Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed

Significance Seeds are complex structures that are comprised of the embryo, endosperm, and seed coat. Despite their importance for food, fiber, and fuel, the cellular processes that characterize different regions of the seed are not known. We profiled gene activity genome-wide in every organ, tissue, and cell type of Arabidopsis seeds from fertilization through maturity. The resulting mRNA datasets provide unique insights into the cellular processes that occur in understudied seed regions, revealing unexpected overlaps in the functional identities of seed regions and enabling predictions of gene regulatory networks. This dataset is an essential resource for studies of seed biology. Seeds are complex structures that consist of the embryo, endosperm, and seed-coat regions that are of different ontogenetic origins, and each region can be further divided into morphologically distinct subregions. Despite the importance of seeds for food, fiber, and fuel globally, little is known of the cellular processes that characterize each subregion or how these processes are integrated to permit the coordinated development of the seed. We profiled gene activity genome-wide in every organ, tissue, and cell type of Arabidopsis seeds from fertilization through maturity. The resulting mRNA datasets offer the most comprehensive description of gene activity in seeds with high spatial and temporal resolution, providing unique insights into the function of understudied seed regions. Global comparisons of mRNA populations reveal unexpected overlaps in the functional identities of seed subregions. Analyses of coexpressed gene sets suggest that processes that regulate seed size and filling are coordinated across several subregions. Predictions of gene regulatory networks based on the association of transcription factors with enriched DNA sequence motifs upstream of coexpressed genes identify regulators of seed development. These studies emphasize the utility of these datasets as an essential resource for the study of seed biology.
Kidney transplantation improves arterial function measured by pulse wave analysis and endothelium-independent dilatation in uraemic patients despite deterioration of glucose metabolism.

BACKGROUND The aim of this study is to investigate the effect of kidney transplantation on arterial function in relation to changes in glucose metabolism. METHODS Included were 40 kidney recipients (Tx group, age 38 ± 13 years) and 40 patients without known diabetes remaining on the waiting list for kidney transplantation (uraemic control group, age 47 ± 11 years). Arterial function was estimated by the pulse wave velocity (PWV) of the carotid-femoral pulse wave, aortic augmentation index (AIX), flow-mediated (FMD) and nitroglycerin-induced vasodilatation (NID) of the brachial artery performed before transplantation and after 12 months. PWV recorded sequentially at the carotid and femoral artery is an estimate of arterial stiffness; AIX is an integrated index of vascular and ventricular function. FMD and NID are the dilatory capacities of the brachial artery after increased flow (endothelium dependent) and after nitroglycerin administration (endothelium independent). The insulin resistance was estimated by the insulin sensitivity index (ISI). RESULTS AIX was reduced from 27% (17-33) to 14% (7-25) (P = 0.01) after 1 year in the Tx group and remained stable in uraemic controls (P = 0.001, between groups), and NID increased from 11% (7-16) to 18% (12-23) (P = 0.0005). At baseline, carotid-femoral PWV was similar in the Tx group, uraemic controls and healthy controls and it did not change significantly after transplantation. ISI deteriorated in the Tx group from 7.2 ± 4.0 to 5.0 ± 3.0 (P = 0.005) and remained stable in uraemic controls (7.9 ± 5.1 vs 8.5 ± 4.9, NS). Mean arterial blood pressure decreased from 105 ± 13 to 96 ± 11 mmHg (P = 0.005) in the Tx group despite a 20% lower use of antihypertensive agents. CONCLUSIONS Arterial function measured by AIX and NID was improved 1 year after kidney transplantation. This was associated with a decline in blood pressure and seen inspite of an increase in insulin resistance.
Novel PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD).

