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Working memory (WM) enables the temporary storage of limited information and is a central component of higher order cognitive function. Irrelevant and/or distracting information can have a negative impact on WM processing and suppressing such incoming stimuli is critical to maintaining adequate performance. However, the neural mechanisms and dynamics underlying such distractor inhibition remain poorly understood. In the current study, we enrolled 46 healthy adults (Mage: 27.92, Nfemale: 28) who completed a Sternberg type WM task with high- and low-distractor conditions during magnetoencephalography (MEG). MEG data were transformed into the time-frequency domain and significant task-related oscillatory responses were imaged to identify the underlying anatomical areas. Whole-brain paired t-tests, with cluster-based permutation testing for multiple comparisons correction, were performed to assess differences between the low- and high-distractor conditions for each oscillatory response. Across conditions, we found strong alpha and beta oscillations (i.e., decreases relative to baseline) and increases in theta power throughout the encoding and maintenance periods. Whole-brain contrasts revealed significantly stronger alpha and beta oscillations in bilateral prefrontal regions during maintenance in high- compared to low-distractor trials, with the stronger beta oscillations being centered on the left dorsolateral prefrontal cortex and right inferior frontal gyrus, while those for alpha being within the right anterior prefrontal cortices and the right middle frontal gyrus. These findings suggest that alpha and beta oscillations in the bilateral prefrontal cortices play a major role in the inhibition of distracting information during WM maintenance. Our results also contribute to prior research on cognitive control and functional inhibition, in which prefrontal regions have been widely implicated.

Despite effective antiretroviral therapy, cognitive impairment remains prevalent among people with HIV (PWH) and decrements in executive function are particularly prominent. One component of executive function is cognitive flexibility, which integrates a variety of executive functions to dynamically adapt one's behavior in response to changing contextual demands. Though substantial work has illuminated HIV-related aberrations in brain function, it remains unclear how the neural oscillatory dynamics serving cognitive flexibility are affected by HIV-related alterations in neural functioning. Herein, 149 participants (PWH: 74; seronegative controls: 75) between the ages of 29–76 years completed a perceptual feature matching task that probes cognitive flexibility during high-density magnetoencephalography (MEG). Neural responses were decomposed into the time-frequency domain and significant oscillatory responses in the theta (4–8 Hz), alpha (10–16 Hz), and gamma (74–98 Hz) spectral windows were imaged using a beamforming approach. Whole-brain voxel-wise comparisons were then conducted on these dynamic functional maps to identify HIV-related differences in the neural oscillatory dynamics supporting cognitive flexibility. Our findings indicated group differences in alpha oscillatory activity in the cingulo-opercular cortices, and differences in gamma activity were found in the cerebellum. Across all participants, alpha and gamma activity in these regions were associated with performance on the cognitive flexibility task. Further, PWH who had been treated with antiretroviral therapy for a longer duration and those with higher current CD4 counts had alpha responses that more closely resembled those of seronegative controls, suggesting that optimal clinical management of HIV infection is associated with preserved neural dynamics supporting cognitive flexibility.

Tidal turbines are one source of marine renewable energy but development of tidal power is hampered by uncertainties in fish-turbine interaction impacts. Current knowledge gaps exist in efforts to quantify risks, as empirical data and modeling studies have characterized components of fish approach and interaction with turbines, but a comprehensive model that quantifies conditional occurrence probabilities of fish approaching and then interacting with a turbine in sequential steps is lacking. We combined empirical acoustic density measurements of Pacific herring (Clupea pallasii) and when data limited, published probabilities in an impact probability model that includes approach, entrainment, interactions, and avoidance of fish with axial or cross-flow tidal turbines. Interaction impacts include fish collisions with stationary turbine components, blade strikes by rotating blades, and/or a collision followed by a blade strike. Impact probabilities for collision followed by a blade strike were lowest with estimates ranging from 0.0000242 to 0.0678, and highest for blade strike ranging from 0.000261 to 0.40. Maximum probabilities occurred for a cross-flow turbine at night with no active or passive avoidance. Estimates were lowest when probabilities were conditional on sequential events, and when active and passive avoidance was included for an axial-flow turbine during the day. As expected, conditional probabilities were typically lower than analogous independent events and literature values. Estimating impact probabilities for Pacific herring in Admiralty Inlet, Washington, United States for two device types illustrates utilization of existing data and simultaneously identifies data gaps needed to fully calculate empirical-based probabilities for any site-species combination.

