty.

BACKGROUND: The Comprehensive Care for Joint Replacement bundle was created to decrease total knee arthroplasty (TKA) cost. To help accomplish this, there is a focus on reducing TKA readmissions. However, there is a lack of national representative sample of all-payer hospital admissions to direct strategy, identify risk factors for readmission, and understand actual readmission cost. METHODS: We used the Nationwide Readmission Database to examine national readmission rates, predictors of readmission, and associated readmission costs for elective TKA procedures. We fit a multivariable logistic regression model to examine factors associated with readmission. Then, we determined mean readmission costs and calculated the readmission cost when distributed across the entire TKA population. RESULTS: We identified 224,465 patients having TKA across all states participating in the Nationwide Readmission Database. The mean unadjusted 30-day TKA readmission rate was 4%. The greatest predictors of readmission were congestive heart failure (odds ratio [OR] 2.51, 95% confidence interval [CI] 2.62-2.80), renal disease (OR 2.19, 95% CI 2.03-2.37), and length of stay greater than 4 days (OR 2.4, 95% CI 2.25-2.61). The overall median cost for each readmission was $6753 ± 175. Extrapolating the readmission cost for the entire TKA population resulted in the readmission cost being 2% of the overall 30-day procedure cost. CONCLUSIONS: A major focus of the Comprehensive Care for Joint Replacement bundle is improving cost and quality by limiting readmission rates. TKA readmissions are low and comprise a small percentage of total TKA cost, suggesting that they may not be the optimal measure of quality care or a significant driver of overall cost.

[Interaction of MIF gene -173G/C polymorphism and GPX1 gene 594C/T polymorphism with high-fat diet in ulcerative colitis].

OBJECTIVE: To investigate the interaction of single nucleotide polymorphisms of macrophage migration inhibitory factor (MIF) gene -173G/C and glutathione peroxidase 1(GPX1) gene 594C/T polymorphisms and high-fat diet in ulcerative colitis (UC). METHODS: The genetic polymorphisms of MIF -173G/C and GPX1 594C/T were determined with a polymorphism-polymerase chain reaction (PCR)-endonuclease method in peripheral blood leukocytes derived from 1500 UC cases and 1500 healthy controls. RESULTS: The frequencies of MIF -173CC and GPX1 594TT were 55.60% and 55.73% in the UC cases and 16.67% and 16.47% in the healthy controls, respectively. Statistical tests also showed a significant difference in the frequencies between the two groups (P<0.01; P<0.01, respectively). Individuals carrying MIF -173CC also had a significantly higher risk of UC compared with those with MIF -173GG (OR=6.8662, 95%CI: 4.5384-9.6158). Individuals carrying GPX1 594TT had a high risk of UC (OR=7.0854, 95%CI: 4.4702-10.5283). Combined analysis showed that the percentages of MIF -173CC/GPX1 594TT in the UC and control groups were 31.00% and 2.73%, respectively (P<0.01). Individuals carrying MIF -173CC/GPX1 594TT had a high risk of UC (OR=49.0113, 95%CI: 31.7364-61.8205). The high-fat diet rate of the case group was significantly higher than that of the control group (OR=3.3248, 95%CI: 1.9461-5.0193, P<0.01), and statistic analysis suggested an interaction between high-fat diet and MIF -173CC and GPX1 594TT which increase risk of UC (γ =6.9293; γ =6.9942). CONCLUSION: MIF -173CC and GPX1 594TT and high-fat diet are the risk factors for UC, and the significant interactions between genetic polymorphisms of MIF -173G/C, GPX1 594C/T and high-fat diet may increase the risk for UC.

Correlation between Helicobacter pylori infection and polymorphism of adiponectin gene promoter-11391G/A, superoxide dismutase gene innonalcoholic fatty liver disease.

