Miracle-dz/UniFAR-FTUs huggingface dataset:
Degeneration and Regeneration of Murine Skeletal Neuromuscular Junctions after Intramuscular Injection with a Sublethal Dose of Clostridium sordellii Lethal Toxin

ABSTRACT Clostridium sordellii lethal toxin (LT), a 250-kDa protein which is the bacteria's major virulence factor, belongs to a family of large clostridial cytotoxins which glucosylate small GTP-binding proteins. Here, we report the results of our ex vivo analysis of the structure and function of skeletal neuromuscular tissue obtained from mice at various times after intramuscular injection of a sublethal dose of LT (0.25 ng/g of body wt). The toxin caused, within 24 h, pronounced localized edema, inflammation, myofibril disassembly, and degeneration of skeletal muscle fibers in the injected area, and it glucosylated the muscle tissue's small GTPases. Regeneration of the damaged fibers was evident 6 to 9 days postinjury and was completed by 60 days. The expression of dystrophin, laminin, and fast and neonatal myosin in regenerating fibers, detected by immunofluorescence microscopy, confirmed that LT does not impair the high regenerative capacity of murine skeletal muscle fibers. Functional studies revealed that LT affects muscle contractility and neuromuscular transmission. However, partial recovery of nerve-evoked muscle twitches and tetanic contractions was observed by day 15 postinjection, and extensive remodeling of the neuromuscular junction's nerve terminals and clusters of muscle acetylcholine receptors was still evident 30 days postinjection. In conclusion, to the best of our knowledge, this is the first report to characterize the degeneration and regeneration of skeletal neuromuscular tissue after in vivo exposure to a large clostridial cytotoxin. In addition, our data may provide an explanation for the severe neuromuscular alterations accompanying wound infections caused by C. sordellii.
Experimental infections with Cooperia oncophora (Railliet, 1918) in calves. Results of single infections with two graded dose levels of larvae

SUMMARY Two experiments were carried out in which calves reared parasite-free were infected with a single dose of 3rd-stage larvae of Cooperia oncophora. In the first experiment the calves received 20000 or 200000 infective larvae and they were autopsied 28 or 56 days after the infection. In the second experiment the doses were the same but the animals were killed 14, 84 or 140 days after infection. If a dose of 20000 was given, clinical signs were never observed, while at a dose level of 200000 the weight gain was less on 56 and 84 days after the infection compared with the low-infected groups or the control animals. After 140 days the differences in weight gain were compensated. Faecal egg output was higher in the 200000 groups only in the first period of patency, thereafter the calves in the 20000 groups produced more. No obvious differences between the two infection levels were observed with regard to the haematological data. In the low-infected groups worm counts were only slightly lower when the results after 28 days were compared with those after 56 days. Also, the worm numbers after 14 days were almost equal to those after 84 days, while at 140 days 1 animal still had the same number, the other one had lost its worm burden. In the high-infected groups the worm loss was much quicker. After 28 days a great part of the population had already been lost. Obviously, at the 200000 level the reaction of the host against the parasite was much stronger. Adult worms were expelled at a higher rate than early 4th-larval stages. In the first experiment worm measurements revealed differences between the length of females, males and spicules of males, these being significantly longer in the low-infected groups. Analysis of the distribution of worms over the small intestine showed that in the low-infected groups worms were mainly restricted to the first 6 metres. In the high-infected groups the worm population was distributed more evenly over the whole small intestine.
Mitochondrial Targeting of the Arabidopsis F1-ATPase γ-Subunit via Multiple Compensatory and Synergistic Presequence Motifs[W]