We present 1.8 yr of near-daily Swift monitoring of the bright, strongly variable Type 1 active galactic nucleus (AGN) Fairall 9. Totaling 575 successful visits, this is the largest such campaign reported to date. Variations within the UV/optical are well correlated, with longer wavelengths lagging shorter wavelengths in the direction predicted by thin-disk/lamppost models. The correlations are improved by “detrending,” subtracting a second-order polynomial fit to the UV/optical light curves to remove long-term trends that are not of interest to this study. Extensive testing indicates detrending with higher-order polynomials removes too much intrinsic variability signal on reverberation timescales. These data provide the clearest detection to date of interband lags within the UV, indicating that neither emission from a large disk nor diffuse continuum emission from the broad-line region (BLR) can independently explain the full observed lag spectrum. The observed X-ray flux variations are poorly correlated with those in the UV/optical. Further, subdivision of the data into four ∼160 days light curves shows that the UV/optical lag spectrum is highly stable throughout the four periods, but the X-ray to UV lags are unstable, significantly changing magnitude and even direction from one period to the next. This indicates the X-ray to UV relationship is more complex than predicted by the simple reprocessing model often adopted for AGN. A “bowl” model (lamppost irradiation and blackbody reprocessing on a disk with a steep rim) fit suggests the disk thickens at a distance (∼10 lt-day) and temperature (∼8000 K) consistent with the inner edge of the BLR.

Abstract Background Cerebellar ataxia refers to the disturbance in movement resulting from cerebellar dysfunction. It manifests as inaccurate movements with delayed onset and overshoot, especially when movements are repetitive or rhythmic. Identification of ataxia is integral to the diagnosis and assessment of severity, and is important in monitoring progression and improvement. Ataxia is identified and assessed by clinicians observing subjects perform standardised movement tasks that emphasise ataxic movements. Our aim in this paper was to use data recorded from motion sensors worn while subjects performed these tasks, in order to make an objective assessment of ataxia that accurately modelled the clinical assessment. Methods Inertial measurement units and a Kinect© system were used to record motion data while control and ataxic subjects performed four instrumented version of upper extremities tests, i.e. finger chase test (FCT), finger tapping test (FTT), finger to nose test (FNT) and dysdiadochokinesia test (DDKT). Kinematic features were extracted from this data and correlated with clinical ratings of severity of ataxia using the Scale for the Assessment and Rating of Ataxia (SARA). These features were refined using Feed Backward feature Elimination (the best performing method of four). Using several different learning models, including Linear Discrimination, Quadratic Discrimination Analysis, Support Vector Machine and K-Nearest Neighbour these extracted features were used to accurately discriminate between ataxics and control subjects. Leave-One-Out cross validation estimated the generalised performance of the diagnostic model as well as the severity predicting regression model. Results The selected model accurately ( $$96.4\%$$ 96.4 % ) predicted the clinical scores for ataxia and correlated well with clinical scores of the severity of ataxia ( $$rho = 0.8$$ r h o = 0.8 , $$p < 0.001$$ p < 0.001 ). The severity estimation was also considered in a 4-level scale to provide a rating that is familiar to the current clinically-used rating of upper limb impairments. The combination of FCT and FTT performed as well as all four test combined in predicting the presence and severity of ataxia. Conclusion Individual bedside tests can be emulated using features derived from sensors worn while bedside tests of cerebellar ataxia were being performed. Each test emphasises different aspects of stability, timing, accuracy and rhythmicity of movements. Using the current models it is possible to model the clinician in identifying ataxia and assessing severity but also to identify those test which provide the optimum set of data. Trial registration Human Research and Ethics Committee, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia (HREC Reference Number: 11/994H/16).

