Fibronectin matrix assembly is essential for cell condensation during chondrogenesis.

PubMed

Singh, Purva; Schwarzbauer, Jean E

2014-10-15

Mesenchymal cell condensation is the initiating event in endochondral bone formation. Cell condensation is followed by differentiation into chondrocytes, which is accompanied by induction of chondrogenic gene expression. Gene mutations involved in chondrogenesis cause chondrodysplasias and other skeletal defects. Using mesenchymal stem cells (MSCs) in an in vitro chondrogenesis assay, we found that knockdown of the diastrophic dysplasia (DTD) sulfate transporter (DTDST, also known as SLC26A2), which is required for normal cartilage development, blocked cell condensation and caused a significant reduction in fibronectin matrix. Knockdown of fibronectin with small interfering RNAs (siRNAs) also blocked condensation. Fibrillar fibronectin matrix was detected prior to cell condensation, and its levels increased during and after condensation. Inhibition of fibronectin matrix assembly by use of the functional upstream domain (FUD) of adhesin F1 from Streptococcus pyogenes prevented cell condensation by MSCs and also by the chondrogenic cell line ATDC5. Our data show that cell condensation and induction of chondrogenesis depend on fibronectin matrix assembly and DTDST, and indicate that this transporter is required earlier in chondrogenesis than previously appreciated. They also raise the possibility that certain of the skeletal defects in DTD patients might derive from the link between DTDST, fibronectin matrix and condensation. © 2014. Published by The Company of Biologists Ltd.

Hydrophilic polyurethane matrix promotes chondrogenesis of mesenchymal stem cells☆

PubMed Central

Nalluri, Sandeep M.; Krishnan, G. Rajesh; Cheah, Calvin; Arzumand, Ayesha; Yuan, Yuan; Richardson, Caley A.; Yang, Shuying; Sarkar, Debanjan

2016-01-01

Segmental polyurethanes exhibit biphasic morphology and can control cell fate by providing distinct matrix guided signals to increase the chondrogenic potential of mesenchymal stem cells (MSCs). Polyethylene glycol (PEG) based hydrophilic polyurethanes can deliver differential signals to MSCs through their matrix phases where hard segments are cell-interactive domains and PEG based soft segments are minimally interactive with cells. These coordinated communications can modulate cell–matrix interactions to control cell shape and size for chondrogenesis. Biphasic character and hydrophilicity of polyurethanes with gel like architecture provide a synthetic matrix conducive for chondrogenesis of MSCs, as evidenced by deposition of cartilage-associated extracellular matrix. Compared to monophasic hydrogels, presence of cell interactive domains in hydrophilic polyurethanes gels can balance cell–cell and cell–matrix interactions. These results demonstrate the correlation between lineage commitment and the changes in cell shape, cell–matrix interaction, and cell–cell adhesion during chondrogenic differentiation which is regulated by polyurethane phase morphology, and thus, represent hydrophilic polyurethanes as promising synthetic matrices for cartilage regeneration. PMID:26046282

Hydrophilic polyurethane matrix promotes chondrogenesis of mesenchymal stem cells.

PubMed

Nalluri, Sandeep M; Krishnan, G Rajesh; Cheah, Calvin; Arzumand, Ayesha; Yuan, Yuan; Richardson, Caley A; Yang, Shuying; Sarkar, Debanjan

2015-09-01

Segmental polyurethanes exhibit biphasic morphology and can control cell fate by providing distinct matrix guided signals to increase the chondrogenic potential of mesenchymal stem cells (MSCs). Polyethylene glycol (PEG) based hydrophilic polyurethanes can deliver differential signals to MSCs through their matrix phases where hard segments are cell-interactive domains and PEG based soft segments are minimally interactive with cells. These coordinated communications can modulate cell-matrix interactions to control cell shape and size for chondrogenesis. Biphasic character and hydrophilicity of polyurethanes with gel like architecture provide a synthetic matrix conducive for chondrogenesis of MSCs, as evidenced by deposition of cartilage-associated extracellular matrix. Compared to monophasic hydrogels, presence of cell interactive domains in hydrophilic polyurethanes gels can balance cell-cell and cell-matrix interactions. These results demonstrate the correlation between lineage commitment and the changes in cell shape, cell-matrix interaction, and cell-cell adhesion during chondrogenic differentiation which is regulated by polyurethane phase morphology, and thus, represent hydrophilic polyurethanes as promising synthetic matrices for cartilage regeneration. Copyright © 2015 Elsevier B.V. All rights reserved.

Osmolyte Type and the Osmolarity Level Affect Chondrogenesis of Mesenchymal Stem Cells.

PubMed

Ahmadyan, Sorour; Kabiri, Mahboubeh; Hanaee-Ahvaz, Hana; Farazmand, Ali

2018-06-01

The inductive effects of increased osmolarity on chondrogenesis are well approved. However, the effects of the osmolyte agent invoked to induce hyperosmolarity are largely neglected. Herein, we scrutinized how hyperosmotic conditions acquired by addition of different osmolytes would impact chondrogenesis. We briefly assessed whether such conditions would differentially affect hypertrophy and angiogenesis during MSC chondrogenesis. Chondrogenic and hypertrophic marker expression along with VEGF secretion during adipose-derived (AD)-MSC chondrogenesis under three osmolarity levels (350, 450, and 550 mOsm) using three different osmolytes (NaCl, sorbitol, and PEG) were assessed. MTT assay, qRT-PCR, immunocytochemistry, Alcian Blue staining, ELISA, and ALP assays proved osmolyte-type dependent effects of hyperosmolarity on chondrogenesis, hypertrophy, and angiogenesis. At same osmolarity level, PEG had least cytotoxic/cytostatic effect and most prohibitive effects on angiogenesis. As expected, all hyperosmolar conditions led to enhanced chondrogenesis with slightly varying degrees. PEG and sorbitol had higher chondro-promotive and hypertrophy-suppressive effects compared to NaCl, while NaCl had exacerbated hypertrophy. We observed that TonEBP was involved in osmoadaptation of all treatments in varying degrees. Of importance, we highlighted differential effects of hyperosmolarity obtained by different osmolytes on the efficacy of chondrogenesis and more remarkably on the induction/suppression of cartilage pathologic markers. Our study underlies the need for a more vigilant exploitation of physicobiochemical inducers in order to maximize chondrogenesis while restraining unwanted hypertrophy and angiogenesis.

Melatonin rescued interleukin 1β-impaired chondrogenesis of human mesenchymal stem cells.

PubMed

Gao, Bo; Gao, Wenjie; Wu, Zizhao; Zhou, Taifeng; Qiu, Xianjian; Wang, Xudong; Lian, Chengjie; Peng, Yan; Liang, Anjing; Qiu, Jincheng; Zhu, Yuanxin; Xu, Caixia; Li, Yibing; Su, Peiqiang; Huang, Dongsheng

2018-06-14

Osteoarthritis (OA) is a widespread arthritic disease and a primary cause of disability. Increasing evidence suggests that inflammation has a pivotal part in its pathogenesis. Interleukin-1β (IL-1β) is a primary mediator of local inflammatory processes in OA. Current therapies for OA mainly focus on the symptoms of the advanced stage of the disease. The possible utilization of bone marrow mesenchymal stem cells (BMSCs) to regenerate cartilage is an appealing method, but in the case of OA requires chondrogenesis to take place within an inflamed environment. Our previous study showed that melatonin (MLT) can promote chondrogenic differentiation of MSCs, but whether MLT can rescue IL-1β-impaired chondrogenesis in human BMSCs has not yet been established. MLT, which can have anti-inflammatory and prochondrogenic effects, has demonstrated potential in defeating IL-1β-induced inhibition of chondrogenesis and further study should be conducted. Human bone marrow-derived MSCs were separated and cultured based on our system that was already documented. A high-density micromass culture system was used for the chondrogenic differentiation of human BMSCs, which was also described previously. Human BMSCs were induced for chondrogenesis for 7, 14, and 21 days with the treatment of IL-1β and MLT. The cultured cartilage pellets were then evaluated by morphology, extracellular matrix accumulation, and chondrogenic, metabolic, and apoptotic marker expression. Furthermore, cell apoptosis was assessed by TUNEL assay. The phosphorylation level P65 and IκBα of the NF-κB pathway activity was explored on day 21 of chondrogenic differentiation of BMSCs. The current evaluation showed that MLT can save IL-1β-impaired chondrogenesis of human BMSCs in different aspects. Firstly, MLT can restore the chondrogenic pellet size, and rescue matrix synthesis and accumulation. Secondly, MLT can upregulate chondrogenic marker COL2A1 expression at both mRNA and protein levels, and also regulate

Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature

PubMed Central

Deprez, Pierre M. L.; Nichane, Miloud G.; Lengelé, Benoît G.; Rezsöhazy, René; Nyssen-Behets, Catherine

2013-01-01

In a previous study using transgenic mice ectopically expressing Hoxa2 during chondrogenesis, we associated the animal phenotype to human idiopathic proportionate short stature. Our analysis showed that this overall size reduction was correlated with a negative influence of Hoxa2 at the first step of endochondral ossification. However, the molecular pathways leading to such phenotype are still unknown. Using protein immunodetection and histological techniques comparing transgenic mice to controls, we show here that the persistent expression of Hoxa2 in chondrogenic territories provokes a general down-regulation of the main factors controlling the differentiation cascade, such as Bapx1, Bmp7, Bmpr1a, Ihh, Msx1, Pax9, Sox6, Sox9 and Wnt5a. These data confirm the impairment of chondrogenic differentiation by Hoxa2 overexpression. They also show a selective effect of Hoxa2 on endochondral ossification processes since Gdf5 and Gdf10, and Bmp4 or PthrP were up-regulated and unmodified, respectively. Since Hoxa2 deregulation in mice induces a proportionate short stature phenotype mimicking human idiopathic conditions, our results give an insight into understanding proportionate short stature pathogenesis by highlighting molecular factors whose combined deregulation may be involved in such a disease. PMID:24129174

Dynamic compression of rabbit adipose-derived stem cells transfected with insulin-like growth factor 1 in chitosan/gelatin scaffolds induces chondrogenesis and matrix biosynthesis.

PubMed

Li, Jianjun; Zhao, Qun; Wang, Enbo; Zhang, Chuanhui; Wang, Guangbin; Yuan, Quan

2012-05-01

Articular cartilage is routinely subjected to mechanical forces and growth factors. Adipose-derived stem cells (ASCs) are multi-potent adult stem cells and capable of chondrogenesis. In the present study, we investigated the comparative and interactive effects of dynamic compression and insulin-like growth factor-I (IGF-I) on the chondrogenesis of rabbit ASCs in chitosan/gelatin scaffolds. Rabbit ASCs with or without a plasmid overexpressing of human IGF-1 were cultured in chitosan/gelatin scaffolds for 2 days, then subjected to cyclic compression with 5% strain and 1 Hz for 4 h per day for seven consecutive days. Dynamic compression induced chondrogenesis of rabbit ASCs by activating calcium signaling pathways and up-regulating the expression of Sox-9. Dynamic compression plus IGF-1 overexpression up-regulated expression of chondrocyte-specific extracellular matrix genes including type II collagen, Sox-9, and aggrecan with no effect on type X collagen expression. Furthermore, dynamic compression and IGF-1 expression promoted cellular proliferation and the deposition of proteoglycan and collagen. Intracellular calcium ion concentration and peak currents of Ca(2+) ion channels were consistent with chondrocytes. The tissue-engineered cartilage from this process had excellent mechanical properties. When applied together, the effects achieved by the two stimuli (dynamic compression and IGF-1) were greater than those achieved by either stimulus alone. Our results suggest that dynamic compression combined with IGF-1 overexpression might benefit articular cartilage tissue engineering in cartilage regeneration. Copyright © 2011 Wiley Periodicals, Inc.

Chemical modification of extracellular matrix by cold atmospheric plasma-generated reactive species affects chondrogenesis and bone formation

PubMed Central

Eisenhauer, Peter; Chernets, Natalie; Song, You; Dobrynin, Danil; Pleshko, Nancy; Steinbeck, Marla J.; Freeman, Theresa A.

2017-01-01

The goal of this study was to investigate whether cold plasma generated by dielectric barrier discharge (DBD) modifies extracellular matrices (ECM) to influence chondrogenesis and endochondral ossification. Replacement of cartilage by bone during endochondral ossification is essential in fetal skeletal development, bone growth and fracture healing. Regulation of this process by the ECM occurs through matrix remodelling, involving a variety of cell attachment molecules and growth factors, which influence cell morphology and protein expression. The commercially available ECM, Matrigel, was treated with microsecond or nanosecond pulsed (µsp or nsp, respectively) DBD frequencies conditions at the equivalent frequencies (1 kHz) or power (~1 W). Recombinant human bone morphogenetic protein-2 was added and the mixture subcutaneously injected into mice to simulate ectopic endochondral ossification. Two weeks later, the masses were extracted and analysed by microcomputed tomography. A significant increase in bone formation was observed in Matrigel treated with µsp DBD compared with control, while a significant decrease in bone formation was observed for both nsp treatments. Histological and immunohistochemical analysis showed Matrigel treated with µsp plasma increased the number of invading cells, the amount of vascular endothelial growth factor and chondrogenesis while the opposite was true for Matrigel treated with nsp plasma. In support of the in vivo Matrigel study, 10 T1/2 cells cultured in vitro on µsp DBD-treated type I collagen showed increased expression of adhesion proteins and activation of survival pathways, which decreased with nsp plasma treatments. These results indicate DBD modification of ECM can influence cellular behaviours to accelerate or inhibit chondrogenesis and endochondral ossification. PMID:27510797

Genome‐Wide MicroRNA and Gene Analysis of Mesenchymal Stem Cell Chondrogenesis Identifies an Essential Role and Multiple Targets for miR‐140‐5p

PubMed Central

Tselepi, Maria; Gómez, Rodolfo; Woods, Steven; Hui, Wang; Smith, Graham R.; Shanley, Daryl P.; Clark, Ian M.; Young, David A.

2015-01-01

Abstract microRNAs (miRNAs) are abundantly expressed in development where they are critical determinants of cell differentiation and phenotype. Accordingly miRNAs are essential for normal skeletal development and chondrogenesis in particular. However, the question of which miRNAs are specific to the chondrocyte phenotype has not been fully addressed. Using microarray analysis of miRNA expression during mesenchymal stem cell chondrogenic differentiation and detailed examination of the role of essential differentiation factors, such as SOX9, TGF‐β, and the cell condensation phase, we characterize the repertoire of specific miRNAs involved in chondrocyte development, highlighting in particular miR‐140 and miR‐455. Further with the use of mRNA microarray data we integrate miRNA expression and mRNA expression during chondrogenesis to underline the particular importance of miR‐140, especially the ‐5p strand. We provide a detailed identification and validation of direct targets of miR‐140‐5p in both chondrogenesis and adult chondrocytes with the use of microarray and 3′UTR analysis. This emphasizes the diverse array of targets and pathways regulated by miR‐140‐5p. We are also able to confirm previous experimentally identified targets but, additionally, identify a novel positive regulation of the Wnt signaling pathway by miR‐140‐5p. Wnt signaling has a complex role in chondrogenesis and skeletal development and these findings illustrate a previously unidentified role for miR‐140‐5p in regulation of Wnt signaling in these processes. Together these developments further highlight the role of miRNAs during chondrogenesis to improve our understanding of chondrocyte development and guide cartilage tissue engineering. Stem Cells 2015;33:3266–3280 PMID:26175215

Enhancement of mesenchymal stem cell chondrogenesis with short-term low intensity pulsed electromagnetic fields.

PubMed

Parate, Dinesh; Franco-Obregón, Alfredo; Fröhlich, Jürg; Beyer, Christian; Abbas, Azlina A; Kamarul, Tunku; Hui, James H P; Yang, Zheng

2017-08-25

Pulse electromagnetic fields (PEMFs) have been shown to recruit calcium-signaling cascades common to chondrogenesis. Here we document the effects of specified PEMF parameters over mesenchymal stem cells (MSC) chondrogenic differentiation. MSCs undergoing chondrogenesis are preferentially responsive to an electromagnetic efficacy window defined by field amplitude, duration and frequency of exposure. Contrary to conventional practice of administering prolonged and repetitive exposures to PEMFs, optimal chondrogenic outcome is achieved in response to brief (10 minutes), low intensity (2 mT) exposure to 6 ms bursts of magnetic pulses, at 15 Hz, administered only once at the onset of chondrogenic induction. By contrast, repeated exposures diminished chondrogenic outcome and could be attributed to calcium entry after the initial induction. Transient receptor potential (TRP) channels appear to mediate these aspects of PEMF stimulation, serving as a conduit for extracellular calcium. Preventing calcium entry during the repeated PEMF exposure with the co-administration of EGTA or TRP channel antagonists precluded the inhibition of differentiation. This study highlights the intricacies of calcium homeostasis during early chondrogenesis and the constraints that are placed on PEMF-based therapeutic strategies aimed at promoting MSC chondrogenesis. The demonstrated efficacy of our optimized PEMF regimens has clear clinical implications for future regenerative strategies for cartilage.

Comparison of Simulated Microgravity and Hydrostatic Pressure for Chondrogenesis of hASC.

PubMed

Mellor, Liliana F; Steward, Andrew J; Nordberg, Rachel C; Taylor, Michael A; Loboa, Elizabeth G

2017-04-01

Cartilage tissue engineering is a growing field due to the lack of regenerative capacity of native tissue. The use of bioreactors for cartilage tissue engineering is common, but the results are controversial. Some studies suggest that microgravity bioreactors are ideal for chondrogenesis, while others show that mimicking hydrostatic pressure is crucial for cartilage formation. A parallel study comparing the effects of loading and unloading on chondrogenesis has not been performed. The goal of this study was to evaluate chondrogenesis of human adipose-derived stem cells (hASC) under two different mechanical stimuli relative to static culture: microgravity and cyclic hydrostatic pressure (CHP). Pellets of hASC were cultured for 14 d under simulated microgravity using a rotating wall vessel bioreactor or under CHP (7.5 MPa, 1 Hz, 4 h · d-1) using a hydrostatic pressure vessel. We found that CHP increased mRNA expression of Aggrecan, Sox9, and Collagen II, caused a threefold increase in sulfated glycosaminoglycan production, and resulted in stronger vimentin staining intensity and organization relative to microgravity. In addition, Wnt-signaling patterns were altered in a manner that suggests that simulated microgravity decreases chondrogenic differentiation when compared to CHP. Our goal was to compare chondrogenic differentiation of hASC using a microgravity bioreactor and a hydrostatic pressure vessel, two commonly used bioreactors in cartilage tissue engineering. Our results indicate that CHP promotes hASC chondrogenesis and that microgravity may inhibit hASC chondrogenesis. Our findings further suggest that cartilage formation and regeneration might be compromised in space due to the lack of mechanical loading.Mellor LF, Steward AJ, Nordberg RC, Taylor MA, Loboa EG. Comparison of simulated microgravity and hydrostatic pressure for chondrogenesis of hASC. Aerosp Med Hum Perform. 2017; 88(4):377-384.

[Molecular cloning, expression of rat Msx-1 and Msx-2 during early embryo genesis and roles for mandibular chondrogenesis].

PubMed

Ishiguro, S

1999-03-01

Quail-chick chimera experiments have shown a contribution of carnial neural crest cells to the craniofacial skeletal elements. Moreover, tissue interactions between epithelial-mesenchymal interaction during early facial process development are required for both skeletal differentiation and morphogenesis. In this study, it was observed that Msx homeobox containing genes expressed in the facial process were important molecules of cartilage morphogenesis. Rat cDNAs were isolated and encoded by Msx-1 and -2, and then the expression patterns using in situ hybridization were investigated during early rat face development. These genes were correlatively expressed in the cranial neural crest forming area (E 9.5 dpc) and the facial process (E 12.5 dpc). Antisence inhibition of Msx genes in the E 12.5 mandibular process exhibited the alteration of their gene expression and cartilage patterns. Antisence inhibition of Msx-1 induced lack of the medial portion of cartilage, and antisence inhibition of Msx-2 enhanced chondrogenesis of mandibular process under the organ culture condition. Thus it was concluded that expression of Msx genes during mandibular process development comprises important signals of chondrogenesis.

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures.

PubMed

Juhász, Tamás; Matta, Csaba; Somogyi, Csilla; Katona, Éva; Takács, Roland; Soha, Rudolf Ferenc; Szabó, István A; Cserháti, Csaba; Sződy, Róbert; Karácsonyi, Zoltán; Bakó, Eva; Gergely, Pál; Zákány, Róza

2014-03-01

Biomechanical stimuli play important roles in the formation of articular cartilage during early foetal life, and optimal mechanical load is a crucial regulatory factor of adult chondrocyte metabolism and function. In this study, we undertook to analyse mechanotransduction pathways during in vitro chondrogenesis. Chondroprogenitor cells isolated from limb buds of 4-day-old chicken embryos were cultivated as high density cell cultures for 6 days. Mechanical stimulation was carried out by a self-designed bioreactor that exerted uniaxial intermittent cyclic load transmitted by the culture medium as hydrostatic pressure and fluid shear to differentiating cells. The loading scheme (0.05 Hz, 600 Pa; for 30 min) was applied on culturing days 2 and 3, when final commitment and differentiation of chondroprogenitor cells occurred in this model. The applied mechanical load significantly augmented cartilage matrix production and elevated mRNA expression of several cartilage matrix constituents, including collagen type II and aggrecan core protein, as well as matrix-producing hyaluronan synthases through enhanced expression, phosphorylation and nuclear signals of the main chondrogenic transcription factor Sox9. Along with increased cAMP levels, a significantly enhanced protein kinase A (PKA) activity was also detected and CREB, the archetypal downstream transcription factor of PKA signalling, exhibited elevated phosphorylation levels and stronger nuclear signals in response to mechanical stimuli. All the above effects were diminished by the PKA-inhibitor H89. Inhibition of the PKA-independent cAMP-mediators Epac1 and Epac2 with HJC0197 resulted in enhanced cartilage formation, which was additive to that of the mechanical stimulation, implying that the chondrogenesis-promoting effect of mechanical load was independent of Epac. At the same time, PP2A activity was reduced following mechanical load and treatments with the PP2A-inhibitor okadaic acid were able to mimic the effects of

Effects of Doxycycline on Mesenchymal Stem Cell Chondrogenesis and Cartilage Repair

PubMed Central

Friel, Nicole A.; Chu, Constance R.

2017-01-01

Objective Strategies to improve cartilage repair tissue quality after bone marrow cell-based procedures may reduce later development of osteoarthritis. Doxycycline is inexpensive, well-tolerated, and has been shown to reduce matrix-metalloproteinases (MMP) and osteoarthritis progression. This study tests the hypotheses that doxycycline reduces MMP, enhances chondrogenesis of human bone marrow-derived mesenchymal stem cells (hMSC), and improves in vivo cartilage repair. Design Ninety hMSC pellets were cultured in chondrogenic media with either 0-, 1- or 2-μg/mL doxycycline. Pellets were evaluated with stereomicroscopy, proteoglycan assay, qRT-PCR, and histology. Osteochondral defects (OCD) were created in the trochlear grooves of 24-Sprague-Dawley rats treated with/without oral doxycycline. Rats were sacrificed at 12-weeks and repair tissues were examined grossly and histologically. Results hMSC pellets with 1-μg/mL (p=0.014) and 2-μg/mL (p=0.002) doxycycline had larger areas than pellets without doxycycline. hMSC pellets with 2-μg/mL doxycycline showed reduced mmp-13 mRNA (p=0.010) and protein at 21-days. Proteoglycan, DNA contents, and mRNA expressions of chondrogenic genes were similar (p>0.05). For the in vivo study, while the histological scores were similar between the two groups (p=0.116), the gross scores of the OCD repair tissues in doxycycline-treated rats were higher at 12-weeks (p=0.017), reflective of improved repair quality. The doxycycline-treated repairs also showed lower MMP-13 protein (p=0.029). Conclusions This study shows that doxycycline improves hMSC chondrogenesis and decreases MMP-13 in pellet cultures and within rat OCDs. Doxycycline exerted no negative effect on multiple measures of chondrogenesis and cartilage repair. These data support potential use of doxycycline to improve cartilage repair to delay the onset of osteoarthritis. PMID:23186943

Specification of jaw identity by the Hand2 transcription factor

PubMed Central

Funato, Noriko; Kokubo, Hiroki; Nakamura, Masataka; Yanagisawa, Hiromi; Saga, Yumiko

2016-01-01

Acquisition of the lower jaw (mandible) was evolutionarily important for jawed vertebrates. In humans, syndromic craniofacial malformations often accompany jaw anomalies. The basic helix-loop-helix transcription factor Hand2, which is conserved among jawed vertebrates, is expressed in the neural crest in the mandibular process but not in the maxillary process of the first branchial arch. Here, we provide evidence that Hand2 is sufficient for upper jaw (maxilla)-to-mandible transformation by regulating the expression of homeobox transcription factors in mice. Altered Hand2 expression in the neural crest transformed the maxillae into mandibles with duplicated Meckel’s cartilage, which resulted in an absence of the secondary palate. In Hand2-overexpressing mutants, non-Hox homeobox transcription factors were dysregulated. These results suggest that Hand2 regulates mandibular development through downstream genes of Hand2 and is therefore a major determinant of jaw identity. Hand2 may have influenced the evolutionary acquisition of the mandible and secondary palate. PMID:27329940

Stem Cells in Aggregate Form to Enhance Chondrogenesis in Hydrogels

PubMed Central

Sridharan, BanuPriya; Lin, Staphany M.; Hwu, Alexander T.; Laflin, Amy D.; Detamore, Michael S.

2015-01-01

There are a variety of exciting hydrogel technologies being explored for cartilage regenerative medicine. Our overall goal is to explore whether using stem cells in an aggregate form may be advantageous in these applications. 3D stem cell aggregates hold great promise as they may recapitulate the in vivo skeletal tissue condensation, a property that is not typically observed in 2D culture. We considered two different stem cell sources, human umbilical cord Wharton’s jelly cells (hWJCs, currently being used in clinical trials) and rat bone marrow-derived mesenchymal stem cells (rBMSCs). The objective of the current study was to compare the influence of cell phenotype, aggregate size, and aggregate number on chondrogenic differentiation in a generic hydrogel (agarose) platform. Despite being differing cell sources, both rBMSC and hWJC aggregates were consistent in outperforming cell suspension control groups in biosynthesis and chondrogenesis. Higher cell density impacted biosynthesis favorably, and the number of aggregates positively influenced chondrogenesis. Therefore, we recommend that investigators employing hydrogels consider using cells in an aggregate form for enhanced chondrogenic performance. PMID:26719986

Effect of chondrocyte-derived early extracellular matrix on chondrogenesis of placenta-derived mesenchymal stem cells.

PubMed

Park, Yong-Beom; Seo, Sinji; Kim, Jin-A; Heo, Jin-Chul; Lim, Young-Cheol; Ha, Chul-Won

2015-06-24

The extracellular matrix (ECM) surrounding cells contains a variety of proteins that provide structural support and regulate cellular functions. Previous studies have shown that decellularized ECM isolated from tissues or cultured cells can be used to improve cell differentiation in tissue engineering applications. In this study we evaluated the effect of decellularized chondrocyte-derived ECM (CDECM) on the chondrogenesis of human placenta-derived mesenchymal stem cells (hPDMSCs) in a pellet culture system. After incubation with or without chondrocyte-derived ECM in chondrogenic medium for 1 or 3 weeks, the sizes and wet masses of the cell pellets were compared with untreated controls (hPDMSCs incubated in chondrogenic medium without chondrocyte-derived ECM). In addition, histologic analysis of the cell pellets (Safranin O and collagen type II staining) and quantitative reverse transcription-PCR analysis of chondrogenic markers (aggrecan, collagen type II, and SOX9) were carried out. Our results showed that the sizes and masses of hPDMSC pellets incubated with chondrocyte-derived ECM were significantly higher than those of untreated controls. Differentiation of hPDMSCs (both with and without chondrocyte-derived ECM) was confirmed by Safranin O and collagen type II staining. Chondrogenic marker expression and glycosaminoglycan (GAG) levels were significantly higher in hPDMSC pellets incubated with chondrocyte-derived ECM compared with untreated controls, especially in cells precultured with chondrocyte-derived ECM for 7 d. Taken together, these results demonstrate that chondrocyte-derived ECM enhances the chondrogenesis of hPDMSCs, and this effect is further increased by preculture with chondrocyte-derived ECM. This preculture method for hPDMSC chondrogenesis represents a promising approach for cartilage tissue engineering.

Chondrogenesis of infrapatellar fat pad derived adipose stem cells in 3D printed chitosan scaffold.

PubMed

Ye, Ken; Felimban, Raed; Traianedes, Kathy; Moulton, Simon E; Wallace, Gordon G; Chung, Johnson; Quigley, Anita; Choong, Peter F M; Myers, Damian E

2014-01-01

Infrapatellar fat pad adipose stem cells (IPFP-ASCs) have been shown to harbor chondrogenic potential. When combined with 3D polymeric structures, the stem cells provide a source of stem cells to engineer 3D tissues for cartilage repair. In this study, we have shown human IPFP-ASCs seeded onto 3D printed chitosan scaffolds can undergo chondrogenesis using TGFβ3 and BMP6. By week 4, a pearlescent, cartilage-like matrix had formed that penetrated the top layers of the chitosan scaffold forming a 'cap' on the scaffold. Chondrocytic morphology showed typical cells encased in extracellular matrix which stained positively with toluidine blue. Immunohistochemistry demonstrated positive staining for collagen type II and cartilage proteoglycans, as well as collagen type I. Real time PCR analysis showed up-regulation of collagen type II, aggrecan and SOX9 genes when IPFP-ASCs were stimulated by TGFβ3 and BMP6. Thus, IPFP-ASCs can successfully undergo chondrogenesis using TGFβ3 and BMP6 and the cartilage-like tissue that forms on the surface of 3D-printed chitosan scaffold may prove useful as an osteochondral graft.

Developmentally inspired programming of adult human mesenchymal stromal cells toward stable chondrogenesis.

PubMed

Occhetta, Paola; Pigeot, Sebastien; Rasponi, Marco; Dasen, Boris; Mehrkens, Arne; Ullrich, Thomas; Kramer, Ina; Guth-Gundel, Sabine; Barbero, Andrea; Martin, Ivan

2018-05-01

It is generally accepted that adult human bone marrow-derived mesenchymal stromal cells (hMSCs) are default committed toward osteogenesis. Even when induced to chondrogenesis, hMSCs typically form hypertrophic cartilage that undergoes endochondral ossification. Because embryonic mesenchyme is obviously competent to generate phenotypically stable cartilage, it is questioned whether there is a correspondence between mesenchymal progenitor compartments during development and in adulthood. Here we tested whether forcing specific early events of articular cartilage development can program hMSC fate toward stable chondrogenesis. Inspired by recent findings that spatial restriction of bone morphogenetic protein (BMP) signaling guides embryonic progenitors toward articular cartilage formation, we hypothesized that selective inhibition of BMP drives the phenotypic stability of hMSC-derived chondrocytes. Two BMP type I receptor-biased kinase inhibitors were screened in a microfluidic platform for their time- and dose-dependent effect on hMSC chondrogenesis. The different receptor selectivity profile of tested compounds allowed demonstration that transient blockade of both ALK2 and ALK3 receptors, while permissive to hMSC cartilage formation, is necessary and sufficient to maintain a stable chondrocyte phenotype. Remarkably, even upon compound removal, hMSCs were no longer competent to undergo hypertrophy in vitro and endochondral ossification in vivo, indicating the onset of a constitutive change. Our findings demonstrate that adult hMSCs effectively share properties of embryonic mesenchyme in the formation of transient but also of stable cartilage. This opens potential pharmacological strategies to articular cartilage regeneration and more broadly indicates the relevance of developmentally inspired protocols to control the fate of adult progenitor cell systems.

The 'invisible hand': regulation of RHO GTPases by RHOGDIs.

PubMed

Garcia-Mata, Rafael; Boulter, Etienne; Burridge, Keith

2011-07-22

The 'invisible hand' is a term originally coined by Adam Smith in The Theory of Moral Sentiments to describe the forces of self-interest, competition and supply and demand that regulate the resources in society. This metaphor continues to be used by economists to describe the self-regulating nature of a market economy. The same metaphor can be used to describe the RHO-specific guanine nucleotide dissociation inhibitor (RHOGDI) family, which operates in the background, as an invisible hand, using similar forces to regulate the RHO GTPase cycle.

The invisible hand: regulation of RHO GTPases by RHOGDIs

PubMed Central

Garcia-Mata, Rafael; Boulter, Etienne; Burridge, Keith

2011-01-01

Preface The 'invisible hand' is a term originally coined by Adam Smith in the Theory of Moral Sentiments to describe the forces of self-interest, competition, and supply and demand that regulate the resources in society. This metaphor continues to be used by economists to describe the self-regulating nature of a market economy. The same metaphor can be used to describe the RHO-specific guanine nucleotide dissociation inhibitor (RHOGDI) family, which operates in the background, as an invisible hand, using similar forces to regulate the RHO GTPase cycle. PMID:21779026

HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development.

PubMed

Laurent, Frédéric; Girdziusaite, Ausra; Gamart, Julie; Barozzi, Iros; Osterwalder, Marco; Akiyama, Jennifer A; Lincoln, Joy; Lopez-Rios, Javier; Visel, Axel; Zuniga, Aimée; Zeller, Rolf

2017-05-23

The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation. One of these is Snai1, an EMT master regulator whose expression is lost from Hand2-deficient AVCs. Re-expression of Snai1 in mutant AVC explants partially restores this EMT and mesenchymal cell migration. Furthermore, the HAND2-interacting enhancers in the Snai1 genomic landscape are active in embryonic hearts and other Snai1-expressing tissues. These results show that HAND2 directly regulates the molecular cascades initiating AVC cardiac valve development. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development

DOE PAGES

Laurent, Frédéric; Girdziusaite, Ausra; Gamart, Julie; ...

2017-05-23

The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation. One of these is Snai1, an EMT master regulator whose expression is lost frommore » Hand2-deficient AVCs. Re-expression of Snai1 in mutant AVC explants partially restores this EMT and mesenchymal cell migration. Furthermore, the HAND2-interacting enhancers in the Snai1 genomic landscape are active in embryonic hearts and other Snai1-expressing tissues. These results show that HAND2 directly regulates the molecular cascades initiating AVC cardiac valve development.« less

HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laurent, Frédéric; Girdziusaite, Ausra; Gamart, Julie

The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation. One of these is Snai1, an EMT master regulator whose expression is lost frommore » Hand2-deficient AVCs. Re-expression of Snai1 in mutant AVC explants partially restores this EMT and mesenchymal cell migration. Furthermore, the HAND2-interacting enhancers in the Snai1 genomic landscape are active in embryonic hearts and other Snai1-expressing tissues. These results show that HAND2 directly regulates the molecular cascades initiating AVC cardiac valve development.« less

Crystallization and X-ray diffraction analysis of the HMG domain of the chondrogenesis master regulator Sox9 in complex with a ChIP-Seq-identified DNA element

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vivekanandan, Saravanan; Moovarkumudalvan, Balasubramanian; Lescar, Julien

Sox9 is a fundamental sex-determining gene and the master regulator of chondrogenesis, and is involved in the development of various vital organs such as testes, kidney, heart and brain, and in skeletal development. Similar to other known Sox transcription factors, Sox9 recognizes and binds DNA with the consensus sequence C(T/A)TTG(T/A)(T/A) through the highly conserved HMG domain. Nonetheless, the molecular basis of the functional specificity of Sox9 in key developmental processes is still unclear. As an initial step towards a mechanistic understanding of Sox9 transcriptional regulation, the current work describes the details of the purification of the mouse Sox9 HMG domainmore » (mSox9HMG), its crystallization in complex with a ChIP-Seq-identified FOXP2 promoter DNA element and the X-ray diffraction data analysis of this complex. The mSox9HMG–FOXP2 promoter DNA complex was crystallized by the hanging-drop vapour-diffusion method using 20% PEG 3350 in 200 mMsodium/potassium phosphate with 100 mMbis-tris propane at pH 8.5. The crystals diffracted to 2.7 Å resolution and the complex crystallized in the tetragonal space groupP4 12 12, with unit-cell parametersa=b= 99.49,c= 45.89 Å. Crystal-packing parameters revealed that asymmetric unit contained one mSox9HMG–FOXP2 promoter DNA complex with an estimated solvent content of 64%.« less

A Suppressive Antagonism Evidences Progesterone and Estrogen Receptor Pathway Interaction with Concomitant Regulation of Hand2, Bmp2 and ERK during Early Decidualization

PubMed Central

Mestre-Citrinovitz, Ana C.; Kleff, Veronika; Vallejo, Griselda

2015-01-01

Progesterone receptor and estrogen receptor participate in growth and differentiation of the different rat decidual regions. Steroid hormone receptor antagonists were used to study steroid regulation of decidualization. Here we describe a suppressive interaction between progesterone receptor (onapristone) and estrogen receptor (ICI182780) antagonists and their relation to a rescue phenomenon with concomitant regulation of Hand2, Bmp2 and p-ERK1/2 during the early decidualization steps. Phenotypes of decidua development produced by antagonist treatments were characterized by morphology, proliferation, differentiation, angiogenesis and expression of signaling molecules. We found that suppression of progesterone receptor activity by onapristone treatment resulted in resorption of the implantation sites with concomitant decrease in progesterone and estrogen receptors, PCNA, KI67 antigen, DESMIN, CCND3, CX43, Prl8a2, and signaling players such as transcription factor Hand2, Bmp2 mRNAs and p-ERK1/2. Moreover, FGF-2 and Vegfa increased as a consequence of onapristone treatment. Implantation sites from antagonist of estrogen receptor treated rats developed all decidual regions, but showed an anomalous blood vessel formation at the mesometrial part of the decidua. The deleterious effect of onapristone was partially counteracted by the impairment of estrogen receptor activity with rescue of expression levels of hormone steroid receptors, proliferation and differentiation markers, and the induction of a probably compensatory increase in signaling molecules Hand2, Bmp2 and ERK1/2 activation compared to oil treated controls. This novel drug interaction during decidualization could be applied to pathological endometrial cell proliferation processes to improve therapies using steroid hormone receptor targets. PMID:25897495

Human immunodeficiency virus type 1 enhancer-binding protein 3 is essential for the expression of asparagine-linked glycosylation 2 in the regulation of osteoblast and chondrocyte differentiation.

PubMed

Imamura, Katsuyuki; Maeda, Shingo; Kawamura, Ichiro; Matsuyama, Kanehiro; Shinohara, Naohiro; Yahiro, Yuhei; Nagano, Satoshi; Setoguchi, Takao; Yokouchi, Masahiro; Ishidou, Yasuhiro; Komiya, Setsuro

2014-04-04

Human immunodeficiency virus type 1 enhancer-binding protein 3 (Hivep3) suppresses osteoblast differentiation by inducing proteasomal degradation of the osteogenesis master regulator Runx2. In this study, we tested the possibility of cooperation of Hivep1, Hivep2, and Hivep3 in osteoblast and/or chondrocyte differentiation. Microarray analyses with ST-2 bone stroma cells demonstrated that expression of any known osteochondrogenesis-related genes was not commonly affected by the three Hivep siRNAs. Only Hivep3 siRNA promoted osteoblast differentiation in ST-2 cells, whereas all three siRNAs cooperatively suppressed differentiation in ATDC5 chondrocytes. We further used microarray analysis to identify genes commonly down-regulated in both MC3T3-E1 osteoblasts and ST-2 cells upon knockdown of Hivep3 and identified asparagine-linked glycosylation 2 (Alg2), which encodes a mannosyltransferase residing on the endoplasmic reticulum. The Hivep3 siRNA-mediated promotion of osteoblast differentiation was negated by forced Alg2 expression. Alg2 suppressed osteoblast differentiation and bone formation in cultured calvarial bone. Alg2 was immunoprecipitated with Runx2, whereas the combined transfection of Runx2 and Alg2 interfered with Runx2 nuclear localization, which resulted in suppression of Runx2 activity. Chondrocyte differentiation was promoted by Hivep3 overexpression, in concert with increased expression of Creb3l2, whose gene product is the endoplasmic reticulum stress transducer crucial for chondrogenesis. Alg2 silencing suppressed Creb3l2 expression and chondrogenesis of ATDC5 cells, whereas infection of Alg2-expressing virus promoted chondrocyte maturation in cultured cartilage rudiments. Thus, Alg2, as a downstream mediator of Hivep3, suppresses osteogenesis, whereas it promotes chondrogenesis. To our knowledge, this study is the first to link a mannosyltransferase gene to osteochondrogenesis.

The influence of ferucarbotran on the chondrogenesis of human mesenchymal stem cells

PubMed Central

Henning, Tobias D; Sutton, Elizabeth J; Kim, Anne; Golovko, Daniel; Horvai, Andrew; Ackerman, Larry; Sennino, Barbara; McDonald, Donald; Lotz, Jeffrey; Daldrup-Link, Heike E

2010-01-01

For in vivo applications of magnetically labeled stem cells, biological effects of the labeling procedure have to be precluded. This study evaluates the effect of different Ferucarbotran cell labeling protocols on chondrogenic differentiation of human mesenchymal stem cells (hMSC) as well as their implications for MR imaging. hMSC were labeled with Ferucarbotran using various protocols: Cells were labeled with 100μg Fe/ml for 4h and 18h and additional samples were cultured for 6 or 12 days after the 18-hour labeling. Supplementary samples were labeled by transfection with protamine sulfate. Iron uptake was quantified by ICP-spectrometry and labeled cells were investigated by transmission electron microscopy and by immunostaining for ferucarbotran. The differentiation potential of labeled cells was compared to unlabeled controls by staining with alcian blue and hematoxylin & eosin, then quantified by measurements of glucosaminoglycans (GAG). Contrast agent effect at 3T was investigated on day 1 and day 14 of chondrogenic differentiation by measuring signal-to-noise ratios on T2-SE and T2*-GE-sequences. Iron uptake was significant for all labeling protocols (p< 0.05). The uptake was highest after transfection with protamine sulfate (25.65 ± 3.96 pg/cell) and lowest at an incubation time of 4h without transfection (3.21 ± 0.21 pg/cell). While chondrogenic differentiation was decreased using all labeling protocols, the decrease in GAG synthesis was not significant after labeling for 4h without transfection. After labeling by simple incubation, chondrogenesis was found to be dose-dependent. MR imaging showed markedly lower SNR values of all labeled cells compared to the unlabeled controls. This contrast agent effect persisted for 14 days and the duration of differentiation. Magnetic labeling of hMSC with ferucarbotran inhibits chondrogenesis in a dose-dependent manner when using simple incubation techniques. When decreasing the incubation time to 4h, inhibition of

TGF-β but not BMP signaling induces prechondrogenic condensation through ATP oscillations during chondrogenesis.

PubMed

Kwon, Hyuck Joon

2012-08-10

Although both TGF-β and BMP signaling enhance expression of adhesion molecules during chondrogenesis, TGF-β but not BMP signaling can initiate condensation of uncondensed mesenchymal cells. However, it remains unclear what causes the differential effects between TGF-β and BMP signaling on prechondrogenic condensation. Our previous report demonstrated that ATP oscillations play a critical role in prechondrogenic condensation. Thus, the current study examined whether ATP oscillations are associated with the differential actions of TGF-β and BMP signaling on prechondrogenic condensation. The result revealed that while both TGF-β1 and BMP2 stimulated chondrogenic differentiation, TGF-β1 but not BMP2 induced prechondrogenic condensation. It was also found that TGF-β1 but not BMP2 induced ATP oscillations and inhibition of TGF-β but not BMP signaling prevented insulin-induced ATP oscillations. Moreover, blockage of ATP oscillations inhibited TGF-β1-induced prechondrogenic condensation. In addition, TGF-β1-driven ATP oscillations and prechondrogenic condensation depended on Ca(2+) influx via voltage-dependent calcium channels. This study suggests that Ca(2+)-driven ATP oscillations mediate TGF-β-induced the initiation step of prechondrogenic condensation and determine the differential effects between TGF-β and BMP signaling on chondrogenesis. Copyright © 2012 Elsevier Inc. All rights reserved.

Phosphate and calcium are required for TGFbeta-mediated stimulation of ANK expression and function during chondrogenesis.

PubMed

Oca, Paulina; Zaka, Raihana; Dion, Arnold S; Freeman, Theresa A; Williams, Charlene J

2010-08-01

The expression of ANK, a key player in biomineralization, is stimulated by treatment with TGFbeta. The purpose of this study was to determine whether TGFbeta stimulation of ANK expression during chondrogenesis was dependent upon the influx of calcium and phosphate into cells. Treatment of ATDC5 cells with TGFbeta increased ANK expression during all phases of chondrogenic differentiation, particularly at day 14 (proliferation) and day 32 (mineralizing hypertrophy) of culture. Phosphate uptake studies in the presence and absence of phosphonoformic acid (PFA), a competitive inhibitor of the type III Na(+)/Pi channels Pit-1 and Pit-2, indicated that the stimulation of ANK expression by TGFbeta required the influx of phosphate, specifically by the Pit-1 transporter, at all phases of differentiation. At hypertrophy, when alkaline phosphatase is highly expressed, inhibition of its activity with levamisole also abrogated the stimulatory effect of TGFbeta on ANK expression, further illustrating that Pi availability and uptake by the cells is necessary for stimulation of ANK expression in response to TGFbeta. Since previous studies of endochondral ossification in the growth plate have shown that L-type calcium channels are essential for chondrogenesis, we investigated their role in the TGFbeta-stimulated ANK response in ATDC5 cells. Treatment with nifedipine to inhibit calcium influx via the L-type channel Cav1.2 (alpha(1C)) inhibited the TGFbeta stimulated increase in ANK expression at all phases of chondrogenesis. Our findings indicate that TGFbeta stimulation of ANK expression is dependent upon the influx of phosphate and calcium into ATDC5 cells at all stages of differentiation.

CARTILAGE OLIGOMERIC MATRIX PROTEIN ENHANCES MATRIX ASSEMBLY DURING CHONDROGENESIS OF HUMAN MESENCHYMAL STEM CELLS

PubMed Central

Haleem-Smith, Hana; Calderon, Raul; Song, Yingjie; Tuan, Rocky S.; Chen, Faye H.

2011-01-01

Cartilage oligomeric matrix protein/thrombospondin-5 (COMP/TSP5) is an abundant cartilage extracellular matrix (ECM) protein that interacts with major cartilage ECM components, including aggrecan and collagens. To test our hypothesis that COMP/TSP5 functions in the assembly of the ECM during cartilage morphogenesis, we have employed mesenchymal stem cell (MSC) chondrogenesis in vitro as a model to examine the effects of COMP over-expression on neo-cartilage formation. Human bone marrow-derived MSCs were transfected with either full-length COMP cDNA or control plasmid, followed by chondrogenic induction in three-dimensional pellet or alginate-hydrogel culture. MSC chondrogenesis and ECM production was estimated based on quantitation of sulfated glycosaminoglycan (sGAG) accumulation, immunohistochemistry of the presence and distribution of cartilage ECM proteins, and real-time RT-PCR analyis of mRNA expression of cartilage markers. Our results showed that COMP over-expression resulted in increased total sGAG content during the early phase of MSC chondrogenesis, and increased immuno-detectable levels of aggrecan and collagen type II in the ECM of COMP-transfected pellet and alginate cultures, indicating more abundant cartilaginous matrix. COMP transfection did not significantly increase the transcript levels of the early chondrogenic marker, Sox9, or aggrecan, suggesting that enhancement of MSC cartilage ECM was effected at post-transcriptional levels. These findings strongly suggest that COMP functions in mesenchymal chondrogenesis by enhancing cartilage ECM organization and assembly. The action of COMP is most likely mediated not via direct changes in cartilage matrix gene expression but via interactions of COMP with other cartilage ECM proteins, such as aggrecan and collagens, that result in enhanced assembly and retention. PMID:22095699

Chondrogenesis of the branchial skeleton in embryonic sea lamprey, Petromyzon marinus.

