ResearchPad - anatomy-and-physiology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[A low caffeine dose improves maximal strength, but not relative muscular endurance in either heavier-or lighter-loads, or perceptions of effort or discomfort at task failure in females]]> https://www.researchpad.co/article/elastic_article_8324 The body of literature considering caffeine as an ergogenic aid has primarily considered typically aerobic based exercise, male participants and moderate-to large-caffeine doses. With this in mind the aim of this project was to explore the effects of a low-caffeine dose upon maximal voluntary contraction (MVC) and muscular endurance (time to task failure, TTF) at heavier-and lighter-loads.MethodsNineteen physically active, habitual caffeine consuming females randomly performed four testing conditions; two with a low-dose of caffeine (100 mg equating to mean = 1.5 ± 0.18 mg·kg−1) and two placebo conditions, where they performed a maximal strength test (MVC) knee extension at 45° followed by a task of relative muscular endurance (sustained isometric contraction for TTF) using either heavier-(70% MVC) and lighter-(30% MVC) loads. Each participant performed each load condition following both caffeine and placebo consumption. Immediately following cessation of the muscular endurance test participants were asked to report their rating of perceived effort (RPE) and rating of perceived discomfort (RPD).ResultsAnalyses revealed a significant effect for caffeine upon MVC compared to placebo (p = 0.007). We also found a significantly greater TTF for the lighter-compared to the heavier-load condition (p < 0.0001); however, there was no significant effect comparing caffeine to placebo (p = 0.2368), but insufficient precision of estimates to infer equivalence in either lighter-(p = 0.750) or heavier-load (p = 0.262) conditions. There were no statistically significant effects for caffeine compared with placebo, or lighter-compared with heavier-loads, for RPE and RPD (all p > 0.05). RPE was statistically equivalent between caffeine and placebo for both lighter-(p = 0.007) and heavier-load (p = 0.002) conditions and RPD for heavier-(p = 0.006) but not lighter-load (p = 0.136).DiscussionThis is the first study to demonstrate a positive effect on strength from a low caffeine dose in female participants. However, it is unclear whether caffeine positively impacts upon relative muscular endurance in either heavier-or lighter-loads. Further, both RPE and RPD appear to be relatively similar during isometric tasks performed to task failure independently of caffeine supplementation or load. These findings may have implications for persons wishing to avoid side-effects or withdrawal symptoms associated with larger caffeine doses whilst still attaining the positive strength responses. ]]> <![CDATA[Size matters: micro-evolution in Polynesian rats highlights body size changes as initial stage in evolution]]> https://www.researchpad.co/article/N2dd55868-5849-4fff-8cf7-11bb065f2041

Microevolutionary patterns in populations of introduced rodent species have often been the focus of analytic studies for their potential relevance to understanding vertebrate evolution. The Polynesian rat (Rattus exulans) is an excellent proxy species because of its wide geographic and temporal distribution: its native and introduced combined range spans half the globe and it has been living for at least seven centuries wherever it was introduced. The objective of this study was to assess the effects of long-term isolation (insularity; up to 4,000 years) and geographic variables on skull shape variation using geometric morphometrics. A sample of 513 specimens from 103 islands and four mainland areas was analysed. This study, to my knowledge the first to extensively sample introduced rats, analysed 59 two-dimensional landmarks on the skull. Landmarks were obtained in three separate aspects (dorsal, lateral, ventral skull view). The coordinate data were then subjected to a multivariate ordination analysis (principal components analysis, or PCA), multivariate regressions, and a canonical variates analysis (CVA). Three measures of disparity were evaluated for each view. The results show that introduced Polynesian rats evolve skull shapes that conform to the general mammalian interspecific pattern of cranial evolutionary allometry (CREA), with proportionally longer snouts in larger specimens. In addition, larger skulls are more tubular in shape than the smaller skulls, which are more balloon-shaped with a rounder and wider braincase relative to those of large skulls. This difference is also observed between the sexes (sexual dimorphism), due to the slightly larger average male size. Large, tubular skulls with long snouts are typical for Polynesia and Remote Oceania, where no native mammals occur. The greater disparity of Polynesian rats on mammal species-poor islands (’exulans-only’ region) provides further insight into how diversity may affect diversification through ecological release from predators and competitors.