BACKGROUND Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal disorder with an incidence of 1:1000. Mutations in two genes (PKD1 and PKD2) have been identified as causative. Eighty-five percent of patients with ADPKD carry their mutation in the PKD1 gene. So far, > 500 mutations for PKD1 and > 120 mutations for PKD2, respectively, are known. METHODS In this study, we performed mutation analysis of PKD1 and PKD2 by exon sequencing in patients during routine molecular diagnostics for ADPKD. RESULTS In total, 60 mutations were identified in 93 patients representing a mutation detection efficiency of 64.5%. Fifty-two mutations were identified in PKD1 (86.7%) and 8 in PKD2 (13.3%). These include 41 novel mutations detected in PKD1 and 5 novel mutations in PKD2. Accordingly, our data expand the spectrum of known PKD mutations by 8% for PKD1 (41/513) and 4.2% for PKD2 (5/120). These results are in agreement with the detection ranges of 42%, 63% and 64% for definitive disease-causing mutations, and 78%, 86% and 89% for all identified variants reported in several comprehensive mutation screening reports. CONCLUSIONS The increased number of known mutations will facilitate future studies into genotype-phenotype correlations.
Crystallization of CO2 ice and the absence of amorphous CO2 ice in space

Carbon dioxide (CO2) is one of the most relevant and abundant species in astrophysical and atmospheric media. In particular, CO2 ice is present in several solar system bodies, as well as in interstellar and circumstellar ice mantles. The amount of CO2 in ice mantles and the presence of pure CO2 ice are significant indicators of the temperature history of dust in protostars. It is therefore important to know if CO2 is mixed with other molecules in the ice matrix or segregated and whether it is present in an amorphous or crystalline form. We apply a multidisciplinary approach involving IR spectroscopy in the laboratory, theoretical modeling of solid structures, and comparison with astronomical observations. We generate an unprecedented highly amorphous CO2 ice and study its crystallization both by thermal annealing and by slow accumulation of monolayers from the gas phase under an ultrahigh vacuum. Structural changes are followed by IR spectroscopy. We also devise theoretical models to reproduce different CO2 ice structures. We detect a preferential in-plane orientation of some vibrational modes of crystalline CO2. We identify the IR features of amorphous CO2 ice, and, in particular, we provide a theoretical explanation for a band at 2,328 cm−1 that dominates the spectrum of the amorphous phase and disappears when the crystallization is complete. Our results allow us to rule out the presence of pure and amorphous CO2 ice in space based on the observations available so far, supporting our current view of the evolution of CO2 ice.
Comparison of 4- and 8-h dialysis sessions in thrice-weekly in-centre haemodialysis: a prospective, case-controlled study.

BACKGROUND Longer dialysis sessions may improve outcome in haemodialysis (HD) patients. We compared the clinical and laboratory outcomes of 8- and 4-h thrice-weekly HD. METHODS Two-hundred and forty-seven HD patients who agreed to participate in a thrice-weekly 8-h in-centre nocturnal HD (NHD) treatment and 247 age-, sex-, diabetes status- and HD duration-matched control cases to 4-h conventional HD (CHD) were enrolled in this prospective controlled study. Echocardiography and psychometric measurements were performed at baseline and at the 12th month. The primary outcome was 1-year overall mortality. RESULTS Overall mortality rates were 1.77 (NHD) and 6.23 (CHD) per 100 patient-years (P = 0.01) during a mean 11.3 ± 4.7 months of follow-up. NHD treatment was associated with a 72% risk reduction for overall mortality compared to the CHD treatment (hazard ratio = 0.28, 95% confidence interval 0.09-0.85, P = 0.02). Hospitalization rate was lower in the NHD arm. Post-HD body weight and serum albumin levels increased in the NHD group. Use of antihypertensive medications and erythropoietin declined in the NHD group. In the NHD group, left atrium and left ventricular end-diastolic diameters decreased and left ventricular mass index regressed. Both use of phosphate binders and serum phosphate level decreased in the NHD group. Cognitive functions improved in the NHD group, and quality of life scores deteriorated in the CHD group. CONCLUSIONS Eight-hour thrice-weekly in-centre NHD provides morbidity and possibly mortality benefits compared to conventional 4-h HD.
Social Adaptability Index: application and outcomes in a dialysis population.

