Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct inhibitory effects of simvastatin on matrix accumulation in cultured murine mesangial cells.

BACKGROUND 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been demonstrated to suppress glomerular injuries in various renal diseases. These agents inhibit in vitro proliferation of several cell types, including mesangial cells. This effect indicates the ability to ameliorate mesangioproliferative lesions, independent of the improvement of hypercholesterolemia. On the other hand, it is not clear whether HMG-CoA reductase inhibitors directly regulate extracellular matrix (ECM) accumulation from mesangial cells. METHODS In this study, to examine the in vitro effects of simvastatin, an HMG-CoA reductase inhibitor, on mRNA expressions of matrix proteins, growth factors, and matrix turnover proteins, we incubated cultured murine mesangial cells stimulated by fetal calf serum (FCS) with or without simvastatin for 24 hours, and Northern analysis was performed. RESULTS Simvastatin showed a slightly suppressive effect on mRNA expression of type IV collagen and fibronectin and a slightly up-regulative effect on that of type I collagen, whereas mRNA expression of type III collagen was markedly up-regulated. mRNA expression of platelet-derived growth factor (PDGF)-B chain and PDGF receptor beta-subunit was suppressed, whereas that of transforming growth factor-beta (TGF-beta) was not affected by simvastatin. Concerning matrix turnover proteins, simvastatin markedly reduced mRNA expression of plsminogen activator inhibitor-1 (PAI-1) without affecting the expression of tissue-type plasminogen activator (tPA). CONCLUSION These results suggest type-specific modulation of matrix protein production independent of TGF-beta and the suppressive effects of autocrine PDGF by administration of HMG-CoA reductase inhibitors in mesangial cells. Moreover, the beneficial effects of these agents on matrix protein accumulation may be through promoting ECM degradation derived from PAI-1 suppression.
Emerging drugs for renal failure

Renal failure involves a significant impairment of the essential functions of the kidney, which can be either acute with sudden and rapid onset (acute renal failure [ARF]) or chronic with gradual onset (chronic renal failure [CRF]). ARF, if detected early, may be halted or reversed, whereas CRF is generally irreversible. Without treatment or intervention, both forms of renal failure lead to end stage renal failure (ESRF) or end stage renal disease (ESRD), requiring renal replacement therapy (RRT) in the form of dialysis or renal transplantation for survival. However, provision of RRT requires expert teams working in specialised units, making therapy of patients with renal failure expensive; furthermore, RRT is complex, with its own complications. Although pharmacological interventions have shown promise in experimental models, these have not been as successful in the clinical setting (e.g., administration of atrial natriuretic peptide, low-dose dopamine). At present, drugs are administered during CRF to either reduce one of the many risk factors of CRF (e.g., angiotensin-converting enzyme inhibitors, statins) or to deal with the consequences of CRF (e.g., erythropoietin, calcitriol). Recent evidence suggests that some of these interventions may provide further direct beneficial effects via reduction of renal inflammation. Although these interventions have greatly improved the prospects for patients suffering ESRF, the development of novel drugs and therapies with which to reduce the consequences of renal failure and ESRD remain topics of great interest. This article reviews the therapies available for the prevention and management of renal failure in adults and describes, in detail, emerging drugs and novel interventions that may soon become available for the treatment or prevention of ESRF.
Elevated muscle glycogen and anaerobic energy production during exhaustive exercise in man.