]]>
<![CDATA[Bi-Level ventilation decreases pulmonary shunt and modulates neuroinflammation in a cardiopulmonary resuscitation model]]> https://www.researchpad.co/article/Nfc29e3d5-af29-453c-bdc8-d5378300b77b

Background

Optimal ventilation strategies during cardiopulmonary resuscitation are still heavily debated and poorly understood. So far, no convincing evidence could be presented in favour of outcome relevance and necessity of specific ventilation patterns. In recent years, alternative models to the guideline-based intermittent positive pressure ventilation (IPPV) have been proposed. In this randomized controlled trial, we evaluated a bi-level ventilation approach in a porcine model to assess possible physiological advantages for the pulmonary system as well as resulting changes in neuroinflammation compared to standard measures.

Methods

Sixteen male German landrace pigs were anesthetized and instrumented with arterial and venous catheters. Ventricular fibrillation was induced and the animals were left untreated and without ventilation for 4 minutes. After randomization, the animals were assigned to either the guideline-based group (IPPV, tidal volume 8–10 ml/kg, respiratory rate 10/min, FiO21.0) or the bi-level group (inspiratory pressure levels 15–17 cmH2O/5cmH2O, respiratory rate 10/min, FiO21.0). Mechanical chest compressions and interventional ventilation were initiated and after 5 minutes, blood samples, including ventilation/perfusion measurements via multiple inert gas elimination technique, were taken. After 8 minutes, advanced life support including adrenaline administration and defibrillations were started for up to 4 cycles. Animals achieving ROSC were monitored for 6 hours and lungs and brain tissue were harvested for further analyses.

Results

Five of the IPPV and four of the bi-level animals achieved ROSC. While there were no significant differences in gas exchange or hemodynamic values, bi-level treated animals showed less pulmonary shunt directly after ROSC and a tendency to lower inspiratory pressures during CPR. Additionally, cytokine expression of tumour necrosis factor alpha was significantly reduced in hippocampal tissue compared to IPPV animals.

Conclusion

Bi-level ventilation with a constant positive end expiratory pressure and pressure-controlled ventilation is not inferior in terms of oxygenation and decarboxylation when compared to guideline-based IPPV ventilation. Additionally, bi-level ventilation showed signs for a potentially ameliorated neurological outcome as well as less pulmonary shunt following experimental resuscitation. Given the restrictions of the animal model, these advantages should be further examined.

]]>
<![CDATA[Translation, validation and test–retest reliability of the VISA-G patient-reported outcome tool into Danish (VISA-G.DK)]]> https://www.researchpad.co/article/Nf89af4f4-10ef-47f3-8cef-52d177514e1a

The Victorian Institute of Sport Assessment (VISA) questionnaire model is based on item response theory using a graded response (responses reflect increasing difficulty). The purpose of the VISA-G is to monitor patient outcomes and evaluate treatment strategies for people with greater trochanteric pain syndrome (GTPS). The primary aim of the current study was to translate and culturally adapt the VISA-G into a Danish context (DK) through forward and back translation and cognitive interviews. The second aim was to establish test–retest reliability and face validity of the VISA-G into a Danish context (DK). No major disagreements were observed between the original and translated versions of the questionnaire. A total of 58 heterogenous asymptomatic, and 49 symptomatic respondents (response rate: 92% and 78% respectively) completed the VISA-G.DK twice, 1 week apart. The VISA-G.DK had excellent internal consistency (Cronbach’s alpha: asymptomatic = 0.86; symptomatic = 0.98). The test–retest reliability was excellent for the total score: ICC: 0.961 (95% CI [0.933–0.978]). Standard Error Measurement was calculated to be 0.6. Bland–Altman plots showed no significant or relevant differences from test to retest in the total score with mean differences below 1 (0.61). The minimal detectable change was 3.17 for both groups. The VISA-G.DK was found to be valid, reliable and acceptable for use in the Danish population.

