Inhibition of gap junction and adherens junction assembly by connexin and A-CAM antibodies

We examined the roles of the extracellular domains of a gap junction protein and a cell adhesion molecule in gap junction and adherens junction formation by altering cell interactions with antibody Fab fragments. Using immunoblotting and immunocytochemistry we demonstrated that Novikoff cells contained the gap junction protein, connexin43 (Cx43), and the cell adhesion molecule, A-CAM (N-cadherin). Cells were dissociated in EDTA, allowed to recover, and reaggregated for 60 min in media containing Fab fragments prepared from a number of antibodies. We observed no cell-cell dye transfer 4 min after microinjection in 90% of the cell pairs treated with Fab fragments of antibodies for the first or second extracellular domain of Cx43, the second extracellular domain of connexin32 (Cx32) or A-CAM. Cell-cell dye transfer was detected within 30 s in cell pairs treated with control Fab fragments (pre-immune serum, antibodies to the rat major histocompatibility complex or the amino or carboxyl termii of Cx43). We observed no gap junctions by freeze-fracture EM and no adherens junctions by thin section EM between cells treated with the Fab fragments that blocked cell-cell dye transfer. Gap junctions were found on approximately 50% of the cells in control samples using freeze-fracture EM. We demonstrated with reaggregated Novikoff cells that: (a) functional interactions of the extracellular domains of the connexins were necessary for the formation of gap junction channels; (b) cell interactions mediated by A-CAM were required for gap junction assembly; and (c) Fab fragments of antibodies for A-CAM or connexin extracellular domains blocked adherens junction formation

Protoplanetary Disk Masses in the Young NGC 2024 Cluster

We present the results from a Submillimeter Array survey of the 887 micron continuum emission from the protoplanetary disks around 95 young stars in the young cluster NGC 2024. Emission was detected from 22 infrared sources, with flux densities from ~5 to 330 mJy; upper limits (at 3sigma) for the other 73 sources range from 3 to 24 mJy. For standard assumptions, the corresponding disk masses range from ~0.003 to 0.2Msolar, with upper limits at 0.002--0.01Msolar. The NGC 2024 sample has a slightly more populated tail at the high end of its disk mass distribution compared to other clusters, but without more information on the nature of the sample hosts it remains unclear if this difference is statistically significant or a superficial selection effect. Unlike in the Orion Trapezium, there is no evidence for a disk mass dependence on the (projected) separation from the massive star IRS2b in the NGC 2024 cluster. We suggest that this is due to either the cluster youth or a comparatively weaker photoionizing radiation field.Comment: ApJ, in pres

DISTRIBUCIÓN DE ROEDORES RESERVORIOS DEL VIRUS CAUSANTE DEL SÍNDROME PULMONAR POR HANTAVIRUS Y REGIONES DE POSIBLE RIESGO EN MÉXICO

We determined distributions of rodent species known as reservoirs of Sin Nombre virus, causal agent for the hantavirus pulmonary syndrome (HPS). In the absence of HPS cases reported in Mexico, this study aimed to identify potential risk regions for HPS based on distributions of these rodent reservoirs. We modeled species’ ecological niches and projected them as potential distributions using point occurrence data, environmental digital maps, the genetic algorithm GARP (Genetic Algorithm for Rule-set Prediction), and GIS. We determined potential distributions of three rodents known to serve as reservoirs for Sin Nombre virus, four additional rodent species that may also play a role, as well as all Peromsycus species, considered as potential reservoirs for Sin Nombre virus or other hantaviruses in Mexico. Geographic locations of HPS cases coincided significantly with modeled potential distributions of the three principal rodent reservoirs in the United States. In Mexico, distributions of rodent reservoirs and potential rodent reservoirs covered ample geographic regions. Rural human populations potentially exposed to HPS (living under marginal housing conditions and with a geographic coincidence with reservoir distributions), were estimated at 650,000 - 1,750,000 persons. The geographic coincidence between rodent reservoirs and HPS cases in the United States suggests that areas of high risk for HPS will be related to rodent reservoir distributions in Mexico. Since Mexico holds ecological and social conditions amply appropriate for HPS outbreaks, we predict that (1) HPS cases will be detected across broad geographic regions coinciding with rodent reservoir distributions in Mexico, and (2) HPS will prove to be more frequent in Mexico than in the United States.Se determinó la distribución geográfica de los roedores identificados como reservorios del virus Sin Nombre y otros posibles hantavirus en México, causante del síndrome pulmonar por hantavirus (SPH). Ante la ausencia de casos de SPH documentados en México, este estudio pretende identificar posibles regiones de riesgo, considerando la distribución geográfica de los roedores reservorios. Se modeló el nicho ecológico de las especies de roedores reservorios del virus, y se proyectó en mapas para estimar distribuciones potenciales, usando localidades de colecta, mapas ambientales digitales, el algoritmo genético de cómputo GARP (Genetic Algorithm for Rule-set Prediction, por sus siglas en inglés) y un sistema de información geográfico. Se incluyeron distribuciones potenciales de tres especies conocidas como reservorios importantes de hantavirus en Estados Unidos, cuatro especies de roedores que se consideran reservorios potenciales del virus en México y de todas las demás especies del género Peromyscus. Las localidades geográficas de los casos de SPH detectados en humanos en los Estados Unidos coincidieron de forma significativamente mayor que en un modelo al azar, con las distribuciones potenciales de los tres roedores reservorios. En México, los roedores reservorios y los roedores potencialmente reservorios, cubren extensas zonas geográficas, identificándose amplias regiones de posible riesgo de transmisión de hantavirus. La población potencialmente expuesta a la infección, considerando las características de vivienda rural y la distribución potencial de especies de roedores reservorios del virus, se estimó entre 650,000 y 1’750,000 personas. La coincidencia geográfica significativa entre la distribución de roedores reservorios con los casos de SPH reportados en los Estados Unidos, sugiere que la distribución de los roedores reservorios se correlaciona con áreas de riesgo de SPH. Ante la similitud entre México y las regiones de riesgo en los Estados Unidos respecto a sus condiciones biológicas, ecológicas y sociales propicias para la transmisión de SPH, predecimos que (1) en México se detectarán casos de SPH en amplias zonas geográficas, las cuales coinciden con las distribuciones de roedores reservorios y, (2) se va a registrar una mayor tasa de transmisión de SPH en México que en los Estados Unidos

