Detection of Optogenetic Stimulation in Somatosensory Cortex by Non-Human Primates - Towards Artificial Tactile Sensation

Neuroprosthesis research aims to enable communication between the brain and external assistive devices while restoring lost functionality such as occurs from stroke, spinal cord injury or neurodegenerative diseases. In future closed-loop sensorimotor prostheses, one approach is to use neuromodulation as direct stimulus to the brain to compensate for a lost sensory function and help the brain to integrate relevant information for commanding external devices via, e.g. movement intention. Current neuromodulation techniques rely mainly of electrical stimulation. Here we focus specifically on the question of eliciting a biomimetically relevant sense of touch by direct stimulus of the somatosensory cortex by introducing optogenetic techniques as an alternative to electrical stimulation. We demonstrate that light activated opsins can be introduced to target neurons in the somatosensory cortex of non-human primates and be optically activated to create a reliably detected sensation which the animal learns to interpret as a tactile sensation localized within the hand. The accomplishment highlighted here shows how optical stimulation of a relatively small group of mostly excitatory somatosensory neurons in the nonhuman primate brain is sufficient for eliciting a useful sensation from data acquired by simultaneous electrophysiology and from behavioral metrics. In this first report to date on optically neuromodulated behavior in the somatosensory cortex of nonhuman primates we do not yet dissect the details of the sensation the animals exerience or contrast it to those evoked by electrical stimulation, issues of considerable future interest.     

Transport adenosine triphosphatase activity in the rat cornea

Summary The sodium-potassium activated adenosine triphosphatase (NaKATPase) activity of the rat cornea was investigated histochemically using a Pb²⁺-precipitation technique in which adenosine triphosphate (ATP) is used as substrate and two methods for potassium-dependent para-nitrophenyl-phosphatase (K-NPPase) activity.With all the three techniques used it was demonstrated that the sodium-potassium-activated adenosine triphosphatase (NaK-ATPase) activity is localized in the cell membranes of the endothelium whereas a much weaker activity was observed in the epithelium. When the Pb²⁺-technique was used, the epithelial cell membranes showed a weaker reaction in the presence of ouabain. This activity was only Mg²⁺-dependent and was presumably due to an Mg²⁺-dependent ATPase.The validity of the histochemical techniques for NaK-ATPase activity is discussed. The results emphasize the importance of the endothelium as the main site of Na⁺ transport in the cornea. Small amounts of the enzyme are also present in the epithelium, which seems to be rich in Mg²⁺-ATPase. Provided that careful controls are performed, all the methods give consistent results in the cornea.The work is part of an eye research project by Arto Palkama and supported by grants from the Sigrid Jusélius Foundation, Helsinki, Finland, to A.P. and from the Finnish Cultural Foundation, Helsinki, Finland, to T.T. and M.P.The authors are grateful to Miss Irma Hiltunen for skilful technical assistance     

Prevalencia de infección por coronavirus SARS-CoV-2 en pacientes y profesionales de un hospital de media y larga estancia en España

Background and goalsThe aim of the study is to know the prevalence of SARS-CoV-2 infection in patients and professional staff of a medium or long-stay hospital during the peak period of the pandemic in Spain, spring 2020.Material and methodsAt the end of February 2020, we developed at the hospital a strategy to diagnose the SARS-CoV-2 infection consisting of complementing the realization of PCR tests at real time with a quick technique of lateral flow immunochromatography to detect IgG and IgM antibodies against the virus. We also developed a protocol to realize those diagnostic tests and considered an infection (current or past) a positive result in any of the above tests.We included 524 participants in the study (230 patients and 294 hospital staff), and divided them into hospital patients and Hemodialysis outpatients. Furthermore, we divided the hospital staff into healthcare and non-healthcare staff. The documented period was from March, 20^th to April, 21^st, 2020.Results26 out of 230 patients tested positive in any of the diagnostic techniques (PCR, antibodies IgG, IgM) with a 11.30% prevalence. According to patients groups, we got a 14.38% prevalence in hospital patients vs. 5.95% in outpatients, with a significantly higher risk in admitted patients after adjustment for age and gender (OR=3,309, 95%CI: 1,154-9,495).24 out of 294 hospital staff tested positive in any of the diagnostic techniques, with a 8.16% prevalence. According to the groups, we got a 8.91% prevalence in healthcare staff vs. 4.26% in non-healthcare staff. Thus, we do not see any statistically significant differences between hospital staff and patients as far as prevalence is concerned (P=0,391), (OR=2,200, 95%CI: 0,500-9,689).ConclusionsThe result of the study was a quite low prevalence rate of SARS-CoV-2 infection, in both patients and hospital staff, being the hospital patients’ prevalence rate higher than the outpatients’, and the healthcare staff higher than the non-healthcare's. Combining PCR tests (gold standard) with antibodies tests proved useful as a diagnostic strategy.     

Biofilm and planktonic Enterococcus faecalis elicit different responses from host phagocytes in vitro

Enterococcus faecalis is a commensal organism of the gastrointestinal tract but can also cause serious opportunistic infections. In addition to high levels of antibiotic resistance, the ability to form biofilms on abiotic surfaces and on in-dwelling devices within the host complicates treatment strategies and successful outcomes of antibiotic therapy. Despite rapid advances made in recent years in understanding the genomics and virulence of this organism, much remains to be learned regarding the host response to enterococcal infections. In this study, we investigated the interaction of RAW264.7 macrophages and JAWS II dendritic cells with biofilm and planktonic E.?faecalis, in vitro. Specifically, we compared phagocytosis, intracellular survival, secretion of proinflammatory cytokines, and the activation and maturation of phagocytes. Our results revealed that both macrophages and dendritic cells phagocytize biofilm mode cells at levels equal to or better than their planktonic counterparts. Internalized biofilm bacteria showed relatively greater survival at 24?h in macrophages than in dendritic cells and led to slightly higher expression of phagocyte activation markers. Macrophages infected with biofilm cells also secreted lower levels of proinflammatory cytokines studied. Overall, these results suggest that biofilm E.?faecalis may be better adapted to overcome host defenses in vivo.     