]]>
<![CDATA[Monitoring the training dose and acute fatigue response during elbow flexor resistance training using a custom-made resistance band]]> https://www.researchpad.co/article/N19432758-35dd-4005-8ef7-ff1d97e80206

Background

Home-based resistance training offers an alternative to traditional, hospital-based or rehabilitation center-based resistance training and has attracted much attention recently. However, without the supervision of a therapist or the assistance of an exercise monitoring system, one of the biggest challenges of home-based resistance training is that the therapist may not know if the patient has performed the exercise as prescribed. A lack of objective measurements limits the ability of researchers to evaluate the outcome of exercise interventions and choose suitable training doses.

Objective

To create an automated and objective method for segmenting resistance force data into contraction phase-specific segments and calculate the repetition number and time-under-tension (TUT) during elbow flexor resistance training. A pilot study was conducted to evaluate the performance of the segmentation algorithm and to show the capability of the system in monitoring the compliance of patients to a prescribed training program in a practical resistance training setting.

Methods

Six subjects (three male and three female) volunteered to participate in a fatigue and recovery experiment (5 min intermittent submaximal contraction (ISC); 1 min rest; 2 min ISC). A custom-made resistance band was used to help subjects perform biceps curl resistance exercises and the resistance was recorded through a load cell. The maximum and minimum values of the force-derivative were obtained as distinguishing features and a segmentation algorithm was proposed to divide the biceps curl cycle into concentric, eccentric and isometric contraction, and rest phases. Two assessors, who were unfamiliar with the study, were recruited to manually pick the visually observed cut-off point between two contraction phases and the TUT was calculated and compared to evaluate performance of the segmentation algorithm.

Results

The segmentation algorithm was programmatically implemented and the repetition number and contraction-phase specific TUT were calculated. During isometric, the average TUT (3.75 ± 0.62 s) was longer than the prescribed 3 s, indicating that most subjects did not perform the exercise as prescribed. There was a good TUT agreement and contraction segment agreement between the proposed algorithm and the assessors.

Conclusion

The good agreement in TUT between the proposed algorithm and the assessors indicates that the proposed algorithm can correctly segment the contraction into contraction phase-specific parts, thereby providing clinicians and researchers with an automated and objective method for quantifying home-based elbow flexor resistance training. The instrument is easy to use and cheap, and the segmentation algorithm is programmatically implemented, indicating good application prospect of the method in a practical setting.

]]>
<![CDATA[Within-person coupling of estradiol, testosterone, and cortisol in women athletes]]> https://www.researchpad.co/article/N23c181c2-bfbe-43ce-8f6c-7e968ca85f5a

Purpose

In variety of settings cortisol and testosterone are positively “coupled.” That is, within-person fluctuations of cortisol and testosterone levels occur in parallel—increases and decreases in one hormone are associated with corresponding increases and decreases in the other. The present report explored hormone coupling in women athletes in two studies selected because they included measurements of salivary levels of cortisol, testosterone, and estradiol—a hormone that has been only infrequently studied in the context of competitive athletics.

Methods

Consenting members of Emory University’s varsity volleyball and soccer teams gave saliva samples on multiple occasions in the run-up to and over the course of two different intercollegiate contests.

Results

Volleyball and soccer players showed remarkably similar hormone-specific patterns of increase in relationship to the different stages of competition—before warm-up, after warm-up, and after competition. For both the volleyball and soccer team, Hierarchical Linear Model (HLM) analyses showed estradiol as being significantly coupled with testosterone which was also coupled with cortisol.

Conclusions

This is, apparently, the first report of significant within-person coupling between estradiol and testosterone in the context of competitive athletic stress. These two hormones may be coupled in a wide variety of circumstances not limited to ones involving sport competition, and results reported here should encourage exploration of the extent to which coordinated fluctuations in estradiol, testosterone, and cortisol levels are present in other, more neutral settings and the ways in which the coordination of these fluctuating hormone levels may benefit human performance.