This work dissects the function of the N-terminal presequence of the Arabidopsis F1-ATPase γ-subunit, identifying multiple motifs that act at different steps of import to target this protein to the mitochondria. These motifs exhibit complex functional relationships, with some acting redundantly and others working synergistically. The majority of mitochondrial proteins are encoded in the nuclear genome and imported into mitochondria posttranslationally from the cytosol. An N-terminal presequence functions as the signal for the import of mitochondrial proteins. However, the functional information in the presequence remains elusive. This study reports the identification of critical sequence motifs from the presequence of Arabidopsis thaliana F1-ATPase γ-subunit (pFAγ). pFAγ was divided into six 10–amino acid segments, designated P1 to P6 from the N to the C terminus, each of which was further divided into two 5–amino acid subdivisions. These P segments and their subdivisions were substituted with Ala residues and fused to green fluorescent protein (GFP). Protoplast targeting experiments using these GFP constructs revealed that pFAγ contains several functional sequence motifs that are dispersed throughout the presequence. The sequence motifs DQEEG (P4a) and VVRNR (P5b) were involved in translocation across the mitochondrial membranes. The sequence motifs IAARP (P2b) and IAAIR (P3a) participated in binding to mitochondria. The sequence motifs RLLPS (P2a) and SISTQ (P5a) assisted in pulling proteins into the matrix, and the sequence motif IAARP (P2b) functioned in Tom20-dependent import. In addition, these sequence motifs exhibit complex relationships, including synergistic functions. Thus, multiple sequence motifs dispersed throughout the presequence are proposed to function cooperatively during protein import into mitochondria.
The parameterization of all plants stabilized by a proportional-derivative controller

In this paper, we examine the parameterization of all plants stabilized by a proportional-derivative (PD) controller. A PD controller is a kind of Proportional-Integral-Derivative (PID) controllers. The PID controller structure is the most widely used one in industrial applications. Recently, if stabilizing PID controllers for the plant exist, the parameterization of all stabilizing PID controllers has been considered. However, no paper examines the parameterization of all plants stabilized by a PID controller. In this paper, we clarify the parameterization of all plants stabilized by a PD controller. In addition, we present the parameterization of all stabilizing PD controllers for the plant stabilized by a PD controller.
Structural and functional basis of protein phosphatase 5 substrate specificity

Significance The activity of many proteins is dependent on molecular chaperones and their accessory proteins, cochaperones. The ability of a cohort of kinases, many of which are oncogenic, to transduce signals is promoted by the heat shock protein 90 (Hsp90) chaperone and Cdc37 cochaperone, and requires the removal of a phosphate from Cdc37 by protein phosphatase 5 (PP5). We present the crystal structure of PP5 with Cdc37 trapped in the active site. The structure reveals how PP5 can associate with different substrates and previously unknown determinants of specificity. Our findings show kinase release from the chaperone complex is critically dependent on this dephosphorylation and that combined inhibition of both Hsp90 and PP5 could provide an effective therapeutic strategy for treating cancers addicted to these kinases. The serine/threonine phosphatase protein phosphatase 5 (PP5) regulates hormone- and stress-induced cellular signaling by association with the molecular chaperone heat shock protein 90 (Hsp90). PP5-mediated dephosphorylation of the cochaperone Cdc37 is essential for activation of Hsp90-dependent kinases. However, the details of this mechanism remain unknown. We determined the crystal structure of a Cdc37 phosphomimetic peptide bound to the catalytic domain of PP5. The structure reveals PP5 utilization of conserved elements of phosphoprotein phosphatase (PPP) structure to bind substrate and provides a template for many PPP–substrate interactions. Our data show that, despite a highly conserved structure, elements of substrate specificity are determined within the phosphatase catalytic domain itself. Structure-based mutations in vivo reveal that PP5-mediated dephosphorylation is required for kinase and steroid hormone receptor release from the chaperone complex. Finally, our data show that hyper- or hypoactivity of PP5 mutants increases Hsp90 binding to its inhibitor, suggesting a mechanism to enhance the efficacy of Hsp90 inhibitors by regulation of PP5 activity in tumors.
[Pre- and postoperative functional status of patients subjected to anterior cruciate ligament reconstruction associated with knee dislocation].