OBJECTIVE: To investigate the correlation between Helicobacter pylori (H. Pylori) infection and polymorphism of adiponectin gene promoter -11391G/A, extracellular superoxide dismutase (EC-SOD) gene in nonalcoholic fatty liver disease (NAFLD).
 METHODS: From June, 2010 to July, 2014, a hospital-based 1:1 matched case-control study was carried out, with 600 cases of NAFLD and 600 healthy people in the First Affiliated Hospital of Xinxiang Medical University. The genetic polymorphisms of adiponectin gene promoter -11391G/A and EC-SOD were analyzed by polymorphism-polymerase chain reaction (PCR) technique in peripheral blood leukocytes of the subjects. 14C-urea breath test (14C-UBT) was used to test 14C disntegration per minute (DPM) for evaluating the infections status of H. Pylori. The synergistic effect between the two mutants and the gene-environment interaction of the genotypes with H. Pylori infection were analyzed.
 RESULTS: The frequencies of -11391G/A (AA) and EC-SOD (CG+GG) were 50.67% and 50.33% in NAFLD cases, 23.83% and 24.17% in healthy controls, respectively. Statistical tests showed significantly higher frequencies of -11391G/A (AA) and EC-SOD (CG+GG) in the NAFLD group (-11391G/A: P=0.0051; EC-SOD: P=0.0057). The risk of NAFLD with -11391G/A (AA) was significantly higher than those with -11391G/A(GG+GA) (OR=3.2822, 95% CI 1.9170 to 5.2039). The individuals who carried EC-SOD (CG+GG) had a high risk of NAFLD (OR=3.1800, 95% CI 1.7974 to 5.2391). Combined analysis of the polymorphisms showed that percentage of -11391G/A (AA)/EC-SOD (CG+GG) in the NAFLD group was significantly higher than that in the control groups (25.50% vs 5.83%, P=0.0039). The people who carried with -11391G/A (AA)/EC-SOD (CG+GG) had a high risk of NAFLD (OR=10.3190, 95% CI 8.1869 to 20.5102). The H. Pylori infection rate in the NAFLD group was significantly higher than that in the control group (OR=3.1667, 95% CI 1.9139 to 5.7443, P=0.0062), and statistical analysis suggested a positive correlation between H. Pylori infection and NAFLD with -11391G/A (AA) and EC-SOD (CG+GG) (-11391G/A: γ=1.8532; EC-SOD: γ=1.7899).
 CONCLUSION: These carriers of -11391G/A(AA) and EC-SOD (CG+GG) genotypes may have a high risk of NAFLD, and the gene genotypes can interact with H. Pylori infection in the pathogenesis of NAFLD. Therefore, effective prevention measures for NAFLD should consider eradicating H. Pylori or regulating gene expression.

[Interaction between polymorphisms of TLR4 gene G11367C in 3' untranslated region and IκB-α Hae III in acute pancreatitis and the degree of severity].

