Multimodal evaluation of network activity and optogenetic interventions in human hippocampal slices.

Seizures are made up of the coordinated activity of networks of neurons, suggesting that control of neurons in the pathologic circuits of epilepsy could allow for control of the disease. Optogenetics has been effective at stopping seizure-like activity in non-human disease models by increasing inhibitory tone or decreasing excitation, although this effect has not been shown in human brain tissue. Many of the genetic means for achieving channelrhodopsin expression in non-human models are not possible in humans, and vector-mediated methods are susceptible to species-specific tropism that may affect translational potential.

Evolutionarily conserved brainstem architecture enables gravity-guided vertical navigation.

The sensation of gravity anchors our perception of the environment and is important for navigation. However, the neural circuits that transform gravity into commands for navigation are undefined. We first determined that larval zebrafish (Danio rerio) navigate vertically by maintaining a consistent heading across a series of upward climb or downward dive bouts.

Partial information decomposition for continuous variables based on shared exclusions: Analytical formulation and estimation.

Describing statistical dependencies is foundational to empirical scientific research. For uncovering intricate and possibly nonlinear dependencies between a single target variable and several source variables within a system, a principled and versatile framework can be found in the theory of partial information decomposition (PID). Nevertheless, the majority of existing PID measures are restricted to categorical variables, while many systems of interest in science are continuous.

Data-driven derivation of an adverse outcome pathway linking vascular endothelial growth factor receptor (VEGFR), endocrine disruption, and atherosclerosis.

Dysregulation of vascular endothelial growth factor (VEGF) and its receptor (VEGFR) contributes to atherosclerosis and cardiovascular disease (CVD), making it a potential target for CVD risk assessment. High-throughput screening (HTS) approaches have resulted in large-scale in vitro data, providing mechanistic information that can help assess chemical toxicity and identify molecular ini­tiating events (MIEs) of adverse outcome pathways (AOPs). AOPs represent a logical sequence of biological responses contributing to toxicity and are valuable tools to inform chemical risk assessment.

Behavioral control through the direct, focal silencing of neuronal activity.

The ability to optically stimulate and inhibit neurons has revolutionized neuroscience research. Here, we present a direct, potent, user-friendly chemical approach for optically silencing neurons. We have rendered saxitoxin (STX), a naturally occurring paralytic agent, transiently inert through chemical protection with a previously undisclosed nitrobenzyl-derived photocleavable group.

Persistent GDNF Expression 45 Months after Putaminal Infusion of AAV2-GDNF in a Patient with Parkinson's Disease.

Objective: Gene therapy by convection-enhanced delivery of type 2 adeno-associated virus-glial cell derived neurotrophic factor (AAV2-GDNF) to the bilateral putamina seeks to increase GDNF gene expression and treat Parkinson's disease (PD).

Methods: A 63-year-old man with advanced PD received AAV2-GDNF in a clinical trial. He died from pneumonia after anterior cervical discectomy and fusion 45 months later.

A randomized feasibility trial of medium chain triglyceride-supplemented ketogenic diet in people with Parkinson's disease.

Background: A ketogenic diet (KD) may benefit people with neurodegenerative disorders marked by mitochondrial depolarization/insufficiency, including Parkinson's disease (PD).

Objective: Evaluate whether a KD supplemented by medium chain triglyceride (MCT-KD) oil is feasible and acceptable for PD patients. Furthermore, we explored the effects of MCT-KD on blood ketone levels, metabolic parameters, levodopa absorption, mobility, nonmotor symptoms, simple motor and cognitive tests, autonomic function, and resting-state electroencephalography (rsEEG).

A feedback-driven brain organoid platform enables automated maintenance and high-resolution neural activity monitoring.

The analysis of tissue cultures, particularly brain organoids, requires a sophisticated integration and coordination of multiple technologies for monitoring and measuring. We have developed an automated research platform enabling independent devices to achieve collaborative objectives for feedback-driven cell culture studies. Our approach enables continuous, communicative, non-invasive interactions within an Internet of Things (IoT) architecture among various sensing and actuation devices, achieving precisely timed control of biological experiments.

A brainstem circuit for gravity-guided vertical navigation.

The sensation of gravity anchors our perception of the environment and is crucial for navigation. However, the neural circuits that transform gravity into commands for navigation are undefined. We first determined that larval zebrafish () navigate vertically by maintaining a consistent heading across a series of upward climb or downward dive bouts.

Perturbation and resilience of the gut microbiome up to 3 months after β-lactams exposure in healthy volunteers suggest an important role of microbial β-lactamases.

Background: Antibiotics notoriously perturb the gut microbiota. We treated healthy volunteers either with cefotaxime or ceftriaxone for 3 days, and collected in each subject 12 faecal samples up to day 90. Using untargeted and targeted phenotypic and genotypic approaches, we studied the changes in the bacterial, phage and fungal components of the microbiota as well as the metabolome and the β-lactamase activity of the stools.