INTRODUCTION The injury of the cruciate ligaments secondary to knee dislocation is caused by high energy trauma; its incidence rate is less than 0.02%; there are multiple treatments, with surgery being the most common one. OBJECTIVE To determine the functional characteristics of patients who underwent cruciate ligament plasty and sustained knee dislocation. MATERIAL AND METHODS An observational, prospective, cross-sectional study was conducted including all adult patients with a diagnosis of cruciate ligament injury resulting from knee dislocation who were surgically treated from January 2006 to December 2007. Two knee functional assessment scales were used. RESULTS A total of 16 patients were included, 12 males and 4 females; mean age was 32.1 years. The Knee Society Clinical Rating Scale had a positive correlation with the Lysholm Knee Scoring Scale (r = 0.836) with p = 0.001. DISCUSSION The functional results of patients treated surgically are diverse. This study was not conducted as a controlled clinical trial due to the absence of randomization, which was not possible due to the infrequency of the condition. CONCLUSIONS It will be necessary to confirm the results after a longer follow-up and in a comparative, double-blind study of patients undergoing surgery.
An improved high throughput heteroduplex mutation detection system for screening BRCA2 mutations—fluorescent mutation detection (F‐MD)

We describe an improved, fast, automated method for screening large genes such as BRCA2 for germline genomic mutations. The method is based on heteroduplex analysis, and has been adapted for a high throughput application by combining the fluorescent technology of automated sequencers and robotic sample handling. This novel approach allows the entire BRCA2 gene to be screened with appropriate overlaps in four lanes of an ABI 377 gel. The method will detect all types of mutations, especially point mutations, more reliably and robustly than other commonly used conformational sensitive methods (e.g. CSGE). In addition we show that this approach, which relies on band shift detection, is able to detect single base substitutions that have hitherto only been detectable by direct sequencing methods. Hum Mutat 17:220–232, 2001. © 2001 Wiley‐Liss, Inc.
Further empirical research on Diffusion Theory Paradigm applied in Network News Communication of crisis event

Based on our 2010's study that applied the Diffusion Theory Paradigm to analyze the Network News Communication of Crisis Event, this paper names the idea that the cumulated number of online news discussion follows the S-shaped curve over time in Diffusion Theory field as “Liang - Lv” Hypothesis. Then, it test the “Liang - Lv” Hypothesis for advancing the research by using more samples. This paper focuses on a single piece of news and goes along two study paths. One of them is the one-news-more-websites path; the other is the more-news-one-website path.
Market Efficiency of Ruble-RMB Exchange Rates: Long-run Equilibrium, VAR Estimates and Granger Causality Tests

China-Russia Ruble-RMB currency swap agreement may have long-run and short-run exchange risks for China. This paper mainly aims to investigate the informational efficiency of Ruble-RMB foreign exchange market. Methods used include the ADF and PP tests, the Perron test, the Johansen trace and Engle-Granger tests, vector autoregressive model and Granger causality test. Cointegration does not exist between the exchange rates of Ruble, dollar, euro, yen and pound to RMB, suggesting long-run informationally efficient. We constructed a first-differenced VAR for these exchange rates. We find a unidirectional Granger causality from euro-RMB exchange rate to Ruble-RMB exchange rate, suggesting short-run informationally inefficient. Hence, the Ruble-RMB foreign exchange market violates the efficient market hypothesis (EMH) and the Ruble-RMB currency swaps may not receive diversification benefits in the short run. KEYWORD: Cointegration; exchange rate; efficient market hypothesis; Granger causality; structural break; vector autoregressive model International Conference on Social Science, Education Management and Sports Education (SSEMSE 2015) © 2015. The authors Published by Atlantis Press 1327 Exchange rates comprise those of Ruble to RMB (RUB) and US dollar to RMB (DOLLAR). They also include those of the euro to RMB (EURO), Japanese yen to RMB (YEN), and pound to RMB (POUND). Excluding weekends and holidays, data has 963 daily observations from 4 January 2011 to December 24, 2014 (China Foreign Exchange 2014). Table 1. Statistics for the exchange rate of one hundred foreign currency to RMB. Variable DOLLAR EURO YEN POUND RUB Mean 627.80 837.99 7.05 1004.89 19.55 Median 628.60 829.65 7.41 1002.85 19.84 Maximum 663.49 964.45 8.37 1085.18 23.77 Minimum 609.30 748.48 5.05 915.62 8.82 Standard Deviation 13.45 45.00 1.01 34.74 2.44 Skewness 0.72 0.80 (0.17) (0.02) (0.98) Kurtosis 2.70 3.14 1.38 2.37 5.02 Jarque-Bera 85.75 102.56 109.63 16.03 318.42 p-value 0.00 0.00 0.00 0.00 0.00
Shedding of Microvesicles from Microglia Contributes to the Effects Induced by Metabotropic Glutamate Receptor 5 Activation on Neuronal Death

