Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct External Signals Trigger Sequential Release of Apical Organelles during Erythrocyte Invasion by Malaria Parasites

The invasion of erythrocytes by Plasmodium merozoites requires specific interactions between host receptors and parasite ligands. Parasite proteins that bind erythrocyte receptors during invasion are localized in apical organelles called micronemes and rhoptries. The regulated secretion of microneme and rhoptry proteins to the merozoite surface to enable receptor binding is a critical step in the invasion process. The sequence of these secretion events and the external signals that trigger release are not known. We have used time-lapse video microscopy to study changes in intracellular calcium levels in Plasmodium falciparum merozoites during erythrocyte invasion. In addition, we have developed flow cytometry based methods to measure relative levels of cytosolic calcium and study surface expression of apical organelle proteins in P. falciparum merozoites in response to different external signals. We demonstrate that exposure of P. falciparum merozoites to low potassium ion concentrations as found in blood plasma leads to a rise in cytosolic calcium levels through a phospholipase C mediated pathway. Rise in cytosolic calcium triggers secretion of microneme proteins such as the 175 kD erythrocyte binding antigen (EBA175) and apical membrane antigen-1 (AMA-1) to the merozoite surface. Subsequently, interaction of EBA175 with glycophorin A (glyA), its receptor on erythrocytes, restores basal cytosolic calcium levels and triggers release of rhoptry proteins. Our results identify for the first time the external signals responsible for the sequential release of microneme and rhoptry proteins during erythrocyte invasion and provide a starting point for the dissection of signal transduction pathways involved in regulated exocytosis of these key apical organelles. Signaling pathway components involved in apical organelle discharge may serve as novel targets for drug development since inhibition of microneme and rhoptry secretion can block invasion and limit blood-stage parasite growth.
Class I and Class II Chitin Synthases Are Involved in Septum Formation in the Filamentous Fungus Aspergillus nidulans

ABSTRACT The class II and class I chitin synthases of the filamentous fungus Aspergillus nidulans are encoded by chsA and chsC, respectively. Previously, we presented several lines of evidence suggesting that ChsA and ChsC have overlapping functions in maintaining cell wall integrity. In order to determine the functions of these chitin synthases, we employed electron and fluorescence microscopy and investigated in detail the cell wall of a ΔchsA ΔchsC double mutant (ΔAC mutant) along with the localization of ChsA and ChsC. In the lateral cell wall of the ΔAC mutant, electron-transparent regions were thickened. Septa of the ΔAC mutant were aberrantly thick and had a large pore. Some septa were located abnormally close to adjacent septa. A functional hemagglutinin (HA)-tagged ChsA (HA-ChsA) and a functional FLAG-tagged ChsC (FLAG-ChsC) were each localized to a subset of septation sites. Comparison with the localization pattern of actin, which is known to localize at forming septa, suggested that ChsA and ChsC transiently exist at the septation sites during and shortly after septum formation. Double staining of HA-ChsA and FLAG-ChsC indicated that their localizations were not identical but partly overlapped at the septation sites. Fluorescence of FLAG-ChsC, but not of HA-ChsA, was also observed at hyphal tips. These data indicate that ChsA and ChsC share overlapping roles in septum formation.
Worldwide Reported Use of IV Tissue Plasminogen Activator for Acute Ischemic Stroke

