ERK2 alone drives inflammatory pain but cooperates with ERK1 in sensory neuron survival

Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are highly homologous yet distinct components of signal transduction pathways known to regulate cell survival and function. Recent evidence indicates an isoform-specific role for ERK2 in pain processing and peripheral sensitization. However, the function of ERK2 in primary sensory neurons has not been directly tested. To dissect the isoform-specific function of ERK2 in sensory neurons, we used mice with Cre-loxP-mediated deletion of ERK2 in Na(v)1.8(+) sensory neurons that are predominantly nociceptors. We find that ERK2, unlike ERK1, is required for peripheral sensitization and cold sensation. We also demonstrate that ERK2, but not ERK1, is required to preserve epidermal innervation in a subset of peptidergic neurons. Additionally, deletion of both ERK isoforms in Na(v)1.8(+) sensory neurons leads to neuron loss not observed with deletion of either isoform alone, demonstrating functional redundancy in the maintenance of sensory neuron survival. Thus, ERK1 and ERK2 exhibit both functionally distinct and redundant roles in sensory neurons. SIGNIFICANCE STATEMENT ERK1/2 signaling affects sensory neuron function and survival. However, it was not clear whether ERK isoform-specific roles exist in these processes postnatally. Previous work from our laboratory suggested either functional redundancy of ERK isoforms or a predominant role for ERK2 in pain; however, the tools to discriminate between these possibilities were not available at the time. In the present study, we use new genetic knock-out lines to demonstrate that ERK2 in sensory neurons is necessary for development of inflammatory pain and for postnatal maintenance of peptidergic epidermal innervation. Interestingly, postnatal loss of both ERK isoforms leads to a profound loss of sensory neurons. Therefore, ERK1 and ERK2 display both functionally distinct and redundant roles in sensory neurons

Gas-Particle Partitioning of Atmospheric Hg(II) and Its Effect on Global Mercury Deposition

Atmospheric deposition of Hg(II) represents a major input of mercury to surface environments. The phase of Hg(II) (gas or particle) has important implications for deposition. We use long-term observations of reactive gaseous mercury (RGM, the gaseous component of Hg(II)), particle-bound mercury (PBM, the particulate component of Hg(II)), fine particulate matter (PM2.5), and temperature (T) at five sites in North America to derive an empirical gas-particle partitioning relationship log10(K−1) = (10±1)–(2500±300)/T where K = (PBM/PM2.5)/RGM with PBM and RGM in common mixing ratio units, PM2.5 in μg m−3, and T in K. This relationship is within the range of previous work but is based on far more extensive data from multiple sites. We implement this empirical relationship in the GEOS-Chem global 3-D Hg model to partition Hg(II) between the gas and particle phases. The resulting gas-phase fraction of Hg(II) ranges from over 90 % in warm air with little aerosol to less than 10 % in cold air with high aerosol. Hg deposition to high latitudes increases because of more efficient scavenging of particulate Hg(II) by precipitating snow. Model comparison to Hg observations at the North American surface sites suggests that subsidence from the free troposphere (warm air, low aerosol) is a major factor driving the seasonality of RGM, while elevated PBM is mostly associated with high aerosol loads. Simulation of RGM and PBM at these sites is improved by including fast in-plume reduction of Hg(II) emitted from coal combustion and by assuming that anthropogenic particulate Hg(p) behaves as semi-volatile Hg(II) rather than as a refractory particulate component. We improve the simulation of Hg wet deposition fluxes in the US relative to a previous version of GEOS-Chem; this largely reflects independent improvement of the washout algorithm. The observed wintertime minimum in wet deposition fluxes is attributed to inefficient snow scavenging of gas-phase Hg(II).Earth and Planetary SciencesEngineering and Applied Science