OBJECTIVE: To investigate the interaction between polymorphism of Toll-like receptor 4 (TLR4) gene G11367C in 3' untranslated region (UTR) and inhibitor of nuclear factor kappaB (IκB)-α Hae III in acute pancreatitis (AP) and the degree of severity.
 METHODS: A total of 450 patients with confirmed AP (AP group), who came from the First Affiliated Hospital of Xinxiang Medical College from May 2013 to June 2015, were divided into a mild AP subgroup (MAP subgroup), a moderately severe AP (MSAP subgroup), and a severe acute AP (SAP subgroup) (n=150 in each group). One hundred fifty healthy persons were served as a control group. There was no significant difference in age, gender, ethnicity and birthplace among all groups. The genetic polymorphisms of TLR4 gene G11367C in 3' untranslated region and IκB-α Hae III were analyzed by polymerase chain reaction (PCR). Eligible participants were personally interviewed by a questionnaire. Unconditional logistic regression model and single factor analysis were performed to calculate the adjusted odds ratios (OR) and 95% confidence intervals (95% CI) of G11367C and IκB-α Hae III polymorphisms, respectively. The interaction of nucleotide polymorphisms was analyzed.
 RESULTS: The frequencies of G11367C (GC), IκB-α Hae III (AG) and IκB-α Hae III (GG) were 69.56%, 33.78% and 36.22% in the AP group; 49.33%, 24.67% and 26.00% in the MAP subgroup; 70.67%, 34.67% and 36.67% in the MSAP subgroup; 88.67%, 42.00% and 46.00% in the SAP subgroup and 26.67%, 14.00% and 14.67% in the control group, respectively. There was significant difference in the frequencies betweenc the AP group and the control group, or among each AP subgroup (all P<0.01). The risk of AP was significantly increased in the subjects with G11367C (GC) genotype (ORAP=6.2828, ORMAP=2.6776, ORMSAP=6.6250, ORSAP=21.5147), which was also increased in those with IκB-α Hae III (AG) genotype (ORAP=5.7369, ORMAP=2.5277, ORMSAP=6.1824, ORSAP=17.8572) and in those with IκB-α Hae III (GG) genotype (ORAP=5.8724, ORMAP=2.5902, ORMSAP=6.4027, ORSAP=18.9022). The combined analysis of the polymorphisms showed that the percentage of G11367C (GC)/ IκB-α Hae III (GG) in the AP group, the MAP subgroup, the MSAP subgroup, the SAP subgroup and the control groups was 26.44%, 12.67%, 26.00%, 40.67% and 4.00%, respectively, with significant difference in the frequency among all groups (all P<0.01). The people who carried with Pro12Ala (AA)/Pro198Leu (LL) had a high risk of AP (ORAP=30.1314, ORMAP=6.7612, ORMSAP=39.5000, ORSAP=401.5833), and the statistical analysis suggested a positive interaction between Pro12Ala (AA) and Pro198Leu (LL) in increasing the risk of AP (All γ>1). Similarly, there were also positive interactions in the pathogenesis of AP between G11367C (GC) and IκB-α Hae III (AG) (All γ>1). 
 CONCLUSION: These carriers of G11367C(GC), IκB-α Hae III(AG) and IκB-α Hae III (GG) genotypes may have a high risk of AP occurency, and there are significant interactions between genetic polymorphisms of G11367C and IκB-α Hae III, which increaes the risk of the occurrence and development of AP.

Correlations between polymorphisms of extracellular superoxide dismutase, aldehyde dehydrogenase-2 genes, as well as drinking behavior and pancreatic cancer.

OBJECTIVE: To investigate the correlation between drinking behavior combined with polymorphisms of extracellular superoxide dismutase (EC-SOD) and aldehyde dehydrogenase-2 (ALDH2) genes and pancreatic cancer. METHODS: The genetic polymorphisms of EC-SOD and ALDH2 were analyzed by polymerase chain reaction restriction fragment length polymorphism in the peripheral blood leukocytes obtained from 680 pancreatic cancer cases and 680 non-cancer controls. Subsequently the frequency of genotype was compared between the pancreatic cancer patients and the healthy controls.The relationship of drinking with pancreatic cancer was analyzed. RESULTS: The frequencies of EC-SOD (C/G) and ALDH2 variant genotypes were 37.35% and 68.82% respectively in the pancreatic cancer cases, and were significantly higher than those in the healthy controls (21.03% and 44.56%, all P<0.01). People who carried EC-SOD (C/G) (OR=2.24, 95% CI= 1.81-4.03, P<0.01) or ALDH2 variant genotypes (OR=2.75, 95% CI=1.92-4.47, P<0.01) had a high risk to develop pancreatic cancer. Those who carried EC-SOD (C/G) genotype combined with ALDH2 variant genotype had a high risk for pancreatic cancer (29.56% vs. 6.76%, OR=7.69, 95% CI=3.58-10.51, P<0.01). The drinking rate of the pancreatic cancer group (64.12%) was significantly higher than that of the control group (40.15%; OR=2.66, 95% CI=1.30-4.42, P<0.01). An interaction between drinking and EC-SOD (C/G)/ALDH2 variant genotypes increased the risk of occurrence of pancreatic cancer (OR=25.00, 95% CI= 11.87-35.64, P<0.01). CONCLUSION: EC-SOD (C/G), ALDH2 variant genotypes and drinking might be the risk factors of pancreatic cancer.