Background and Purpose Intravenous tissue plasminogen activator is the most effective treatment for acute ischemic stroke, and its use may therefore serve as an indicator of the available level of acute stroke care. The greatest burden of stroke is in low- and middle-income countries, but the extent to which intravenous tissue plasminogen activator is used in these countries is unreported. Summary of Review A systematic review was performed searching each country name AND ‘stroke’ OR ‘tissue plasminogen activator’ OR ‘thrombolysis’ using PubMed, Embase, Global Health, African Index Medicus, and abstracts published in the International Journal of Stroke (Jan. 1, 1996–Oct. 1, 2012). The reported use of intravenous tissue plasminogen activator was then analyzed according to country-level income status, total expenditure on health per capita, and mortality and disability-adjusted life years due to stroke. There were 118 780 citations reviewed. Of 214 countries and independent territories, 64 (30%) reported use of intravenous tissue plasminogen activator for acute ischemic stroke in the medical literature: 3% (1/36) low-income, 19% (10/54) lower-middle-income, 33% (18/54) upper-middle-income, and 50% (35/70) high-income-countries (test for trend, P < 0·001). When considering country-level determinants of reported intravenous tissue plasminogen activator use for acute ischemic stroke, total healthcare expenditure per capita (odds ratio 3·3 per 1000 international dollar increase, 95% confidence interval 1·4–9·9, P = 0·02) and reported mortality rate from cerebrovascular disease (odds ratio 1·02, 95% confidence interval 0·99–1·06, P = 0·02) were significant, but reported disability-adjusted life years from cerebrovascular diseases and gross national income per capita were not (P > 0·05). Of the 10 countries with the highest disability-adjusted life years due to stroke, only one reported intravenous tissue plasminogen activator use. Conclusions By reported use, intravenous tissue plasminogen activator for acute ischemic stroke is available to some patients in approximately one-third of countries. Access to advanced acute stroke care is most limited where the greatest burden of cerebrovascular disease is reported.
System propose for Be acquainted with newborn cry emotion using linear frequency cepstral coefficient

In this paper, we mainly paying attention on mechanization of Infant's Cry. For this implementation we use LFCC for feature extraction and VQ codebook for toning samples using LBG algorithm. The newborn crying samples composed from various crying baby having 0-6 months age. There are 27 babie's sound as training data, each of which represents the 7 hungry infant cries, 4 sleepy infant cries, 10 in pain infant cries, and 6 uncomfortable infant cries. The testing data is one of the traning newborn crying sample. The discovery of infant cries based the least amount distance of Euclidean distance. The, classification of the cry in four classes neh for hunger owh for sleepy, heh for discomfort, eair for lower gas. Here for classification of the cry our system is alienated into two phases. First is training phase, in which LFCC is used for feature extraction, and then VQ codebooks are engender to compress the feature vectors. Second is the testing stage in which features extraction and codebook production of samples are recurring. Here, estimation of the codebook blueprint of samples to the all the existing patterns in the database are carried based on Euclidian distance between them. LFCC efficiently take into safekeeping the lower as well as higher frequency characteristics than MFCC, hence we will get high-quality results over MFCC.
Enabling PROFINET devices to work in IoT: Characterization and requirements

The rise of Internet of Things (IoT) has impacted the industrial automation world. Traditional fleldbus and new fieldbus based on Real Time Ethernet (as PROFINET) have been challenged to include IoT solutions, whose real possibilities are still under evaluation. On the other hand, there are properties of industrial automation devices (e.g. robustness, “proven in use”, explosion proof) that may be useful also in typical IoT scenarios (e.g. building automation). Therefore, the paper proposes a reversed approach, where a new architecture enables the use of existing, legacy, industry-grade devices (e.g. PROFINET Sensors, actuators, and Programmable Logic controllers - PLC) to be used across the Internet. In the proposed system, the PROFINET network can be put into work by means of transparent proxies that use IoT paradigms. The paper presents and discusses a set of basic requirements and a preliminary performance evaluation of a sample application. The results show that the 99-percentile of the transfer time (from proxy to proxy) in the proposed system is less than 100ms, and it is stable even varying the PROFINET cycle time.
Parent-teacher concordance for DSM-IV attention-deficit/hyperactivity disorder in a clinic-referred sample.

OBJECTIVE To examine concordance between parent and teacher reports of DSM-IV attention-deficit/hyperactivity disorder (ADHD) and its symptoms. METHOD Parents and teachers of 74 clinically referred children were interviewed using the ADHD module of the Diagnostic Interview Schedule for Children. Parent-teacher agreement for the diagnosis of ADHD and its subtypes, as defined in DSM-IV, as well as parent-teacher concordance of in-school ADHD symptoms, was examined. RESULTS Agreement between parents and teachers was found to be relatively poor, with virtually no agreement for individual ADHD subtypes. Diagnoses based on either parent or teacher report frequently yielded a diagnosis of either inattentive or hyperactive-impulsive subtype of ADHD. However, when cross-informant data were used to form diagnoses, these subtypes became relatively rare, with most cases meeting criteria for ADHD combined type. In addition, parent reports of in-school behavior were more highly correlated with their own reports of their child's behavior at home than with teacher reports of their child's behavior in school. CONCLUSIONS These data suggest that the diagnosis of ADHD inattentive or hyperactive-impulsive subtype based on data from a single informant may be of questionable validity, and they point to the importance of using multiple informants when diagnosing this disorder in clinically referred samples.
Implicit-Explicit Runge-Kutta Schemes for Hyperbolic Systems and Kinetic Equations in the Diffusion Limit

