Real-time robot topological localization and mapping with limited visual sampling in simulated buried pipe networks.

Our work introduces a real-time robotic localization and mapping system for buried pipe networks. The system integrates exploration and navigation with an localization and topological mapping algorithm. This algorithm is selectively activated at topologically key locations, such as junctions.

Longitudinal machine learning uncouples healthy aging factors from chronic disease risks.

To understand human longevity, inherent aging processes must be distinguished from known etiologies leading to age-related chronic diseases. Such deconvolution is difficult to achieve because it requires tracking patients throughout their entire lives. Here, we used machine learning to infer health trajectories over the entire adulthood age range using extrapolation from electronic medical records with partial longitudinal coverage.

Brain-wide representations of behavior spanning multiple timescales and states in C. elegans.

Changes in an animal's behavior and internal state are accompanied by widespread changes in activity across its brain. However, how neurons across the brain encode behavior and how this is impacted by state is poorly understood. We recorded brain-wide activity and the diverse motor programs of freely moving C.

Neurodevelopment: Maintaining function during circuit reconfiguration.

Neural circuits change during development or following experience by adding neurons and rewiring connections, but mapping such processes is technically daunting. A new study traces maturation of an entire circuit in subcellular detail, revealing continuous functionality under gradual structural change.

Tumor-reactive antibodies evolve from non-binding and autoreactive precursors.

The tumor microenvironment hosts antibody-secreting cells (ASCs) associated with a favorable prognosis in several types of cancer. Patient-derived antibodies have diagnostic and therapeutic potential; yet, it remains unclear how antibodies gain autoreactivity and target tumors. Here, we found that somatic hypermutations (SHMs) promote antibody antitumor reactivity against surface autoantigens in high-grade serous ovarian carcinoma (HGSOC).

Plasticity in gustatory and nociceptive neurons controls decision making in C. elegans salt navigation.

A conventional understanding of perception assigns sensory organs the role of capturing the environment. Better sensors result in more accurate encoding of stimuli, allowing for cognitive processing downstream. Here we show that plasticity in sensory neurons mediates a behavioral switch in C.

Personalized lab test models to quantify disease potentials in healthy individuals.

Standardized lab tests are central for patient evaluation, differential diagnosis and treatment. Interpretation of these data is nevertheless lacking quantitative and personalized metrics. Here we report on the modeling of 2.

Resilience of neural networks for locomotion.

Locomotion is an essential behaviour for the survival of all animals. The neural circuitry underlying locomotion is therefore highly robust to a wide variety of perturbations, including injury and abrupt changes in the environment. In the short term, fault tolerance in neural networks allows locomotion to persist immediately after mild to moderate injury.

A multi-scale brain map derived from whole-brain volumetric reconstructions.

Animal nervous system organization is crucial for all body functions and its disruption can lead to severe cognitive and behavioural impairment. This organization relies on features across scales-from the localization of synapses at the nanoscale, through neurons, which possess intricate neuronal morphologies that underpin circuit organization, to stereotyped connections between different regions of the brain. The sheer complexity of this organ means that the feat of reconstructing and modelling the structure of a complete nervous system that is integrated across all of these scales has yet to be achieved.

Inhibition Underlies Fast Undulatory Locomotion in .

Inhibition plays important roles in modulating the neural activities of sensory and motor systems at different levels from synapses to brain regions. To achieve coordinated movement, motor systems produce alternating contractions of antagonist muscles, whether along the body axis or within and among limbs, which often involves direct or indirect cross-inhibitory pathways. In the nematode , a small network involving excitatory cholinergic and inhibitory GABAergic motoneurons generates the dorsoventral alternation of body-wall muscles that supports undulatory locomotion.

Home hospice for older people with advanced dementia: a pilot project.

Background: Dementia is a terminal illness making the palliative and hospice approach to care appropriate for older people with advanced dementia.

Objective: To examine clinical and health services outcomes of a quality improvement pilot project to provide home hospice care for older people with advanced dementia.

Study Design: Twenty older people with advanced dementia being treated in the Maccabi Healthcare Services homecare program, received home hospice care as an extension of their usual care for 6-7 months (or until they died) from a multidisciplinary team who were available 24/7.

Signatures of proprioceptive control in locomotion.

Animal neuromechanics describes the coordinated self-propelled movement of a body, subject to the combined effects of internal neural control and mechanical forces. Here we use a computational model to identify effects of neural and mechanical modulation on undulatory forward locomotion of , with a focus on proprioceptively driven neural control. We reveal a fundamental relationship between body elasticity and environmental drag in determining the dynamics of the body and demonstrate the manifestation of this relationship in the context of proprioceptively driven control.

Neural Architecture of Hunger-Dependent Multisensory Decision Making in C. elegans.

