Vimentin filaments integrate low-complexity domains in a complex helical structure.

Intermediate filaments (IFs) are integral components of the cytoskeleton. They provide cells with tissue-specific mechanical properties and are involved in numerous cellular processes. Due to their intricate architecture, a 3D structure of IFs has remained elusive. Here we use cryo-focused ion-beam milling, cryo-electron microscopy and tomography to obtain a 3D structure of vimentin IFs (VIFs). VIFs assemble into a modular, intertwined and flexible helical structure of 40 α-helices in cross-section, organized into five protofibrils. Surprisingly, the intrinsically disordered head domains form a fiber in the lumen of VIFs, while the intrinsically disordered tails form lateral connections between the protofibrils. Our findings demonstrate how protein domains of low sequence complexity can complement well-folded protein domains to construct a biopolymer with striking mechanical strength and stretchability.

Biodegradable plastics in Mediterranean coastal environments feature contrasting microbial succession.

Plastic pollution of the ocean is a top environmental concern. Biodegradable plastics present a potential "solution" in combating the accumulation of plastic pollution, and their production is currently increasing. While these polymers will contribute to the future plastic marine debris budget, very little is known still about the behavior of biodegradable plastics in different natural environments. In this study, we molecularly profiled entire microbial communities on laboratory confirmed biodegradable polybutylene sebacate-co-terephthalate (PBSeT) and polyhydroxybutyrate (PHB) films, and non-biodegradable conventional low-density polyethylene (LDPE) films that were incubated in situ in three different coastal environments in the Mediterranean Sea. Samples from a pelagic, benthic, and eulittoral habitat were taken at five timepoints during an incubation period of 22 months. We assessed the presence of potential biodegrading bacterial and fungal taxa and contrasted them against previously published in situ disintegration data of these polymers. Scanning electron microscopy imaging complemented our molecular data. Putative plastic degraders occurred in all environments, but there was no obvious "core" of shared plastic-specific microbes. While communities varied between polymers, the habitat predominantly selected for the underlying communities. Observed disintegration patterns did not necessarily match community patterns of putative plastic degraders.

Multimodal layer modelling reveals in vivo pathology in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease characterized by the loss of motor control. Current understanding of ALS pathology is largely based on post-mortem investigations at advanced disease stages. A systematic in vivo description of the microstructural changes that characterize early stage ALS, and their subsequent development, is so far lacking. Recent advances in ultra-high field (7 T) MRI data modelling allow us to investigate cortical layers in vivo. Given the layer-specific and topographic signature of ALS pathology, we combined submillimetre structural 7 T MRI data (qT1, QSM), functional localizers of body parts (upper limb, lower limb, face) and layer modelling to systematically describe pathology in the primary motor cortex (M1), in 12 living ALS patients with reference to 12 matched controls. Longitudinal sampling was performed for a subset of patients. We calculated multimodal pathology maps for each layer (superficial layer, layer 5a, layer 5b, layer 6) of M1 to identify hot spots of demyelination, iron and calcium accumulation in different cortical fields. We show preserved mean cortical thickness and layer architecture of M1, despite significantly increased iron in layer 6 and significantly increased calcium in layer 5a and superficial layer, in patients compared to controls. The behaviourally first-affected cortical field shows significantly increased iron in L6 compared to other fields, while calcium accumulation is atopographic and significantly increased in the low myelin borders between cortical fields compared to the fields themselves. A subset of patients with longitudinal data shows that the low myelin borders are particularly disrupted and that calcium hot spots, but to a lesser extent iron hot spots, precede demyelination. Finally, we highlight that a very slow progressing patient (Patient P4) shows a distinct pathology profile compared to the other patients. Our data show that layer-specific markers of in vivo pathology can be identified in ALS patients with a single 7 T MRI measurement after first diagnosis, and that such data provide critical insights into the individual disease state. Our data highlight the non-topographic architecture of ALS disease spread and the role of calcium, rather than iron accumulation, in predicting future demyelination. We also highlight a potentially important role of low myelin borders, that are known to connect to multiple areas within the M1 architecture, in disease spread. Finally, the distinct pathology profile of a very-slow progressing patient (Patient P4) highlights a distinction between disease duration and progression. Our findings demonstrate the importance of in vivo histology imaging for the diagnosis and prognosis of neurodegenerative diseases such as ALS.