We consider implicit-explicit (IMEX) Runge--Kutta (R-K) schemes for hyperbolic systems with stiff relaxation in the so-called diffusion limit. In such a regime the system relaxes towards a convection-diffusion equation. The first objective of this paper is to show that traditional partitioned IMEX R-K schemes will relax to an explicit scheme for the limit equation with no need of modification of the original system. Of course the explicit scheme obtained in the limit suffers from the classical parabolic stability restriction on the time step. The main goal of this paper is to present an approach, based on IMEX R-K schemes, that in the diffusion limit relaxes to an IMEX R-K scheme for the convection-diffusion equation, in which the diffusion is treated implicitly. This is achieved by a novel reformulation of the problem, and subsequent application of IMEX R-K schemes to it. An analysis of such schemes to the reformulated problem shows that the schemes reduce to IMEX R-K schemes for the limit equation, unde.
Toxic (Pb, Cd, Hg) and essential (Fe, Cu, Zn, Mn) metal content of liver tissue of some domestic and bush animals in Ghana

Accumulation of toxic metals in liver, a rich natural source of essential elements, can present health risks to regular consumers of liver. A total of 35 fresh liver samples of cow, sheep, goat, pig, grass-cutter (Thryonomys swinderianus), gaint rat (Cricetomys gambianus), red deer (Cervus elaphus), chicken and antelope (Antilocapra americana) were obtained from three different markets in Accra and Kumasi, Ghana. Samples were analyzed using atomic absorption spectrometry and an automatic mercury analyzer. Levels of iron in the grass-cutter and pig of 500.5–645.4 mg kg−1 were the highest in the animal livers examined. Mn concentrations were highest in grass-cutter and rat liver, ranging 16.5–30.2 mg kg−1. The safe Cu and Zn permissible limits of 20 and 50 mg kg−1 were exceeded in 70 and 75% of the liver samples, respectively. Generally, for each animal group studied, at least 50% of the sample livers exceeded the Cd permissible limit of 0.5 mg kg−1. The levels of Pb, which ranged 1.3–13.8 mg kg−1, exceeded the proposed European Commission (EC) limit of 0.5 mg kg−1. Care must be taken by regular consumers of the iron-rich animal livers of grass-cutter, pig and rat because they also had the highest levels of Pb (in grass-cutter and pig) and Cd (in grass-cutter, rat and pig). The liver samples analyzed for Hg had values far below the permissible limit of 0.5 mg kg−1.
Injuries and Medical Issues in Softball

Softball is enjoyed by millions of female and male athletes of all ages and competitive levels. Windmill pitchers are at risk for developing overuse injuries in the throwing arm. Improper mechanics and lack of pitch counts may increase the risk for developing a pitching-related injury. Softball-related overuse injuries include proximal biceps tendinitis, upper extremity stress fractures, and ulnar neuritis. Acute injuries commonly occur in the lower extremity and include both fractures and ligamentous injuries. Sliding injuries account for a significant number of these lower extremity injuries. The addition of breakaway bases and mandatory use of protective headgear by defensive players may decrease acute injuries commonly seen in softball. Off-season programs should stress proper throwing and sliding mechanics, core conditioning, and a lower extremity neuromuscular education program.
Studies on the Mechanism of Epinephrine-induced Hyperglycemia in Man: Evidence for Participation of Pancreatic Glucagon Secretion

