Effects of interstitial fluid flow and cell compression in FAK and SRC activities in chondrocytes

Indiana University-Purdue University Indianapolis (IUPUI)Articular cartilage is subjected to dynamic mechanical loading during normal daily activities. This complex mechanical loading, including cell deformation and interstitial fluid flow, affects chondrocyte mechano-chemical signaling and subsequent cartilage homeostasis and remodeling. Focal adhesion kinase (FAK) and Src are known to be main mechanotransduction proteins, but little is known about the effect of mechanical loading on FAK and Src under its varying magnitudes and types. In this study, we addressed two questions using C28/I2 chondrocytes subjected to the different types and magnitudes of mechanical loading: Does a magnitude of the mechanical loading affect activities of FAK and Src? Does a type of the mechanical loading also affect their activities? Using fluorescence resonance energy transfer (FRET)-based FAK and Src biosensor in live C28/I2 chondrocytes, we monitored the effects of interstitial fluid flow and combined effects of cell deformation/interstitial fluid flow on FAK and Src activities. The results revealed that both FAK and Src activities in C28/I2 chondrocytes were dependent on the different magnitudes of the applied fluid flow. On the other hand, the type of mechanical loading differently affected FAK and Src activities. Although FAK and Src displayed similar activities in response to interstitial fluid flow only, simultaneous application of cell deformation and interstitial fluid flow induced differential FAK and Src activities possibly due to the additive effects of cell deformation and interstitial fluid flow on Src, but not on FAK. Collectively, the data suggest that the intensities and types of mechanical loading are critical in regulating FAK and Src activities in chondrocytes

Latino Family Engagement in a Network of Catholic Bilingual Schools

In this article, we examine how a Network of Catholic Bilingual Schools (NCBS) serves Latino populations by examining the leadership’s narratives of the school services and outreach. By employing a survey with 16 principals in the NCBS, we argue that the rate of engagement is similar between Latino and non-Latino parents, although the nature of the activities varied. Despite the long-held belief that Latino parents are less likely to participate in schooling than non-Latino parents, we found that Latino parents committed their participation in schools across cultural, linguistic, or religious activities. We highlight how principals acknowledge and describe Latino families’ involvement as highly invested in their children’s education and their aspirations toward proficiency in both languages, Spanish and English as well a deep-rooted commitment to Catholic value

Chemoselective Oxidation of 6,13-Bis(decylthio) Pentacene

Organic semiconductors present much potential for industrial use because of their possible low cost production, Pentacene and pentacene derivatives are promising candidates for organic semiconductor research since their ^-conjugated electronic structures possess small HOMO- LUMO gaps and high field effect mobility. Whereas there is much potential in devices made from pentacenes they do however undergo short lifetimes and poor processability due to photodegradation and poor solubility of pentacene. Previous research has shown that the pentacene lifetime and solubility can be enhanced by arylthio and alkylthio substituents placed on the pentacene backbone. For example 6,13-i?/s(decylthio)pentacene was one of the longest lived pentacene derivative known and it has been shown to exhibit excellent solubility in a variety of organic solvents. This research was performed to chemically control the chemoselective oxidation of the compound 6,13-5/s(decylthio)pentacene to produce a new pentacene derivative bearing either sulfoxide or sulfone functional groups thus forming a new pentacene derivative which may show greater photoxidative resistance. The products of this experiment were as follows: 6-(decylsulfinyl)-13-decylthio)pentacene and 6,13- £/5(decylsulfmyI)pentacene as characterized by NMR, UV, mass spectra, and electrochemical techniques. The half-life of 6-(decylsulfinyl)-13-decylthio)pentacene was longer (2900 min) compared to the starting material and 6,13-5/.v(decylsulfinyl)pentacene. However, both products had similar HOMO-LUMO gaps as determined by cyclic voltammetry. Using 0.5 equivalent of mCPBA gave the maximum yield (76%) of 6-(decylsulfmyl)-13-decylthio)pentacene. This product was a better semiconductor due to higher stability

Factors affecting employees' problem-solving skills in technology-rich environments in Japan and Korea

This study conducts an analysis about the impact of basic background, cultural capital, skill use, and participation in training on employees’ problem-solving proficiency in Japan and Korea based on data from the Programme for the International Assessment of Adult Competencies Survey (PIAAC). This research compared four clusters (basic background, cultural capital, participation in training, skill usage) to determine the factors affecting problem-solving skills in technology-rich environments (PSTRE) in Japan and Korea. In addition, we examined whether aging moderate the relationship between skill usage and participation in training and PSTRE. The finding shows that PSTRE is associated with the basic background, cultural capital, and skill usage. Moreover, the interaction effect between the use of skill at home and age is statistically significant in Japan. Our results provide new insights for vocational psychology and work-life research in the context of employers, employees, as well as policymakers