BACKGROUND Patient groups associated with disparities in health care are usually defined on the basis of race, gender or geographic location. Social Adaptability Index (SAI), calculated based on education, marital status, income, employment and substance abuse, has been strongly associated with clinical outcome in other patient populations and may be used to identify individuals at risk. We used data from the United States Renal Data System to evaluate the role of SAI in survival of patients on dialysis. METHODS We used Cox model analyses to study the association between SAI and patient survival in patients with ESRD on dialysis, as well as in the subgroups based on age, race, sex, comorbidites and diabetic status. RESULTS We analyzed 3396 patients (age of ESRD onset 56.9 ± 16.1 years, 54.2% males, 64.2% white, 30.3% African-American). Mean SAI of the entire population was 7.1 ± 2.5 (range 0-12 points). SAI was higher in whites (7.4 ± 2.4) than in African-Americans (6.5 ± 2.5) (analysis of variance, P <0.001) and greater in men (7.4 ± 2.4) than in women (6.7 ± 2.5) (t-test, P <0.001). In a Cox model adjusted for potential confounders, SAI was associated with decreased mortality [hazards ratio of 0.97 (95% confidence interval 0.95-0.99), P = 0.006]. Subgroup analysis demonstrated an association of SAI with survival in most of the subgroups. Potential limitations of the study include reverse causality, possible misclassification and retrospective design. CONCLUSION We demonstrated that SAI is significantly associated with mortality in dialysis patients. SAI could be used to identify individuals at risk for inferior clinical outcomes.
Kidney function, albuminuria and age-related macular degeneration in NHANES III.

BACKGROUND Age-related macular degeneration (AMD) and kidney disease may have shared risk factors, including cardiovascular disease risk factors; additionally AMD and dense deposit disease share a common causal link, with both associated with polymorphisms in the complement pathway. Accordingly, we explored a population-based cohort of US adults to examine if markers of kidney disease identify a higher risk population for prevalent AMD. METHODS A cross-sectional nested case-control study matching on age, sex and race was performed using data on adult participants in the Third National Health and Nutrition Examination Survey. Predictor variables included urine albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR). Study outcomes included late AMD, defined as neovascular disease or geographic atrophy (5:1 matching), and a composite of both early AMD, defined as soft drusen or pigment irregularities with or without any drusen, and late AMD (1:1 matching). RESULTS There were 51 participants with late AMD and 865 with any AMD. In conditional logistic regression adjusting for diabetes, hypertension and total cholesterol, lower eGFR was independently associated with late AMD [odds ratio (OR) = 3.05, 95% confidence interval (CI): 1.51-6.13], while albuminuria was not significant. For any AMD, neither albuminuria nor eGFR were significant in adjusted models. In sensitivity analyses excluding diabetics, albuminuria was associated with any AMD (OR = 1.56, 95% CI: 1.11-1.29 and 1.57, 95% CI: 0.61-3.69 for micro- and macroalbuminuria, respectively, P = 0.03). CONCLUSIONS Late AMD is more common among individuals with reduced kidney function. Whether this association reflects a common causal pathway or shared risk factors such as hypertension requires additional investigation.
Acute kidney injury in patients admitted to a liver intensive therapy unit with paracetamol-induced hepatotoxicity.