Gain-of-function polymorphisms in the transcription factor IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing systemic lupus erythematosus. However, the IRF5-expressing cell type(s) responsible for lupus pathogenesis in vivo is not known. We now show that monoallelic IRF5 deficiency in B cells markedly reduced disease in a murine lupus model. In contrast, similar reduction of IRF5 expression in macrophages, monocytes, and neutrophils did not reduce disease severity. B cell receptor and TLR7 signaling synergized to promote IRF5 phosphorylation and increase IRF5 protein expression, with these processes being independently regulated. This synergy increased B cell–intrinsic IL-6 and TNF-α production, both key requirements for germinal center (GC) responses, with IL-6 and TNF-α production in vitro and in vivo being substantially lower with loss of 1 allele of IRF5. Mechanistically, TLR7-dependent IRF5 nuclear translocation was reduced in B cells from IRF5-heterozygous mice. In addition, we show in multiple lupus models that IRF5 expression was dynamically regulated in vivo with increased expression in GC B cells compared with non-GC B cells and with further sequential increases during progression to plasmablasts and long-lived plasma cells. Overall, a critical threshold level of IRF5 in B cells was required to promote disease in murine lupus.

IntroductionCholesterol levels have been associated with age-related cognitive decline, however, such an association has not been comprehensively explored in people with Parkinson’s disease (PD). To address this uncertainty, the current cross-sectional study examined the cholesterol profile and cognitive performance in a cohort of PD patients.MethodsCognitive function was evaluated using two validated assessments (ACE-R and SCOPA-COG) in 182 people with PD from the Australian Parkinson’s Disease Registry. Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and Triglyceride (TRG) levels were examined within this cohort. The influence of individual lipid subfractions on domain-specific cognitive performance was investigated using covariate-adjusted generalised linear models.ResultsFemales with PD exhibited significantly higher lipid subfraction levels (TC, HDL, and LDL) when compared to male counterparts. While accounting for covariates, HDL levels were strongly associated with poorer performance across multiple cognitive domains in females but not males. Conversely, TC and LDL levels were not associated with cognitive status in people with PD.ConclusionHigher serum HDL associates with poorer cognitive function in females with PD and presents a sex-specific biomarker for cognitive impairment in PD.

Predation mortality can influence the distribution and abundance of fish populations. While predation is often assessed using direct observations of prey consumption, potential predation can be predicted from co-occurring predator and prey densities under varying environmental conditions. Juvenile Pacific salmon Oncorhynchus spp. (i.e., smolts) from the Columbia River Basin experience elevated mortality during the transition from estuarine to ocean habitat, but a thorough understanding of the role of predation remains incomplete. We used a Holling type II functional response to estimate smolt predation risk based on observations of piscivorous seabirds (sooty shearwater [Ardenna griseus] and common murre [Uria aalge]) and local densities of alternative prey fish including northern anchovy (Engraulis mordax) in Oregon and Washington coastal waters during May and June 2010-2012. We evaluated predation risk relative to the availability of alternative prey and physical factors including turbidity and Columbia River plume area, and compared risk to returns of adult salmon. Seabirds and smolts consistently co-occurred at sampling stations throughout most of the study area (mean = 0.79 ± 0.41, SD), indicating that juvenile salmon are regularly exposed to avian predators during early marine residence. Predation risk for juvenile coho (Oncorhynchus kisutch), yearling Chinook salmon (O. tshawytscha), and subyearling Chinook salmon was on average 70% lower when alternative prey were present. Predation risk was greater in turbid waters, and decreased as water clarity increased. Juvenile coho and yearling Chinook salmon predation risk was lower when river plume surface areas were greater than 15,000 km2, while the opposite was estimated for subyearling Chinook salmon. These results suggest that plume area, turbidity, and forage fish abundance near the mouth of the Columbia River, all of which are influenced by river discharge, are useful indicators of potential juvenile salmon mortality that could inform salmonid management.