Site-1 protease inhibits mitochondrial respiration by controlling the TGF-β target gene Mss51

The mitochondrial response to changes in cellular energy demand is necessary for cellular adaptation and organ function. Many genes are essential in orchestrating this response, including the transforming growth factor (TGF)-β1 target gene Mss51, an inhibitor of skeletal muscle mitochondrial respiration. Although Mss51 is implicated in the pathophysiology of obesity and musculoskeletal disease, how Mss51 is regulated is not entirely understood. Site-1 protease (S1P) is a key activator of several transcription factors required for cellular adaptation. However, the role of S1P in muscle is unknown. Here, we identify S1P as a negative regulator of muscle mass and mitochondrial respiration. S1P disruption in mouse skeletal muscle reduces Mss51 expression and increases muscle mass and mitochondrial respiration. The effects of S1P deficiency on mitochondrial activity are counteracted by overexpressing Mss51, suggesting that one way S1P inhibits respiration is by regulating Mss51. These discoveries expand our understanding of TGF-β signaling and S1P function

Prospects of micromass culture technology in tissue engineering

Tissue engineering of bone and cartilage tissue for subsequent implantation is of growing interest in cranio- and maxillofacial surgery. Commonly it is performed by using cells coaxed with scaffolds. Recently, there is a controversy concerning the use of artificial scaffolds compared to the use of a natural matrix. Therefore, new approaches called micromass technology have been invented to overcome these problems by avoiding the need for scaffolds. Technically, cells are dissociated and the dispersed cells are then reaggregated into cellular spheres. The micromass technology approach enables investigators to follow tissue formation from single cell sources to organised spheres in a controlled environment. Thus, the inherent fundamentals of tissue engineering are better revealed. Additionally, as the newly formed tissue is devoid of an artificial material, it resembles more closely the in vivo situation. The purpose of this review is to provide an insight into the fundamentals and the technique of micromass cell culture used to study bone tissue engineering

Methodological considerations for kinematic analysis of upper limbs in healthy and poststroke adults Part II: a systematic review of motion capture systems and kinematic metrics

To review the methods used to analyze the kinematics of upper limbs (ULs) of healthy and poststroke adults, namely the motion capture systems and kinematic metrics. A database of articles published in the last decade was compiled using the following search terms combinations: (“upper extremity” OR “upper limb” OR arm) AND (kinematic OR motion OR movement) AND (analysis OR assessment OR measurement). The articles included in this review: (1) had the purpose to analyze objectively three-dimension kinematics of ULs, (2) studied functional movements or activities of daily living involving ULs, and (3) studied healthy and/or poststroke adults. Fourteen articles were included (four studied a healthy sample, three analyzed poststroke patients, and seven examined both poststroke and healthy participants). Most articles used optoelectronic systems with markers; however, the presentation of laboratory and task-specific errors is missing. Markerless systems, used in some studies, seem to be promising alternatives for implementation of kinematic analysis in hospitals and clinics, but the literature proving their validity is scarce. Most articles analyzed “joint kinematics” and “end-point kinematics,” mainly related with reaching. The different stroke locations of the samples were not considered in their analysis and only three articles described their psychometric properties. Future research should validate portable motion capture systems, document their specific error at the acquisition place and for the studied task, include grasping and manipulation analysis, and describe psychometric properties.info:eu-repo/semantics/publishedVersio

Embryonic stem cells in scaffold-free three-dimensional cell culture: osteogenic differentiation and bone generation

