Miracle-dz/UniFAR-FTUs huggingface dataset:
Tpa1p Is Part of an mRNP Complex That Influences Translation Termination, mRNA Deadenylation, and mRNA Turnover in Saccharomyces cerevisiae

ABSTRACT In this report, we show that the Saccharomyces cerevisiae protein Tpa1p (for termination and polyadenylation) influences translation termination efficiency, mRNA poly(A) tail length, and mRNA stability. Tpa1p is encoded by the previously uncharacterized open reading frame YER049W. Yeast strains carrying a deletion of the TPA1 gene (tpa1Δ) exhibited increased readthrough of stop codons, and coimmunoprecipitation assays revealed that Tpa1p interacts with the translation termination factors eRF1 and eRF3. In addition, the tpa1Δ mutation led to a 1.5- to 2-fold increase in the half-lives of mRNAs degraded by the general 5′→3′ pathway or the 3′→5′ nonstop decay pathway. In contrast, this mutation did not have any affect on the nonsense-mediated mRNA decay pathway. Examination of mRNA poly(A) tail length revealed that poly(A) tails are longer than normal in a tpa1Δ strain. Consistent with a potential role in regulating poly(A) tail length, Tpa1p was also found to coimmunoprecipitate with the yeast poly(A) binding protein Pab1p. These results suggest that Tpa1p is a component of a messenger ribonucleoprotein complex bound to the 3′ untranslated region of mRNAs that affects translation termination, deadenylation, and mRNA decay.
Dissimilar Frequency of Hepatoblastomas and Hepatic Cystadenomas and Adenocarcinomas Arising in Hepatocellular Neoplasms of D2B6F1 Mice Initiated with N-Nitrosodiethylamine and Subsequently Given Aroclor-1254, Dichlorodiphenyltrichloroethane, or Phenobarbital

Aroclor-1254 (Ar-1254) and dichlorodiphenyltrichloroethane (DDT) were compared to phenobarbital (PB) for their ability to promote hepatocellular proliferative lesions to hepatocellular adenomas and carcinomas and to hepatoblastomas in D2B6F1 male mice initiated with N-nitrosodiethylamine (NDEA). Hepatocellular neoplasms developed in all mice given NDEA and were more numerous in mice fed promoters. Multiplicities decreased in the order Ar-1254 > PB > DDT, indicating that Ar-1254 was more potent than either PB or DDT at the dosage levels used. PB was the most effective of the 3 agents in stimulating the evolution of hepatocellular neoplasms to hepatoblastoma. The incidence of hepatoblastomas in the NDEA.PB group was 72% but was only 27% in NDEA-initiated, DDT-promoted mice and 33% in low-dose and only 9% in high-dose Ar-1254-promoted mice. In contrast, lesions resembling benign and malignant cholangiocellular neoplasms were frequently found within hepatocellular tumors in Ar-1254-promoted mice but not in mice fed PB or DDT, either alone or after NDEA. Some cystic glandular structures in Ar-1254-promoted mice contained mucous cells, argentaffin cells, and Paneth cells and thus constituted intestinal metaplasia. Hepatoblastoma and intestinal metaplasia/cholangiocellular tumor morphology appear to constitute different patterns of genetic programming induced by certain promoters in expanding clones of initiated hepatocytes, on favorable genetic backgrounds such as that of D2B6F1 male mice.
Activity Level Assessment Using a Smart Cushion for People with a Sedentary Lifestyle

As a sedentary lifestyle leads to numerous health problems, it is important to keep constant motivation for a more active lifestyle. A large majority of the worldwide population, such as office workers, long journey vehicle drivers and wheelchair users, spends several hours every day in sedentary activities. The postures that sedentary lifestyle users assume during daily activities hide valuable information that can reveal their wellness and general health condition. Aiming at mining such underlying information, we developed a cushion-based system to assess their activity levels and recognize the activity from the information hidden in sitting postures. By placing the smart cushion on the chair, we can monitor users’ postures and body swings, using the sensors deployed in the cushion. Specifically, we construct a body posture analysis model to recognize sitting behaviors. In addition, we provided a smart cushion that effectively combine pressure and inertial sensors. Finally, we propose a method to assess the activity levels based on the evaluation of the activity assessment index (AAI) in time sliding windows. Activity level assessment can be used to provide statistical results in a defined period and deliver recommendation exercise to the users. For practical implications and actual significance of results, we selected wheelchair users among the participants to our experiments. Features in terms of standard deviation and approximate entropy were compared to recognize the activities and activity levels. The results showed that, using the novel designed smart cushion and the standard deviation features, we are able to achieve an accuracy of (>89%) for activity recognition and (>98%) for activity level recognition.
A comparison of cochlear microphonics and N1 in audiogenic-seizure-susceptible and control rats.