Association of Radiation Dose to the Amygdala-Orbitofrontal Network with Emotion Recognition Task Performance in Patients with Low-Grade and Benign Brain Tumors.

BACKGROUND: Although data are limited, difficulty in social cognition occurs in up to 83% of patients with brain tumors. It is unknown whether cranial radiation therapy (RT) dose to the amygdala-orbitofrontal network can impact social cognition. METHODS: We prospectively enrolled 51 patients with low-grade and benign brain tumors planned for cranial RT. We assessed longitudinal changes on an emotion recognition task (ERT) that measures the ability to recognize emotional states by displaying faces expressing six basic emotions and their association with the RT dose to the amygdala-orbitofrontal network. ERT outcomes included the median time to choose a response (ERTOMDRT) or correct response (ERTOMDCRT) and total correct responses (ERTHH). RESULTS: The RT dose to the amygdala-orbitofrontal network was significantly associated with longer median response times on the ERT. Increases in median response times occurred at lower doses than decreases in total correct responses. The medial orbitofrontal cortex was the most important variable on regression trees predicting change in the ERTOMDCRT. DISCUSSION: This is, to our knowledge, the first study to show that off-target RT dose to the amygdala-orbitofrontal network is associated with performance on a social cognition task, a facet of cognition that has previously not been mechanistically studied after cranial RT.

The phenotype of delirium based on a close reading of diagnostic criteria.

OBJECTIVE: Although delirium is well known to acute care clinicians, the features required for its diagnosis and how to understand and operationalize them remain sticking points in the field. To clarify the delirium phenotype, we present a close reading of past and current sets of delirium diagnostic criteria. METHODS: We first differentiate the delirium syndrome (i.e., features evaluated at bedside) from additional criteria required for diagnosis. Next, we align related features across diagnostic systems and examine them in context to determine intent. Where criteria are ambiguous, we review common delirium instruments to illustrate how they have been interpreted. RESULTS: An acute disturbance in attention is universally attested across diagnostic systems. A second core feature denotes confusion and has been included across systems as disturbance in awareness, impaired consciousness, and thought disorganization. This feature may be better understood as a disturbance in thought clarity and operationalized in terms of neuropsychological domains thereby clearly linking it to global neurocognitive disturbance. Altered level of activity describes a third core feature, including motor and sleep/wake cycle disturbances. Excluding stupor (wherein mental content cannot be assessed due to reduced arousal) from delirium, as in DSM-5-TR, is appropriate for a psychiatric diagnosis, but the brain injury exclusion in ICD-11 is unjustified. CONCLUSIONS: The delirium phenotype involves a disturbance in attention, qualitative thought clarity, and quantitative activity level, including in relation to expected sleep/wake cycles. Future diagnostic systems should include a severity threshold and specify that delirium diagnosis refers to a 24-h period.

Adopting a child perspective for exposome research on mental health and cognitive development - Conceptualisation and opportunities.

Mental disorders among children and adolescents pose a significant global challenge. The exposome framework covering the totality of internal, social and physical exposures over a lifetime provides opportunities to better understand the causes of and processes related to mental health, and cognitive functioning. The paper presents a conceptual framework on exposome, mental health, and cognitive development in children and adolescents, with potential mediating pathways, providing a possibility for interventions along the life course. The paper underscores the significance of adopting a child perspective to the exposome, acknowledging children's specific vulnerability, including differential exposures, susceptibility of effects and capacity to respond; their susceptibility during development and growth, highlighting neurodevelopmental processes from conception to young adulthood that are highly sensitive to external exposures. Further, critical periods when exposures may have significant effects on a child's development and future health are addressed. The paper stresses that children's behaviour, physiology, activity pattern and place for activities make them differently vulnerable to environmental pollutants, and calls for child-specific assessment methods, currently lacking within today's health frameworks. The importance of understanding the interplay between structure and agency is emphasized, where agency is guided by social structures and practices and vice-versa. An intersectional approach that acknowledges the interplay of social and physical exposures as well as a global and rural perspective on exposome is further pointed out. To advance the exposome field, interdisciplinary efforts that involve multiple scientific disciplines are crucial. By adopting a child perspective and incorporating an exposome approach, we can gain a comprehensive understanding of how exposures impact children's mental health and cognitive development leading to better outcomes.