Extracorporeal formation of mineralized bone-like tissue is still an unsolved challenge in tissue engineering. Embryonic stem cells may open up new therapeutic options for the future and should be an interesting model for the analysis of fetal organogenesis. Here we describe a technique for culturing embryonic stem cells (ESCs) in the absence of artificial scaffolds which generated mineralized miromasses. Embryonic stem cells were harvested and osteogenic differentiation was stimulated by the addition of dexamethasone, ascorbic acid, and ß-glycerolphosphate (DAG). After three days of cultivation microspheres were formed. These spherical three-dimensional cell units showed a peripheral zone consisting of densely packed cell layers surrounded by minerals that were embedded in the extracellular matrix. Alizarine red staining confirmed evidence of mineralization after 10 days of DAG stimulation in the stimulated but not in the control group. Transmission electron microscopy demonstrated scorching crystallites and collagenous fibrils as early indication of bone formation. These extracellular structures resembled hydroxyl apatite-like crystals as demonstrated by distinct diffraction patterns using electron diffraction analysis. The micromass culture technique is an appropriate model to form three-dimensional bone-like micro-units without the need for an underlying scaffold. Further studies will have to show whether the technique is applicable also to pluripotent stem cells of different origin

Can a Plantar Pressure-Based Tongue-Placed Electrotactile Biofeedback Improve Postural Control Under Altered Vestibular and Neck Proprioceptive Conditions?

We investigated the effects of a plantar pressure-based tongue-placed electrotactile biofeedback on postural control during quiet standing under normal and altered vestibular and neck proprioceptive conditions. To achieve this goal, fourteen young healthy adults were asked to stand upright as immobile as possible with their eyes closed in two Neutral and Extended head postures and two conditions of No-biofeedback and Biofeedback. The underlying principle of the biofeedback consisted of providing supplementary information related to foot sole pressure distribution through a wireless embedded tongue-placed tactile output device. Centre of foot pressure (CoP) displacements were recorded using a plantar pressure data acquisition system. Results showed that (1) the Extended head posture yielded increased CoP displacements relative to the Neutral head posture in the No-biofeedback condition, with a greater effect along the anteroposterior than mediolateral axis, whereas (2) no significant difference between the two Neutral and Extended head postures was observed in the Biofeedback condition. The present findings suggested that the availability of the plantar pressure-based tongue-placed electrotactile biofeedback allowed the subjects to suppress the destabilizing effect induced by the disruption of vestibular and neck proprioceptive inputs associated with the head extended posture. These results are discussed according to the sensory re-weighting hypothesis, whereby the central nervous system would dynamically and selectively adjust the relative contributions of sensory inputs (i.e., the sensory weights) to maintain upright stance depending on the sensory contexts and the neuromuscular constraints acting on the subject

Characteristics of outdoor falls among older people: A qualitative study

Background Falls are a major threat to older people’s health and wellbeing. Approximately half of falls occur in outdoor environments but little is known about the circumstances in which they occur. We conducted a qualitative study to explore older people’s experiences of outdoor falls to develop understanding of how they may be prevented. Methods We conducted nine focus groups across the UK (England, Wales, and Scotland). Our sample was from urban and rural settings and different environmental landscapes. Participants were aged 65+ and had at least one outdoor fall in the past year. We analysed the data using framework and content analyses. Results Forty-four adults aged 65 – 92 took part and reported their experience of 88 outdoor falls. Outdoor falls occurred in a variety of contexts, though reports suggested the following scenarios may have been more frequent: when crossing a road, in a familiar area, when bystanders were around, and with an unreported or unknown attribution. Most frequently, falls resulted in either minor or moderate injury, feeling embarrassed at the time of the fall, and anxiety about falling again. Ten falls resulted in fracture, but no strong pattern emerged in regard to the contexts of these falls. Anxiety about falling again appeared more prevalent among those that fell in urban settings and who made more visits into their neighbourhood in a typical week. Conclusions This exploratory study has highlighted several aspects of the outdoor environment that may represent risk factors for outdoor falls and associated fear of falling. Health professionals are recommended to consider outdoor environments as well as the home setting when working to prevent falls and increase mobility among older people

Optimizing Critical Illness Recovery: Perspectives and Solutions from the Caregivers of ICU Survivors

Objectives: To understand the unmet needs of caregivers of ICU survivors, how they accessed support post ICU, and the key components of beneficial ICU recovery support systems as identified from a caregiver perspective. Design: International, qualitative study. Subjects: We conducted 20 semistructured interviews with a diverse group of caregivers in the United States, the United Kingdom, and Australia, 11 of whom had interacted with an ICU recovery program. Setting: Seven hospitals in the United States, United Kingdom, and Australia. Interventions: None. Measurements and Main Results: Content analysis was used to explore prevalent themes related to unmet needs, as well as perceived strategies to improve ICU outcomes. Post-ICU care was perceived to be generally inadequate. Desired caregiver support fell into two main categories: practical support and emotional support. Successful care delivery initiatives included structured programs, such as post discharge telephone calls, home health programs, post-ICU clinics, and peer support groups, and standing information resources, such as written educational materials and online resources. Conclusions: This qualitative, multicenter, international study of caregivers of critical illness survivors identified consistently unmet needs, means by which caregivers accessed support post ICU, and several care mechanisms identified by caregivers as supporting optimal ICU recovery