PubMed

Morrison, S L; Campbell, C K; Wright, G M

2000-11-01

This study provides concise temporal and spatial characteristics of branchial chondrogenesis in embryonic sea lamprey, Petromyzon marinus, using high resolution light microscopy, transmission electron, and immunoelectron microscopy. Prechondrogenic condensations representing the first branchial arch appeared first in the mid-region of the third pharyngeal arch at 13 days post-fertilization (pf). Cartilage differentiation, defined by the presence of the unique, fibrillar, non-collagenous matrix protein characteristic of branchial cartilage, was first observed at 14 days pf. Development of lamprey branchial cartilage appeared unusual compared to that in jawed fishes, in that precartilage condensations appear as a one-cell wide orderly stack of flattened cells that extend by the addition of one dorsal and one ventral condensation. Development of lamprey gill arches from three condensations that fuse to form a single skeletal element differs from the developing gill arches of jawed fishes, where more than one skeletal element forms from a single condensation. The initial orderly arrangement of cells in the lamprey branchial prechondrogenic condensations remains throughout development. Once chondrification of the condensations begins, the branchial arches start to grow. Initially, growth occurs as a result of matrix secretion and cell migration. Later in development, the arches grow mainly by cell proliferation and enlargement. This study defines the morphology and timing of lamprey branchial chondrogenesis. Studies of lamprey chondrogenesis provide not only insight into the developmental biology of a unique non-collagenous cartilage in a primitive vertebrate but also into the general evolution of the skeletal system in vertebrates. Copyright 2000 Wiley-Liss, Inc.

Bioreactor mechanically guided 3D mesenchymal stem cell chondrogenesis using a biocompatible novel thermo-reversible methylcellulose-based hydrogel.

PubMed

Cochis, A; Grad, S; Stoddart, M J; Farè, S; Altomare, L; Azzimonti, B; Alini, M; Rimondini, L

2017-03-23

Autologous chondrocyte implantation for cartilage repair represents a challenge because strongly limited by chondrocytes' poor expansion capacity in vitro. Mesenchymal stem cells (MSCs) can differentiate into chondrocytes, while mechanical loading has been proposed as alternative strategy to induce chondrogenesis excluding the use of exogenous factors. Moreover, MSC supporting material selection is fundamental to allow for an active interaction with cells. Here, we tested a novel thermo-reversible hydrogel composed of 8% w/v methylcellulose (MC) in a 0.05 M Na 2 SO 4 solution. MC hydrogel was obtained by dispersion technique and its thermo-reversibility, mechanical properties, degradation and swelling were investigated, demonstrating a solution-gelation transition between 34 and 37 °C and a low bulk degradation (<20%) after 1 month. The lack of any hydrogel-derived immunoreaction was demonstrated in vivo by mice subcutaneous implantation. To induce in vitro chondrogenesis, MSCs were seeded into MC solution retained within a porous polyurethane (PU) matrix. PU-MC composites were subjected to a combination of compression and shear forces for 21 days in a custom made bioreactor. Mechanical stimulation led to a significant increase in chondrogenic gene expression, while histological analysis detected sulphated glycosaminoglycans and collagen II only in loaded specimens, confirming MC hydrogel suitability to support load induced MSCs chondrogenesis.

Bioreactor mechanically guided 3D mesenchymal stem cell chondrogenesis using a biocompatible novel thermo-reversible methylcellulose-based hydrogel

PubMed Central

Cochis, A.; Grad, S.; Stoddart, M. J.; Farè, S.; Altomare, L.; Azzimonti, B.; Alini, M.; Rimondini, L.

2017-01-01

Autologous chondrocyte implantation for cartilage repair represents a challenge because strongly limited by chondrocytes’ poor expansion capacity in vitro. Mesenchymal stem cells (MSCs) can differentiate into chondrocytes, while mechanical loading has been proposed as alternative strategy to induce chondrogenesis excluding the use of exogenous factors. Moreover, MSC supporting material selection is fundamental to allow for an active interaction with cells. Here, we tested a novel thermo-reversible hydrogel composed of 8% w/v methylcellulose (MC) in a 0.05 M Na2SO4 solution. MC hydrogel was obtained by dispersion technique and its thermo-reversibility, mechanical properties, degradation and swelling were investigated, demonstrating a solution-gelation transition between 34 and 37 °C and a low bulk degradation (<20%) after 1 month. The lack of any hydrogel-derived immunoreaction was demonstrated in vivo by mice subcutaneous implantation. To induce in vitro chondrogenesis, MSCs were seeded into MC solution retained within a porous polyurethane (PU) matrix. PU-MC composites were subjected to a combination of compression and shear forces for 21 days in a custom made bioreactor. Mechanical stimulation led to a significant increase in chondrogenic gene expression, while histological analysis detected sulphated glycosaminoglycans and collagen II only in loaded specimens, confirming MC hydrogel suitability to support load induced MSCs chondrogenesis. PMID:28332587

Successful chondrogenesis within scaffolds, using magnetic stem cell confinement and bioreactor maturation.

PubMed

Luciani, Nathalie; Du, Vicard; Gazeau, Florence; Richert, Alain; Letourneur, Didier; Le Visage, Catherine; Wilhelm, Claire

2016-06-01

Tissue engineering strategies, such as cellularized scaffolds approaches, have been explored for cartilage replacement. The challenge, however, remains to produce a cartilaginous tissue incorporating functional chondrocytes and being large and thick enough to be compatible with the replacement of articular defects. Here, we achieved unprecedented cartilage tissue production into a porous polysaccharide scaffold by combining of efficient magnetic condensation of mesenchymal stem cells, and dynamic maturation in a bioreactor. In optimal conditions, all the hallmarks of chondrogenesis were enhanced with a 50-fold increase in collagen II expression compared to negative control, an overexpression of aggrecan and collagen XI, and a very low expression of collagen I and RUNX2. Histological staining showed a large number of cellular aggregates, as well as an increased proteoglycan synthesis by chondrocytes. Interestingly, electron microscopy showed larger chondrocytes and a more abundant extracellular matrix. In addition, the periodicity of the neosynthesized collagen fibers matched that of collagen II. These results represent a major step forward in replacement tissue for cartilage defects. A combination of several innovative technologies (magnetic cell seeding, polysaccharide porous scaffolds, and dynamic maturation in bioreactor) enabled unprecedented successful chondrogenesis within scaffolds. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Sprouty2 regulates endochondral bone formation by modulation of RTK and BMP signaling

PubMed Central

Joo, Adriane; Long, Roger; Cheng, Zhiqiang; Alexander, Courtney; Chang, Wenhan; Klein, Ophir D.

2016-01-01

Skeletal development is regulated by the coordinated activity of signaling molecules that are both produced locally by cartilage and bone cells and also circulate systemically. During embryonic development and postnatal bone remodeling, receptor tyrosine kinase (RTK) superfamily members play critical roles in the proliferation, survival, and differentiation of chondrocytes, osteoblasts, osteoclasts, and other bone cells. Recently, several molecules that regulate RTK signaling have been identified, including the four members of the Sprouty (Spry) family (Spry1–4). We report that Spry2 plays an important role in regulation of endochondral bone formation. Mice in which the Spry2 gene has been deleted have defective chondrogenesis and endochondral bone formation, with a postnatal decrease in skeletal size and trabecular bone mass. In these constitutive Spry2 mutants, both chondrocytes and osteoblasts undergo increased cell proliferation and impaired terminal differentiation. Tissue-specific Spry2 deletion by either osteoblast- (Col1-Cre) or chondrocyte- (Col2-Cre) specific drivers led to decreased relative bone mass, demonstrating the critical role of Spry2 in both cell types. Molecular analyses of signaling pathways in Spry2−/− mice revealed an unexpected upregulation of BMP signaling and decrease in RTK signaling. These results identify Spry2 as a critical regulator of endochondral bone formation that modulates signaling in both osteoblast and chondrocyte lineages. PMID:27130872

Chondrogenesis in a hyaluronic acid scaffold: comparison between chondrocytes and MSC from bone marrow and adipose tissue.

PubMed

Jakobsen, Rune B; Shahdadfar, Aboulghassem; Reinholt, Finn P; Brinchmann, Jan E

2010-10-01

Treatment of focal lesions of the articular cartilage of the knee using chondrocytes in a hyaluronic acid (HA) scaffold is already being investigated in clinical trials. An alternative may be to use mesenchymal stem cells (MSC). We have compared articular chondrocytes with MSC from human bone marrow (BM) and adipose tissue (AT), all cultured in HA scaffolds, for their ability to express genes and synthesize proteins associated with chondrogenesis. The cells were expanded in monolayer cultures. After seeding into the scaffold, the chondrocytes were maintained in medium, while the two MSC populations were given a chondrogenic differentiation medium. Chondrogenesis was assessed by real-time RT-PCR for chondrocyte-associated genes, by immunohistochemistry and by ELISA for collagens in the supernatant. Redifferentiation of the dedifferentiated chondrocytes in the HA scaffold was shown by a modest increase in type II collagen mRNA (COL2A1) and reduction in COL1A1. BM-MSC expressed 600-fold higher levels of COL2A1 than chondrocytes after 3 weeks in the scaffold. The levels of aggrecan (AGC1) and COL1A1 were similar for chondrocyte and BM-MSC scaffold cultures, while COL10A1 was higher in the BM-MSC. AT-MSC expressed levels of COL2A1 and COL1A1 similar to chondrocytes, but less AGC1 and COL10A1. Surprisingly, little collagen II protein was observed in the scaffold. Instead, collagen II was found in the culture medium. Chondrogenesis in HA scaffolds was more efficient using BM-MSC than AT-MSC or chondrocytes. Some of the secreted collagen II escaped entrapment in the extracellular space and was detected in the culture medium.

Enhanced chondrogenesis with upregulation of PKR using a novel hydrostatic pressure bioreactor.

PubMed

Kim, Jeonghyun; Montagne, Kevin; Ushida, Takashi; Furukawa, Katsuko

2015-01-01

In this study, we developed a novel bioreactor to load hydrostatic pressure to promote chondrogenesis of prechondrogenic ATDC5 cells in as little as 3 days. Furthermore, we showed that loading hydrostatic pressure induced the upregulation of PKR, which is known to participate in mechanotransduction in various models.

Fli1 and Ets1 have distinct roles in connective tissue growth factor/CCN2 gene regulation and induction of the profibrotic gene program.

PubMed

Nakerakanti, Sashidhar S; Kapanadze, Bagrat; Yamasaki, Masaomi; Markiewicz, Margaret; Trojanowska, Maria

2006-09-01

CCN2 (connective tissue growth factor), an important regulator of angiogenesis, chondrogenesis, and wound healing, is overexpressed in a majority of fibrotic diseases and in various tumors. This study investigated regulation of CCN2 gene expression by Ets family of transcription factors, focusing on two members, Fli1 and Ets1, with deregulated expression during fibrosis and tumorigenesis. We show that Ets1 and Fli1 have opposite effects on CCN2 gene expression. Ets1 functions as an activator of CCN2 transcription, whereas Fli1 acts as a repressor. A functional Ets binding site was mapped at -114 within the CCN2 promoter. This site not only mediates stimulation by Ets factors, including Ets1, Ets2, and GABPalpha/beta, but is also required for the transforming growth factor (TGF)-beta response. The contrasting functions of Ets1 and Fli1 in regulation of the CCN2 gene were confirmed by suppressing their endogenous levels using adenoviral vectors expressing specific small interfering RNAs. Additional experiments using chromatin immunoprecipitation assays have revealed that in fibroblasts both Ets1 and Fli1 occupy the CCN2 promoter. TGF-beta stimulation resulted in displacement of Fli1 from the CCN2 promoter and a transient inhibition of Fli1 synthesis. Moreover, reduction of Fli1 expression resulted in up-regulation of COL1A1 and COL1A2 genes and down-regulation of the MMP1 gene. Thus, inhibition of Fli1 recapitulated some of the key effects of TGF-beta, suggesting that Fli1 suppression is involved in activation of the profibrotic gene program in fibroblasts. On the other hand, activation of the CCN2 gene downstream of Ets1 is consistent with its role in angiogenesis and extracellular matrix remodeling. This study strongly supports a critical role of Fli1 and Ets1 in the pathological extracellular matrix regulation during fibrosis and cancer.

Recent Insights into the Regulation of the Growth Plate

PubMed Central

Lui, Julian C.; Nilsson, Ola; Baron, Jeffrey

2014-01-01

For most bones, elongation is driven primarily by chondrogenesis at the growth plates. This process results from chondrocyte proliferation, hypertrophy, and extracellular matrix secretion and is carefully orchestrated by complex networks of local paracrine factors and modulated by endocrine factors. We review here recent advances in the understanding of growth plate physiology. These advances include new approaches to study expression patterns of large numbers of genes in the growth plate, using microdissection followed by microarray. This approach has been combined with genome-wide association studies to provide insights into the regulation of the human growth plate. We also review recent studies elucidating the roles of bone morphogenetic proteins, fibroblast growth factors, C-type natriuretic peptide, and suppressor of cytokine signaling in the local regulation of growth plate chondrogenesis and longitudinal bone growth. PMID:24740736

MicroRNA-363 negatively regulates the left ventricular determining transcription factor HAND1 in human embryonic stem cell-derived cardiomyocytes.

PubMed

Wagh, Vilas; Pomorski, Alexander; Wilschut, Karlijn J; Piombo, Sebastian; Bernstein, Harold S

2014-06-06

Posttranscriptional control of mRNA by microRNA (miRNA) has been implicated in the regulation of diverse biologic processes from directed differentiation of stem cells through organism development. We describe a unique pathway by which miRNA regulates the specialized differentiation of cardiomyocyte (CM) subtypes. We differentiated human embryonic stem cells (hESCs) to cardiac progenitor cells and functional CMs, and characterized the regulated expression of specific miRNAs that target transcriptional regulators of left/right ventricular-subtype specification. From >900 known human miRNAs in hESC-derived cardiac progenitor cells and functional CMs, a subset of differentially expressed cardiac miRNAs was identified, and in silico analysis predicted highly conserved binding sites in the 3'-untranslated regions (3'UTRs) of Hand-and-neural-crest-derivative-expressed (HAND) genes 1 and 2 that are involved in left and right ventricular development. We studied the temporal and spatial expression patterns of four miRNAs in differentiating hESCs, and found that expression of miRNA (miR)-363, miR-367, miR-181a, and miR-181c was specific for stage and site. Further analysis showed that miR-363 overexpression resulted in downregulation of HAND1 mRNA and protein levels. A dual luciferase reporter assay demonstrated functional interaction of miR-363 with the full-length 3'UTR of HAND1. Expression of anti-miR-363 in-vitro resulted in enrichment for HAND1-expressing CM subtype populations. We also showed that BMP4 treatment induced the expression of HAND2 with less effect on HAND1, whereas miR-363 overexpression selectively inhibited HAND1. These data show that miR-363 negatively regulates the expression of HAND1 and suggest that suppression of miR-363 could provide a novel strategy for generating functional left-ventricular CMs.

Glycosylation of DMP1 Is Essential for Chondrogenesis of Condylar Cartilage.

PubMed

Weng, Y; Liu, Y; Du, H; Li, L; Jing, B; Zhang, Q; Wang, X; Wang, Z; Sun, Y

2017-12-01

The mandibular condylar cartilage (MCC) shoulders force for the subchondral bone during mastication. The cartilage matrix contains various large molecules, such as type I, II, and X collagens and proteoglycans (PGs), which jointly play essential roles in maintaining cartilage characteristics. PGs play key roles in maintaining the elasticity of cartilage and providing a cushion against mastication forces. In addition to the well-known PGs, DMP1-PG, which is the PG form of dentin matrix protein 1 (DMP1), is a newly identified PG. DMP1 is proteolytically processed in vivo, and the N-terminus is glycosylated into its PG form-that is, DMP1-PG, which is highly expressed not only in tooth and bone but also in the matrix of the MCC. However, the specific functions of DMP1-PG in the MCC remain unclear. In human temporomandibular joint osteoarthritis and hyperocclusion model rat specimens, PGs are significantly downregulated, and DMP1-PG is the most prominently affected PG. To further investigate the role of DMP1-PG in condylar chondrogenesis, a glycosylation site mutant (S 89 -G 89 ) mouse model was established with knock-in methods. In the MCC of the S89G-DMP1 mice, the glycosylation level of DMP1 was significantly downregulated, and a series of abnormal developmental and pathologic changes could be observed. The morphologic changes included thinner cartilage layers, deformations of the MCC, and disordered arrangements of the chondrocytes, and an earlier onset of temporomandibular joint osteoarthritis-like changes was observed. In addition, markers of chondrogenesis were downregulated, and the matrix of the MCC displayed OA phenotypes in the S89G-DMP1 mice. Further investigations showed that the transforming growth factor β signaling molecules were affected in the MCC after the loss of DMP1-PG. In addition, the loss of DMP1-PG significantly accelerated the progression of cartilage injuries in the hyperocclusion models. Given these findings, we investigated the significant

Comparative Chondrogenesis of Human Cell Sources in 3D Scaffolds

PubMed Central

Tıg̑lı, R. Seda; Ghosh, Sourabh; Laha, Michael M.; Shevde, Nirupama K.; Daheron, Laurence; Gimble, Jeffrey; Gümüşdereliog̑lu, Menemşe; Kaplan, David L.

2009-01-01

Cartilage tissue can be engineered by starting from a diversity of cell sources, including stem-cell based and primary cell-based platforms. Selecting an appropriate cell source for the process of cartilage tissue engineering or repair is critical and challenging due to the variety of cell options available. In this study, cellular responses of isolated human chondrocytes, human embryonic stem cells and mesenchymal stem cells (MSCs) derived from three sources, human embryonic stem cells, bone marrow and adipose tissue, were assessed for chondrogenic potential in 3D culture. All cell sources were characterized by FACS analysis to compare expression of some surface markers. The cells were differentiated in two different biomaterial matrices, silk and chitosan scaffolds, in the presence and absence of bone morphogenetic protein 6 (BMP-6) along with the standard chondrogenic differentiating factors. Embryonic stem cells derived MSCs showed unique characteristics with preserved chondrogenic phenotype in both scaffolds with regard to chondrogenesis, as determined by real time RT-PCR, histological and microscopic analyses. After 4 weeks of cultivation, embryonic stem cells derived MSCs were promising for chondrogenesis, particularly in the silk scaffolds with BMP-6. The results suggest that cell source differences are important to consider with regard to chondrogenic outcomes and with the variables addressed here, the human embryonic stem cells derived MSCs were the preferred cell source. PMID:19382119

Gdf11 is a negative regulator of chondrogenesis and myogenesis in the developing chick limb.

PubMed

Gamer, L W; Cox, K A; Small, C; Rosen, V

2001-01-15

GDF11, a new member of the TGF-beta gene superfamily, regulates anterior/posterior patterning in the axial skeleton during mouse embryogenesis. Gdf11 null mice display skeletal abnormalities that appear to represent anterior homeotic transformations of vertebrae consistent with high levels of Gdf11 expression in the primitive streak, presomitic mesoderm, and tail bud. However, despite strong Gdf11 expression in the limb throughout development, this structure does not appear to be affected in the knockout mice. In order to understand this dichotomy of Gdf11 expression versus Gdf11 function, we identified the chicken Gdf11 gene and studied its role during limb formation. In the early limb bud, Gdf11 transcripts are detected in the subectodermal mesoderm at the distal tip, in a region overlapping the progress zone. At these stages, Gdf11 is excluded from the central core mesenchyme where precartilaginous condensations will form. Later in development, Gdf11 continues to be expressed in the distal most mesenchyme and can also be detected more proximally, in between the forming skeletal elements. When beads incubated in GDF11 protein were implanted into the early wing bud, GDF11 caused severe truncations of the limb that affected both the cartilage elements and the muscle. Limb shortening appeared to be the result of an inhibition of chondrogenesis and myogenesis and using an in vitro micromass assay, we confirmed the negative effects of GDF11 on both myogenic and chondrogenic cell differentiation. Analysis of molecular markers of skeletal patterning revealed that GDF11 induced ectopic expression of Hoxd-11 and Hoxd-13, but not of Hoxa-11, Hoxa-13, or the Msx genes. These data suggest that GDF11 may be involved in controlling the late distal expression of the Hoxd genes during limb development and that misregulation of these Hox genes by excess GDF11 may cause some of the observed alterations in skeletal element shape. In addition, GDF11 induced the expression of its own

Fibroblast growth factor receptors in in vitro and in vivo chondrogenesis: relating tissue engineering using adult mesenchymal stem cells to embryonic development.

PubMed

Hellingman, Catharine A; Koevoet, Wendy; Kops, Nicole; Farrell, Eric; Jahr, Holger; Liu, Wei; Baatenburg de Jong, Robert J; Frenz, Dorothy A; van Osch, Gerjo J V M

2010-02-01

Adult mesenchymal stem cells (MSCs) are considered promising candidate cells for therapeutic cartilage and bone regeneration. Because tissue regeneration and embryonic development may involve similar pathways, understanding common pathways may lead to advances in regenerative medicine. In embryonic limb development, fibroblast growth factor receptors (FGFRs) play a role in chondrogenic differentiation. The aim of this study was to investigate and compare FGFR expression in in vivo embryonic limb development and in vitro chondrogenesis of MSCs. Our study showed that in in vitro chondrogenesis of MSCs three sequential stages can be found, as in embryonic limb development. A mesenchymal condensation (indicated by N-cadherin) is followed by chondrogenic differentiation (indicated by collagen II), and hypertrophy (indicated by collagen X). FGFR1-3 are expressed in a stage-dependent pattern during in vitro differentiation and in vivo embryonic limb development. In both models FGFR2 is clearly expressed by cells in the condensation phase. No FGFR expression was observed in differentiating and mature hyaline chondrocytes, whereas hypertrophic chondrocytes stained strongly for all FGFRs. To evaluate whether stage-specific modulation of chondrogenic differentiation in MSCs is possible with different subtypes of FGF, FGF2 and FGF9 were added to the chondrogenic medium during different stages in the culture process (early or late). FGF2 and FGF9 differentially affected the amount of cartilage formed by MSCs depending on the stage in which they were added. These results will help us understand the role of FGF signaling in chondrogenesis and find new tools to monitor and control chondrogenic differentiation.

Dynamic hydrostatic pressure enhances differentially the chondrogenesis of meniscal cells from the inner and outer zone.

PubMed

Zellner, J; Mueller, M; Xin, Y; Krutsch, W; Brandl, A; Kujat, R; Nerlich, M; Angele, P

2015-06-01

This study analyses the influence of dynamic hydrostatic pressure on chondrogenesis of human meniscus-derived fibrochondrocytes and explores the differences in chondrogenic differentiation under loading conditions between cells derived from the avascular inner zone and vascularized outer region of the meniscus. Aggregates of human fibrochondrocytes with cell origin from the inner region or with cell origin from the outer region were generated. From the two groups of either cell origin, aggregates were treated with dynamic hydrostatic pressure (1Hz for 4h; 0.55-5.03MPa, cyclic sinusoidal) from day 1 to day 7. The other aggregates served as unloaded controls. At day 0, 7, 14 and 21 aggregates were harvested for evaluation including histology, immunostaining and ELISA analysis for glycosaminoglycan (GAG) and collagen II. Loaded aggregates were found to be macroscopically larger and revealed immunohistochemically enhanced chondrogenesis compared to the corresponding controls. Loaded or non-loaded meniscal cells from the outer zone showed a higher potential and earlier onset of chondrogenesis compared to the cells from the inner part of the meniscus. This study suggests that intrinsic factors like cell properties in the different areas of the meniscus and their reaction on mechanical load might play important roles in designing Tissue Engineering strategies for meniscal repair in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chlorpyrifos exposure affects fgf8, sox9, and bmp4 expression required for cranial neural crest morphogenesis and chondrogenesis in Xenopus laevis embryos.

PubMed

Tussellino, Margherita; Ronca, Raffaele; Carotenuto, Rosa; Pallotta, Maria M; Furia, Maria; Capriglione, Teresa

2016-10-01

Chlorpyrifos (CPF) is an organophosphate insecticide used primarily to control foliage and soil-borne insect pests on a variety of food and feed crops. In mammals, maternal exposure to CPF has been reported to induce dose-related abnormalities such as slower brain growth and cerebral cortex thinning. In lower vertebrates, for example, fish and amphibians, teratogenic activity of this compound is correlated with several anatomical alterations. Little is known about the effects of CPF on mRNA expression of genes involved in early development of the anatomical structures appearing abnormal in embryos. This study investigated the effects of exposure to different CPF concentrations (10, 15 and 20 mg/L) on Xenopus laevis embryos from stage 4/8 to stage 46. Some of the morphological changes we detected in CPF-exposed embryos included cranial neural crest cell (NCC)-derived structures. For this reason, we analyzed the expression of select genes involved in hindbrain patterning (egr2), cranial neural crest chondrogenesis, and craniofacial development (fgf8, bmp4, sox9, hoxa2 and hoxb2). We found that CPF exposure induced a reduction in transcription of all the genes involved in NCC-dependent chondrogenesis, with largest reductions in fgf8 and sox9; whereas, in hindbrain, we did not find any alterations in egr2 expression. Changes in the expression of fgf8, bmp4, and sox9, which are master regulators of several developmental pathways, have important implications. If these changes are confirmed to belong to a general pattern of alterations in vertebrates prenatally exposed to OP, they might be useful to assess damage during vertebrate embryo development. Environ. Mol. Mutagen. 57:589-604, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Hand2 inhibits kidney specification while promoting vein formation within the posterior mesoderm

PubMed Central

Perens, Elliot A; Garavito-Aguilar, Zayra V; Guio-Vega, Gina P; Peña, Karen T; Schindler, Yocheved L; Yelon, Deborah

2016-01-01

Proper organogenesis depends upon defining the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that set the boundaries of the IM are poorly understood. Here, we show that the bHLH transcription factor Hand2 limits the size of the embryonic kidney by restricting IM dimensions. The IM is expanded in zebrafish hand2 mutants and is diminished when hand2 is overexpressed. Within the posterior mesoderm, hand2 is expressed laterally adjacent to the IM. Venous progenitors arise between these two territories, and hand2 promotes venous development while inhibiting IM formation at this interface. Furthermore, hand2 and the co-expressed zinc-finger transcription factor osr1 have functionally antagonistic influences on kidney development. Together, our data suggest that hand2 functions in opposition to osr1 to balance the formation of kidney and vein progenitors by regulating cell fate decisions at the lateral boundary of the IM. DOI: http://dx.doi.org/10.7554/eLife.19941.001 PMID:27805568

In Vivo Chondrogenesis in 3D Bioprinted Human Cell-laden Hydrogel Constructs

PubMed Central

Möller, Thomas; Hägg, Daniel; Brantsing, Camilla; Rotter, Nicole; Apelgren, Peter; Lindahl, Anders; Kölby, Lars; Gatenholm, Paul

2017-01-01

Background: The three-dimensional (3D) bioprinting technology allows creation of 3D constructs in a layer-by-layer fashion utilizing biologically relevant materials such as biopolymers and cells. The aim of this study is to investigate the use of 3D bioprinting in a clinically relevant setting to evaluate the potential of this technique for in vivo chondrogenesis. Methods: Thirty-six nude mice (Balb-C, female) received a 5- × 5- × 1-mm piece of bioprinted cell-laden nanofibrillated cellulose/alginate construct in a subcutaneous pocket. Four groups of printed constructs were used: (1) human (male) nasal chondrocytes (hNCs), (2) human (female) bone marrow–derived mesenchymal stem cells (hBMSCs), (3) coculture of hNCs and hBMSCs in a 20/80 ratio, and (4) Cell-free scaffolds (blank). After 14, 30, and 60 days, the scaffolds were harvested for histological, immunohistochemical, and mechanical analysis. Results: The constructs had good mechanical properties and keep their structural integrity after 60 days of implantation. For both the hNC constructs and the cocultured constructs, a gradual increase of glycosaminoglycan production and hNC proliferation was observed. However, the cocultured group showed a more pronounced cell proliferation and enhanced deposition of human collagen II demonstrated by immunohistochemical analysis. Conclusions: In vivo chondrogenesis in a 3D bioprinted human cell-laden hydrogel construct has been demonstrated. The trophic role of the hBMSCs in stimulating hNC proliferation and matrix deposition in the coculture group suggests the potential of 3D bioprinting of human cartilage for future application in reconstructive surgery. PMID:28280669

In Vivo Chondrogenesis in 3D Bioprinted Human Cell-laden Hydrogel Constructs.

PubMed

Möller, Thomas; Amoroso, Matteo; Hägg, Daniel; Brantsing, Camilla; Rotter, Nicole; Apelgren, Peter; Lindahl, Anders; Kölby, Lars; Gatenholm, Paul

2017-02-01

The three-dimensional (3D) bioprinting technology allows creation of 3D constructs in a layer-by-layer fashion utilizing biologically relevant materials such as biopolymers and cells. The aim of this study is to investigate the use of 3D bioprinting in a clinically relevant setting to evaluate the potential of this technique for in vivo chondrogenesis. Thirty-six nude mice (Balb-C, female) received a 5- × 5- × 1-mm piece of bioprinted cell-laden nanofibrillated cellulose/alginate construct in a subcutaneous pocket. Four groups of printed constructs were used: (1) human (male) nasal chondrocytes (hNCs), (2) human (female) bone marrow-derived mesenchymal stem cells (hBMSCs), (3) coculture of hNCs and hBMSCs in a 20/80 ratio, and (4) Cell-free scaffolds (blank). After 14, 30, and 60 days, the scaffolds were harvested for histological, immunohistochemical, and mechanical analysis. The constructs had good mechanical properties and keep their structural integrity after 60 days of implantation. For both the hNC constructs and the cocultured constructs, a gradual increase of glycosaminoglycan production and hNC proliferation was observed. However, the cocultured group showed a more pronounced cell proliferation and enhanced deposition of human collagen II demonstrated by immunohistochemical analysis. In vivo chondrogenesis in a 3D bioprinted human cell-laden hydrogel construct has been demonstrated. The trophic role of the hBMSCs in stimulating hNC proliferation and matrix deposition in the coculture group suggests the potential of 3D bioprinting of human cartilage for future application in reconstructive surgery.

Chondrogenesis of Human Bone Marrow Mesenchymal Stem Cells in 3-Dimensional, Photocrosslinked Hydrogel Constructs: Effect of Cell Seeding Density and Material Stiffness

PubMed Central

Sun, Aaron X.; Lin, Hang; Fritch, Madalyn R.; Shen, He; Alexander, Pete G.; DeHart, Michael; Tuan, Rocky S.

2018-01-01

Three-dimensional hydrogel constructs incorporated with live stem cells that support chondrogenic differentiation and maintenance offer a promising regenerative route towards addressing the limited self-repair capabilities of articular cartilage. In particular, hydrogel scaffolds that augment chondrogenesis and recapitulate the native physical properties of cartilage, such as compressive strength, can potentially be applied in point-of-care procedures. We report here the synthesis of two new materials, [poly-L-lactic acid/polyethylene glycol/poly-L-lactic acid] (PLLA-PEG 1000) and [poly-D,L-lactic acid/polyethylene glycol/poly-D,L-lactic acid] (PDLLA-PEG 1000), that are biodegradable, biocompatible (>80% viability post fabrication), and possess high, physiologically relevant mechanical strength (~1,500 to 1,800 kPa). This study examined the effects of physiologically relevant cell densities (4, 8, 20, and 50 × 106/mL) and hydrogel stiffnesses (~150kPa to ~1,500 kPa Young’s moduli) on chondrogenesis of human bone marrow stem cells incorporated in hydrogel constructs fabricated with these materials and a previously characterized PDLLA-PEG 4000. Results showed that 20 × 106 cells/mL, under a static culture condition, was the most efficient cell seeding density for extracellular matrix (ECM) production on the basis of hydroxyproline and glycosaminoglycan content. Interestingly, material stiffness did not significantly affect chondrogenesis, but rather material concentration was correlated to chondrogenesis with increasing levels at lower concentrations based on ECM production, chondrogenic gene expression, and histological analysis. These findings establish optimal cell densities for chondrogenesis within three-dimensional cell-incorporated hydrogels, inform hydrogel material development for cartilage tissue engineering, and demonstrate the efficacy and potential utility of PDLLA-PEG 1000 for point-of-care treatment of cartilage defects. PMID:28611002

Prx1 and Prx2 cooperatively regulate the morphogenesis of the medial region of the mandibular process

PubMed Central

Balic, Anamaria; Adams, Douglas; Mina, Mina

2009-01-01

Mice lacking both Prx1 and Prx2 display severe abnormalities in the mandible. Our analysis showed that complete loss of Prx gene products leads to growth abnormalities in the mandibular processes evident as early as E10.5 associated with changes in the survival of the mesenchyme in the medial region. Changes in the gene expression in the medial and lateral regions were related to gradual loss of a subpopulation of mesenchyme in the medial region expressing eHand. Our analysis also showed that Prx gene products are required for the initiation and maintenance of chondrogenesis and terminal differentiation of the chondrocytes in the caudal and rostral ends of Meckel’s cartilage. The fusion of the mandibular processes in the Prx1/Prx2 double mutants is caused by accelerated ossification. These observations together show that during mandibular morphogenesis Prx gene products play multiple roles including the cell survival, the region-specific terminal differentiation of Meckelian chondrocytes and osteogenesis. PMID:19777594

Reduced COX-2 expression in aged mice is associated with impaired fracture healing.

PubMed

Naik, Amish A; Xie, Chao; Zuscik, Michael J; Kingsley, Paul; Schwarz, Edward M; Awad, Hani; Guldberg, Robert; Drissi, Hicham; Puzas, J Edward; Boyce, Brendan; Zhang, Xinping; O'Keefe, Regis J

2009-02-01

The cellular and molecular events responsible for reduced fracture healing with aging are unknown. Cyclooxygenase 2 (COX-2), the inducible regulator of prostaglandin E(2) (PGE(2)) synthesis, is critical for normal bone repair. A femoral fracture repair model was used in mice at either 7-9 or 52-56 wk of age, and healing was evaluated by imaging, histology, and gene expression studies. Aging was associated with a decreased rate of chondrogenesis, decreased bone formation, reduced callus vascularization, delayed remodeling, and altered expression of genes involved in repair and remodeling. COX-2 expression in young mice peaked at 5 days, coinciding with the transition of mesenchymal progenitors to cartilage and the onset of expression of early cartilage markers. In situ hybridization and immunohistochemistry showed that COX-2 is expressed primarily in early cartilage precursors that co-express col-2. COX-2 expression was reduced by 75% and 65% in fractures from aged mice compared with young mice on days 5 and 7, respectively. Local administration of an EP4 agonist to the fracture repair site in aged mice enhanced the rate of chondrogenesis and bone formation to levels observed in young mice, suggesting that the expression of COX-2 during the early inflammatory phase of repair regulates critical subsequent events including chondrogenesis, bone formation, and remodeling. The findings suggest that COX-2/EP4 agonists may compensate for deficient molecular signals that result in the reduced fracture healing associated with aging.

SMAD3 and SMAD4 have a more dominant role than SMAD2 in TGFβ-induced chondrogenic differentiation of bone marrow-derived mesenchymal stem cells

PubMed Central

de Kroon, Laurie M. G.; Narcisi, Roberto; van den Akker, Guus G. H.; Vitters, Elly L.; Blaney Davidson, Esmeralda N.; van Osch, Gerjo J. V. M.; van der Kraan, Peter M.

2017-01-01

To improve cartilage formation by bone marrow-derived mesenchymal stem cells (BMSCs), the signaling mechanism governing chondrogenic differentiation requires better understanding. We previously showed that the transforming growth factor-β (TGFβ) receptor ALK5 is crucial for chondrogenesis induced by TGFβ. ALK5 phosphorylates SMAD2 and SMAD3 proteins, which then form complexes with SMAD4 to regulate gene transcription. By modulating the expression of SMAD2, SMAD3 and SMAD4 in human BMSCs, we investigated their role in TGFβ-induced chondrogenesis. Activation of TGFβ signaling, represented by SMAD2 phosphorylation, was decreased by SMAD2 knockdown and highly increased by SMAD2 overexpression. Moreover, TGFβ signaling via the alternative SMAD1/5/9 pathway was strongly decreased by SMAD4 knockdown. TGFβ-induced chondrogenesis of human BMSCs was strongly inhibited by SMAD4 knockdown and only mildly inhibited by SMAD2 knockdown. Remarkably, both knockdown and overexpression of SMAD3 blocked chondrogenic differentiation. Chondrogenesis appears to rely on a delicate balance in the amount of SMAD3 and SMAD4 as it was not enhanced by SMAD4 overexpression and was inhibited by SMAD3 overexpression. Furthermore, this study reveals that TGFβ-activated phosphorylation of SMAD2 and SMAD1/5/9 depends on the abundance of SMAD4. Overall, our findings suggest a more dominant role for SMAD3 and SMAD4 than SMAD2 in TGFβ-induced chondrogenesis of human BMSCs. PMID:28240243

SMAD3 and SMAD4 have a more dominant role than SMAD2 in TGFβ-induced chondrogenic differentiation of bone marrow-derived mesenchymal stem cells.

PubMed

de Kroon, Laurie M G; Narcisi, Roberto; van den Akker, Guus G H; Vitters, Elly L; Blaney Davidson, Esmeralda N; van Osch, Gerjo J V M; van der Kraan, Peter M

2017-02-27

To improve cartilage formation by bone marrow-derived mesenchymal stem cells (BMSCs), the signaling mechanism governing chondrogenic differentiation requires better understanding. We previously showed that the transforming growth factor-β (TGFβ) receptor ALK5 is crucial for chondrogenesis induced by TGFβ. ALK5 phosphorylates SMAD2 and SMAD3 proteins, which then form complexes with SMAD4 to regulate gene transcription. By modulating the expression of SMAD2, SMAD3 and SMAD4 in human BMSCs, we investigated their role in TGFβ-induced chondrogenesis. Activation of TGFβ signaling, represented by SMAD2 phosphorylation, was decreased by SMAD2 knockdown and highly increased by SMAD2 overexpression. Moreover, TGFβ signaling via the alternative SMAD1/5/9 pathway was strongly decreased by SMAD4 knockdown. TGFβ-induced chondrogenesis of human BMSCs was strongly inhibited by SMAD4 knockdown and only mildly inhibited by SMAD2 knockdown. Remarkably, both knockdown and overexpression of SMAD3 blocked chondrogenic differentiation. Chondrogenesis appears to rely on a delicate balance in the amount of SMAD3 and SMAD4 as it was not enhanced by SMAD4 overexpression and was inhibited by SMAD3 overexpression. Furthermore, this study reveals that TGFβ-activated phosphorylation of SMAD2 and SMAD1/5/9 depends on the abundance of SMAD4. Overall, our findings suggest a more dominant role for SMAD3 and SMAD4 than SMAD2 in TGFβ-induced chondrogenesis of human BMSCs.

Study on the effects of gradient mechanical pressures on the proliferation, apoptosis, chondrogenesis and hypertrophy of mandibular condylar chondrocytes in vitro.

PubMed

Li, Hui; Huang, Linjian; Xie, Qianyang; Cai, Xieyi; Yang, Chi; Wang, Shaoyi; Zhang, Min

2017-01-01

To investigate the effects of gradient mechanical pressure on chondrocyte proliferation, apoptosis, and the expression of markers of chondrogenesis and chondrocyte hypertrophy. Mandibular condylar chondrocytes from 5 rabbits were cultured in vitro, and pressed with static pressures of 50kPa, 100kPa, 150kPa and 200kPa for 3h, respectively. The chondrocytes cultured without pressure (0kPa) were used as control. Cell proliferation, apoptosis, and the expression of aggrecan (AGG), collagen II (COL2), collagen X (COL10), alkaline phosphatase (ALP) were investigated. Ultrastructures of the pressurized chondrocytes under transmission electron microscopy (TEM) were observed. Chondrocyte proliferation increased at 100kPa and decreased at 200kPa. Chondrocyte apoptosis increased with peak pressure at 200kPa in a dose-dependent manner. Chondrocyte necrosis increased at 200kPa. The expression of AGG increased at 200kPa. The expression of COL2 decreased at 50kPa and increased at 150kPa. The expression of COL10 and ALP increased at 150kPa. Ultrastructure of the pressurized chondrocytes under TEM showed: at 100kPa, cells were enlarged with less cellular microvillus and a bigger nucleus; at 200kPa, cells shrank with the sign of apoptosis, and apoptosis cells were found. The mechanical loading of 150kPa is the moderate pressure for chondrocyte: cell proliferation and apoptosis is balanced, necrosis is reduced, and chondrogenesis and chondrocyte hypertrophy are promoted. When the pressure is lower, chondrogenesis and chondrocyte hypertrophy are inhibited. At 200kPa, degeneration of cartilage is implied. Copyright © 2016 Elsevier Ltd. All rights reserved.

Studies of chondrogenesis in rotating systems

NASA Technical Reports Server (NTRS)

Duke, P. J.; Daane, E. L.; Montufar-Solis, D.

1993-01-01

A great deal of energy has been exerted over the years researching methods for regenerating and repairing bone and cartilage. Several techniques, especially bone implants and grafts, show great promise for providing a remedy for many skeletal disorders and chondrodystrophies. The bioreactor (rotating-wall vessel, RWV) is a cell culture system that creates a nurturing environment conducive to cell aggregation. Chondrocyte cultures have been studied as implants for repair and replacement of damaged and missing bone and cartilage since 1965 [Chesterman and Smith, J Bone Joint Surg 50B:184-197, 1965]. The ability to use large, tissue-like cartilage aggregates grown in the RWV would be of great clinical significance in treating skeletal disorders. In addition, the RWV may provide a superior method for studying chondrogenesis and chondrogenic mutations. Because the RWV is also reported to simulate many of the conditions of microgravity it is a very useful ground-based tool for studying how cell systems will react to microgravity.

Intracellular biosynthesis of lipids and cholesterol by Scap and Insig in mesenchymal cells regulates long bone growth and chondrocyte homeostasis.

PubMed

Tsushima, Hidetoshi; Tang, Yuning J; Puviindran, Vijitha; Hsu, Shu-Hsuan Claire; Nadesan, Puviindran; Yu, Chunying; Zhang, Hongyuan; Mirando, Anthony J; Hilton, Matthew J; Alman, Benjamin A

2018-06-13

During enchondral ossification, mesenchymal cells express genes regulating the intracellular biosynthesis of cholesterol and lipids. Here we investigated conditional deletion of Scap or Insig1 and Insig2 (inhibits or activates intracellular biosynthesis respectively). Mesenchymal condensation and chondrogenesis was disrupted in mice lacking Scap in mesenchymal progenitors, while mice lacking the Insig genes in mesenchymal progenitors had short limbs, but normal chondrogenesis. Mice lacking Scap in chondrocytes showed severe dwarfism, with ectopic hypertrophic cells, while deletion of Insig genes in chondrocytes caused a mild dwarfism and shorting of the hypertrophic zone. In-vitro studies showed that intracellular cholesterol in chondrocytes can derive from exogenous and endogenous sources, but that exogenous sources cannot completely overcome the phenotypic effect of Scap deficiency. Genes encoding cholesterol biosynthetic proteins are regulated by Hedgehog (Hh) signaling, and Hh signaling is also regulated by intracellular cholesterol in chondrocytes, suggesting a feedback loop in chondrocyte differentiation. Precise regulation of intracellular biosynthesis is required for chondrocyte homeostasis and long bone growth, and this data supports pharmacologic modulation of cholesterol biosynthesis as a therapy for select cartilage pathologies. © 2018. Published by The Company of Biologists Ltd.

Analysis of the Effects of Five Factors Relevant to In Vitro Chondrogenesis of Human Mesenchymal Stem Cells Using Factorial Design and High Throughput mRNA-Profiling

PubMed Central

Jakobsen, Rune B.; Østrup, Esben; Zhang, Xiaolan; Mikkelsen, Tarjei S.; Brinchmann, Jan E.

2014-01-01

The in vitro process of chondrogenic differentiation of mesenchymal stem cells for tissue engineering has been shown to require three-dimensional culture along with the addition of differentiation factors to the culture medium. In general, this leads to a phenotype lacking some of the cardinal features of native articular chondrocytes and their extracellular matrix. The factors used vary, but regularly include members of the transforming growth factor β superfamily and dexamethasone, sometimes in conjunction with fibroblast growth factor 2 and insulin-like growth factor 1, however the use of soluble factors to induce chondrogenesis has largely been studied on a single factor basis. In the present study we combined a factorial quality-by-design experiment with high-throughput mRNA profiling of a customized chondrogenesis related gene set as a tool to study in vitro chondrogenesis of human bone marrow derived mesenchymal stem cells in alginate. 48 different conditions of transforming growth factor β 1, 2 and 3, bone morphogenetic protein 2, 4 and 6, dexamethasone, insulin-like growth factor 1, fibroblast growth factor 2 and cell seeding density were included in the experiment. The analysis revealed that the best of the tested differentiation cocktails included transforming growth factor β 1 and dexamethasone. Dexamethasone acted in synergy with transforming growth factor β 1 by increasing many chondrogenic markers while directly downregulating expression of the pro-osteogenic gene osteocalcin. However, all factors beneficial to the expression of desirable hyaline cartilage markers also induced undesirable molecules, indicating that perfect chondrogenic differentiation is not achievable with the current differentiation protocols. PMID:24816923

Transfection of gene regulation nanoparticles complexed with pDNA and shRNA controls multilineage differentiation of hMSCs.

PubMed

Kim, Hye Jin; Yi, Se Won; Oh, Hyun Jyung; Lee, Jung Sun; Park, Ji Sun; Park, Keun-Hong

2018-05-29

Overexpression and knockdown of specific proteins can control stem cell differentiation for therapeutic purposes. In this study, we fabricated RUNX2, SOX9, and C/EBPα plasmid DNAs (pDNAs) and ATF4-targeting shRNA (shATF4) to induce osteogenesis, chondrogenesis, and adipogenesis of human mesenchymal stem cells (hMSCs). The pDNAs and shATF4 were complexed with TRITC-gene regulation nanoparticles (GRN). Osteogenesis-related gene expression was reduced at early (12 h) and late (36 h) time points after co-delivery of shATF4 and SOX9 or C/EBPα pDNA, respectively, and osteogenesis was inhibited in these hMSCs. By contrast, osteogenesis-related genes were highly expressed upon co-delivery of RUNX2 and ATF4 pDNAs. DEX in GRN enhanced chondrogenic differentiation. Expression of osteogenesis-, chondrogenesis-, and adipogenesis-related genes was higher in hMSCs transfected with NPs complexed with RUNX2 and ATF4 pDNAs, shATF4 and SOX9 pDNA, and shATF4 and C/EBPα pDNA for 72 h than in control hMSCs, respectively. Moreover, delivery of these NPs also increased expression of osteogenesis-, chondrogenesis-, and adipogenesis-related proteins. These alterations in expression led to morphological changes, indicating that hMSCs differentiated into osteoblasts, chondrocytes, and adipose cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer

PubMed Central

Charité, Jeroen; McFadden, David G.; Merlo, Giorgio; Levi, Giovanni; Clouthier, David E.; Yanagisawa, Masashi; Richardson, James A.; Olson, Eric N.

2001-01-01

Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix–loop–helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis. PMID:11711438

Interplay between stiffness and degradation of architectured gelatin hydrogels leads to differential modulation of chondrogenesis in vitro and in vivo.