1. The effect of elevated muscle glycogen on anaerobic energy production, and glycogenolytic and glycolytic rates was examined in man by using the one‐legged knee extension model, which enables evaluation of metabolism in a well‐defined muscle group. 2. Six subjects performed very intense exercise to exhaustion (EX1) with one leg with normal glycogen (control) and one with a very high concentration (HG). With each leg, the exhaustive exercise was repeated after 1 h of recovery (EX2). Prior to and immediately after each exercise bout, a muscle biopsy was taken from m. vastus lateralis of the active leg for determination of glycogen, lactate, creatine phosphate (CP) and nucleotide concentrations. Measurements of leg blood flow and femoral arterial‐venous differences for oxygen content, lactate, glucose, free fatty acids and potassium were performed before and regularly during the exhaustive exercises. 3. Muscle glycogen concentration prior to EX1 was 87.0 and 176.8 mmol (kg wet wt)‐1 for the control and HG leg, respectively, and the decreases during exercise were 26.3 (control) and 25.6 (HG) mmol (kg wet wt)‐1. The net glycogen utilization rate was not related to pre‐exercise muscle glycogen concentration. Muscle lactate concentration at the end of EX1 was 18.8 (control) and 16.1 (HG) mmol (kg wet wt)‐1, and the net lactate production (including lactate release) was 26.5 (control) and 23.6 (HG) mmol (kg wet wt)‐1. Rate of lactate production was unrelated to initial muscle glycogen level. Time to exhaustion for EX1 was the same for the control leg (2.82 min) and HG leg (2.92 min). 4. Muscle glycogen concentration before EX2 was 14 mmol (kg wet wt)‐1 lower than prior to EX1. During EX2 the muscle glycogen decline of 19.6 mmol (kg wet wt)‐1 for the control leg was less than for the HG leg (26.2 mmol (kg wet wt)‐1). The muscle lactate concentrations at the end of EX2 were about 7‐8 mmol (kg wet wt)‐1 lower compared to EX1, and the net lactate production was reduced by 40%. The exercise time during EX2 was 0.35 min shorter for the control leg, while no difference was observed for the HG leg. 5. Total reduction in ATP and CP was similar during the four exercise bouts, while a higher accumulation of inosine monophosphate (IMP) occurred during EX2 for the control leg (0.72 mmol (kg wet wt)‐1) compared to the HG leg (0.20 mmol (kg wet wt)‐1). (ABSTRACT TRUNCATED AT 400 WORDS)
Differential neural activity in the recognition of old versus new events: An Activation Likelihood Estimation Meta‐Analysis

This study presents a meta‐analysis comparing hit and correct rejection (CR) conditions across 48 fMRI studies. Old/new (hit > CR) effects associated most consistently with (1) components of the default‐mode network, including the left angular gyrus, bilateral precuneus, and bilateral posterior cingulate regions, which may support the mental re‐experiencing of an old event, or ecphory; (2) components of the cognitive‐control network, involving the left dorsolateral and dorsomedial prefrontal cortex and bilateral intraparietal sulcus regions, which may mediate memory and non‐memory control functions; and (3) the caudate nucleus, a key part of the brain's reward system that may support the satisfaction tied to target‐detection. Direct comparisons of old/new effects between item versus source retrieval and “remember” versus “know” retrieval yielded three main sets of findings. First, default‐mode network regions showed greater old/new effects in conditions associated with richer ecphoric processing. Second, cognitive‐control network regions showed greater old/new effects in conditions associated with a greater demand for strategic‐retrieval processing. Third, the caudate nucleus showed greater old/new effects in conditions tied to greater confidence in target‐detection. New/old (CR > hit) effects most strongly associated with the bilateral medial temporal lobe, possibly reflecting greater encoding‐related activity for new than for old items, and the right posterior middle temporal regions, possibly reflecting repetition‐related neural priming for old items. In conclusion, neural activity distinguishing old from new events comprises an ensemble of multiple memory‐specific activities, including encoding, retrieval, and priming, as well as multiple types of more general cognitive activities, including default‐mode, cognitive‐control, and reward processing. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.
Statistical measurements of BER fluctuations due to PMD in 10-Gb/s optical transmissions

Polarization-mode dispersion induces signal fading and fluctuating power penalties in optical systems. The intrinsic uncertainty of the bit error rate (BER) measurements combined to the time needed to perform power adjustments for a power penalty measurement can completely distort the statistics of the as-measured power penalties. We show that measuring the BER statistics and using the receiver sensitivity power dependence gives a better measurement of the power penalty statistics. The influence of the statistics of error detection in the measurements must be considered in order to define the correct measuring time for each situation.
Does peer support help patients with heart failure? Finding the perfect match.