Although Arctic marine ecosystems are changing rapidly, year-round monitoring is currently very limited and presents multiple challenges unique to this region. The Chukchi Ecosystem Observatory (CEO) described here uses new sensor technologies to meet needs for continuous, high-resolution, and year-round observations across all levels of the ecosystem in the biologically productive and seasonally ice-covered Chukchi Sea off the northwest coast of Alaska. This mooring array records a broad suite of variables that facilitate observations, yielding better understanding of physical, chemical, and biological couplings, phenologies, and the overall state of this Arctic shelf marine ecosystem. While cold temperatures and 8 months of sea ice cover present challenging conditions for the operation of the CEO, this extreme environment also serves as a rigorous test bed for innovative ecosystem monitoring strategies. Here, we present data from the 2015–2016 CEO deployments that provide new perspectives on the seasonal evolution of sea ice, water column structure, and physical properties, annual cycles in nitrate, dissolved oxygen, phytoplankton blooms, and export, zooplankton abundance and vertical migration, the occurrence of Arctic cod, and vocalizations of marine mammals such as bearded seals. These integrated ecosystem observations are being combined with ship-based observations and modeling to produce a time series that documents biological community responses to changing seasonal sea ice and water temperatures while establishing a scientific basis for ecosystem management.

Whether or not neurogenesis occurs in the adult substantia nigra pars compacta (SNc) is an important question relevant for developing better treatments for the motor symptoms of Parkinson's disease (PD). Although controversial, it is generally believed that dividing cells here remain undifferentiated or differentiate into glia, not neurons. However, there is a suggestion that Nestin-expressing neural precursor cells (NPCs) in the adult SNc have a propensity to differentiate into neurons, which we sought to confirm in the present study. Adult (>8-weeks old) transgenic NesCreERT2/GtROSA or NesCreERT2/R26eYFP mice were used to permanently label Nestin-expressing cells and their progeny with β-galactosidase (β-gal) or enhanced yellow fluorescent protein (eYFP), respectively. Most β-gal+ or eYFP+ cells were found in the ependymal lining of the midbrain aqueduct (Aq) and in the midline ventral to Aq. Smaller but significant numbers were in the periaqueductal gray (PAG), the ventral tegmental area (VTA), and in SNc. Low-level basal proliferation was evidenced by a modest increase in number of β-gal+ or eYFP+ cells over time, fewer β-gal+ or eYFP+ cells when mice were administered the anti-mitotic agent Cytarabine, and incorporation of the proliferation marker bromodeoxyuridine (BrdU) in a very small number of β-gal+ cells. No evidence of migration was found, including no immunoreactivity against the migration markers doublecortin (DCX) or polysialic acid neural cell adhesion molecule (PSA-NCAM), and no dispersal of β-gal+ or eYFP+ cells through the midbrain parenchyma over time. However, β-gal+ or eYFP+ cells did increase in size and express higher levels of mature neuronal genes over time, indicating growth and neuronal differentiation. In mice whose SNc dopamine neurons had been depleted with 6-hydroxy-dopamine, a model of PD, there were ~2-fold more β-gal+ cells in SNc specifically, although the proportion that were also NeuN+ was not affected. Remarkably, as early as 4 days following putative Nestin-expression, many β-gal+ or eYFP+ cells had mature neuronal morphology and were NeuN+. Furthermore, mature neuronal β-gal+ cells were immunoreactive against the self-renewal or pluripotency marker sex determining region Y-box 2 (Sox2). Overall, our data support the notion that some Nestin-expressing, presumably NPCs, have a limited capacity for proliferation, no capacity for migration, and a propensity to generate new neurons within the microenvironment of the adult midbrain. However, our data also suggest that significant numbers of extant midbrain neurons express Nestin and other classical neurogenesis markers in contexts that are presumably not neurogenic. These findings foreshadow duplicitous roles for Nestin and other molecules that are traditionally associated with neurogenesis in the adult midbrain, which should be considered in future PD research.