Bacterial diversity of biofilms on polyhydroxybutyrate exposed to marine conditions: Ex-situ vs. in-situ tests.

Biofilms form on any available surface and, depending on the characteristics of the material and the environmental conditions, biodegradation can take place. We compared the bacterial composition of polyhydroxybutyrate (PHB)-related biofilm communities from marine ex-situ and in-situ tests to assess the differences in diversity and abundance between these two biofilms. This comparison will help to better assess the transferability of tank tests to real-life scenarios. The in-situ tests were set up in the Mediterranean Sea on the Island of Elba, Italy where PHB-tensile bars were lodged in the sediments. This created a water-exposed aerobic and mud-planted anaerobic scenario. The ex-situ tests were modeled after in-situ tests and performed in temperature-controlled tanks. The PHB-related biofilms were harvested after 240 days of exposure along with planktonic bacteria, and particle- and sediment-related biofilm. The bacterial composition was elucidated using 16S rDNA sequencing. Biofilms harvested from the in-situ test were more diverse, less even, and contained more rare species compared to biofilms from the ex-situ test. The PHB-related biofilm was characterized by a higher abundance of the bacterial order Desulfobacterales. The composition of PHB-related biofilm varied significantly between the two tests and between aerobic and anaerobic conditions. The composition of PHB-related biofilm was significantly different from planktonic bacteria, particle, and sediment-related biofilm, showing the influence of PHB on the biofilm composition. Thus, the ex-situ tank test for PHB degradation cannot, in terms of bacterial composition, simulate the in-situ conditions to their full extent.

Layer-specific vulnerability is a mechanism of topographic map aging.

Topographic maps form a critical feature of cortical organization, yet are poorly described with respect to their microstructure in the living aging brain. We acquired quantitative structural and functional 7T-MRI data from younger and older adults to characterize layer-wise topographic maps of the primary motor cortex (M1). Using parcellation-inspired techniques, we show that quantitative T1 and Quantitative Susceptibility Maps values of the hand, face, and foot areas differ significantly, revealing microstructurally distinct cortical fields in M1. We show that these fields are distinct in older adults and that myelin borders between them do not degenerate. We further show that the output layer 5 of M1 shows a particular vulnerability to age-related increased iron, while layer 5 and the superficial layer show increased diamagnetic substance, likely reflecting calcifications. Taken together, we provide a novel 3D model of M1 microstructure, where body parts form distinct structural units, but layers show specific vulnerability toward increased iron and calcium in older adults. Our findings have implications for understanding sensorimotor organization and aging, in addition to topographic disease spread.

Role of non-classical monocytes in HIV-associated vascular cognitive impairment.

Despite antiretroviral treatment (cART), people living with HIV (PLWH) are more susceptible to neurocognitive impairment (NCI), probably due to synergistic/additive contribution of traditional cerebrovascular risk factors. Specifically, altered blood brain barrier (BBB) and transmigration of inflammatory monocytes are risk factors for developing cerebral small vessel disease (CSVD). In order to investigate if inflammatory monocytes exacerbate CSVD and cognitive impairment, 110 PLWH on cART and 110 age-, sex- and Reynold’s cardiovascular risk score-matched uninfected individuals were enrolled. Neuropsychological testing, brain magnetic resonance imaging and whole blood analyses to measure platelet-monocyte interaction and monocyte, endothelial activation were performed. Results demonstrated that PLWH exhibited increased levels of platelet-monocyte complexes (PMCs) and higher expression of activation molecules on PMCs. PLWH with CSVD had the poorest cognitive performance and the highest circulating levels of non-classical monocytes which exhibited significant inverse correlation with each other. Furthermore, markers of monocyte and endothelium activation were significantly positively correlated indicating BBB impairment. Our results confirm that interaction with platelets activates and drives monocytes towards an inflammatory phenotype in PLWH. In particular, elevated levels of non-classical monocytes may represent a common pathway to neuroinflammation, CSVD and subsequent cognitive impairment, warranting further longitudinal studies to evaluate responsiveness of this potential biomarker.

Cognitive and neuroimaging outcomes in individuals with benign and low-grade brain tumours receiving radiotherapy: a protocol for a prospective cohort study.