Match making has been an intriguing and reoccurring theme in books, songs, plays, and movies. Parents have been doing it for generations … tirelessly working to find the right match for their unmarried children. Close friends launch similar campaigns to help single friends find a life partner. Sometimes parents and friends hit the jackpot. Sometimes the results of the most well-intentioned matches end in an evening of painful tragedy or unintended comedy. Unfortunately, the majority of subjects of these heroic efforts know that the chances are slim that the connection will result in a match. Article see p 246 In this issue of Circulation: Heart Failure , Heisler et al1 designed an elegant effectiveness study to test the hypothesis that an intervention in which patients recently discharged from the hospitals with heart failure (HF) were matched with similar peers, and the pair was instructed to call each other weekly for information and support would improve all-cause hospitalization and all-cause mortality, as well as increase social support and quality of life. All the participants were recently discharged from the hospital with a diagnosis of HF and were unable or unwilling to attend an outpatient HF program. Patients were randomized to 1 of 2 groups: a peer-support intervention with weekly phone calls or an intervention that …
Analysis of the intracellular amino acid pool and proteins from whole cells of Rhizobium japonicum.

The amino acid composition of proteins from whole cells of Rhizobium japonicum was determined. The proteins contain only those amino acids commonly associated with bacteria and in ratios approximately equal to those which have been reported in other bacterial genera. Analysis of the intracellular amino acid pool showed relatively large amounts of alanine, glutamate and lysine. These amino acids are normally associated with the peptidoglycan layer of bacterial cell walls leading to speculation that the pool observed was for the synthesis of cell wall precursors rather than for general protein synthesis. The high levels of alanine relative to the other amino acids can also be explained by the operation of alanine dehydrogenase, (E.C. 1.4.1.1) which is an assiniilatory enzyme for ammonia.
Substance misuse in adolescents

There is increasing evidence that substance misuse among British adolescents is escalating ([Miller & Plant, 1996][1]; [Sutherland & Willner, 1998][2]). Swadi (1992) found that, among adolescents aged 12–17 years referred to mental health services, the prevalence of drug use was 13.1% (16.3% among
Integrating ARC grid middleware with Taverna workflows

SUMMARY This work presents two independent approaches for a seamless integration of computational grids with the bioinformatics workflow suite Taverna. These are supported by a unique relational database to link applications with grid resources and presents those as workflow elements. A web portal facilitates its collaborative maintenance. The first approach implements a gateway service to handle authentication certificates and all communication with the grid. It reads the database to spawn web services for workflow elements which are in turn used by Taverna. The second approach lets Taverna communicate with the grid on its own, by means of a newly developed plug-in. It reads the database and executes the needed tasks directly on the grid. While the gateway service is non-intrusive, the plug-in has technical advantages, e.g. by allowing data to remain on the grid while being passed between workflow elements. AVAILABILITY http://grid.inb. uni-luebeck.de/
Periodontal infections and diabetes mellitus: when will the puzzle be complete?

The article in last month’s issue of the Journal of Clinical Periodontology on the effects of periodontal therapy in patients with type 2 diabetes (Navarro-Sanchez et al. 2007) is the latest in a series of manuscripts that have been published in the journal in the past 12 months (Engebretson et al. 2006, 2007, Lalla et al. 2006, 2007a, Bakhshandeh et al. 2007, Davila-Perez et al. 2007, Lim et al. 2007, Jones et al. 2007a, b), shedding new light on the periodontitis–diabetes link. This is a welcome trend; research on this important and complex association is of prime significance. This guest editorial reflects on the current evidence of the association between these two common chronic conditions, focuses on the topic of periodontal therapy effects on the diabetic state with the opportunity of the January issue Jones et al. (2007a, b) study, highlights the gaps in our knowledge and offers a view to important future research directions in the field.
Traducción automática entre chino y español: ¿dónde estamos?