Although numerous studies have shown that cochlear impairment exists in audiogenic-seizure (AGS)-susceptible mice, there is only one report of cochlear potentials obtained from AGS-susceptible rats. To investigate the hypothesis that cochlear impairment also exists in AGS rats, cochlear microphonics (CM) and the primary afferent activity of the auditory division of the eighth cranial nerve (N1) were studied in AGS rats. AGS rats were obtained from the Veterans Administration Medical Center (Shreveport, La.) colony of Sprague Dawley derived animals, and control rats were obtained from Sprague Dawley, Inc. Two school bells ringing simultaneously were used to produce a sound of approximately 115 dB (AGS test stimulus). Exposure to the AGS test stimulus was once per week for three consecutive weeks. Chloramphenicol was used to treat the frequent otitis media found in the colony of AGS rats. Two categories of AGS-susceptible and control rats were studied: (1) rats exposed to the AGS test stimulus and chloramphenicol regimen; and (2) rats not receiving these treatments. All rats were anesthetized with i.p. Dial-Urethane and prepared for cochlear round window recording. Cochlear microphonics were recorded in response to a click stimulus. A significant decrease in cochlear sensitivity was seen in both groups of AGS rats when compared to appropriate controls as reflected by a 25-35 dB shift in all CM and N1 input-output functions. These results support the hypothesis that a functional cochlear impairment exists in the AGS rat.
The effect of UGT1A and UGT2B polymorphisms on colorectal cancer risk: Haplotype associations and gene–environment interactions

UDP‐glucuronosyltransferases (UGTs) play an important role in the phase II metabolism of exogenous and endogenous compounds. As colorectal cancer (CRC) etiology is thought to involve the biotransformation of dietary factors, UGT polymorphisms may affect CRC risk by altering levels of exposure. Genotyping of over 1800 Caucasian subjects was completed to identify the role of genetic variation in nine UGT1A and five UGT2B genes on CRC risk. Unconditional logistic regression and haplotype analyses were conducted to identify associations with CRC risk and potential gene‐environment interactions. UGT1A haplotype analysis found that the T‐G haplotype in UGT1A10 exon 1 (block 2: rs17864678, rs10929251) decreased cancer risk for the colon [proximal (OR = 0.28, 95% CI = 0.11–0.69) and for the distal colon (OR = 0.32, 95% CI = 0.12–0.91)], and that the C‐T‐G haplotype in the 3′ region flanking the UGT1A shared exons (block 11: rs7578153, rs10203853, rs6728940) increased CRC risk in males (OR = 2.56, 95% CI = 1.10–5.95). A haplotype in UGT2B15 containing a functional variant (rs4148269, K523T) and an intronic SNP (rs6837575) was found to affect rectal cancer risk overall (OR = 2.57, 95% CI = 1.21–5.04) and in females (OR = 3.08, 95% CI = 1.08–8.74). An interaction was found between high NSAID use and the A‐G‐T haplotype (block 10: rs6717546, rs1500482, rs7586006) in the UGT1A shared exons that decreased CRC risk. This suggests that UGT genetic variation alters CRC risk differently by anatomical sub‐site and gender and that polymorphisms in the UGT1A shared exons may have a regulatory effect on gene expression that allows for the protective effect of NSAIDs on CRC risk. © 2014 Wiley Periodicals, Inc.
Assessment of the Number and Expression of P-Type H+-ATPase Genes in Tomato

Seven genomic fragments encoding isoforms of tomato (Lycopersicon esculentum) plasma membrane H+-ATPase were cloned and characterized. Genomic DNA gel-blot analysis indicated that probes corresponding to LHA1 through LHA7 hybridized to a common set of seven to nine restriction fragments at moderate stringency and to single, distinct fragments at high stringency. RNA gel-blot and polymerase chain reaction (PCR)-based RNA analyses indicated that LHA1, LHA2, and LHA4 transcripts were present in all organs examined (roots, hypocotyls, stems, immature leaves, mature leaves, green fruit, and red ripe fruit). LHA1 mRNA was present at similar abundance in all organs, LHA2 mRNA was most abundant in hypocotyls and leaves, and LHA4 mRNA was most abundant in roots and hypocotyls. RNA gel-blot and RNA-based PCR assays indicated that LHA3, LHA5, LHA6, and LHA7 mRNA was present at very low or nondetectable levels in all organs, suggesting that these genes are either expressed at very low levels or in organs not examined or that they are regulated by hormonal or environmental cues that were not tested. Indoleacetic acid (IAA) treatment of tomato hypocotyl segments resulted in modest changes in abundance of LHA1, LHA2, and LHA4 transcripts, but these changes were not correlated with the time course of IAA-induced growth. In addition, constitutively silent LHA genes were not activated by IAA. These results indicate that at least seven genomic sequences are present in tomato that may encode plasma membrane H+-ATPases, at least three of which are expressed relatively abundantly at the mRNA level.
The oxidative stress response in yeast cells involves changes in the stability of Aft1 regulon mRNAs