]]>
<![CDATA[Partial Inhibition of Adipose Tissue Lipolysis Improves Glucose Metabolism and Insulin Sensitivity Without Alteration of Fat Mass]]> https://www.researchpad.co/article/5989da54ab0ee8fa60b8e8ac

Partial inhibition of adipose tissue lipolysis does not increase fat mass but improves glucose metabolism and insulin sensitivity through modulation of fatty acid turnover and induction of fat cell de novo lipogenesis.

]]>
<![CDATA[An Insight into the Transcriptome of the Digestive Tract of the Bloodsucking Bug, Rhodnius prolixus]]> https://www.researchpad.co/article/5989d9e8ab0ee8fa60b6c009

The bloodsucking hemipteran Rhodnius prolixus is a vector of Chagas' disease, which affects 7–8 million people today in Latin America. In contrast to other hematophagous insects, the triatomine gut is compartmentalized into three segments that perform different functions during blood digestion. Here we report analysis of transcriptomes for each of the segments using pyrosequencing technology. Comparison of transcript frequency in digestive libraries with a whole-body library was used to evaluate expression levels. All classes of digestive enzymes were highly expressed, with a predominance of cysteine and aspartic proteinases, the latter showing a significant expansion through gene duplication. Although no protein digestion is known to occur in the anterior midgut (AM), protease transcripts were found, suggesting secretion as pro-enzymes, being possibly activated in the posterior midgut (PM). As expected, genes related to cytoskeleton, protein synthesis apparatus, protein traffic, and secretion were abundantly transcribed. Despite the absence of a chitinous peritrophic membrane in hemipterans - which have instead a lipidic perimicrovillar membrane lining over midgut epithelia - several gut-specific peritrophin transcripts were found, suggesting that these proteins perform functions other than being a structural component of the peritrophic membrane. Among immunity-related transcripts, while lysozymes and lectins were the most highly expressed, several genes belonging to the Toll pathway - found at low levels in the gut of most insects - were identified, contrasting with a low abundance of transcripts from IMD and STAT pathways. Analysis of transcripts related to lipid metabolism indicates that lipids play multiple roles, being a major energy source, a substrate for perimicrovillar membrane formation, and a source for hydrocarbons possibly to produce the wax layer of the hindgut. Transcripts related to amino acid metabolism showed an unanticipated priority for degradation of tyrosine, phenylalanine, and tryptophan. Analysis of transcripts related to signaling pathways suggested a role for MAP kinases, GTPases, and LKBP1/AMP kinases related to control of cell shape and polarity, possibly in connection with regulation of cell survival, response of pathogens and nutrients. Together, our findings present a new view of the triatomine digestive apparatus and will help us understand trypanosome interaction and allow insights into hemipteran metabolic adaptations to a blood-based diet.

]]>
<![CDATA[Protein Kinase Activity of Phosphoinositide 3-Kinase Regulates Cytokine-Dependent Cell Survival]]> https://www.researchpad.co/article/5989da1bab0ee8fa60b7ceee

The protein kinase activity of PI3K phosphorylates specific serine residues in growth factor receptors to promote cell survival; these events are constitutively activated in some leukemias.

]]>
<![CDATA[Preexisting Japanese Encephalitis Virus Neutralizing Antibodies and Increased Symptomatic Dengue Illness in a School-Based Cohort in Thailand]]> https://www.researchpad.co/article/5989db01ab0ee8fa60bc6db6

Background

Dengue viruses (DENVs) and Japanese encephalitis virus (JEV) have significant cross-reactivity in serological assays; the clinical implications of this remain undefined. An improved understanding of whether and how JEV immunity modulates the clinical outcome of DENV infection is important as large-scale DENV vaccine trials will commence in areas where JEV is co-endemic and/or JEV immunization is routine.

