The present study reports alterations of task-based functional brain connectivity in a group of 11 cosmonauts after a long-duration spaceflight, compared to a healthy control group not involved in the space program. To elicit the postural and locomotor sensorimotor mechanisms that are usually most significantly impaired when space travelers return to Earth, a plantar stimulation paradigm was used in a block design fMRI study. The motor control system activated by the plantar stimulation involved the pre-central and post-central gyri, SMA, SII/operculum, and, to a lesser degree, the insular cortex and cerebellum. While no post-flight alterations were observed in terms of activation, the network-based statistics approach revealed task-specific functional connectivity modifications within a broader set of regions involving the activation sites along with other parts of the sensorimotor neural network and the visual, proprioceptive, and vestibular systems. The most notable findings included a post-flight increase in the stimulation-specific connectivity of the right posterior supramarginal gyrus with the rest of the brain; a strengthening of connections between the left and right insulae; decreased connectivity of the vestibular nuclei, right inferior parietal cortex (BA40) and cerebellum with areas associated with motor, visual, vestibular, and proprioception functions; and decreased coupling of the cerebellum with the visual cortex and the right inferior parietal cortex. The severity of space motion sickness symptoms was found to correlate with a post- to pre-flight difference in connectivity between the right supramarginal gyrus and the left anterior insula. Due to the complex nature and rapid dynamics of adaptation to gravity alterations, the post-flight findings might be attributed to both the long-term microgravity exposure and to the readaptation to Earth’s gravity that took place between the landing and post-flight MRI session. Nevertheless, the results have implications for the multisensory reweighting and gravitational motor system theories, generating hypotheses to be tested in future research.
Non-alcoholic fatty liver disease (NAFLD) is the worldwide most common cause of chronic liver pathology, which prevalence strongly correlates with the increasing incidence of diabetes, obesity and metabolic syndrome in the general population. Simple steatosis, the earliest NAFLD stage, usually remains asymptomatic, and appropriate changes in the lifestyle, as well as the diet, can reverse the affected liver into the healthy state. The potential of simple steatosis to progress into severe fibrotic stages and to facilitate carcinogenesis necessitates timely NAFLD detection and risk stratification in community-based healthcare settings. Since their initial discovery a decade ago, extracellular circulating miRNAs have been found in all human biological fluids including blood and shown to hold great promises as non-invasive biomarkers. Normally, intracellular miRNAs participate in the regulation of gene expression, but once released by dying/dead cells they remain highly stable in the extracellular environment for prolonged periods. Therefore, circulating miRNA profiles can reflect the ongoing pathogenic processes in body's tissues and organs, and enable highly sensitive non-invasive diagnosis of multiple disorders. A non-urgent character of the NAFLD-related decision-making justifies the use of chronic liver diseases as an excellent test case for examining the practical utility of circulating miRNAs as biomarkers for longitudinal monitoring of human health. In this review, we summarize the state-of-the-art in the field of early diagnosis of NAFLD using circulating blood miRNAs, and stress the necessity of additional experimental validation of their diagnostic potential. We further emphasize on the potential diagnostics promises of other cell-free RNA species found in human biological fluids.
We examined the effect of involuntary attention switching (related to mismatch negativity generation in the oddball paradigm) on fatigue development during trials of different durations. The experiment consisted of two trials, long (40 min) and short (15 min), and two experimental conditions in each trial: the simple reaction task (deviants-only paradigm) and the stimuli recognition task (oddball paradigm). In each condition, a participant responded to each target acoustic stimulus by squeezing a handgrip dynamometer. We found the significantly lower rates of fatigue development in the short-trial deviants-only paradigm compared to the long trial. The short- and the long-trial oddball paradigms differed significantly from both the short- and the long-trial deviants-only paradigms. The results demonstrated that the fatigue developed differently depending on the expected trial duration. The involuntary activation of attention broke this subconscious regulative mechanism leading to increase of the compression force during the long trial and its decrease during the short. © 2016 Aleksandrov, Knyazeva, Stankevich, Dmitrieva and Shestakova.
The cardiac action potential (AP) is commonly recoded as an integral signal from isolated myocytes or ensembles of myocytes (with intracellular microelectrodes and extracellular macroelectrodes, respectively). These signals, however, do not provide a direct measure of activity of ion channels and transporters located in two major compartments of a cardiac myocyte: surface sarcolemma and the T-tubule system, which differentially contribute to impulse propagation and excitation-contraction (EC) coupling. In the present study we investigated electrical properties of myocytes within perfused intact rat heart employing loose patch recording with narrow-tip (2 μm diameter) extracellular electrodes. Using this approach, we demonstrated two distinct types of electric signals with distinct waveforms (single peak and multi-peak AP; AP1 and AP2, respectively) during intrinsic pacemaker activity. These two types of waveforms depend on the position of the electrode tip on the myocyte surface. Such heterogeneity of electrical signals was lost when electrodes of larger pipette diameter were used (5 or 10 μm), which indicates that the electric signal was assessed from a region of <5 μm. Importantly, both pharmacological and mathematical simulation based on transverse (T)-tubular distribution suggested that while the AP1 and the initial peak of AP2 are predominantly attributable to the fast, inward Na+ current in myocyte's surface sarcolemma, the late components of AP2 are likely representative of currents associated with L-type Ca2+ channel and Na+/Ca2+ exchanger (NCX) currents which are predominantly located in T-tubules. Thus, loose patch recording with narrow-tip pipette provides a valuable tool for studying cardiac electric activity on the subcellular level in the intact heart.