Microwave assisted synthesis and solid-state characterization of lithocholyl amides of isomeric aminopyridines

Microwave (MW) assisted synthesis and solid state structural characterizations of novel lithocholyl amides of 2-, 3-, and 4-aminopyridine are reported. It is shown that the MW technique is a proper method in the preparation of N-lithocholyl amides of isomeric aminopyridines. It offers many advantages compared to conventional heating. The molecular and crystal structures as well as the polymorphic and hydrated forms of prepared conjugates with their thermodynamic stabilities have been characterized by means of high resolution liquid- and solid-state NMR spectroscopy, single crystal and powder X-ray diffraction, and thermogravimetric analysis. Owing to the many biological functions of bile acids and amino substituted nitrogen heterocycles, knowledge of the crystal packing of these novel conjugates may have relevance for potential pharmaceutical applications.     

Heavy resistance exercise training and skeletal muscle androgen receptor expression in younger and older men

Effects of heavy resistance exercise on serum testosterone and skeletal muscle androgen receptor (AR) concentrations were examined before and after a 21-week resistance training period. Seven healthy untrained young adult men (YT) and ten controls (YC) as well as ten older men (OT) and eight controls (OC) volunteered as subjects. Heavy resistance exercise bouts (5 × 10 RM leg presses) were performed before and after the training period. Muscle biopsies were obtained before and 1h and 48 h after the resistance exercise bouts from m.vastus lateralis (VL) to determine cross-sectional area of muscle fibers (fCSA) and AR mRNA expression and protein concentrations. No changes were observed in YC and OC while resistance training led to significant increases in maximal strength of leg extensors (1 RM), fCSA and lean body mass in YT and OT. Acute increases occurred in serum testosterone concentrations due to resistance exercises but basal testosterone remained unaltered. Mean AR mRNA expression and protein concentration remained unchanged after heavy resistance exercise bouts compared to pre-values. The individual pre- to post-training changes in resting (pre-exercise) AR protein concentration correlated with the changes in fCSA and lean body mass in the combined group of YT and OT. Similarly, it correlated with the changes in 1 RM in YT. Although mean AR expression did not changed due to the resistance exercise training, the present findings suggest that the individual changes of AR protein concentration in skeletal muscle following resistance training may have an impact on training-induced muscular adaptations in both younger and older men.     

Memory-based mismatch response to frequency changes in rats

Any occasional changes in the acoustic environment are of potential importance for survival. In humans, the preattentive detection of such changes generates the mismatch negativity (MMN) component of event-related brain potentials. MMN is elicited to rare changes ('deviants') in a series of otherwise regularly repeating stimuli ('standards'). Deviant stimuli are detected on the basis of a neural comparison process between the input from the current stimulus and the sensory memory trace of the standard stimuli. It is, however, unclear to what extent animals show a similar comparison process in response to auditory changes. To resolve this issue, epidural potentials were recorded above the primary auditory cortex of urethane-anesthetized rats. In an oddball condition, tone frequency was used to differentiate deviants interspersed randomly among a standard tone. Mismatch responses were observed at 60-100 ms after stimulus onset for frequency increases of 5% and 12.5% but not for similarly descending deviants. The response diminished when the silent inter-stimulus interval was increased from 375 ms to 600 ms for +5% deviants and from 600 ms to 1000 ms for +12.5% deviants. In comparison to the oddball condition the response also diminished in a control condition in which no repetitive standards were presented (equiprobable condition). These findings suggest that the rat mismatch response is similar to the human MMN and indicate that anesthetized rats provide a valuable model for studies of central auditory processing.     

Recovery after heavy resistance exercise and skeletal muscle androgen receptor and insulin-like growth factor-I isoform expression in strength trained men

The effects of heavy resistance exercise on skeletal muscle androgen receptor (AR) protein concentration and mRNAs of AR, insulin-like growth factor-I (IGF)-IEa, and mechano growth factor (MGF) expression were examined from biopsies of vastus lateralis (VL) muscle before and 48 hours after heavy resistance exercise (5 × 10 repetition maximum [RM] leg press and 4 × 10RM squats) in 8 adult strength trained men. The present exercise induced an acute decrease in maximal isometric force and increased serum total testosterone (T) and free testosterone (FT) concentrations. During 2 recovery days, maximal isometric force and subjective perception of physical fitness remained significantly lowered, whereas serum creatine kinase activity, subjective muscle soreness, and muscle swelling (i.e., thickness of VL by ultrasound) were significantly increased compared to pre-exercise values. Subjective perception of physical fitness was followed up to 7 days, and by 6 days postexercise, it was elevated above the pre-exercise level. Basal T and FT concentrations remained unaltered after the exercise. No statistically significant changes were observed in AR protein or mRNA expression, but IGF-IEa (p < 0.05) and MGF (p < 0.05) mRNA expression were increased compared to pre-exercise levels. These findings indicate that IGF-IEa and MGF responses may be related to acute regenerative processes in muscle because of exercise and may contribute to muscular adaptation to resistance exercise. Subjective perception of physical fitness suggests that recovery over a pre-exercise level of the present type of heavy resistance exercise can take approximately 6 days.