Methods and Findings

The association between preexisting JEV neutralizing antibodies (NAbs) and the clinical severity of DENV infection was evaluated in a prospective school-based cohort in Thailand that captured asymptomatic, non-hospitalized, and hospitalized DENV infections. Covariates considered included age, baseline DENV antibody status, school of attendance, epidemic year, and infecting DENV serotype. 942 children experienced at least one DENV infection between 1998 and 2002, out of 3,687 children who were enrolled for at least one full year. In crude analysis, the presence of JEV NAbs was associated with an increased occurrence of symptomatic versus asymptomatic infection (odds ratio [OR] = 1.55, 95% CI: 1.08–2.23) but not hospitalized illness or dengue hemorrhagic fever (DHF). The association was strongest in children with negative DENV serology (DENV-naive) (OR = 2.75, 95% CI: 1.12–6.72), for whom the presence of JEV NAbs was also associated with a symptomatic illness of longer duration (5.4 days for JEV NAb+ versus 2.6 days for JEV NAb-, p = 0.048). JEV NAbs were associated with increased DHF in younger children with multitypic DENV NAb profiles (OR = 4.05, 95% CI: 1.18 to 13.87). Among those with JEV NAbs, the association with symptomatic illness did not vary by antibody titer.

Interpretation

The prior existence of JEV NAbs was associated with an increased probability of symptomatic as compared to asymptomatic DENV illness. These findings are in contrast to previous studies suggesting an attenuating effect of heterologous flavivirus immunity on DENV disease severity.

]]>
<![CDATA[PICK1 and ICA69 Control Insulin Granule Trafficking and Their Deficiencies Lead to Impaired Glucose Tolerance]]> https://www.researchpad.co/article/5989db12ab0ee8fa60bcc62e

PICK1 and ICA69, proteins containing a BAR domain, regulate the biogenesis and maturation of insulin granules in mice.

]]>
<![CDATA[Inducible and Targeted Deletion of the ERK5 MAP Kinase in Adult Neurogenic Regions Impairs Adult Neurogenesis in the Olfactory Bulb and Several Forms of Olfactory Behavior]]> https://www.researchpad.co/article/5989da9dab0ee8fa60ba4744

Although adult-born neurons in the subventricular zone (SVZ) and olfactory bulb (OB) have been extensively characterized at the cellular level, their functional impact on olfactory behavior is still highly controversial with many conflicting results reported in the literature. Furthermore, signaling mechanisms regulating adult SVZ/OB neurogenesis are not well defined. Here we report that inducible and targeted deletion of erk5, a MAP kinase selectively expressed in the adult neurogenic regions of the adult brain, impairs adult neurogenesis in the SVZ and OB of transgenic mice. Although erk5 deletion had no effect on olfactory discrimination among discrete odorants in the habituation/dishabituation assay, it reduced short-term olfactory memory as well as detection sensitivity to odorants and pheromones including those evoking aggression and fear. Furthermore, these mice show impaired acquisition of odor-cued associative olfactory learning, a novel phenotype that had not been previously linked to adult neurogenesis. These data suggest that ERK5 MAP kinase is a critical kinase signaling pathway regulating adult neurogenesis in the SVZ/OB, and provide strong evidence supporting a functional role for adult neurogenesis in several distinct forms of olfactory behavior.

]]>
<![CDATA[The Redox State of Transglutaminase 2 Controls Arterial Remodeling]]> https://www.researchpad.co/article/5989db05ab0ee8fa60bc8226

While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2), the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub) cellular localization, substrates, and its specific mode of action during small artery inward remodeling. We found that inward remodeling of isolated mouse mesenteric arteries by exogenous TG2 required the presence of a reducing agent. The effect of TG2 depended on its cross-linking activity, as indicated by the lack of effect of mutant TG2. The cell-permeable reducing agent DTT, but not the cell-impermeable reducing agent TCEP, induced translocation of endogenous TG2 and high membrane-bound transglutaminase activity. This coincided with inward remodeling, characterized by a stiffening of the artery. The remodeling could be inhibited by a TG2 inhibitor and by the nitric oxide donor, SNAP. Using a pull-down assay and mass spectrometry, 21 proteins were identified as TG2 cross-linking substrates, including fibronectin, collagen and nidogen. Inward remodeling induced by low blood flow was associated with the upregulation of several anti-oxidant proteins, notably glutathione-S-transferase, and selenoprotein P. In conclusion, these results show that a reduced state induces smooth muscle membrane-bound TG2 activity. Inward remodeling results from the cross-linking of vicinal matrix proteins, causing a stiffening of the arterial wall.