BACKGROUND Paracetamol overdose can cause acute kidney injury (AKI) independent of its hepatotoxic effects. We aimed to determine the prevalence of AKI (AKI Network definition) in those with paracetamol-induced hepatotoxicity, identify factors associated with development, assess impact on the outcomes of patient survival and length of stay and determine the proportion of patients recovering renal function (estimated glomerular filtration rate > 60 mL/min) by the time of hospital discharge or transfer out. METHODS Between 2000 and 2007, patients admitted to a tertiary referral liver intensive therapy unit (LITU) with paracetamol-induced hepatotoxicity were identified from a prospectively maintained database and evaluated. RESULTS Those receiving a liver transplant were excluded (n = 54), leaving 302 patients. Renal function remained normal in 21%, the remainder developing AKI (Stages 1-8%, 2-6% and 3-65%). Vasopressor requirement, mechanical ventilation, higher admission phosphate and lower sodium levels along with a higher Day 3 lactate and lower haematocrit were associated with AKI. In survivors with AKI, 51% had recovery of renal function, while 7% remained dialysis dependant although none required it chronically. Overall, there was 25% mortality, all having Stage 3 AKI but AKI was only a univariate not multivariate predictor of reduced patient survival. AKI independently predicted longer length of stay. CONCLUSIONS AKI is very common in critically ill patients with paracetamol-induced hepatotoxicity requiring LITU admission. Although outcomes are poorer with AKI than with normal renal function, they are better than those found in other intensive therapy unit populations. Gradual recovery of renal function is seen in all patients.
Post-operative acute kidney injury in patients with renal cell carcinoma is a potent risk factor for new-onset chronic kidney disease after radical nephrectomy.

BACKGROUND Radical nephrectomy is a significant risk factor for chronic kidney disease (CKD). There are few reports on the renal outcome of acute kidney injury (AKI) after radical nephrectomy. The aim of this study was to determine the incidence of AKI and whether post-operative AKI is associated with new-onset CKD after radical nephrectomy for renal cell cancer (RCC). METHODS We conducted a retrospective study of 519 adult patients (>40 years old) with normal renal function who underwent unilateral radical nephrectomy for a solitary renal cortical tumour and were pathologically diagnosed with RCC between January 2000 and February 2007. Post-operative AKI was classed using risk, injury, failure, loss and end-stage kidney disease (RIFLE) criteria. CKD was defined as a decrease in estimated glomerular filtration rate (GFR) to <60 mL/min/1.73 m(2). RESULTS According to the RIFLE criteria, 165 of 175 patients fell into the AKI risk category, 8 patients fell into the AKI injury category and 2 patients fell into the AKI failure category. Multivariate analysis revealed that older age [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.00-1.05], male gender (OR 3.13, 95% CI 1.91-5.12), higher body mass index (OR 1.08, 95% CI 1.01-1.15), smaller RCC size (OR 0.87, 95% CI 0.81-0.93) and higher preoperative GFR (OR 1.04, 95% CI 1.03-1.06) were independent risk factors for post-operative AKI. CKD was more prevalent in the AKI risk group than in patients without AKI 1 year after surgery (54.7% versus 43.9%, respectively; P = 0.006) and 3 years after surgery (50% versus 32%, respectively; P = 0.003). Patients who experienced post-operative AKI had a 4.24-fold higher risk of new-onset CKD after multiple adjustments were made to the data (95% CI 2.28-7.89, P < 0.001). CONCLUSION AKI after radical nephrectomy in patients with RCC is a potent risk factor for new-onset CKD. Prevention of post-operative AKI is essential for reducing the incidence of CKD after nephrectomy.
Influence of MRP2 on MPA pharmacokinetics in renal transplant recipients-results of the Pharmacogenomic Substudy within the Symphony Study.