FK506-binding protein-like and FK506-binding protein 8 regulate dual leucine zipper kinase degradation and neuronal responses to axon injury

The dual leucine zipper kinase (DLK) is a key regulator of axon regeneration and degeneration in response to neuronal injury; however, regulatory mechanisms of the DLK function via its interacting proteins are largely unknown. To better understand the molecular mechanism of DLK function, we performed yeast two-hybrid screening analysis and identified FK506-binding protein-like (FKBPL, also known as WAF-1/CIP1 stabilizing protein 39) as a DLK-binding protein. FKBPL binds to the kinase domain of DLK and inhibits its kinase activity. In addition, FKBPL induces DLK protein degradation through ubiquitin-dependent pathways. We further assessed other members in the FKBP protein family and found that FK506-binding protein 8 (FKBP8) also induced DLK degradation. We identified the lysine 271 residue in the kinase domain as a major site of DLK ubiquitination and SUMO3 conjugation and was thus responsible for regulating FKBP8-mediated proteasomal degradation that was inhibited by the substitution of the lysine 271 to arginine. FKBP8-mediated degradation of DLK is mediated by autophagy pathway because knockdown of Atg5 inhibited DLK destabilization. We show that in vivo overexpression of FKBP8 delayed the progression of axon degeneration and suppressed neuronal death after axotomy in sciatic and optic nerves. Taken together, this study identified FKBPL and FKBP8 as novel DLK-interacting proteins that regulate DLK stability via the ubiquitin-proteasome and lysosomal protein degradation pathways

New Cube Root Algorithm Based on Third Order Linear Recurrence Relation in Finite Field

In this paper, we present a new cube root algorithm in finite field $\mathbb{F}_{q}$ with $q$ a power of prime, which extends the Cipolla-Lehmer type algorithms \cite{Cip,Leh}. Our cube root method is inspired by the work of Müller \cite{Muller} on quadratic case. For given cubic residue $c \in \mathbb{F}_{q}$ with $q \equiv 1 \pmod{9}$, we show that there is an irreducible polynomial $f(x)=x^{3}-ax^{2}+bx-1$ with root $\alpha \in \mathbb{F}_{q^{3}}$ such that $Tr(\alpha^{\frac{q^{2}+q-2}{9}})$ is a cube root of $c$. Consequently we find an efficient cube root algorithm based on third order linear recurrence sequence arising from $f(x)$. Complexity estimation shows that our algorithm is better than previously proposed Cipolla-Lehmer type algorithms

Trace Expression of r-th Root over Finite Field

Efficient computation of $r$-th root in $\mathbb F_q$ has many applications in computational number theory and many other related areas. We present a new $r$-th root formula which generalizes Müller\u27s result on square root, and which provides a possible improvement of the Cipolla-Lehmer algorithm for general case. More precisely, for given $r$-th power $c\in \mathbb F_q$, we show that there exists $\alpha \in \mathbb F_{q^r}$ such that $Tr\left(\alpha^\frac{(\sum_{i=0}^{r-1}q^i)-r}{r^2}\right)^r=c$ where $Tr(\alpha)=\alpha+\alpha^q+\alpha^{q^2}+\cdots +\alpha^{q^{r-1}}$ and $\alpha$ is a root of certain irreducible polynomial of degree $r$ over $\mathbb F_q$

Matrix rigidity regulates spatiotemporal dynamics of Cdc42 activity and vacuole formation kinetics of endothelial colony forming cells

Recent evidence has shown that endothelial colony forming cells (ECFCs) may serve as a cell therapy for improving blood vessel formation in subjects with vascular injury, largely due to their robust vasculogenic potential. The Rho family GTPase Cdc42 is known to play a primary role in this vasculogenesis process, but little is known about how extracellular matrix (ECM) rigidity affects Cdc42 activity during the process. In this study, we addressed two questions: Does matrix rigidity affect Cdc42 activity in ECFC undergoing early vacuole formation? How is the spatiotemporal activation of Cdc42 related to ECFC vacuole formation? A fluorescence resonance energy transfer (FRET)-based Cdc42 biosensor was used to examine the effects of the rigidity of three-dimensional (3D) collagen matrices on spatiotemporal activity of Cdc42 in ECFCs. Collagen matrix stiffness was modulated by varying the collagen concentration and therefore fibril density. The results showed that soft (150 Pa) matrices induced an increased level of Cdc42 activity compared to stiff (1 kPa) matrices. Time-course imaging and colocalization analysis of Cdc42 activity and vacuole formation revealed that Cdc42 activity was colocalized to the periphery of cytoplasmic vacuoles. Moreover, soft matrices generated faster and larger vacuoles than stiff matrices. The matrix-driven vacuole formation was enhanced by a constitutively active Cdc42 mutant, but significantly inhibited by a dominant-negative Cdc42 mutant. Collectively, the results suggest that matrix rigidity is a strong regulator of Cdc42 activity and vacuole formation kinetics, and that enhanced activity of Cdc42 is an important step in early vacuole formation in ECFCs