]]>
<![CDATA[Real-Time Analysis of Drosophila Post-Embryonic Haemocyte Behaviour]]> https://www.researchpad.co/article/5989dab7ab0ee8fa60bad6c8

Background

The larval stage of the model organism Drosophila is frequently used to study host-pathogen interactions. During embryogenesis the cellular arm of the immune response, consisting of macrophage-like cells known as plasmatocytes, is extremely motile and functions to phagocytise pathogens and apoptotic bodies, as well as produce extracellular matrix. The cellular branch of the larval (post-embryonic) innate immune system consists of three cell types—plasmatocytes, crystal cells and lamellocytes—which are involved in the phagocytosis, encapsulation and melanisation of invading pathogens. Post-embryonic haemocyte motility is poorly understood thus further characterisation is required, for the purpose of standardisation.

Methodology

In order to examine post-embryonic haemocyte cytoskeletal dynamics or migration, the most commonly used system is in vitro cell lines. The current study employs an ex vivo system (an adaptation of in vitro cell incubation using primary cells), in which primary larval or pre-pupal haemocytes are isolated for short term analysis, in order to discover various aspects of their behaviour during events requiring cytoskeleton dynamics.

Significance

The ex vivo method allows for real-time analysis and manipulation of primary post-embryonic haemocytes. This technique was used to characterise, and potentially standardised, larval and pre-pupal haemocyte cytoskeleton dynamics, assayed on different extracellular matrices. Using this method it was determined that, while larval haemocytes are unable to migrate, haemocytes recovered from pre-pupae are capable of migration.

]]>
<![CDATA[Infant Brain Atlases from Neonates to 1- and 2-Year-Olds]]> https://www.researchpad.co/article/5989d9d5ab0ee8fa60b659b9

Background

Studies for infants are usually hindered by the insufficient image contrast, especially for neonates. Prior knowledge, in the form of atlas, can provide additional guidance for the data processing such as spatial normalization, label propagation, and tissue segmentation. Although it is highly desired, there is currently no such infant atlas which caters for all these applications. The reason may be largely due to the dramatic early brain development, image processing difficulties, and the need of a large sample size.

Methodology

To this end, after several years of subject recruitment and data acquisition, we have collected a unique longitudinal dataset, involving 95 normal infants (56 males and 39 females) with MRI scanned at 3 ages, i.e., neonate, 1-year-old, and 2-year-old. State-of-the-art MR image segmentation and registration techniques were employed, to construct which include the templates (grayscale average images), tissue probability maps (TPMs), and brain parcellation maps (i.e., meaningful anatomical regions of interest) for each age group. In addition, the longitudinal correspondences between age-specific atlases were also obtained. Experiments of typical infant applications validated that the proposed atlas outperformed other atlases and is hence very useful for infant-related studies.

Conclusions

We expect that the proposed infant 0–1–2 brain atlases would be significantly conducive to structural and functional studies of the infant brains. These atlases are publicly available in our website, http://bric.unc.edu/ideagroup/free-softwares/.

