Miracle-dz/UniFAR-FTUs huggingface dataset:
Arabidopsis Nuclear-Encoded Plastid Transit Peptides Contain Multiple Sequence Subgroups with Distinctive Chloroplast-Targeting Sequence Motifs[W]

The N-terminal transit peptides of nuclear-encoded plastid proteins are necessary and sufficient for their import into plastids, but the information encoded by these transit peptides remains elusive, as they have a high sequence diversity and lack consensus sequences or common sequence motifs. Here, we investigated the sequence information contained in transit peptides. Hierarchical clustering on transit peptides of 208 plastid proteins showed that the transit peptide sequences are grouped to multiple sequence subgroups. We selected representative proteins from seven of these multiple subgroups and confirmed that their transit peptide sequences are highly dissimilar. Protein import experiments revealed that each protein contained transit peptide–specific sequence motifs critical for protein import into chloroplasts. Bioinformatics analysis identified sequence motifs that were conserved among members of the identified subgroups. The sequence motifs identified by the two independent approaches were nearly identical or significantly overlapped. Furthermore, the accuracy of predicting a chloroplast protein was greatly increased by grouping the transit peptides into multiple sequence subgroups. Based on these data, we propose that the transit peptides are composed of multiple sequence subgroups that contain distinctive sequence motifs for chloroplast targeting.
Down-regulation of the TaGW 2 gene by RNA int rference results in decreased gr in size and weight in wheat

In mammals, cadmium is widely considered as a non-genotoxic carcinogen acting through a methylation-dependent epigenetic mechanism. Here, the effects of Cd treatment on the DNA methylation patten are examined together with its effect on chromatin reconfiguration in Posidonia oceanica. DNA methylation level and pattern were analysed in actively growing organs, under short(6 h) and long(2 d or 4 d) term and low (10 mM) and high (50 mM) doses of Cd, through a Methylation-Sensitive Amplification Polymorphism technique and an immunocytological approach, respectively. The expression of one member of the CHROMOMETHYLASE (CMT) family, a DNA methyltransferase, was also assessed by qRT-PCR. Nuclear chromatin ultrastructure was investigated by transmission electron microscopy. Cd treatment induced a DNA hypermethylation, as well as an up-regulation of CMT, indicating that de novo methylation did indeed occur. Moreover, a high dose of Cd led to a progressive heterochromatinization of interphase nuclei and apoptotic figures were also observed after long-term treatment. The data demonstrate that Cd perturbs the DNA methylation status through the involvement of a specific methyltransferase. Such changes are linked to nuclear chromatin reconfiguration likely to establish a new balance of expressed/repressed chromatin. Overall, the data show an epigenetic basis to the mechanism underlying Cd toxicity in plants.
Effect of elevat d CO 2 on phosphor s nutrition of phosphate-deficien Arabi opsis thalian ( L . ) Heynh under different nitrogen forms

In mammals, cadmium is widely considered as a non-genotoxic carcinogen acting through a methylation-dependent epigenetic mechanism. Here, the effects of Cd treatment on the DNA methylation patten are examined together with its effect on chromatin reconfiguration in Posidonia oceanica. DNA methylation level and pattern were analysed in actively growing organs, under short(6 h) and long(2 d or 4 d) term and low (10 mM) and high (50 mM) doses of Cd, through a Methylation-Sensitive Amplification Polymorphism technique and an immunocytological approach, respectively. The expression of one member of the CHROMOMETHYLASE (CMT) family, a DNA methyltransferase, was also assessed by qRT-PCR. Nuclear chromatin ultrastructure was investigated by transmission electron microscopy. Cd treatment induced a DNA hypermethylation, as well as an up-regulation of CMT, indicating that de novo methylation did indeed occur. Moreover, a high dose of Cd led to a progressive heterochromatinization of interphase nuclei and apoptotic figures were also observed after long-term treatment. The data demonstrate that Cd perturbs the DNA methylation status through the involvement of a specific methyltransferase. Such changes are linked to nuclear chromatin reconfiguration likely to establish a new balance of expressed/repressed chromatin. Overall, the data show an epigenetic basis to the mechanism underlying Cd toxicity in plants.
Thiol synthetas s of legumes : immunogold localization and differen ial ge e regulatio by phytohormones