In man, epinephrine induces increases in plasma levels of glucagon, a lipolytic and hyperglycemic hormone. To determine glucagon's contribution to this hyperglycemia and lipolysis, the effects of inhibition of pancreatic alpha-cell responses to epinephrine were investigated with somatostatin and adrenergic receptor blockade. To avoid ambiguities that might result from concomitant changes in endogenous insulin secretion, these studies were performed in juvenile-type, insulin-deficient diabetic subjects. Compared with normal subjects, the diabetics had excessive glucagon responses to epinephrine, which had been infused to attain circulating levels within the range found in man in severe stress. Both somatostatin and propranolol completely prevented glucagon responses and diminished the glycemic response to epinephrine by 40 to 50 per cent. Free fatty acid responses to epinephrine were completely prevented by propranolol but unaffected with somatostatin. Phentolamine had no effect on glucose, free fatty acid, or glucagon responses to epinephrine. These studies demonstrate that epinephrine, via a betaadrenergic receptor mechanism, causes excessive plasma glucagon elevation in human diabetes mellitus and indicate that this hyperglucagonemia participates in the hyperglycemic, but not the lipolytic, response to epinephrine. Catecholamine-induced hyperglucagonemia may thus provide an additional explanation for the deterioration in carbohydrate tolerance associated with stress.
Metabolic analysis of antibody producing CHO cells in fed‐batch production

Chinese hamster ovary (CHO) cells are commonly used for industrial production of recombinant proteins in fed batch or alternative production systems. Cells progress through multiple metabolic stages during fed‐batch antibody (mAb) production, including an exponential growth phase accompanied by lactate production, a low growth, or stationary phase when specific mAb production increases, and a decline when cell viability declines. Although media composition and cell lineage have been shown to impact growth and productivity, little is known about the metabolic changes at a molecular level. Better understanding of cellular metabolism will aid in identifying targets for genetic and metabolic engineering to optimize bioprocess and cell engineering. We studied a high expressing recombinant CHO cell line, designated high performer (HP), in fed‐batch productions using stable isotope tracers and biochemical methods to determine changes in central metabolism that accompany growth and mAb production. We also compared and contrasted results from HP to a high lactate producing cell line that exhibits poor growth and productivity, designated low performer (LP), to determine intrinsic metabolic profiles linked to their respective phenotypes. Our results reveal alternative metabolic and regulatory pathways for lactate and TCA metabolite production to those reported in the literature. The distribution of key media components into glycolysis, TCA cycle, lactate production, and biosynthetic pathways was shown to shift dramatically between exponential growth and stationary (production) phases. We determined that glutamine is both utilized more efficiently than glucose for anaplerotic replenishment and contributes more significantly to lactate production during the exponential phase. Cells shifted to glucose utilization in the TCA cycle as growth rate decreased. The magnitude of this metabolic switch is important for attaining high viable cell mass and antibody titers. We also found that phosphoenolpyruvate carboxykinase (PEPCK1) and pyruvate kinase (PK) are subject to differential regulation during exponential and stationary phases. The concomitant shifts in enzyme expression and metabolite utilization profiles shed light on the regulatory links between cell metabolism, media metabolites, and cell growth. Biotechnol. Bioeng. 2013; 110: 1735–1747. © 2013 Wiley Periodicals, Inc.
4-(2'-Methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-iodobenzamido]ethyl] piperazine and 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p- fluorobenzamido]ethyl]piperazine, two new antagonists at pre- and postsynaptic serotonin-1A receptors.

p-MPPI [4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-iodobenzamido] ethylpiperazine] and p-MPPF [4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p- fluorobenzamido]ethyl]piperazine] competitively antagonized 5-HT1A receptor activation in the rat, as measured by hypothermia, forepaw treading and 5-HT turnover; they exhibited to partial agonist activity on any of these measures. When given i.p., p-MPPI and p-MPPF dose-dependently antagonized the hypothermia induced by 8-hydroxy-2- (di-n-propylamino)tetralin (8-OH-DPAT) (0.5 mg/kg), with approximate ID50 of 5 and 3 mg/kg, respectively. The inhibitory effect caused by a fixed dose of p-MPPI (6 mg/kg) or p-MPPF (3 mg/kg) was surmounted by higher doses of 8-OH-DPAT. p-MPPI and p-MPPF also attenuated the hypothermia induced by gepirone. Forepaw treading caused by 8-OH-DPAT (2 mg/kg) in reserpine-pretreated rats (1 mg/kg, s.c., 18-24 hr before the experiment) was dose-dependently antagonized by p-MPPI and p-MPPF with approximate ID50 of 3 and 0.7 mg/kg, respectively. p-MPPI also antagonized forepaw treading induced by 5-methoxy-N,N,-dimethyltryptamine (5-MeODMT) (5 mg/kg) and this antagonism was competitively overcome by higher doses of 5-methoxy-N,N,-dimethyltryptamine. p-MPPI and p-MPPF were able to antagonize the 8-OH-DPAT-(0.5 mg/kg) induced reduction in the 5-HIAA/5-HT ratio, a measure of 5-HT turnover in the hippocampus or striatum. No hypothermia or reciprocal forepaw treading was produced by either drug when given at doses as high as 10 mg/kg. Neither p-MPPI nor p-MPPF (10 mg/kg) given alone significantly altered the ratio of 5-HIAA/5-HT in the hippocampus or striatum. Also, binding of [3H]p-MPPF to hippocampal membranes was unaltered by the addition of 100 microM guanylyl-imidodiphosphate to the incubation medium. In conclusion, p-MPPI and p-MPPF behave, in vivo, as competitive antagonists of both postsynaptic 5-HT1A receptors and somatodendritic 5-HT1A autoreceptors.
Mangiferin ameliorates Porphyromonas gingivalis‐induced experimental periodontitis by inhibiting phosphorylation of nuclear factor‐&kgr;B and Janus kinase 1–signal transducer and activator of transcription signaling pathways