INTRODUCTION: Radiation-induced cognitive decline (RICD) occurs in 50%-90% of adult patients 6 months post-treatment. In patients with low-grade and benign tumours with long expected survival, this is of paramount importance. Despite advances in radiation therapy (RT) treatment delivery, better understanding of structures important for RICD is necessary to improve cognitive outcomes. We hypothesise that RT may affect network topology and microstructural integrity on MRI prior to any gross anatomical or apparent cognitive changes. In this longitudinal cohort study, we aim to determine the effects of RT on brain structural and functional integrity and cognition. METHODS AND ANALYSIS: This study will enroll patients with benign and low-grade brain tumours receiving partial brain radiotherapy. Patients will receive either hypofractionated (>2 Gy/fraction) or conventionally fractionated (1.8-2 Gy/fraction) RT. All participants will be followed for 12 months, with MRIs conducted pre-RT and 6-month and 12 month post-RT, along with a battery of neurocognitive tests and questionnaires. The study was initiated in late 2018 and will continue enrolling through 2024 with final follow-ups completing in 2025. The neurocognitive battery assesses visual and verbal memory, attention, executive function, processing speed and emotional cognition. MRI protocols incorporate diffusion tensor imaging and resting state fMRI to assess structural connectivity and functional connectivity, respectively. We will estimate the association between radiation dose, imaging metrics and cognitive outcomes. ETHICS AND DISSEMINATION: This study has been approved by the Research Subjects Review Board at the University of Rochester (STUDY00001512: Cognitive changes in patients receiving partial brain radiation). All results will be published in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04390906.

Generating environmental sampling and testing data for micro- and nanoplastics for use in life cycle impact assessment.

Ongoing efforts focus on quantifying plastic pollution and describing and estimating the related magnitude of exposure and impacts on human and environmental health. Data gathered during such work usually follows a receptor perspective. However, Life Cycle Assessment (LCA) represents an emitter perspective. This study examines existing data gathering and reporting approaches for field and laboratory studies on micro- and nanoplastics (MNPs) exposure and effects relevant to LCA data inputs. The outcomes indicate that receptor perspective approaches do not typically provide suitable or sufficiently harmonised data. Improved design is needed in the sampling, testing and recording of results using harmonised, validated and comparable methods, with more comprehensive reporting of relevant data. We propose a three-level set of requirements for data recording and reporting to increase the potential for LCA studies and models to utilise data gathered in receptor-oriented studies. We show for which purpose such data can be used as inputs to LCA, particularly in life cycle impact assessment (LCIA) methods. Implementing these requirements will facilitate proper integration of the potential environmental impacts of plastic losses from human activity (e.g. litter) into LCA. Then, the impacts of plastic emissions can eventually be connected and compared with other environmental issues related to anthropogenic activities.

Longitudinal Effects of Combination Antiretroviral Therapy on Cognition and Neuroimaging Biomarkers in Treatment-Naive People With HIV.

BACKGROUND AND OBJECTIVES: While combination antiretroviral therapy (cART) has dramatically increased the life expectancy of people with HIV (PWH), nearly 50% develop HIV-associated neurocognitive disorders. This may be due to previously uncontrolled HIV viral replication, immune activation maintained by residual viral replication or activation from other sources, or cART-associated neurotoxicity. The aim of this study was to determine the effect of cART on cognition and neuroimaging biomarkers in PWH before and after initiation of cART compared with that in HIV-negative controls (HCs) and HIV elite controllers (ECs) who remain untreated. METHODS: We recruited 3 groups of participants from the University of Rochester, McGovern Medical School, and SUNY Upstate Medical University: (1) ART treatment-naive PWH; (2) age-matched HCs; and (3) ECs. Participants underwent brain MRI and clinical and neuropsychological assessments at baseline, 1 year, and 2 years. PWH were also assessed 12 weeks after initiating cART. Volumetric analysis and fractal dimensionality (FD) were calculated for cortical and subcortical regions. Mixed effect regressions examined the effect of group and imaging variables on cognition. RESULTS: We enrolled 47 PWH, 58 HCs, and 10 ECs. At baseline, PWH had worse cognition and lower cortical volumes than HCs. Cognition improved after initiation of cART and remained stable over time. Greater cortical thickness was associated with better cognition at baseline; greater FD of parietal, temporal, and occipital lobes was associated with better cognition at baseline and longitudinally. At baseline, ECs had worse cognition, lower cortical thickness, and lower FD in all 4 lobes and caudate than PWH and HCs. Greater cortical thickness, hippocampal volumes, and FD of frontal, temporal, and occipital lobes were associated with better cognition longitudinally. DISCUSSION: Initiation of cART in PWH is associated with improvement in brain structure and cognition. However, significant differences persist over time when compared with HCs. Similar trends in ECs suggest that results are due to HIV infection rather than treatment. Stronger associations between cognition and FD suggest this imaging metric may be a more sensitive marker of neuronal injury than cortical thickness and volumetric measures.