BACKGROUND The aim of this study was to determine the relationship between single-nucleotide polymorphisms (SNPs) in MRP2 genes and mycophenolic acid (MPA) pharmacokinetics in renal transplant recipients of the Symphony Pharmacogenomic substudy. METHODS Sixty-six renal transplant recipients of eight Spanish centres were randomized into four branches of immunosuppressive regimen: low dose of cyclosporine, standard dose of cyclosporine, tacrolimus and sirolimus, all in addition to mycophenolate mofetil and steroids. Fifty-five patients were genotyped for SNPs in MRP2, C24T and C3972T. Pharmacokinetic sampling was done before MPA administration and up to 12 h post-dose at Day 7, 1 month and 3 months post-transplant. Relationships of area under the curve (AUC) of MPA and MPAG plasma sampling with the presence of MRP2 SNPs and with the immunosuppressive regimens were studied. RESULTS At steady-state conditions, MPA-reduced exposure was observed in C24T variant allele in MRP2 (CC: 68.73 ± 6.78; *T: 48.12 ± 4.90, P = 0.023); no significant differences linked to C3972T SNP were observed. Taking into account groups of treatment, lower MPA AUC in variant allele of C24T was only found under macrolides treatment with statistically significant differences at Month 3 (Tac and SRL, CC: 86.52 ± 10.98 versus *T: 41.99 ± 4.82, P = 0.001; CsA, CC: 52.31 ± 5.30 versus *T: 54.24 ± 8.30, P = 0.772); for C3972T, the same tendency was found but differences at steady state did not reach statistical significance. CONCLUSIONS Renal transplant recipients T carriers of C24T MRP2 with macrolides treatment were associated with reduced MPA AUC in steady-state conditions. Patients treated with cyclosporine lost the effect of this polymorphism.
Prospects of elimination of HIV with test-and-treat strategy

Recently, there has been much debate about the prospects of eliminating HIV from high endemic countries by a test-and-treat strategy. This strategy entails regular HIV testing in the entire population and starting antiretroviral treatment immediately in all who are found to be HIV infected. We present the concept of the elimination threshold and investigate under what conditions of treatment uptake and dropout elimination of HIV is feasible. We used a deterministic model incorporating an accurate description of disease progression and variable infectivity. We derived explicit expressions for the basic reproduction number and the elimination threshold. Using estimates of exponential growth rates of HIV during the initial phase of epidemics, we investigated for which populations elimination is within reach. The concept of the elimination threshold allows an assessment of the prospects of elimination of HIV from information in the early phase of the epidemic. The relative elimination threshold quantifies prospects of elimination independently of the details of the transmission dynamics. Elimination of HIV by test-and-treat is only feasible for populations with very low reproduction numbers or if the reproduction number is lowered significantly as a result of additional interventions. Allowing low infectiousness during primary infection, the likelihood of elimination becomes somewhat higher. The elimination threshold is a powerful tool for assessing prospects of elimination from available data on epidemic growth rates of HIV. Empirical estimates of the epidemic growth rate from phylogenetic studies were used to assess the potential for elimination in specific populations.
Renal transplantation in light chain amyloidosis: coming out of the cupboard.

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Highly potent, synthetically accessible prostratin analogs induce latent HIV expression in vitro and ex vivo

Highly active antiretroviral therapy (HAART) decreases plasma viremia below the limits of detection in the majority of HIV-infected individuals, thus serving to slow disease progression. However, HAART targets only actively replicating virus and is unable to eliminate latently infected, resting CD4+ T cells. Such infected cells are potentially capable of reinitiating virus replication upon cessation of HAART, thus leading to viral rebound. Agents that would eliminate these reservoirs, when used in combination with HAART, could thus provide a strategy for the eradication of HIV. Prostratin is a preclinical candidate that induces HIV expression from latently infected CD4+ T cells, potentially leading to their elimination through a virus-induced cytopathic effect or host anti-HIV immunity. Here, we report the synthesis of a series of designed prostratin analogs and report in vitro and ex vivo studies of their activity relevant to induction of HIV expression. Members of this series are up to 100-fold more potent than the preclinical lead (prostratin) in binding to cell-free PKC, and in inducing HIV expression in a latently infected cell line and prostratin-like modulation of cell surface receptor expression in primary cells from HIV-negative donors. Significantly, selected members were also tested for HIV induction in resting CD4+ T cells isolated from infected individuals receiving HAART and were found to exhibit potent induction activity. These more potent agents and by extension related tunable analogs now accessible through the studies described herein should facilitate research and preclinical advancement of this strategy for HIV/AIDS eradication.