Multipurpose silicon photonics signal processor core

[EN] Integrated photonics changes the scaling laws of information and communication systems offering architectural choices that combine photonics with electronics to optimize performance, power, footprint, and cost. Application-specific photonic integrated circuits, where particular circuits/chips are designed to optimally perform particular functionalities, require a considerable number of design and fabrication iterations leading to long development times. A different approach inspired by electronic Field Programmable Gate Arrays is the programmable photonic processor, where a common hardware implemented by a two-dimensional photonic waveguide mesh realizes different functionalities through programming. Here, we report the demonstration of such reconfigurable waveguide mesh in silicon. We demonstrate over 20 different functionalities with a simple seven hexagonal cell structure, which can be applied to different fields including communications, chemical and biomedical sensing, signal processing, multiprocessor networks, and quantum information systems. Our work is an important step toward this paradigm.J.C. acknowledges funding from the ERC Advanced Grant ERC-ADG-2016-741415 UMWP-Chip, I.G. acknowledges the funding through the Spanish MINECO Ramon y Cajal program. D.P. acknowledges financial support from the UPV through the FPI predoctoral funding scheme. D.J.T. acknowledges funding from the Royal Society for his University Research Fellowship.Pérez-López, D.; Gasulla Mestre, I.; Crudgington, L.; Thomson, DJ.; Khokhar, AZ.; Li, K.; Cao, W.... (2017). Multipurpose silicon photonics signal processor core. Nature Communications. 8(1925):1-9. https://doi.org/10.1038/s41467-017-00714-1S1981925Doerr, C. R. & Okamoto, K. Advances in silica planar lightwave circuits. J. 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Transcatheter or surgical aortic-valve replacement in intermediate-risk patients

BACKGROUND: Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aorticvalve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients. METHODS: We randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort. RESULTS: The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan–Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoralaccess cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic-valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation. CONCLUSIONS: In intermediate-risk patients, TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313

Dynamic Visuomotor Transformation Involved with Remote Flying of a Plane Utilizes the ‘Mirror Neuron’ System

Brain regions involved with processing dynamic visuomotor representational transformation are investigated using fMRI. The perceptual-motor task involved flying (or observing) a plane through a simulated Red Bull Air Race course in first person and third person chase perspective. The third person perspective is akin to remote operation of a vehicle. The ability for humans to remotely operate vehicles likely has its roots in neural processes related to imitation in which visuomotor transformation is necessary to interpret the action goals in an egocentric manner suitable for execution. In this experiment for 3rd person perspective the visuomotor transformation is dynamically changing in accordance to the orientation of the plane. It was predicted that 3rd person remote flying, over 1st, would utilize brain regions composing the ‘Mirror Neuron’ system that is thought to be intimately involved with imitation for both execution and observation tasks. Consistent with this prediction differential brain activity was present for 3rd person over 1st person perspectives for both execution and observation tasks in left ventral premotor cortex, right dorsal premotor cortex, and inferior parietal lobule bilaterally (Mirror Neuron System) (Behaviorally: 1st>3rd). These regions additionally showed greater activity for flying (execution) over watching (observation) conditions. Even though visual and motor aspects of the tasks were controlled for, differential activity was also found in brain regions involved with tool use, motion perception, and body perspective including left cerebellum, temporo-occipital regions, lateral occipital cortex, medial temporal region, and extrastriate body area. This experiment successfully demonstrates that a complex perceptual motor real-world task can be utilized to investigate visuomotor processing. This approach (Aviation Cerebral Experimental Sciences ACES) focusing on direct application to lab and field is in contrast to standard methodology in which tasks and conditions are reduced to their simplest forms that are remote from daily life experience

Advancing nursing practice : the emergence of the role of Advanced Practice Nurse in Saudi Arabia