An Automated Tongue Tracker for Quantifying Bulbar Function in ALS.

Introduction: Bulbar symptoms, including difficulty swallowing and speaking, are common in amyotrophic lateral sclerosis (ALS) and other neurological disorders, such as stroke. The presence of bulbar symptoms provides important information regarding clinical outcomes, such as survival time after diagnosis. Nevertheless, there are currently no easily accessible, quantitative methods to measure bulbar function in patients. Methods: We developed an open-source tool called Tongue Tracker (TT) to quantify bulbar function by training a neural network to track kinematic tongue features of short video clips of lateral tongue movements. We tested 16 healthy controls and ten patients with ALS, of whom two patients were clinically diagnosed with bulbar-onset type and eight patients were clinically diagnosed with limb-onset type. Of the limb-onset patients, five patients also showed symptoms of bulbar impairment. Results: We validated TT by comparing the results with manual delineation of tongue movements in the clips. We demonstrate an early-stage bulbar-onset patient who showed fewer and slower tongue sweeps compared to healthy controls and limb-onset patients and we show that five bulbar-impaired limb-onset patients have a different tongue kinematic profile compared to healthy controls. Discussion: TT may serve to detect quantitative markers of bulbar dysfunction in ALS and other motor disorders, such as stroke, by identifying signatures of spasticity or muscle weakness that affects tongue movement speed and/or tongue movement topography.

Vimentin intermediate filaments and filamentous actin form unexpected interpenetrating networks that redefine the cell cortex.

The cytoskeleton of eukaryotic cells is primarily composed of networks of filamentous proteins, F-actin, microtubules, and intermediate filaments. Interactions among the cytoskeletal components are important in determining cell structure and in regulating cell functions. For example, F-actin and microtubules work together to control cell shape and polarity, while the subcellular organization and transport of vimentin intermediate filament (VIF) networks depend on their interactions with microtubules. However, it is generally thought that F-actin and VIFs form two coexisting but separate networks that are independent due to observed differences in their spatial distribution and functions. In this paper, we present a closer investigation of both the structural and functional interplay between the F-actin and VIF cytoskeletal networks. We characterize the structure of VIFs and F-actin networks within the cell cortex using structured illumination microscopy and cryo-electron tomography. We find that VIFs and F-actin form an interpenetrating network (IPN) with interactions at multiple length scales, and VIFs are integral components of F-actin stress fibers. From measurements of recovery of cell contractility after transient stretching, we find that the IPN structure results in enhanced contractile forces and contributes to cell resilience. Studies of reconstituted networks and dynamic measurements in cells suggest direct and specific associations between VIFs and F-actin. From these results, we conclude that VIFs and F-actin work synergistically, both in their structure and in their function. These results profoundly alter our understanding of the contributions of the components of the cytoskeleton, particularly the interactions between intermediate filaments and F-actin.

Early environmental quality and life-course mental health effects: The Equal-Life project.