]]>
<![CDATA[Long-Term Bezafibrate Treatment Improves Skin and Spleen Phenotypes of the mtDNA Mutator Mouse]]> https://www.researchpad.co/article/5989d9e1ab0ee8fa60b69818

Pharmacological agents, such as bezafibrate, that activate peroxisome proliferator-activated receptors (PPARs) and PPAR γ coactivator-1α (PGC-1α) pathways have been shown to improve mitochondrial function and energy metabolism. The mitochondrial DNA (mtDNA) mutator mouse is a mouse model of aging that harbors a proofreading-deficient mtDNA polymerase γ. These mice develop many features of premature aging including hair loss, anemia, osteoporosis, sarcopenia and decreased lifespan. They also have increased mtDNA mutations and marked mitochondrial dysfunction. We found that mutator mice treated with bezafibrate for 8-months had delayed hair loss and improved skin and spleen aging-like phenotypes. Although we observed an increase in markers of fatty acid oxidation in these tissues, we did not detect a generalized increase in mitochondrial markers. On the other hand, there were no improvements in muscle function or lifespan of the mutator mouse, which we attributed to the rodent-specific hepatomegaly associated with fibrate treatment. These results showed that despite its secondary effects in rodent’s liver, bezafibrate was able to improve some of the aging phenotypes in the mutator mouse. Because the associated hepatomegaly is not observed in primates, long-term bezafibrate treatment in humans could have beneficial effects on tissues undergoing chronic bioenergetic-related degeneration.

]]>
<![CDATA[Increased Endothelial Cell-Leukocyte Interaction in Murine Schistosomiasis: Possible Priming of Endothelial Cells by the Disease]]> https://www.researchpad.co/article/5989dad7ab0ee8fa60bb83fb

Background and Aims

Schistosomiasis is an intravascular parasitic disease associated with inflammation. Endothelial cells control leukocyte transmigration and vascular permeability being modulated by pro-inflammatory mediators. Recent data have shown that endothelial cells primed in vivo in the course of a disease keep the information in culture. Herein, we evaluated the impact of schistosomiasis on endothelial cell-regulated events in vivo and in vitro.

Methodology and Principal Findings

The experimental groups consisted of Schistosoma mansoni-infected and age-matched control mice. In vivo infection caused a marked influx of leukocytes and an increased protein leakage in the peritoneal cavity, characterizing an inflamed vascular and cellular profile. In vitro leukocyte-mesenteric endothelial cell adhesion was higher in cultured cells from infected mice as compared to controls, either in the basal condition or after treatment with the pro-inflammatory cytokine tumor necrosis factor (TNF). Nitric oxide (NO) donation reduced leukocyte adhesion to endothelial cells from control and infected groups; however, in the later group the effect was more pronounced, probably due to a reduced NO production. Inhibition of control endothelial NO synthase (eNOS) increased leukocyte adhesion to a level similar to the one observed in the infected group. Besides, the adhesion of control leukocytes to endothelial cells from infected animals is similar to the result of infected animals, confirming that schistosomiasis alters endothelial cells function. Furthermore, NO production as well as the expression of eNOS were reduced in cultured endothelial cells from infected animals. On the other hand, the expression of its repressor protein, namely caveolin-1, was similar in both control and infected groups.

Conclusion/Significance

Schistosomiasis increases vascular permeability and endothelial cell-leukocyte interaction in vivo and in vitro. These effects are partially explained by a reduced eNOS expression. In addition, our data show that the disease primes endothelial cells in vivo, which keep the acquired phenotype in culture.

]]>
<![CDATA[Glucocorticoid-Induced Leucine Zipper (GILZ) Antagonizes TNF-α Inhibition of Mesenchymal Stem Cell Osteogenic Differentiation]]> https://www.researchpad.co/article/5989da5aab0ee8fa60b8fa7a

Tumor necrosis factor-alpha (TNF-α) is a potent proinflammatory cytokine that inhibits osteoblast differentiation while stimulating osteoclast differentiation and bone resorption. TNF-α activates MAP kinase pathway leading to inhibition of osterix (Osx) expression. TNF-α also induces the expression of E3 ubiquitin ligase protein Smurf1 and Smurf2 and promotes degradation of Runx2, another key transcription factor regulating osteoblast differentiation and bone formation. We showed previously that overexpression of glucocorticoid (GC)-induced leucine zipper (GILZ) enhances osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs). We and others also showed that GILZ is a GC effecter and mediates GC anti-inflammatory activity. In this study, we asked the question whether GILZ retains its osteogenic activity while functioning as an anti-inflammatory mediator. To address this question, we infected mouse bone marrow MSCs with retroviruses expressing GILZ and induced them for osteogenic differentiation in the presence or absence of TNF-α. Our results show that overexpression of GILZ antagonized the inhibitory effects of TNF-α on MSC osteogenic differentiation and the mRNA and protein expression of Osx and Runx2, two pivotal osteogenic regulators. Further studies show that these antagonistic actions occur via mechanisms involving GILZ inhibition of TNF-α-induced ERK MAP kinase activation and protein degradation. These results suggest that GILZ may have therapeutic potential as a novel anti-inflammation therapy.