An essential function of sphingolipids in yeast cell division.

Ceramides are bioactive lipids and precursors to sphingolipids. They have been shown to take part in a wide variety of different physiological processes in eukaryotic organisms and are thought to be toxic at high concentrations. Ceramide is synthesized by condensation of the sphingoid base sphinganine and a fatty acyl CoA by ceramide synthases, a family of enzymes that differ in their specificity for the length of the acyl CoA substrate. We have engineered a yeast strain where the endogenous ceramide synthase has been replaced by one of the putative enzymes from cotton. As a result, the yeast strain produces C18 rather than C26 ceramides showing that the cotton protein is a bona fide ceramide synthase with specificity towards C18 acyl CoA. Strikingly, the accumulation of C18 ceramide is not toxic in Saccharomyces cerevisiae. This allows survival of the yeast after deletion of the normally essential AUR1 (inositol phosphorylceramide synthase) gene permitting us to address the essential roles of sphingolipids. Deletion of AUR1 allows cell growth, but leads to a defect in cytokinesis, which takes twice as long as in wild-type strains. Nuclear division and recruitment of septins is apparently not affected, but cytokinesis is delayed and cell separation is incomplete.

Understanding the Role of Urology Practice Organization and Racial Composition in Prostate Cancer Treatment Disparities.

PURPOSE: Black men have a higher risk of prostate cancer diagnosis and mortality but are less likely to receive definitive treatment. The impact of structural aspects on treatment is unknown but may lead to actionable insights to mitigate disparities. We sought to examine the associations between urology practice organization and racial composition and treatment patterns for Medicare beneficiaries with incident prostate cancer. METHODS: Using a 20% sample of national Medicare data, we identified beneficiaries diagnosed with prostate cancer between January 2010 and December 2015 and followed them through 2016. We linked urologists to their practices with tax identification numbers. We then linked patients to practices on the basis of their primary urologist. We grouped practices into quartiles on the basis of their proportion of Black patients. We used multilevel mixed-effects models to identify treatment associations. RESULTS: We identified 54,443 patients with incident prostate cancer associated with 4,194 practices. Most patients were White (87%), and 9% were Black. We found wide variation in racial practice composition and practice segregation. Patients in practices with the highest proportion of Black patients had the lowest socioeconomic status (43.1%), highest comorbidity (9.9% with comorbidity score ≥ 3), and earlier age at prostate cancer diagnosis (33.5% age 66-69 years; P < .01). Black patients had lower odds of definitive therapy (adjusted odds ratio, 0.87; 95% CI, 0.81 to 0.93) and underwent less treatment than White patients in every practice context. Black patients in practices with higher proportions of Black patients had higher treatment rates than Black patients in practices with lower proportions. Black patients had lower predicted probability of treatment (66%) than White patients (69%; P < .05). CONCLUSION: Despite Medicare coverage, we found less definitive treatment among Black beneficiaries consistent with ongoing prostate cancer treatment disparities. Our findings are reflective of the adverse effects of practice segregation and structural racism, highlighting the need for multilevel interventions.

Phylogenomic Analysis of Cytochrome P450 Gene Superfamily and Their Association with Flavonoids Biosynthesis in Peanut (Arachis hypogaea L.).