BACKGROUND: There is increasing evidence that a complex interplay of factors within environments in which children grows up, contributes to children's suboptimal mental health and cognitive development. The concept of the life-course exposome helps to study the impact of the physical and social environment, including social inequities, on cognitive development and mental health over time. METHODS: Equal-Life develops and tests combined exposures and their effects on children's mental health and cognitive development. Data from eight birth-cohorts and three school studies (N = 240.000) linked to exposure data, will provide insights and policy guidance into aspects of physical and social exposures hitherto untapped, at different scale levels and timeframes, while accounting for social inequities. Reasoning from the outcome point of view, relevant stakeholders participate in the formulation and validation of research questions, and in the formulation of environmental hazards. Exposure assessment combines GIS-based environmental indicators with omics approaches and new data sources, forming the early-life exposome. Statistical tools integrate data at different spatial and temporal granularity and combine exploratory machine learning models with hypothesis-driven causal modeling. CONCLUSIONS: Equal-Life contributes to the development and utilization of the exposome concept by (1) integrating the internal, physical and social exposomes, (2) studying a distinct set of life-course effects on a child's development and mental health (3) characterizing the child's environment at different developmental stages and in different activity spaces, (4) looking at supportive environments for child development, rather than merely pollutants, and (5) combining physical, social indicators with novel effect markers and using new data sources describing child activity patterns and environments.

Diverse methylotrophic methanogenic archaea cause high methane emissions from seagrass meadows.

Marine coastlines colonized by seagrasses are a net source of methane to the atmosphere. However, methane emissions from these environments are still poorly constrained, and the underlying processes and responsible microorganisms remain largely unknown. Here, we investigated methane turnover in seagrass meadows of Posidonia oceanica in the Mediterranean Sea. The underlying sediments exhibited median net fluxes of methane into the water column of ca. 106 µmol CH4 ⋅ m-2 ⋅ d-1 Our data show that this methane production was sustained by methylated compounds produced by the plant, rather than by fermentation of buried organic carbon. Interestingly, methane production was maintained long after the living plant died off, likely due to the persistence of methylated compounds, such as choline, betaines, and dimethylsulfoniopropionate, in detached plant leaves and rhizomes. We recovered multiple mcrA gene sequences, encoding for methyl-coenzyme M reductase (Mcr), the key methanogenic enzyme, from the seagrass sediments. Most retrieved mcrA gene sequences were affiliated with a clade of divergent Mcr and belonged to the uncultured Candidatus Helarchaeota of the Asgard superphylum, suggesting a possible involvement of these divergent Mcr in methane metabolism. Taken together, our findings identify the mechanisms controlling methane emissions from these important blue carbon ecosystems.

Fixel-Based Analysis and Free Water Corrected DTI Evaluation of HIV-Associated Neurocognitive Disorders.

Background: White matter (WM) damage is a consistent finding in HIV-infected (HIV+) individuals. Previous studies have evaluated WM fiber tract-specific brain regions in HIV-associated neurocognitive disorders (HAND) using diffusion tensor imaging (DTI). However, DTI might lack an accurate biological interpretation, and the technique suffers from several limitations. Fixel-based analysis (FBA) and free water corrected DTI (fwcDTI) have recently emerged as useful techniques to quantify abnormalities in WM. Here, we sought to evaluate FBA and fwcDTI metrics between HIV+ and healthy controls (HIV-) individuals. Using machine learning classifiers, we compared the specificity of both FBA and fwcDTI metrics in their ability to distinguish between individuals with and without cognitive impairment in HIV+ individuals. Methods: Forty-two HIV+ and 52 HIV- participants underwent MRI exam, clinical, and neuropsychological assessments. FBA metrics included fiber density (FD), fiber bundle cross section (FC), and fiber density and cross section (FDC). We also obtained fwcDTI metrics such as fractional anisotropy (FAT) and mean diffusivity (MDT). Tract-based spatial statistics (TBSS) was performed on FAT and MDT. We evaluated the correlations between MRI metrics with cognitive performance and blood markers, such as neurofilament light chain (NfL), and Tau protein. Four different binary classifiers were used to show the specificity of the MRI metrics for classifying cognitive impairment in HIV+ individuals. Results: Whole-brain FBA showed significant reductions (up to 15%) in various fiber bundles, specifically the cerebral peduncle, posterior limb of internal capsule, middle cerebellar peduncle, and superior corona radiata. TBSS of fwcDTI metrics revealed decreased FAT in HIV+ individuals compared to HIV- individuals in areas consistent with those observed in FBA, but these were not significant. Machine learning classifiers were consistently better able to distinguish between cognitively normal patients and those with cognitive impairment when using fixel-based metrics as input features as compared to fwcDTI metrics. Conclusion: Our findings lend support that FBA may serve as a potential in vivo biomarker for evaluating and monitoring axonal degeneration in HIV+ patients at risk for neurocognitive impairment.