La traduccion automatica ha recibido mucho interes en el campo del procesado del lenguaje natural porque es un tema de interes social. Al mismo tiempo se trata de un problema interesante a nivel academico porque engloba diferentes tareas del tratamiento del lenguaje textual como la desambiguacion lexica, el parseado o el reconocimiento de entidades. Este articulo presenta los ultimos avances en esta area para las dos lenguas que encabezan el ranking de numero de habitantes nativos: el chino y espanol. La investigacion en traduccion automatica para ambos incluye aproximaciones basadas en reglas como estadisticas. El hecho que ambas aproximaciones esten activas deja el camino abierto para hacer una aproximacion hibrida. De este modo, utilizando el caso particular del chino y espanol, este articulo: (1) describe las motivaciones economicas, sociales y academicas de este para ambos idiomas; (2) revisa, describe y muestra experimentos de las dos aproximaciones mas populares de traduccion automatica (basada en reglas y estadistica); (3) y dibuja lineas futuras que estan siendo muy populares en el campo como es la aproximacion hibrida.
Notice of RetractionInfluence of Methyl Jasmonate on Cell Membrane Permeability and Ajmalicine Accumulation in Salt-Stressed Catharanthus roseus Suspension Cells

The influence of methyl jasmonate (MeJA) and NaCl on a Catharanthus roseus suspension cell culture with high production of ajmalicine was investigated. Suspension cell cultures were treated with 100 mM NaCl or 100 μM MeJA or both for 3 d before harvesting, and measurements were then performed. NaCl treatment increased both the cell membrane permeability and ajmalicine accumulation. MeJA treatment promoted ajmalicine accumulation and maintained membrane permeability of cells under salt stress. However, a cumulative effect of both factors on the accumulation of ajmalicine was not found. Our results suggest that the higher ajmalicine accumulation in the medium after treatment with NaCl was associated with the cell membrane permeability.
Recessive osteogenesis imperfecta caused by LEPRE1 mutations: clinical documentation and identification of the splice form responsible for prolyl 3-hydroxylation

Background: Recessive forms of osteogenesis imperfecta (OI) may be caused by mutations in LEPRE1, encoding prolyl 3-hydroxylase-1 (P3H1) or in CRTAP, encoding cartilage associated protein. These proteins constitute together with cyclophilin B (CyPB) the prolyl 3-hydroxylation complex that hydroxylates the Pro986 residue in both the type I and type II collagen α1-chains. Methods: We screened LEPRE1, CRTAP and PPIB (encoding CyPB) in a European/Middle Eastern cohort of 20 lethal/severe OI patients without a type I collagen mutation. Results: Four novel homozygous and compound heterozygous mutations were identified in LEPRE1 in four probands. Two probands survived the neonatal period, including one patient who is the eldest reported patient (177/12 years) so far with P3H1 deficiency. At birth, clinical and radiologic features were hardly distinguishable from those in patients with autosomal dominant (AD) severe/lethal OI. Follow-up data reveal that the longer lived patients develop a severe osteochondrodysplasia that overlaps with, but has some distinctive features from, AD OI. A new splice site mutation was identified in two of the four probands, affecting only one of three LEPRE1 mRNA splice forms, detected in this study. The affected splice form encodes a 736 amino acid (AA) protein with a “KDEL” endoplasmic reticulum retention signal. While western blotting and immunocytochemical analysis of fibroblast cultures revealed absence of this P3H1 protein, mass spectrometry and SDS-urea-PAGE data showed severe reduction of α1(I)Pro986 3-hydroxylation and overmodification of type I (pro)collagen chains in skin fibroblasts of the patients. Conclusion: These findings suggest that the 3-hydroxylation function of P3H1 is restricted to the 736AA splice form.
The Discovery of Vitamin B12

The discovery of vitamin B12, the elucidation of its role in metabolism, and the effects and treatment of its deficiency occurred in distinct phases over more than 100 years, and it was the subject of two separate Nobel Prizes. The valuable contribution of clinical reports and studies of patients with pernicious anemia throughout the 19th century resulted in enough clinical definition to allow Minot and Murphy to put together the first hallmark study on treatment of the condition, leading them to a Nobel Prize. These researchers were not the first to suggest that an inadequacy of nutrients was the cause of pernicious anemia, but their particular input was a carefully designed intervention in well-characterized pernicious anemia patients, of a special diet containing large amounts of liver. They found consistent improvement in the clinical and blood status of all subjects, most of whom remained on remission indefinitely. After the successful intervention studies, the next advance was made by Castle who discovered that a gastric component, which he called intrinsic factor, was missing in pernicious anemia. Many years later, intrinsic factor was found to be a glycoprotein that formed a complex with vitamin B12, promoting its absorption through ileal receptors. The vitamin was isolated by two groups simultaneously and was crystallized and characterized in the laboratory of Dorothy Hodgkin, contributing to her Nobel Prize in 1964. Subsequently, the various biochemical roles of vitamin B12 were elucidated, including its important interaction with folate and their common link with megaloblastic anemia. Many of the early clinical studies recognized that vitamin B12 deficiency also caused a severe neuropathy leading to paralysis and death, while post mortem analysis demonstrated spinal cord demyelination. Vitamin B12 is still the subject of intense research and, in particular, its role in preventing these irreversible neurological lesions remains unclear.
Phylogenetic and trait similarity to a native species predict herbivory on non-native oaks