In mammals, cadmium is widely considered as a non-genotoxic carcinogen acting through a methylation-dependent epigenetic mechanism. Here, the effects of Cd treatment on the DNA methylation patten are examined together with its effect on chromatin reconfiguration in Posidonia oceanica. DNA methylation level and pattern were analysed in actively growing organs, under short(6 h) and long(2 d or 4 d) term and low (10 mM) and high (50 mM) doses of Cd, through a Methylation-Sensitive Amplification Polymorphism technique and an immunocytological approach, respectively. The expression of one member of the CHROMOMETHYLASE (CMT) family, a DNA methyltransferase, was also assessed by qRT-PCR. Nuclear chromatin ultrastructure was investigated by transmission electron microscopy. Cd treatment induced a DNA hypermethylation, as well as an up-regulation of CMT, indicating that de novo methylation did indeed occur. Moreover, a high dose of Cd led to a progressive heterochromatinization of interphase nuclei and apoptotic figures were also observed after long-term treatment. The data demonstrate that Cd perturbs the DNA methylation status through the involvement of a specific methyltransferase. Such changes are linked to nuclear chromatin reconfiguration likely to establish a new balance of expressed/repressed chromatin. Overall, the data show an epigenetic basis to the mechanism underlying Cd toxicity in plants.
Inflammation-Related Gene Polymorphisms and Colorectal Adenoma

Chronic inflammation has been reported to be a risk factor for colorectal neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with colorectal adenoma, a precursor of colorectal cancer. We investigated the association of colorectal adenoma with 19 single nucleotide polymorphisms in a range of important proinflammatory (IL1B, IL6, IL8, TNF, and LTA) and anti-inflammatory (IL4, IL10, and IL13) cytokines and other inflammation-related genes (PTGS2 and PPARG) in a case-control study of risk factors for colorectal polyps in which all participants (ages 18-74 years) had undergone colonoscopy or sigmoidoscopy. The study sample comprised 244 cases of colorectal adenoma and 231 polyp-free controls. Compared with being homozygous for the common allele, heterozygosity at the IL1B −31 (C>T) locus was associated with an odds ratio (OR) for colorectal adenoma of 1.8 [95% confidence interval (95% CI), 1.2-2.9]. Homozygous carriers of the IL8 −251-A allele were at 2.7-fold increased risk of adenoma (95% CI, 1.5-4.9) compared with homozygosity for the common T allele, whereas carriage of at least one IL8 −251-A allele conferred a 1.5 increased odds of disease (95% CI, 1.0-2.4). Among non–nonsteroidal anti-inflammatory drug users, there was a statistically significant association between the IL10 −819-T/T genotype and adenoma compared with the common IL10 −819-C/C genotype (OR, 3.9; 95% CI, 1.1-13.6), which was not evident among nonsteroidal anti-inflammatory drug users (OR, 0.7; 95% CI, 0.3-1.5; Pinteraction = 0.01). These exploratory data provide evidence that polymorphic variation in genes that regulate inflammation could alter risk for colorectal adenoma. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1126–31)
Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular matrix

Zens et al. present a workflow to structurally characterize natively preserved extracellular matrix (ECM) using lift-out cryo-FIBSEM and cryo-ET. Employing cell-derived matrices to mimic authentic ECM, they reveal the intricate network of extracellular fibers in the context of matrix-secreting cells. Their findings expand the structural atlas of the ECM.
Modeling the degree of persistence in Croatian tourism

The Croatian tourism sector has been affected by a number of negative and positive shocks since the beginning of the 1990s. To examine the impact of shocks on tourism, the authors employ fractional integration techniques as a means to gauge the degree of persistence of such shocks. Based on monthly data from January 1995 to December 2013, they find that the respective tourism indicators contain seasonal unit roots. An examination of the seasonally differenced tourism time series reveals that the fractional differencing parameter, d, with allowance for an autocorrelated error process, is strictly below 1, implying that shocks are transitory and disappear relatively quickly.
Flow-aware traffic control for a content-centric network