The Multi-temporal and Multi-dimensional Global Urban Centre Database to Delineate and Analyse World Cities.

Monitoring sustainable urban development requires comparable geospatial information on cities across several thematic domains. Here we present the first global database combining such information with city extents. The Global Human Settlement Urban Centre Database (GHS-UCDB) is produced by geospatial data integration to characterise more than 10,000 urban centres worldwide.

Internet-Connected Cortical Organoids for Project-Based Stem Cell and Neuroscience Education.

The introduction of Internet-connected technologies to the classroom has the potential to revolutionize STEM education by allowing students to perform experiments in complex models that are unattainable in traditional teaching laboratories. By connecting laboratory equipment to the cloud, we introduce students to experimentation in pluripotent stem cell (PSC)-derived cortical organoids in two different settings: using microscopy to monitor organoid growth in an introductory tissue culture course and using high-density (HD) multielectrode arrays (MEAs) to perform neuronal stimulation and recording in an advanced neuroscience mathematics course. We demonstrate that this approach develops interest in stem cell and neuroscience in the students of both courses.

Multisensory navigational strategies of hatchling fish for dispersal.

Animals influence how they disperse in the environment by sensing local cues and adapting how they move. However, controlling dispersal can present a particular challenge early in life when animals tend to be more limited in their capacities to sense and move. To what extent and by what mechanisms can newly hatched fish control how they disperse? Here, we reveal hatchling sensorimotor mechanisms for controlling dispersal by combining swim tracking and precise sensory manipulations of a model species, zebrafish.

Anatomical Diversity of the Adult Corticospinal Tract Revealed by Single-Cell Transcriptional Profiling.

The corticospinal tract (CST) forms a central part of the voluntary motor apparatus in all mammals. Thus, injury, disease, and subsequent degeneration within this pathway result in chronic irreversible functional deficits. Current strategies to repair the damaged CST are suboptimal in part because of underexplored molecular heterogeneity within the adult tract.

Internet-connected cortical organoids for project-based stem cell and neuroscience education.

The introduction of internet-connected technologies to the classroom has the potential to revolutionize STEM education by allowing students to perform experiments in complex models that are unattainable in traditional teaching laboratories. By connecting laboratory equipment to the cloud, we introduce students to experimentation in pluripotent stem cell-derived cortical organoids in two different settings: Using microscopy to monitor organoid growth in an introductory tissue culture course, and using high density multielectrode arrays to perform neuronal stimulation and recording in an advanced neuroscience mathematics course. We demonstrate that this approach develops interest in stem cell and neuroscience in the students of both courses.

Relationships of hospitalization outcomes and timing to endoscopy in non-variceal upper gastrointestinal bleeding: A nationwide analysis.

Background: The optimal timing of esophagogastroduodenoscopy (EGD) and the impact of clinico-demographic factors on hospitalization outcomes in non-variceal upper gastrointestinal bleeding (NVUGIB) remains an area of active research.

Aim: To identify independent predictors of outcomes in patients with NVUGIB, with a particular focus on EGD timing, anticoagulation (AC) status, and demographic features.

Methods: A retrospective analysis of adult patients with NVUGIB from 2009 to 2014 was performed using validated ICD-9 codes from the National Inpatient Sample database.

The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope: A multicenter retrospective international study.

Background: Duodenoscope-related multidrug-resistant organism (MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography (ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy.

Electrophysiological Characterization of a Variant with Tremor Phenotype.

Background: The concept of a myopathy with associated tremor ("myogenic tremor") in humans has been previously described for specific (Myosin-Binding Protein C) variants. Here we report for the first time an individual with tremor who was found to have a de-novo likely pathogenic variant in Myosin Heavy Chain 7 (MYH7

Unlabelled: We provide a detailed electrophysiological characterization of the tremor syndrome in a human individual with a myopathy and this pathogenic MYH7 variant to provide further insight in the phenotypic spectrum and pathomechanism of myogenic tremors in skeletal sarcomeric myopathies.

Methods: Electromyographic recordings were obtained from facial muscles, as well as bilateral upper and lower extremities.

Association of polygenic risk score with response to deep brain stimulation in Parkinson's disease.

Background: Deep brain stimulation (DBS) is a well-established treatment option for select patients with Parkinson's Disease (PD). However, response to DBS varies, therefore, the ability to predict who will have better outcomes can aid patient selection. Some PD-related monogenic mutations have been reported among factors that influence response to DBS.

Neural valuation of rewards and punishments in posttraumatic stress disorder: a computational approach.

Posttraumatic stress disorder (PTSD) is associated with changes in fear learning and decision-making, suggesting involvement of the brain's valuation system. Here we investigate the neural mechanisms of subjective valuation of rewards and punishments in combat veterans. In a functional MRI study, male combat veterans with a wide range of posttrauma symptoms (N = 48, Clinician Administered PTSD Scale, CAPS-IV) made a series of choices between sure and uncertain monetary gains and losses.