Saccharomyces cerevisiae can import iron through a high‐affinity system consisting of the Ftr1/Fet3‐mediated reductive pathway and the siderophore‐mediated non‐reductive one. Expression of components of the high‐affinity system is controlled by the Aft1 transcriptional factor. In this study we show that, upon oxidative stress, Aft1 is transitorily internalized into the nucleus, followed by transcription activation of components of its regulon. In these conditions, the mRNA levels of the genes of the non‐reductive pathway become increased, while those of FTR1 and FET3 remain low because of destabilization of the mRNAs. Consequently, the respective protein levels also remain low. Such mRNA destabilization is mediated by the general 5′–3′ mRNA decay pathway and is independent of the RNA binding protein Cth2. Yeast cells are hypersensitive to peroxides in growth conditions where only the high‐affinity reductive pathway is functional for iron assimilation. On the contrary, peroxide does not affect growth when iron uptake occurs exclusively through the non‐reductive pathway. This reinforces the idea that upon oxidative stress S. cerevisiae cells redirect iron assimilation through the non‐reductive pathway to minimize oxidative damage by the ferrous ions, which are formed during iron import through the Ftr1/Fet3 complexes.
Assessment of reproducibility in depletion and enrichment workflows for plasma proteomics using label‐free quantitative data‐independent LC‐MS

Quantitation in plasma‐based proteomics necessitates the reproducible removal of highly abundant proteins to enable the less abundant proteins to be visible to the mass spectrometer. We have evaluated immunodepletion (proteoprep20) and enrichment (Bio‐Rad beads), as the current predominant approaches. Label‐free analysis offers an opportunity to estimate the effectiveness of this approach without incorporating chemical labels. Human plasma samples were used to quantitatively assess the reproducibility of these two methods using nano‐LC‐data‐independent acquisition MS. We have selected 18 candidate proteins and a comparison of both methodologies showed that both of the methods were reproducible and fell below 20% residual SD. With the same candidate proteins, individual inter‐day variability for the samples was also processed, allowing us to monitor instrument reproducibility. Overall, a total of 131 proteins were identified by both methods with 272 proteins identified by enrichment and 200 identified by immunodepletion. Reproducibility of measurements of the amount of protein in the processed sample for individual proteins is within analytically acceptable standards for both methodologies. This enables both methods to be used for biomarker studies. However, when sample is limited, enrichment is not suitable as larger volumes (>1.0 mL) are required. In experiments where sample is not limited then a greater number of proteins can be reliably identified using enrichment.
Bcl-3 Expression Promotes Cell Survival following Interleukin-4 Deprivation and Is Controlled by AP1 and AP1-Like Transcription Factors

ABSTRACT We have analyzed the interleukin-4 (IL-4)-triggered mechanisms implicated in cell survival and show here that IL-4 deprivation induces apoptotic cell death but does not modulate Bcl-2 or Bcl-x expression. Since Bcl-x expression is insufficient to ensure cell survival in the absence of IL-4, we speculate that additional molecules replace the antiapoptotic role of Bcl-2 and Bcl-x in an alternative IL-4-triggered pathway. Cell death is associated with Bcl-3 downregulation and Bcl-3 expression blocks IL-4 deprivation-induced apoptosis, suggesting that Bcl-3 acts as a survival factor in the absence of growth factor. To characterize the IL-4-induced regulation of murine Bcl-3 expression, we cloned the promoter of this gene. Sequencing of the promoter showed no TATA box element but did reveal binding sites for AP1, AP1-like, and SP1 transcription factors. Retardation gels showed that IL-4 specifically induces AP1 and AP1-like binding activity and that mutation of these binding sites abolishes the IL-4-induced Bcl-3 promoter activity, suggesting that these transcription factors are important in Bcl-3 promoter transactivation. IL-4 deprivation induces downregulation of Jun expression and upregulation of Fos expression, both of which are proteins involved in the formation of AP1 and AP1-like transcription factors. Overexpression of Jun family proteins transactivates the promoter and restores Bcl-3 expression in the absence of IL-4 stimulation. Taken together, these data describe a new biological role for Bcl-3 and define the regulatory pathway implicated in Bcl-3 expression.
Community-acquired pneumonia