Metabotropic glutamate (mGlu) receptor 5 is involved in neuroinflammation and has been shown to mediate reduced inflammation and neurotoxicity and to modify microglia polarization. On the other hand, blockade of mGlu5 receptor results in inhibition of microglia activation. To dissect this controversy, we investigated whether microvesicles (MVs) released from microglia BV2 cells could contribute to the communication between microglia and neurons and whether this interaction was modulated by mGlu5 receptor. Activation of purinergic ionotropic P2X7 receptor with the stable ATP analog benzoyl-ATP (100 μM) caused rapid MVs shedding from BV2 cells. Ionic currents through P2X7 receptor increased in BV2 cells pretreated for 24 h with the mGlu5 receptor agonist CHPG (200 μM) as by patch-clamp recording. This increase was blunted when microglia cells were activated by exposure to lipopolysaccharide (LPS; 0.1 μg/ml for 6 h). Accordingly, a greater amount of MVs formed after CHPG treatment, an effect prevented by the mGlu5 receptor antagonist MTEP (100 μM), as measured by expression of flotillin, a membrane protein enriched in MVs. Transferred MVs were internalized by SH-SY5Y neurons where they did not modify neuronal death induced by a low concentration of rotenone (0.1 μM for 24 h), but significantly increased rotenone neurotoxicity when shed from CHPG-treated BV2 cells. miR146a was increased in CHPG-treated MVs, an effect concealed in MVs from LPS-activated BV2 cells that showed per se an increase in miRNA146a levels. The present data support a role for microglia-shed MVs in mGlu5-mediated modulation of neuronal death and identify miRNAs as potential critical mediators of this interaction.
Synaptic ionotropic glutamate receptors and plasticity are developmentally altered in the CA1 field of Fmr1 knockout mice

Fragile X syndrome is one of the most common forms of mental retardation, yet little is known about the physiological mechanisms causing the disease. In this study, we probed the ionotropic glutamate receptor content in synapses of hippocampal CA1 pyramidal neurons in a mouse model for fragile X (Fmr1 KO2). We found that Fmr1 KO2 mice display a significantly lower AMPA to NMDA ratio than wild‐type mice at 2 weeks of postnatal development but not at 6–7 weeks of age. This ratio difference at 2 weeks postnatally is caused by down‐regulation of the AMPA and up‐regulation of the NMDA receptor components. In correlation with these changes, the induction of NMDA receptor‐dependent long‐term potentiation following a low‐frequency pairing protocol is increased in Fmr1 KO2 mice at this developmental stage but not later in maturation. We propose that ionotropic glutamate receptors, as well as potentiation, are altered at a critical time point for hippocampal network development, causing long‐term changes. Associated learning and memory deficits would contribute to the fragile X mental retardation phenotype.
The Novel Type II Prolyl 4-Hydroxylase Is the Main Enzyme Form in Chondrocytes and Capillary Endothelial Cells, whereas the Type I Enzyme Predominates in Most Cells*

Procollagen-proline dioxygenase (EC 1.14.11.2), an α2β2 tetramer in vertebrates, plays a central role in the synthesis of all collagens. Recently an isoform of the α subunit, the α(II) subunit, was characterized in man and mouse and found to form a tetramer with the same β subunit as the previously known α(I) subunit. We report here that the (α(I))2β2 type I tetramer is the main enzyme form in most cell types and tissues and that its contribution to total prolyl 4-hydroxylase activity in cultured cells increases in confluence. Surprisingly, however, the (α(II))2β2 type II enzyme was found to represent at least about 70% of the total prolyl 4-hydroxylase activity in cultured mouse chondrocytes and about 80% in mouse cartilage, the corresponding percentage in mouse bone being about 45% and that in many other mouse tissues about 10% or less. Immunofluorescence studies on samples from a fetal human foot confirmed these data and additionally indicated that the type II enzyme represents the main or only enzyme form in capillary endothelial cells. Thus the type II prolyl 4-hydroxylase is likely to play a major role in the development of cartilages and cartilaginous bones and also of capillaries.
Gender dimorphism following injury: making the connection from bench to bedside

