In the area of nanopore technology, detection methods are based on the recorded electrical signal induced by ionic transport through the nanopore.This signal also is often used to determine the nanopore diameter. Thus fundamental understanding of ionic transport at the nanoscale is essential, because ions do not in general exhibit bulk-like behavior. Indeed, at low salt concentration, the conductance-concentration relation does not follow a bulk-like linear law. In addition, for small nanopores, surface effects can prevail over bulk transport. In order to illustrate this phenomenon, we have tailored high aspect ratio (conical and cylindrical), putatively uncharged nanopores using tracketching on PET Film and atomic layer deposition technique. Starting from experimental results, we will discuss different approaches to fitting the data, including a simple phenomenological model, commonly used to determine nanopore diameter, and a more sophisticated mesoscopic model based on the space charge model. Application of the mesoscopic model leads us to conclude that, surprisingly, a weak surface charge density is needed to fit the transport model to the experimental data. To go further, molecular dynamic simulations were also performed on a system modeled to resemble as closely as possible the experimental one. From different nanopore geometries and the adsorption of hydrophibic polypeptides, we will attempt to explain the origin of the weak surfacecharge.

The tubular lipid membranes (TLMs) pulled out from vesicles are often used in in vitro studies of the interactions between curvature-inducing proteins and highly curved membranes. The protein molecules adsorbed at the membrane surface deform the TLM and couple with each other due to the induced strain. Here we propose an approach which models the single curvature-inducing protein action on the lipid bilayer by the multipole, the superposition of the point forces applied to the membrane in the region of the protein adsorption. We show that to be localized in the area of the protein size at the TLM surface, the force multipoles satisfying the mechanical equilibrium conditions should be composed of three or more point forces. The protein coupling energy mediated by the membrane strain is studied in detail. In the region of the tubular membrane stability the maximal distance between two neighboring interacting protein-induced force multipoles is estimated to be of the order of the TLM cross section perimeter. In the vicinity of the TLM instability in the region of the vanishing stretching force applied to the TLM, the interaction radius increases drastically. The high affinity of the single curvature-inducing protein molecule to the regions in the vicinity of the TLM ends is explained and related to the boundary conditions in the experimental set-ups. The reasons for the aggregate formation on the membrane surface are also discussed.

Patients with vascular parkinsonism have higher cognitive decline and more basal ganglia lesions. We aimed to evaluate the relationship of cognitive impairment with functional connectivity between the basal ganglia and cingulate cortex in vascular parkinsonism.;Thirty patients (8 with vascular parkinsonism and 22 with Parkinson disease) and 23 controls were enrolled. The Mattis Dementia Rating Scale and the Stroop Task were used to assess cognitive decline. MR imaging examinations included T1-MPRAGE, FLAIR, and resting-state fMRI sequences. MPRAGE was segmented to obtain basal ganglia and cingulate cortex volumes. FLAIR was segmented to obtain white matter hyperintensity lesion volume. Resting-state fMRI sequences were used to compare basal ganglia functional connectivity with the cingulate cortex between patients and controls.;Patients with vascular parkinsonism exhibited impaired attention, resistance to interference, and inhibitory control and an increased number of errors on the Stroop Task. They also had higher caudate nucleus and white matter hyperintensity lesion volumes, which were positively correlated (ρ = 0.75, P < .0001). Caudate nucleus functional connectivity with the perigenual anterior cingulate cortex was increased in patients with vascular parkinsonism compared with controls and patients with Parkinson disease, and it was positively correlated with the caudate nucleus volume (ρ = 0.44, P = .016). Caudate nucleus functional connectivity with the posterior cingulate cortex was decreased in patients with vascular parkinsonism compared with controls and negatively correlated with the number of errors on the Stroop test (ρ = -0.51, P = .0003).;In patients with vascular parkinsonism, cognitive decline could be related to changes of caudate nucleus functional connectivity with the cingulate cortex at resting-state, which may be induced by ischemia-related remodelling.

Pancreatic β-cells modulate insulin secretion through rapid sensing of blood glucose and integration of gut-derived signals. Increased insulin demand during pregnancy and obesity alters islet function and mass and leads to gestational diabetes mellitus and type 2 diabetes in predisposed individuals. However, it is unclear how blood-borne factors dynamically access the islets of Langerhans. Thus, understanding the changes in circulating molecule distribution that accompany compensatory β-cell expansion may be key to developing novel antidiabetic therapies. Here, using two-photon microscopy in vivo in mice, we demonstrate that islets are almost instantly exposed to peaks of circulating molecules, which rapidly pervade the tissue before clearance. In addition, both gestation and short-term high-fat-diet feeding decrease molecule extravasation and uptake rates in vivo in islets, independently of β-cell expansion or islet blood flow velocity. Together, these data support a role for islet vascular permeability in shaping β-cell adaptive responses to metabolic demand by modulating the access and sensing of circulating molecules.

Characterization of normal age-related changes in resting state brain networks associated with working memory performance is a major prerequisite for studying neurodegenerative diseases. The aim of this study was to investigate the relationship between performing a working memory task (under MRI) and resting-state brain networks in a large cohort of healthy elderly subjects (n=337). Functional connectivity and interactions between networks were assessed within the default mode (DMN), salience (SN), and right and left central executive (CEN) networks in two groups of subjects classed by their performance (low and high). The low performance group showed lower functional connectivity in both the DMN and SN, and higher functional connectivity in the right and left CEN compared to the high performance group. Overall the functional connectivity within the DMN and the CEN were correlated. The lower functional connectivity within the DMN and SN in the low performance group is suggestive of altered attentional and memory processes and/or altered motivation. The higher functional connectivity within the CEN could be related to compensatory mechanisms, without which the subjects would have even lower performances. The correlation between the DMN and CEN suggests a modulation between the lower functional connectivity within the DMN and the higher functional connectivity within the CEN when performance is reduced. Finally, this study suggests that performance modifications in healthy elderly subjects are associated with reorganization of functional connectivity within the DMN, SN, and CEN.

We investigate over a 12-year period the association between regional cerebral blood flow (CBF) and cardiovascular risk factors in a prospective cohort of healthy older adults (81.96 ± 3.82 year-old) from the Cognitive REServe and Clinical ENDOphenotype (CRESCENDO) study. Cardiovascular risk factors were measured over 12 years, and gray matter CBF was measured at the end of the study from high-resolution magnetic resonance imaging using arterial spin labeling. The association between cardiovascular risk factors, their long-term change, and CBF was assessed using multivariate linear regression models. Women were observed to have higher CBF than men (p < 0.05). Increased mean arterial pressure (MAP) over the 12-year period was correlated with a low cerebral blood flow (p < 0.05, R(2) = 0.21), whereas no association was detected between CBF and MAP at the time of imaging. High levels of glycemia tended to be associated with low cerebral blood flow values (p < 0.05). Age, alcohol consumption, smoking status, body mass index, history of cardiovascular disease, and hypertension were not associated with CBF. Our main result suggests that change in MAP is the most significant predictor of future CBF in older adults.