Purpose of review This review examines the epidemiology, diagnosis, prognosis, treatment and prevention of community-acquired pneumonia (CAP) in adults. Recent findings CAP is a significant cause of morbidity and mortality. Streptococcus pneumoniae is the most common CAP pathogen; however, microbial cause varies by geographic location and host factors. Identification of a microbial cause in CAP remains challenging – 30–65% of cases do not have a pathogen isolated. The use of molecular techniques in addition to culture, serology and urinary antigen testing has improved diagnostic yield. Scoring systems are useful for CAP prognostication and site of care decisions. Studies evaluating novel biomarkers including pro-B-type natriuretic peptide and procalcitonin suggest potential adjunctive roles in CAP prognosis. Guideline-based treatment for CAP has changed little in recent years. Effective and timely antimicrobial therapy is crucial in optimizing outcomes and should be based on local antimicrobial susceptibility patterns. Macrolides may have additional anti-inflammatory properties and a mortality benefit in severe CAP. Preventive strategies include immunization and modification of specific patient risk factors. Summary CAP is common and causes considerable morbidity and mortality. A comprehensive approach including advanced diagnostic testing, effective and timely antimicrobial therapy and prevention is required to optimize CAP outcomes.
Salivary anti-Ro60 and anti-Ro52 Antibody Profiles to Diagnose Sjögren’s Syndrome

Simple and non-invasive saliva-based diagnostics may be useful for the identification, understanding, and monitoring of autoimmune and infectious diseases. Previously, Luciferase Immunoprecipitation Systems (LIPS) were used for sensitive detection of patient serum autoantibodies in Sjögren’s Syndrome (SjS), a chronic autoimmune disease affecting the salivary and lacrimal glands. Here we explored the ability of LIPS to diagnose SjS based on IgG autoantibodies in patient saliva. From LIPS testing, anti-Ro60 autoantibodies were detected in the saliva of 70% (19/27) of SjS patients with 96% specificity. Positive anti-Ro60 autoantibodies were also found in 70% of the matched serum samples (96% specificity). LIPS detected Ro52 autoantibodies in the saliva and serum of 67% of SjS patients with 100% specificity. Overall, the autoantibody titers in saliva were approximately 4000-fold lower by volume than serum, but still distinguished seropositive patients from controls. These results suggest that LIPS salivary-based testing for SjS autoantibodies is a practical alternative to serum and compatible with point-of-care testing.
Twenty-four-hour profiles of acylated and total ghrelin: relationship with glucose levels and impact of time of day and sleep.

CONTEXT The acylation of ghrelin is essential for its stimulatory effects on GH release and appetite. Most of the physiology of ghrelin has been defined based on the assay of total ghrelin (TG), which mainly reflects levels of unacylated ghrelin. Whether levels of acylated ghrelin (AG) are influenced by circadian time and sleep and impact glucose regulation under physiologic conditions is not known. METHODS Blood was sampled at 10- to 30-min intervals for 24 h in 14 healthy young lean men under controlled conditions of activity, light-dark cycle, and sleep-wake schedule. The subjects ingested three identical carbohydrate-rich meals at 5-h intervals. Sleep was polygraphically monitored. Levels of TG and AG were measured by RIA. The 24-h profiles of glucose and insulin levels were assessed simultaneously. RESULTS Postprandial glucose concentrations were positively correlated with mean levels of AG but not TG, independently of insulin. Postprandial suppression and rebound of AG and TG occurred in parallel and were not impacted by time of day. The nocturnal elevation of AG and TG reflects the postdinner rebound curbed by an inhibitory effect of sleep. The ratio of AG to TG was lower during sleep than during wake, consistent with a reduction of orexigenic signal. CONCLUSIONS Individual differences in AG levels may be an important predictor of overall glucose control under physiological conditions. Sleep, but not time of day, impacts postprandial TG and AG responses. The inhibitory effect of sleep on ghrelin release and acylation is consistent with the association between sleeping and fasting.
Diversity of soil actinomycetes in yunnan, china