Introduced plants tend to experience less herbivory than natives, although herbivore loads vary widely. Herbivores may switch hosts onto an introduced plant for at least two reasons. They may recognize the novel plant as a potential host based on similarity of the plant's traits to the traits of one of its native hosts, a similarity that may or may not exhibit phylogenetic signal. Alternatively, herbivores may feed optimally, assessing which introduced plants provide the best nutrition irrespective of similarity to native species. Here, we created a phylogeny of 57 oak (Quercus) taxa, which were grown outside of their ranges in a common botanical garden that contained one abundant native oak (Quercus lobata). We used the phylogeny to estimate the phylogenetic conservatism of herbivory by two feeding guilds of insects (leaf chewers and leaf miners) and 11 plant traits expected to affect herbivore performance. We found high phylogenetic signal in chewing damage but not mining damage and all traits except for leaf maturation time. Introduced oaks that are more closely related to the native oak received more chewing and mining damage than distantly related oaks, and introduced oaks that had greater overall similarity in leaf traits also received higher chewing damage but not mining damage. These results demonstrate that interactions between introduced plants and their herbivores are driven independently by traits that track plant phylogeny and leaf traits that likely affect herbivore performance.
Renal Protective Effect in Hypertensive Patients: The High Doses of Angiotensin II Receptor Blocker (HARB) Study

Angiotensin receptor blockers (ARBs) are the recommended first-line antihypertensive treatment for managing chronic kidney disease, and strict blood pressure (BP) regulation is crucial for the reduction of proteinuria. Valsartan and candesartan are commonly used ARBs in Japan, with maximum permissible doses of 160 mg/day and 12 mg/day, respectively. We evaluated BP and proteinuria after changeover from the maximum dose of candesartan to the maximum dose of valsartan, in 55 poorly controlled hypertensive patients undergoing candesartan treatment who were unable to achieve optimal BP according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004). We measured BP and pulse rate and assessed urinary protein excretion (UPE) before and after changeover. Changeover was associated with decreases in systolic BP and diastolic BP from 158/89 mmHg to 150/86 mmHg (p<0.01). Changeover was also associated with a reduction in UPE adjusted to urinary creatinine from 0.35±0.19 g/g creatinine to 0.19±0.37 g/g creatinine (p=0.0271) in patients who had high urinary protein levels prior to changeover without significant decreases in BP (p=0.0184). According to multiple regression analysis, higher UPE (p<0.0001) and a lower glomerular filtration rate (GFR) (p=0.0011) prior to changeover were independently correlated with reduction in UPE. Our results suggest that the maximum dose of valsartan is more effective than the maximum dose of candesartan for reducing BP and proteinuria.
Association between mycoplasma pneumoniae infection and asthma : a meta-analysis and systematic reviews

Mycoplasma pneumoniae (MP) is caused by both upper and lower respiratory infections and could lead to serious complications. Recent publications have revealed that MP is associated with asthma; however, a single study may be affected by many factors and is controversial. In this study, a meta-analysis was performed to review the potential association between asthma occurrence and MP infection. According to the inclusion and exclusion criteria, an electronic search of the PubMed database identified 11 case-control studies involving a total of 1069 patients and 854 control cases. This meta-analysis showed that asthma patients had an MP antibody titer that was 2.69 times significantly higher than the control group (P = 0.0001, OR = 2.69, 95% CI: 1.62-4.46). These results indicate a strong relationship between MP infection and asthma.