Cytochrome P450s (CYPs) constitute extensive enzyme superfamilies in the plants, playing pivotal roles in a multitude of biosynthetic and detoxification pathways essential for growth and development, such as the flavonoid biosynthesis pathway. However, CYPs have not yet been systematically studied in the cultivated peanuts (Arachis hypogaea L.), a globally significant cash crop. This study addresses this knowledge deficit through a comprehensive genome-wide analysis, leading to the identification of 589 AhCYP genes in peanuts. Through phylogenetic analysis, all AhCYPs were systematically classified into 9 clans, 43 gene families. The variability in the number of gene family members suggests specialization in biological functions. Intriguingly, both tandem duplication and fragment duplication events have emerged as pivotal drivers in the evolutionary expansion of the AhCYP superfamily. Ka/Ks analysis underscored the substantial influence of strong purifying selection on the evolution of AhCYPs. Furthermore, we selected 21 genes encoding 8 enzymes associated with the flavonoid pathway. The results of quantitative real-time PCR (qRT-PCR) experiments unveiled stage-specific expression patterns during the development of peanut testa, with discernible variations between pink and red testa. Importantly, we identified a direct correlation between gene expression levels and the accumulation of metabolites. These findings offer valuable insights into elucidating the comprehensive functions of AhCYPs and the underlying mechanisms governing the divergent accumulation of flavonoids in testa of different colors.

Comparative proteomics indicates that biosynthesis of pectic precursors is important for cotton fiber and Arabidopsis root hair elongation.

The quality of cotton fiber is determined by its final length and strength, which is a function of primary and secondary cell wall deposition. Using a comparative proteomics approach, we identified 104 proteins from cotton ovules 10 days postanthesis with 93 preferentially accumulated in the wild type and 11 accumulated in the fuzzless-lintless mutant. Bioinformatics analysis indicated that nucleotide sugar metabolism was the most significantly up-regulated biochemical process during fiber elongation. Seven protein spots potentially involved in pectic cell wall polysaccharide biosynthesis were specifically accumulated in wild-type samples at both the protein and transcript levels. Protein and mRNA expression of these genes increased when either ethylene or lignoceric acid (C24:0) was added to the culture medium, suggesting that these compounds may promote fiber elongation by modulating the production of cell wall polymers. Quantitative analysis revealed that fiber primary cell walls contained significantly higher amounts of pectin, whereas more hemicellulose was found in ovule samples. Significant fiber growth was observed when UDP-L-rhamnose, UDP-D-galacturonic acid, or UDP-D-glucuronic acid, all of which were readily incorporated into the pectin fraction of cell wall preparations, was added to the ovule culture medium. The short root hairs of Arabidopsis uer1-1 and gae6-1 mutants were complemented either by genetic transformation of the respective cotton cDNA or by adding a specific pectin precursor to the growth medium. When two pectin precursors, produced by either UDP-4-keto-6-deoxy-D-glucose 3,5-epimerase 4-reductase or by UDP-D-glucose dehydrogenase and UDP-D-glucuronic acid 4-epimerase successively, were used in the chemical complementation assay, wild-type root hair lengths were observed in both cut1 and ein2-5 Arabidopsis seedlings, which showed defects in C24:0 biosynthesis or ethylene signaling, respectively. Our results suggest that ethylene and C24:0 may promote cotton fiber and Arabidopsis root hair growth by activating the pectin biosynthesis network, especially UDP-L-rhamnose and UDP-D-galacturonic acid synthesis.

Arabidopsis transcription factor TCP4 represses chlorophyll biosynthesis to prevent petal greening.