Background: The roots of advanced practice nursing can be traced back to the 1890s, but the Nurse Practitioner (NP) emerged in Western countries during the 1960s in response to the unmet health care needs of populations in rural areas. These early NPs utilized the medical model of care to assess, diagnose and treat. Nursing has since grown as a profession, with its own unique and distinguishable, holistic, science-based knowledge, which is complementary within the multidisciplinary team. Today Advanced Practice Nurses (APNs) demonstrate nursing expertise in clinical practice, education, research and leadership, and are no longer perceived as “physician replacements” or assistants. Saudi Arabia has yet to define, legislate or regulate Advanced Practice Nursing. Aims: This article aims to disseminate information from a Saudi Advanced Practice Nurse thought leadership meeting, to chronicle the history of Advanced Practice Nursing within the Kingdom of Saudi Arabia, while identifying strategies for moving forward. Conclusion: It is important to build an APN model based on Saudi health care culture and patient population needs, while recognizing global historical underpinnings. Ensuring that nursing continues to distinguish itself from other health care professions, while securing a seat at the multidisciplinary health care table will be instrumental in advancing the practice of nursing

The role of the cerebellum in adaptation: ALE meta‐analyses on sensory feedback error

It is widely accepted that unexpected sensory consequences of self‐action engage the cerebellum. However, we currently lack consensus on where in the cerebellum, we find fine‐grained differentiation to unexpected sensory feedback. This may result from methodological diversity in task‐based human neuroimaging studies that experimentally alter the quality of self‐generated sensory feedback. We gathered existing studies that manipulated sensory feedback using a variety of methodological approaches and performed activation likelihood estimation (ALE) meta‐analyses. Only half of these studies reported cerebellar activation with considerable variation in spatial location. Consequently, ALE analyses did not reveal significantly increased likelihood of activation in the cerebellum despite the broad scientific consensus of the cerebellum's involvement. In light of the high degree of methodological variability in published studies, we tested for statistical dependence between methodological factors that varied across the published studies. Experiments that elicited an adaptive response to continuously altered sensory feedback more frequently reported activation in the cerebellum than those experiments that did not induce adaptation. These findings may explain the surprisingly low rate of significant cerebellar activation across brain imaging studies investigating unexpected sensory feedback. Furthermore, limitations of functional magnetic resonance imaging to probe the cerebellum could play a role as climbing fiber activity associated with feedback error processing may not be captured by it. We provide methodological recommendations that may guide future studies

Listening to a conversation with aggressive content expands the interpersonal space

The distance individuals maintain between themselves and others can be defined as ‘interpersonal space’. This distance can be modulated both by situational factors and individual characteristics. Here we investigated the influence that the interpretation of other people interaction, in which one is not directly involved, may have on a person’s interpersonal space. In the current study we measured, for the first time, whether the size of interpersonal space changes after listening to other people conversations with neutral or aggressive content. The results showed that the interpersonal space expands after listening to a conversation with aggressive content relative to a conversation with a neutral content. This finding suggests that participants tend to distance themselves from an aggressive confrontation even if they are not involved in it. These results are in line with the view of the interpersonal space as a safety zone surrounding one’s body

Effects of prophylactic knee bracing on patellar tendon loading parameters during functional sports tasks in recreational athletes

Purpose This study investigated the efects of prophylactic knee bracing on patellar tendon loading parameters. Methods Twenty recreational athletes (10 male and 10 female) from diferent athletic disciplines performed run, cut and single leg hop movements under two conditions (prophylactic knee brace/no-brace). Lower extremity kinetics and kinematics were examined using a piezoelectric force plate and three-dimensional motion capture system. Patellar tendon loading was explored using a mathematical modelling approach, which accounted for co-contraction of the knee lexors. Tendon loading parameters were examined using 2 (brace) × 3 (movement) × 2 (sex) mixed ANOVAs. Results Tendon instantaneous load rate was signiicantly reduced in female athletes in the run (brace 289.14 BW/s no-brace 370.06 BW/s) and cut (brace 353.17 BW/s/no-brace 422.01 BW/s) conditions whilst wearing the brace. Conclusions Female athletes may be able to attenuate their risk from patellar tendinopathy during athletic movements, through utilization of knee bracing, although further prospective research into the prophylactic efects of knee bracing is required before this can be clinically substantiated