Terrestrial-type nitrogen-fixing symbiosis between seagrass and a marine bacterium.

Symbiotic N2-fixing microorganisms have a crucial role in the assimilation of nitrogen by eukaryotes in nitrogen-limited environments1-3. Particularly among land plants, N2-fixing symbionts occur in a variety of distantly related plant lineages and often involve an intimate association between host and symbiont2,4. Descriptions of such intimate symbioses are lacking for seagrasses, which evolved around 100 million years ago from terrestrial flowering plants that migrated back to the sea5. Here we describe an N2-fixing symbiont, 'Candidatus Celerinatantimonas neptuna', that lives inside seagrass root tissue, where it provides ammonia and amino acids to its host in exchange for sugars. As such, this symbiosis is reminiscent of terrestrial N2-fixing plant symbioses. The symbiosis between Ca. C. neptuna and its host Posidonia oceanica enables highly productive seagrass meadows to thrive in the nitrogen-limited Mediterranean Sea. Relatives of Ca. C. neptuna occur worldwide in coastal ecosystems, in which they may form similar symbioses with other seagrasses and saltmarsh plants. Just like N2-fixing microorganisms might have aided the colonization of nitrogen-poor soils by early land plants6, the ancestors of Ca. C. neptuna and its relatives probably enabled flowering plants to invade nitrogen-poor marine habitats, where they formed extremely efficient blue carbon ecosystems7.

Disintegration half-life of biodegradable plastic films on different marine beach sediments.

The seafloor is considered the major sink for plastic debris in the world's oceans. Biodegradable polymers are available on the market as a substitute for conventional plastic and could potentially end up in the same environment. To gain more insight into the effects of different sediments on the degradation rate of biodegradable plastic we performed two iterative seawater tank experiments. First, to test the effect of sediment grain size, film of Mater-Bi HF03V, a blend of thermoplastic starch and biodegradable polyesters, was placed on the surface of mud as well as on four different grain size fractions of beach sand. Disintegration half-life was shortest on mud (139 days) and increased with the grain size of the beach sediment fractions (63-250 µm: 296 days; 250-500 µm: 310 days; 500-1,000 µm: 438 days; >1,000 µm: 428 days). We assume that the higher surface-to-volume ratio in fine sediment compared to coarse sediment led to a higher bacterial abundance and thus to faster disintegration rates. In a follow-up experiment, the <500 µm fraction of sediment from four different beaches around Isola d'Elba, Italy, was used to test plastic disintegration as above. Additionally, polyhydroxybutyrate (PHB, MIREL P5001) was used as a positive control and high-density polyethylene (HD-PE) as a negative control. No disintegration was observed for HD-PE. Mater-Bi HF03V and PHB disintegrated significantly differently on sediment from different sites, with half-lives of Mater-Bi HF03V ranging from 72 to 368 days and of PHB from 112 to 215 days. Here, the half-life was shortest on slightly coarser sediment and at potentially anthropogenically impacted sites. We assume that the effect of the grain size on the disintegration rate was masked by other parameters influencing the microbial community and activity. Understanding the parameters driving biodegradation is key to reliably report the range of disintegration rates occurring under the various conditions in different ecosystems.

Neurophysiological biomarkers to optimize deep brain stimulation in movement disorders.

Intraoperative neurophysiological information could increase accuracy of surgical deep brain stimulation (DBS) lead placement. Subsequently, DBS therapy could be optimized by specifically targeting pathological activity. In Parkinson's disease, local field potentials (LFPs) excessively synchronized in the beta band (13-35 Hz) correlate with akinetic-rigid symptoms and their response to DBS therapy, particularly low beta band suppression (13-20 Hz) and high frequency gamma facilitation (35-250 Hz). In dystonia, LFPs abnormally synchronize in the theta/alpha (4-13 Hz), beta and gamma (60-90 Hz) bands. Phasic dystonic symptoms and their response to DBS correlate with changes in theta/alpha synchronization. In essential tremor, LFPs excessively synchronize in the theta/alpha and beta bands. Adaptive DBS systems will individualize pathological characteristics of neurophysiological signals to automatically deliver therapeutic DBS pulses of specific spatial and temporal parameters.