PubMed

Sarem, Melika; Arya, Neha; Heizmann, Miriam; Neffe, Axel T; Barbero, Andrea; Gebauer, Tim P; Martin, Ivan; Lendlein, Andreas; Shastri, V Prasad

2018-03-15

The limited capacity of cartilage to heal large lesions through endogenous mechanisms has led to extensive effort to develop materials to facilitate chondrogenesis. Although physical-chemical properties of biomaterials have been shown to impact in vitro chondrogenesis, whether these findings are translatable in vivo is subject of debate. Herein, architectured 3D hydrogel scaffolds (ArcGel) (produced by crosslinking gelatin with ethyl lysine diisocyanate (LDI)) were used as a model system to investigate the interplay between scaffold mechanical properties and degradation on matrix deposition by human articular chondrocytes (HAC) from healthy donors in vitro and in vivo. Using ArcGel scaffolds of different tensile and shear modulus, and degradation behavior; in this study, we compared the fate of ex vivo engineered ArcGels-chondrocytes constructs, i.e. the traditional tissue engineering approach, with thede novoformation of cartilaginous tissue in HAC laden ArcGels in an ectopic nude mouse model. While the softer and fast degrading ArcGel (LNCO3) was more efficient at promoting chondrogenic differentiation in vitro, upon ectopic implantation, the stiffer and slow degrading ArcGel (LNCO8) was superior in maintaining chondrogenic phenotype in HAC and retention of cartilaginous matrix. Furthermore, surprisingly the de novo formation of cartilage tissue was promoted only in LNCO8. Since HAC cultured for only three days in the LNCO8 environment showed upregulation of hypoxia-associated genes, this suggests a potential role for hypoxia in the observed in vivo outcomes. In summary, this study sheds light on how immediate environment (in vivo versus in vitro) can significantly impact the outcomes of cell-laden biomaterials. In this study, 3D architectured hydrogels (ArcGels) with different mechanical and biodegradation properties were investigated for their potential to promote formation of cartilaginous matrix by human articular chondrocytes in vitro and in vivo. Two

Oxygen tension regulates the osteogenic, chondrogenic and endochondral phenotype of bone marrow derived mesenchymal stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheehy, Eamon J.; Buckley, Conor T.; Kelly, Daniel J., E-mail: kellyd9@tcd.ie

2012-01-06

Highlights: Black-Right-Pointing-Pointer Expansion in low oxygen enhances MSC proliferation and osteogenesis. Black-Right-Pointing-Pointer Differentiation in low oxygen enhances chondrogenesis and suppresses hypertrophy. Black-Right-Pointing-Pointer Oxygen can regulate the MSC phenotype for use in tissue engineering applications. -- Abstract: The local oxygen tension is a key regulator of the fate of mesenchymal stem cells (MSCs). The objective of this study was to investigate the effect of a low oxygen tension during expansion and differentiation on the proliferation kinetics as well as the subsequent osteogenic and chondrogenic potential of MSCs. We first hypothesised that expansion in a low oxygen tension (5% pO{sub 2}) wouldmore » improve both the subsequent osteogenic and chondrogenic potential of MSCs compared to expansion in a normoxic environment (20% pO{sub 2}). Furthermore, we hypothesised that chondrogenic differentiation in a low oxygen environment would suppress hypertrophy of MSCs cultured in both pellets and hydrogels used in tissue engineering strategies. MSCs expanded at 5% pO{sub 2} proliferated faster forming larger colonies, resulting in higher cell yields. Expansion at 5% pO{sub 2} also enhanced subsequent osteogenesis of MSCs, whereas differentiation at 5% pO{sub 2} was found to be a more potent promoter of chondrogenesis than expansion at 5% pO{sub 2}. Greater collagen accumulation, and more intense staining for collagen types I and X, was observed in pellets maintained at 20% pO{sub 2} compared to 5% pO{sub 2}. Both pellets and hydrogels stained more intensely for type II collagen when undergoing chondrogenesis in a low oxygen environment. Differentiation at 5% pO{sub 2} also appeared to inhibit hypertrophy in both pellets and hydrogels, as demonstrated by reduced collagen type X and Alizarin Red staining and alkaline phosphatase activity. This study demonstrates that the local oxygen environment can be manipulated in vitro to either

Conditional Expression of Wnt4 during Chondrogenesis Leads to Dwarfism in Mice

PubMed Central

Lee, Hu-Hui; Behringer, Richard R.

2007-01-01

Wnts are expressed in the forming long bones, suggesting roles in skeletogenesis. To examine the action of Wnts in skeleton formation, we developed a genetic system to conditionally express Wnt4 in chondrogenic tissues of the mouse. A mouse Wnt4 cDNA was introduced into the ubiquitously expressed Rosa26 (R26) locus by gene targeting in embryonic stem (ES) cells. The expression of Wnt4 from the R26 locus was blocked by a neomycin selection cassette flanked by loxP sites (floxneo) that was positioned between the Rosa26 promoter and the Wnt4 cDNA, creating the allele designated R26floxneoWnt4. Wnt4 expression was activated during chondrogenesis using Col2a1-Cre transgenic mice that express Cre recombinase in differentiating chondrocytes. R26floxneoWnt4; Col2a1-Cre double heterozygous mice exhibited a growth deficiency, beginning approximately 7 to 10 days after birth, that resulted in dwarfism. In addition, they also had craniofacial abnormalities, and delayed ossification of the lumbar vertebrae and pelvic bones. Histological analysis revealed a disruption in the organization of the growth plates and a delay in the onset of the primary and secondary ossification centers. Molecular studies showed that Wnt4 overexpression caused decreased proliferation and altered maturation of chondrocytes. In addition, R26floxneoWnt4; Col2a1-Cre mice had decreased expression of vascular endothelial growth factor (VEGF). These studies demonstrate that Wnt4 overexpression leads to dwarfism in mice. The data indicate that Wnt4 levels must be regulated in chondrocytes for normal growth plate development and skeletogenesis. Decreased VEGF expression suggests that defects in vascularization may contribute to the dwarf phenotype. PMID:17505543

Cartilage fragments from osteoarthritic knee promote chondrogenesis of mesenchymal stem cells without exogenous growth factor induction.

PubMed

Chen, Chia-Chun; Liao, Cheng-Hao; Wang, Yao-Horng; Hsu, Yuan-Ming; Huang, Shih-Horng; Chang, Chih-Hung; Fang, Hsu-Wei

2012-03-01

Extracellular matrix (ECM) is thought to participate significantly in guiding the differentiation process of mesenchymal stem cells (MSCs). In this study, we hypothesized that cartilage fragments from osteoarthritic knee could promote chondrogenesis of MSCs. Nonworn parts of cartilage tissues were obtained during total knee arthroplasty (TKA) surgery. Cartilage fragments and MSCs were wrapped into fibrin glue; and the constructs were implanted subcutaneously into nude mice. Histological analysis showed neocartilage-like structure with positive Alcian blue staining in the cartilage fragment-fibrin-MSC constructs. However, constructs with only MSCs in fibrin showed condensed appearance like MSCs in the pellet culture. Gene expression of type II collagen in the constructs with 60 mg cartilage fragments were significantly elevated after 4 weeks of implantation. Conversely, the constructs without cartilage fragments failed to express type II collagen, which indicated MSCs did not differentiate into a chondrogenic lineage. In conclusion, we demonstrated the effect of cartilage fragments from osteoarthritic knee in promoting chondrogenic differentiation of MSCs. This may be a favorable strategy for MSC chondrogenesis without exogenous growth factor induction. Copyright © 2011 Orthopaedic Research Society.

Energy stress-induced lncRNA HAND2-AS1 represses HIF1α-mediated energy metabolism and inhibits osteosarcoma progression

PubMed Central

Kang, Yao; Zhu, Xiaojun; Xu, Yanyang; Tang, Qinglian; Huang, Zongwen; Zhao, Zhiqiang; Lu, Jinchang; Song, Guohui; Xu, Huaiyuan; Deng, Chuangzhong; Wang, Jin

2018-01-01

During recent years, long noncoding RNAs (lncRNAs) have been recognized as key regulators in the development and progression of human cancers, however, their roles in osteosarcoma metabolism are still not well understood. The present study aims to investigate the expression profiles and potential modulation of specific lncRNA(s) in osteosarcoma metabolism. The high-throughput Hiseq sequencing was performed to screen for abnormally expressed lncRNAs in osteosarcoma cells cultured under glucose starvation condition, and lncRNA HAND2-AS1 was eventually identified as one that was significantly up-regulated when compared with normal cultured cells. Mechanistic investigations indicated that knockdown of HAND2-AS1 abrogated the energy stress-induced effect on cell apoptosis and proliferation, and promoted osteosarcoma progression. Moreover, knockdown of HAND2-AS1 promoted glucose uptake, lactate production, and the expression level of a serious of enzymes that involved in energy metabolism. Subsequently, RNA pull-down and RNA immuneprecipitation revealed that, upon energy stress, HAND2-AS1 regulated osteosarcoma metabolism through sequestering FBP1 from binding to HIF1α, thereby releasing HIF1α expression and promoting the protein level. Taken together, our integrated approach reveals a regulatory mechanism by lncRNA HAND2-AS1 to control energy metabolism and tumor development in osteosarcoma. Thus, HAND2-AS1 may be a potential biomarker and therapeutic target for the repression of osteosarcoma metabolism. PMID:29637006

Cyclic compression maintains viability and induces chondrogenesis of human mesenchymal stem cells in fibrin gel scaffolds.

PubMed

Pelaez, Daniel; Huang, Chun-Yuh Charles; Cheung, Herman S

2009-01-01

Mechanical loading has long been shown to modulate cartilage-specific extracellular matrix synthesis. With joint motion, cartilage can experience mechanical loading in the form of compressive, tensile or shearing load, and hydrostatic pressure. Recent studies have demonstrated the capacity of unconfined cyclic compression to induce chondrogenic differentiation of human mesenchymal stem cell (hMSC) in agarose culture. However, the use of a nonbiodegradable material such as agarose limits the applicability of these constructs. Of the possible biocompatible materials available for tissue engineering, fibrin is a natural regenerative scaffold, which possesses several desired characteristics including a controllable degradation rate and low immunogenicity. The objective of the present study was to determine the capability of fibrin gels for supporting chondrogenesis of hMSCs under cyclic compression. To optimize the system, three concentrations of fibrin gel (40, 60, and 80 mg/mL) and three different stimulus frequencies (0.1, 0.5, and 1.0 Hz) were used to examine the effects of cyclic compression on viability, proliferation and chondrogenic differentiation of hMSCs. Our results show that cyclic compression (10% strain) at frequencies >0.5 Hz and gel concentration of 40 mg/mL fibrinogen appears to maintain cellular viability within scaffolds. Similarly, variations in gel component concentration and stimulus frequency can be modified such that a significant chondrogenic response can be achieved by hMSC in fibrin constructs after 8 h of compression spread out over 2 days. This study demonstrates the suitability of fibrin gel for supporting the cyclic compression-induced chondrogenesis of mesenchymal stem cells.

Variations in chondrogenesis of human bone marrow-derived mesenchymal stem cells in fibrin/alginate blended hydrogels

PubMed Central

Ma, Kun; Titan, Ashley L.; Stafford, Melissa; Zheng, Chun hua; Levenston, Marc E.

2012-01-01

Fibrin and alginate hydrogels have been widely used to support chondrogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs) for articular cartilage and fibrocartilage tissue engineering, with distinct advantages and disadvantages to each material. Attempting to produce a gel scaffold exhibiting beneficial characteristics of both materials, we fabricated fibrin/alginate blended hydrogels at various blend ratios and evaluated the gel morphology, mechanical properties and their support for BM-MSC chondrogenesis. Results show that when the fibrin/alginate ratio decreased, the fibrin architecture transitioned from uniform to interconnected fibrous and finally to disconnected islands against an alginate background, with opposing trends in the alginate architecture. Fibrin maintained gel extensibility and promoted cell proliferation, while alginate improved the gel biostability and better supported glycosaminoglycan and collagen II production and chondrogenic gene expression. Blended gels had physical and biological characteristics intermediate between fibrin and alginate. Of the blends examined, FA 40:8 (40 mg/mL fibrinogen blended with 8 mg/mL alginate) was found to be the most appropriate group for future studies on tension-driven BM-MSC fibrochondrogenesis. As BM-MSC differentiation appeared to vary between fibrin and alginate regions of blended scaffolds, this study also highlighted the potential to develop spatially heterogeneous tissues through manipulating the heterogeneity of scaffold composition. PMID:22750738

Hand2 loss-of-function in Hand1-expressing Cells Reveals Distinct Roles In Epicardial And Coronary Vessel Development

PubMed Central

Barnes, Ralston M.; Firulli, Beth A.; VanDusen, Nathan J.; Morikawa, Yuka; Conway, Simon J.; Cserjesi, Peter; Vincentz, Joshua W.; Firulli, Anthony B.

2011-01-01

Rationale The bHLH transcription factors Hand1 and Hand2 are essential for embryonic development. Given their requirement for cardiogenesis, it is imperative to determine their impact on cardiovascular function. Objective Deduce the role of Hand2 within the epicardium. Method & Results We engineered a Hand1 allele expressing Cre recombinase. Cardiac Hand1 expression is largely limited to cells of the primary heart field, overlapping little with Hand2 expression. Hand1 is expressed within the septum transversum (ST) and the Hand1-lineage marks the proepicardial organ and epicardium. To examine Hand factor functional overlap, we conditionally deleted Hand2 from Hand1-expressing cells. Hand2 mutants display defective epicardialization and fail to form coronary arteries, coincident with altered ECM deposition and Pdgfr expression. Conclusion These data demonstrate a hierarchal relationship whereby transient Hand1 ST expression defines epicardial precursors that are subsequently dependent upon Hand2 function. PMID:21350214

Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures.

PubMed

Kakar, Sanjeev; Einhorn, Thomas A; Vora, Siddharth; Miara, Lincoln J; Hon, Gregory; Wigner, Nathan A; Toben, Daniel; Jacobsen, Kimberly A; Al-Sebaei, Maisa O; Song, Michael; Trackman, Philip C; Morgan, Elise F; Gerstenfeld, Louis C; Barnes, George L

2007-12-01

Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to

Murine Mesenchymal Stem Cell Commitment to Differentiation is Regulated by Mitochondrial Dynamics

PubMed Central

Forni, Maria Fernanda; Peloggia, Julia; Trudeau, Kyle; Shirihai, Orian; Kowaltowski, Alicia J.

2015-01-01

Mouse skin mesenchymal stem cells (msMSCs) are dermis CD105+CD90+CD73+CD29+CD34− mesodermal precursors which, after in vitro induction, undergo chondro, adipo and osteogenesis. Extensive metabolic reconfiguration has been found to occur during differentiation, and the bioenergetic status of a cell is known to be dependent on the quality and abundance of the mitochondrial population, which may be regulated by fusion and fission. However, little is known regarding the impact of mitochondrial dynamics on the differentiation process. We addressed this knowledge gap by isolating MSCs from Swiss female mice, inducing these cells to differentiate into osteo, chondro and adipocytes and measuring changes in mass, morphology, dynamics and bioenergetics. Mitochondrial biogenesis was increased in adipogenesis, as evaluated through confocal microscopy, citrate synthase activity and mtDNA content. The early steps of adipo and osteogenesis involved mitochondrial elongation, as well as increased expression of mitochondrial fusion proteins Mfn1 and 2. Chondrogenesis involved a fragmented mitochondrial phenotype, increased expression of fission proteins Drp1, Fis1 and 2 and enhanced mitophagy. These events were accompanied by profound bioenergetic alterations during the commitment period. Moreover, knockdown of Mfn2 in adipo and osteogenesis and the overexpression of a dominant negative form of Drp1 during chondrogenesis resulted in a loss of differentiation ability. Overall, we find that mitochondrial morphology and its regulating processes of fission/fusion are modulated early on during commitment, leading to alterations in the bioenergetic profile that are important for differentiation. We thus propose a central role for mitochondrial dynamics in the maintenance/commitment of mesenchymal stem cells. PMID:26638184

NF-kappaB specifically activates BMP-2 gene expression in growth plate chondrocytes in vivo and in a chondrocyte cell line in vitro.

PubMed

Feng, Jian Q; Xing, Lianping; Zhang, Jiang-Hong; Zhao, Ming; Horn, Diane; Chan, Jeannie; Boyce, Brendan F; Harris, Stephen E; Mundy, Gregory R; Chen, Di

2003-08-01

Bone morphogenetic protein-2 (BMP-2) regulates growth plate chondrogenesis during development and postnatal bone growth, but the control mechanisms of BMP-2 expression in growth plate chondrocytes are unknown. Here we have used both in vitro and in vivo approaches to demonstrate that transcription factor, NF-kappaB, regulates BMP-2 gene expression in chondrocytes. Two putative NF-kappaB response elements were found in the -2712/+165 region of the BMP-2 gene. Cotransfection of mutant I-kappaBalpha expression plasmids with BMP-2 promoter-luciferase reporters into TMC-23 chondrocyte cell line suppressed BMP-2 transcription. Mutations in NF-kappaB response elements in the BMP-2 gene lead to decreases in BMP-2 promoter activity. Electrophoretic mobility shift assay using nuclear extracts from TMC-23 chondrocytic cells revealed that the NF-kappaB subunits p50 and p65 bound to the NF-kappaB response elements of the BMP-2 gene. Thus, NF-kappaB may positively regulate BMP-2 gene transcription. Consistent with these findings, expression of BMP-2 mRNA was significantly reduced in growth plate chondrocytes in NF-kappaB p50/p52 dKO mice, which associated with decreased numbers of 5-bromo-2'-deoxyuridine (BrdUrd)-positive cells in the proliferating zone of growth plate in these mice. Therefore, in postnatal growth plate chondrocytes, expression of BMP-2 is regulated by NF-kappaB, which may play an important role in chondrogenesis.

Evaluation of a functional hand orthosis combined with electrical stimulation adjunct to arm-hand rehabilitation in subacute stroke patients with a severely to moderately affected hand function.

PubMed

Franck, Johan Anton; Smeets, Rob Johannes Elise Marie; Seelen, Henk Alexander Maria

2018-01-09

To investigate the usability and effectiveness of a functional hand orthosis, combined with electrical stimulation adjunct to therapy-as-usual, on functional use of the moderately/severely impaired hand in sub-acute stroke patients. Single case experiment (A-B-A'-design) involving eight sub-acute stroke patients. The functional hand orthosis and electrical stimulation were used for six weeks, four days/week, 45'/day. Action_Research_Arm_Test, Intrinsic_Motivation_Inventory. At group level, patients improved 19.2 points (median value) (interquartile range: [8.8, 29.5] points) on the Action_Research_Arm_Test (p = 0.001). After correcting for spontaneous recovery and/or therapy-as-usual effects Action_Research_Arm_Test scores still improved significantly (median: 17.2 points; interquartile range: [5.1, 29.2] points) (p = 0.002). At individual level, six patients had improved as to arm-hand skill performance at follow-up (p < = 0.010). In one patient, arm-hand skill performance improvement did not attain statistical significance. In another patient, no arm-hand skill performance improvement was observed. Average Intrinsic_Motivation_Inventory sub-scores were between 4.6 and 6.3 (maximum: 7), except for 'perceived pressure/tension' (3.3). Sub-acute stroke patients who display only little/modest improvement on their capacity to perform daily activities, seem to benefit from training with a dynamic arm orthosis in combination with electrical stimulation. Patients' perceived intrinsic motivation and sense of self-regulation was high. Implications for rehabilitation Arm-hand training featuring the dynamic hand orthosis in combination with electrical stimulation shows a shift from no dexterity to dexterity. As to the users' experience regarding the dynamic hand orthosis, patients perceive a high-intrinsic motivation and sense of self-regulation. Combining the orthosis with electrical stimulation creates opportunities for a nonfunctional hand towards task

The bHLH transcription factor Hand is regulated by Alk in the Drosophila embryonic gut

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varshney, Gaurav K.; Palmer, Ruth H.

2006-12-29

During embryonic development the midgut visceral muscle is formed by fusion of cells within the visceral mesoderm, a process initiated by the specification of a specialised cell type, the founder cell, within this tissue. Activation of the receptor tyrosine kinase Anaplastic lymphoma kinase (Alk) in the developing visceral muscle of Drosophila melanogaster initiates a signal transduction pathway required for muscle fusion. In this paper, we have investigated downstream components which are regulated by this novel signalling pathway. Here we show that Alk-mediated signal transduction drives the expression of the bHLH transcription factor Hand in vivo. Loss of Alk function resultsmore » in a complete lack of Hand expression in this tissue, whereas Alk gain of function results in an expansion of Hand expression. Finally, we have investigated the process of muscle fusion in the gut of Hand mutant animals and can find no obvious defects in this process, suggesting that Hand is not critical for visceral muscle fusion per se.« less

Functional role of Runx3 in the regulation of aggrecan expression during cartilage development.

PubMed

Wigner, Nathan A; Soung, Do Y; Einhorn, Thomas A; Drissi, Hicham; Gerstenfeld, Louis C

2013-11-01

Runx2 and Runx3 are known to be expressed in the growth plate during endochondral bone formation. Here we addressed the functional role of Runx3 as distinct from Runx2 by using two models of postnatal bone repair: fracture healing that proceeds by an endochondral process and marrow ablation that proceeds by only an intramembranous process. Both Runx2 and Runx3 mRNAs were differentially up regulated during fracture healing. In contrast, only Runx2 showed increased expression after marrow ablation. During fracture healing, Runx3 was expressed earlier than Runx2, was concurrent with the period of chondrogenesis, and coincident with maximal aggrecan expression a protein associated with proliferating and permanent cartilage. Immunohistological analysis showed Runx3 protein was also expressed by chondrocytes in vivo. In contrast, Runx2 was expressed later during chondrocyte hypertrophy, and primary bone formation. The functional activities of Runx3 during chondrocyte differentiation were assessed by examining its regulatory actions on aggrecan gene expression. Aggrecan mRNA levels and aggrecan promoter activity were enhanced in response to the over-expression of either Runx2 and Runx3 in ATDC5 chondrogenic cell line, while sh-RNA knocked down of each Runx protein showed that only Runx3 knock down specifically suppressed aggrecan mRNA expression and promoter activity. ChIP assay demonstrated that Runx3 interactions were selective to sites within the aggrecan promoter and were only observed during early periods of chondrogenesis before hypertrophy. Our studies suggest that Runx3 positively regulates aggrecan expression and suggest that its function is more limited to cartilage development than to bone. In aggregate these data further suggest that the various members of the Runx transcription factors are involved in the coordination of chondrocyte development, maturation, and hypertrophy during endochondral bone formation. Copyright © 2013 Wiley Periodicals, Inc.

Chondrogenesis and cartilage tissue engineering: the longer road to technology development.

PubMed

Mahmoudifar, Nastaran; Doran, Pauline M

2012-03-01

Joint injury and disease are painful and debilitating conditions affecting a substantial proportion of the population. The idea that damaged cartilage in articulating joints might be replaced seamlessly with tissue-engineered cartilage is of obvious commercial interest because the market for such treatments is large. Recently, a wealth of new information about the complex biology of chondrogenesis and cartilage has emerged from stem cell research, including increasing evidence of the role of physical stimuli in directing differentiation. The challenge for the next generation of tissue engineers is to identify the key elements in this new body of knowledge that can be applied to overcome current limitations affecting cartilage synthesis in vitro. Here we review the status of cartilage tissue engineering and examine the contribution of stem cell research to technology development for cartilage production. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of single and combined low frequency electromagnetic fields and simulated microgravity on gene expression of human mesenchymal stem cells during chondrogenesis

PubMed Central

Hammerschmid, Florian; Blum, Helmut; Krebs, Stefan; Redeker, Julia I.; Holzapfel, Boris M.; Jansson, Volkmar; Müller, Peter E.

2016-01-01

Introduction Low frequency electromagnetic fields (LF-EMF) and simulated microgravity (SMG) have been observed to affect chondrogenesis. A controlled bioreactor system was developed to apply LF-EMF and SMG singly or combined during chondrogenic differentiation of human mesenchymal stem cells (hMSCs) in 3D culture. Material and methods An external motor gear SMG bioreactor was combined with magnetic Helmholtz coils for EMF (5 mT; 15 Hz). Pellets of hMSCs (±TGF-β3) were cultured (P5) under SMG, LF-EMF, LF-EMF/SMG and control (1 g) conditions for 3 weeks. Sections were stained with safranin-O and collagen type II. Gene expression was evaluated by microarray and real-time polymerase chain reaction analysis. Results Simulated microgravity application significantly changed gene expression; specifically, COLXA1 but also COL2A1, which represents the chondrogenic potential, were reduced (p < 0.05). Low frequency electromagnetic fields application showed no gene expression changes on a microarray basis. LF-EMF/SMG application obtained significant different expression values from cultures obtained under SMG conditions with a re-increase of COL2A1, therefore rescuing the chondrogenic potential, which had been lowered by SMG. Conclusions Simulated microgravity lowered hypertrophy but also the chondrogenic potential of hMSCs. Combined LF-EMF/SMG provided a rescue effect of the chondrogenic potential of hMSCs although no LF-EMF effect was observed under optimal conditions. The study provides new insights into how LF-EMF and SMG affect chondrogenesis of hMSCs and how they generate interdependent effects. PMID:29765449

Discovery of novel differentiation markers in the early stage of chondrogenesis by glycoform-focused reverse proteomics and genomics.

PubMed

Ishihara, Takeshi; Kakiya, Kiyoshi; Takahashi, Koji; Miwa, Hiroto; Rokushima, Masatomo; Yoshinaga, Tomoyo; Tanaka, Yoshikazu; Ito, Takaomi; Togame, Hiroko; Takemoto, Hiroshi; Amano, Maho; Iwasaki, Norimasa; Minami, Akio; Nishimura, Shin-Ichiro

2014-01-01

Osteoarthritis (OA) is one of the most common chronic diseases among adults, especially the elderly, which is characterized by destruction of the articular cartilage. Despite affecting more than 100 million individuals all over the world, therapy is currently limited to treating pain, which is a principal symptom of OA. New approaches to the treatment of OA that induce regeneration and repair of cartilage are strongly needed. To discover potent markers for chondrogenic differentiation, glycoform-focused reverse proteomics and genomics were performed on the basis of glycoblotting-based comprehensive approach. Expression levels of high-mannose type N-glycans were up-regulated significantly at the late stage of differentiation of the mouse chondroprogenitor cells. Among 246 glycoproteins carrying this glycotype identified by ConA affinity chromatography and LC/MS, it was demonstrated that 52% are classified as cell surface glycoproteins. Gene expression levels indicated that mRNAs for 15 glycoproteins increased distinctly in the earlier stages during differentiation compared with Type II collagen. The feasibility of mouse chondrocyte markers in human chondrogenesis model was demonstrated by testing gene expression levels of these 15 glycoproteins during differentiation in human mesenchymal stem cells. The results showed clearly an evidence of up-regulation of 5 genes, ectonucleotide pyrophosphatase/phosphodiesterase family member 1, collagen alpha-1(III) chain, collagen alpha-1(XI) chain, aquaporin-1, and netrin receptor UNC5B, in the early stages of differentiation. These cell surface 5 glycoproteins become highly sensitive differentiation markers of human chondrocytes that contribute to regenerative therapies, and development of novel therapeutic reagents. © 2013.

Chondrogenesis of Human Adipose-Derived Stem Cells by In Vivo Co-graft with Auricular Chondrocytes from Microtia.

PubMed

Cai, Zhen; Pan, Bo; Jiang, Haiyue; Zhang, Lixia

2015-06-01

To evaluate the efficiency of chondrogenesis of human adipose-derived stem cells (ADSCs) induced by auricular chondrocytes from microtia via subcutaneous co-graft in nude mice. Human ADSCs and auricular chondrocytes were mixed at the ratio of 7:3 and suspended in 0.2 ml of Pluronic F-127 (5.0 × 10(7) cells/ml), and injected into Balb/c nude mice as the experimental group (Exp group). The same quantity of auricular chondrocytes (Ctr.1 group) or ADSCs (Ctr.2 group) in 0.2 ml of Pluronic F-127 was set as positive and negative control groups. The mixture of auricular chondrocytes (1.5 × 10(7) cells/ml) in 0.2 ml of Pluronic F-127 was set as the low concentration of chondrocyte control group (Ctr.3). At 8 weeks after grafting, the newly generated tissue pellets were isolated for morphological examination, haematoxylin and eosin staining, toluidine blue staining and safranin O staining of glycosaminoglycan (GAG), Masson's trichrome staining and immunohistochemical staining of type II collagen, and Verhoeff-iron-hematoxylin staining of elastic fibers. GAG content was determined by Alcian blue colorimetric method, and mRNA expression of type II collagen and aggrecan were examined by real-time PCR. Cartilage-like tissue with a white translucent appearance and good elasticity was generated in the Exp and Ctr.1 groups. The tissue pellets in the Ctr.2 and Ctr.3 groups were much smaller than those in the Ctr.1 group. The mature cartilage lacunas could be observed in the Exp and Ctr.1 groups, while were rarely seen in the Ctr.3 group and not observed in the Ctr.2 group. The expression of cartilage-specific extracellular matrix such as type II collagen, GAG content, aggrecan, and elastic fibers in the Exp group was similar to that in the Ctr.1 group, whereas the expression of these extracellular matrix substances was significantly lower in the Ctr.2 and Ctr.3 groups (both P < 0.01). Auricular chondrocytes from microtia can efficiently promote the chondrogenic differentiation

Recombinant human type II collagen hydrogel provides a xeno-free 3D micro-environment for chondrogenesis of human bone marrow-derived mesenchymal stromal cells.

PubMed

Muhonen, Virpi; Narcisi, Roberto; Nystedt, Johanna; Korhonen, Matti; van Osch, Gerjo J V M; Kiviranta, Ilkka

2017-03-01

Recombinant human type II collagen (rhCII) hydrogel was tested as a xeno-free micro-environment for the chondrogenesis of human bone marrow-derived mesenchymal stromal cells (BM-MSCs). The rhCII hydrogels were seeded with BM-MSCs and cultured in a xeno-free chondro-inductive medium for 14, 28 and 84 days. High-density pellet cultures served as controls. The samples were subjected to biochemical, histological and gene expression analyses. Although the cells deposited glycosaminoglycans into the extracellular space significantly more slowly in the rhCII hydrogels compared to the high-density pellets, a similar potential of matrix deposition was reached by the end of the 84-day culture. At day 28 of culture, the gene expression level for cartilage marker genes (i.e. genes encoding for Sox9 transcription factor, Collagen type II and Aggrecan) were considerably lower in the rhCII hydrogels than in the high-density pellets, but at the end of the 84-day culture period, all the cartilage marker genes analysed were expressed at a similar level. Interestingly, the expression of the matrix metallopeptidases (MMP)-13, MMP-14 and MMP-8, i.e. extracellular collagen network-degrading enzymes, were transiently upregulated in the rhCII hydrogel, indicating active matrix reorganization. This study demonstrated that the rhCII hydrogel functions as a xeno-free platform for BM-MSC chondrogenesis, although the process is delayed. The reversible catabolic reaction evoked by the rhCII hydrogel might be beneficial in graft integration in vivo and pinpoints the need to further explore the use of hydrogels containing recombinant extracellular matrix (ECM) proteins to induce the chondrogenesis of MSCs. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Osteochondral lesions of the ankle joint in professional soccer players: treatment with autologous matrix-induced chondrogenesis.

PubMed

Valderrabano, Victor; Barg, Alexej; Alattar, Abdulhameed; Wiewiorski, Martin

2014-12-01

Acute and recurrent ankle sprains and other trauma to the ankle joint are common injuries in soccer and can be accompanied by or result in osteochondral lesions of the ankle joint, majorly of the talus. Conservative treatment frequently fails. Several operative treatment techniques exist; however, the choice of the right procedure is difficult due to lack of literature with a high level of evidence. We present our treatment method for acute and chronic ankle osteochondral lesions with cystic formation approached by a new surgical technique combining bone plasty and a collagen matrix (autologous matrix-induced chondrogenesis). Therapeutic, Level IV: Case series. © 2014 The Author(s).

Effects of hydrostatic pressure and transforming growth factor-beta 3 on adult human mesenchymal stem cell chondrogenesis in vitro.

PubMed

Miyanishi, Keita; Trindade, Michael C D; Lindsey, Derek P; Beaupré, Gary S; Carter, Dennis R; Goodman, Stuart B; Schurman, David J; Smith, R Lane

2006-06-01

This study examined the effects of intermittent hydrostatic pressure (IHP) and transforming growth factor-beta 3 on chondrogenesis of adult human mesenchymal stem cells (hMSCs) in vitro. Chondrogenic gene expression was determined by quantifying mRNA signal levels for SOX9, a transcription factor critical for cartilage development and the cartilage matrix proteins, aggrecan and type II collagen. Extracellular matrix production was determined by weight and histology. IHP was applied to hMSCs in pellet culture at a level of 10 MPa and a frequency of 1 Hz for 4 h per day for periods of 3, 7, and 14 days. hMSCs responded to addition of TGF-beta 3 (10 ng/mL) with a greater than 10-fold increase (p < 0.01) in mRNA levels for each, SOX9, type II collagen, and aggrecan during a 14-day culture period. Applying IHP in the presence of TGF-beta 3 further increased the mRNA levels for these proteins by 1.9-, 3.3-, and 1.6-fold, respectively, by day 14. Chondrogenic mRNA levels were increased with just exposure to IHP. Extracellular matrix deposition of type II collagen and aggrecan increased in the pellets as a function of treatment conditions and time of culture. This study demonstrated adjunctive effects of IHP on TGF-beta 3-induced chondrogenesis and suggests that mechanical loading can facilitate articular cartilage tissue engineering.

29 CFR 1926.301 - Hand tools.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Tools-Hand and Power § 1926.301 Hand tools. (a) Employers shall not issue or permit the use of unsafe hand tools. (b) Wrenches, including adjustable, pipe, end...

Delta-like 1/Fetal Antigen-1 (Dlk1/FA1) Is a Novel Regulator of Chondrogenic Cell Differentiation via Inhibition of the Akt Kinase-dependent Pathway*

PubMed Central

Chen, Li; Qanie, Diyako; Jafari, Abbas; Taipaleenmaki, Hanna; Jensen, Charlotte H.; Säämänen, Anna-Marja; Sanz, Maria Luisa Nueda; Laborda, Jorge; Abdallah, Basem M.; Kassem, Moustapha

2011-01-01

Delta-like 1 (Dlk1, also known as fetal antigen-1, FA1) is a member of Notch/Delta family that inhibits adipocyte and osteoblast differentiation; however, its role in chondrogenesis is still not clear. Thus, we overexpressed Dlk1/FA1 in mouse embryonic ATDC5 cells and tested its effects on chondrogenic differentiation. Dlk1/FA1 inhibited insulin-induced chondrogenic differentiation as evidenced by reduction of cartilage nodule formation and gene expression of aggrecan, collagen Type II and X. Similar effects were obtained either by using Dlk1/FA1-conditioned medium or by addition of a purified, secreted, form of Dlk1 (FA1) directly to the induction medium. The inhibitory effects of Dlk1/FA1 were dose-dependent and occurred irrespective of the chondrogenic differentiation stage: proliferation, differentiation, maturation, or hypertrophic conversion. Overexpression or addition of the Dlk1/FA1 protein to the medium strongly inhibited the activation of Akt, but not the ERK1/2, or p38 MAPK pathways, and the inhibition of Akt by Dlk1/FA1 was mediated through PI3K activation. Interestingly, inhibition of fibronectin expression by siRNA rescued the Dlk1/FA1-mediated inhibition of Akt, suggesting interaction of Dlk1/FA1 and fibronectin in chondrogenic cells. Our results identify Dlk1/FA1 as a novel regulator of chondrogenesis and suggest Dlk1/FA1 acts as an inhibitor of the PI3K/Akt pathways that leads to its inhibitory effects on chondrogenesis. PMID:21724852

Curcumin inhibits cellular condensation and alters microfilament organization during chondrogenic differentiation of limb bud mesenchymal cells.

PubMed

Kim, Dong Kyun; Kim, Song Ja; Kang, Shin Sung; Jin, Eun Jung

2009-09-30

Curcumin is a well known natural polyphenol product isolated from the rhizome of the plant Curcuma longa, anti-inflammatory agent for arthritis by inhibiting synthesis of inflammatory prostaglandins. However, the mechanisms by which curcumin regulates the functions of chondroprogenitor, such as proliferation, precartilage condensation, cytoskeletal organization or overall chondrogenic behavior, are largely unknown. In the present report, we investigated the effects and signaling mechanism of curcumin on the regulation of chondrogenesis. Treating chick limb bud mesenchymal cells with curcumin suppressed chondrogenesis by stimulating apoptotic cell death. It also inhibited reorganization of the actin cytoskeleton into a cortical pattern concomitant with rounding of chondrogenic competent cells and down-regulation of integrin beta1 and focal adhesion kinase (FAK) phosphorylation. Curcumin suppressed the phosphorylation of Akt leading to Akt inactivation. Activation of Akt by introducing a myristoylated, constitutively active form of Akt reversed the inhibitory actions of curcumin during chondrogenesis. In summary, for the first time, we describe biological properties of curcumin during chondrogenic differentiation of chick limb bud mesenchymal cells. Curcumin suppressed chondrogenesis by stimulating apoptotic cell death and down-regulating integrin-mediated reorganization of actin cytoskeleton via modulation of Akt signaling.

The association between hand eczema and nickel allergy has weakened among young women in the general population following the Danish nickel regulation: results from two cross-sectional studies.

PubMed

Thyssen, Jacob Pontoppidan; Linneberg, Allan; Menné, Torkil; Nielsen, Niels Henrik; Johansen, Jeanne Duus

2009-12-01

An association between nickel contact allergy and hand eczema has previously been demonstrated. In 1990, Denmark regulated the extent of nickel release in the ear-piercing process as well as nickel release from consumer products. This study aimed to evaluate the effect of the Danish nickel regulation by comparing the prevalence of concomitant nickel allergy and hand eczema observed in two repeated cross-sectional studies performed in the same general population in Copenhagen. In 1990 and 2006, 3881 18-69 year olds completed a postal questionnaire and were patch tested with nickel. Data were analysed by logistic regression analyses and associations were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The prevalence of concomitant nickel contact allergy and a history of hand eczema decreased among 18-35-year-old women from 9.0% in 1990 to 2.1% in 2006 (P < 0.01). The association between nickel contact allergy and a history of hand eczema decreased in this age group between 1990 (OR = 3.63; CI = 1.33-9.96) and 2006 (OR = 0.65; CI = 0.29-1.46). Among older women, no significant changes were observed in the association between nickel contact allergy and hand eczema. Regulatory control of nickel exposure may have reduced the effect of nickel on hand eczema in the young female population.

Evaluation of a Hand Washing Program for 2nd-Graders

ERIC Educational Resources Information Center

Tousman, Stuart; Arnold, Dani; Helland, Wealtha; Roth, Ruth; Heshelman, Nannatte; Castaneda, Oralia; Fischer, Emily; O'Neil, Kristen; Bileto, Stephanie

2007-01-01

The purpose of this project was to determine if a multiple-week learner-centered hand washing program could improve hand hygiene behaviors of 2nd-graders in a northern Illinois public school system. Volunteers from the Rockford Hand Washing Coalition went into 19 different classrooms for 4 consecutive weeks and taught a learner-centered program.…

The Changing Integrin Expression and a Role for Integrin β8 in the Chondrogenic Differentiation of Mesenchymal Stem Cells

PubMed Central

LaPointe, Vanessa L. S.; Verpoorte, Amanda; Stevens, Molly M.

2013-01-01

Many cartilage tissue engineering approaches aim to differentiate human mesenchymal stem cells (hMSCs) into chondrocytes and develop cartilage in vitro by targeting cell-matrix interactions. We sought to better inform the design of cartilage tissue engineering scaffolds by understanding how integrin expression changes during chondrogenic differentiation. In three models of in vitro chondrogenesis, we studied the temporal change of cartilage phenotype markers and integrin subunits during the differentiation of hMSCs. We found that transcript expression of most subunits was conserved across the chondrogenesis models, but was significantly affected by the time-course of differentiation. In particular, ITGB8 was up-regulated and its importance in chondrogenesis was further established by a knockdown of integrin β8, which resulted in a non-hyaline cartilage phenotype, with no COL2A1 expression detected. In conclusion, we performed a systematic study of the temporal changes of integrin expression during chondrogenic differentiation in multiple chondrogenesis models, and revealed a role for integrin β8 in chondrogenesis. This work enhances our understanding of the changing adhesion requirements of hMSCs during chondrogenic differentiation and underlines the importance of integrins in establishing a cartilage phenotype. PMID:24312400

Smart Prosthetic Hand Technology - Phase 2

DTIC Science & Technology

2011-05-01

identification and estimation, hand motion estimation, intelligent embedded systems and control, robotic hand and biocompatibility and signaling. The...Smart Prosthetics, Bio- Robotics , Intelligent EMG Signal Processing, Embedded Systems and Intelligent Control, Inflammatory Responses of Cells, Toxicity...estimation, intelligent embedded systems and control, robotic hand and biocompatibility and signaling. The developed identification algorithm using a new

Hand dysfunction in type 2 diabetes mellitus: Systematic review with meta-analysis.

PubMed

Gundmi, Shubha; Maiya, Arun G; Bhat, Anil K; Ravishankar, N; Hande, Manjunatha H; Rajagopal, K V

2018-03-01

People with type 2 diabetes mellitus frequently show complications in feet and hands. However, the literature has mostly focused on foot complications. The disease can affect the strength and dexterity of the hands, thereby reducing function. This systematic review and meta-analysis focused on identifying the existing evidence on how type 2 diabetes mellitus affects hand strength, dexterity and function. We searched MEDLINE via PubMed, CINHAL, Scopus and Web of Science, and the Cochrane central register of controlled trials for reports of studies of grip and pinch strength as well as hand dexterity and function evaluated by questionnaires comparing patients with type 2 diabetes mellitus and healthy controls that were published between 1990 and 2017. Data are reported as standardized mean difference (SMD) or mean difference (MD) and 95% confidence intervals (CIs). Among 2077 records retrieved, only 7 full-text articles were available for meta-analysis. For both the dominant and non-dominant hand, type 2 diabetes mellitus negatively affected grip strength (SMD: -1.03; 95% CI: -2.24 to 0.18 and -1.37, -3.07 to 0.33) and pinch strength (-1.09, -2.56 to 0.38 and -1.12, -2.73 to 0.49), although not significantly. Dexterity of the dominant hand did not differ between diabetes and control groups but was poorer for the non-dominant hand, although not significantly. Hand function was worse for diabetes than control groups in 2 studies (MD: -8.7; 95% CI: -16.88 to -1.52 and 4.69, 2.03 to 7.35). This systematic review with meta-analysis suggested reduced hand function, specifically grip and pinch strength, for people with type 2 diabetes mellitus versus healthy controls. However, the sample size for all studies was low. Hence, we need studies with adequate sample size and randomized controlled trials to provide statistically significant results. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network.

PubMed

Li, Bing; Balasubramanian, Karthika; Krakow, Deborah; Cohn, Daniel H

2017-12-20

Chondrogenesis is the earliest stage of skeletal development and is a highly dynamic process, integrating the activities and functions of transcription factors, cell signaling molecules and extracellular matrix proteins. The molecular mechanisms underlying chondrogenesis have been extensively studied and multiple key regulators of this process have been identified. However, a genome-wide overview of the gene regulatory network in chondrogenesis has not been achieved. In this study, employing RNA sequencing, we identified 332 protein coding genes and 34 long non-coding RNA (lncRNA) genes that are highly selectively expressed in human fetal growth plate chondrocytes. Among the protein coding genes, 32 genes were associated with 62 distinct human skeletal disorders and 153 genes were associated with skeletal defects in knockout mice, confirming their essential roles in skeletal formation. These gene products formed a comprehensive physical interaction network and participated in multiple cellular processes regulating skeletal development. The data also revealed 34 transcription factors and 11,334 distal enhancers that were uniquely active in chondrocytes, functioning as transcriptional regulators for the cartilage-selective genes. Our findings revealed a complex gene regulatory network controlling skeletal development whereby transcription factors, enhancers and lncRNAs participate in chondrogenesis by transcriptional regulation of key genes. Additionally, the cartilage-selective genes represent candidate genes for unsolved human skeletal disorders.

Mentor's hand hygiene practices influence student's hand hygiene rates.

PubMed

Snow, Michelle; White, George L; Alder, Stephen C; Stanford, Joseph B

2006-02-01

There were 3 objectives for this prospective quasiexperimental study. The first was to determine the effect of mentor's hand hygiene practices on student's hand hygiene rates during clinical rotations. The second was to assess the difference in hand hygiene rates for students with and without prior medical experience. The third was to assess the student's opinion and beliefs regarding hand hygiene. Sixty students enrolled in a certified nursing program were selected to participate in the study. Each study group was observed twice during the 30-day span. The first observational period was conducted on day 1 of clinical rotation. The second observational period was conducted on day 30 of clinical rotation. Students were observed for hand hygiene. Also assessed were medical experience, sex, gloving, age, and mentor's hand hygiene practices. After observational period 2, a brief questionnaire was given to students to determine their opinion and beliefs regarding hand hygiene. The questionnaire was divided into 5 sections: student's commitment to hand hygiene, their perception of hand hygiene inconvenience, the necessity of hand hygiene, the student's ability to perform hand hygiene, and their opinion on the frequency of medical staff's hand hygiene. The mentor's practice of hand hygiene was the strongest predictor of the student's rate of hand hygiene for both observational periods (P < .01). Furthermore, students without prior medical experience had a significant increase in hand hygiene rates when comparing observational period 1 to observational period 2 (P < .01). Glove usage was associated with increased hand hygiene rates by 50% during observational period 1 (P = .01) and 44% during observational period 2 (P < .01). Male students during observational period 1 practiced hand hygiene 30% less often than female students (P < .01); however, during observational period 2, there was no significant difference between hand hygiene rates for males and females (P = .82

System description document for the Anthrobot-2: A dexterous robot hand

NASA Technical Reports Server (NTRS)

Ali, Michael S.; Engler, Charles, Jr.

1991-01-01

The Anthrobot-2 is an anatomically correct, fully functioning robot hand. The number of fingers, the proportions of the links, the placement and motion of the thumb, and the shape of the palm follow those of the human hand. Each of the finger and thumb joints are servo-controlled. The Anthrobot-2 also includes a two-degree-of-freedom wrist. The entire package, including wrist, hand, and actuators, will mount on the ends of a variety of industrial manipulators. A patent has been applied for on the design. The Anthrobot-2 will be useful in tasks where dexterous manipulation or telemanipulation are required.

Purinergic Signaling Regulates the Transforming Growth Factor-β3-Induced Chondrogenic Response of Mesenchymal Stem Cells to Hydrostatic Pressure.

PubMed

Steward, Andrew J; Kelly, Daniel J; Wagner, Diane R

2016-06-01

Although hydrostatic pressure (HP) is known to regulate chondrogenic differentiation of mesenchymal stromal/stem cells (MSCs), improved insight into the mechanotransduction of HP may form the basis for novel tissue engineering strategies. Previously, we demonstrated that matrix stiffness and calcium ion (Ca(++)) mobility regulate the mechanotransduction of HP; however, the mechanisms, by which these Ca(++) signaling pathways are initiated, are currently unknown. The purinergic pathway, in which adenosine triphosphate (ATP) is released and activates P-receptors to initiate Ca(++) signaling, plays a key role in the mechanotransduction of compression, but has yet to be investigated with regard to HP. Therefore, the objective of this study was to investigate the interplay between purinergic signaling, matrix stiffness, and the chondrogenic response of MSCs to HP. Porcine bone marrow-derived MSCs were seeded into soft or stiff agarose hydrogels and subjected to HP (10 MPa at 1 Hz for 4 h/d for 21 days) or kept in free swelling conditions. Stiff constructs were incubated with pharmacological inhibitors of extracellular ATP, P2 receptors, or hemichannels, or without any inhibitors as a control. As with other loading modalities, HP significantly increased ATP release in the control group; however, inhibition of hemichannels completely abrogated this response. The increase in sulfated glycosaminoglycan (sGAG) synthesis and vimentin reorganization observed in the control group in response to HP was suppressed in the presence of all three inhibitors, suggesting that purinergic signaling is involved in the mechanoresponse of MSCs to HP. Interestingly, ATP was released from both soft and stiff hydrogels in response to HP, but HP only enhanced chondrogenesis in the stiff hydrogels, indicating that matrix stiffness may act downstream of purinergic signaling to regulate the mechanoresponse of MSCs to HP. Addition of exogenous ATP did not replicate the effects of HP on

[Microsurgical 2nd toe transfer for catastrophic hand reconstruction].

PubMed

Placer, A; Lozano, Ja

2007-01-01

The correct reconstruction of the catastrophic hand requires complex surgical techniques. The microsurgical transference of a toe is indicated when all other reconstructive options are shown to be useless for the reconstruction of the required clamp function. In this clinical note we set out the case of a 32 year old man, who came to our accident and emergency department after suffering a traffic accident. After exploration the diagnosis was that of catastrophic left hand, among other policontusions. Urgent surgery was carried out, saving the maximum possible viable structures. The immediate result of this surgery was a hand with 1st, 4th and 5th functional fingers. As the essential clamp function between the 1st and 4th or 5th fingers was not totally satisfactory, we decided to reconstruct the 3rd finger of his hand with his ipsilateral 2nd toe. All pertinent studies to determine vascularisation of the flap were carried out in planning the surgery, and the microsurgical transfer was then realized, which was successful. Today, after a suitable rehabilitation, the patient has recovered a satisfactory function of heavy and fine clamp in the operated hand. Toe to hand transfer is a good option for finger reconstruction and its function. Rehabilitation is the key to functional recovery.