Background. Heightened impulsivity has been reported in a subset of people with Parkinson’s disease (PwP) and is considered a risk factor for the development of impulse control disorders (ICDs). However, at present, there are no recognised biochemical markers of heightened impulsivity. Objectives. To determine if ceruloplasmin, a serum marker involved in the regulation of iron and copper homeostasis, is associated with trait impulsivity in PwP. Methods. The study measured serum ceruloplasmin and impulsivity using the Barratt Impulsiveness Scale (BIS-11) in an Australian cohort of 214 PwP. Multivariate general linear models (GLMs) were used to identify whether higher serum ceruloplasmin levels (>75th percentile) were significantly predictive of BIS-11 scores. Results. Serum ceruloplasmin was higher in females with PD (p

Commercial viability of Marine Renewable Energy (MRE) is progressing but no national or international monitoring standards have been established for wave or tidal energy sites. Standardized monitoring within and across MRE sectors is necessary to expedite project permitting/consenting, detect environmental impacts, and enable comparison among sites and technologies. Acoustic backscatter from a bottom-deployed platform at a pilot wave energy site off Newport, Oregon was compared to data collected at a tidal turbine site in Admiralty Inlet, Washington. Metrics that describe fish and macrozooplankton densities and vertical distributions derived from acoustic backscattered energy were compared using wavelets and Autoregressive Moving Average models (ARMA). Average density and vertical distribution values significantly differed between sites. Metrics of density and location in the water column displayed diel (24 h) and tidal (12 h) cycles. Dispersion of animals in the water column varied at 64- and 128-h periods at both sites. Applicability of methods in both sectors suggests that a standard approach to biological monitoring is possible. Stationary acoustics and analytic methods presented here can be used to characterize pre-installation conditions and refine post-installation monitoring to site-specific characteristics to ensure cost-effective detection of impacts associated with MRE development.

Background. Studies attempting to elucidate an association between homocysteine and symptom progression in Parkinson’s disease (PD) have had largely discrepant findings. This study aimed to investigate elevated serum homocysteine levels and symptom progression in a cohort of PD patients. Methods. Serum homocysteine, folate, and vitamin B12 levels were measured in 205 people with PD and 78 age-matched healthy controls. People with Parkinson’s disease underwent a battery of clinical assessments to evaluate symptom severity, including motor (MDS-UPDRS) and cognitive (ACE-R) assessments. Multivariate generalised linear models were created, controlling for confounding variables, and were used to determine whether serum markers are associated with various symptom outcome measures. Results. People with Parkinson’s disease displayed significantly elevated homocysteine levels (p

The inflammatory response within the central nervous system (CNS) is a tightly regulated cascade of events which is a balance of both cytotoxic and cytotrophic effects which determine the outcome of an injury. The two effects are inextricably linked, particularly in traumatic brain injury or stroke, where permanent dysfunction is often observed. Chronic brain inflammation is a key barrier to regeneration. This is considered a toxic, growth inhibitory mechanism; yet, the inflammatory response must also be considered as a mechanism that can be exploited as protective and reparative. Repurposing this complex response is the challenge for tissue engineers: to design treatments to repair and regenerate damaged tissue after brain insult. Astrocytes are important cells within the CNS which play a key role after traumatic brain injury. A comprehensive understanding of their functions—both cytotrophic and cytotoxic—will enable designed materials and drug delivery approaches for improved treatment options post traumatic injury. Understanding, evaluating, and designing biomaterials that match the healthy neural environment to temporally alter the inflammatory cascade represent a promise neural tissue engineering strategy to optimise repair and regeneration after injury.