The content-centric networking (CCN) paradigm proposed by PARC holds considerable promise as the architecture for the future Internet but remains incomplete. In this paper we argue that it is necessary to supplement CCN with mechanisms enabling controlled sharing of network bandwidth by concurrent flows. Traffic control is necessary to ensure low latency for conversational and streaming flows and to realize satisfactory bandwidth sharing between elastic flows. These objectives can be realized using “network neutral” traffic controls based on per-flow fair bandwidth sharing. The paper describes necessary CCN mechanisms and discusses the strategies to be implemented by end systems and routers. A simulation-based performance evaluation demonstrates the effectiveness of the proposed mechanisms and and the impact of possible strategies. We describe our experience in implementing some of the mechanisms using the CCNx prototype software.
Modulation of TNF‐α, interleukin‐6, and interleukin‐10 by nebivolol–valsartan and nebivolol–lisinopril polytherapy in SHR rats

Abstract Antihypertensive drug therapies have demonstrated their capacity to modulate the inflammatory processes associated with hypertension, leading to improvements in disease progression. Given the prevalent use of polytherapy in treating most hypertensive patients, comprehending the time‐dependent effects of combination treatments on inflammation becomes imperative. In this study, spontaneously hypertensive rats (SHR) were divided into seven groups (n = 6): (i) SHR + vehicle, (ii) SHR + nebivolol, (iii) SHR + valsartan, (iv) SHR + lisinopril, (v) SHR + nebivolol–valsartan, (vi) SHR + nebivolol–lisinopril, and (vii) WKY + vehicle. Blood pressure was measured using the tail‐cuff method. Temporal alterations in inflammatory cytokines TNF‐α, IL‐6, and IL‐10 were assessed in serum through ELISA and mRNA expression in aortic tissue via qPCR after 1, 2, and 4 weeks of treatment with nebivolol, lisinopril, valsartan, and their respective combinations. Histological alterations in the aorta were assessed. The findings indicated that combined treatments reduced systolic and diastolic blood pressure in SHR. The nebivolol and lisinopril combination demonstrated a significant decrease in IL‐6 serum and mRNA expression at both 1 week and 4 weeks into the treatment. Additionally, TNF‐α mRNA expression also showed a reduction with this combination at the same time points. Particularly, nebivolol–valsartan significantly decreased TNF‐α serum and mRNA expression after one and four weeks of treatment. Furthermore, an elevation in serum IL‐10 levels was observed with both combination treatments starting from the second week onwards. This study provides compelling evidence that concurrent administration of nebivolol with lisinopril or valsartan exerts time‐dependent effects, reducing proinflammatory cytokines TNF‐α and IL‐6 while modifying IL‐10 levels in an experimental hypertensive model.
Species Differences in Tissue Distribution and Enzyme Activities of Arylacetamide Deacetylase in Human, Rat, and Mouse

Human arylacetamide deacetylase (AADAC) is a major esterase responsible for the hydrolysis of clinical drugs such as flutamide, phenacetin, and rifampicin. Thus, AADAC is considered to be a relevant enzyme in preclinical drug development, but there is little information about species differences with AADAC. This study investigated the species differences in the tissue distribution and enzyme activities of AADAC. In human, AADAC mRNA was highly expressed in liver and the gastrointestinal tract, followed by bladder. In rat and mouse, AADAC mRNA was expressed in liver at the highest level, followed by the gastrointestinal tract and kidney. The expression levels in rat tissues were approximately 7- and 10-fold lower than those in human and mouse tissues, respectively. To compare the catalytic efficiency of AADAC among three species, each recombinant AADAC was constructed, and enzyme activities were evaluated by normalizing with the expression levels of AADAC. Flutamide and phenacetin hydrolase activities were detected by the recombinant AADAC of all species. In flutamide hydrolysis, liver microsomes of all species showed similar catalytic efficiencies, despite the lower AADAC mRNA expression in rat liver. In phenacetin hydrolysis, rat liver microsomes showed approximately 4- to 6.5-fold lower activity than human and mouse liver microsomes. High rifampicin hydrolase activity was detected only by recombinant human AADAC and human liver and jejunum microsomes. Taken together, the results of this study clarified the species differences in the tissue distribution and enzyme activities of AADAC and facilitate our understanding of species differences in drug hydrolysis.
Serodiagnosis of Tuberculosis in Asian Elephants (Elephas maximus) in Southern India: A Latent Class Analysis

