Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of ...N-methyl-D-aspartate (NMDA) receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor (NMDAR) signaling specifically in FS PV interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDAR activity, FS PV interneurons, gamma oscillations and behavior, we generated mice lacking NMDAR neurotransmission only in PV cells (PV-Cre/NR1f/f mice). Here, we show that mutant mice exhibit enhanced baseline cortical gamma rhythms, impaired gamma rhythm induction after optogenetic drive of PV interneurons and reduced sensitivity to the effects of NMDAR antagonists on gamma oscillations and stereotypies. Mutant mice show largely normal behaviors except for selective cognitive impairments, including deficits in habituation, working memory and associative learning. Our results provide evidence for the critical role of NMDAR in PV interneurons for expression of normal gamma rhythms and specific cognitive behaviors.
Solute carrier (SLC) transporters represent 52 families of membrane transport proteins that function in endogenous compound homeostasis and xenobiotic disposition, and have been exploited in drug ...delivery and therapeutic targeting strategies. In particular, the SLC16 family that encodes for the 14 isoforms of the monocarboxylate transporter (MCT) family plays a significant role in the absorption, tissue distribution, and clearance of both endogenous and exogenous compounds. MCTs are required for the transport of essential cell nutrients and for cellular metabolic and pH regulation. Recent publications have indicated their novel roles in disease, and thus their potential as biomarkers and new therapeutic targets in disease are under investigation. More research into MCT isoform function, specificity, expression, and regulation will allow researchers to exploit the potential utility of MCTs in the clinic as therapeutic targets and prognostic factors of disease.
Objective
Hearing loss affects over 1.23 billion people globally. It has been proposed that hearing impairment negatively impacts on cognition. Some studies have demonstrated a faster rate of decline ...in cognition, and increased risk of incident all‐cause dementia. This finding is not ubiquitous. This study used meta‐analysis to examine the evidence‐base regarding the relationship between hearing and cognition.
Design
A systematic review of the literature and meta‐analyses of study findings were conducted. Published and grey literature was reviewed. Papers were included if they studied the relationship between hearing and cognition in adults with and without hearing impairment.
Main outcome measures
Meta‐analyses examined evidence for and against seven questions. Is cognition poorer in individuals with normal hearing compared to (i) untreated or (ii) treated hearing impairment, is cognition associated with degree of hearing impairment in (iii) untreated and/or (iv) treated hearing, is cognition (v) different in untreated compared to treated hearing impairment, (vii) does cognition improve after intervention, and (vii) how is hearing impairment differentially associated with cognitive ability across six domains of cognition?
Results
The 33 included studies contributed 40 samples, with a total of 602 participants with untreated hearing impairment, 672 participants with treated hearing impairment, 176 healthy controls, and 4260 individuals with a range of hearing impairment with/without treatment. The results demonstrated that cognition is significantly poorer in (i) individuals with untreated hearing and remains poorer in (ii) treated hearing impairment compared to normal hearers. The degree of cognitive deficit is significantly associated with the degree of hearing impairment in both (iii) untreated and (iv) treated hearing impairment. Furthermore, (v) hearing intervention significantly improves cognition. Finally, (vii) hearing impairment impacted on all domains of cognition.
Conclusions
This meta‐analysis suggests that hearing impairment is associated with cognitive problems. However, due to diversity within studies, small sample sizes, the failure to control for premorbid and other health factors, this conclusion may be premature.
The μeV axion is a well-motivated extension to the standard model. The Axion Dark Matter eXperiment (ADMX) collaboration seeks to discover this particle by looking for the resonant conversion of ...dark-matter axions to microwave photons in a strong magnetic field. In this Letter, we report results from a pathfinder experiment, the ADMX "Sidecar," which is designed to pave the way for future, higher mass, searches. This testbed experiment lives inside of and operates in tandem with the main ADMX experiment. The Sidecar experiment excludes masses in three widely spaced frequency ranges (4202-4249, 5086-5799, and 7173-7203 MHz). In addition, Sidecar demonstrates the successful use of a piezoelectric actuator for cavity tuning. Finally, this publication is the first to report data measured using both the TM_{010} and TM_{020} modes.