Insulin Secretion and Incretin Hormone Concentration in Women with Previous Gestational Diabetes Mellitus

BackgroundWe examined the change in the levels of incretin hormone and effects of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) on insulin secretion in women with previous gestational diabetes (pGDM).MethodsA 75-g oral glucose tolerance test (OGTT) was conducted on 34 women with pGDM. In addition, 11 women with normal glucose tolerance, matched for age, height and weight, were also tested. The insulin, GIP, GLP-1, and glucagon concentrations were measured, and their anthropometric and biochemical markers were also measured.ResultsAmong 34 women with pGDM, 18 had normal glucose tolerance, 13 had impaired glucose tolerance (IGT) and 1 had diabetes. No significant differences were found in GLP-1 concentration between the pGDM and control group. However, a significantly high level of glucagon was present in the pGDM group at 30 minutes into the OGTT. The GIP concentration was elevated at 30 minutes and 60 minutes in the pGDM group. With the exception of the 30-minute timepoint, women with IGT had significantly high blood glucose from 0 to 120 minutes. However, there was no significant difference in insulin or GLP-1 concentration. The GIP level was significantly high from 0 to 90 minutes in patients diagnosed with IGT.ConclusionGLP-1 secretion does not differ between pGDM patients and normal women. GIP was elevated, but that does not seem to induce in increase in insulin secretion. Therefore, we conclude that other factors such as heredity and environment play important roles in the development of type 2 diabetes

Efficacy of smartphone application-based multi-domain cognitive training in older adults without dementia

BackgroundAs the population ages and the prevalence of dementia increases, there is a growing emphasis on the importance of cognitive training to prevent dementia. A smartphone application-based cognitive training software program, BeauBrain Trainer (BBT), has been developed to provide better access to cognitive training for older adults. Numerous studies have revealed the effectiveness of cognitive training using a cognitive assessment tool. However, relatively few studies have evaluated brain activation using brain imaging as a result of improved cognitive function.MethodsAll participants were required to download the BBT, an Android-based application for cognitive training, onto their own smartphone or tablet computer and to engage in cognitive training at home. Older adults without dementia were enrolled in this study, including 51 participants in the intervention group and 50 participants in the control group. The BBT comprised a set of 12 cognitive tasks, including two tasks in each of the following six cognitive domains: attention, language, calculation, visuospatial function, memory, and frontal/executive function. Each cognitive task was divided into four blocks based on its level of difficulty. A 16-week cognitive training was designed to carry out cognitive tasks using a total of 48 blocks (12 tasks × 4 levels) for at least 1.5 h per day, 5 days per week. All participants in the intervention group were given BBT tasks that gradually increased in difficulty level, which they submitted through a smartphone application daily for 16 weeks. The researchers monitored the participants’ task performance records on the website and encouraged participants to engage in cognitive training through regular contact. This study was conducted to investigate the improvement in cognitive function and the activation pattern of the frontal cortex in older adults participating in smartphone application-based cognitive training. The cognitive assessment tool was the BeauBrain cognitive screening test (CST), a tablet-based computerized cognitive screening test. The activation pattern of the frontal cortex was measured using functional near-infrared spectroscopy (fNIRS). Additionally, this study aimed to determine the positive effects of cognitive training on everyday functioning and psychological states using a questionnaire.ResultsOf 101 participants, 85 older adults without dementia (84.1%) who completed the study protocol were included in the statistical analysis. There were 41 participants (80.3%) in the intervention group and 44 participants (88.0%) in the control group. A two-way repeated-measures analysis of variance (ANOVA) was used to compare the cognitive scores over a 16-week period between the intervention and control groups. According to the CST results, the intervention group exhibited a statistically significant increase in the language subtest scores, specifically the phonemic word fluency test, compared to those of the control group. The fNIRS results revealed greater activation in the dorsolateral prefrontal cortex during the STROOP incongruent task in the intervention group than did the control group. However, the effectiveness of cognitive training was not observed across a variety of rating scales, including everyday functioning, depression, self-efficacy, attention, and subjective memory complaints.ConclusionThis study revealed that a smartphone-based cognitive training application led to improvements in phonemic generative naming ability and activation of the prefrontal cortex in older adults without dementia. This study is meaningful because it confirmed that cognitive training is partially effective in enhancing frontal lobe function. It also provided information on the brain mechanisms related to the effects of cognitive training using fNIRS