Green petals pose a challenge for pollinators to distinguish flowers from leaves, but they are valuable as a specialty flower trait. However, little is understood about the molecular mechanisms that underlie the development of green petals. Here, we report that CINCINNATA (CIN)-like TEOSINTE BRANCHED 1/CYCLOIDEA/PCF (TCP) proteins play key roles in the control of petal color. The septuple tcp2/3/4/5/10/13/17 mutant produced flowers with green petals due to chlorophyll accumulation. Expression of TCP4 complemented the petal phenotype of tcp2/3/4/5/10/13/17. We found that chloroplasts were converted into leucoplasts in the distal parts of wild-type petals but not in the proximal parts during flower development, whereas plastid conversion was compromised in the distal parts of tcp2/3/4/5/10/13/17 petals. TCP4 and most CIN-like TCPs were predominantly expressed in distal petal regions, consistent with the green-white pattern in wild-type petals and the petal greening observed in the distal parts of tcp2/3/4/5/10/13/17 petals. RNA-sequencing data revealed that most chlorophyll biosynthesis genes were downregulated in the white distal parts of wild-type petals, but these genes had elevated expression in the distal green parts of tcp2/3/4/5/10/13/17 petals and the green proximal parts of wild-type petals. We revealed that TCP4 repressed chlorophyll biosynthesis by directly binding to the promoters of PROTOCHLOROPHYLLIDE REDUCTASE (PORB), DIVINYL REDUCTASE (DVR), and SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1), which are known to promote petal greening. We found that the conversion of chloroplasts to leucoplasts and the green coloration in the proximal parts of petals appeared to be conserved among plant species. Our findings uncover a major molecular mechanism that underpins the formation of petal color patterns and provide a foundation for the breeding of plants with green flowers.

1-Aminocyclopropane-1-carboxylic acid synthase 2 is phosphorylated by calcium-dependent protein kinase 1 during cotton fiber elongation.

The reaction catalyzed by 1-aminocyclopropane-1-carboxylic acid synthase (ACS) is proposed to be the rate-limiting step in ethylene biosynthesis, which has been found as one of the most up-regulated metabolic pathways during cotton fiber development. However, the transcripts of the identified ACS genes did not increase in a similar manner as those of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) genes, implicating a possible post-transcriptional modification or regulatory mechanism. In this work, cotton ACS2 was shown to interact with Ca(2+)-dependent protein kinase 1 (CPK1). Bacterially expressed and purified recombinant ACS2 was phosphorylated by CPK1 in vitro and site-directed mutagenesis studies suggest that ACS2 S460 is a possible phosphorylation site for CPK1. Phosphorylated ACS2 significantly increased ACS activity, leading to elevated ethylene production. We thus speculated that CPK1 is involved in cotton fiber growth regulation by phosphorylating ACS2, which results in enhanced ethylene production in vitro.

Burnout Among Urologists from Denmark and Michigan.

OBJECTIVE: To investigate the prevalence of burnout among Danish and American urologists. METHODS: An email invitation was sent with 2 reminders spaced by 14 days intervals to members of the Danish Urological Association and urologists at the University of Michigan to participate in a survey consisting of the 2 item Maslach Burnout Inventory. Burnout was defined as reporting "once a week," "a few times a week," or "everyday" on either the emotional exhaustion or depersonalization domains of the Maslach Burnout Inventory. Two open-ended questions were added to the survey for the Danish urologists, these were then qualitatively analyzed using thematic analysis. Categorial variables were compared using Chi square analysis. RESULTS: The response rate was 193 of 387 (49.9%) for the Danish urologists and 43 of 64 (67.1%) among American urologists. The prevalence of burnout for the American and Danish cohorts was identified in 4 (44.4%) of the American residents and 10 (32.3%) of the American attendings compared to 2 (3%) of Danish residents and 16 (12.7%) of Danish attendings. The difference in rate of burnout between Danish residents and attendings was statistically significant (P= .03). Burnout was statistically significantly different between American and Danish residents (P<.01) and attendings (P <.01). There was a statistically significant difference in rates of burnout between American and the Danish female urologists (P = .02) and similarly among male urologists (P <.01). CONCLUSION: This study demonstrated low rates of burnout among Danish urologists and a significant difference in burnout between residents and attendings from Michigan compared to Danish residents and attendings.