BACKGROUND AND OBJECTIVE Mangiferin is a natural polyphenol compound with anti-inflammatory properties. However, there have been few reports on the effect of mangiferin on periodontitis. Here, we investigated the anti-inflammatory effects of this compound on experimental periodontitis and the underlying mechanisms. MATERIAL AND METHODS Mice were inoculated with Porphyromonas gingivalis to induce periodontitis, and treated with mangiferin orally (50 mg/kg bodyweight, once a day) for 8 wk. Then, the alveolar bone loss was examined using a scanning electronic microscope. Expression of tumor necrosis factor-α (TNF-α) and the phosphorylation levels of nuclear factor-κB (NF-κB) and Janus kinase 1-signal transducer and activator of adhesion (JAK1-STAT) pathways in the gingival epithelium were detected using western blot analysis and immunohistochemical staining. RESULTS The results showed that mice with periodontitis exhibited greater alveolar bone loss, stronger expression of TNF-α and higher phosphorylation levels of NF-κB and JAK1-STAT1/3 pathways in gingival epithelia, compared with control mice with no periodontitis. Moreover, treatment with mangiferin could significantly inhibit alveolar bone loss, TNF-α production and phosphorylation of NF-κB and JAK1-STAT1/3 pathways in gingival epithelia. CONCLUSION Mangiferin has anti-inflammatory effects on periodontitis, which is associated with its ability to down-regulate the phosphorylation of NF-κB and JAK1-STAT1/3 pathways in gingival epithelia.
Ipsilateral cortical projections to areas 3a, 3b, and 4 in the macaque monkey

In the macaque monkey area 3a of the cerebral cortex separates area 4, a primary motor cortical field, from somatosensory area 3b, which has a subcortical input mainly from cutaneous mechanoreceptive neurons. That each of these cortical areas has a unique thalamic input was illustrated in the preceding paper. In the present experiments the cortical afferent projections to these 3 areas of the sensorimotor cortex monkey were visualized and compared, using 4 differentiable fluorescent dyes as axonal retrogradely transported labels. The cortical projection patterns to areas 3a, 3b, and 4 were similar in that they each consisted of (a) a “halo” of input from the immediately surrounding cortex, and (b) discrete projections from one or more remote cortical areas. However, the pattern of remote inputs from precentral, mesial, and posterior parietal cortex was different for each of the 3 cortical target areas. The cortical input configuration was least complex for area 3b, its remote input projecting mainly from insular cortex. The pattern of discrete cortical inputs to the motor area 4, however, was more complex, with projections from the cingulate motor area (24c/d), the supplementary motor area, postarcuate cortex, insular cortex, and postcentral areas 2/5. Area 3a, in addition to the proximal projections from the immediately surrounding cortex, also received input from the supplementary motor area, cingulate motor cortex, insular cortex, and areas 2/5. Thus, this pattern of cortical input to area 3a resembled more closely that of the adjacent motor rather than that of the somatosensory area 3b. Contrasting with this, however, the thalamic input to area 3a was largely from somatosensory VPLc (abbreviations from Olszewski [1952] The Thalamus of the Macaca mulatta. Basel: Karger) and not from VPLo (with input from cerebellum, and projecting to precentral motor areas). © 1993 Wiley‐Liss, Inc.