A Closed Chondromimetic Environment within Magnetic-Responsive Liquified Capsules Encapsulating Stem Cells and Collagen II/TGF-β3 Microparticles.

PubMed

Correia, Clara R; Gil, Sara; Reis, Rui L; Mano, João F

2016-06-01

TGF-β3 is enzymatically immobilized by transglutaminase-2 action to poly(l-lactic acid) microparticles coated with collagen II. Microparticles are then encapsulated with stem cells inside liquified spherical compartments enfolded with a permselective shell through layer-by-layer adsorption. Magnetic nanoparticles are electrostatically bound to the multilayered shell, conferring magnetic-response ability. The goal of this study is to engineer a closed environment inside which encapsulated stem cells would undergo a self-regulated chondrogenesis. To test this hypothesis, capsules are cultured in chondrogenic differentiation medium without TGF-β3. Their biological outcome is compared with capsules encapsulating microparticles without TGF-β3 immobilization and cultured in normal chondrogenic differentiation medium containing soluble TGF-β3. Glycosaminoglycans quantification demosntrates that similar chondrogenesis levels are achieved. Moreover, collagen fibrils resembling the native extracellular matrix of cartilage can be observed. Importantly, the genetic evaluation of characteristic cartilage markers confirms the successful chondrogenesis, while hypertrophic markers are downregulated. In summary, the engineered capsules are able to provide a suitable and stable chondrogenesis environment for stem cells without the need of TGF-β3 supplementation. This kind of self-regulated capsules with softness, robustness, and magnetic responsive characteristics is expected to provide injectability and in situ fixation, which is of great advantage for minimal invasive strategies to regenerate cartilage. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

29 CFR 1910.138 - Hand protection.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 5 2011-07-01 2011-07-01 false Hand protection. 1910.138 Section 1910.138 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR OCCUPATIONAL SAFETY AND HEALTH STANDARDS Personal Protective Equipment § 1910.138 Hand protection. (a) General...

29 CFR 1910.138 - Hand protection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 5 2010-07-01 2010-07-01 false Hand protection. 1910.138 Section 1910.138 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR OCCUPATIONAL SAFETY AND HEALTH STANDARDS Personal Protective Equipment § 1910.138 Hand protection. (a) General...

Hand1 overexpression inhibits medulloblastoma metastasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Asuthkar, Swapna; Guda, Maheedhara R.; Martin, Sarah E.

2016-08-19

Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Current treatment includes surgery, radiation and chemotherapy. However, ongoing treatment in patients is further classified according to the presence or absence of metastasis. Since metastatic medulloblastoma are refractory to current treatments, there is need to identify novel biomarkers that could be used to reduce metastatic potential, and more importantly be targeted therapeutically. Previously, we showed that ionizing radiation-induced uPAR overexpression is associated with increased accumulation of β-catenin in the nucleus. We further demonstrated that uPAR protein act as cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand1. Amongmore » the histological subtypes classical and desmoplastic subtypes account for the majority while large cell/anaplastic variant is most commonly associated with metastatic disease. In this present study using immunohistochemical approach and patient data mining for the first time, we demonstrated that Hand1 expression is observed to be downregulated in all the subtypes of medulloblastoma. Previously we showed that Hand1 overexpression regulated medulloblastoma angiogenesis and here we investigated the role of Hand1 in the context of Epithelial-Mesenchymal Transition (EMT). Moreover, UW228 and D283 cells overexpressing Hand1 demonstrated decreased-expression of mesenchymal markers (N-cadherin, β-catenin and SOX2); metastatic marker (SMA); and increased expression of epithelial marker (E-cadherin). Strikingly, human pluripotent stem cell antibody array showed that Hand1 overexpression resulted in substantial decrease in pluripotency markers (Nanog, Oct3/4, Otx2, Flk1) suggesting that Hand1 expression may be essential to attenuate the EMT and our findings underscore a novel role for Hand1 in medulloblastoma metastasis. - Highlights: • Hand1 expression is downregulated in Medulloblastoma. • Hand1 over

29 CFR 1915.133 - Hand tools.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 7 2011-07-01 2011-07-01 false Hand tools. 1915.133 Section 1915.133 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS FOR SHIPYARD EMPLOYMENT Tools and Related Equipment § 1915.133 Hand...

Electrostatics effects on Ca(2+) binding and conformational changes in EF-hand domains: Functional implications for EF-hand proteins.

PubMed

Ababou, Abdessamad; Zaleska, Mariola

2015-12-01

Mutations of Gln41 and Lys75 with nonpolar residues in the N-terminal domain of calmodulin (N-Cam) revealed the importance of solvation energetics in conformational change of Ca(2+) sensor EF-hand domains. While in general these domains have polar residues at these corresponding positions yet the extent of their conformational response to Ca(2+) binding and their Ca(2+) binding affinity can be different from N-Cam. Consequently, here we address the charge state of the polar residues at these positions. The results show that the charge state of these polar residues can affect substantially the conformational change and the Ca(2+) binding affinity of our N-Cam variants. Since all the variants kept their conformational activity in the presence of Ca(2+) suggests that the differences observed among them mainly originate from the difference in their molecular dynamics. Hence we propose that the molecular dynamics of Ca(2+) sensor EF-hand domains is a key factor in the multifunctional aspect of EF-hand proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

Digit ratio (2D:4D) and hand preference for writing in the BBC Internet Study.

PubMed

Manning, J T; Peters, M

2009-09-01

The ratio of the length of the second to the fourth digit (2D:4D) may be negatively correlated with prenatal testosterone. Hand preference has been linked with prenatal testosterone and 2D:4D. Here we show that 2D:4D is associated with hand preference for writing in a large internet sample (n>170,000) in which participants self-reported their finger lengths. We replicated a significant association between right 2D:4D and writing hand preference (low right 2D:4D associated with left hand preference) as well as a significant correlation between writing hand preference and the difference between left and right 2D:4D or Dr-l (low Dr-l associated with left hand preference). A new significant correlation between left 2D:4D and writing hand preference was also shown (high left 2D:4D associated with left hand preference). There was a clear interaction between writing hand preference and 2D:4D: The left 2D:4D was significantly larger than the right 2D:4D in male and female left-handed writers, and the right hand 2D:4D was significantly larger than the left hand 2D:4D in male and female right-handed writers.

Hand1 overexpression inhibits medulloblastoma metastasis.

PubMed

Asuthkar, Swapna; Guda, Maheedhara R; Martin, Sarah E; Antony, Reuben; Fernandez, Karen; Lin, Julian; Tsung, Andrew J; Velpula, Kiran K

2016-08-19

Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Current treatment includes surgery, radiation and chemotherapy. However, ongoing treatment in patients is further classified according to the presence or absence of metastasis. Since metastatic medulloblastoma are refractory to current treatments, there is need to identify novel biomarkers that could be used to reduce metastatic potential, and more importantly be targeted therapeutically. Previously, we showed that ionizing radiation-induced uPAR overexpression is associated with increased accumulation of β-catenin in the nucleus. We further demonstrated that uPAR protein act as cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand1. Among the histological subtypes classical and desmoplastic subtypes account for the majority while large cell/anaplastic variant is most commonly associated with metastatic disease. In this present study using immunohistochemical approach and patient data mining for the first time, we demonstrated that Hand1 expression is observed to be downregulated in all the subtypes of medulloblastoma. Previously we showed that Hand1 overexpression regulated medulloblastoma angiogenesis and here we investigated the role of Hand1 in the context of Epithelial-Mesenchymal Transition (EMT). Moreover, UW228 and D283 cells overexpressing Hand1 demonstrated decreased-expression of mesenchymal markers (N-cadherin, β-catenin and SOX2); metastatic marker (SMA); and increased expression of epithelial marker (E-cadherin). Strikingly, human pluripotent stem cell antibody array showed that Hand1 overexpression resulted in substantial decrease in pluripotency markers (Nanog, Oct3/4, Otx2, Flk1) suggesting that Hand1 expression may be essential to attenuate the EMT and our findings underscore a novel role for Hand1 in medulloblastoma metastasis. Copyright © 2016 Elsevier Inc. All rights reserved.

29 CFR 1926.1422 - Signals-hand signal chart.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 8 2014-07-01 2014-07-01 false Signals-hand signal chart. 1926.1422 Section 1926.1422 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Construction § 1926.1422 Signals—hand signal chart. Hand signal charts must be either posted on the equipment...

29 CFR 1926.1422 - Signals-hand signal chart.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 8 2013-07-01 2013-07-01 false Signals-hand signal chart. 1926.1422 Section 1926.1422 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Construction § 1926.1422 Signals—hand signal chart. Hand signal charts must be either posted on the equipment...

29 CFR 1926.1422 - Signals-hand signal chart.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 8 2012-07-01 2012-07-01 false Signals-hand signal chart. 1926.1422 Section 1926.1422 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Construction § 1926.1422 Signals—hand signal chart. Hand signal charts must be either posted on the equipment...

National regulations for diagnostics in health surveillance, therapy and compensation of hand-transmitted vibration injury in Japan.

PubMed

Yamada, Shin'ya

2002-01-01

During the period of technological innovation and rapid economic development, portable power tools were introduced on a large scale in Japan. Vibration disease from the operation of those tools and its prevention and therapy became urgent social problems in the 1970s. This paper aims to introduce national regulations in Japan for diagnostics in the health surveillance, certification, therapy and compensation of vibration disease and evaluates them in the present perspective. Relevant laws, regulations and administrative directives were described in chronological order. Effect of those laws, regulations and directives were evaluated by statistics. Relevant regulations were established in 1947 and were revised in the 1960s and 1970s. According to those regulations, administrative directives were issued. Relevant vibration-disease statistics improved from the 1970s to 1990s. The annual ratio of workers examined was 95% to 100% in national forests (NFs), 47.3% in 1980 and 40.8% in 1990 in private industry (PI). The number of workers certified in NFs was 1,796 from 1971-1975, with a decrease to nine from 1991-1995, while in PI there were 9,783 from 1976-1980, decreasing to 2,331 from 1991-1995. However, in the construction industry the number increased again in the 1990s. The top four workers certified by the type of tool from 1994-1997 were operators of rock drills, chainsaws, pick hammers and concrete vibrators. The annual number of workers under treatment (at highest level) was 3,605 (1982; NFs) and 13,501 (1987; PI), with a decrease to 3,481 (1997; NFs) and 8,958 (1997; PI). Regulations for compensation covered 3,670 workers from 1965 to 1997 (NFs) and 22,723 from 1976 to 1997 (PI) in medical treatment benefits, and 189 (NFs) and 15,448 (PI) in disability benefits during the same term. The national regulations developed in Japan since 1965 for health surveillance, certification, therapy and compensation of hand-transmitted vibration disease have proven effective for

49 CFR 236.819 - Switch, hand operated.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Switch, hand operated. 236.819 Section 236.819 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Switch, hand operated. A non-interlocked switch which can only be operated manually. ...

49 CFR 236.819 - Switch, hand operated.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Switch, hand operated. 236.819 Section 236.819 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Switch, hand operated. A non-interlocked switch which can only be operated manually. ...

49 CFR 236.819 - Switch, hand operated.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Switch, hand operated. 236.819 Section 236.819 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Switch, hand operated. A non-interlocked switch which can only be operated manually. ...

49 CFR 236.819 - Switch, hand operated.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Switch, hand operated. 236.819 Section 236.819 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Switch, hand operated. A non-interlocked switch which can only be operated manually. ...

49 CFR 236.819 - Switch, hand operated.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Switch, hand operated. 236.819 Section 236.819 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Switch, hand operated. A non-interlocked switch which can only be operated manually. ...

Teaching and Learning Hand in Hand: Adaptive Teaching and Self-Regulated Learning

ERIC Educational Resources Information Center

Randi, Judi

2017-01-01

This article presents case studies of two novice teachers and their mentors who, without formal knowledge of self-regulation theory, established a classroom environment that promoted self-regulated learning. This case was drawn from a larger descriptive study of novice teachers learning to integrate a student-centered visual literacy instructional…

Right-Handed Neutrinos and the 2 TeV $W'$ Boson

DOE PAGES

Coloma, Pilar; Dobrescu, Bogdan A.; Lopez-Pavon, Jacobo

2015-12-30

The CMS e +e -jj events of invariant mass near 2 TeV are consistent with a W' boson decaying into an electron and a right-handed neutrino whose TeV-scale mass is of the Dirac type. We show that the Dirac partner of the right-handed electron-neutrino can be the right-handed tau-neutrino. Furthermore, a prediction of this model is that the sum of the τ +e +jj and τ -e -jj signal cross sections equals twice that for e +e -jj. The Standard Model neutrinos acquire Majorana masses and mixings compatible with neutrino oscillation data.

Clues from hands/Part 2. Personal details about patients revealed by hand examination.

PubMed

Schilli, Karen Danielle; Stricklin, Sherea Monica; Payne, Katie Sue; Rader, Ryan Kent; Stoecker, William V

2014-01-01

This is the second part of a two-part article on personal details revealed by hand examination. Examining hands to determine daily activities was the focus of Part 1 in the July/August 2014 Missouri Medicine. Personal traits and preferences, including pets, nutrition and psychology are presented here. These articles serve as a guide for visual clues on the hands to discern a patient's daily activities and personal preference, thereby providing social information that may help establish rapport between patient and physician and may have medical significance.

Leukemia/lymphoma-related factor, a POZ domain-containing transcriptional repressor, interacts with histone deacetylase-1 and inhibits cartilage oligomeric matrix protein gene expression and chondrogenesis.

PubMed

Liu, Chuan-ju; Prazak, Lisa; Fajardo, Marc; Yu, Shuang; Tyagi, Neetu; Di Cesare, Paul E

2004-11-05

Mutations in the human cartilage oligomeric matrix protein (COMP) gene have been linked to the development of pseudoachondroplasia and multiple epiphyseal dysplasia. We previously cloned the promoter region of the COMP gene and delineated a minimal negative regulatory element (NRE) that is both necessary and sufficient to repress its promoter (Issack, P. S., Fang, C. H., Leslie, M. P., and Di Cesare, P. E. (2000) J. Orthop. Res. 18, 345-350; Issack, P. S., Liu, C. J., Prazak, L., and Di Cesare, P. E. (2004) J. Orthop. Res. 22, 751-758). In this study, a yeast one-hybrid screen for proteins that associate with the NRE led to the identification of the leukemia/lymphoma-related factor (LRF), a transcriptional repressor that contains a POZ (poxvirus zinc finger) domain, as an NRE-binding protein. LRF bound directly to the NRE both in vitro and in living cells. Nine nucleotides (GAGGGTCCC) in the 30-bp NRE are essential for binding to LRF. LRF showed dose-dependent inhibition of COMP-specific reporter gene activity, and exogenous overexpression of LRF repressed COMP gene expression in both rat chondrosarcoma cells and bone morphogenetic protein-2-treated C3H10T1/2 progenitor cells. In addition, LRF also inhibited bone morphogenetic protein-2-induced chondrogenesis in high density micromass cultures of C3H10T1/2 cells, as evidenced by lack of expression of other chondrocytic markers, such as aggrecan and collagen types II, IX, X, and XI, and by Alcian blue staining. LRF associated with histone deacetylase-1 (HDAC1), and experiments utilizing the HDAC inhibitor trichostatin A revealed that LRF-mediated repression requires deacetylase activity. LRF is the first transcription factor found to bind directly to the COMP gene promoter, to recruit HDAC1, and to regulate both COMP gene expression and chondrogenic differentiation.

Picornavirus 2A protease regulates stress granule formation to facilitate viral translation

PubMed Central

Yang, Xiaodan; Hu, Zhulong; Fan, Shanshan; Zhang, Qiang; Zhong, Yi; Guo, Dong; Qin, Yali

2018-01-01

Stress granules (SGs) contain stalled messenger ribonucleoprotein complexes and are related to the regulation of mRNA translation. Picornavirus infection can interfere with the formation of SGs. However, the detailed molecular mechanisms and functions of picornavirus-mediated regulation of SG formation are not clear. Here, we found that the 2A protease of a picornavirus, EV71, induced atypical stress granule (aSG), but not typical stress granule (tSG), formation via cleavage of eIF4GI. Furthermore, 2A was required and sufficient to inhibit tSGs induced by EV71 infection, sodium arsenite, or heat shock. Infection of 2A protease activity-inactivated recombinant EV71 (EV71-2AC110S) failed to induce aSG formation and only induced tSG formation, which is PKR and eIF2α phosphorylation-dependent. By using a Renilla luciferase mRNA reporter system and RNA fluorescence in situ hybridization assay, we found that EV71-induced aSGs were beneficial to viral translation through sequestering only cellular mRNAs, but not viral mRNAs. In addition, we found that the 2A protease of other picornaviruses such as poliovirus and coxsackievirus also induced aSG formation and blocked tSG formation. Taken together, our results demonstrate that, on one hand, EV71 infection induces tSG formation via the PKR-eIF2α pathway, and on the other hand, 2A, but not 3C, blocks tSG formation. Instead, 2A induces aSG formation by cleaving eIF4GI to sequester cellular mRNA but release viral mRNA, thereby facilitating viral translation. PMID:29415027

Inspections of hand washing supplies and hand sanitizer in public schools.

PubMed

Ramos, Mary M; Blea, Mary; Trujillo, Rebecca; Greenberg, Cynthia

2010-10-01

Hand washing and hand antisepsis are proven infection control measures in the school setting, yet barriers such as lack of soap, paper towels, and hand sanitizer can hinder compliance. This pilot study measured the prevalence of hand cleaning supplies in public schools. Ten school districts (93 schools) participated in school nurse inspections. In November 2008, 90 schools (97%) reported their inspection results. Among 697 total bathrooms, 88.8% had soap and 91.7% had paper towels or hand dryers. Hand sanitizer was reported in 1.2% of bathrooms and 15.2% of cafeterias. No difference was observed between boys' and girls' bathrooms, or primary and secondary schools, in the prevalence of soap or paper towels/hand dryers. Hand washing supplies were generally available in public school bathrooms. Alcohol-based hand sanitizer in school bathrooms was reported occasionally and should be discouraged. Hand sanitizer in a supervised setting, the school cafeteria, was not often reported and should be promoted.

Hand disorders, hand function, and activities of daily living in elderly men with type 2 diabetes.

PubMed

Cederlund, Ragnhild I; Thomsen, Niels; Thrainsdottir, Soley; Eriksson, Karl-Fredrik; Sundkvist, Göran; Dahlin, Lars B

2009-01-01

This study aimed to examine hand disorders, symptoms, overall hand function, activities of daily living (ADLs), and life satisfaction in elderly men with type 2 diabetes mellitus (DM), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). Subjects were interviewed and evaluated with a battery of clinical and laboratory tests, including hand assessment, and a questionnaire. HbA1c differed between groups (highest in DM, especially in long-term DM). Limited joint motion (LJM), for example, prayer sign and Dupuytren's contracture, was most common in individuals with DM, followed by individuals with IGT, as compared to those with NGT. Vibrotactile sense was impaired symmetrically in the index and little fingers in DM. However, there were no differences for sensibility, dexterity, grip strength, and cold intolerance between groups. Individuals with long-term (>15 years) DM were more affected regarding sensibility and ADL than individuals with short-term DM, who had more sleep disturbances. ADL difficulties were less among IGT subjects. Vibrotactile sense showed correlations with Semmes-Weinstein monofilament test and static two-point discrimination. Dupuytren's contracture and impaired vibrotactile sense in finger pulps occurred in patients with DM but not in those with IGT, although LJM occurred in both IGT and DM patients. A longer duration of DM was associated with more severe neuropathy and ADL difficulties. Life satisfaction was high, and hand disorders did not have a significant impact on ADL.

Human Mesenchymal Stem Cells Pretreated with Interleukin-1β and Stimulated with Bone Morphogenetic Growth Factor-3 Enhance Chondrogenesis.

PubMed

Hingert, Daphne; Barreto Henriksson, Helena; Brisby, Helena

2018-05-01

Low back pain is one of the most common ailments in western countries afflicting more than 80% of the population, and the main cause is considered to be degeneration of intervertebral discs. Interleukin-1β (IL-1β) is a vital inflammatory cytokine found in abundance in degenerated disc environment, whereas bone morphogenetic growth factor-3 (BMP-3) is believed to promote chondrogenesis through transforming growth factor-beta (TGF-β) pathway. The aim was to study the effects of BMP-3, IL-1β, and combination (pretreatment with IL-1β) on human mesenchymal stem cells (hMSCs) encapsulated in PuraMatrix™ hydrogel (Phg) especially in the absence of TGF-β in order to investigate the proliferation and differentiation ability of hMSCs over 28-day period. One hundred microliters of hMSCs' cell suspension was encapsulated between two layers of 100 μL hydrogels forming a sandwich-like structure. The encapsulated hMSCs were cultured in two sets of media, chondrogenic (C) and nonchondrogenic (nC) media, along with addition of BMP-3 (10 ng/mL) and IL-1β (10 ng/mL). To study the combined effects of BMP-3 and IL-1β, the encapsulated hMSCs were first pretreated with relevant media containing IL-1β for 24 h, and then the media was replaced by media containing BMP-3 for the remaining experimental time period. IL-1β pretreatment was carried out in both C and nC media. The samples were collected at day 7, 14, and 28. Proliferation and differentiation of hMSCs into chondrocyte-like cells were observed in all samples. Proteoglycan accumulation was observed in pretreatment samples in C media. The protein and gene expression of Sox-9 and COL2A1, respectively, showed the occurrence of chondrogenesis in all samples. High cell viability, proliferation, and differentiation were achieved in this in vitro model confirming that BMP-3 alone in the absence of TGF-β could drive hMSCs into chondrogenic lineage. Pretreatment with IL-1β followed by BMP-3 stimulation resulted in high

49 CFR 392.82 - Using a hand-held mobile telephone.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Definitions. For the purpose of this section only, driving means operating a commercial motor vehicle on a... SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS DRIVING OF.... (a)(1) No driver shall use a hand-held mobile telephone while driving a CMV. (2) No motor carrier...

49 CFR 392.82 - Using a hand-held mobile telephone.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Definitions. For the purpose of this section only, driving means operating a commercial motor vehicle on a... SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS DRIVING OF.... (a)(1) No driver shall use a hand-held mobile telephone while driving a CMV. (2) No motor carrier...

49 CFR 392.82 - Using a hand-held mobile telephone.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Definitions. For the purpose of this section only, driving means operating a commercial motor vehicle on a... SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS DRIVING OF.... (a)(1) No driver shall use a hand-held mobile telephone while driving a CMV. (2) No motor carrier...

Rap1b Is an Effector of Axin2 Regulating Crosstalk of Signaling Pathways During Skeletal Development.

PubMed

Maruyama, Takamitsu; Jiang, Ming; Abbott, Alycia; Yu, H-M Ivy; Huang, Qirong; Chrzanowska-Wodnicka, Magdalena; Chen, Emily I; Hsu, Wei

2017-09-01

Recent identification and isolation of suture stem cells capable of long-term self-renewal, clonal expanding, and differentiating demonstrate their essential role in calvarial bone development, homeostasis, and injury repair. These bona fide stem cells express a high level of Axin2 and are able to mediate bone regeneration and repair in a cell autonomous fashion. The importance of Axin2 is further demonstrated by its genetic inactivation in mice causing skeletal deformities resembling craniosynostosis in humans. The fate determination and subsequent differentiation of Axin2+ stem cells are highly orchestrated by a variety of evolutionary conserved signaling pathways including Wnt, FGF, and BMP. These signals are often antagonistic of each other and possess differential effects on osteogenic and chondrogenic cell types. However, the mechanisms underlying the interplay of these signaling transductions remain largely elusive. Here we identify Rap1b acting downstream of Axin2 as a signaling interrogator for FGF and BMP. Genetic analysis reveals that Rap1b is essential for development of craniofacial and body skeletons. Axin2 regulates Rap1b through modulation of canonical BMP signaling. The BMP-mediated activation of Rap1b promotes chondrogenic fate and chondrogenesis. Furthermore, by inhibiting MAPK signaling, Rap1b mediates the antagonizing effect of BMP on FGF to repress osteoblast differentiation. Disruption of Rap1b in mice not only enhances osteoblast differentiation but also impairs chondrocyte differentiation during intramembranous and endochondral ossifications, respectively, leading to severe defects in craniofacial and body skeletons. Our findings reveal a dual role of Rap1b in development of the skeletogenic cell types. Rap1b is critical for balancing the signaling effects of BMP and FGF during skeletal development and disease. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

49 CFR 176.320 - Use of hand flashlights.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Requirements for Class 3 (Flammable) and Combustible Liquid Materials § 176.320 Use of hand flashlights. Each hand flashlight used on deck near or in any hold or compartment containing a Class 3 (flammable) liquid... Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY...

49 CFR 176.320 - Use of hand flashlights.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Requirements for Class 3 (Flammable) and Combustible Liquid Materials § 176.320 Use of hand flashlights. Each hand flashlight used on deck near or in any hold or compartment containing a Class 3 (flammable) liquid... Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY...

49 CFR 176.320 - Use of hand flashlights.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Requirements for Class 3 (Flammable) and Combustible Liquid Materials § 176.320 Use of hand flashlights. Each hand flashlight used on deck near or in any hold or compartment containing a Class 3 (flammable) liquid... Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY...

49 CFR 176.320 - Use of hand flashlights.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Requirements for Class 3 (Flammable) and Combustible Liquid Materials § 176.320 Use of hand flashlights. Each hand flashlight used on deck near or in any hold or compartment containing a Class 3 (flammable) liquid... Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY...

49 CFR 176.320 - Use of hand flashlights.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Requirements for Class 3 (Flammable) and Combustible Liquid Materials § 176.320 Use of hand flashlights. Each hand flashlight used on deck near or in any hold or compartment containing a Class 3 (flammable) liquid... Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY...

Ptn functions downstream of C/EBPβ to mediate the effects of cAMP on uterine stromal cell differentiation through targeting Hand2 in response to progesterone.

PubMed

Yu, Hai-Fan; Tao, Ran; Yang, Zhan-Qing; Wang, Kai; Yue, Zhan-Peng; Guo, Bin

2018-02-01

Ptn is a pleiotropic growth factor involving in the regulation of cellular proliferation and differentiation, but its biological function in uterine decidualization remains unknown. Here, we showed that Ptn was highly expressed in the decidual cells, and could induce the proliferation of uterine stromal cells and expression of Prl8a2 and Prl3c1 which were two well-established differentiation markers for decidualization, suggesting an important role of Ptn in decidualization. In the uterine stromal cells, progesterone stimulated the expression of Ptn accompanied with an accumulation of intracellular cAMP level. Silencing of Ptn impeded the induction of progesterone and cAMP on the differentiation of uterine stromal cells. Administration of PKA inhibitor H89 resulted in a blockage of progesterone on Ptn expression. Further analysis evidenced that regulation of progesterone and cAMP on Ptn was mediated by C/EBPβ. During in vitro decidualization, knockdown of Ptn could weaken the up-regulation of Prl8a2 and Prl3c1 elicited by C/EBPβ overexpression, while constitutive activation of Ptn reversed the repressive effects of C/EBPβ siRNA on the expression of Prl8a2 and Prl3c1. Meanwhile, Ptn might mediate the regulation of C/EBPβ on Hand2 which was a downstream target of Ptn in the differentiation of uterine stromal cells. Attenuation of Ptn or C/EBPβ by specific siRNA blocked the stimulation of Hand2 by progesterone and cAMP. Collectively, Ptn may play a vital role in the progesterone-induced decidualization pathway. © 2017 Wiley Periodicals, Inc.

Indian hedgehog signaling triggers Nkx3.2 protein degradation during chondrocyte maturation

PubMed Central

Choi, Seung-Won; Jeong, Da-Un; Kim, Jeong-Ah; Lee, Boyoung; Joeng, Kyu Sang; Long, Fanxin; Kim, Dae-Won

2015-01-01

The Indian hedgehog (Ihh) pathway plays an essential role in facilitating chondrocyte hypertrophy and bone formation during skeletal development. Nkx3.2 is initially induced in chondrocyte precursor cells, maintained in early-stage chondrocytes, and down-regulated in terminal-stage chondrocytes. Consistent with these expression patterns, Nkx3.2 has been shown to enhance chondrocyte differentiation and cell survival, while inhibiting chondrocyte hypertrophy and apoptosis. Thus, in this work, we investigate whether Nkx3.2, an early stage chondrogenic factor, can be regulated by Ihh, a key regulator for chondrocyte hypertrophy. Here, we show that Ihh signaling can induce proteasomal degradation of Nkx3.2. In addition, we found that Ihh can suppress levels of Lrp (Wnt co-receptor) and Sfrp (Wnt antagonist) expression, which, in turn, may selectively enhance Lrp-independent non-canonical Wnt pathways in chondrocyte. In agreement with these findings, Ihh-induced Nkx3.2 degradation requires Wnt5a, which is capable of triggering Nkx3.2 degradation. Finally, we found that Nkx3.2 protein levels in chondrocytes are remarkably elevated in mice defective in Ihh signaling by deletion of either Ihh or Smoothened. Thus, these results suggest that Ihh/Wnt5a signaling may play a role in negative regulation of Nkx3.2 for appropriate progression of chondrocyte hypertrophy during chondrogenesis. PMID:22507129

Hand-held optical imager (Gen-2): improved instrumentation and target detectability

PubMed Central

Gonzalez, Jean; DeCerce, Joseph; Erickson, Sarah J.; Martinez, Sergio L.; Nunez, Annie; Roman, Manuela; Traub, Barbara; Flores, Cecilia A.; Roberts, Seigbeh M.; Hernandez, Estrella; Aguirre, Wenceslao; Kiszonas, Richard

2012-01-01

Abstract. Hand-held optical imagers are developed by various researchers towards reflectance-based spectroscopic imaging of breast cancer. Recently, a Gen-1 handheld optical imager was developed with capabilities to perform two-dimensional (2-D) spectroscopic as well as three-dimensional (3-D) tomographic imaging studies. However, the imager was bulky with poor surface contact (∼30%) along curved tissues, and limited sensitivity to detect targets consistently. Herein, a Gen-2 hand-held optical imager that overcame the above limitations of the Gen-1 imager has been developed and the instrumentation described. The Gen-2 hand-held imager is less bulky, portable, and has improved surface contact (∼86%) on curved tissues. Additionally, the forked probe head design is capable of simultaneous bilateral reflectance imaging of both breast tissues, and also transillumination imaging of a single breast tissue. Experimental studies were performed on tissue phantoms to demonstrate the improved sensitivity in detecting targets using the Gen-2 imager. The improved instrumentation of the Gen-2 imager allowed detection of targets independent of their location with respect to the illumination points, unlike in Gen-1 imager. The developed imager has potential for future clinical breast imaging with enhanced sensitivity, via both reflectance and transillumination imaging. PMID:23224163

FoxA family members are crucial regulators of the hypertrophic chondrocyte differentiation program

PubMed Central

Ionescu, Andreia; Kozhemyakina, Elena; Nicolae, Claudia; Kaestner, Klaus H.; Olsen, Bjorn R.; Lassar, Andrew B.

2012-01-01

During endochondral ossification small immature chondrocytes enlarge to form hypertrophic chondrocytes, which express collagen X. In this work, we demonstrate that FoxA factors are induced during chondrogenesis, bind to conserved binding sites in the collagen X enhancer, and can promote the expression of a collagen X-luciferase reporter in both chondrocytes and fibroblasts. In addition, we demonstrate by both gain and loss of function analyses that FoxA factors play a crucial role driving the expression of both endogenous collagen X and other hypertrophic chondrocyte-specific genes. Mice engineered to lack expression of both FoxA2 and FoxA3 in their chondrocytes display defects in chondrocyte hypertrophy, alkaline phosphatase expression, and mineralization in their sternebrae and in addition exhibit postnatal dwarfism that is coupled to significantly decreased expression of both collagen X and MMP13 in their growth plates. Together, our findings indicate that FoxA family members are crucial regulators of the hypertrophic chondrocyte differentiation program. PMID:22595668

29 CFR 780.315 - Local hand harvest laborers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 3 2011-07-01 2011-07-01 false Local hand harvest laborers. 780.315 Section 780.315 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR STATEMENTS OF GENERAL...) Statutory Provisions § 780.315 Local hand harvest laborers. (a) A requirement of the exemption is that an...

Silk-ionomer and silk-tropoelastin hydrogels as charged three-dimensional culture platforms for the regulation of hMSC response.

PubMed

Calabrese, Rossella; Raia, Nicole; Huang, Wenwen; Ghezzi, Chiara E; Simon, Marc; Staii, Cristian; Weiss, Anthony S; Kaplan, David L

2017-09-01

The response of human bone marrow-derived mesenchymal stem cells (hMSCs) encapsulated in three-dimensional (3D) charged protein hydrogels was studied. Combining silk fibroin (S) with recombinant human tropoelastin (E) or silk ionomers (I) provided protein composite alloys with tunable physicochemical and biological features for regulating the bioactivity of encapsulated hMSCs. The effects of the biomaterial charges on hMSC viability, proliferation and chondrogenic or osteogenic differentiation were assessed. The silk-tropoelastin or silk-ionomers hydrogels supported hMSC viability, proliferation and differentiation. Gene expression of markers for chondrogenesis and osteogenesis, as well as biochemical and histological analysis, showed that hydrogels with different S/E and S/I ratios had different effects on cell fate. The negatively charged hydrogels upregulated hMSC chondrogenesis or osteogenesis, with or without specific differentiation media, and hydrogels with higher tropoelastin content inhibited the differentiation potential even in the presence of the differentiation media. The results provide insight on charge-tunable features of protein-based biomaterials to control hMSC differentiation in 3D hydrogels, as well as providing a new set of hydrogels for the compatible encapsulation and utility for cell functions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Interplay of VEGFa and MMP2 regulates invasion of glioblastoma.

PubMed

Gong, Jie; Zhu, Shugan; Zhang, Yuan; Wang, Jiangang

2014-12-01

Neovascularization plays a substantial role in the regulation of invasion of glioblastoma. However, the underlying molecular basis remains largely unknown. Both vascular endothelial growth factor a (VEGFa) and matrix metalloproteinases 2 (MMP2) are essential for cancer neovascularization and cancer invasion in that they promote endothelial mitogenesis and permeability, and promote extracellular matrix degradation, respectively. In the current study, we found strong positive correlation of VEGFa and phosphorylated MMP2 levels in the glioblastoma from the patients. Thus, we used a human glioblastoma line, A-172, to examine the interaction of VEGFa and MMP2. We found that overexpression of VEGFa in A-172 cells increased MMP2 levels, while inhibition of VEGFa in A-172 cells decreased MMP2 levels. On the other hand, forced changes in MMP2 levels in A-172 cells did not affect VEGFa levels. These data suggest that VEGFa may regulate MMP2 in glioblastoma, while MMP2 did not appear to affect VEGFa levels. We then examined the signaling pathways involved in the regulation of MMP2 levels by VEGFa. Application of a specific extracellular-related kinase 1/2 (ERK1/2) inhibitor, but not application of either an protein kinase B (Akt) inhibitor, or a Jun N-terminal kinase (JNK) inhibitor to VEGFa-overexpressing A-172 cells substantially abolished the effect of VEGFa on MMP2 activation, suggesting that VEGFa may increase MMP2 levels via ERK/mitogen-activated protein kinase (MAPK), but not phosphatidylinositol 3-kinase (PI3K) or JNK signaling pathways in glioblastoma. Moreover, adapted VEGFa levels were found to directly and positively affect the glioblastoma development in an intracranial glioblastoma implantation model. Taken together, our data suggest that anti-VEGFa treatment in glioblastoma may inhibit neovascularization not only by VEGFa itself but also by its regulatory effect on MMP2.

29 CFR 1926.1422 - Signals-hand signal chart.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 8 2011-07-01 2011-07-01 false Signals-hand signal chart. 1926.1422 Section 1926.1422 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Cranes and Derricks in...

32 CFR 935.131 - Right-hand side of the road.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Right-hand side of the road. 935.131 Section 935... INSULAR REGULATIONS WAKE ISLAND CODE Motor Vehicle Code § 935.131 Right-hand side of the road. Each person driving a motor vehicle on Wake Island shall drive on the right-hand side of the road, except where...

32 CFR 935.131 - Right-hand side of the road.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 6 2014-07-01 2014-07-01 false Right-hand side of the road. 935.131 Section 935... INSULAR REGULATIONS WAKE ISLAND CODE Motor Vehicle Code § 935.131 Right-hand side of the road. Each person driving a motor vehicle on Wake Island shall drive on the right-hand side of the road, except where...

32 CFR 935.131 - Right-hand side of the road.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Right-hand side of the road. 935.131 Section 935... INSULAR REGULATIONS WAKE ISLAND CODE Motor Vehicle Code § 935.131 Right-hand side of the road. Each person driving a motor vehicle on Wake Island shall drive on the right-hand side of the road, except where...

32 CFR 935.131 - Right-hand side of the road.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Right-hand side of the road. 935.131 Section 935... INSULAR REGULATIONS WAKE ISLAND CODE Motor Vehicle Code § 935.131 Right-hand side of the road. Each person driving a motor vehicle on Wake Island shall drive on the right-hand side of the road, except where...

32 CFR 935.131 - Right-hand side of the road.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 6 2012-07-01 2012-07-01 false Right-hand side of the road. 935.131 Section 935... INSULAR REGULATIONS WAKE ISLAND CODE Motor Vehicle Code § 935.131 Right-hand side of the road. Each person driving a motor vehicle on Wake Island shall drive on the right-hand side of the road, except where...

Interplay between the chalcone cardamonin and selenium in the biosynthesis of Nrf2-regulated antioxidant enzymes in intestinal Caco-2 cells.

PubMed

De Spirt, Silke; Eckers, Anna; Wehrend, Carina; Micoogullari, Mustafa; Sies, Helmut; Stahl, Wilhelm; Steinbrenner, Holger

2016-02-01

Selenoenzymes and nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated phase II enzymes comprise key components of the cellular redox and antioxidant systems, which show multiple interrelations. Deficiency of the micronutrient selenium (Se) and impaired biosynthesis of selenoproteins have been reported to result in induction of Nrf2 target genes. Conversely, transcription of the selenoenzymes glutathione peroxidase 2 (GPx2) and thioredoxin reductase 1 (TrxR1) is up-regulated upon Nrf2 activation. Here, we have studied the interplay between Se and the secondary plant metabolite cardamonin, an Nrf2-activating chalcone, in the regulation of Nrf2-controlled antioxidant enzymes. Se-deficient and Se-repleted (sodium selenite-supplemented) human intestinal Caco-2 cells were exposed to cardamonin. Uptake of cardamonin by the Caco-2 cells was independent of their Se status. Cardamonin strongly induced gene expression of GPx2 and TrxR1. However, cardamonin treatment did not result in elevated GPx or TrxR activity and protein levels, possibly relating to a concomitant down-regulation of O-phosphoseryl-tRNA(Sec) kinase (PSTK), an enzyme involved in translation of selenoprotein mRNAs. On the other hand, induction of the Nrf2-regulated enzyme heme oxygenase 1 (HO-1) by cardamonin was diminished in Se-replete compared to Se-deficient cells. Our findings suggest that cardamonin interferes with the biosynthesis of Nrf2-regulated selenoenzymes, in contrast to the Nrf2-activating isothiocyanate compound sulforaphane, which has been shown earlier to synergize with Se-mediated cytoprotection. Conversely, the cellular Se status apparently affects the cardamonin-mediated induction of non-selenoprotein antioxidant enzymes such as HO-1. Copyright © 2015 Elsevier Inc. All rights reserved.

Reduction in finger blood flow induced by hand-transmitted vibration: effect of hand elevation.

PubMed

Ye, Ying; Mauro, Marcella; Bovenzi, Massimo; Griffin, Michael J

2015-10-01

This study investigated the effect of hand elevation on reductions in finger blood flow (FBF) induced by hand-transmitted vibration. Fourteen males attended six sessions on six separate days, with a control sessions and a vibration session (125-Hz vibration at 44 ms(-2) rms) with the right hand supported at each of three elevations: 20 cm below heart level (HL), at HL, and 20 cm above HL. Finger blood flow on the left and right hand was measured every 30 s during each 25-min session comprised of five periods: (1) no force and no vibration (5 min), (2) 2-N force and no vibration (5 min), (3) 2-N force and vibration (5 min), (4) 2-N force and no vibration (5 min), and (5) no force and no vibration (5 min). Without vibration, FBF decreased with increasing elevation of the hand. During vibration of the right hand, FBF reduced on both hands. With elevation of the right hand, the percentage reduction in FBF due to vibration (relative to FBF on the same finger at the same elevation before exposure to vibration) was similar on the middle and little fingers of both hands. After cessation of vibration, there was delayed return of FBF with all three hand heights. Vibration of one hand reduces FBF on both exposed and unexposed hands, with the reduction dependent on the elevation of the hand. The mechanisms responsible for vibration-induced reductions in FBF seem to reduce blood flow as a percentage of the blood flow without vibration. Tasks requiring the elevation of the hands will be associated with lower FBF, and the FBF will be reduced further if there is exposure to hand-transmitted vibration.

[Does the hand solely belong in the hands of a qualified hand surgeon?

PubMed

Güven, Asim; Kols, Kerstin; Fischer, Klaus; Schönberger, Michael; Allert, Sixtus

2017-09-01

Background In Germany, Hand Surgery is an additional qualification that can only be obtained by a three-year training after a completed residency in General Surgery, Plastic Surgery or Trauma and Orthopaedic Surgery. Nevertheless, injuries and diseases of the hand are also treated by physicians without this particular qualification. It is questionable whether these treatments more often lead to medical malpractice. Material and Methods 376 charges of medical malpractice in surgical treatments of the hand and forearm that were closed in 2014 and 2015 were collected by the Arbitration Board for Medical Liability Issues of the Medical Association of North Germany.Cases with proven medical malpractice were classified by the qualification of the physician in charge and analysed. A statistical analysis was performed with the use of the program SPSS (IBM). Results Medical malpractice was proven in 42 of 113 cases with an attending physician who held the additional qualification for Hand Surgery (37.2 %). For physicians without this qualification, the figures were 79 out of 155 (51.0 %) in the group of trauma and orthopaedic surgeons and 54 out of 108 (50.0 %) in the group of general surgeons. The differences between the hand surgeons and the trauma and orthopaedic surgeons (p = 0.017) and between hand surgeons and general surgeons were significant (p = 0.037). Conclusions It was shown that physicians with an additional qualification in hand surgery had signifcantly fewer proven medical malpratice cases than physicians without this qualification. The following trends were observed in the cases of the physicians without the additional qualification in hand surgery: underestimation of the severity of trauma to soft tissues and infections of the hand, errors in the surgical examination of the hand, including functional tests of tendons and nerves, as well as in diagnostic findings after X-ray studies of the hand. Georg Thieme Verlag KG Stuttgart · New York.

Role of DNA Methylation and Epigenetic Silencing of HAND2 in Endometrial Cancer Development

PubMed Central

Hayward, Jane D.; Kannan, Athilakshmi; Mould, Tim; West, James; Zikan, Michal; Cibula, David; Fiegl, Heidi; Lee, Shih-Han; Wik, Elisabeth; Hadwin, Richard; Arora, Rupali; Lemech, Charlotte; Turunen, Henna; Pakarinen, Päivi; Jacobs, Ian J.; Salvesen, Helga B.; Bagchi, Milan K.; Bagchi, Indrani C.; Widschwendter, Martin

2013-01-01

Background Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development. Methods and Findings Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to

Efficacy of alcohol-based hand sanitizer on hands soiled with dirt and cooking oil.

PubMed

Pickering, Amy J; Davis, Jennifer; Boehm, Alexandria B

2011-09-01

Handwashing education and promotion are well established as effective strategies to reduce diarrhea and respiratory illness in countries around the world. However, access to reliable water supplies has been identified as an important barrier to regular handwashing in low-income countries. Alcohol-based hand sanitizer (ABHS) is an effective hand hygiene method that does not require water, but its use is not currently recommended when hands are visibly soiled. This study evaluated the efficacy of ABHS on volunteers' hands artificially contaminated with Escherichia coli in the presence of dirt (soil from Tanzania) and cooking oil. ABHS reduced levels of E. coli by a mean of 2.33 log colony forming units (CFU) per clean hand, 2.32 log CFU per dirt-covered hand, and 2.13 log CFU per oil-coated hand. No significant difference in efficacy was detected between hands that were clean versus dirty or oily. ABHS may be an appropriate hand hygiene method for hands that are moderately soiled, and an attractive option for field settings in which access to water and soap is limited.

9 CFR 2.2 - Acknowledgement of regulations and standards.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Acknowledgement of regulations and standards. 2.2 Section 2.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.2 Acknowledgement of regulations and...

9 CFR 2.2 - Acknowledgement of regulations and standards.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Acknowledgement of regulations and standards. 2.2 Section 2.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.2 Acknowledgement of regulations and...

9 CFR 2.2 - Acknowledgement of regulations and standards.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Acknowledgement of regulations and standards. 2.2 Section 2.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.2 Acknowledgement of regulations and...

9 CFR 2.2 - Acknowledgement of regulations and standards.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Acknowledgement of regulations and standards. 2.2 Section 2.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.2 Acknowledgement of regulations and...

9 CFR 2.2 - Acknowledgement of regulations and standards.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Acknowledgement of regulations and standards. 2.2 Section 2.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.2 Acknowledgement of regulations and...

Chondrogenesis of Embryonic Stem Cell-Derived Mesenchymal Stem Cells Induced by TGFβ1 and BMP7 Through Increased TGFβ Receptor Expression and Endogenous TGFβ1 Production.

PubMed

Lee, Patrick T; Li, Wan-Ju

2017-01-01

For decades stem cells have proven to be invaluable to the study of tissue development. More recently, mesenchymal stem cells (MSCs) derived from embryonic stem cells (ESCs) (ESC-MSCs) have emerged as a cell source with great potential for the future of biomedical research due to their enhanced proliferative capability compared to adult tissue-derived MSCs and effectiveness of musculoskeletal lineage-specific cell differentiation compared to ESCs. We have previously compared the properties and differentiation potential of ESC-MSCs to bone marrow-derived MSCs. In this study, we evaluated the potential of TGFβ1 and BMP7 to induce chondrogenic differentiation of ESC-MSCs compared to that of TGFβ1 alone and further investigated the cellular phenotype and intracellular signaling in response to these induction conditions. Our results showed that the expression of cartilage-associated markers in ESC-MSCs induced by the TGFβ1 and BMP7 combination was increased compared to induction with TGFβ1 alone. The TGFβ1 and BMP7 combination upregulated the expression of TGFβ receptor and the production of endogenous TGFβs compared to TGFβ1 induction. The growth factor combination also increasingly activated both of the TGF and BMP signaling pathways, and inhibition of the signaling pathways led to reduced chondrogenesis of ESC-MSCs. Our findings suggest that by adding BMP7 to TGFβ1-supplemented induction medium, ESC-MSC chondrogenesis is upregulated through increased production of endogenous TGFβ and activities of TGFβ and BMP signaling. J. Cell. Biochem. 118: 172-181, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

49 CFR 218.103 - Hand-operated switches, including crossover switches.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Hand-operated switches, including crossover switches. 218.103 Section 218.103 Transportation Other Regulations Relating to Transportation (Continued... Equipment, Switches, and Fixed Derails § 218.103 Hand-operated switches, including crossover switches. (a)(1...

49 CFR 218.103 - Hand-operated switches, including crossover switches.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Hand-operated switches, including crossover switches. 218.103 Section 218.103 Transportation Other Regulations Relating to Transportation (Continued... Equipment, Switches, and Fixed Derails § 218.103 Hand-operated switches, including crossover switches. (a)(1...

49 CFR 218.103 - Hand-operated switches, including crossover switches.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Hand-operated switches, including crossover switches. 218.103 Section 218.103 Transportation Other Regulations Relating to Transportation (Continued... Equipment, Switches, and Fixed Derails § 218.103 Hand-operated switches, including crossover switches. (a)(1...

49 CFR 218.103 - Hand-operated switches, including crossover switches.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Hand-operated switches, including crossover switches. 218.103 Section 218.103 Transportation Other Regulations Relating to Transportation (Continued... Equipment, Switches, and Fixed Derails § 218.103 Hand-operated switches, including crossover switches. (a)(1...

49 CFR 218.103 - Hand-operated switches, including crossover switches.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Hand-operated switches, including crossover switches. 218.103 Section 218.103 Transportation Other Regulations Relating to Transportation (Continued... Equipment, Switches, and Fixed Derails § 218.103 Hand-operated switches, including crossover switches. (a)(1...