Background Mycobacterium tuberculosis, a causative agent of chronic tuberculosis disease, is widespread among some animal species too. There is paucity of information on the distribution, prevalence and true disease status of tuberculosis in Asian elephants (Elephas maximus). The aim of this study was to estimate the sensitivity and specificity of serological tests to diagnose M. tuberculosis infection in captive elephants in southern India while simultaneously estimating sero-prevalence. Methodology/Principal Findings Health assessment of 600 elephants was carried out and their sera screened with a commercially available rapid serum test. Trunk wash culture of select rapid serum test positive animals yielded no animal positive for M. tuberculosis isolation. Under Indian field conditions where the true disease status is unknown, we used a latent class model to estimate the diagnostic characteristics of an existing (rapid serum test) and new (four in-house ELISA) tests. One hundred and seventy nine sera were randomly selected for screening in the five tests. Diagnostic sensitivities of the four ELISAs were 91.3–97.6% (95% Credible Interval (CI): 74.8–99.9) and diagnostic specificity were 89.6–98.5% (95% CI: 79.4–99.9) based on the model we assumed. We estimate that 53.6% (95% CI: 44.6–62.8) of the samples tested were free from infection with M. tuberculosis and 15.9% (97.5% CI: 9.8 - to 24.0) tested positive on all five tests. Conclusions/Significance Our results provide evidence for high prevalence of asymptomatic M. tuberculosis infection in Asian elephants in a captive Indian setting. Further validation of these tests would be important in formulating area-specific effective surveillance and control measures.
Chemoprevention of Esophageal Cancer with Black Raspberries, Their Component Anthocyanins, and a Major Anthocyanin Metabolite, Protocatechuic Acid

Diets containing either freeze-dried black raspberries (BRBs) or their polyphenolic anthocyanins (ACs) have been shown to inhibit the development of N-nitrosomethylbenzylamine (NMBA)–induced esophageal cancer in rats. The present study was conducted to determine whether PCA, a major microbial metabolite of black raspberry (BRB) ACs, also prevents NMBA-induced esophageal cancer in rats. F344 rats were injected with NMBA three times a week for 5 weeks and then fed control or experimental diets containing 6.1% BRBs, an anthocyanin (AC)-enriched fraction derived from BRBs, or protocatechuic acid (PCA). Animals were exsanguinated at weeks 15, 25, and 35 to quantify the development of preneoplastic lesions and tumors in the esophagus, and to relate this to the expression of inflammatory biomarkers. At weeks 15 and 25, all experimental diets were equally effective in reducing NMBA-induced esophageal tumorigenesis, as well as in reducing the expression of pentraxin-3 (PTX3), a cytokine produced by peripheral blood mononuclear cells in response to interleukin (IL)-1β and TNF-α. All experimental diets were also active at reducing tumorigenesis at week 35; however, the BRB diet was significantly more effective than the AC and PCA diets. Furthermore, all experimental diets inhibited inflammation in the esophagus via reducing biomarker (COX-2, iNOS, p-NF-κB, and sEH) and cytokine (PTX3) expression. Overall, our data suggest that BRBs, their component ACs, and PCA inhibit NMBA-induced esophageal tumorigenesis, at least in part, by their inhibitory effects on genes associated with inflammation. Cancer Prev Res; 7(6); 574–84. ©2014 AACR.
Influence of melatonin on free radical‐induced changes in rat pancreatic beta‐cells in vitro

Free radicals may produce cytotoxicity to pancreatic islets under pathophysiological conditions. The aim of our in vitro investigations was to compare functional and morphological changes in pancreatic beta‐cells induced by reactive oxygen species (ROS) generated by alloxan or xanthine oxidase/hypoxanthine (XO/HX), respectively. We demonstrate that short‐term exposure to alloxan or to XO/HX leads to a temporarily elevated insulin release from isolated pancreatic islets. On application of alloxan, this effect is caused by beta‐cell necrosis and can be prevented by administration of melatonin, while in contrast, XO/HX did not lead to long‐term morphological changes in the majority of the cells. Among the cells destroyed by alloxan, only necrosis could be detected, while in contrast, some apoptotic cells were identified by the terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labeling (TUNEL) reaction and electron microscopic examinations of cells treated with XO/HX. Melatonin was able to prevent the changes caused by alloxan, but failed to influence the alterations caused by XO/HX. Using electron spin resonance and lipid peroxidation assay, respectively, it was confirmed that melatonin effectively detoxifies hydroxyl radicals. Therefore, we believe that hydroxyl radicals are the toxic principle of alloxan, but not of XO/HX toxicity.
The minimum orbital period in thermal time-scale mass transfer

