Cell-Cell Contact Preserves Cell Viability via Plakoglobin

Control over cell viability is a fundamental property underlying numerous physiological processes. Cell spreading on a substrate was previously demonstrated to be a major factor in determining the viability of individual cells. In multicellular organisms, cell-cell contact is likely to play a significant role in regulating cell vitality, but its function is easily masked by cell-substrate interactions, thus remains incompletely characterized. In this study, we show that suspended immortalized human keratinocyte sheets with persisting intercellular contacts exhibited significant contraction, junctional actin localization, and reinforcement of cell-cell adhesion strength. Further, cells within these sheets remain viable, in contrast to trypsinized cells suspended without either cell-cell or cell-substrate contact, which underwent apoptosis at high rates. Suppression of plakoglobin weakened cell-cell adhesion in cell sheets and suppressed apoptosis in suspended, trypsinized cells. These results demonstrate that cell-cell contact may be a fundamental control mechanism governing cell viability and that the junctional protein plakoglobin is a key regulator of this process. Given the near-ubiquity of plakoglobin in multicellular organisms, these findings could have significant implications for understanding cell adhesion, modeling disease progression, developing therapeutics and improving the viability of tissue engineering protocols

A neuron-in-capillary platform for facile collection and mass spectrometric characterization of a secreted neuropeptide

The integration of microfluidic devices-which efficiently handle small liquid volumes-with separations/mass spectrometry (MS) is an effective approach for profiling the neurochemistry occurring in selected neurons. Interfacing the microfluidic cell culture to the mass spectrometer is challenging because of geometric and scaling issues. Here we demonstrate the hyphenation of a neuron-in-capillary platform to a solid phase extraction device and off-line MS. A primary neuronal culture of Aplysia californica neurons was established directly inside a cylindrical polyimide capillary. The approach also uses a particle-embedded monolith to condition neuropeptide releasates collected from several Aplysia neurons cultured in the capillary, with the subsequent characterization of released peptides via MS. This system presents a number of advances compared to more traditional microfluidic devices fabricated with polydimethylsiloxane. These include low cost, easy access to cell culture, rigidity, ease of transport, and minimal fluid handling. The cylindrical geometry of the platform allows convenient interface with a wide range of analytical tools that utilize capillary columnsclos

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Large-Scale Brain Networks in Board Game Experts: Insights from a Domain-Related Task and Task-Free Resting State

Cognitive performance relies on the coordination of large-scale networks of brain regions that are not only temporally correlated during different tasks, but also networks that show highly correlated spontaneous activity during a task-free state. Both task-related and task-free network activity has been associated with individual differences in cognitive performance. Therefore, we aimed to examine the influence of cognitive expertise on four networks associated with cognitive task performance: the default mode network (DMN) and three other cognitive networks (central-executive network, dorsal attention network, and salience network). During fMRI scanning, fifteen grandmaster and master level Chinese chess players (GM/M) and fifteen novice players carried out a Chinese chess task and a task-free resting state. Modulations of network activity during task were assessed, as well as resting-state functional connectivity of those networks. Relative to novices, GM/Ms showed a broader task-induced deactivation of DMN in the chess problem-solving task, and intrinsic functional connectivity of DMN was increased with a connectivity pattern associated with the caudate nucleus in GM/Ms. The three other cognitive networks did not exhibit any difference in task-evoked activation or intrinsic functional connectivity between the two groups. These findings demonstrate the effect of long-term learning and practice in cognitive expertise on large-scale brain networks, suggesting the important role of DMN deactivation in expert performance and enhanced functional integration of spontaneous activity within widely distributed DMN-caudate circuitry, which might better support high-level cognitive control of behavior

The prevalence of hyperuricemia in China: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>The prevalence of hyperuricemia varied in different populations and it appeared to be increasing in the past decades. Recent studies suggest that hyperuricemia is an independent risk factor for cardiovascular disease. However, there has not yet been a systematic analysis of the prevalence of hyperuricemia in China.</p> <p>Methods</p> <p>Epidemiological investigations on hyperuricemia in China published in journals were identified manually and on-line by using CBMDISC, Chongqing VIP database and CNKI database. Those Reported in English journals were identified using MEDLINE database. Selected studies had to describe an original study defined by strict screening and diagnostic criteria. The fixed effects model or random effects model was employed according to statistical test for homogeneity.</p> <p>Results</p> <p>Fifty-nine studies were selected, the statistical information of which was collected for systematic analysis. The results showed that the pooled prevalence of hyperuricemia in male was 21.6% (95%CI: 18.9%-24.6%), but it was only 8.6% (95%CI: 8.2%-10.2%) in female. It was found that thirty years was the risk point age in male and it was fifty years in female.</p> <p>Conclusions</p> <p>The prevalence of hyperuricemia is different as the period of age and it increases after 30 years in male and 50 in female. Interventions are necessary to change the risk factors before the key age which is 30 years in male and 50 in female.</p

Identification of Radiopure Titanium for the LZ Dark Matter Experiment and Future Rare Event Searches

The LUX-ZEPLIN (LZ) experiment will search for dark matter particle interactions with a detector containing a total of 10 tonnes of liquid xenon within a double-vessel cryostat. The large mass and proximity of the cryostat to the active detector volume demand the use of material with extremely low intrinsic radioactivity. We report on the radioassay campaign conducted to identify suitable metals, the determination of factors limiting radiopure production, and the selection of titanium for construction of the LZ cryostat and other detector components. This titanium has been measured with activities of $^{238}$U$_{e}$~$<$1.6~mBq/kg, $^{238}$U$_{l}$~$<$0.09~mBq/kg, $^{232}$Th$_{e}$~$=0.28\pm 0.03$~mBq/kg, $^{232}$Th$_{l}$~$=0.25\pm 0.02$~mBq/kg, $^{40}$K~$<$0.54~mBq/kg, and $^{60}$Co~$<$0.02~mBq/kg (68\% CL). Such low intrinsic activities, which are some of the lowest ever reported for titanium, enable its use for future dark matter and other rare event searches. Monte Carlo simulations have been performed to assess the expected background contribution from the LZ cryostat with this radioactivity. In 1,000 days of WIMP search exposure of a 5.6-tonne fiducial mass, the cryostat will contribute only a mean background of $0.160\pm0.001$(stat)$\pm0.030$(sys) counts

The LUX-ZEPLIN (LZ) Experiment

We describe the design and assembly of the LUX-ZEPLIN experiment, a direct detection search for cosmic WIMP dark matter particles. The centerpiece of the experiment is a large liquid xenon time projection chamber sensitive to low energy nuclear recoils. Rejection of backgrounds is enhanced by a Xe skin veto detector and by a liquid scintillator Outer Detector loaded with gadolinium for efficient neutron capture and tagging. LZ is located in the Davis Cavern at the 4850' level of the Sanford Underground Research Facility in Lead, South Dakota, USA. We describe the major subsystems of the experiment and its key design features and requirements