Surgical Videos with Synchronised Vertical 2-Split Screens Recording the Surgeons' Hand Movement.

PubMed

Kaneko, Hiroki; Ra, Eimei; Kawano, Kenichi; Yasukawa, Tsutomu; Takayama, Kei; Iwase, Takeshi; Terasaki, Hiroko

2015-01-01

To improve the state-of-the-art teaching system by creating surgical videos with synchronised vertical 2-split screens. An ultra-compact, wide-angle point-of-view camcorder (HX-A1, Panasonic) was mounted on the surgical microscope focusing mostly on the surgeons' hand movements. In combination with the regular surgical videos obtained from the CCD camera in the surgical microscope, synchronised vertical 2-split-screen surgical videos were generated with the video-editing software. Using synchronised vertical 2-split-screen videos, residents of the ophthalmology department could watch and learn how assistant surgeons controlled the eyeball, while the main surgeons performed scleral buckling surgery. In vitrectomy, the synchronised vertical 2-split-screen videos showed the surgeons' hands holding the instruments and moving roughly and boldly, in contrast to the very delicate movements of the vitrectomy instruments inside the eye. Synchronised vertical 2-split-screen surgical videos are beneficial for the education of young surgical trainees when learning surgical skills including the surgeons' hand movements. © 2015 S. Karger AG, Basel.

The Robonaut 2 Hand - Designed to do Work with Tools

NASA Technical Reports Server (NTRS)

Bridgwater, L. B.; Ihrke, C. A.; Diftler, M. A.; Abdallah, M. E.; Radford, N. A.; Rogers, J. M.; Yayathi, S.; Askew, R. S.; Linn, D. M.

2011-01-01

The second generation Robonaut hand has many advantages over its predecessor. This mechatronic device is more dexterous and has improved force control and sensing giving it the capability to grasp and actuate a wider range of tools. It can achieve higher peak forces at higher speeds than the original. Developed as part of a partnership between General Motors and NASA, the hand is designed to more closely approximate a human hand. Having a more anthropomorphic design allows the hand to attain a larger set of useful grasps for working with human interfaces. Key to the hand s improved performance is the use of lower friction drive elements and a redistribution of components from the hand to the forearm, permitting more sensing in the fingers and palm where it is most important. The following describes the design, mechanical/electrical integration, and control features of the hand. Lessons learned during the development and initial operations along with planned refinements to make it more effective are presented.

EF-hand proteins and the regulation of actin-myosin interaction in the eutardigrade Hypsibius klebelsbergi (tardigrada).

PubMed

Prasath, Thiruketheeswaran; Greven, Hartmut; D'Haese, Jochen

2012-06-01

Many tardigrade species resist harsh environmental conditions by entering anhydrobiosis or cryobiosis. Desiccation as well as freeze resistance probably leads to changes of the ionic balance that includes the intracellular calcium concentration. In order to search for protein modifications affecting the calcium homoeostasis, we studied the regulatory system controlling actin-myosin interaction of the eutardigrade Hypsibius klebelsbergi and identified full-length cDNA clones for troponin C (TnC, 824 bp), calmodulin (CaM, 1,407 bp), essential myosin light chain (eMLC, 1,015 bp), and regulatory myosin light chain (rMLC, 984 bp) from a cDNA library. All four proteins belong to the EF-hand superfamily typified by a calcium coordinating helix-loop-helix motif. Further, we cloned and obtained recombinant TnC and both MLCs. CaM and TnC revealed four and two potential calcium-binding domains, respectively. Gel mobility shift assays demonstrated calcium-induced conformational transition of TnC. From both MLCs, only the rMLC showed one potential N-terminal EF-hand domain. Additionally, sequence properties suggest phosphorylation of this myosin light chain. Based on our results, we suggest a dual-regulated system at least in somatic muscles for tardigrades with a calcium-dependent tropomyosin-troponin complex bound to the actin filaments and a phosphorylation of the rMLC turning on and off both actin and myosin. Our results indicate no special modifications of the molecular structure and function of the EF-hand proteins in tardigrades. Phylogenetic trees of 131 TnCs, 96 rMLCs, and 62 eMLCs indicate affinities to Ecdysozoa, but also to some other taxa suggesting that our results reflect the complex evolution of these proteins rather than phylogenetic relationships. © 2012 WILEY PERIODICALS, INC.

Regulation of NucB2/Nesfatin-1 throughout rat pregnancy.

PubMed

Garcés, María F; Poveda, Natalia E; Sanchez, Elizabeth; Sánchez, Ángel Y; Bravo, Susana B; Vázquez, María J; Diéguez, Carlos; Nogueiras, Rubén; Caminos, Jorge E

2014-06-22

Nesfatin-1 is an anorexigenic neuropeptide derived by post-translational cleavage from the N-terminus region DNA binding/EF-hand/acidic amino acid rich region (NEFA)/nucleobindin2 (NucB2) protein through proteolytic prohormone convertases. This neuropeptide was originally localized in different appetite controlling areas such as the hypothalamic paraventricular nucleus, arcuate nucleus, supraoptic nucleus, lateral hypothalamic area, and nucleus tractus solitarius. The objective of this study was to determine the expression and the changes that occur to mRNA and protein of NucB2 and Nesfatin-1 serum levels during gestation. This study utilized molecular and immunological approaches to investigate the expression and regulation of NucB2/Nesfatin-1 protein throughout gestation in rat fed under ad libitum and food restricted conditions (30% nutrient restriction). NucB2 was immunolocalized in the amnion and decidua of the rat placenta. Nesfatin-1 serum levels were measured by radioimmunoassay on gestational days 12, 16, 19 and 21, showing a significant (p<0.01) decrease in serum levels after day 12 until the end of gestation in rats fed ad libitum. These results were correlated with the analysis of NucB2 mRNA, with a significant (p<0.01) reduction observed in both the mRNA and protein of NucB2 during the gestational days 12, 16 and 21. It was also observed that food restriction decreases Nesfatin-1 serum levels and NucB2 placental expression at day 16 of gestation when compared to pregnant rats fed ad libitum. This study illustrates for the first time through molecular and immunological approaches the NucB2 expression and regulation on rat placenta and that this peptide is regulated throughout pregnancy. Consistent with previous reports, our results provide additional evidence supporting the role of NucB2 protein as an anorexigenic peptide that may contribute to the regulation of feeding behavior and energy homeostasis. NucB2/Nesfatin-1 might play an important metabolic

Hospital hand hygiene opportunities: where and when (HOW2)? The HOW2 Benchmark Study.

PubMed

Steed, Connie; Kelly, J William; Blackhurst, Dawn; Boeker, Sue; Diller, Thomas; Alper, Paul; Larson, Elaine

2011-02-01

Measurement and monitoring of health care workers' hand hygiene compliance (i.e., actions/opportunities) is a key component of strategies to eliminate hospital-acquired infections. Little data exist on the expected number of hand hygiene opportunities (HHOs) in various hospital settings, however. The purpose of this study was to estimate HHOs in 2 types of hospitals--large teaching and small community--and 3 different clinical areas-medical-surgical intensive care units, general medical wards, and emergency departments. HHO data were collected through direct observations using the World Health Organization's monitoring methodology. Estimates of HHOs were developed for 12-hour AM/PM shifts and 24-hour time frames. During 436.7 hours of observation, 6,640 HHOs were identified. Estimates of HHOs ranged from 30 to 179 per patient-day on inpatient wards and from 1.84 to 5.03 per bed-hour in emergency departments. Significant differences in HHOs were found between the 2 hospital types and among the 3 clinical areas. This study is the first to use the World Health Organization's data collection methodology to estimate HHOs in general medical wards and emergency departments. These data can be used as denominator estimates to calculate hand hygiene compliance rates when product utilization data are available. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

25 CFR 167.2 - General regulations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false General regulations. 167.2 Section 167.2 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER NAVAJO GRAZING REGULATIONS § 167.2 General regulations. Part 166 of this subchapter authorizes the Commissioner of Indian Affairs to regulate...

25 CFR 167.2 - General regulations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false General regulations. 167.2 Section 167.2 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER NAVAJO GRAZING REGULATIONS § 167.2 General regulations. Part 166 of this subchapter authorizes the Commissioner of Indian Affairs to regulate...

Hand placement near the visual stimulus improves orientation selectivity in V2 neurons

PubMed Central

Sergio, Lauren E.; Crawford, J. Douglas; Fallah, Mazyar

2015-01-01

Often, the brain receives more sensory input than it can process simultaneously. Spatial attention helps overcome this limitation by preferentially processing input from a behaviorally-relevant location. Recent neuropsychological and psychophysical studies suggest that attention is deployed to near-hand space much like how the oculomotor system can deploy attention to an upcoming gaze position. Here we provide the first neuronal evidence that the presence of a nearby hand enhances orientation selectivity in early visual processing area V2. When the hand was placed outside the receptive field, responses to the preferred orientation were significantly enhanced without a corresponding significant increase at the orthogonal orientation. Consequently, there was also a significant sharpening of orientation tuning. In addition, the presence of the hand reduced neuronal response variability. These results indicate that attention is automatically deployed to the space around a hand, improving orientation selectivity. Importantly, this appears to be optimal for motor control of the hand, as opposed to oculomotor mechanisms which enhance responses without sharpening orientation selectivity. Effector-based mechanisms for visual enhancement thus support not only the spatiotemporal dissociation of gaze and reach, but also the optimization of vision for their separate requirements for guiding movements. PMID:25717165

Musculoskeletal disorders of the hand in type 2 diabetes mellitus: prevalence and its associated factors.

PubMed

Mustafa, Khader N; Khader, Yousef S; Bsoul, Amal K; Ajlouni, Kamel

2016-07-01

To assess the prevalence of musculoskeletal disorders of the hand among adult patients with type 2 diabetes mellitus (T2DM) and their relation to disease duration, glycemic control and microvascular complications. A cross-sectional study was conducted at the National Center for Diabetes, Endocrinology and Genetics in Amman, Jordan. One thousand patients with T2DM were included in this study (mean age 57.8 ± 9.5 years, 52.2% females and 47.8% males). Hand disorders were seen in 69.5% of patients, limited joint mobility (LJM) was the most prevalent (63.1%) condition followed by Dupuytren's contracture (DC) (18.6%). Trigger finger, thick skin and carpal tunnel syndrome (CTS) were found in 7.2%, 6.2% and 5.5% of patients, respectively. One disorder was seen in 45.4% of patients, two in18.2%, three in 4.9%, four in 0.9%, while only 0.1% of patients had all disorders. Female gender, age over 60 years and long duration of diabetes were associated with hand abnormalities. Hypertension was significantly associated with DC while retinopathy was associated with increased odds of thick skin, DC and CTS with P-values 0.037, < 0.005 and 0.002, respectively. Hand disorders are very common in T2DM. Female gender, old age, duration of diabetes, retinopathy and hypertension were significantly associated with hand disorders in T2DM. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

49 CFR 236.528 - Restrictive condition resulting from open hand-operated switch; requirement.

Code of Federal Regulations, 2013 CFR

2013-10-01

...-operated switch; requirement. 236.528 Section 236.528 Transportation Other Regulations Relating to... Instructions; Roadway § 236.528 Restrictive condition resulting from open hand-operated switch; requirement. When a facing point hand-operated switch is open one-fourth inch or more, a trailing point hand...

49 CFR 236.528 - Restrictive condition resulting from open hand-operated switch; requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

...-operated switch; requirement. 236.528 Section 236.528 Transportation Other Regulations Relating to... Instructions; Roadway § 236.528 Restrictive condition resulting from open hand-operated switch; requirement. When a facing point hand-operated switch is open one-fourth inch or more, a trailing point hand...

49 CFR 236.528 - Restrictive condition resulting from open hand-operated switch; requirement.

Code of Federal Regulations, 2012 CFR

2012-10-01

...-operated switch; requirement. 236.528 Section 236.528 Transportation Other Regulations Relating to... Instructions; Roadway § 236.528 Restrictive condition resulting from open hand-operated switch; requirement. When a facing point hand-operated switch is open one-fourth inch or more, a trailing point hand...

PLOD2 regulated by transcription factor FOXA1 promotes metastasis in NSCLC

PubMed Central

Du, Hongzhi; Chen, Yulong; Hou, Xiaoying; Huang, Yue; Wei, Xiaohui; Yu, Xiaowen; Feng, Shuyun; Wu, Yao; Zhan, Meixiao; Shi, Xin; Lin, Sensen; Lu, Ligong; Yuan, Shengtao; Sun, Li

2017-01-01

In multiple types of tumors, fibrotic collagen is regarded as the 'highway' for cancer cell migration, which is mainly modified by lysyl hydroxylase 2 (PLOD2). The previous findings have demonstrated that the expression of PLOD2 was regulated by multiple factors, including HIF-1α, TGF-β and microRNA-26a/b. Although PLOD2 was confirmed to be related to poor prognosis in lung adenocarcinoma, the regulatory mechanism and function of PLOD2 in human lung adenocarcinoma is poorly understood. On the other hand, upregulation or hyperactivation of epidermal growth factor receptor is considered as a prognostic marker in many cancers, especially in non-small-cell lung cancer (NSCLC). In this study, we found that PLOD2 was elevated in NSCLC specimens and positively links to NSCLC poor prognosis. Gain- and loss-of-function studies and orthotopic implantation metastasis model pinpointed that PLOD2 promotes NSCLC metastasis directly by enhancing migration and indirectly by inducing collagen reorganization. In addition, we revealed that PLOD2 was regulated by PI3K/AKT-FOXA1 axis. The transcription factor FOXA1 directly bound to the PLOD2 promoter, and turned on PLOD2 transcription. In summary, our findings revealed a regulatory mechanism of NSCLC metastasis through EGFR-PI3K/AKT-FOXA1-PLOD2 pathway, and provided PLOD2 as a therapeutic target for NSCLC treatment. PMID:29072684

The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells.

PubMed

Zacharopoulou, Nefeli; Tsapara, Anna; Kallergi, Galatea; Schmid, Evi; Alkahtani, Saad; Alarifi, Saud; Tsichlis, Philip N; Kampranis, Sotirios C; Stournaras, Christos

2018-05-14

The epigenetic factor KDM2B is a histone demethylase expressed in various tumors. Recently, we have shown that KDM2B regulates actin cytoskeleton organization, small Rho GTPases signaling, cell-cell adhesion and migration of prostate tumor cells. In the present study, we addressed its role in regulating EMT and small GTPases expression in colon tumor cells. We used RT-PCR for the transcriptional analysis of various genes, Western blotting for the assessment of protein expression and immunofluorescence microscopy for visualization of fluorescently labeled proteins. We report here that KDM2B regulates EZH2 and BMI1 in HCT116 colon tumor cells. Knockdown of this epigenetic factor induced potent up-regulation of the protein levels of the epithelial markers E-cadherin and ZO-1, while the mesenchymal marker N-cadherin was downregulated. On the other hand, KDM2B overexpression downregulated the levels of both epithelial markers and upregulated the mesenchymal marker, suggesting control of EMT by KDM2B. In addition, RhoA, RhoB and RhoC protein levels diminished upon KDM2B-knockdown, while all three small GTPases became upregulated in KDM2B-overexpressing HCT116 cell clones. Interestingly, Rac1 GTPase level increased upon KDM2B-knockdown and diminished in KDM2B-overexpressing HCT116 colon tumor- and DU-145 prostate cancer cells. These results establish a clear functional role of the epigenetic factor KDM2B in the regulation of EMT and small-GTPases expression in colon tumor cells and further support the recently postulated oncogenic role of this histone demethylase in various tumors. © 2018 The Author(s). Published by S. Karger AG, Basel.

Access to waterless hand sanitizer improves student hand hygiene behavior in primary schools in Nairobi, Kenya.

PubMed

Pickering, Amy J; Davis, Jennifer; Blum, Annalise G; Scalmanini, Jenna; Oyier, Beryl; Okoth, George; Breiman, Robert F; Ram, Pavani K

2013-09-01

Handwashing is difficult in settings with limited resources and water access. In primary schools within urban Kibera, Kenya, we investigated the impact of providing waterless hand sanitizer on student hand hygiene behavior. Two schools received a waterless hand sanitizer intervention, two schools received a handwashing with soap intervention, and two schools received no intervention. Hand cleaning behavior after toilet use was monitored for 2 months using structured observation. Hand cleaning after toileting was 82% at sanitizer schools (N = 2,507 toileting events), 38% at soap schools (N = 3,429), and 37% at control schools (N = 2,797). Students at sanitizer schools were 23% less likely to have observed rhinorrhea than control students (P = 0.02); reductions in student-reported gastrointestinal and respiratory illness symptoms were not statistically significant. Providing waterless hand sanitizer markedly increased student hand cleaning after toilet use, whereas the soap intervention did not. Waterless hand sanitizer may be a promising option to improve student hand cleansing behavior, particularly in schools with limited water access.

Hand coverage by alcohol-based handrub varies: Volume and hand size matter.

PubMed

Zingg, Walter; Haidegger, Tamas; Pittet, Didier

2016-12-01

Visitors of an infection prevention and control conference performed hand hygiene with 1, 2, or 3 mL ultraviolet light-traced alcohol-based handrub. Coverage of palms, dorsums, and fingertips were measured by digital images. Palms of all hand sizes were sufficiently covered when 2 mL was applied, dorsums of medium and large hands were never sufficiently covered. Palmar fingertips were sufficiently covered when 2  or 3 mL was applied, and dorsal fingertips were never sufficiently covered. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Prevalence of hand disorders in type 2 diabetes mellitus and its correlation with microvascular complications.

PubMed

Pandey, A; Usman, K; Reddy, H; Gutch, M; Jain, N; Qidwai, Sa

2013-07-01

Physicians have long recognized the association between diabetes mellitus and several pathologic conditions of the hand. The most commonly recognized maladies are limited joint mobility (LJM), Dupuytren's disease (DD), trigger finger (TF), and carpal tunnel syndrome (CTS). Incidence of these hand disorders has increased in the setting of diabetes. Collectively, these are described as diabetic hand syndrome. The aims were to find out the prevalence of hand disorders in diabetic patients, and to study the relation of these hand disorders with microvascular complications. This is an observational cross-sectional case-control study done over a period of 1 year Patients of type 2 DM, of age < 65 years, who visited Gandhi Memorial Hospital, Lucknow were enrolled and were described as cases. Age- and sex-matched nondiabetic individuals were taken in the control group. The data were analyzed using software SPSS. SPSS Inc. Released 2008. SPSS Statistics for Windows, Version 17.0. Chicago: SPSS Inc. Means and standard deviations were computed; the Student t-test and Chi-square (χ(2)) test were used as appropriate. A total of 400 subjects were studied, 200 each in the case and control groups. Of total 200 diabetic patients, 30% (60/200) patients had neuropathy, 37.5% (75/200) had nephropathy, and 44.5% (89/200) patients had retinopathy. In the study population, 67% patients were having one or more hand disorders, in which LJM was found in 40.5% (81/200) patients, DD was found in 19% (38/200) patients, TF in 16.5% (33/200), and CTS in 14% (28/200) patients. This study shows a high prevalence of hand disorders in diabetic patients and also correlates with the duration of type 2 DM, LJM being the most common hand disorder and more common in patients who have microvascular complications.

Plant chimeric Ca2+/Calmodulin-dependent protein kinase. Role of the neural visinin-like domain in regulating autophosphorylation and calmodulin affinity

NASA Technical Reports Server (NTRS)

Sathyanarayanan, P. V.; Cremo, C. R.; Poovaiah, B. W.

2000-01-01

Chimeric Ca(2+)/calmodulin-dependent protein kinase (CCaMK) is characterized by a serine-threonine kinase domain, an autoinhibitory domain, a calmodulin-binding domain and a neural visinin-like domain with three EF-hands. The neural visinin-like Ca(2+)-binding domain at the C-terminal end of the CaM-binding domain makes CCaMK unique among all the known calmodulin-dependent kinases. Biological functions of the plant visinin-like proteins or visinin-like domains in plant proteins are not well known. Using EF-hand deletions in the visinin-like domain, we found that the visinin-like domain regulated Ca(2+)-stimulated autophosphorylation of CCaMK. To investigate the effects of Ca(2+)-stimulated autophosphorylation on the interaction with calmodulin, the equilibrium binding constants of CCaMK were measured by fluorescence emission anisotropy using dansylated calmodulin. Binding was 8-fold tighter after Ca(2+)-stimulated autophosphorylation. This shift in affinity did not occur in CCaMK deletion mutants lacking Ca(2+)-stimulated autophosphorylation. A variable calmodulin affinity regulated by Ca(2+)-stimulated autophosphorylation mediated through the visinin-like domain is a new regulatory mechanism for CCaMK activation and calmodulin-dependent protein kinases. Our experiments demonstrate the existence of two functional molecular switches in a protein kinase regulating the kinase activity, namely a visinin-like domain acting as a Ca(2+)-triggered switch and a CaM-binding domain acting as an autophosphorylation-triggered molecular switch.

Long term type 1 diabetes is associated with hand pain, disability and stiffness but not with structural hand osteoarthritis features – The Dialong hand study

PubMed Central

Magnusson, Karin; Bech Holte, Kristine; Juel, Niels Gunnar; Brox, Jens Ivar; Hagen, Kåre Birger; Haugen, Ida Kristin; Berg, Tore Julsrud

2017-01-01

Objective To explore whether having long-term type 1 diabetes (>45 years) is associated with a higher prevalence of radiographic hand OA, erosive hand OA and increased hand pain, disability and stiffness. Methods In total N = 96 persons with type 1 diabetes diagnosed before 1970 were included (mean [SD] age: 62.2 [7.4], mean [SD] HbA1c: 7.43 [0.80] and N = 49 [51%] men). Regular measurements of their HbA1c were obtained till 2015. We included N = 69 healthy controls without any diabetes (mean [SD] age: 63.0 [7.0], mean [SD] HbA1c: 5.41 [0.32], N = 29 [42%] men). The groups were compared for radiographic hand OA (Kellgren-Lawrence grade ≥2 in ≥1 joint) and erosive hand OA (central erosions in ≥1 joint), Australian/Canadian index (AUSCAN) for hand pain, disability and stiffness using regression analyses adjusted for age, sex, educational level and waist circumference. Results We found no associations between having long term type 1 diabetes and more prevalent radiographic hand OA (OR = 0.83, 95% CI = 0.38–1.81). We found a trend towards higher prevalence of erosive hand OA in diabetes patients (OR = 2.96, 95% CI = 0.82–10.64). Strong and consistent associations were observed between long term type 1 diabetes and increased hand pain (B = 2.78, 95% CI = 1.65–3.91), disability (B = 5.30, 95% CI = 3.48–7.12) and stiffness (B = 2.00, 95% CI = 1.33–2.67). These associations were particularly strong for women and participants below the median age of 61 years. Conclusion Long-term type 1 diabetes was not associated with radiographic hand OA, but was strongly associated with hand pain, disability and stiffness. The association between diabetes and erosive hand OA warrants further investigation. PMID:28510594

49 CFR 229.87 - Hand-operated switches.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Hand-operated switches. 229.87 Section 229.87 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Safety Requirements Electrical System § 229...

Access to Waterless Hand Sanitizer Improves Student Hand Hygiene Behavior in Primary Schools in Nairobi, Kenya

PubMed Central

Pickering, Amy J.; Davis, Jennifer; Blum, Annalise G.; Scalmanini, Jenna; Oyier, Beryl; Okoth, George; Breiman, Robert F.; Ram, Pavani K.

2013-01-01

Handwashing is difficult in settings with limited resources and water access. In primary schools within urban Kibera, Kenya, we investigated the impact of providing waterless hand sanitizer on student hand hygiene behavior. Two schools received a waterless hand sanitizer intervention, two schools received a handwashing with soap intervention, and two schools received no intervention. Hand cleaning behavior after toilet use was monitored for 2 months using structured observation. Hand cleaning after toileting was 82% at sanitizer schools (N = 2,507 toileting events), 38% at soap schools (N = 3,429), and 37% at control schools (N = 2,797). Students at sanitizer schools were 23% less likely to have observed rhinorrhea than control students (P = 0.02); reductions in student-reported gastrointestinal and respiratory illness symptoms were not statistically significant. Providing waterless hand sanitizer markedly increased student hand cleaning after toilet use, whereas the soap intervention did not. Waterless hand sanitizer may be a promising option to improve student hand cleansing behavior, particularly in schools with limited water access. PMID:23836575

The use of biodegradable PLGA nanoparticles to mediate SOX9 gene delivery in human mesenchymal stem cells (hMSCs) and induce chondrogenesis.

PubMed

Kim, Jae-Hwan; Park, Ji Sun; Yang, Han Na; Woo, Dae Gyun; Jeon, Su Yeon; Do, Hyun-Jin; Lim, Hye-Young; Kim, Jung Mo; Park, Keun-Hong

2011-01-01

In stem cell therapy, transfection of specific genes into stem cells is an important technique to induce cell differentiation. To perform gene transfection in human mesenchymal stem cells (hMSCs), we designed and fabricated a non-viral vector system for specific stem cell differentiation. Several kinds of gene carriers were evaluated with regard to their transfection efficiency and their ability to enhance hMSCs differentiation. Of these delivery vehicles, biodegradable poly (DL-lactic-co-glycolic acid) (PLGA) nanoparticles yielded the best results, as they complexed with high levels of plasmid DNA (pDNA), allowed robust gene expression in hMSCs, and induced chondrogenesis. Polyplexing with polyethylenimine (PEI) enhanced the cellular uptake of SOX9 DNA complexed with PLGA nanoparticles both in vitro and in vivo. The expression of enhanced green fluorescent protein (EGFP) and SOX9 increased up to 75% in hMSCs transfected with PEI/SOX9 complexed PLGA nanoparticles 2 days after transfection. SOX9 gene expression was evaluated by RT-PCR, real time-qPCR, glycosaminoglycan (GAG)/DNA levels, immunoblotting, histology, and immunofluorescence. Copyright © 2010 Elsevier Ltd. All rights reserved.

The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis

PubMed Central

Liu, Chia-Feng; Lefebvre, Véronique

2015-01-01

SOX9 is a transcriptional activator required for chondrogenesis, and SOX5 and SOX6 are closely related DNA-binding proteins that critically enhance its function. We use here genome-wide approaches to gain novel insights into the full spectrum of the target genes and modes of action of this chondrogenic trio. Using the RCS cell line as a faithful model for proliferating/early prehypertrophic growth plate chondrocytes, we uncover that SOX6 and SOX9 bind thousands of genomic sites, frequently and most efficiently near each other. SOX9 recognizes pairs of inverted SOX motifs, whereas SOX6 favors pairs of tandem SOX motifs. The SOX proteins primarily target enhancers. While binding to a small fraction of typical enhancers, they bind multiple sites on almost all super-enhancers (SEs) present in RCS cells. These SEs are predominantly linked to cartilage-specific genes. The SOX proteins effectively work together to activate these SEs and are required for in vivo expression of their associated genes. These genes encode key regulatory factors, including the SOX trio proteins, and all essential cartilage extracellular matrix components. Chst11, Fgfr3, Runx2 and Runx3 are among many other newly identified SOX trio targets. SOX9 and SOX5/SOX6 thus cooperate genome-wide, primarily through SEs, to implement the growth plate chondrocyte differentiation program. PMID:26150426

The Rubber Hand Illusion: Feeling of Ownership and Proprioceptive Drift Do Not Go Hand in Hand

PubMed Central

Rohde, Marieke; Di Luca, Massimiliano; Ernst, Marc O.

2011-01-01

In the Rubber Hand Illusion, the feeling of ownership of a rubber hand displaced from a participant's real occluded hand is evoked by synchronously stroking both hands with paintbrushes. A change of perceived finger location towards the rubber hand (proprioceptive drift) has been reported to correlate with this illusion. To measure the time course of proprioceptive drift during the Rubber Hand Illusion, we regularly interrupted stroking (performed by robot arms) to measure perceived finger location. Measurements were made by projecting a probe dot into the field of view (using a semi-transparent mirror) and asking participants if the dot is to the left or to the right of their invisible hand (Experiment 1) or to adjust the position of the dot to that of their invisible hand (Experiment 2). We varied both the measurement frequency (every 10 s, 40 s, 120 s) and the mode of stroking (synchronous, asynchronous, just vision). Surprisingly, with frequent measurements, proprioceptive drift occurs not only in the synchronous stroking condition but also in the two control conditions (asynchronous stroking, just vision). Proprioceptive drift in the synchronous stroking condition is never higher than in the just vision condition. Only continuous exposure to asynchronous stroking prevents proprioceptive drift and thus replicates the differences in drift reported in the literature. By contrast, complementary subjective ratings (questionnaire) show that the feeling of ownership requires synchronous stroking and is not present in the asynchronous stroking condition. Thus, subjective ratings and drift are dissociated. We conclude that different mechanisms of multisensory integration are responsible for proprioceptive drift and the feeling of ownership. Proprioceptive drift relies on visuoproprioceptive integration alone, a process that is inhibited by asynchronous stroking, the most common control condition in Rubber Hand Illusion experiments. This dissociation implies that

The Protein Kinase CK2 Mediates Cross-Talk between Auxin- and Salicylic Acid-Signaling Pathways in the Regulation of PINOID Transcription

PubMed Central

Armengot, Laia; Caldarella, Eleonora; Marquès-Bueno, Maria Mar; Martínez, M. Carmen

2016-01-01

The protein kinase CK2 is a ubiquitous and highly conserved enzyme, the activity of which is vital for eukaryotic cells. We recently demonstrated that CK2 modulates salicylic acid (SA) homeostasis in Arabidopsis thaliana, and that functional interplay between CK2 and SA sustains transcriptional expression of PIN-FORMED (PIN) genes. In this work, we show that CK2 also plays a key role in the transcriptional regulation of PINOID (PID), an AGC protein kinase that modulates the apical/basal localization of auxin-efflux transporters. We show that PID transcription is up-regulated by auxin and by SA and that CK2 is involved in both pathways. On the one hand, CK2 activity is required for proteosome-dependent degradation of AXR3, a member of the AUX/IAA family of auxin transcriptional repressors that must be degraded to activate auxin-responsive gene expression. On the other hand, the role of CK2 in SA homeostasis and, indirectly, in SA-driven PID transcription, was confirmed by using Arabidopsis NahG transgenic plants, which cannot accumulate SA. In conclusion, our results evidence a role for CK2 as a functional link in the negative cross-talk between auxin- and SA-signaling. PMID:27275924

Gen-2 hand-held optical imager towards cancer imaging: reflectance and transillumination phantom studies.

PubMed

Gonzalez, Jean; Roman, Manuela; Hall, Michael; Godavarty, Anuradha

2012-01-01

Hand-held near-infrared (NIR) optical imagers are developed by various researchers towards non-invasive clinical breast imaging. Unlike these existing imagers that can perform only reflectance imaging, a generation-2 (Gen-2) hand-held optical imager has been recently developed to perform both reflectance and transillumination imaging. The unique forked design of the hand-held probe head(s) allows for reflectance imaging (as in ultrasound) and transillumination or compressed imaging (as in X-ray mammography). Phantom studies were performed to demonstrate two-dimensional (2D) target detection via reflectance and transillumination imaging at various target depths (1-5 cm deep) and using simultaneous multiple point illumination approach. It was observed that 0.45 cc targets were detected up to 5 cm deep during transillumination, but limited to 2.5 cm deep during reflectance imaging. Additionally, implementing appropriate data post-processing techniques along with a polynomial fitting approach, to plot 2D surface contours of the detected signal, yields distinct target detectability and localization. The ability of the gen-2 imager to perform both reflectance and transillumination imaging allows its direct comparison to ultrasound and X-ray mammography results, respectively, in future clinical breast imaging studies.

* Hypoxia for Mesenchymal Stem Cell Expansion and Differentiation: The Best Way for Enhancing TGFß-Induced Chondrogenesis and Preventing Calcifications in Alginate Beads.

PubMed

Henrionnet, Christel; Liang, Gai; Roeder, Emilie; Dossot, Manuel; Wang, Hui; Magdalou, Jacques; Gillet, Pierre; Pinzano, Astrid

2017-09-01

We examined the respective influence of a sequential or a continuous hypoxia during expansion and transforming growth factor beta 1-driven chondrogenic differentiation of human bone marrow mesenchymal stem cells (MSCs). The differentiation was performed within alginate beads, a classical tool for the implantation of MSCs within the joint. The standard normoxic 2D (expansion) and 3D (differentiation) MSCs cultures served as reference. To determine the quality of chondrogenesis, we analyzed typical markers such as type II and X collagens, SOX9, COMP, versican, and aggrecan mRNAs using polymerase chain reaction and we assessed the production of type II collagen and hypoxia-inducible factor (HIF)-1α by histological stainings. We simultaneously assessed the expression of osteogenic mRNAs (Alkaline Phosphatase, RUNX2, and Osteocalcin) and the presence of micro-calcifications by Alizarin red and Raman spectroscopy. Chondrogenic differentiation is clearly improved by hypoxia in 3D. Best results were obtained when the entire process, that is, 2D expansion and 3D differentiation, was performed under continuous 5% hypoxic condition. In addition, no calcification (hydroxyapatite, proved by RAMAN) was observed after 2D hypoxic expansion even in the case of a normoxic differentiation, in contrast with controls. Finally, a better chondrogenic differentiation of human MSCs is achieved when a reduced oxygen tension is applied during both expansion and differentiation times, avoiding in vitro osteogenic commitment of cells and subsequently the calcification deposition.

Hand-to-Hand Model for Bioelectrical Impedance Analysis to Estimate Fat Free Mass in a Healthy Population

PubMed Central

Lu, Hsueh-Kuan; Chiang, Li-Ming; Chen, Yu-Yawn; Chuang, Chih-Lin; Chen, Kuen-Tsann; Dwyer, Gregory B.; Hsu, Ying-Lin; Chen, Chun-Hao; Hsieh, Kuen-Chang

2016-01-01

This study aimed to establish a hand-to-hand (HH) model for bioelectrical impedance analysis (BIA) fat free mass (FFM) estimation by comparing with a standing position hand-to-foot (HF) BIA model and dual energy X-ray absorptiometry (DXA); we also verified the reliability of the newly developed model. A total of 704 healthy Chinese individuals (403 men and 301 women) participated. FFM (FFMDXA) reference variables were measured using DXA and segmental BIA. Further, regression analysis, Bland–Altman plots, and cross-validation (2/3 participants as the modeling group, 1/3 as the validation group; three turns were repeated for validation grouping) were conducted to compare tests of agreement with FFMDXA reference variables. In male participants, the hand-to-hand BIA model estimation equation was calculated as follows: FFMmHH = 0.537 h2/ZHH − 0.126 year + 0.217 weight + 18.235 (r2 = 0.919, standard estimate of error (SEE) = 2.164 kg, n = 269). The mean validated correlation coefficients and limits of agreement (LOAs) of the Bland–Altman analysis of the calculated values for FFMmHH and FFMDXA were 0.958 and −4.369–4.343 kg, respectively, for hand-to-foot BIA model measurements for men; the FFM (FFMmHF) and FFMDXA were 0.958 and −4.356–4.375 kg, respectively. The hand-to-hand BIA model estimating equation for female participants was FFMFHH = 0.615 h2/ZHH − 0.144 year + 0.132 weight + 16.507 (r2 = 0.870, SEE = 1.884 kg, n = 201); the three mean validated correlation coefficient and LOA for the hand-to-foot BIA model measurements for female participants (FFMFHH and FFMDXA) were 0.929 and −3.880–3.886 kg, respectively. The FFMHF and FFMDXA were 0.942 and −3.511–3.489 kg, respectively. The results of both hand-to-hand and hand-to-foot BIA models demonstrated similar reliability, and the hand-to-hand BIA models are practical for assessing FFM. PMID:27775642

25 CFR 249.2 - Area regulations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Area regulations. 249.2 Section 249.2 Indians BUREAU OF... Provisions § 249.2 Area regulations. (a) The Secretary of the Interior may upon request of an Indian tribe, request of a State Governor, or upon his own motion, and upon finding that Federal regulation of Indian...

25 CFR 249.2 - Area regulations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Area regulations. 249.2 Section 249.2 Indians BUREAU OF... Provisions § 249.2 Area regulations. (a) The Secretary of the Interior may upon request of an Indian tribe, request of a State Governor, or upon his own motion, and upon finding that Federal regulation of Indian...

Nudging to improve hand hygiene.

PubMed

Caris, M G; Labuschagne, H A; Dekker, M; Kramer, M H H; van Agtmael, M A; Vandenbroucke-Grauls, C M J E

2018-04-01

Hand hygiene is paramount to prevent healthcare-associated infections, but improving compliance is challenging. When healthcare workers seldom encounter healthcare-associated infections, they will consider the odds of causing infections through poor hand hygiene negligible. Cognitive biases such as these may induce non-compliance. Nudging, 'a friendly push to encourage desired behaviour', could provide an easily implemented, inexpensive measure to address cognitive biases and thus support hand hygiene interventions. To investigate whether behavioural nudges, displayed as posters, can increase the use of alcohol-based hand rub. We developed nudges based on a systematic review of previously described cognitive biases, and tested these through a cross-sectional survey among the target audience. We then conducted a controlled before-after trial on two hospital wards, to assess the effect of these nudges on the use of alcohol-based hand rub, measured with electronic dispensers. Poisson regression analyses adjusted for workload showed that nudges displayed next to dispensers increased their overall use on one ward [poster 1: relative risk: 1.6 (95% confidence interval: 1.2-2.2); poster 2: 1.7 (1.2-2.5)] and during doctor's rounds on both wards [poster 1: ward A: 1.7 (1.1-2.6); ward B: 2.2 (1.3-3.8)]. Use of dispensers without adjacent nudges did not increase. Nudges based on cognitive biases that play a role in hand hygiene, and displayed as posters, could provide an easy, inexpensive measure to increase use of alcohol-based hand rub. When applying nudges to change behaviour, it is important to identify the right nudge for the right audience. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Fitting a hand-glove prosthesis to enhance the reconstructed mutilated hand.

PubMed

Leow, M E; Kour, A K; Pereira, B P; Pho, R W

1998-03-01

Microsurgical reconstruction of the severely mutilated hand aimed at improving prehensile functions often does not address the esthetic aspects of the hand. The poor appearance of the reconstructed hand affects its active display and use. A hand-glove prosthesis may be prescribed in this instance to enhance the overall form and function of the mutilated hand. We reviewed 16 cases of mutilating hand injuries in which surgical reconstructions were performed and the patients were subsequently fitted with a hand-glove prosthesis to augment the outcome. An improved appearance was achieved in all patients fitted with the prosthesis. The patients' sense of confidence was also enhanced, which in turn promoted the active and open use of the reconstructed hands. While prescribed primarily to improve the appearance of the reconstructed hands, these prostheses were documented to enhance the physical hand functions in 11 cases by increasing the span of the hand and providing an opposable post and a palmar base for holding and for anchorage. The prosthesis enhanced assistive functions of the reconstructed hands and freed the contralateral normal hand for use in bimanual activities, such as holding a wallet and taking out money, supporting a note pad for writing, and holding a plate at buffet receptions. At the 18-month follow-up visit, 13 (87%) of the patients continued to use their prosthesis. Wear and tear were problems associated with the frequent use of the prosthesis. The expected life span of the prosthesis with daily use ranged from 2 to 3 years. All the patients acknowledged that the prosthesis played a role in their rehabilitation and that it helped them to overcome the initial psychological trauma and to come to terms with their physical loss.

Ability of Hand Hygiene Interventions Using Alcohol-Based Hand Sanitizers and Soap To Reduce Microbial Load on Farmworker Hands Soiled during Harvest.

PubMed

de Aceituno, Anna Fabiszewski; Bartz, Faith E; Hodge, Domonique Watson; Shumaker, David J; Grubb, James E; Arbogast, James W; Dávila-Aviña, Jorgé; Venegas, Fabiola; Heredia, Norma; García, Santos; Leon, Juan S

2015-11-01

Effective hand hygiene is essential to prevent the spread of pathogens on produce farms and reduce foodborne illness. The U.S. Food and Drug Administration Food Safety Modernization Act Proposed Rule for Produce Safety recommends the use of soap and running water for hand hygiene of produce handlers. The use of alcohol-based hand sanitizer (ABHS) may be an effective alternative hygiene intervention where access to water is limited. There are no published data on the efficacy of either soap or ABHS-based interventions to reduce microbial contamination in agricultural settings. The goal of this study was to assess the ability of two soap-based (traditional or pumice) and two ABHS-based (label-use or two-step) hygiene interventions to reduce microbes (coliforms, Escherichia coli, and Enterococcus spp.) and soil (absorbance of hand rinsate at 600 nm [A600]) on farmworker hands after harvesting produce, compared with the results for a no-hand-hygiene control. With no hand hygiene, farmworker hands were soiled (median A600, 0.48) and had high concentrations of coliforms (geometric mean, 3.4 log CFU per hand) and Enterococcus spp. (geometric mean, 5.3 log CFU per hand) after 1 to 2 h of harvesting tomatoes. Differences in microbial loads in comparison to the loads in the control group varied by indicator organism and hygiene intervention (0 to 2.3 log CFU per hand). All interventions yielded lower concentrations of Enterococcus spp. and E. coli (P < 0.05), but not of coliforms, than were found in the control group. The two-step ABHS intervention led to significantly lower concentrations of coliforms and Enterococcus spp. than the pumice soap and label-use ABHS interventions (P < 0.05) and was the only intervention to yield significantly fewer samples with E. coli than were found in the control group (P < 0.05). All interventions removed soil from hands (P < 0.05), soap-based interventions more so than ABHS-based interventions (P < 0.05). ABHS-based interventions were

Hand Eczema

PubMed Central

Agarwal, Uma Shankar; Besarwal, Raj Kumar; Gupta, Rahul; Agarwal, Puneet; Napalia, Sheetal

2014-01-01

Hand eczema is often a chronic, multifactorial disease. It is usually related to occupational or routine household activities. Exact etiology of the disease is difficult to determine. It may become severe enough and disabling to many of patients in course of time. An estimated 2-10% of population is likely to develop hand eczema at some point of time during life. It appears to be the most common occupational skin disease, comprising 9-35% of all occupational diseases and up to 80% or more of all occupational contact dermatitis. So, it becomes important to find the exact etiology and classification of the disease and to use the appropriate preventive and treatment measures. Despite its importance in the dermatological practice, very few Indian studies have been done till date to investigate the epidemiological trends, etiology, and treatment options for hand eczema. In this review, we tried to find the etiology, epidemiology, and available treatment modalities for chronic hand eczema patients. PMID:24891648

Keep your hands crossed: the valence-by-left/right interaction is related to hand, not side, in an incongruent hand-response key assignment.

PubMed

de la Vega, Irmgard; Dudschig, Carolin; De Filippis, Mónica; Lachmair, Martin; Kaup, Barbara

2013-02-01

The body-specificity hypothesis (Casasanto, 2009) associates positive emotional valence and the space surrounding the dominant hand, and negative valence and the space surrounding the non-dominant hand. This effect has not only been found for manual responses, but also for the left and right side. In the present study, we investigated whether this compatibility effect still shows when hand and side carry incongruent information, and whether it is then related to hand or to side. We conducted two experiments which used an incongruent hand-response key assignment, that is, participants had their hands crossed. Participants were instructed to respond with their right vs. left hand (Experiment 1) or with the right vs. left key (Experiment 2). In both experiments, a compatibility effect related to hand emerged, indicating that the association between hand and valence overrides the one between side and valence when hand and side carry contradicting information. Copyright © 2013 Elsevier B.V. All rights reserved.

HandTutor™ enhanced hand rehabilitation after stroke--a pilot study.

PubMed

Carmeli, Eli; Peleg, Sara; Bartur, Gadi; Elbo, Enbal; Vatine, Jean-Jacques

2011-12-01

This study assessed the potential therapeutic benefi t of using HandTutor™ in combination with traditional rehabilitation in a post-stroke sub-acute population. The study compares an experimental group receiving traditional therapy combined with HandTutorTM treatment, against a control group receiving only traditional therapy. An assessor-blinded, randomized controlled pilot trial, was conducted in the Reuth rehabilitation unit in Israel. Thirty-one stroke patients in the sub-acute phase, were randomly assigned to one of the two groups (experimental or control) in sets of three. The experimental group (n = 16) underwent a hand rehabilitation programme using the HandTutorTM combined with traditional therapy. The control group (n = 15) received only traditional therapy. The treatment schedules for both groups were of similar duration and frequency. Improvements were evaluated using three indicators: 1) The Brunnström-Fugl-Meyer (FM) test, 2) the Box and Blocks (B&B) test and 3) improvement parameters as determined by the HandTutorTM software. Following 15 consecutive treatment sessions, a signifi cant improvement was observed within the experimental group (95% confi dence intervals) compared with the control group: B&B p = 0.015; FM p = 0.041, HandTutor™ performance accuracy on x axis and performance accuracy on y axis p < 0.0003. The results from this pilot study support further investigation of the use of the HandTutorTM in combination with traditional occupational therapy and physiotherapy during post stroke hand function rehabilitation.

Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiou, Michael; Xu Yue; Longaker, Michael T.

2006-05-05

Adipose-derived mesenchymal cells (AMCs) have demonstrated a great capacity for differentiating into bone, cartilage, and fat. Studies using bone marrow-derived mesenchymal cells (BMSCs) have shown that fibroblast growth factor (FGF)-2, a potent mitogenic factor, plays an important role in tissue engineering due to its effects in proliferation and differentiation for mesenchymal cells. The aim of this study was to investigate the function of FGF-2 in AMC chondrogenic differentiation and its possible contributions to cell-based therapeutics in skeletal tissue regeneration. Data demonstrated that FGF-2 significantly promoted the proliferation of AMCs and enhanced chondrogenesis in three-dimensional micromass culture. Moreover, priming AMCs withmore » treatment of FGF-2 at 10 ng/ml demonstrated that cells underwent chondrogenic phenotypic differentiation, possibly by inducing N-Cadherin, FGF-receptor 2, and transcription factor Sox9. Our results indicated that FGF-2 potentiates chondrogenesis in AMCs, similar to its functions in BMSCs, suggesting the versatile potential applications of FGF-2 in skeletal regeneration and cartilage repair.« less

7 CFR 319.77-2 - Regulated articles.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Regulated articles. 319.77-2 Section 319.77-2....77-2 Regulated articles. In order to prevent the spread of gypsy moth from Canada into noninfested... section are designated as regulated articles. Regulated articles may be imported into the United States...

7 CFR 319.77-2 - Regulated articles.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Regulated articles. 319.77-2 Section 319.77-2....77-2 Regulated articles. In order to prevent the spread of gypsy moth from Canada into noninfested... section are designated as regulated articles. Regulated articles may be imported into the United States...

7 CFR 319.77-2 - Regulated articles.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Regulated articles. 319.77-2 Section 319.77-2....77-2 Regulated articles. In order to prevent the spread of gypsy moth from Canada into noninfested... section are designated as regulated articles. Regulated articles may be imported into the United States...

7 CFR 301.91-2 - Regulated articles.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Regulated articles. 301.91-2 Section 301.91-2... Regulations § 301.91-2 Regulated articles. The following are regulated articles: (a) Logs, pulpwood, branches...) Any other product, article, or means of conveyance, of any character whatsoever, not covered by...

7 CFR 319.77-2 - Regulated articles.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Regulated articles. 319.77-2 Section 319.77-2....77-2 Regulated articles. In order to prevent the spread of gypsy moth from Canada into noninfested... section are designated as regulated articles. Regulated articles may be imported into the United States...

7 CFR 301.91-2 - Regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.91-2 Section 301.91-2... Regulations § 301.91-2 Regulated articles. The following are regulated articles: (a) Logs, pulpwood, branches...) Any other product, article, or means of conveyance, of any character whatsoever, not covered by...

7 CFR 301.91-2 - Regulated articles.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Regulated articles. 301.91-2 Section 301.91-2... Regulations § 301.91-2 Regulated articles. The following are regulated articles: (a) Logs, pulpwood, branches...) Any other product, article, or means of conveyance, of any character whatsoever, not covered by...

7 CFR 301.91-2 - Regulated articles.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Regulated articles. 301.91-2 Section 301.91-2... Regulations § 301.91-2 Regulated articles. The following are regulated articles: (a) Logs, pulpwood, branches...) Any other product, article, or means of conveyance, of any character whatsoever, not covered by...