]]>
<![CDATA[Tracking Blood Glucose and Predicting Prediabetes in Chinese Children and Adolescents: A Prospective Twin Study]]> https://www.researchpad.co/article/5989d9d5ab0ee8fa60b65888

We examined the tracking of blood glucose, the development of prediabetes, and estimated their genetic contributions in a prospective, healthy, rural Chinese twin cohort. This report includes 1,766 subjects (998 males, 768 females) aged 6–21 years at baseline who completed a 6-year follow-up study. Oral glucose tolerance test was performed for all subjects at both baseline and follow-up. We found that subjects with low fasting plasma glucose (FPG) or 2 h post-load glucose (PG) levels at baseline tended to remain at the low level at follow-up. Subjects in the top tertile of baseline plasma glucose tended to have a higher risk of developing prediabetes at follow-up compared to the low tertile: in males, 37.6% vs. 27.6% for FPG and 37.2% vs. 25.7% for 2hPG, respectively; in females, 31.0% vs. 15.4% for FPG and 28.9% vs. 15.1% for 2 h PG, respectively. Genetic factors explained 43% and 41% of the variance of FPG, and 72% and 47% for impaired fasting glucose for males and females, respectively; environmental factors substantially contribute to 2hPG status and impaired glucose tolerance. In conclusion, in this cohort of healthy rural Chinese children and adolescents, we demonstrated that both FPG and 2hPG tracked well and was a strong predictor of prediabetes. The high proportion of children with top tertile of blood glucose progressed to prediabetes, and the incidence of prediabetes has a male predominance. Genetic factors play more important role in fasting than postload status, most of which was explained by unique environmental factors.

]]>
<![CDATA[Beta-Adrenergic Modulation of Tremor and Corticomuscular Coherence in Humans]]> https://www.researchpad.co/article/5989dab8ab0ee8fa60bada45

Coherence between the bioelectric activity of sensorimotor cortex and contralateral muscles can be observed around 20 Hz. By contrast, physiological tremor has a dominant frequency around 10 Hz. Although tremor has multiple sources, it is partly central in origin, reflecting a component of motoneuron discharge at this frequency. The motoneuron response to ∼20 Hz descending input could be altered by non-linear interactions with ∼10 Hz motoneuron firing. We investigated this further in eight healthy human subjects by testing the effects of the beta-adrenergic agents propranolol (non-selective β-antagonist) and salbutamol (β2-agonist), which are known to alter the size of physiological tremor. Corticomuscular coherence was assessed during an auxotonic precision grip task; tremor was quantified using accelerometry during index finger extension. Experiments with propranolol used a double-blind, placebo-controlled crossover design. A single oral dose of propranolol (40 mg) significantly increased beta band (15.3–32.2 Hz) corticomuscular coherence compared with placebo, but reduced tremor in the 6.2–11.9 Hz range. Salbutamol (2.5 mg) was administered by inhalation. Whilst salbutamol significantly increased tremor amplitude as expected, it did not change corticomuscular coherence. The opposite direction of the effects of propranolol on corticomuscular coherence and tremor, and the fact that salbutamol enhances tremor but does not affect coherence, implies that the magnitude of corticomuscular coherence is little influenced by non-linear interactions with 10 Hz oscillations in motoneurons or the periphery. Instead, we suggest that propranolol and salbutamol may affect both tremor and corticomuscular coherence partly via a central site of action.

]]>