Micro-connectomics: probing the organization of neuronal networks at the cellular scale.

Defining the organizational principles of neuronal networks at the cellular scale, or micro-connectomics, is a key challenge of modern neuroscience. In this Review, we focus on graph theoretical parameters of micro-connectome topology, often informed by economical principles that conceptually originated with Ramón y Cajal's conservation laws. First, we summarize results from studies in intact small organisms and in samples from larger nervous systems. We then evaluate the evidence for an economical trade-off between biological cost and functional value in the organization of neuronal networks. Various results suggest that many aspects of neuronal network organization are indeed the outcome of competition between these two fundamental selection pressures.This work was supported by the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by the Nature Publishing Group

Characterization of the non-functional Fas ligand of gld mice

Mice homozygous for either the gld or Ipr mutation develop autoimmune diseases and progressive lymphadenopathy. The Ipr mutation Is characterized by the absence of unctional Fas, whereas gld mice exhibit an inactive FasL due to a point mutation proximal to the extracellular C-terminus. The structural repercussions of this amino acid substitution remain unknown. Here we report that FasL Is expressed at similar levels on the surface of activated T lymphocytes from gld and wild-type mice. Using a polyclonal anti-FasL antibody, Indistinguishable amounts of a 40 kDa protein are detected In both gld and wild-type splenocytes. The molecular model of FasL, based on the known structure of TNF-α, predicts that the Phe→Leu gld mutation is located at the protomer interface which Is close to the FasR Interaction site. We conclude that the gld mutation allows normal FasL biosynthesis, surface expression and ollgomerlzatlon, but induces structural alterations to the Fas binding region leading to the phenotypic changes observe

Serum neurofilament light chain in behavioral variant frontotemporal dementia

Objective To determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD). Methods Blood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration-related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry. Results At baseline, serum NfL level correlated with CSFNfL (bvFTD r = 0.706, p < 0.0001;AD/MCI r = 0.666, p = 0.0003). Highest serum levels were observed in bvFTD (p < 0 0.0001 vs Con and MCI, p = 0.0078 vs AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with 91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL increased in bvFTD and AD (p = 0.0039 and p = 0.0006, respectively). At baseline and follow-up, NfL correlated with functional scores of patients with bvFTD (e.g., CDR-SOB [baseline] r = 0.4157, p = 0.0006;[follow-up] r = 0.5629, p < 0.0001) and with atrophy in the gray and white matter of many brain regions including frontal and subcortical areas (e.g., frontal lobe: r = -0.5857, p < 0.0001;95% confidence interval -0.7415 to -0.3701). For patients with AD/MCI, NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline] r = 0.6624, p < 0.0001;[follow-up] r = 0.5659, p = 0.0003) but not with regional brain volumes. Conclusions As serum NfL correlates with functional impairment and brain atrophy in bvFTD at different disease stages, we propose it as marker of disease severity, paving the way for its future use as outcome measure for clinical trials. Classification of evidence This study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia

Key criteria for developing ecosystem service indicators to inform decision making

Decision makers are increasingly interested in information from ecosystem services (ES) assessments. Scientists have for long recognised the importance of selecting appropriate indicators. Yet, while the amount and variety of indicators developed by scientists seems to increase continuously, the extent to which the indicators truly inform decision makers is often unknown and questioned. In this viewpoint paper, we reflect and provide guidance on how to develop appropriate ES indicators for informing decision making, building on scientific literature and practical experience collected from researchers involved in seven case studies. We synthesized 16 criteria for ES indicator selection and organized them according to the widely used categories of credibility, salience, legitimacy (CSL). We propose to consider additional criteria related to feasibility (F), as CSL criteria alone often seem to produce indicators which are unachievable in practice. Considering CSL & F together requires a combination of scientific knowledge, communication skills, policy and governance insights and on-field experience. We present a checklist to evaluate CSL & F of your ES indicators. This checklist helps to detect and mitigate critical shortcomings in an early phase of the development process, and aids the development of effective indicators to inform actual policy decisions

Micro-connectomics: probing the organization of neuronal networks at the cellular scale.

Defining the organizational principles of neuronal networks at the cellular scale, or micro-connectomics, is a key challenge of modern neuroscience. In this Review, we focus on graph theoretical parameters of micro-connectome topology, often informed by economical principles that conceptually originated with Ramón y Cajal's conservation laws. First, we summarize results from studies in intact small organisms and in samples from larger nervous systems. We then evaluate the evidence for an economical trade-off between biological cost and functional value in the organization of neuronal networks. Various results suggest that many aspects of neuronal network organization are indeed the outcome of competition between these two fundamental selection pressures.This work was supported by the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by the Nature Publishing Group

Steering the electron in H2+ by nuclear wave packet dynamics

By combining carrier-envelope phase (CEP) stable light fields and the traditional method of optical pump-probe spectroscopy we study electron localization in dissociating H[subscript 2][superscript +] molecular ions. Localization and localizability of electrons is observed to strongly depend on the time delay between the two CEP-stable laser pulses with a characteristic periodicity corresponding to the oscillating molecular wave packet. Variation of the pump-probe delay time allows us to uncover the underlying physical mechanism for electron localization, which are two distinct sets of interfering dissociation channels that exhibit specific temporal signatures in their asymmetry response