7 CFR 301.91-2 - Regulated articles.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Regulated articles. 301.91-2 Section 301.91-2... Regulations § 301.91-2 Regulated articles. The following are regulated articles: (a) Logs, pulpwood, branches...) Any other product, article, or means of conveyance, of any character whatsoever, not covered by...

Overexpression and Down-Regulation of Barley Lipoxygenase LOX2.2 Affects Jasmonate-Regulated Genes and Aphid Fecundity

PubMed Central

Losvik, Aleksandra; Beste, Lisa; Glinwood, Robert; Ivarson, Emelie; Stephens, Jennifer; Zhu, Li-Hua; Jonsson, Lisbeth

2017-01-01

Aphids are pests on many crops and depend on plant phloem sap as their food source. In an attempt to find factors improving plant resistance against aphids, we studied the effects of overexpression and down-regulation of the lipoxygenase gene LOX2.2 in barley (Hordeum vulgare L.) on the performance of two aphid species. A specialist, bird cherry-oat aphid (Rhopalosiphum padi L.) and a generalist, green peach aphid (Myzus persicae Sulzer) were studied. LOX2.2 overexpressing lines showed up-regulation of some other jasmonic acid (JA)-regulated genes, and antisense lines showed down-regulation of such genes. Overexpression or suppression of LOX2.2 did not affect aphid settling or the life span on the plants, but in short term fecundity tests, overexpressing plants supported lower aphid numbers and antisense plants higher aphid numbers. The amounts and composition of released volatile organic compounds did not differ between control and LOX2.2 overexpressing lines. Up-regulation of genes was similar for both aphid species. The results suggest that LOX2.2 plays a role in the activation of JA-mediated responses and indicates the involvement of LOX2.2 in basic defense responses. PMID:29257097

FHF2 isoforms differentially regulate Nav1.6 mediated resurgent sodium currents in dorsal root ganglion neurons

PubMed Central

Barbosa, Cindy; Xiao, Yucheng; Johnson, Andrew J.; Xie, Wenrui; Strong, Judith A.; Zhang, Jun-Ming; Cummins, Theodore R.

2017-01-01

Nav1.6 and Nav1.6 mediated resurgent currents have been implicated in several pain pathologies. However, our knowledge of how fast resurgent currents are modulated in neurons is limited. Our study explored the potential regulation of Nav1.6 mediated resurgent currents by isoforms of Fibroblast growth Factor Homologous factor 2 (FHF2) in an effort to address the gap in our knowledge. FHF2 isoforms colocalize with Nav1.6 in peripheral sensory neurons. Cell line studies suggest that these proteins differentially regulate inactivation. In particular, FHF2A mediates long-term inactivation, a mechanism proposed to compete with the open-channel blocker mechanism that mediates resurgent currents. On the other hand, FHF2B lacks the ability to mediate long-term inactivation and may delay inactivation favoring open-channel block. Based on these observations, we hypothesized that FHF2A limits resurgent currents, whereas, FHF2B enhances resurgent currents. Overall our results suggest that FHF2A negatively regulates fast resurgent current by enhancing long-term inactivation and delaying recovery. In contrast FHF2B positively regulated resurgent current and did not alter long-term inactivation. Chimeric constructs of FHF2A and Navβ4 (likely the endogenous open channel blocker in sensory neurons) exhibited differential effects on resurgent currents suggesting that specific regions within FHF2A and Navβ4 have important regulatory functions. Our data also indicate FHFAs and FHF2B isoform expression are differentially regulated in a radicular pain model and that associated neuronal hyperexcitability is substantially attenuated by a FHFA peptide. As such, these findings suggest that FHF2A and FHF2B regulate resurgent current in sensory neurons and may contribute to hyperexcitability associated with some pain pathologies. PMID:27999940

FGFR3 induces degradation of BMP type I receptor to regulate skeletal development.

PubMed

Qi, Huabing; Jin, Min; Duan, Yaqi; Du, Xiaolan; Zhang, Yuanquan; Ren, Fangli; Wang, Yinyin; Tian, Qingyun; Wang, Xiaofeng; Wang, Quan; Zhu, Ying; Xie, Yangli; Liu, Chuanju; Cao, Xu; Mishina, Yuji; Chen, Di; Deng, Chu-xia; Chang, Zhijie; Chen, Lin

2014-07-01

Fibroblast growth factors (FGFs) and their receptors (FGFRs) play significant roles in vertebrate organogenesis and morphogenesis. FGFR3 is a negative regulator of chondrogenesis and multiple mutations with constitutive activity of FGFR3 result in achondroplasia, one of the most common dwarfisms in humans, but the molecular mechanism remains elusive. In this study, we found that chondrocyte-specific deletion of BMP type I receptor a (Bmpr1a) rescued the bone overgrowth phenotype observed in Fgfr3 deficient mice by reducing chondrocyte differentiation. Consistently, using in vitro chondrogenic differentiation assay system, we demonstrated that FGFR3 inhibited BMPR1a-mediated chondrogenic differentiation. Furthermore, we showed that FGFR3 hyper-activation resulted in impaired BMP signaling in chondrocytes of mouse growth plates. We also found that FGFR3 inhibited BMP-2- or constitutively activated BMPR1-induced phosphorylation of Smads through a mechanism independent of its tyrosine kinase activity. We found that FGFR3 facilitates BMPR1a to degradation through Smurf1-mediated ubiquitination pathway. We demonstrated that down-regulation of BMP signaling by BMPR1 inhibitor dorsomorphin led to the retardation of chondrogenic differentiation, which mimics the effect of FGF-2 on chondrocytes and BMP-2 treatment partially rescued the retarded growth of cultured bone rudiments from thanatophoric dysplasia type II mice. Our findings reveal that FGFR3 promotes the degradation of BMPR1a, which plays an important role in the pathogenesis of FGFR3-related skeletal dysplasia. Copyright © 2014 Elsevier B.V. All rights reserved.

Diving into Science. Hands-On Water-Related Experiments. Grades 2-4.

ERIC Educational Resources Information Center

Perdue, Peggy K.

This book contains hands-on ocean-related laboratory activities. Major chapter hearings are: (1) "Water Experiments" (dealing with the physical nature of water and listing 10 activities); (2) "Ocean-Going Vessels" (studying the principles of boats, with three experiments); (3) "Experiments Using Shells" (containing four activities); (4) "Sand…

15 CFR 2.7 - Supplementary regulations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Supplementary regulations. 2.7 Section... SETTLEMENT OF CLAIMS UNDER THE FEDERAL TORT CLAIMS ACT § 2.7 Supplementary regulations. (a) The Assistant General Counsel for Finance and Litigation may from time to time issue such supplementary regulations or...

The epigenetic regulation of SOX9 by miR-145 in human chondrosarcoma.

PubMed

Mak, Isabella W Y; Singh, Shalini; Turcotte, Robert; Ghert, Michelle

2015-01-01

Chondrosarcoma is the most common primary bone malignancy in the adult population with a high rate of pulmonary metastasis. Chondrosarcoma is managed with surgical excision as the tumors do not respond well to conventional chemotherapy or radiation therapy. Thus, there exists a dire need to develop systemic treatment options to target chondrosarcoma cells for metastatic spread. We hypothesized that the expression of miR-145 is low in chondrosarcoma, leading to decreased transcriptional control of SOX9 (the master regulator of chondrogenesis), and downstream activation of the transcription factor ETV5. We have previously shown that ETV5 activates MMP-2 expression in chondrosarcoma, which in turn increases local bone matrix resorption. In this study, we confirm high expression of SOX9 in human chondrosarcoma using real-time PCR, Western blotting, and immunofluorescence. An ETV5 promoter-reporter plasmid was transfected into chondrosarcoma cells to determine if SOX9 directly regulates the expression of ETV5. Co-transfection of the ETV5 promoter-plasmid with SOX9 lentivirus significantly increased the luciferase activity derived from the ETV5 promoter, from which the regulatory relationship between SOX9 and ETV5 is established. MiR-145 was found to be down-regulated in chondrosarcoma cell lines, patient samples, and further confirmed with a public sarcoma database. After stable miR-145 lentiviral transfection, the subsequent mRNA expression levels of SOX9, ETV5, and MMP-2 were significantly decreased in chondrosarcoma cells. The results generated by this study may have important clinical significance in the treatment of patients with chondrosarcoma in that targeted miRNA may have the potential to downregulate the upstream activators of proteases such as MMP-2. © 2014 Wiley Periodicals, Inc.

49 CFR 218.109 - Hand-operated fixed derails.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Hand-operated fixed derails. 218.109 Section 218.109 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Handling Equipment, Switches, and Fixed...

49 CFR 218.109 - Hand-operated fixed derails.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Hand-operated fixed derails. 218.109 Section 218.109 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Handling Equipment, Switches, and Fixed...

49 CFR 218.109 - Hand-operated fixed derails.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Hand-operated fixed derails. 218.109 Section 218.109 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Handling Equipment, Switches, and Fixed...

49 CFR 218.109 - Hand-operated fixed derails.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Hand-operated fixed derails. 218.109 Section 218.109 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Handling Equipment, Switches, and Fixed...

49 CFR 218.109 - Hand-operated fixed derails.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Hand-operated fixed derails. 218.109 Section 218.109 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Handling Equipment, Switches, and Fixed...

29 CFR Appendix A to Subpart Cc of... - Standard Hand Signals

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 8 2012-07-01 2012-07-01 false Standard Hand Signals A Appendix A to Subpart CC of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Construction Pt. 1926, Subpt. CC, App. A Appendix A to Subpart CC of Part 1926—Standard Hand Signals ER09AU10...

29 CFR Appendix A to Subpart Cc of... - Standard Hand Signals

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 8 2014-07-01 2014-07-01 false Standard Hand Signals A Appendix A to Subpart CC of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Construction Pt. 1926, Subpt. CC, App. A Appendix A to Subpart CC of Part 1926—Standard Hand Signals ER09AU10...

29 CFR Appendix A to Subpart Cc of... - Standard Hand Signals

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 8 2013-07-01 2013-07-01 false Standard Hand Signals A Appendix A to Subpart CC of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Construction Pt. 1926, Subpt. CC, App. A Appendix A to Subpart CC of Part 1926—Standard Hand Signals ER09AU10...

29 CFR Appendix A to Subpart Cc of... - Standard Hand Signals

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 8 2011-07-01 2011-07-01 false Standard Hand Signals A Appendix A to Subpart CC of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Cranes and Derricks in...

Regulation of scapula development.

PubMed

Huang, Ruijin; Christ, Bodo; Patel, Ketan

2006-12-01

The scapula is a component of the shoulder girdle. Its structure has changed greatly during evolution. For example, in humans it is a large quite flat triangular bone whereas in chicks it is a long blade like structure. In this review we describe the mechanisms that control the formation of the scapula. To assimilate our understanding regarding the development of the scapula blade we start by addressing the issue concerning the origin of the scapula. Experiments using somite extirpation, chick-quail cell marking system and genetic cell labelling techniques in a variety of species have suggested that the scapula had its origin in the somites. For example we have shown in the chick that the scapula blade originates from the somite, while the cranial part, which articulates with the upper limb, is derived from the somatopleure of the forelimb field. In the second and third part of the review we discuss the compartmental origin of this bone and the signalling molecules that control the scapula development. It is very interesting that the scapula blade originates from the dorsal compartment, dermomyotome, which has been previously been associated as a source of muscle and dermis, but not of cartilage. Thus, the development of the scapula blade can be considered a case of dermomyotomal chondrogenesis. Our results show that the dermomyotomal chondrogenesis differ from the sclerotomal chondrogenesis. Firstly, the scapula precursors are located in the hypaxial domain of the dermomyotome, from which the hypaxial muscles are derived. The fate of the scapula precursors, like the hypaxial muscle, is controlled by ectoderm-derived signals and BMPs from the lateral plate mesoderm. Ectoderm ablation and inhibition of BMP activity interfers the scapula-specific Pax1 expression and scapula blade formation. However, only somite cells in the cervicothoracic transition region appear to be committed to form scapula. This indicates that the intrinsic segment specific information

78 FR 68907 - Agency Information Collection (Hand and Finger Conditions Disability Benefits Questionnaire...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-15

... DEPARTMENT OF VETERANS AFFAIRS [OMB Control No. 2900-NEW] Agency Information Collection (Hand and... written comments on the collection of information through www.Regulations.gov , or to Office of... Control No. 2900- NEW (Hand and Finger Conditions Disability Benefits Questionnaire)'' in any...

48 CFR 3401.104-2 - Arrangement of regulations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Arrangement of regulations. 3401.104-2 Section 3401.104-2 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL ED ACQUISITION REGULATION SYSTEM Purpose, Authority, Issuance 3401.104-2...

FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line.

PubMed

Matsuzaki, Hidenori; Lee, Suni; Maeda, Megumi; Kumagai-Takei, Naoko; Nishimura, Yasumitsu; Otsuki, Takemi

2016-09-01

Asbestos is known to cause malignant mesothelioma and lung cancer. Recent studies implicate tumor immunity in the development of various tumors, including malignant mesothelioma. In order to establish an in vitro T-cell model to clarify the effects of long-term exposure of asbestos on tumor immunity, in this study, human T-cell line MT-2 cells were cultured with asbestos for longer than 8 months and the resultant cells (MT-2Rst) were assessed for the expression of forkhead transcription factor FoxO1. Gene expression analysis revealed that the amount of FoxO1 mRNA decreased after long-term exposure of the MT-2 cells to asbestos. In accordance with this reduction in FoxO1, pro-apoptotic Foxo1 target genes Puma, Fas ligand and Bim were also seen to be down-regulated in MT-2Rst cells. Furthermore, shRNA-mediated knock-down of FoxO1 reduced the number of apoptotic parental MT-2 cells after treatment with asbestos. On the other hand, over-expression of FoxO1 did not affect asbestos-induced apoptosis in MT-2Rst cells. These results suggested that FoxO1 played an important role in regulating asbestos-induced apoptosis and confirmed the presence of multiple pathways regulating resistance to asbestos in MT-2Rst cells.

7 CFR 301.89-2 - Regulated articles.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Regulated articles. 301.89-2 Section 301.89-2... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Karnal Bunt § 301.89-2 Regulated articles. The following are regulated articles: (a) Conveyances, including trucks, railroad cars, and other...

7 CFR 301.89-2 - Regulated articles.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Regulated articles. 301.89-2 Section 301.89-2... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Karnal Bunt § 301.89-2 Regulated articles. The following are regulated articles: (a) Conveyances, including trucks, railroad cars, and other...

7 CFR 301.89-2 - Regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.89-2 Section 301.89-2... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Karnal Bunt § 301.89-2 Regulated articles. The following are regulated articles: (a) Conveyances, including trucks, railroad cars, and other...

7 CFR 301.89-2 - Regulated articles.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Regulated articles. 301.89-2 Section 301.89-2... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Karnal Bunt § 301.89-2 Regulated articles. The following are regulated articles: (a) Conveyances, including trucks, railroad cars, and other...

7 CFR 301.89-2 - Regulated articles.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Regulated articles. 301.89-2 Section 301.89-2... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Karnal Bunt § 301.89-2 Regulated articles. The following are regulated articles: (a) Conveyances, including trucks, railroad cars, and other...

Structural Integration and Control of Peerless Human-like Prosthetic Hand

NASA Astrophysics Data System (ADS)

Dave, Ankit; Muthu, P.; Karthikraj, V.; Latha, S.

2018-04-01

Limb damage can create severe disturbance in movement and operative abilities wherein the prosthetic rehabilitation has the potential to replace function and enhance the quality of life. This paper presents a humanlike prosthetic hand using such unique design concept of hand model using artificial bones, ligaments, and tendons controlled using Arduino. Amongst various platforms available, Arduino is known for its adaptability, adoration and low cost. The design of prosthetic hand has a unique structure with all carpal, metacarpal, and phalanges which are bones of the hand. These bones are attached to each other following the pattern of human hand using the polymeric rubber as a functioning ligament. Furthermore, this structure of finger is driven by tendons attached to all fingers and passes through the ligaments working as pulley resulting in more degrees of freedom. The motor can twitch the tendons to achieve the action of fingers. Thus the servos, controlled by an Arduino, are used to regulate the movement mechanism of the prosthetic hand.

Ca2+ Binding to EF Hands 1 and 3 Is Essential for the Interaction of Apoptosis-Linked Gene-2 with Alix/AIP1 in Ocular Melanoma†

PubMed Central

Subramanian, Lalita; Polans, Arthur S.; Walker, Teresa M.; van Ginkel, Paul R.; Bhattacharya, Saswati; Dellaria, Julia M.; Crabb, John W.; Cox, Jos; Durussel, Isabelle; Palczewski, Krzysztof

2005-01-01

Apoptosis-linked gene-2 (ALG-2) encodes a 22 kDa Ca2+-binding protein of the penta EF-hand family that is required for programmed cell death in response to various apoptotic agents. Here, we demonstrate that ALG-2 mRNA and protein are down-regulated in human uveal melanoma cells compared to their progenitor cells, normal melanocytes. The down regulation of ALG-2 may provide melanoma cells with a selective advantage. ALG-2 and its putative target molecule, Alix/AIP1, are localized primarily in the cytoplasm of melanocytes and melanoma cells independent of the intracellular Ca2+ concentration or the activation of apoptosis. Cross-linking and analytical centrifugation studies support a single-species dimer conformation of ALG-2, also independent of Ca2+ concentration. However, binding of Ca2+ to both EF-1 and EF-3 is necessary for ALG-2 interaction with Alix/AIP1 as demonstrated using surface plasmon resonance spectroscopy. Mutations in EF-5 result in reduced target interaction without alteration in Ca2+ affinity. The addition of N-terminal ALG-2 peptides, residues 1–22 or residues 7–17, does not alter the interaction of ALG-2 or an N-terminal deletion mutant of ALG-2 with Alix/AIP1, as might be expected from a model derived from the crystal structure of ALG-2. Fluorescence studies of ALG-2 demonstrate that an increase in surface hydrophobicity is primarily due to Ca2+ binding to EF-3, while Ca2+ binding to EF-1 has little effect on surface exposure of hydrophobic residues. Together, these data indicate that gross surface hydrophobicity changes are insufficient for target recognition. PMID:15366927

PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site

PubMed Central

Bothe, Ingo; Deng, Su; Baylies, Mary

2014-01-01

Cell-cell fusion is a regulated process that requires merging of the opposing membranes and underlying cytoskeletons. However, the integration between membrane and cytoskeleton signaling during fusion is not known. Using Drosophila, we demonstrate that the membrane phosphoinositide PI(4,5)P2 is a crucial regulator of F-actin dynamics during myoblast fusion. PI(4,5)P2 is locally enriched and colocalizes spatially and temporally with the F-actin focus that defines the fusion site. PI(4,5)P2 enrichment depends on receptor engagement but is upstream or parallel to actin remodeling. Regulators of actin branching via Arp2/3 colocalize with PI(4,5)P2 in vivo and bind PI(4,5)P2 in vitro. Manipulation of PI(4,5)P2 availability leads to impaired fusion, with a reduction in the F-actin focus size and altered focus morphology. Mechanistically, the changes in the actin focus are due to a failure in the enrichment of actin regulators at the fusion site. Moreover, improper localization of these regulators hinders expansion of the fusion interface. Thus, PI(4,5)P2 enrichment at the fusion site encodes spatial and temporal information that regulates fusion progression through the localization of activators of actin polymerization. PMID:24821989

Surgical hand disinfection with a propanol-based hand rub: equivalence of shorter application times.

PubMed

Kampf, G; Ostermeyer, C; Heeg, P

2005-04-01

The aim of this study was to determine the efficacy of a propanol-based hand rub at application times shorter than 3 min. The bacterial pre-value was obtained from the finger tips (prEN 12791). Subjects treated their hands with the reference procedure (n-propanol, 60%) for 3 min or the product (crossover design). Sterillium was applied for 3, 2, 1.5 and 1 min. Four other preparations were tested for 1 min. Post-values (immediate effect) were taken from one hand, and the other hand was gloved for 3h. After the gloves were removed, the second post-value was taken (sustained effect). Sterillium was more effective than the reference procedure at 3, 2 and 1.5 min (immediate and sustained effect). The immediate effect after 1 min was significantly lower [mean log(10) reduction factor (RF): 1.91+/-0.90 vs. 2.52+/-0.95; P=0.001], whereas the sustained effect was not (mean RF: 1.81+/-1.06 vs. 2.05+/-1.14; P=0.204). All other preparations failed the efficacy requirement at 1 min for both the immediate and sustained effect. Using 2 x 3 mL Sterillium for a total of 1.5 min for surgical hand disinfection was at least as effective as the 3-min reference disinfection.

Back to basics: hand hygiene and surgical hand antisepsis.

PubMed

Spruce, Lisa

2013-11-01

Health care-associated infections (HAIs) are a significant issue in the United States and throughout the world, but following proper hand hygiene practices is the most effective and least expensive way to prevent HAIs. Hand hygiene is inexpensive and protects patients and health care personnel alike. The four general types of hand hygiene that should be performed in the perioperative environment are washing hands that are visibly soiled, hand hygiene using alcohol-based products, surgical hand scrubs, and surgical hand scrubs using an alcohol-based surgical hand rub product. Barriers to proper hand hygiene may include not thinking about it, forgetting, skin irritation, a lack of role models, or a lack of a safety culture. One strategy for improving hand hygiene practices is monitoring hand hygiene as part of a quality improvement project, but the most important aspect for perioperative team members is to set an example for other team members by following proper hand hygiene practices and reminding each other to perform hand hygiene. Copyright © 2013 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Different regulation of P-glycoprotein function between Caco-2 and Caki-1 cells by ezrin, radixin and moesin proteins.

PubMed

Yano, Kentaro; Otsuka, Kyoma; Kato, Yuko; Kawabata, Hideaki; Ohmori, Shinya; Arakawa, Hiroshi; Ogihara, Takuo

2016-03-01

P-glycoprotein (P-gp) mediates efflux of many xenobiotics, including therapeutic drugs, from normal and tumour tissues, and its functional localization on the plasma membrane of cells is regulated by scaffold proteins, such as ezrin, radixin and moesin (ERM proteins). We previously reported that radixin is involved in post-translational regulation of P-gp in hepatocellular carcinoma HepG2 cells and mouse small intestine, but not in mouse kidney. Here, we investigated whether the role of ERM proteins in regulation of P-gp transport activity in cancers is the same as that in the corresponding normal tissues, using human colon adenocarcinoma (Caco-2) cells and renal carcinoma (Caki-1) cells. In Caco-2 cells, radixin silencing alone reduced the P-gp-mediated intracellular accumulation of rhodamine123 (Rho123), while the mRNA level of P-gp was unchanged. Thus, it appears that only radixin among the ERMs regulates P-gp activity in Caco-2 cells. On the other hand, none of the ERM proteins influenced P-gp activity in Caki-1 cells. The regulation of P-gp by ERM proteins is different between Caco-2 and Caki-1 cells. Moreover, these regulatory properties are the same as those of the corresponding normal tissues, and suggest that tissue-specific differences in the regulation of P-gp by ERM proteins are retained in cancerous tissues. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

7 CFR 301.74-2 - Regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.74-2 Section 301.74-2... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Plum Pox § 301.74-2 Regulated articles. The following are regulated articles: (a) All plant material and plant parts of Prunus (stone fruit) species...

7 CFR 301.74-2 - Regulated articles.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Regulated articles. 301.74-2 Section 301.74-2... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Plum Pox § 301.74-2 Regulated articles. The following are regulated articles: (a) All plant material and plant parts of Prunus (stone fruit) species...

7 CFR 301.74-2 - Regulated articles.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Regulated articles. 301.74-2 Section 301.74-2... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Plum Pox § 301.74-2 Regulated articles. The following are regulated articles: (a) All plant material and plant parts of Prunus (stone fruit) species...

7 CFR 301.74-2 - Regulated articles.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Regulated articles. 301.74-2 Section 301.74-2... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Plum Pox § 301.74-2 Regulated articles. The following are regulated articles: (a) All plant material and plant parts of Prunus (stone fruit) species...

7 CFR 301.74-2 - Regulated articles.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Regulated articles. 301.74-2 Section 301.74-2... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Plum Pox § 301.74-2 Regulated articles. The following are regulated articles: (a) All plant material and plant parts of Prunus (stone fruit) species...

Aquaporin-2 Regulation in Health and Disease

PubMed Central

Radin, M. Judith; Yu, Ming-Jiun; Stoedkilde, Lene; Miller, R. Lance; Hoffert, Jason D.; Frokiaer, Jorgen; Pisitkun, Trairak; Knepper, Mark A.

2012-01-01

Aquaporin-2 (AQP2), the vasopressin-regulated water channel of the renal collecting duct, is dysregulated in numerous water balance disorders in humans and animals including those associated with polyuria (e.g. urinary tract obstruction, hypokalemia, inflammation, and lithium toxicity) and dilutional hyponatremia (e.g. SIADH). Normal regulation of AQP2 by vasopressin involves two independent regulatory mechanisms: 1) short-term regulation of AQP2 trafficking to and from the apical plasma membrane, and 2) long term regulation of the total abundance of the AQP2 protein in the cells. Most water balance disorders are the result of dysregulation of processes that regulate the total abundance of AQP2 in collecting duct cells. In general, the level of AQP2 in a collecting duct cell is determined by a balance between production via translation of AQP2 mRNA and removal via degradation and/or secretion into the urine in exosomes. AQP2 abundance increases in response to vasopressin chiefly due to increased translation subsequent to increases in AQP2 mRNA. Vasopressin-mediated regulation AQP2 gene transcription is poorly understood, although several transcription factor binding elements in the 5’ flanking region of the AQP2 gene have been identified and candidate transcription factors corresponding to these element have been discovered in proteomics studies. Here we review progress in this area and discuss elements of vasopressin signaling in the collecting duct that may impinge on regulation of AQP2 in health and in the context of examples of polyuric diseases. PMID:23130944

The mirror illusion: does proprioceptive drift go hand in hand with sense of agency?

PubMed Central

Tajima, Daisuke; Mizuno, Tota; Kume, Yuichiro; Yoshida, Takako

2015-01-01

Vection can be regarded as the illusion of “whole-body” position perception. In contrast, the mirror illusion is that of “body-part” position perception. When participants viewed their left hands in a mirror positioned along the midsaggital axis while moving both hands synchronously, they hardly noticed the spatial offset between the hand in the mirror and the obscured real right hand. This illusion encompasses two phenomena: proprioceptive drift and sense of agency. Proprioceptive drift represented a perceptual change in the position of the obscured hand relative to that of the hand in the mirror. Sense of agency referred to the participants' subjective sense of controlling body image as they would their own bodies. We examined the spatial offset between these two phenomena. Participants responded to a two-alternative forced choice (2AFC) question regarding the subjective position of their right hands and questionnaires regarding sense of agency at various positions of the right hand. We analyzed the 2AFC data using a support vector machine and compared its classification result and the questionnaire results. Our data analysis suggested that the two phenomena were observed in concentric space, but the estimated range of the proprioceptive drift was slightly narrower than the range of agency. Although this outcome can be attributed to differences in measurement or analysis, to our knowledge, this is the first report to suggest that proprioceptive drift and sense of agency are concentric and almost overlap. PMID:25774145

48 CFR 2301.105-2 - Arrangement of regulations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Arrangement of regulations. 2301.105-2 Section 2301.105-2 Federal Acquisition Regulations System SOCIAL SECURITY ADMINISTRATION GENERAL SOCIAL SECURITY ACQUISITION REGULATION SYSTEM Purpose, Authority, Issuance 2301.105-2 Arrangement...

48 CFR 2501.104-2 - Arrangement of regulations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Arrangement of regulations. 2501.104-2 Section 2501.104-2 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL FEDERAL ACQUISITION REGULATIONS SYSTEM Purpose, Authority, Issuance 2501.104-2 Arrangement of...

48 CFR 1601.104-2 - Arrangement of regulation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Arrangement of regulation. 1601.104-2 Section 1601.104-2 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL FEDERAL ACQUISITION REGULATIONS SYSTEM...

48 CFR 1601.104-2 - Arrangement of regulation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Arrangement of regulation. 1601.104-2 Section 1601.104-2 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL FEDERAL ACQUISITION REGULATIONS SYSTEM...

48 CFR 1601.104-2 - Arrangement of regulation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Arrangement of regulation. 1601.104-2 Section 1601.104-2 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL FEDERAL ACQUISITION REGULATIONS SYSTEM...

48 CFR 1601.104-2 - Arrangement of regulation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Arrangement of regulation. 1601.104-2 Section 1601.104-2 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL FEDERAL ACQUISITION REGULATIONS SYSTEM...

48 CFR 1601.104-2 - Arrangement of regulation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Arrangement of regulation. 1601.104-2 Section 1601.104-2 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL FEDERAL ACQUISITION REGULATIONS SYSTEM...

iHand: an interactive bare-hand-based augmented reality interface on commercial mobile phones

NASA Astrophysics Data System (ADS)

Choi, Junyeong; Park, Jungsik; Park, Hanhoon; Park, Jong-Il

2013-02-01

The performance of mobile phones has rapidly improved, and they are emerging as a powerful platform. In many vision-based applications, human hands play a key role in natural interaction. However, relatively little attention has been paid to the interaction between human hands and the mobile phone. Thus, we propose a vision- and hand gesture-based interface in which the user holds a mobile phone in one hand but sees the other hand's palm through a built-in camera. The virtual contents are faithfully rendered on the user's palm through palm pose estimation, and reaction with hand and finger movements is achieved that is recognized by hand shape recognition. Since the proposed interface is based on hand gestures familiar to humans and does not require any additional sensors or markers, the user can freely interact with virtual contents anytime and anywhere without any training. We demonstrate that the proposed interface works at over 15 fps on a commercial mobile phone with a 1.2-GHz dual core processor and 1 GB RAM.

Hand Hygiene – Evaluation of Three Disinfectant Hand Sanitizers in a Community Setting

PubMed Central

Babeluk, Rita; Jutz, Sabrina; Mertlitz, Sarah; Matiasek, Johannes; Klaus, Christoph

2014-01-01

Hand hygiene is acknowledged as the single most important measure to prevent nosocomial infections in the healthcare setting. Similarly, in non-clinical settings, hand hygiene is recognised as a key element in helping prevent the spread of infectious diseases. The aim of this study was to evaluate the efficacy of three different disinfectant hand sanitizers in reducing the burden of bacterial hand contamination in 60 healthy volunteers in a community setting, both before and after education about the correct use of hand sanitizers. The study is the first to evaluate the efficacy and ease of use of different formulations of hand rubs used by the general population. The products tested were: Sterillium (perfumed, liquid), desderman pure gel (odorless, gel) and Lavit (perfumed, spray). Sterillium and desderman are EN1500 (hygienic hand rub) certified products (available in pharmacy) and Lavit is non EN1500 certified and available in supermarkets. The two EN1500 certified products were found to be significantly superior in terms of reducing bacterial load. desderman pure gel, Sterillium and Lavit reduced the bacterial count to 6.4%, 8.2% and 28.0% respectively. After education in the correct use of each hand rub, the bacterial load was reduced even further, demonstrating the value of education in improving hand hygiene. Information about the testers' perceptions of the three sanitizers, together with their expectations of a hand sanitizer was obtained through a questionnaire. Efficacy, followed by skin compatibility were found to be the two most important attributes of a hand disinfectant in our target group. PMID:25379773

Hand preference and skilled hand performance among individuals with successful rightward conversions of the writing hand.

PubMed

Porac, Clare

2009-03-01

Searleman and Porac (2001) studied lateral preference patterns among successfully switched left-hand writers, left-hand writers with no switch pressure history, and left-hand writers who did not switch when pressured. They concluded that left-handers who successfully shift to right-hand writing are following an inherent right-sided lateralisation pattern that they already possess. Searleman and Porac suggested that the neural mechanisms that control lateralisation in the successfully switched individuals are systematically different from those of other groups of left-handers. I examined patterns of skilled and less-skilled hand preference and skilled hand performance in a sample of 394 adults (ages 18-94 years). The sample contained successfully switched left-hand writers, left-handers pressured to shift who remained left-hand writers, left-handers who did not experience shift pressures, and right-handers. Both skilled hand preference and skilled hand performance were shifted towards the right side in successfully switched left-hand writers. This group also displayed mixed patterns of hand preference and skilled hand performance in that they were not as right-sided as "natural" right-handers nor were they as left-sided as the two left-hand writing groups, which did not differ from each other. The experience of being pressured to switch to right-hand writing was not sufficient to shift lateralisation patterns; the pressures must be experienced in the context of an underlying neural control mechanism that is amenable to change as a result of these external influences.

Sports Activity After Reconstruction of Osteochondral Lesions of the Talus With Autologous Spongiosa Grafts and Autologous Matrix-Induced Chondrogenesis.

PubMed

Wiewiorski, Martin; Werner, Lorenzo; Paul, Jochen; Anderson, Andrew E; Barg, Alexej; Valderrabano, Victor

2016-10-01

For the treatment of osteochondral lesions of the talus (OCLTs), autologous matrix-induced chondrogenesis (AMIC) is a safe 1-step procedure with good clinical and radiological results. However, data regarding postoperative sports activity after AMIC are limited. To identify significant factors influencing the rate of postoperative sports and recreational activities. Case series; Level of evidence, 4. The sports and recreational activities of 60 patients (mean age, 34.9 ± 11.5 years) undergoing the AMIC procedure were retrospectively analyzed at a mean of 46.9 ± 17.8 months (range, 24.5-87.0 months) postoperatively. The visual analog scale (VAS) for pain score, Tegner activity scale score, activity rating scale (ARS) score, and satisfaction with surgery outcomes were assessed. Corrective calcaneal osteotomy was performed in 38 of 60 (63.3%) patients. Ligament repair was performed in 41 of 60 (68.3%) patients. The mean VAS score improved significantly from 6.9 ± 1.6 points (range, 5-10 points) preoperatively to 2.3 ± 1.9 points (range, 0-6 points) at latest follow-up (P < .001). No significant change in the mean Tegner activity scale score (3.3 ± 2.0 preoperatively to 3.4 ± 2.2 postoperatively; P = .526) and the mean ARS score (2.6 ± 4.3 preoperatively to 2.3 ± 3.4 postoperatively; P = .874) was noted. The percentage of patients involved in sports activity before the onset of symptoms became significantly lower at the time of surgery (from 95.0% to 53.3%; P < .001); no significant difference was noted postoperatively (from 53.3% to 58.3%; P = .663). No significant difference of the weekly sports frequency and the duration of sports activity was found postoperatively. Patients undergoing AMIC repair of an OCLT participate at a similar low postoperative sports and recreational activity level compared with the preoperative level. © 2016 The Author(s).

Sulfated hyaluronic acid hydrogels with retarded degradation and enhanced growth factor retention promote hMSC chondrogenesis and articular cartilage integrity with reduced hypertrophy.

PubMed

Feng, Qian; Lin, Sien; Zhang, Kunyu; Dong, Chaoqun; Wu, Tianyi; Huang, Heqin; Yan, Xiaohui; Zhang, Li; Li, Gang; Bian, Liming

2017-04-15

Recently, hyaluronic acid (HA) hydrogels have been extensively researched for delivering cells and drugs to repair damaged tissues, particularly articular cartilage. However, the in vivo degradation of HA is fast, thus limiting the clinical translation of HA hydrogels. Furthermore, HA cannot bind proteins with high affinity because of the lack of negatively charged sulfate groups. In this study, we conjugated tunable amount of sulfate groups to HA. The sulfated HA exhibits significantly slower degradation by hyaluronidase compared to the wild type HA. We hypothesize that the sulfation reduces the available HA octasaccharide substrate needed for the effective catalytic action of hyaluronidase. Moreover, the sulfated HA hydrogels significantly improve the protein sequestration, thereby effectively extending the availability of the proteinaceous drugs in the hydrogels. In the following in vitro study, we demonstrate that the HA hydrogel sulfation exerts no negative effect on the viability of encapsulated human mesenchymal stem cells (hMSCs). Furthermore, the sulfated HA hydrogels promote the chondrogenesis and suppresses the hypertrophy of encapsulated hMSCs both in vitro and in vivo. Moreover, intra-articular injections of the sulfated HA hydrogels avert the cartilage abrasion and hypertrophy in the animal osteoarthritic joints. Collectively, our findings demonstrate that the sulfated HA is a promising biomaterial for the delivery of therapeutic agents to aid the regeneration of injured or diseased tissues and organs. In this paper, we conjugated sulfate groups to hyaluronic acid (HA) and demonstrated the slow degradation and growth factor delivery of sulfated HA. Furthermore, the in vitro and in vivo culture of hMSCs laden HA hydrogels proved that the sulfation of HA hydrogels not only promotes the chondrogenesis of hMSCs but also suppresses hypertrophic differentiation of the chondrogenically induced hMSCs. The animal OA model study showed that the injected

The efficacy of different models of smoke-free laws in reducing exposure to second-hand smoke: a multi-country comparison.

PubMed

Ward, Mark; Currie, Laura M; Kabir, Zubair; Clancy, Luke

2013-05-01

Exposure to second-hand tobacco smoke is a serious public health concern and while all EU Member States have enacted some form of regulation aimed at limiting exposure, the scope of these regulations vary widely and many countries have failed to enact comprehensive legislation creating smoke-free workplaces and indoor public places. To gauge the effectiveness of different smoke-free models we compared fine particles from second-hand smoke in hospitality venues before and after the implementation of smoking bans in France, Greece, Ireland, Italy, Portugal, Turkey, and Scotland. Data on PM2.5 fine particle concentration levels were recorded in 338 hospitality venues across these countries before and after the implementation of smoke-free legislation. Changes in mean PM2.5 concentrations during the period from pre- to post-legislation were then compared across countries. While a reduction in PM2.5 was observed in all countries, those who had enacted and enforced more fully comprehensive smoke-free legislation experienced the greatest reduction in second-hand tobacco smoke. Comprehensive smoke-free laws are more effective than partial laws in reducing exposure to second-hand tobacco smoke. Also, any law, regardless of scope must be actively enforced in order to have the desired impact. There is continued need for surveillance of smoke-free efforts in all countries. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

7 CFR 301.51-2 - Regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.51-2 Section 301.51-2... Regulated articles. The following are regulated articles: (a) Firewood (all hardwood species), and green... (sycamore), Populus (poplar), Salix (willow), Sorbus (mountain ash), and Ulmus (elm). (b) Any other article...

7 CFR 301.51-2 - Regulated articles.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Regulated articles. 301.51-2 Section 301.51-2... Regulated articles. The following are regulated articles: (a) Firewood (all hardwood species), and green...), Sorbus (mountain ash), and Ulmus (elm). (b) Any other article, product, or means of conveyance not...

7 CFR 301.51-2 - Regulated articles.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Regulated articles. 301.51-2 Section 301.51-2... Regulated articles. The following are regulated articles: (a) Firewood (all hardwood species), and green...), Sorbus (mountain ash), and Ulmus (elm). (b) Any other article, product, or means of conveyance not...

7 CFR 301.51-2 - Regulated articles.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Regulated articles. 301.51-2 Section 301.51-2... Regulated articles. The following are regulated articles: (a) Firewood (all hardwood species), and green...), Sorbus (mountain ash), and Ulmus (elm). (b) Any other article, product, or means of conveyance not...

PTH 1-34 Ameliorates the Osteopenia and Delayed Healing of Stabilized Tibia Fracture in Mice with Achondroplasia Resulting from Gain-Of-Function Mutation of FGFR3

PubMed Central

Chen, Hangang; Sun, Xianding; Yin, Liangjun; Chen, Shuai; Zhu, Ying; Huang, Junlan; Jiang, Wanling; Chen, Bo; Zhang, Ruobin; Chen, Lin; Nie, Mao; Xie, Yangli; Deng, Zhongliang

2017-01-01

Bone fracture healing is processed through multiple stages including the cartilaginous callus formation and its transition to bony callus. FGFR3 negatively regulates chondrogenesis and enhances osteogenesis during skeleton development. We previously found in mice carrying gain-of-function mutation of FGFR3 that FGFR3 delays the healing of un-stabilized fracture that heals mainly through endochondral ossification. Since fracture is regularly treated in clinics with rigid fixation, and stabilized fracture is healed largely through intramembranous ossification, we asked whether FGFR3, a key regulator of osteogenesis, also affect the regeneration of stabilized fracture. We found that gain-of-function mutation of FGFR3 inhibits the initiation of chondrogenesis and the subsequent bone formation. We further studied whether PTH1-34 can improve the osteopenia and delayed healing of the stabilized tibia fracture in mice with achondroplasia. Fracture healing was evaluated by radiography, micro-CT, biomechanical tests, histology, and real-time polymerase chain reaction (RT-PCR) analysis. We found that PTH 1-34 can alleviate the decreased bone mass and compromised architecture in ACH mice. Histological analysis revealed that administration of PTH1-34 increased the size of both the total callus and cartilaginous callus at 14 days after the surgery in ACH mice. RT-PCR data suggested that systemic PTH1-34 accelerated the initiation of chondrogenesis and chondrocyte maturation (earlier and higher levels of expression of chondrogenesis related markers) and enhanced the osteogenic differentiation in the fracture callus in ACH mice. These results indicate that the PTH1-34 administration resulted in an enhanced callus formation during bone fracture healing in ACH mice, which is at least in part mediated by an increase of cartilaginous callus at early stage and the promotion of bone formation in bony callus. In summary, in this study we revealed that FGFR3 delays the regeneration of

Extracellular Protease Inhibition Alters the Phenotype of Chondrogenically Differentiating Human Mesenchymal Stem Cells (MSCs) in 3D Collagen Microspheres.

PubMed

Han, Sejin; Li, Yuk Yin; Chan, Barbara Pui

2016-01-01

Matrix remodeling of cells is highly regulated by proteases and their inhibitors. Nevertheless, how would the chondrogenesis of mesenchymal stem cells (MSCs) be affected, when the balance of the matrix remodeling is disturbed by inhibiting matrix proteases, is incompletely known. Using a previously developed collagen microencapsulation platform, we investigated whether exposing chondrogenically differentiating MSCs to intracellular and extracellular protease inhibitors will affect the extracellular matrix remodeling and hence the outcomes of chondrogenesis. Results showed that inhibition of matrix proteases particularly the extracellular ones favors the phenotype of fibrocartilage rather than hyaline cartilage in chondrogenically differentiating hMSCs by upregulating type I collagen protein deposition and type II collagen gene expression without significantly altering the hypertrophic markers at gene level. This study suggests the potential of manipulating extracellular proteases to alter the outcomes of hMSC chondrogenesis, contributing to future development of differentiation protocols for fibrocartilage tissues for intervertebral disc and meniscus tissue engineering.

Extracellular Protease Inhibition Alters the Phenotype of Chondrogenically Differentiating Human Mesenchymal Stem Cells (MSCs) in 3D Collagen Microspheres

PubMed Central

Han, Sejin; Li, Yuk Yin; Chan, Barbara Pui

2016-01-01

Matrix remodeling of cells is highly regulated by proteases and their inhibitors. Nevertheless, how would the chondrogenesis of mesenchymal stem cells (MSCs) be affected, when the balance of the matrix remodeling is disturbed by inhibiting matrix proteases, is incompletely known. Using a previously developed collagen microencapsulation platform, we investigated whether exposing chondrogenically differentiating MSCs to intracellular and extracellular protease inhibitors will affect the extracellular matrix remodeling and hence the outcomes of chondrogenesis. Results showed that inhibition of matrix proteases particularly the extracellular ones favors the phenotype of fibrocartilage rather than hyaline cartilage in chondrogenically differentiating hMSCs by upregulating type I collagen protein deposition and type II collagen gene expression without significantly altering the hypertrophic markers at gene level. This study suggests the potential of manipulating extracellular proteases to alter the outcomes of hMSC chondrogenesis, contributing to future development of differentiation protocols for fibrocartilage tissues for intervertebral disc and meniscus tissue engineering. PMID:26760956

7 CFR 301.51-2 - Regulated articles.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Regulated articles. 301.51-2 Section 301.51-2... Regulated articles. The following are regulated articles: (a) Firewood (all hardwood species), and green... (elm). (b) Any other article, product, or means of conveyance not covered by paragraph (a) of this...

Waterless Hand Rub Versus Traditional Hand Scrub Methods for Preventing the Surgical Site Infection in Orthopedic Surgery.

PubMed

Iwakiri, Kentaro; Kobayashi, Akio; Seki, Masahiko; Ando, Yoshiyuki; Tsujio, Tadao; Hoshino, Masatoshi; Nakamura, Hiroaki

2017-11-15

MINI: Fourteen hundred consecutive patients were investigated for evaluating the utility of waterless hand rub before orthopaedic surgery. The risk in the surgical site infection incidence was the same, but costs of liquids used for hand hygiene were cheaper and the hand hygiene time was shorter for waterless protocol, compared with traditional hand scrub. A retrospective cohort study with prospectively collected data. The aim of this study was to compare SSI incidences, the cost of hand hygiene agents, and hand hygiene time between the traditional hand scrub and the waterless hand rub protocols before orthopedic surgery. Surgical site infections (SSI) prolong hospitalization and are a leading nosocomial cause of morbidity and a source of excess cost. Recently, a waterless hand rub protocol comprising alcohol based chlorhexidine gluconate for use before surgery was developed, but no studies have yet examined its utility in orthopedic surgery. Fourteen hundred consecutive patients who underwent orthopedic surgery (spine, joint replacement, hand, and trauma surgeries) in our hospital since April 1, 2012 were included. A total of 712 cases underwent following traditional hand scrub between April 1, 2012 and April 30, 2013 and 688 cases underwent following waterless hand rub between June 1, 2013 and April 30, 2014. We compared SSI incidences within all and each subcategory between two hand hygiene protocols. All patients were screened for SSI within 1 year after surgery. We compared the cost of hand hygiene agents and hand hygiene time between two groups. The SSI incidences were 1.3% (9 of 712) following the traditional protocol (2 deep and 7 superficial infections) and 1.1% (8 of 688) following the waterless protocol (all superficial infections). There were no significant differences between the two groups. The costs of liquids used for one hand hygiene were about $2 for traditional hand scrub and less than $1 for waterless hand rub. The mean hand hygiene time was 264

Relationship between limited joint mobility of the hand and diabetic foot risk in patients with type 2 diabetes.

PubMed

Mineoka, Yusuke; Ishii, Michiyo; Tsuji, Akiko; Komatsu, Yoriko; Katayama, Yuko; Yamauchi, Mitsuko; Yamashita, Aki; Hashimoto, Yoshitaka; Nakamura, Naoto; Katsumi, Yasukazu; Isono, Motohide; Fukui, Michiaki

2017-06-01

Foot ulceration is a serious problem for patients with type 2 diabetes (T2D), and the early detection of risks for this condition is important to prevent complications. The present cross-sectional study in T2D patients determined the relationship between limited joint mobility (LJM) of the hand and diabetic foot risk classified using the criteria of the International Working Group on the Diabetic Foot (IWGDF). Relationships between LJM of the hand and foot risk according to IWGDF category, HbA1c, age, body mass index, blood pressure, estimated glomerular filtration (eGFR), and diabetic complications (including diabetic peripheral neuropathy [DPN] and peripheral arterial disease [PAD]) were evaluated in 528 consecutive T2D patients. Poor glycemic control was defined as HbA1c ≥ 7%. Patients with LJM of the hand were older and had a longer duration of diabetes, a higher prevalence of diabetic complications, including DPN and PAD, and a higher IWDGF category (all P < 0.001). Multivariate logistic regression analysis revealed that the foot risk assessed with IWDGF category was correlated with age (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.01-1.06; P = 0.001), poor glycemic control (OR 1.66; 95% CI 1.00-2.77; P = 0.04), eGFR (OR 0.98; 95% CI 0.97-0.99; P = 0.02), and the presence of LJM of the hand (OR 3.86; 95% CI 2.21-6.86; P < 0.001). The results demonstrate a correlation between LJM of the hand and foot risk. Diagnosis of diabetic hand is simple and non-invasive, and is thus a useful method for assessing the risk of diabetic foot in T2D patients. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Comparative study of presurgical hand hygiene with hydroalcoholic solution versus traditional presurgical hand hygiene.