Since 1978, about 4,200 soil samples have been collected from 22 selected areas of various vegetational and climatic types throughout the province of Yunnan. Actinomycetes of 29 genera were isolated by the methods employed. The correlations between diversity and climate were grouped into tropical, subtropical plateau, cool temperate mountain, and snowy mountain types. Actinomycete populations of the first two types were more complex than were the other ones. Correlations between actinomycete diversity and vegetation were also attempted. Six types of vegetation were compared. The diversity of actinomycetes was greatest in soil samples of a primeval forest, with an average of 9.0 genera isolated, followed by secondary forest and vegetable farmland samples, with averages of 6.7 and 6.5 genera isolated, respectively. The upper limit for the occurrence of thermophilic actinomycetes is about 3,500 m above sea level in Yunnan. Psychrophilic actinomycetes were isolated at up to the same altitude. In addition, the drier and poorer the soil was and the cooler the climate was, the lower the count of actinomycetes was and the higher the percentage of streptomycetes observed was. The genus Streptomyces appears to be the most important in ecological function. It represents up to 90% of all soil actinomycete diversity in Yunnan and is likely an important characteristic of the soil actinomycete population.
Prevalence and antimicrobial susceptibility of foodborne bacteria in wild boars (Sus scrofa) and wild deer (Cervus nippon) in Japan.

This study aimed to evaluate the role of wild boars and deer as reservoirs of foodborne bacteria. We investigated the prevalence and antimicrobial susceptibility of Campylobacter spp. , Salmonella spp. , Shiga toxin-producing Escherichia coli (STEC) O157 and O26, and Listeria monocytogenes isolated from wild boars and deer in Japan, from July through December 2010. Campylobacter spp. and Salmonella spp. were isolated from 43.8% (95% confidence interval [CI]: 35.0-52.6) and 7.4% (95% CI: 2.8-12.1) of rectal content samples of wild boars, respectively, but not from wild deer. The most common Campylobacter species was C. lanienae and C. hyointestinalis. The nine Salmonella serovars isolated were S. enterica subsp. enterica serovar Agona (three isolates), S. Narashino (two), S. Enteritidis (one), S. Havana (one), S. Infantis (one), and S. Thompson (one). Five (16%) and 6 (29%) isolates of C. lanienae and C. hyointestinalis, respectively, were resistant to enrofloxacin. STEC O157 and O26 and L. monocytogenes were isolated from 2.3% (95% CI: 0-5.0), 0.8% (95% CI: 0-2.3), and 6.1% (95% CI: 1.7-10.5) of the rectal content samples of wild deer, respectively, but not from wild boars. This first nationwide survey of the prevalence of foodborne bacteria in wild boars and wild deer in Japan suggests that consumption of meat from these animals is associated with the risk of causing infection with these bacteria in humans. Moreover, these animals are potential vehicles for distribution of antimicrobial-resistant bacteria into their habitat. The prevalence and antimicrobial susceptibility of such foodborne bacteria in these wild animals should be monitored periodically.
Neonatal iron exposure induces neurobehavioural dysfunctions in adult mice.

Excess iron in the brain has been implicated in the pathogenesis of several human neurodegenerative disorders, i.e., Parkinson's and Alzheimer's disease. The neonatal period is critical for the establishment of normal iron content in the adult brain. In the present study, the long-term neurobehavioral effects of iron exposure during this period were assessed by treating NMRI mice orally with 0.0, 3.7, or 37.0 mg Fe(2+)/kg body wt on postnatal days 10-12. Spontaneous motor behavior and radial arm maze learning were tested at the age of 3 months. It was found that the mice treated with the higher dose of Fe(2+), 37.0 mg/kg body wt, were hypoactive during the first 20 min of testing but hyperactive during the final 20 min, showing an almost complete lack of habituation of spontaneous activity in the test chambers. These changes were also seen in animals treated with the lower dose of Fe(2+), 3.7 mg/kg body wt, but the effects were less pronounced, indicating a dose-response relationship. In the radial arm maze, the Fe(2+) 37.0 mg/kg group evidenced significantly both more errors in arm choices and longer latencies to acquire all eight pellets. Both dose groups showed attenuated performance increments on successive trials. Analysis of brain iron content indicated significantly more total iron (microgram/g) in the basal ganglia, but not frontal cortex, of the higher, 37 mg/kg, dose group. The knowledge of the long-term effects of iron entering the brain during this critical period of rapid brain growth is limited. Increased amounts of iron in the brain, especially in the basal ganglia, may contribute to neurodegenerative processes.