Despite ongoing prevention efforts, injury remains the leading cause of mortality over the first three decades of life in the United States. Those who survive their initial injury continue to be plagued with the development of sepsis and multiple organ failure and their attributable morbidity and mortality. An important and persistent finding has been that males and females respond differently following traumatic injury and hemorrhagic shock. A significant advancement in the experimental understanding of the gender dimorphism in response to trauma‐hemorrhage and sepsis has occurred. Experimental evidence for the differential effects of sex hormones on cell‐mediated immunity and organ system tolerance of shock continues to expand. Clinical studies, however, have been unable to reproduce these laboratory bench findings consistently. There continues to be a divide between the “bench and bedside” in regard to our understanding of gender‐based differences following injury. Relative to controlled animal experiments, predisposing comorbidities, injury characteristics, and a lack of information about the hormone milieu of the trauma patient disallow reproducible results from clinical analyses. Continued clinical research into potential sex hormone‐based differences, genetic differences, and the cellular and molecular mechanisms responsible for these gender‐based differential responses is required to close this gap. This may ultimately promote therapeutic interventions, which will allow for improved outcomes for males and females in the near future.
Comparison of mean diameters of silicon spheres measured with both spherical fizeau-interferometers of the PTB

The sphere interferometer 2 of the PTB was set up to undercut the measurement uncertainty already reached by the sphere interferometer 1 of the PTB. This was necessary for being able to meet the conditions of the CCM for a redefinition of the SI-unit kilogram where the sphere interferometers are used to measure the volume of the Avogadro spheres. This paper summarizes the comparison measurements between both interferometers and their results.
Brk Activates Rac1 and Promotes Cell Migration and Invasion by Phosphorylating Paxillin

ABSTRACT Brk (for breast tumor kinase) is a nonreceptor tyrosine kinase containing SH3, SH2, and tyrosine kinase catalytic domains. Brk was originally identified from a human metastatic breast tumor, and its overexpression is frequently observed in breast cancer and several other cancer types. However, the molecular mechanism by which this kinase participates in tumorigenesis remains poorly characterized. In the present study, we not only identified paxillin as the binding partner and substrate of Brk but also discovered a novel signaling pathway by which Brk mediates epidermal growth factor (EGF)-induced paxillin phosphorylation. We show that EGF stimulation activates the catalytic activity of Brk, which in turn phosphorylates paxillin at Y31 and Y118. These phosphorylation events promote the activation of small GTPase Rac1 via the function of CrkII. Through this pathway, Brk is capable of promoting cell motility and invasion and functions as a mediator of EGF-induced migration and invasion. In accordance with these functional roles, Brk translocates to membrane ruffles, where it colocalizes with paxillin during cell migration. Together, our findings identify novel signaling and biological roles of Brk and indicate the first potential link between Brk and metastatic malignancy.
Monetary Policy, Income Growth and Price Stability in Malaysia

Malaysia is a rapidly progressing high middle-income economy. As a highly open economy with an increasingly liberalized financial sector, the implementation of a comprehensive macroeconomic policy is a challenging task. This article enquires into the efficacy of money in raising income and stabilizing price level, and it also attempts to identify the effective component of money in this direction over the period 1971–2012. The autoregressive distributed lag (ARDL) approach to co-integration confirms the existence of a long-run relationship among money, income and price level. Error correction mechanism (ECM–ARDL) models with a battery of econometric techniques such as vector autoregression (VAR) model, the Wald test and innovation accounting confirm that only M1 money supply causes a raise in income. Price level, on the other hand, negatively contributes to income. Three components of money supply namely M1, M2 and M3 lead to a raise in price or inflation where M2 money is found to be the most potent component provoking inflation. The role of income is insignificant. Competent management of monetary instruments, therefore, may promote higher income maintaining stability in price level. JEL Classification: E52, E31