PubMed

López Martín, M Beatriz; Erice Calvo-Sotelo, Alejo

To compare presurgical hand hygiene with hydroalcoholic solution following the WHO protocol with traditional presurgical hand hygiene. Cultures of the hands of surgeons and surgical nurses were performed before and after presurgical hand hygiene and after removing gloves at the end of surgery. Cultures were done in 2different days: the first day after traditional presurgical hand hygiene, and the second day after presurgical hand hygiene with hydroalcoholic solution following the WHO protocol. The duration of the traditional hand hygiene was measured and compared with the duration (3min) of the WHO protocol. The cost of the products used in the traditional technique was compared with the cost of the hydroalcoholic solution used. The variability of the traditional technique was determined by observation. Following presurgical hand hygiene with hydroalcoholic solution, colony-forming units (CFU) were detected in 5 (7.3%) subjects, whereas after traditional presurgical hand hygiene CFU were detected in 14 subjects (20.5%) (p < 0.05). After glove removal, the numbers of CFU were similar. The time employed in hand hygiene with hydroalcoholic solution (3min) was inferior to the time employed in the traditional technique (p < 0.05), its cost was less than half, and there was no variability. Compared with other techniques, presurgical hand hygiene with hydroalcoholic solution significantly decreases CFU, has similar latency time, a lower cost, and saves time. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

7 CFR 301.55-2 - Regulated articles.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Regulated articles. 301.55-2 Section 301.55-2... Regulated articles. The following are regulated articles: (a) The South American cactus moth, in any living..., Nopalea, and Opuntia. (c) Any other product, article, or means of conveyance not listed in paragraphs (a...

7 CFR 301.55-2 - Regulated articles.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Regulated articles. 301.55-2 Section 301.55-2... Regulated articles. The following are regulated articles: (a) The South American cactus moth, in any living..., Nopalea, and Opuntia. (c) Any other product, article, or means of conveyance not listed in paragraphs (a...

7 CFR 301.55-2 - Regulated articles.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Regulated articles. 301.55-2 Section 301.55-2... Regulated articles. The following are regulated articles: (a) The South American cactus moth, in any living..., Nopalea, and Opuntia. (c) Any other product, article, or means of conveyance not listed in paragraphs (a...

7 CFR 301.55-2 - Regulated articles.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Regulated articles. 301.55-2 Section 301.55-2... Regulated articles. The following are regulated articles: (a) The South American cactus moth, in any living..., Nopalea, and Opuntia. (c) Any other product, article, or means of conveyance not listed in paragraphs (a...

7 CFR 301.55-2 - Regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.55-2 Section 301.55-2... Regulated articles. The following are regulated articles: (a) The South American cactus moth, in any living..., Nopalea, and Opuntia. (c) Any other product, article, or means of conveyance not listed in paragraphs (a...

15 CFR 2.7 - Supplementary regulations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Supplementary regulations. 2.7 Section 2.7 Commerce and Foreign Trade Office of the Secretary of Commerce PROCEDURES FOR HANDLING AND... General Counsel for Finance and Litigation may from time to time issue such supplementary regulations or...

The left hand doesn't know what the right hand is doing: the disruptive effects of attention to the hands in skilled typewriting.

PubMed

Logan, Gordon D; Crump, Matthew J C

2009-10-01

Everyone knows that attention to the details disrupts skilled performance, but little empirical evidence documents this fact. We show that attention to the hands disrupts skilled typewriting. We had skilled typists type words preceded by cues that told them to type only the letters assigned to one hand or to type all of the letters. Cuing the hands disrupted performance markedly, slowing typing and increasing the error rate (Experiment 1); these deleterious effects were observed even when no keystrokes were actually inhibited (Experiment 3). However, cuing the same letters with colors was not disruptive (Experiment 2). We account for the disruption with a hierarchical control model, in which an inner loop controls the hands and an outer loop controls what is typed. Typing letters using only one hand requires the outer loop to monitor the inner loop's output; the outer loop slows inner-loop cycle time to increase the likelihood of inhibiting responses with the unwanted hand. This produces the disruption.

Stimulus-dependent regulation of nuclear Ca2+ signaling in cardiomyocytes: a role of neuronal calcium sensor-1.

PubMed

Nakao, Shu; Wakabayashi, Shigeo; Nakamura, Tomoe Y

2015-01-01

In cardiomyocytes, intracellular calcium (Ca2+) transients are elicited by electrical and receptor stimulations, leading to muscle contraction and gene expression, respectively. Although such elevations of Ca2+levels ([Ca2+]) also occur in the nucleus, the precise mechanism of nuclear [Ca2+] regulation during different kinds of stimuli, and its relationship with cytoplasmic [Ca2+] regulation are not fully understood. To address these issues, we used a new region-specific fluorescent protein-based Ca2+ indicator, GECO, together with the conventional probe Fluo-4 AM. We confirmed that nuclear Ca2+ transients were elicited by both electrical and receptor stimulations in neonatal mouse ventricular myocytes. Kinetic analysis revealed that electrical stimulation-elicited nuclear Ca2+ transients are slower than cytoplasmic Ca2+ transients, and chelating cytoplasmic Ca2+ abolished nuclear Ca2+ transients, suggesting that nuclear Ca2+ are mainly derived from the cytoplasm during electrical stimulation. On the other hand, receptor stimulation such as with insulin-like growth factor-1 (IGF-1) preferentially increased nuclear [Ca2+] compared to cytoplasmic [Ca2+]. Experiments using inhibitors revealed that electrical and receptor stimulation-elicited Ca2+ transients were mainly mediated by ryanodine receptors and inositol 1,4,5-trisphosphate receptors (IP3Rs), respectively, suggesting different mechanisms for the two signals. Furthermore, IGF-1-elicited nuclear Ca2+ transient amplitude was significantly lower in myocytes lacking neuronal Ca2+ sensor-1 (NCS-1), a Ca2+ binding protein implicated in IP3R-mediated pathway in the heart. Moreover, IGF-1 strengthened the interaction between NCS-1 and IP3R. These results suggest a novel mechanism for receptor stimulation-induced nuclear [Ca2+] regulation mediated by IP3R and NCS-1 that may further fine-tune cardiac Ca2+ signal regulation.

29 CFR 780.315 - Local hand harvest laborers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Agriculture That Is Exempted From the Minimum Wage and Overtime Pay Requirements Under Section 13(a)(6... 29 Labor 3 2010-07-01 2010-07-01 false Local hand harvest laborers. 780.315 Section 780.315 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR STATEMENTS OF GENERAL...

Thermal comfort zone of the hands, feet and head in males and females.

PubMed

Ciuha, Urša; Mekjavic, Igor B

2017-10-01

The present study compared the thermal comfort zones (TCZ) of the hands, feet and head in eight male and eight female participants, assessed with water-perfused segments (WPS). On separate occasions, and separated by a minimum of one day, participants were requested to regulate the temperature of three distal skin regions (hands, feet and head) within their TCZ. On each occasion they donned a specific water-perfused segment (WPS), either gloves, socks or hood for assessing the TCZ of the hands, feet and head, respectively. In the absence of regulation, the temperature of the water perfusing the WPS changed in a saw-tooth manner from 10 to 50°C; by depressing a switch and reversing the direction of the temperature at the limits of the TCZ, each participant defined the TCZ for each skin region investigated. The range of regulated temperatures (upper and lower limits of the TCZ) did not differ between studied skin regions or between genders. Participants however maintained higher head (35.7±0.4°C; p˂0.001) skin temperature (Tsk) compared to hands (34.5±0.8°C) and feet (33.8±1.1°C). When exposed to normothermic conditions, distal skin regions do not differ in ranges of temperatures, perceived as thermally comfortable. Copyright © 2017. Published by Elsevier Inc.

Hand-transmitted vibration and biodynamic response of the human hand-arm: a critical review.

PubMed

Dong, R G; Rakheja, S; Schopper, A W; Han, B; Smutz, W P

2001-01-01

Hand-arm vibration syndrome (HAVS) has been associated with prolonged exposure to vibration transmitted to the human hand-arm system from hand-held power tools, vibrating machines, or hand-held vibrating workpieces. The biodynamic response of the human hand and arm to hand transmitted vibration (HTV) forms an essential basis for effective evaluations of exposures, vibration-attenuation mechanisms, and potential injury mechanisms. The biodynamic response to HTV and its relationship to HAVS are critically reviewed and discussed to highlight the advances and the need for further research. In view of its strong dependence on the nature of HTV and the lack of general agreement on the characteristics of HTV, the reported studies are first reviewed to enhance an understanding of HTV and related issues. The characteristics of HTV and relevant unresolved issues are discussed on the basis of measured data, proposed standards, and measurement methods, while the need for further developments in measurement systems is emphasized. The studies on biodynamic response and their findings are grouped into four categories based on the methodology used and the objective. These include studies on (1) through-the-hand-arm response, expressed in terms of vibration transmissibility; (2) to-the-hand response, expressed in terms of the force-motion relationship of the hand-arm system; (3) to-the-hand biodynamic response function, expressed in terms of vibration energy absorption; and (4) computer modeling of the biodynamic response characteristics.

SaniTwice: a novel approach to hand hygiene for reducing bacterial contamination on hands when soap and water are unavailable.

PubMed

Edmonds, Sarah L; Mann, James; McCormack, Robert R; Macinga, David R; Fricker, Christopher M; Arbogast, James W; Dolan, Michael J

2010-12-01

The risk of inadequate hand hygiene in food handling settings is exacerbated when water is limited or unavailable, thereby making washing with soap and water difficult. The SaniTwice method involves application of excess alcohol-based hand sanitizer (ABHS), hand "washing" for 15 s, and thorough cleaning with paper towels while hands are still wet, followed by a standard application of ABHS. This study investigated the effectiveness of the SaniTwice methodology as an alternative to hand washing for cleaning and removal of microorganisms. On hands moderately soiled with beef broth containing Escherichia coli (ATCC 11229), washing with a nonantimicrobial hand washing product achieved a 2.86 (±0.64)-log reduction in microbial contamination compared with the baseline, whereas the SaniTwice method with 62 % ethanol (EtOH) gel, 62 % EtOH foam, and 70 % EtOH advanced formula gel achieved reductions of 2.64 ± 0.89, 3.64 ± 0.57, and 4.61 ± 0.33 log units, respectively. When hands were heavily soiled from handling raw hamburger containing E. coli, washing with nonantimicrobial hand washing product and antimicrobial hand washing product achieved reductions of 2.65 ± 0.33 and 2.69 ± 0.32 log units, respectively, whereas SaniTwice with 62 % EtOH foam, 70 % EtOH gel, and 70 % EtOH advanced formula gel achieved reductions of 2.87 ± 0.42, 2.99 ± 0.51, and 3.92 ± 0.65 log units, respectively. These results clearly demonstrate that the in vivo antibacterial efficacy of the SaniTwice regimen with various ABHS is equivalent to or exceeds that of the standard hand washing approach as specified in the U.S. Food and Drug Administration Food Code. Implementation of the SaniTwice regimen in food handling settings with limited water availability should significantly reduce the risk of foodborne infections resulting from inadequate hand hygiene.

Hand preferences in two unimanual and two bimanual coordinated tasks in the black-handed spider monkey (Ateles geoffroyi).

PubMed

Motes Rodrigo, Alba; Ramirez Torres, Carlos Eduardo; Hernandez Salazar, Laura Teresa; Laska, Matthias

2018-05-01

Spider monkeys are interesting to study with regard to hand preferences, as they are one of the few primate species that lack a thumb and, thus, are unable to perform a precision grip. Further, being platyrrhine primates, they also largely lack independent motor control of the digits and, thus, have only limited manual dexterity. It was therefore the aim of the present study to assess hand preferences in black-handed spider monkeys ( Ateles geoffroyi ) in 4 tasks differing in task demand: simple unimanual reaching for food and 3 versions of the widely used tube task, including 2 bimanual versions that differ from each other in the degree of fine motor control needed and a unimanual version that does not require coordinated action of the hands. We found that black-handed spider monkeys display significant hand preferences at the individual, but not at the population, level. This was true both in the 2 bimanual coordinated tasks and in the 2 unimanual tasks. Further, our results show that the majority of animals were consistent in the hand they preferred in these 4 tasks. Our findings only partially support the notion that task demand positively correlates with strength of hand preference. Finally, we found that the index finger was the most frequently used digit in all 3 tube tasks, although the animals also used other digits and 2- and 3-finger combinations to extract food from a tube. We conclude that limited manual dexterity does not prevent spider monkeys from displaying strong and consistent hand preferences at the individual level. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

[The diabetic hand].

PubMed

Schiavon, F; Circhetta, C; Dani, L

2004-01-01

Diabetes mellitus is a chronic metabolic condition characterized by persistent hyperglycaemia with resultant morbidity and mortality related to its microvascular and macrovascular complications. In addition diabetes is also associated with several musculoskeletal disorders of the hand, that can be debilitating. There is increased incidence of these abnormalities in patients with type 1 and type 2 diabetes compared with the general population, related to disease duration but not to the age or sex. Typical diabetes associated hand condition include the palmar flexor tenosynovitis, Dupuytren's contracture, syndrome of limited joint mobility, carpal tunnel syndrome, Charcot arthropathy and reflex sympathetic dystrophy. Maintaining good glycaemic control by exercise, diet and drugs improves or prevents the development of these hand rheumatic condition. In this brief report we review the rational therapeutic approach to these disorders.

39 CFR 211.2 - Regulations of the Postal Service.

Code of Federal Regulations, 2011 CFR

2011-07-01

... regulations, all regulations of other agencies of the United States continued in effect as postal regulations... 39 Postal Service 1 2011-07-01 2011-07-01 false Regulations of the Postal Service. 211.2 Section... REGULATIONS § 211.2 Regulations of the Postal Service. (a) The regulations of the Postal Service consist of...

Characterization of the 1st and 2nd EF-hands of NADPH oxidase 5 by fluorescence, isothermal titration calorimetry, and circular dichroism

PubMed Central

2012-01-01

Background Superoxide generated by non-phagocytic NADPH oxidases (NOXs) is of growing importance for physiology and pathobiology. The calcium binding domain (CaBD) of NOX5 contains four EF-hands, each binding one calcium ion. To better understand the metal binding properties of the 1st and 2nd EF-hands, we characterized the N-terminal half of CaBD (NCaBD) and its calcium-binding knockout mutants. Results The isothermal titration calorimetry measurement for NCaBD reveals that the calcium binding of two EF-hands are loosely associated with each other and can be treated as independent binding events. However, the Ca2+ binding studies on NCaBD(E31Q) and NCaBD(E63Q) showed their binding constants to be 6.5 × 105 and 5.0 × 102 M-1 with ΔHs of -14 and -4 kJ/mol, respectively, suggesting that intrinsic calcium binding for the 1st non-canonical EF-hand is largely enhanced by the binding of Ca2+ to the 2nd canonical EF-hand. The fluorescence quenching and CD spectra support a conformational change upon Ca2+ binding, which changes Trp residues toward a more non-polar and exposed environment and also increases its α-helix secondary structure content. All measurements exclude Mg2+-binding in NCaBD. Conclusions We demonstrated that the 1st non-canonical EF-hand of NOX5 has very weak Ca2+ binding affinity compared with the 2nd canonical EF-hand. Both EF-hands interact with each other in a cooperative manner to enhance their Ca2+ binding affinity. Our characterization reveals that the two EF-hands in the N-terminal NOX5 are Ca2+ specific. Graphical abstract PMID:22490336

29 CFR 510.2 - Purpose and scope of regulations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Purpose and scope of regulations. 510.2 Section 510.2 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS... RICO General § 510.2 Purpose and scope of regulations. (a) The purpose of these regulations is to...

The Visible Hand: Markets, Politics, and Regulation in Post-Katrina New Orleans

ERIC Educational Resources Information Center

Jabbar, Huriya

2016-01-01

In this article Huriya Jabbar examines how the regulatory environment in post-Hurricane Katrina New Orleans has influenced choice, incentives, and competition among schools. While previous research has highlighted the mechanisms of competition and individual choice--the "invisible hand"--and the creation of markets in education, Jabbar…

The utility of hand transplantation in hand amputee patients.

PubMed

Alolabi, Noor; Chuback, Jennifer; Grad, Sharon; Thoma, Achilles

2015-01-01

To measure the desirable health outcome, termed utility, and the expected quality-adjusted life years (QALYs) gained with hand composite tissue allotransplantation (CTA) using hand amputee patients and the general public. Using the standard gamble (SG) and time trade-off (TTO) techniques, utilities were obtained from 30 general public participants and 12 amputee patients. The health utility and net QALYs gained or lost with transplantation were computed. A sensitivity analysis was conducted to account for the effects of lifelong immunosuppression on the life expectancy of transplant recipients. Higher scores represent greater utility. Hand amputation mean health utility as measured by the SG and TTO methods, respectively, was 0.72 and 0.80 for the general public and 0.69 and 0.70 for hand amputees. In comparison, hand CTA mean health utility was 0.74 and 0.82 for the general public and 0.83 and 0.86 for amputees. Hand CTA imparted an expected gain of 0.9 QALYs (SG and TTO) in the general public and 7.0 (TTO) and 7.8 (SG) QALYs in hand amputees. A loss of at least 1.7 QALYs was demonstrated when decreasing the life expectancy in the sensitivity analysis in the hand amputee group. Hand amputee patients did not show a preference toward hand CTA with its inherent risks. With this procedure being increasingly adopted worldwide, the benefits must be carefully weighed against the risks of lifelong immunosuppressive therapy. This study does not show clear benefit to advocate hand CTA. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Early growth response 2 and Egr3 are unique regulators in immune system.

PubMed

Taefehshokr, Sina; Key, Yashar Azari; Khakpour, Mansour; Dadebighlu, Pourya; Oveisi, Amin

2017-01-01

The immune system is evolved to defend the body against pathogens and is composed of thousands of complicated and intertwined pathways, which are highly controlled by processes such as transcription and repression of cellular genes. Sometimes the immune system malfunctions and a break down in self-tolerance occurs. This lead to the inability to distinguish between self and non-self and cause attacks on host tissues, a condition also known as autoimmunity, which can result in chronic debilitating diseases. Early growth response genes are family of transcription factors comprising of four members, Egr1, Egr2, Egr3 and Egr4. All of which contain three cyc2-His2 zinc fingers. Initially, Egr2 function was identified in the regulation of peripheral nerve myelination, hindbrain segmentation. Egr3, on the other hand, is highly expressed in muscle spindle development. Egr2 and Egr3 are induced due to the antigen stimulation and this signaling is implemented through the B and T cell receptors in the adaptive immunity. T cell receptor signaling plays a key role in Egr 2 and 3 expressions via their interaction with NFAT molecules. Egr 2 and 3 play a crucial role in regulation of the immune system and their involvement in B and T cell activation, anergy induction and preventing the autoimmune disease has been investigated. The deficiency of these transcription factors has been associated to deficient Cbl-b expression, a resistant to anergy phenotype, and expression of effector and activated T cells.

The Plastic Surgery Hand Curriculum.

PubMed

Silvestre, Jason; Levin, L Scott; Serletti, Joseph M; Chang, Benjamin

2015-12-01

Designing an effective hand rotation for plastic surgery residents is difficult. The authors address this limitation by elucidating the critical components of the hand curriculum during plastic surgery residency. Hand questions on the Plastic Surgery In-Service Training Exam for six consecutive years (2008 to 2013) were characterized by presence of imaging, vignette setting, question taxonomy, answer domain, anatomy, and topic. Answer references were quantified by source and year of publication. Two hundred sixty-six questions were related to hand surgery (22.7 percent of all questions; 44.3 per year) and 61 were accompanied by an image (22.9 percent). Vignettes tended to be clinic- (50.0 percent) and emergency room-based (35.3 percent) (p < 0.001). Questions required decision-making (60.5 percent) over interpretation (25.9 percent) and recall skills (13.5 percent) (p < 0.001). Answers focused on interventions (57.5 percent) over anatomy/pathology (25.2 percent) and diagnoses (17.3 percent) (p < 0.001). Nearly half of the questions focused on the digits. The highest yield topics were trauma (35.3 percent), reconstruction (24.4 percent), and aesthetic and functional problems (14.2 percent). The Journal of Hand Surgery (American volume) (20.5 percent) and Plastic and Reconstructive Surgery (18.0 percent) were the most-cited journals, and the median publication lag was 7 years. Green's Operative Hand Surgery was the most-referenced textbook (41.8 percent). These results will enable trainees to study hand surgery topics with greater efficiency. Faculty can use these results to ensure that tested topics are covered during residency training. Thus, a benchmark is established to improve didactic, clinical, and operative experiences in hand surgery.

[Hand motor dysfunctions in computer users].

PubMed

Shavlovskaia, O A; Shvarkov, S B; Posokhov, S I

2010-01-01

It were studied 239 female typists aged from 16 to 62 years (mean age 20,1±7,8 years) using author's questionnaire for computer typists to assess hand function and develop preventive measures of disturbances revealed. Indirect signs of tunnel hand neuropathy (27,2%), focal hand dystonia (21,4%) and muscular-tonic syndromes of different localization (18%) have been found. Typists are a risk group of fine hand motor dysfunctions. As preventive measures, authors recommend to use computer auxiliary devices, to change a motor stereotype during the day, to make hand "motor holidays", to organize working place.

7 CFR 301.86-2 - Regulated articles.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Regulated articles. 301.86-2 Section 301.86-2... articles. The following are regulated articles: (a) Pale cyst nematodes.2 2 Permit and other requirements... infested or associated field that can carry soil if moved out of the field. (i) Any other product, article...

7 CFR 301.86-2 - Regulated articles.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Regulated articles. 301.86-2 Section 301.86-2... articles. The following are regulated articles: (a) Pale cyst nematodes.2 2 Permit and other requirements... infested or associated field that can carry soil if moved out of the field. (i) Any other product, article...

7 CFR 301.86-2 - Regulated articles.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Regulated articles. 301.86-2 Section 301.86-2... articles. The following are regulated articles: (a) Pale cyst nematodes.2 2 Permit and other requirements... infested or associated field that can carry soil if moved out of the field. (i) Any other product, article...

7 CFR 2.2 - Authority of the Secretary to prescribe regulations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Authority of the Secretary to prescribe regulations. 2.2 Section 2.2 Agriculture Office of the Secretary of Agriculture DELEGATIONS OF AUTHORITY BY THE... prescribe regulations for the government of his department, the conduct of its employees, the distribution...

Hand-to-Hand Model for Bioelectrical Impedance Analysis to Estimate Fat Free Mass in a Healthy Population.

PubMed

Lu, Hsueh-Kuan; Chiang, Li-Ming; Chen, Yu-Yawn; Chuang, Chih-Lin; Chen, Kuen-Tsann; Dwyer, Gregory B; Hsu, Ying-Lin; Chen, Chun-Hao; Hsieh, Kuen-Chang

2016-10-21

This study aimed to establish a hand-to-hand (HH) model for bioelectrical impedance analysis (BIA) fat free mass (FFM) estimation by comparing with a standing position hand-to-foot (HF) BIA model and dual energy X-ray absorptiometry (DXA); we also verified the reliability of the newly developed model. A total of 704 healthy Chinese individuals (403 men and 301 women) participated. FFM (FFM DXA ) reference variables were measured using DXA and segmental BIA. Further, regression analysis, Bland-Altman plots, and cross-validation (2/3 participants as the modeling group, 1/3 as the validation group; three turns were repeated for validation grouping) were conducted to compare tests of agreement with FFM DXA reference variables. In male participants, the hand-to-hand BIA model estimation equation was calculated as follows: FFM m HH = 0.537 h²/Z HH - 0.126 year + 0.217 weight + 18.235 ( r ² = 0.919, standard estimate of error (SEE) = 2.164 kg, n = 269). The mean validated correlation coefficients and limits of agreement (LOAs) of the Bland-Altman analysis of the calculated values for FFM m HH and FFM DXA were 0.958 and -4.369-4.343 kg, respectively, for hand-to-foot BIA model measurements for men; the FFM (FFM m HF ) and FFM DXA were 0.958 and -4.356-4.375 kg, respectively. The hand-to-hand BIA model estimating equation for female participants was FFM F HH = 0.615 h²/Z HH - 0.144 year + 0.132 weight + 16.507 ( r ² = 0.870, SEE = 1.884 kg, n = 201); the three mean validated correlation coefficient and LOA for the hand-to-foot BIA model measurements for female participants (FFM F HH and FFM DXA ) were 0.929 and -3.880-3.886 kg, respectively. The FFM HF and FFM DXA were 0.942 and -3.511-3.489 kg, respectively. The results of both hand-to-hand and hand-to-foot BIA models demonstrated similar reliability, and the hand-to-hand BIA models are practical for assessing FFM.

Hand Matters: Left-Hand Gestures Enhance Metaphor Explanation

ERIC Educational Resources Information Center

Argyriou, Paraskevi; Mohr, Christine; Kita, Sotaro

2017-01-01

Research suggests that speech-accompanying gestures influence cognitive processes, but it is not clear whether the gestural benefit is specific to the gesturing hand. Two experiments tested the "(right/left) hand-specificity" hypothesis for self-oriented functions of gestures: gestures with a particular hand enhance cognitive processes…

21 CFR 862.2 - Regulation of calibrators.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Regulation of calibrators. 862.2 Section 862.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES General Provisions § 862.2 Regulation...

21 CFR 862.2 - Regulation of calibrators.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Regulation of calibrators. 862.2 Section 862.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES General Provisions § 862.2 Regulation...

21 CFR 862.2 - Regulation of calibrators.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Regulation of calibrators. 862.2 Section 862.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES General Provisions § 862.2 Regulation...

21 CFR 862.2 - Regulation of calibrators.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Regulation of calibrators. 862.2 Section 862.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES General Provisions § 862.2 Regulation...

21 CFR 862.2 - Regulation of calibrators.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Regulation of calibrators. 862.2 Section 862.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES General Provisions § 862.2 Regulation...

Dissociable neural responses to hands and non-hand body parts in human left extrastriate visual cortex.

PubMed

Bracci, Stefania; Ietswaart, Magdalena; Peelen, Marius V; Cavina-Pratesi, Cristiana

2010-06-01

Accumulating evidence points to a map of visual regions encoding specific categories of objects. For example, a region in the human extrastriate visual cortex, the extrastriate body area (EBA), has been implicated in the visual processing of bodies and body parts. Although in the monkey, neurons selective for hands have been reported, in humans it is unclear whether areas selective for individual body parts such as the hand exist. Here, we conducted two functional MRI experiments to test for hand-preferring responses in the human extrastriate visual cortex. We found evidence for a hand-preferring region in left lateral occipitotemporal cortex in all 14 participants. This region, located in the lateral occipital sulcus, partially overlapped with left EBA, but could be functionally and anatomically dissociated from it. In experiment 2, we further investigated the functional profile of hand- and body-preferring regions by measuring responses to hands, fingers, feet, assorted body parts (arms, legs, torsos), and non-biological handlike stimuli such as robotic hands. The hand-preferring region responded most strongly to hands, followed by robotic hands, fingers, and feet, whereas its response to assorted body parts did not significantly differ from baseline. By contrast, EBA responded most strongly to body parts, followed by hands and feet, and did not significantly respond to robotic hands or fingers. Together, these results provide evidence for a representation of the hand in extrastriate visual cortex that is distinct from the representation of other body parts.

Dissociable Neural Responses to Hands and Non-Hand Body Parts in Human Left Extrastriate Visual Cortex

PubMed Central

Ietswaart, Magdalena; Peelen, Marius V.; Cavina-Pratesi, Cristiana

2010-01-01

Accumulating evidence points to a map of visual regions encoding specific categories of objects. For example, a region in the human extrastriate visual cortex, the extrastriate body area (EBA), has been implicated in the visual processing of bodies and body parts. Although in the monkey, neurons selective for hands have been reported, in humans it is unclear whether areas selective for individual body parts such as the hand exist. Here, we conducted two functional MRI experiments to test for hand-preferring responses in the human extrastriate visual cortex. We found evidence for a hand-preferring region in left lateral occipitotemporal cortex in all 14 participants. This region, located in the lateral occipital sulcus, partially overlapped with left EBA, but could be functionally and anatomically dissociated from it. In experiment 2, we further investigated the functional profile of hand- and body-preferring regions by measuring responses to hands, fingers, feet, assorted body parts (arms, legs, torsos), and non-biological handlike stimuli such as robotic hands. The hand-preferring region responded most strongly to hands, followed by robotic hands, fingers, and feet, whereas its response to assorted body parts did not significantly differ from baseline. By contrast, EBA responded most strongly to body parts, followed by hands and feet, and did not significantly respond to robotic hands or fingers. Together, these results provide evidence for a representation of the hand in extrastriate visual cortex that is distinct from the representation of other body parts. PMID:20393066

[Hand osteoarthritis].

PubMed

Šenolt, Ladislav

Hand osteoarthritis (OA) is a common chronic disorder causing pain and limitation of mobility of affected joints. The prevalence of hand OA increases with age and more often affects females. Clinical signs obviously do not correlate with radiographic findings - symptomatic hand OA affects approximately 26 % of adult subjects, but radiographic changes can be found in up to two thirds of females and half of males older than 55 years.Disease course differ among individual patients. Hand OA is a heterogeneous disease. Nodal hand OA is the most common subtype affecting interphalangeal joints, thumb base OA affects first carpometacarpal joint. Erosive OA represents a specific subtype of hand OA, which is associated with joint inflammation, more pain, functional limitation and erosive findings on radiographs.Treatment of OA is limited. Analgesics and nonsteroidal anti-inflammatory drugs are the only agents reducing symptoms. New insights into the pathogenesis of disease should contribute to the development of novel effective treatment of hand OA.

Staufen2 regulates neuronal target RNAs.

PubMed

Heraud-Farlow, Jacki E; Sharangdhar, Tejaswini; Li, Xiao; Pfeifer, Philipp; Tauber, Stefanie; Orozco, Denise; Hörmann, Alexandra; Thomas, Sabine; Bakosova, Anetta; Farlow, Ashley R; Edbauer, Dieter; Lipshitz, Howard D; Morris, Quaid D; Bilban, Martin; Doyle, Michael; Kiebler, Michael A

2013-12-26

RNA-binding proteins play crucial roles in directing RNA translation to neuronal synapses. Staufen2 (Stau2) has been implicated in both dendritic RNA localization and synaptic plasticity in mammalian neurons. Here, we report the identification of functionally relevant Stau2 target mRNAs in neurons. The majority of Stau2-copurifying mRNAs expressed in the hippocampus are present in neuronal processes, further implicating Stau2 in dendritic mRNA regulation. Stau2 targets are enriched for secondary structures similar to those identified in the 3' UTRs of Drosophila Staufen targets. Next, we show that Stau2 regulates steady-state levels of many neuronal RNAs and that its targets are predominantly downregulated in Stau2-deficient neurons. Detailed analysis confirms that Stau2 stabilizes the expression of one synaptic signaling component, the regulator of G protein signaling 4 (Rgs4) mRNA, via its 3' UTR. This study defines the global impact of Stau2 on mRNAs in neurons, revealing a role in stabilization of the levels of synaptic targets. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

[Infection control and hand hygiene in nursing homes in Oslo].

PubMed

Sie, Ingrid; Thorstad, Margrete; Andersen, Bjørg Marit

2008-06-26

Nosocomial infections and transmission can be substantially reduced by good infection control. The laws and regulations for infection control in heath care institutions emphasize establishment of infection control programs and improved hand hygiene. Our study reviews some factors that are important for practicing adequate hand hygiene (knowledge about infection control and hand-washing facilities). Health care workers (HCW) in nursing homes in Oslo participated in this study in 2006-2007. A questionnaire was made and SPSS was used to analyse the data . 70.7% of 324 HCW (in 42 nursing homes) answered the questionnaires. Nearly all of the respondents (95.6%) knew about the written procedures for hygiene and infection control; 88.5% knew that an infection control program was in place and about 50% had received information through internal education. Three of four had read the National guidelines for hand hygiene, 77.5% thought that hand disinfection was more effective than hand washing, and 97% reported hand hygiene after contact with a patient having an infection. Dispensers for hand disinfection were situated at central work places. At the same time, 17.9% informed that they worked in more than one place at the same time. This study confirms that most nursing homes in Oslo have an infection control program and training that improves the knowledge and awareness of hand hygiene among HCWs. However, the fact that nursing homes in Oslo have the resources, knowledge and education, is not the same as compliance.

Smart Hand For Manipulators

NASA Astrophysics Data System (ADS)

Fiorini, Paolo

1987-10-01

Sensor based, computer controlled end effectors for mechanical arms are receiving more and more attention in the robotics industry, because commonly available grippers are only adequate for simple pick and place tasks. This paper describes the current status of the research at JPL on a smart hand for a Puma 560 robot arm. The hand is a self contained, autonomous system, capable of executing high level commands from a supervisory computer. The mechanism consists of parallel fingers, powered by a DC motor, and controlled by a microprocessor embedded in the hand housing. Special sensors are integrated in the hand for measuring the grasp force of the fingers, and for measuring forces and torques applied between the arm and the surrounding environment. Fingers can be exercised under position, velocity and force control modes. The single-chip microcomputer in the hand executes the tasks of communication, data acquisition and sensor based motor control, with a sample cycle of 2 ms and a transmission rate of 9600 baud. The smart hand described in this paper represents a new development in the area of end effector design because of its multi-functionality and autonomy. It will also be a versatile test bed for experimenting with advanced control schemes for dexterous manipulation.

Toe-to-hand transfer.

PubMed

Yoshimura, M

1980-07-01

Toe-to-hand transfer was performed in 28 patients, involving 33 fingers, using microvascular technique. Of this number, 26 patients (31 fingers) had experienced trauma, and the remaining 2 patients (2 fingers) had a congenital deformity. The toew used for grafting were the great toe (1), the second tow (30), and third toe (2). Success was achieved in all cases, sensory recovery was good, and remarkable improvement was attained in function and cosmetic appearance. Metacarpal hand, amputation of thumb, and amputation thumb and three fingers were good indications for this procedure, which gave satisfactory aesthetic results, even in patients with amputation of single digits.

Hand contamination during routine care in medical wards: the role of hand hygiene compliance.

PubMed

Monistrol, Olga; López, M Liboria; Riera, Montserrat; Font, Roser; Nicolás, Carme; Escobar, Miguel Angel; Freixas, Núria; Garau, Javier; Calbo, Esther

2013-04-01

The hands of healthcare workers (HCWs) are the most common vehicle for the transmission of micro-organisms from patient to patient and within the healthcare environment. The aim of this study was to evaluate the impact of a multimodal campaign on the type and amount of resident and transient flora and the presence of potential risk factors for hand contamination during routine care. A before-after (PRE and POST periods) interventional study was carried out in medical wards of a tertiary care hospital. Eighty-nine samples were analysed. Samples were cultured immediately before patient contact using a glove-juice method. Data collected included socio-demographic and risk factors for hand contamination. Flora was measured as log10 c.f.u. ml(-1) and evaluated by comparing median values in the PRE and POST periods. Transient flora was isolated from the hands of 67.4 and 46.1 % of HCWs in the PRE and POST periods, respectively (P<0.001). Enterobacteriaceae, Pseudomonas spp. and meticillin-sensitive Staphylococcus aureus were the predominant contaminants. Resident flora was isolated from 92.1 % of HCWs in the PRE period and from 70.8 % in the POST period (P<0.001). The meticillin-resistant coagulase-negative staphylococci log10 c.f.u. count ml(-1) decreased from 1.96 ± 1.2 to 0.89 ± 1.2 (mean ± s d; P<0.001), and the global flora count decreased from 2.77 ± 1.1 to 1.56 ± 1.4 (P<0.001). In the POST period, the wearing of fewer rings (P<0.001), shorter fingernail length (P = 0.008), a shorter time since recent hand hygiene (HH) (P = 0.007) and an increased use of alcohol-based hand rub instead of soap (P<0.001) were documented. The HH multimodal strategy reduced the number of risk factors and the level of HCW hand contamination.

Effectiveness of liquid soap vs. chlorhexidine gluconate for the removal of Clostridium difficile from bare hands and gloved hands.

PubMed

Bettin, K; Clabots, C; Mathie, P; Willard, K; Gerding, D N

1994-11-01

To compare liquid soap versus 4% chlorhexidine gluconate in 4% alcohol for the decontamination of bare or gloved hands inoculated with an epidemic strain of Clostridium difficile. C difficile (6.7 log10 colony-forming units [CFU], 47% spores), was seeded onto bare or latex gloved hands of ten volunteers and allowed to dry. Half the volunteers initially washed with soap and half with chlorhexidine, followed by the other agent 1 week later. Cultures were done with Rodac plates at three sites on the hand: finger/thumbtips, the palmar surfaces of the fingers, and the palm. Statistical comparison was by paired Student's t test. On bare hands, soap and chlorhexidine did not differ in residual bacterial counts on the finger/thumbtips (log10 CFU, 2.0 and 2.1, P = NS) and fingers (log10 CFU, 2.4 and 2.5, P = NS). Counts were too high on bare palms to quantitate. On gloved hands, soap was more effective than chlorhexidine on fingers (log10 CFU 1.3 and 1.7, P < .01) and palms (log10 CFU 1.5 and 2.0, P < .01), but not finger/thumbtips (log10 CFU 1.6 with each, P = NS). Residual C difficile counts were lower on gloved hands than bare hands (P < 0.01 to < 0.0001). The two agents did not differ significantly in residual counts of C difficile on bare hands, but on gloved hands residual counts were lower following soap wash than following chlorhexidine wash. These observations support the use of either soap or chlorhexidine as a handwash for removal of C difficile, but efficacy in the prevention of C difficile transmission must be determined by prospective clinical trials.

SNF1-related protein kinases 2 are negatively regulated by a plant-specific calcium sensor.

PubMed

Bucholc, Maria; Ciesielski, Arkadiusz; Goch, Grażyna; Anielska-Mazur, Anna; Kulik, Anna; Krzywińska, Ewa; Dobrowolska, Grażyna

2011-02-04

SNF1-related protein kinases 2 (SnRK2s) are plant-specific enzymes involved in environmental stress signaling and abscisic acid-regulated plant development. Here, we report that SnRK2s interact with and are regulated by a plant-specific calcium-binding protein. We screened a Nicotiana plumbaginifolia Matchmaker cDNA library for proteins interacting with Nicotiana tabacum osmotic stress-activated protein kinase (NtOSAK), a member of the SnRK2 family. A putative EF-hand calcium-binding protein was identified as a molecular partner of NtOSAK. To determine whether the identified protein interacts only with NtOSAK or with other SnRK2s as well, we studied the interaction of an Arabidopsis thaliana orthologue of the calcium-binding protein with selected Arabidopsis SnRK2s using a two-hybrid system. All kinases studied interacted with the protein. The interactions were confirmed by bimolecular fluorescence complementation assay, indicating that the binding occurs in planta, exclusively in the cytoplasm. Calcium binding properties of the protein were analyzed by fluorescence spectroscopy using Tb(3+) as a spectroscopic probe. The calcium binding constant, determined by the protein fluorescence titration, was 2.5 ± 0.9 × 10(5) M(-1). The CD spectrum indicated that the secondary structure of the protein changes significantly in the presence of calcium, suggesting its possible function as a calcium sensor in plant cells. In vitro studies revealed that the activity of SnRK2 kinases analyzed is inhibited in a calcium-dependent manner by the identified calcium sensor, which we named SCS (SnRK2-interacting calcium sensor). Our results suggest that SCS is involved in response to abscisic acid during seed germination most probably by negative regulation of SnRK2s activity.

Stiff Hands

MedlinePlus

... Stiff Hands Find a hand surgeon near you. Videos Figures Figure 1: Hand splint to help straighten ... or "in." Also, avoid using media types like "video," "article," and "picture." Tip 4: Your results can ...

Hand Fractures

MedlinePlus

... Hand Fractures Find a hand surgeon near you. Videos Hand Fractures Close Popup Figures Figure 1 - Examples ... or "in." Also, avoid using media types like "video," "article," and "picture." Tip 4: Your results can ...

47 CFR 2.100 - International regulations in force.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false International regulations in force. 2.100 Section 2.100 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO....100 International regulations in force. The ITU Radio Regulations, edition of 2004, have been...

EZH1 and EZH2 promote skeletal growth by repressing inhibitors of chondrocyte proliferation and hypertrophy

PubMed Central

Lui, Julian C.; Garrison, Presley; Nguyen, Quang; Ad, Michal; Keembiyehetty, Chithra; Chen, Weiping; Jee, Youn Hee; Landman, Ellie; Nilsson, Ola; Barnes, Kevin M.; Baron, Jeffrey

2016-01-01

Histone methyltransferases EZH1 and EZH2 catalyse the trimethylation of histone H3 at lysine 27 (H3K27), which serves as an epigenetic signal for chromatin condensation and transcriptional repression. Genome-wide associated studies have implicated EZH2 in the control of height and mutations in EZH2 cause Weaver syndrome, which includes skeletal overgrowth. Here we show that the combined loss of Ezh1 and Ezh2 in chondrocytes severely impairs skeletal growth in mice. Both of the principal processes underlying growth plate chondrogenesis, chondrocyte proliferation and hypertrophy, are compromised. The decrease in chondrocyte proliferation is due in part to derepression of cyclin-dependent kinase inhibitors Ink4a/b, while ineffective chondrocyte hypertrophy is due to the suppression of IGF signalling by the increased expression of IGF-binding proteins. Collectively, our findings reveal a critical role for H3K27 methylation in the regulation of chondrocyte proliferation and hypertrophy in the growth plate, which are the central determinants of skeletal growth. PMID:27897169

Hand skin reconstruction from skeletal landmarks.

PubMed

Lefèvre, P; Van Sint Jan, S; Beauthier, J P; Rooze, M

2007-11-01

Many studies related to three-dimensional facial reconstruction have been previously reported. On the other hand, no extensive work has been found in the literature about hand reconstruction as an identification method. In this paper, the feasibility of virtual reconstruction of hand skin based on (1) its skeleton and (2) another hand skin and skeleton used as template was assessed. One cadaver hand and one volunteer's hand have been used. For the two hands, computer models of the bones and skin were obtained from computerized tomography. A customized software allowed locating spatial coordinates of bony anatomical landmarks on the models. From these landmarks, the spatial relationships between the models were determined and used to interpolate the missing hand skin. The volume of the interpolated skin was compared to the real skin obtained from medical imaging for validation. Results seem to indicate that such a method is of interest to give forensic investigators morphological clues related to an individual hand skin based on its skeleton. Further work is in progress to finalize the method.

ONTOGENIC EXPRESSION OF HUMAN CARBOXYLESTERASE-2 AND CYTOCHROME P450 3A4 IN LIVER AND DUODENUM: POSTNATAL SURGE AND ORGAN-DEPENDENT REGULATION1

PubMed Central

Chen, Yi-Tzai; Trzoss, Lynnie; Yang, Dongfang; Yan, Bingfang

2015-01-01

Human carboxylesterase-2 (CES2) and cytochrome P450 3A4 (CYP3A4) are two major drug metabolizing enzymes that play critical roles in hydrolytic and oxidative biotransformation, respectively. They share substrates but may have opposite effect on therapeutic potential such as the metabolism of the anticancer prodrug irinotecan. Both CES2 and CYP3A4 are expressed in the liver and the gastrointestinal tract. This study was conducted to determine whether CES2 and CYP3A4 are expressed under developmental regulation and whether the regulation occurs differentially between the liver and duodenum. A large number of tissues (112) were collected with majority of them from donors at 1-198 days of age. In addition, multi-sampling (liver, duodenum and jejunum) was performed in some donors. The expression was determined at mRNA and protein levels. In the liver, CES2 and CYP3A4 mRNA exhibited a postnatal surge (1 versus 2 months of age) by 2.7 and 29 fold, respectively. CYP3A4 but not CES2 mRNA in certain pediatric groups reached or even exceeded the adult level. The duodenal samples, on the other hand, showed a gene-specific expression pattern at mRNA level. CES2 mRNA increased with age but the opposite was true with CYP3A4 mRNA. The levels of CES2 and CYP3A4 protein, on the other hand, increased with age in both liver and duodenum. The multi-sampling study demonstrated significant correlation of CES2 expression between the duodenum and jejunum. However, neither duodenal nor jejunal expression correlated with hepatic expression of CES2. These findings establish that developmental regulation occurs in a gene and organ-dependent manner. PMID:25724353

Programming of left hand exploits task set but that of right hand depends on recent history.

PubMed

Tang, Rixin; Zhu, Hong

2017-07-01

There are many differences between the left hand and the right hand. But it is not clear if there is a difference in programming between left hand and right hand when the hands perform the same movement. In current study, we carried out two experiments to investigate whether the programming of two hands was equivalent or they exploited different strategies. In the first experiment, participants were required to use one hand to grasp an object with visual feedback or to point to the center of one object without visual feedback on alternate trials, or to grasp an object without visual feedback and to point the center of one object with visual feedback on alternating trials. They then performed the tasks with the other hand. The result was that previous pointing task affected current grasping when it was performed by the left hand, but not the right hand. In experiment 2, we studied if the programming of the left (or right) hand would be affected by the pointing task performed on the previous trial not only by the same hand, but also by the right (or left) hand. Participants pointed and grasped the objects alternately with two hands. The result was similar with Experiment 1, i.e., left-hand grasping was affected by right-hand pointing, whereas right-hand grasping was immune from the interference from left hand. Taken together, the results suggest that when open- and closed-loop trials are interleaved, motor programming of grasping with the right hand was affected by the nature of the online feedback on the previous trial only if it was a grasping trial, suggesting that the trial-to-trial transfer depends on sensorimotor memory and not on task set. In contrast, motor programming of grasping with the left hand can use information about the nature of the online feedback on the previous trial to specify the parameters of the movement, even when the type of movement that occurred was quite different (i.e., pointing) and was performed with the right hand. This suggests that

Toucan hand feeding and nestling growth.

PubMed

St Leger, Judy; Vince, Martin; Jennings, Jerry; McKerney, Erin; Nilson, Erika

2012-05-01

A retrospective analysis of hand-feeding records and growth data from 3 facilities was performed to determine the growth pattern for 8 toucan species raised in captivity. General philosophies of breeding and rearing were similar but approaches to hand-feeding varied. General hand-feeding and chick management records from hatch to fledging were reviewed for 2 of the 3 facilities. Effective hand-feeding formulas were commercially available and minimally modified. Growth curves were developed. Curves approximated typical expected patterns of nestling growth with no loss of weight at fledging. This study provides a basis for hand-feeding protocols and growth curves to assess development.

Hand Washing

MedlinePlus

... study, only 58% of female and 48% of male middle- and high-school students washed their hands after using the bathroom. Yuck! How to Wash Your Hands Correctly There's a right way to wash your hands. Follow these simple ...

All-Arthroscopic Autologous Matrix-Induced Chondrogenesis-Aided Repair of a Patellar Cartilage Defect Using Dry Arthroscopy and a Retraction System.

PubMed

Sadlik, Boguslaw; Puszkarz, Mariusz; Kosmalska, Lidia; Wiewiorski, Martin

2017-11-01

The technique of all-arthroscopic autologous matrix-induced chondrogenesis (AMIC)-aided repair of patellar cartilage lesions using a retraction system and dry arthroscopy has been recently described. We report the first clinical and radiological data at a short-term follow-up. Twelve patients underwent AMIC-aided cartilage repair for a patellar lesion. All steps of the procedure were performed arthroscopically, which include the use of an intra-articularly placed retraction plate for distraction of the patellofemoral joint and evacuation of saline solution for collagen matrix insertion and fixation. Clinical assessment performed before surgery and at a mean follow-up time of 38 months (range: 24-70) included the following scores: Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and visual analog scale (VAS). Magnetic resonance imaging was performed at the follow-up examination, including the magnetic resonance observation of cartilage repair tissue (MOCART) score. The mean KOOS and IKDC scores increased significantly ( p  < 0.01) from 50.3 and 37.4 points preoperatively to 90.1 and 79.4 postoperatively. The VAS score decreased from 7.8 to 2.3 points. Mean MOCART score at follow-up was 58.3 points. Cartilage repair of patellar lesions aided by a retraction system in a dry arthroscopy setup is a promising approach. Further studies are needed to evaluate this procedure and compare it to existing matrix implantation techniques. The level of evidence for the study is 4 (case series). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

2',5'-Dihydroxychalcone down-regulates endothelial connexin43 gap junctions and affects MAP kinase activation.