We show that the usual picture of supersoft X-ray binary evolution as driven by conservative thermal time-scale mass transfer cannot explain the short orbital periods of RX J0537.7–7034 (3.5 h) and 1E 0035.4–7230 (4.1 h). Non-conservative evolution may produce such periods, but requires very significant mass loss, and is highly constrained.
Comparative Composition and Antioxidant Activity of Peptide Fractions Obtained by Ultrafiltration of Egg Yolk Protein Enzymatic Hydrolysates

The objective of the study was to compare the antioxidant activity of two distinct hydrolysates and their peptide fractions prepared by ultrafiltration (UF) using membranes with molecular weight cut-off of 5 and 1 kDa. The hydrolysates were a delipidated egg yolk protein concentrate (EYP) intensively hydrolyzed with a combination of two bacterial proteases, and a phosphoproteins (PPP) extract partially hydrolyzed with trypsin. Antioxidant activity, as determined by the oxygen radical absorbance capacity (ORAC) assay, was low for EYP and PPP hydrolysates with values of 613.1 and 489.2 μM TE·g−1 protein, respectively. UF-fractionation of EYP hydrolysate increased slightly the antioxidant activity in permeate fractions (720.5–867.8 μM TE·g−1 protein). However, ORAC values were increased by more than 3-fold in UF-fractions prepared from PPP hydrolysate, which were enriched in peptides with molecular weight lower than 5 kDa. These UF-fractions were characterized by their lower N/P atomic ratio and higher phosphorus content compared to the same UF-fractions obtained from EYP-TH. They also contained high amounts of His, Met, Leu, and Phe, which are recognized as antioxidant amino acids, but also high content in Lys and Arg which both represent target amino acids of trypsin used for the hydrolysis of PPP.
The Impact of Subclinical Disease and Mechanism of Detection on the Rise in Thyroid Cancer Incidence: A Population-Based Study in Olmsted County, Minnesota During 1935 Through 2012.

BACKGROUND An ongoing epidemic of thyroid carcinoma (TC) has affected Americans since 1975. Understanding the contribution of subclinical disease and the mechanism of such disease detection may help to alter the course of this epidemic. METHODS We used Rochester Epidemiology Project resources to examine the incidence of TC cases, disease specific mortality, and method of diagnosis during 1935 through 2012. During 2000-2012, we also extracted the mechanism of detection of clinically occult tumors. RESULTS The age-adjusted incidence (AAI) for TC increased from 7.1 [95% confidence interval (CI) 5.5-8.8] per 100,000 person-years (p-y) during 1990-1999 to 13.7 [CI 11.8-15.6] per 100,000 p-y during 2000-2012, with no change in disease-specific mortality since 1935. The incidence trend analysis stratified by the mechanism of detection revealed the AAI of clinically recognized TC was 5.5 per 100,000 p-y [CI 3.4-7.5] in 1960-1969, a rate similar to the incidence seen during 2000-2012. However, AAI of clinically occult TC increased from 0.2 per 100,000 p-y [CI 0.0-0.6] in 1935-1949 to 1.9 per 100,000 p-y [CI 1.2-2.9] in 1990-1999 and to 7.4 per 100,000 p-y [CI 6.0-8.8] in 2000-2012. During 2000-2012, the most frequent reasons for recognition of "occult" tumors were (1) incidental discovery during diagnostic neck imaging in 40 (19%), (2) pathology review of specimens from thyroid surgery for benign conditions in 29 (14%), and (3) investigations of patients with symptoms or palpable nodules that were clearly not associated with coexistent but occult TC but triggered the use of diagnostic neck imaging in 37 (27%). CONCLUSIONS In this population-based study conducted in Olmsted County, Minnesota, the rapid increased incidence of TC during 2000-2012 can be completely attributed to the increased diagnosis of occult TCs, which are mainly found through the use of diagnostic neck imaging. The incidence of clinical TC and disease-specific TC mortality remains stable since 1970, implying that the observed increased incidence is due to the increased detection of subclinical lesions.