Little is known about how animals integrate multiple sensory inputs in natural environments to balance avoidance of danger with approach to things of value. Furthermore, the mechanistic link between internal physiological state and threat-reward decision making remains poorly understood. Here we confronted C.

Dynamic and static maintenance of epigenetic memory in pluripotent and somatic cells.

Stable maintenance of gene regulatory programs is essential for normal function in multicellular organisms. Epigenetic mechanisms, and DNA methylation in particular, are hypothesized to facilitate such maintenance by creating cellular memory that can be written during embryonic development and then guide cell-type-specific gene expression. Here we develop new methods for quantitative inference of DNA methylation turnover rates, and show that human embryonic stem cells preserve their epigenetic state by balancing antagonistic processes that add and remove methylation marks rather than by copying epigenetic information from mother to daughter cells.

Nematode locomotion: dissecting the neuronal-environmental loop.

With a fully reconstructed and extensively characterized neural circuit, the nematode Caenorhabditis elegans is a promising model system for integrating our understanding of neuronal, circuit and whole-animal dynamics. Fundamental to addressing this challenge is the need to consider the tight neuronal-environmental coupling that allows the animal to survive and adapt to changing conditions. Locomotion behaviors are affected by environmental variables both at the biomechanical level and via adaptive sensory responses that drive and modulate premotor and motor circuits.

Insights into the binding of GABA to the insect RDL receptor from atomistic simulations: a comparison of models.

The resistance to dieldrin (RDL) receptor is an insect pentameric ligand-gated ion channel (pLGIC). It is activated by the neurotransmitter γ-aminobutyric acid (GABA) binding to its extracellular domain; hence elucidating the atomistic details of this interaction is important for understanding how the RDL receptor functions. As no high resolution structures are currently available, we built homology models of the extracellular domain of the RDL receptor using different templates, including the widely used acetylcholine binding protein and two pLGICs, the Erwinia Chrysanthemi ligand-gated ion channel (ELIC) and the more recently resolved GluCl.

GABA binding to an insect GABA receptor: a molecular dynamics and mutagenesis study.

RDL receptors are GABA-activated inhibitory Cys-loop receptors found throughout the insect CNS. They are a key target for insecticides. Here, we characterize the GABA binding site in RDL receptors using computational and electrophysiological techniques.

Triphasic spike-timing-dependent plasticity organizes networks to produce robust sequences of neural activity.

Synfire chains have long been proposed to generate precisely timed sequences of neural activity. Such activity has been linked to numerous neural functions including sensory encoding, cognitive and motor responses. In particular, it has been argued that synfire chains underlie the precise spatiotemporal firing patterns that control song production in a variety of songbirds.

Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues.

DNA methylation has been comprehensively profiled in normal and cancer cells, but the dynamics that form, maintain and reprogram differentially methylated regions remain enigmatic. Here, we show that methylation patterns within populations of cells from individual somatic tissues are heterogeneous and polymorphic. Using in vitro evolution of immortalized fibroblasts for over 300 generations, we track the dynamics of polymorphic methylation at regions developing significant differential methylation on average.

Proofreading of misincorporated nucleotides in DNA transcription.

The accuracy of DNA transcription is crucial for the proper functioning of the cell. Although RNA polymerases demonstrate selectivity for correct nucleotides, additional active mechanisms of transcriptional error correction are required to achieve observed levels of fidelity. Recent experimental findings have shed light on a particular mechanism of transcriptional error correction involving: (i) diffusive translocation of the RNA polymerase along the DNA (backtracking) and (ii) irreversible RNA cleavage.

Proofreading of misincorporated nucleotides in DNA transcription.

The accuracy of DNA transcription is crucial for the proper functioning of the cell. Although RNA polymerases demonstrate selectivity for correct nucleotides, additional active mechanisms of transcriptional error correction are required to achieve observed levels of fidelity. Recent experimental findings have shed light on a particular mechanism of transcriptional error correction involving: (i) diffusive translocation of the RNA polymerase along the DNA (backtracking) and (ii) irreversible RNA cleavage.

Gait Modulation in C. elegans: An Integrated Neuromechanical Model.

Equipped with its 302-cell nervous system, the nematode Caenorhabditis elegans adapts its locomotion in different environments, exhibiting so-called swimming in liquids and crawling on dense gels. Recent experiments have demonstrated that the worm displays the full range of intermediate behaviors when placed in intermediate environments. The continuous nature of this transition strongly suggests that these behaviors all stem from modulation of a single underlying mechanism.

Primate CpG islands are maintained by heterogeneous evolutionary regimes involving minimal selection.

Mammalian CpG islands are key epigenomic elements that were first characterized experimentally as genomic fractions with low levels of DNA methylation. Currently, CpG islands are defined based on their genomic sequences alone. Here, we develop evolutionary models to show that several distinct evolutionary processes generate and maintain CpG islands.