PubMed

Lee, Yi-Nan; Yeh, Hung-I; Tian, Tin-Yi; Lu, Wen-Wei; Ko, Yu-Shien; Tsai, Cheng-Ho

2002-09-30

We examined the effect of 2',5'-dihydroxychalcone on connexin43 (Cx43) expression and gap-junctional communication in human umbilical vein endothelial cells (HUVEC). The result showed that expression of Cx43 is rapidly reduced by 2',5'-dihydroxychalcone in a dose-dependent manner, Concomitantly, the communication function, determined by fluorescence recovery after photobleaching (FRAP), is decreased. We further investigated whether the mitogen-activated protein (MAP) kinase and the degradation pathway of gap junctions are involved in these processes. Although the change of Cx43 is not affected by the level of fetal calf serum (FCS) used in the medium, activation of MAP kinase varies, depending on the FCS level. At a low level (0.5%), the chalcone inhibits the activation, like PD98059, a specific inhibitor of MAP kinase kinase. However, at a high level (20%), MAP kinase is activated. On the other hand, the chalcone's down-regulating effect on Cx43, while is totally blocked by protease inhibitors leupeptin and N-acetyl-leucyl-norleucinal (ALLN), persists in the presence of PD98059, We concluded that 2',5'-dihydroxychalcone down-regulates Cx43 expression and gap-junctional communication in the HUVEC via enhancement of the proteolysis pathway, and this compound possesses dual effects on MAP kinase activation.

Hand hygiene with alcohol hand rub and gloves reduces the incidence of late onset sepsis in preterm neonates.

PubMed

Janota, Jan; Šebková, Sylva; Višňovská, Magda; Kudláčková, Jana; Hamplová, Drahomíra; Zach, Jiří

2014-10-01

To assess the impact of a hand hygiene protocol, using hand washing, alcohol hand rub and gloves when caring for preterm infants born after 31 weeks of gestation, on the incidence of neonatal late onset sepsis (LOS). All babies delivered between 32 + 0 and 36 + 6 weeks gestation and admitted to the neonatal intensive care unit during a 14-month period were included. We followed a hand hygiene protocol with hand washing and alcohol hand rub (hand rub period) for the first 7 months and a protocol of hand washing, alcohol hand rub and gloves (gloves period) for the second 7 months. The hand rub and gloves groups consisted of 111 and 89 patients, respectively. Five patients were diagnosed with a total of six episodes of LOS in the hand rub group, and the incidence of LOS during the hand rub period was 2.99/1000 hospital days and 54.1/1000 admissions. There were no patients diagnosed with LOS during the gloves period (significant decrease, p = 0.028). Using a hand hygiene protocol with hand washing, hand rub and gloves significantly reduced the incidence of LOS in preterm newborns, and the results suggest that it may produce a sustained improvement in the infection rate. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

34 CFR 673.2 - Applicability of regulations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 3 2011-07-01 2011-07-01 false Applicability of regulations. 673.2 Section 673.2 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION GENERAL PROVISIONS FOR THE FEDERAL PERKINS LOAN PROGRAM, FEDERAL WORK...

34 CFR 673.2 - Applicability of regulations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false Applicability of regulations. 673.2 Section 673.2 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION GENERAL PROVISIONS FOR THE FEDERAL PERKINS LOAN PROGRAM, FEDERAL WORK...

SH2 domain-containing inositol 5-phosphatase (SHIP2) regulates de-novo lipogenesis and secretion of apoB100 containing lipoproteins in HepG2 cells.

PubMed

Gorgani-Firuzjaee, Sattar; Khatami, Shohreh; Adeli, Khosrow; Meshkani, Reza

2015-09-04

Hepatic de-novo lipogenesis and production of triglyceride rich VLDL are regulated via the phosphoinositide 3-kinase cascade, however, the role of a negative regulator of this pathway, the SH2 domain-containing inositol 5-phosphatase (SHIP2) in this process, remains unknown. In the present study, we investigated the molecular link between SHIP2 expression and metabolic dyslipidemia using overexpression or suppression of SHIP2 gene in HepG2 cells. The results showed that overexpression of the wild type SHIP2 gene (SHIP2-WT) led to a higher total lipid content (28%) compared to control, whereas overexpression of the dominant negative SHIP2 gene (SHIP2-DN) reduced total lipid content in oleate treated cells by 40%. Overexpression of SHIP2-WT also led to a significant increase in both secretion of apoB100 containing lipoproteins and de-novo lipogenesis, as demonstrated by an enhancement in secreted apoB100 and MTP expression, increased intra and extracellular triglyceride levels and enhanced expression of lipogenic genes such as SREBP1c, FAS and ACC. On the other hand, overexpression of the SHIP2-DN gene prevented oleate-induced de-novo lipogenesis and secretion of apoB100 containing lipoproteins in HepG2 cells. Collectively, these findings suggest that SHIP2 expression level is a key determinant of hepatic lipogenesis and lipoprotein secretion, and its inhibition could be considered as a potential target for treatment of dyslipidemia. Copyright © 2015 Elsevier Inc. All rights reserved.

Single treatment with ethanol hand rub is ineffective against human rhinovirus--hand washing with soap and water removes the virus efficiently.

PubMed

Savolainen-Kopra, Carita; Korpela, Terttu; Simonen-Tikka, Marja-Leena; Amiryousefi, Ali; Ziegler, Thedi; Roivainen, Merja; Hovi, Tapani

2012-03-01

Ethanol-containing hand rubs are used frequently as a substitute for hand washing with water and soap. However, not all viruses are inactivated by a short term rubbing with alcohol. The capacity of a single round of instructed and controlled hand cleaning with water and soap or ethanol-containing hand rub, respectively, was tested for removal of human rhinovirus administered onto the skin of healthy volunteers on the back of the hands. Hand washing with soap and water appeared to be much more efficient for removing rhinoviruses from skin than rubbing hands with an ethanol-containing disinfectant. After washing with soap and water the virus was detected in 3/9 (33.3%) test persons from the left hand and 1/9 (11.1%) cases from the right hand, whereas the virus was detected invariably by real-time RT-PCR from both hands after cleaning with alcohol hand rub (P-value <0.01). Both substances evaluated clinically were also tested in vitro for virucidal efficacy against Human rhinovirus2 (HRV2) using a standardized assay. Both tested substances were poor within the contact time used in the hand-cleaning test. In conclusion, thorough and conventional hand washing with water and soap can clean efficiently hands contaminated with the virus responsible for an extensive share of common cold episodes. Copyright © 2012 Wiley Periodicals, Inc.

3D Printed Robotic Hand

NASA Technical Reports Server (NTRS)

Pizarro, Yaritzmar Rosario; Schuler, Jason M.; Lippitt, Thomas C.

2013-01-01

Dexterous robotic hands are changing the way robots and humans interact and use common tools. Unfortunately, the complexity of the joints and actuations drive up the manufacturing cost. Some cutting edge and commercially available rapid prototyping machines now have the ability to print multiple materials and even combine these materials in the same job. A 3D model of a robotic hand was designed using Creo Parametric 2.0. Combining "hard" and "soft" materials, the model was printed on the Object Connex350 3D printer with the purpose of resembling as much as possible the human appearance and mobility of a real hand while needing no assembly. After printing the prototype, strings where installed as actuators to test mobility. Based on printing materials, the manufacturing cost of the hand was $167, significantly lower than other robotic hands without the actuators since they have more complex assembly processes.

A natural approach to convey numerical digits using hand activity recognition based on hand shape features

NASA Astrophysics Data System (ADS)

Chidananda, H.; Reddy, T. Hanumantha

2017-06-01

This paper presents a natural representation of numerical digit(s) using hand activity analysis based on number of fingers out stretched for each numerical digit in sequence extracted from a video. The analysis is based on determining a set of six features from a hand image. The most important features used from each frame in a video are the first fingertip from top, palm-line, palm-center, valley points between the fingers exists above the palm-line. Using this work user can convey any number of numerical digits using right or left or both the hands naturally in a video. Each numerical digit ranges from 0 to9. Hands (right/left/both) used to convey digits can be recognized accurately using the valley points and with this recognition whether the user is a right / left handed person in practice can be analyzed. In this work, first the hand(s) and face parts are detected by using YCbCr color space and face part is removed by using ellipse based method. Then, the hand(s) are analyzed to recognize the activity that represents a series of numerical digits in a video. This work uses pixel continuity algorithm using 2D coordinate geometry system and does not use regular use of calculus, contours, convex hull and datasets.

Left-handed Children in Singapore.

ERIC Educational Resources Information Center

Gan, Linda

1998-01-01

Used teacher questionnaires to examine incidence of left-handedness in nearly 2,800 Singaporean children, racial differences in this left-handed population, and educational provisions in preschool and primary school. Findings indicated that 7.5% of preschoolers and 6.3% of primary children were left-handed, with a higher proportion being Chinese…

48 CFR 2501.104-2 - Arrangement of regulations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Arrangement of regulations. 2501.104-2 Section 2501.104-2 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION... material in the FAR, Parts 70 and up are used by the NSFAR. Where the subject matter in the FAR requires no...

48 CFR 2501.104-2 - Arrangement of regulations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Arrangement of regulations. 2501.104-2 Section 2501.104-2 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION... material in the FAR, Parts 70 and up are used by the NSFAR. Where the subject matter in the FAR requires no...

48 CFR 2501.104-2 - Arrangement of regulations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Arrangement of regulations. 2501.104-2 Section 2501.104-2 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION... material in the FAR, Parts 70 and up are used by the NSFAR. Where the subject matter in the FAR requires no...

48 CFR 2501.104-2 - Arrangement of regulations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Arrangement of regulations. 2501.104-2 Section 2501.104-2 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION... material in the FAR, Parts 70 and up are used by the NSFAR. Where the subject matter in the FAR requires no...

34 CFR 462.2 - What regulations apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 3 2011-07-01 2011-07-01 false What regulations apply? 462.2 Section 462.2 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION MEASURING EDUCATIONAL GAIN IN THE NATIONAL REPORTING SYSTEM FOR ADULT EDUCATION...

34 CFR 462.2 - What regulations apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false What regulations apply? 462.2 Section 462.2 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION MEASURING EDUCATIONAL GAIN IN THE NATIONAL REPORTING SYSTEM FOR ADULT EDUCATION...

Moisturizing alcohol hand gels for surgical hand preparation.

PubMed

Jones, R D; Jampani, H; Mulberry, G; Rizer, R L

2000-03-01

With the use of novel formulary technology, unique moisturizing hand gels have been developed that offer significant advantages in perioperative and other health care settings. These advantages include the time-saving capabilities of a waterless formulation, the persistence and effectiveness of a surgical scrub, and the moisturization and protective properties of a lotion. Extensive laboratory and clinical studies, involving in vivo antimicrobial activity against resident and transient flora, skin moisturization on normal and dry skin, and compatibility with latex gloves, have supported these advantages. Nondrying alcohol hand gels can be used for antiseptic hand washing, hand scrubs between procedures (i.e., reentry scrubs), brushless surgical scrubs, moisturizers, and glove-donning aids.

50 CFR 216.2 - Scope of regulations.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF COMMERCE MARINE MAMMALS REGULATIONS GOVERNING THE TAKING AND IMPORTING OF MARINE MAMMALS Introduction § 216.2 Scope of regulations. This part 216 applies solely to marine mammals and marine mammal products as defined in § 216.3. For regulations under the MMPA, with respect to other marine mammals and...

Quantifying the Hawthorne Effect in Hand Hygiene Compliance Through Comparing Direct Observation With Automated Hand Hygiene Monitoring.

PubMed

Hagel, Stefan; Reischke, Jana; Kesselmeier, Miriam; Winning, Johannes; Gastmeier, Petra; Brunkhorst, Frank M; Scherag, André; Pletz, Mathias W

2015-08-01

To quantify the Hawthorne effect of hand hygiene performance among healthcare workers using direct observation. Prospective observational study. Intensive care unit, university hospital. Direct observation of hand hygiene compliance over 48 audits of 2 hours each. Simultaneously, hand hygiene events (HHEs) were recorded using electronic alcohol-based handrub dispensers. Directly observed and electronically recorded HHEs during the 2 hours of direct observation were compared using Spearman correlations and Bland-Altman plots. To quantify the Hawthorne effect, we compared the number of electronically recorded HHEs during the direct observation periods with the re-scaled electronically recorded HHEs in the 6 remaining hours of the 8-hour working shift. A total of 3,978 opportunities for hand hygiene were observed during the 96 hours of direct observation. Hand hygiene compliance was 51% (95% CI, 49%-53%). There was a strong positive correlation between directly observed compliance and electronically recorded HHEs (ρ=0.68 [95% CI, 0.49-0.81], P<.0001). In the 384 hours under surveillance, 4,180 HHEs were recorded by the electronic dispensers. Of those, 2,029 HHEs were recorded during the 96 hours in which direct observation was also performed, and 2,151 HHEs were performed in the remaining 288 hours of the same working shift that were not under direct observation. Healthcare workers performed 8 HHEs per hour when not under observation compared with 21 HHEs per hour during observation. Directly and electronically observed HHEs were in agreement. We observed a marked influence of the Hawthorne effect on hand hygiene performance.

7 CFR 301.50-2 - Regulated articles.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Regulated articles. 301.50-2 Section 301.50-2... articles. The following are regulated articles: (a) Pine products (Pinus spp.), as follows: Bark products... pine wreaths and garlands; and stumps. (b) Any article, product, or means of conveyance not covered by...

7 CFR 301.50-2 - Regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.50-2 Section 301.50-2... articles. The following are regulated articles: (a) Pine products (Pinus spp.), as follows: Bark products... pine wreaths and garlands; and stumps. (b) Any article, product, or means of conveyance not covered by...

7 CFR 301.50-2 - Regulated articles.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Regulated articles. 301.50-2 Section 301.50-2... articles. The following are regulated articles: (a) Pine products (Pinus spp.), as follows: Bark products... pine wreaths and garlands; and stumps. (b) Any article, product, or means of conveyance not covered by...

7 CFR 301.50-2 - Regulated articles.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Regulated articles. 301.50-2 Section 301.50-2... articles. The following are regulated articles: (a) Pine products (Pinus spp.), as follows: Bark products... pine wreaths and garlands; and stumps. (b) Any article, product, or means of conveyance not covered by...

7 CFR 301.50-2 - Regulated articles.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Regulated articles. 301.50-2 Section 301.50-2... articles. The following are regulated articles: (a) Pine products (Pinus spp.), as follows: Bark products... pine wreaths and garlands; and stumps. (b) Any article, product, or means of conveyance not covered by...

Negative Regulation of Type 2 Immunity

PubMed Central

de Kouchkovsky, Dimitri A.; Ghosh, Sourav; Rothlin, Carla V.

2017-01-01

Type 2 immunity encompasses the mechanisms through which the immune system responds to helminths and an array of environmental substances such as allergens. In the developing world, billions of individuals are chronically infected with endemic parasitic helminths. In comparison, in the industrialized world, millions of individuals suffer from dysregulated type 2 immunity, referred to clinically as atopic diseases including asthma, allergic rhinitis and atopic dermatitis. Thus, type 2 immunity must be carefully regulated to mount protective host response yet avoid inappropriate activation and immunopathology. In this review, we describe the keys players and connections at play in type 2 responses and focus on the emerging mechanisms involved in the negative regulation of type 2 immunity. PMID:28082101

7 CFR 301.53-2 - Regulated articles.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Regulated articles. 301.53-2 Section 301.53-2... articles. The following are regulated articles: (a) The emerald ash borer; firewood of all hardwood (non... article, product, or means of conveyance not listed in paragraph (a) of this section may be designated as...

7 CFR 301.53-2 - Regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.53-2 Section 301.53-2... articles. The following are regulated articles: (a) The emerald ash borer; firewood of all hardwood (non... article, product, or means of conveyance not listed in paragraph (a) of this section may be designated as...

7 CFR 301.53-2 - Regulated articles.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Regulated articles. 301.53-2 Section 301.53-2... articles. The following are regulated articles: (a) The emerald ash borer; firewood of all hardwood (non... article, product, or means of conveyance not listed in paragraph (a) of this section may be designated as...

7 CFR 301.53-2 - Regulated articles.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Regulated articles. 301.53-2 Section 301.53-2... articles. The following are regulated articles: (a) The emerald ash borer; firewood of all hardwood (non... article, product, or means of conveyance not listed in paragraph (a) of this section may be designated as...

7 CFR 301.53-2 - Regulated articles.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Regulated articles. 301.53-2 Section 301.53-2... articles. The following are regulated articles: (a) The emerald ash borer; firewood of all hardwood (non... article, product, or means of conveyance not listed in paragraph (a) of this section may be designated as...

Effect of hand paddles and parachute on butterfly coordination.

PubMed

Telles, Thiago; Barroso, Renato; Barbosa, Augusto Carvalho; Salgueiro, Diego Fortes de Souza; Colantonio, Emilson; Andries Júnior, Orival

2015-01-01

This study investigated the effects of hand paddles, parachute and hand paddles plus parachute on the inter-limb coordination of butterfly swimming. Thirteen male swimmers were evaluated in four random maximal intensity conditions: without equipment, with hand paddles, with parachute and with hand paddles + parachute. Arm and leg stroke phases were identified by 2D video analysis to calculate the total time gap (T1: time between hands' entry in the water and high break-even point of the first undulation; T2: time between the beginning of the hand's backward movement and low break-even point of the first undulation; T3: time between the hand's arrival in a vertical plane to the shoulders and high break-even point of the second undulation; T4: time between the hand's release from the water and low break-even point of the second undulation). The swimming velocity was reduced and T1, T2 and T3 increased in parachute and hand paddles + parachute. No changes were observed in T4. Total time gap decreased in parachute and hand paddles + parachute. It is concluded that hand paddles do not influence the arm-to-leg coordination in butterfly, while parachute and hand paddles + parachute do change it, providing a greater propulsive continuity.

Less and less-influence of volume on hand coverage and bactericidal efficacy in hand disinfection.

PubMed

Kampf, Günter; Ruselack, Sigunde; Eggerstedt, Sven; Nowak, Nicolas; Bashir, Muhammad

2013-10-10

Some manufacturers recommend using 1.1 mL per application of alcohol-based handrubs for effective hand disinfection. However, whether this volume is sufficient to cover both hands, as recommended by the World Health Organization, and fulfills current efficacy standards is unknown. This study aimed to determine hand coverage for three handrubs (two gels based on 70% v/v and 85% w/w ethanol and a foam based on 70% v/v ethanol) applied at various volumes. Products were tested at product volumes of 1.1 mL, 2 mL, 2.4 mL as well as 1 and 2 pump dispenser pushes; the foam product was tested in addition at foam volumes of 1.1 mL, 2 mL, and 2.4 mL. Products were supplemented with a fluorescent dye and 15 participants applied products using responsible application techniques without any specific steps but the aim of completely covering both hands. Coverage quality was determined under ultraviolet light by two blinded investigators. Efficacy of the three handrubs was determined according to ASTM E 1174-06 and ASTM E 2755-10. For each experiment, the hands of 12 participants were contaminated with Serratia marcescens and the products applied as recommended (1.1 mL for 70% v/v ethanol products; 2 mL for the 85% w/w ethanol product). Log10-reduction was calculated. Volumes < 2 mL yielded high rates of incomplete coverage (67%-87%) whereas volumes ≥ 2 mL gave lower rates (13%-53%). Differences in coverage were significant between the five volumes tested for all handrubs (p < 0.001; two-way ANOVA) but not between the three handrubs themselves (p = 0.796). Application of 1.1 mL of 70% v/v ethanol rubs reduced contamination by 1.85 log10 or 1.60 log10 (ASTM E 1174-06); this failed the US FDA efficacy requirement of at least 2 log10. Application of 2 mL of the 85% w/w ethanol rub reduced contamination by 2.06 log10 (ASTM E 1174-06), fulfilling the US FDA efficacy requirement. Similar results were obtained according to ASTM E 2755-10. Our data indicated that

Less and less–influence of volume on hand coverage and bactericidal efficacy in hand disinfection

PubMed Central

2013-01-01

Background Some manufacturers recommend using 1.1 mL per application of alcohol-based handrubs for effective hand disinfection. However, whether this volume is sufficient to cover both hands, as recommended by the World Health Organization, and fulfills current efficacy standards is unknown. This study aimed to determine hand coverage for three handrubs (two gels based on 70% v/v and 85% w/w ethanol and a foam based on 70% v/v ethanol) applied at various volumes. Methods Products were tested at product volumes of 1.1 mL, 2 mL, 2.4 mL as well as 1 and 2 pump dispenser pushes; the foam product was tested in addition at foam volumes of 1.1 mL, 2 mL, and 2.4 mL. Products were supplemented with a fluorescent dye and 15 participants applied products using responsible application techniques without any specific steps but the aim of completely covering both hands. Coverage quality was determined under ultraviolet light by two blinded investigators. Efficacy of the three handrubs was determined according to ASTM E 1174-06 and ASTM E 2755-10. For each experiment, the hands of 12 participants were contaminated with Serratia marcescens and the products applied as recommended (1.1 mL for 70% v/v ethanol products; 2 mL for the 85% w/w ethanol product). Log10-reduction was calculated. Results Volumes < 2 mL yielded high rates of incomplete coverage (67%–87%) whereas volumes ≥ 2 mL gave lower rates (13%–53%). Differences in coverage were significant between the five volumes tested for all handrubs (p < 0.001; two-way ANOVA) but not between the three handrubs themselves (p = 0.796). Application of 1.1 mL of 70% v/v ethanol rubs reduced contamination by 1.85 log10 or 1.60 log10 (ASTM E 1174-06); this failed the US FDA efficacy requirement of at least 2 log10. Application of 2 mL of the 85% w/w ethanol rub reduced contamination by 2.06 log10 (ASTM E 1174-06), fulfilling the US FDA efficacy requirement. Similar results were obtained according to ASTM E 2755

Recognizing the Operating Hand and the Hand-Changing Process for User Interface Adjustment on Smartphones.

PubMed

Guo, Hansong; Huang, He; Huang, Liusheng; Sun, Yu-E

2016-08-20

As the size of smartphone touchscreens has become larger and larger in recent years, operability with a single hand is getting worse, especially for female users. We envision that user experience can be significantly improved if smartphones are able to recognize the current operating hand, detect the hand-changing process and then adjust the user interfaces subsequently. In this paper, we proposed, implemented and evaluated two novel systems. The first one leverages the user-generated touchscreen traces to recognize the current operating hand, and the second one utilizes the accelerometer and gyroscope data of all kinds of activities in the user's daily life to detect the hand-changing process. These two systems are based on two supervised classifiers constructed from a series of refined touchscreen trace, accelerometer and gyroscope features. As opposed to existing solutions that all require users to select the current operating hand or confirm the hand-changing process manually, our systems follow much more convenient and practical methods and allow users to change the operating hand frequently without any harm to the user experience. We conduct extensive experiments on Samsung Galaxy S4 smartphones, and the evaluation results demonstrate that our proposed systems can recognize the current operating hand and detect the hand-changing process with 94.1% and 93.9% precision and 94.1% and 93.7% True Positive Rates (TPR) respectively, when deciding with a single touchscreen trace or accelerometer-gyroscope data segment, and the False Positive Rates (FPR) are as low as 2.6% and 0.7% accordingly. These two systems can either work completely independently and achieve pretty high accuracies or work jointly to further improve the recognition accuracy.

Novel calcium recognition constructions in proteins: Calcium blade and EF-hand zone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denesyuk, Alexander I., E-mail: adenesyu@abo.fi; Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino 142290; Permyakov, Sergei E.

Metal ions can regulate various cell processes being first, second or third messengers, and some of them, especially transition metal ions, take part in catalysis in many enzymes. As an intracellular ion, Ca{sup 2+} is involved in many cellular functions from fertilization and contraction, cell differentiation and proliferation, to apoptosis and cancer. Here, we have identified and described two novel calcium recognition environments in proteins: the calcium blade zone and the EF-hand zone, common to 12 and 8 different protein families, respectively. Each of the two environments contains three distinct structural elements: (a) the well-known characteristic Dx[DN]xDG motif; (b) anmore » adjacent structurally identical segment, which binds metal ion in the same way between the calcium blade zone and the EF-hand zone; and (c) the following structurally variable segment, which distinguishes the calcium blade zone from the EF-hand zone. Both zones have sequence insertions between the last residue of the zone and calcium-binding residues in positions V or VI. The long insertion often connects the active and the calcium-binding sites in proteins. Using the structurally identical segments as an anchor, we were able to construct the classical calmodulin type EF-hand calcium-binding site out of two different calcium-binding motifs from two unrelated proteins.« less

Hand preference for sending mobile-phone text messages: associations with sex, writing hand, and throwing hand.

PubMed

Lambert, Anthony; Hallett, Charlene

2009-07-01

Hand preference for sending mobile-phone text messages ("texting") and its relationship with hand preference for other activities were investigated in a questionnaire study with 886 participants. Overall rates of both sinistrality and dextrality were reduced for texting, in comparison with other activities, due to the substantial number of individuals who use both hands simultaneously when performing this activity. Because they both involve verbal expression, it was hypothesised that the association between hand preferences for texting and writing might be stronger than the association between either of these tasks and more spatial activities, such as throwing. This prediction was not confirmed, either in the sample as a whole or in a sub-group of individuals who reported writing and throwing with opposite hands. Females were less likely than males to use their left hand when sending text messages. Implications of these findings are discussed, in relation to theoretical views of handedness and in relation to practical aspects of mobile-phone design.

Thyroid Hormone-Induced Hypertrophy in Mesenchymal Stem Cell Chondrogenesis Is Mediated by Bone Morphogenetic Protein-4

PubMed Central

Karl, Alexandra; Olbrich, Norman; Pfeifer, Christian; Berner, Arne; Zellner, Johannes; Kujat, Richard; Angele, Peter; Nerlich, Michael

2014-01-01

Chondrogenic differentiating mesenchymal stem cells (MSCs) express markers of hypertrophic growth plate chondrocytes. As hypertrophic cartilage undergoes ossification, this is a concern for the application of MSCs in articular cartilage tissue engineering. To identify mechanisms that elicit this phenomenon, we used an in vitro hypertrophy model of chondrifying MSCs for differential gene expression analysis and functional experiments with the focus on bone morphogenetic protein (BMP) signaling. Hypertrophy was induced in chondrogenic MSC pellet cultures by transforming growth factor β (TGFβ) and dexamethasone withdrawal and addition of triiodothyronine. Differential gene expression analysis of BMPs and their receptors was performed. Based on these results, the in vitro hypertrophy model was used to investigate the effect of recombinant BMP4 and the BMP inhibitor Noggin. The enhancement of hypertrophy could be shown clearly by an increased cell size, alkaline phosphatase activity, and collagen type X deposition. Upon induction of hypertrophy, BMP4 and the BMP receptor 1B were upregulated. Addition of BMP4 further enhanced hypertrophy in the absence, but not in the presence of TGFβ and dexamethasone. Thyroid hormone induced hypertrophy by upregulation of BMP4 and this induced enhancement of hypertrophy could be blocked by the BMP antagonist Noggin. BMP signaling is an important modulator of the late differentiation stages in MSC chondrogenesis and the thyroid hormone induces this pathway. As cartilage tissue engineering constructs will be exposed to this factor in vivo, this study provides important insight into the biology of MSC-based cartilage. Furthermore, the possibility to engineer hypertrophic cartilage may be helpful for critical bone defect repair. PMID:23937304

9 CFR 2.26 - Acknowledgment of regulations and standards.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Acknowledgment of regulations and standards. 2.26 Section 2.26 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Registration § 2.26 Acknowledgment of regulations and...

9 CFR 2.26 - Acknowledgment of regulations and standards.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Acknowledgment of regulations and standards. 2.26 Section 2.26 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Registration § 2.26 Acknowledgment of regulations and...

9 CFR 2.26 - Acknowledgment of regulations and standards.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Acknowledgment of regulations and standards. 2.26 Section 2.26 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Registration § 2.26 Acknowledgment of regulations and...

9 CFR 2.26 - Acknowledgment of regulations and standards.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Acknowledgment of regulations and standards. 2.26 Section 2.26 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Registration § 2.26 Acknowledgment of regulations and...

9 CFR 2.26 - Acknowledgment of regulations and standards.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Acknowledgment of regulations and standards. 2.26 Section 2.26 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Registration § 2.26 Acknowledgment of regulations and...

Restoring the IL-1β/NF-κB-induced impaired chondrogenesis by diallyl disulfide in human adipose-derived mesenchymal stem cells via attenuation of reactive oxygen species and elevation of antioxidant enzymes.

PubMed

Bahrampour Juybari, Kobra; Kamarul, Tunku; Najafi, Mohammad; Jafari, Davood; Sharifi, Ali Mohammad

2018-03-26

Strategies based on mesenchymal stem cell (MSC) therapy for restoring injured articular cartilage are not effective enough in osteoarthritis (OA). Due to the enhanced inflammation and oxidative stress in OA microenvironment, differentiation of MSCs into chondrocytes would be impaired. This study aims to explore the effects of diallyl disulfide (DADS) on IL-1β-mediated inflammation and oxidative stress in human adipose derived mesenchymal stem cells (hADSCs) during chondrogenesis. MTT assay was employed to examine the effects of various concentrations of DADS on the viability of hADSCs at different time scales to obtain non-cytotoxic concentration range of DADS. The effects of DADS on IL-1β-induced intracellular ROS generation and lipid peroxidation were evaluated in hADSCs. Western blotting was used to analyze the protein expression levels of IκBα (np), IκBα (p), NF-κB (np) and NF-κB (p). Furthermore, the gene expression levels of antioxidant enzymes in hADSCs and chondrogenic markers at days 7, 14 and 21 of differentiation were measured using qRT-PCR. The results showed that addition of DADS significantly enhanced the mRNA expression levels of antioxidant enzymes as well as reduced ROS elevation, lipid peroxidation, IκBα activation and NF-κB nuclear translocation in hADSCs treated with IL-1β. In addition, DADS could significantly increase the expression levels of IL-1β-induced impaired chondrogenic marker genes in differentiated hADSCs. Treatment with DADS may provide an effective approach to prevent the pro-inflammatory cytokines and oxidative stress as catabolic causes of chondrocyte cell death and enhance the protective anabolic effects by promoting chondrogenesis associated gene expressions in hADSCs exposed to OA condition.

p63 regulates glutaminase 2 expression

PubMed Central

Giacobbe, Arianna; Bongiorno-Borbone, Lucilla; Bernassola, Francesca; Terrinoni, Alessandro; Markert, Elke Katrin; Levine, Arnold J.; Feng, Zhaohui; Agostini, Massimilano; Zolla, Lello; Agrò, Alessandro Finazzi; Notterman, Daniel A.; Melino, Gerry; Peschiaroli, Angelo

2013-01-01

The transcription factor p63 is critical for many biological processes, including development and maintenance of epidermal tissues and tumorigenesis. Here, we report that the TAp63 isoforms regulate cell metabolism through the induction of the mitochondrial glutaminase 2 (GLS2) gene both in primary cells and tumor cell lines. By ChIP analysis and luciferase assay, we confirmed that TAp63 binds directly to the p53/p63 consensus DNA binding sequence within the GLS2 promoter region. Given the critical role of p63 in epidermal differentiation, we have investigated the regulation of GLS2 expression during this process. GLS2 and TAp63 expression increases during the in vitro differentiation of primary human keratinocytes, and depletion of GLS2 inhibits skin differentiation both at molecular and cellular levels. We found that GLS2 and TAp63 expression are concomitantly induced in cancer cells exposed to oxidative stresses. siRNA-mediated depletion of GLS2 sensitizes cells to ROS-induced apoptosis, suggesting that the TAp63/GLS2 axis can be functionally important as a cellular antioxidant pathway in the absence of p53. Accordingly, we found that GLS2 is upregulated in colon adenocarcinoma. Altogether, our findings demonstrate that GLS2 is a bona fide TAp63 target gene, and that the TAp63-dependent regulation of GLS2 is important for both physiological and pathological processes. PMID:23574722

Cytomegalovirus Survival and Transferability and the Effectiveness of Common Hand-Washing Agents against Cytomegalovirus on Live Human Hands

PubMed Central

Stowell, Jennifer D.; Forlin-Passoni, Daniela; Radford, Kay; Bate, Sheri L.; Dollard, Sheila C.; Bialek, Stephanie R.; Cannon, Michael J.

2014-01-01

Congenital cytomegalovirus (CMV) transmission can occur when women acquire CMV while pregnant. Infection control guidelines may reduce risk for transmission. We studied the duration of CMV survival after application of bacteria to the hands and after transfer from the hands to surfaces and the effectiveness of cleansing with water, regular and antibacterial soaps, sanitizer, and diaper wipes. Experiments used CMV AD169 in saliva at initial titers of 1 × 105 infectious particles/ml. Samples from hands or surfaces (points between 0 and 15 min) were placed in culture and observed for at least 2 weeks. Samples were also tested using CMV real-time PCR. After application of bacteria to the hands, viable CMV was recovered from 17/20 swabs at 0 min, 18/20 swabs at 1 min, 5/20 swabs at 5 min, and 4/20 swabs at 15 min. After transfer, duration of survival was at least 15 min on plastic (1/2 swabs), 5 min on crackers and glass (3/4 swabs), and 1 min or less on metal and cloth (3/4 swabs); no viable virus was collected from wood, rubber, or hands. After cleansing, no viable virus was recovered using water (0/22), plain soap (0/20), antibacterial soap (0/20), or sanitizer (0/22). Viable CMV was recovered from 4/20 hands 10 min after diaper wipe cleansing. CMV remains viable on hands for sufficient times to allow transmission. CMV may be transferred to surfaces with reduced viability. Hand-cleansing methods were effective at eliminating viable CMV from hands. PMID:24185855

Cytomegalovirus survival and transferability and the effectiveness of common hand-washing agents against cytomegalovirus on live human hands.

PubMed

Stowell, Jennifer D; Forlin-Passoni, Daniela; Radford, Kay; Bate, Sheri L; Dollard, Sheila C; Bialek, Stephanie R; Cannon, Michael J; Schmid, D Scott

2014-01-01

Congenital cytomegalovirus (CMV) transmission can occur when women acquire CMV while pregnant. Infection control guidelines may reduce risk for transmission. We studied the duration of CMV survival after application of bacteria to the hands and after transfer from the hands to surfaces and the effectiveness of cleansing with water, regular and antibacterial soaps, sanitizer, and diaper wipes. Experiments used CMV AD169 in saliva at initial titers of 1 × 10(5) infectious particles/ml. Samples from hands or surfaces (points between 0 and 15 min) were placed in culture and observed for at least 2 weeks. Samples were also tested using CMV real-time PCR. After application of bacteria to the hands, viable CMV was recovered from 17/20 swabs at 0 min, 18/20 swabs at 1 min, 5/20 swabs at 5 min, and 4/20 swabs at 15 min. After transfer, duration of survival was at least 15 min on plastic (1/2 swabs), 5 min on crackers and glass (3/4 swabs), and 1 min or less on metal and cloth (3/4 swabs); no viable virus was collected from wood, rubber, or hands. After cleansing, no viable virus was recovered using water (0/22), plain soap (0/20), antibacterial soap (0/20), or sanitizer (0/22). Viable CMV was recovered from 4/20 hands 10 min after diaper wipe cleansing. CMV remains viable on hands for sufficient times to allow transmission. CMV may be transferred to surfaces with reduced viability. Hand-cleansing methods were effective at eliminating viable CMV from hands.

48 CFR 245.7311-2 - Safety, security, and fire regulations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Safety, security, and fire regulations. 245.7311-2 Section 245.7311-2 Federal Acquisition Regulations System DEFENSE ACQUISITION... Inventory 245.7311-2 Safety, security, and fire regulations. ...

7 CFR 301.87-2 - Regulated articles.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Regulations § 301.87-2 Regulated articles. (a) Sugarcane plants, whole or in part, including true seed and... for extracting and refining sugarcane juice; and experimental devices, such as devices used for...

7 CFR 301.87-2 - Regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Regulations § 301.87-2 Regulated articles. (a) Sugarcane plants, whole or in part, including true seed and... for extracting and refining sugarcane juice; and experimental devices, such as devices used for...

7 CFR 301.87-2 - Regulated articles.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Regulations § 301.87-2 Regulated articles. (a) Sugarcane plants, whole or in part, including true seed and... for extracting and refining sugarcane juice; and experimental devices, such as devices used for...

7 CFR 301.87-2 - Regulated articles.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Regulations § 301.87-2 Regulated articles. (a) Sugarcane plants, whole or in part, including true seed and... for extracting and refining sugarcane juice; and experimental devices, such as devices used for...

7 CFR 301.87-2 - Regulated articles.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Regulations § 301.87-2 Regulated articles. (a) Sugarcane plants, whole or in part, including true seed and... for extracting and refining sugarcane juice; and experimental devices, such as devices used for...

Antiaging Gene Klotho Enhances Glucose-Induced Insulin Secretion by Up-Regulating Plasma Membrane Levels of TRPV2 in MIN6 β-Cells

PubMed Central

Lin, Yi

2012-01-01

Klotho is a recently discovered antiaging gene. Klotho is expressed in mouse pancreatic islets and in insulinoma β-cells (MIN6 β-cells). The purpose of this study was to investigate whether Klotho plays a role in the regulation of insulin secretion in MIN6 β-cells by overexpression and silencing of Klotho. It is interesting that overexpression of Klotho increased glucose-induced insulin secretion in MIN6 β-cells. Overexpression of mouse Klotho protein also significantly increased plasma membrane levels of transient receptor potential V2 (TRPV2), calcium entry, and the glucose-induced increase in intracellular calcium. On the other hand, knockdown of Klotho by siRNA significantly decreased plasma membrane levels of TRPV2 and attenuated glucose-induced calcium entry and insulin secretion. Tranilast, a selective inhibitor of TRPV2, abolished the promoting effects of overexpression of Klotho on glucose-induced calcium entry and insulin secretion in MIN6 cells. Thus, TRPV2 lies in the downstream of Klotho in the regulation of glucose-induced insulin secretion. This study demonstrated, for the first time, that Klotho may enhance glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 and thus glucose-induced calcium responses. These findings reveal a previously unidentified role of Klotho in the regulation of glucose-induced insulin secretion in MIN6 β-cells. PMID:22597535

Antiaging gene Klotho enhances glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 in MIN6 β-cells.

PubMed

Lin, Yi; Sun, Zhongjie

2012-07-01

Klotho is a recently discovered antiaging gene. Klotho is expressed in mouse pancreatic islets and in insulinoma β-cells (MIN6 β-cells). The purpose of this study was to investigate whether Klotho plays a role in the regulation of insulin secretion in MIN6 β-cells by overexpression and silencing of Klotho. It is interesting that overexpression of Klotho increased glucose-induced insulin secretion in MIN6 β-cells. Overexpression of mouse Klotho protein also significantly increased plasma membrane levels of transient receptor potential V2 (TRPV2), calcium entry, and the glucose-induced increase in intracellular calcium. On the other hand, knockdown of Klotho by siRNA significantly decreased plasma membrane levels of TRPV2 and attenuated glucose-induced calcium entry and insulin secretion. Tranilast, a selective inhibitor of TRPV2, abolished the promoting effects of overexpression of Klotho on glucose-induced calcium entry and insulin secretion in MIN6 cells. Thus, TRPV2 lies in the downstream of Klotho in the regulation of glucose-induced insulin secretion. This study demonstrated, for the first time, that Klotho may enhance glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 and thus glucose-induced calcium responses. These findings reveal a previously unidentified role of Klotho in the regulation of glucose-induced insulin secretion in MIN6 β-cells.

Hmga2 regulates self-renewal of retinal progenitors.

PubMed

Parameswaran, Sowmya; Xia, Xiaohuan; Hegde, Ganapati; Ahmad, Iqbal

2014-11-01

In vertebrate retina, histogenesis occurs over an extended period. To sustain the temporal generation of diverse cell types, retinal progenitor cells (RPCs) must self-renew. However, self-renewal and regulation of RPCs remain poorly understood. Here, we demonstrate that cell-extrinsic factors coordinate with the epigenetic regulator high-mobility group AT-hook 2 (Hmga2) to regulate self-renewal of late retinal progenitor cells (RPCs). We observed that a small subset of RPCs was capable of clonal propagation and retained multipotentiality of parents in the presence of endothelial cells (ECs), known self-renewal regulators in various stem cell niches. The self-renewing effects, also observed in vivo, involve multiple intercellular signaling pathways, engaging Hmga2. As progenitors exhaust during retinal development, expression of Hmga2 progressively decreases. Analyses of Hmga2-expression perturbation, in vitro and in vivo, revealed that Hmga2 functionally helps to mediate cell-extrinsic influences on late-retinal progenitor self-renewal. Our results provide a framework for integrating the diverse intercellular influences elicited by epigenetic regulators for self-renewal in a dynamic stem cell niche: the developing vertebrate retina. © 2014. Published by The Company of Biologists Ltd.

Hand washing frequencies and procedures used in retail food services.

PubMed

Strohbehn, Catherine; Sneed, Jeannie; Paez, Paola; Meyer, Janell

2008-08-01

Transmission of viruses, bacteria, and parasites to food by way of improperly washed hands is a major contributing factor in the spread of foodborne illnesses. Field observers have assessed compliance with hand washing regulations, yet few studies have included consideration of frequency and methods used by sectors of the food service industry or have included benchmarks for hand washing. Five 3-h observation periods of employee (n = 80) hand washing behaviors during menu production, service, and cleaning were conducted in 16 food service operations for a total of 240 h of direct observation. Four operations from each of four sectors of the retail food service industry participated in the study: assisted living for the elderly, childcare, restaurants, and schools. A validated observation form, based on 2005 Food Code guidelines, was used by two trained researchers. Researchers noted when hands should have been washed, when hands were washed, and how hands were washed. Overall compliance with Food Code recommendations for frequency during production, service, and cleaning phases ranged from 5% in restaurants to 33% in assisted living facilities. Procedural compliance rates also were low. Proposed benchmarks for the number of times hand washing should occur by each employee for each sector of food service during each phase of operation are seven times per hour for assisted living, nine times per hour for childcare, 29 times per hour for restaurants, and 11 times per hour for schools. These benchmarks are high, especially for restaurant employees. Implementation would mean lost productivity and potential for dermatitis; thus, active managerial control over work assignments is needed. These benchmarks can be used for training and to guide employee hand washing behaviors.

29 CFR 780.310 - Exemption for local hand harvest laborers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Employment in Agriculture That Is Exempted From the Minimum Wage and Overtime Pay Requirements Under Section... 29 Labor 3 2010-07-01 2010-07-01 false Exemption for local hand harvest laborers. 780.310 Section 780.310 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR...

MeCP2 regulates ethanol sensitivity and intake.

PubMed

Repunte-Canonigo, Vez; Chen, Jihuan; Lefebvre, Celine; Kawamura, Tomoya; Kreifeldt, Max; Basson, Oan; Roberts, Amanda J; Sanna, Pietro Paolo

2014-09-01

We have investigated the expression of chromatin-regulating genes in the prefrontal cortex and in the shell subdivision of the nucleus accumbens during protracted withdrawal in mice with increased ethanol drinking after chronic intermittent ethanol (CIE) vapor exposure and in mice with a history of non-dependent drinking. We observed that the methyl-CpG binding protein 2 (MeCP2) was one of the few chromatin-regulating genes to be differentially regulated by a history of dependence. As MeCP2 has the potential of acting as a broad gene regulator, we investigated sensitivity to ethanol and ethanol drinking in MeCP2(308/) (Y) mice, which harbor a truncated MeCP2 allele but have a milder phenotype than MeCP2 null mice. We observed that MeCP2(308/) (Y) mice were more sensitive to ethanol's stimulatory and sedative effects than wild-type (WT) mice, drank less ethanol in a limited access 2 bottle choice paradigm and did not show increased drinking after induction of dependence with exposure to CIE vapors. Alcohol metabolism did not differ in MeCP2(308/) (Y) and WT mice. Additionally, MeCP2(308/) (Y) mice did not differ from WT mice in ethanol preference in a 24-hour paradigm nor in their intake of graded solutions of saccharin or quinine, suggesting that the MeCP2(308/) (Y) mutation did not alter taste function. Lastly, using the Gene Set Enrichment Analysis algorithm, we found a significant overlap in the genes regulated by alcohol and by MeCP2. Together, these results suggest that MeCP2 contributes to the regulation of ethanol sensitivity and drinking. © 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.

Hand biometric recognition based on fused hand geometry and vascular patterns.

PubMed

Park, GiTae; Kim, Soowon

2013-02-28

A hand biometric authentication method based on measurements of the user's hand geometry and vascular pattern is proposed. To acquire the hand geometry, the thickness of the side view of the hand, the K-curvature with a hand-shaped chain code, the lengths and angles of the finger valleys, and the lengths and profiles of the fingers were used, and for the vascular pattern, the direction-based vascular-pattern extraction method was used, and thus, a new multimodal biometric approach is proposed. The proposed multimodal biometric system uses only one image to extract the feature points. This system can be configured for low-cost devices. Our multimodal biometric-approach hand-geometry (the side view of the hand and the back of hand) and vascular-pattern recognition method performs at the score level. The results of our study showed that the equal error rate of the proposed system was 0.06%.

50 CFR 15.2 - Scope of regulations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... BIRD CONSERVATION ACT Introduction and General Provisions § 15.2 Scope of regulations. (a) The regulations in this part apply to all species of exotic birds, as defined in section 15.3. (b) The provisions...

Planning maximally smooth hand movements constrained to nonplanar workspaces.

PubMed

Liebermann, Dario G; Krasovsky, Tal; Berman, Sigal

2008-11-01

The article characterizes hand paths and speed profiles for movements performed in a nonplanar, 2-dimensional workspace (a hemisphere of constant curvature). The authors assessed endpoint kinematics (i.e., paths and speeds) under the minimum-jerk model assumptions and calculated minimal amplitude paths (geodesics) and the corresponding speed profiles. The authors also calculated hand speeds using the 2/3 power law. They then compared modeled results with the empirical observations. In all, 10 participants moved their hands forward and backward from a common starting position toward 3 targets located within a hemispheric workspace of small or large curvature. Comparisons of modeled observed differences using 2-way RM-ANOVAs showed that movement direction had no clear influence on hand kinetics (p < .05). Workspace curvature affected the hand paths, which seldom followed geodesic lines. Constraining the paths to different curvatures did not affect the hand speed profiles. Minimum-jerk speed profiles closely matched the observations and were superior to those predicted by 2/3 power law (p < .001). The authors conclude that speed and path cannot be unambiguously linked under the minimum-jerk assumption when individuals move the hand in a nonplanar 2-dimensional workspace. In such a case, the hands do not follow geodesic paths, but they preserve the speed profile, regardless of the geometric features of the workspace.

Relative effectiveness of dominant versus non-dominant hand position for rescuer's side of approach during chest compressions between right-handed and left-handed novice rescuers.

PubMed

You, Je Sung; Kim, Hoon; Park, Jung Soo; Baek, Kyung Min; Jang, Mun Sun; Lee, Hye Sun; Chung, Sung Phil; Kim, SeungWhan

2015-03-01

The major components affecting high quality cardiopulmonary resuscitation (CPR) have been defined as the ability of the rescuer, hand position, position of the rescuer and victim, depth and rate of chest compressions, and fatigue. Until now, there have been no studies on dominant versus non-dominant hand position and the rescuer's side of approach. This study was designed to evaluate the effectiveness of hand position and approach side on the quality of CPR between right-handed (RH) and left-handed (LH) novice rescuers. 44 health science university students with no previous experience of basic life support (BLS) volunteered for the study. We divided volunteers into two groups by handedness. Adult BLS was performed on a manikin for 2 min in each session. The sequences were randomly performed on the manikin's left side of approach (Lap) with the rescuer's left hand in contact with the sternum (Lst), Lap/Rst, Rap/Lst and Rap/Rst. We compared the quality of chest compressions between the RH and LH groups according to predetermined positions. A significant decrease in mean compression depth between the two groups was only observed when rescuers performed in the Rap/Lst scenario, regardless of hand dominance. The frequency of correct hand placement also significantly decreased in the Lap/Rst position for the LH group. The performance of novice rescuers during chest compressions is influenced by the position of the dominant hand and the rescuer's side of approach. In CPR training and real world situations, a novice rescuer, regardless of handedness, should consider hand positions for contacting the sternum identical to the side of approach after approaching from the nearest and most accessible side, for optimal CPR performance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

49 CFR 236.202 - Signal governing movements over hand-operated switch.

Code of Federal Regulations, 2014 CFR

2014-10-01

... switch. 236.202 Section 236.202 Transportation Other Regulations Relating to Transportation (Continued...-operated switch. Signal governing movements over hand-operated switch in the facing direction shall display... over the switch in the normal and in the reverse position, the signal shall display its most...