At temperatures up to about 80 degrees C, petroleum in subsurface reservoirs is often biologically degraded, over geological timescales, by microorganisms that destroy hydrocarbons and other ...components to produce altered, denser 'heavy oils'. This temperature threshold for hydrocarbon biodegradation might represent the maximum temperature boundary for life in the deep nutrient-depleted Earth. Most of the world's oil was biodegraded under anaerobic conditions, with methane, a valuable commodity, often being a major by-product, which suggests alternative approaches to recovering the world's vast heavy oil resource that otherwise will remain largely unproduced.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
In this work, we present polarization profiles for 23 millisecond pulsars observed at 820 and 1500 MHz with the Green Bank Telescope as part of the NANOGrav pulsar timing array. We calibrate ...the data using Mueller matrix solutions calculated from observations of PSRs B1929+10 and J1022+1001. We discuss the polarization profiles, which can be used to constrain pulsar emission geometry, and present both the first published radio polarization profiles for nine pulsars and the discovery of very low-intensity average profile components (“microcomponents”) in four pulsars. We obtain the Faraday rotation measures for each pulsar and use them to calculate the Galactic magnetic field parallel to the line of sight for different lines of sight through the interstellar medium. We fit for linear and sinusoidal trends in time in the dispersion measure and Galactic magnetic field and detect magnetic field variations with a period of 1 yr in some pulsars, but overall find that the variations in these parameters are more consistent with a stochastic origin.
In contrast to nitric oxide, which has well established and important roles in the regulation of blood flow and thrombosis, neurotransmission, the normal functioning of the genitourinary system, and ...the inflammation response and host defense, its oxidized metabolites nitrite and nitrate have, until recently, been considered to be relatively inactive. However, this view has been radically revised over the past decade and more. Much evidence has now accumulated demonstrating that nitrite serves as a storage form of nitric oxide, releasing nitric oxide preferentially under acidic and/or hypoxic conditions but also occurring under physiologic conditions: a phenomenon that is catalyzed by a number of distinct mammalian nitrite reductases. Importantly, preclinical studies demonstrate that reduction of nitrite to nitric oxide results in a number of beneficial effects, including vasodilatation of blood vessels and lowering of blood pressure, as well as cytoprotective effects that limit the extent of damage caused by an ischemia/reperfusion insult, with this latter issue having been translated more recently to the clinical setting. In addition, research has demonstrated that the other main metabolite of the oxidation of nitric oxide (i.e., nitrate) can also be sequentially reduced through processing in vivo to nitrite and then nitrite to nitric oxide to exert a range of beneficial effects-most notably lowering of blood pressure, a phenomenon that has also been confirmed recently to be an effective method for blood pressure lowering in patients with hypertension. This review will provide a detailed description of the pathways involved in the bioactivation of both nitrate and nitrite in vivo, their functional effects in preclinical models, and their mechanisms of action, as well as a discussion of translational exploration of this pathway in diverse disease states characterized by deficiencies in bioavailable nitric oxide. SIGNIFICANCE STATEMENT: The past 15 years has seen a major revision in our understanding of the pathways for nitric oxide synthesis in the body with the discovery of the noncanonical pathway for nitric oxide generation known as the nitrate-nitrite-nitric oxide pathway. This review describes the molecular components of this pathway, its role in physiology, potential therapeutics of targeting this pathway, and their impact in experimental models, as well as the clinical translation (past and future) and potential side effects.
Given the high rates of both primary and secondary anterior cruciate ligament (ACL) injuries in multidirectional field sports, there is a need to develop easily accessible methods for practitioners ...to monitor ACL injury risk. Field-based methods to assess knee variables associated with ACL injury are of particular interest to practitioners for monitoring injury risk in applied sports settings. Knee variables or proxy measures derived from wearable inertial measurement units (IMUs) may thus provide a powerful tool for efficient injury risk management. Therefore, the aim of this study was to identify whether there were correlations between laboratory-derived knee variables (knee range of motion (RoM), change in knee moment, and knee stiffness) and metrics derived from IMUs (angular velocities and accelerations) placed on the tibia and thigh, across a range of movements performed in practitioner assessments used to monitor ACL injury risk. Ground reaction forces, three-dimensional kinematics, and triaxial IMU data were recorded from nineteen healthy male participants performing bilateral and unilateral drop jumps, and a 90° cutting task. Spearman's correlations were used to examine the correlations between knee variables and IMU-derived metrics. A significant strong positive correlation was observed between knee RoM and the area under the tibia angular velocity curve in all movements. Significant strong correlations were also observed in the unilateral drop jump between knee RoM, change in knee moment, and knee stiffness, and the area under the tibia acceleration curve (r
= 0.776, r
= -0.712, and r
= -0.765, respectively). A significant moderate correlation was observed between both knee RoM and knee stiffness, and the area under the thigh angular velocity curve (r
= 0.682 and r
= -0.641, respectively). The findings from this study suggest that it may be feasible to use IMU-derived angular velocities and acceleration measurements as proxy measures of knee variables in movements included in practitioner assessments used to monitor ACL injury risk.
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