Viral subversion of B cell responses within secondary lymphoid organs.

Antibodies play a crucial role in virus control. The production of antibodies requires virus-specific B cells to encounter viral antigens in lymph nodes, become activated, interact with different immune cells, proliferate and enter specific differentiation programmes. Each step occurs in distinct lymph node niches, requiring a coordinated migration of B cells between different subcompartments.

Suppression of inflammation and acquired immunity by IL-37.

IL-37 is a unique member of the IL-1 family of cytokines, which functions as a natural suppressor of inflammatory and immune responses. Immune and non-immune cells produce IL-37 precursor following pro-inflammatory stimuli. Following activating cleavage by caspase-1, mature IL-37 translocates to the nucleus, where it suppresses transcription of pro-inflammatory genes.

Reversible immortalisation enables genetic correction of human muscle progenitors and engineering of next-generation human artificial chromosomes for Duchenne muscular dystrophy.

Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combination of large-capacity vectors, such as human artificial chromosomes (HACs), with stem/progenitor cells may overcome this limitation.

Spatial reconstruction of immune niches by combining photoactivatable reporters and scRNA-seq.

Cellular functions are strongly dependent on surrounding cells and environmental factors. Current technologies are limited in their ability to characterize the spatial location and gene programs of cells in poorly structured and dynamic niches. We developed a method, NICHE-seq, that combines photoactivatable fluorescent reporters, two-photon microscopy, and single-cell RNA sequencing (scRNA-seq) to infer the cellular and molecular composition of niches.

Adult leukoencephalopathies with prominent infratentorial involvement can be caused by Erdheim-Chester disease.

Background: Leukoencephalopathies with prominent involvement of cerebellum and brainstem, henceforward called prominent infratentorial leukoencephalopathies (PILs), encompass a variety of inherited and acquired white matter diseases. Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis likely under-diagnosed as cause of adult PIL.

Methods: We reviewed the clinical and laboratory information of ten consecutive sporadic adult patients with PIL of unknown origin, who were investigated for ECD.

Intestinal Flossing Keeps Pathogens at Bay.

Intraepithelial lymphocytes (IELs) are tissue-resident immune cells that surveil the intestine and provide the first line of defense against pathogens. Reporting in Cell, van Konijnenburg et al. (2017) combine high-resolution microscopy and intersectional genetic tools to provide a detailed characterization of IEL dynamics in response to both commensal and pathogenic microorganisms.

Halogenated Agents and Cardiovascular Surgery: Has Mortality Really Decreased?

Halogenated anesthetic agents (desflurane, isoflurane and sevoflurane) may have cardioprotective properties at therapeutic doses against myocardial intraoperative ischemia-reperfusion injury. Cardioprotection mechanisms are related to mitochondrial and anti-apoptotic signaling pathways. Experimentals and human studies have proven that their use may reduce morbidity and mortality in the setting of cardiac surgery, including a reduction in myocardial infarct size and mechanical ventilation needs.

Glycine -methylation in NGR-Tagged Nanocarriers Prevents Isoaspartate formation and Integrin Binding without Impairing CD13 Recognition and Tumor Homing.

NGR (asparagine-glycine-arginine) is a tumor vasculature-homing peptide motif widely used for the functionalization of drugs, nanomaterials and imaging compounds for cancer treatment and diagnosis. Unfortunately, this motif has a strong propensity to undergo rapid deamidation. This reaction, which converts NGR into DGR, is associated with receptor switching from CD13 to integrins, with potentially important manufacturing, pharmacological and toxicological implications.

Neural precursor cell-secreted TGF-β2 redirects inflammatory monocyte-derived cells in CNS autoimmunity.

In multiple sclerosis, the pathological interaction between autoreactive Th cells and mononuclear phagocytes in the CNS drives initiation and maintenance of chronic neuroinflammation. Here, we found that intrathecal transplantation of neural stem/precursor cells (NPCs) in mice with experimental autoimmune encephalomyelitis (EAE) impairs the accumulation of inflammatory monocyte-derived cells (MCs) in the CNS, leading to improved clinical outcome. Secretion of IL-23, IL-1, and TNF-α, the cytokines required for terminal differentiation of Th cells, decreased in the CNS of NPC-treated mice, consequently inhibiting the induction of GM-CSF-producing pathogenic Th cells.

Neuroinflammation drives anxiety and depression in relapsing-remitting multiple sclerosis.

Objective: To explore the inflammatory processes in the pathogenesis of psychiatric symptoms and the prognostic value of psychiatric comorbidities in multiple sclerosis (MS).

Methods: Four hundred five patients with relapsing-remitting (RR) MS underwent psychiatric evaluation by means of Beck Depression Inventory II (BDI-II) and State/Trait Anxiety Inventory (STAI-Y). The inflammatory activity level was assessed by MRI.

Interleukin 37 reverses the metabolic cost of inflammation, increases oxidative respiration, and improves exercise tolerance.

IL-1 family member interleukin 37 (IL-37) has broad antiinflammatory properties and functions as a natural suppressor of innate inflammation. In this study, we demonstrate that treatment with recombinant human IL-37 reverses the decrease in exercise performance observed during systemic inflammation. This effect was associated with a decrease in the levels of plasma and muscle cytokines, comparable in extent to that obtained upon IL-1 receptor blockade.

CD8 T Cells Orchestrate pDC-XCR1 Dendritic Cell Spatial and Functional Cooperativity to Optimize Priming.

Adaptive cellular immunity is initiated by antigen-specific interactions between T lymphocytes and dendritic cells (DCs). Plasmacytoid DCs (pDCs) support antiviral immunity by linking innate and adaptive immune responses. Here we examined pDC spatiotemporal dynamics during viral infection to uncover when, where, and how they exert their functions.

COL6A5 variants in familial neuropathic chronic itch.

Itch is thought to represent the peculiar response to stimuli conveyed by somatosensory pathways shared with pain through the activation of specific neurons and receptors. It can occur in association with dermatological, systemic and neurological diseases, or be the side effect of certain drugs. However, some patients suffer from chronic idiopathic itch that is frequently ascribed to psychological distress and for which no biomarker is available to date.

Reproducibility of dynamic contrast-enhanced MRI and dynamic susceptibility contrast MRI in the study of brain gliomas: a comparison of data obtained using different commercial software.

Purpose: Dynamic susceptibility contrast MRI (DSC) and dynamic contrast-enhanced MRI (DCE) are useful tools in the diagnosis and follow-up of brain gliomas; nevertheless, both techniques leave the open issue of data reproducibility. We evaluated the reproducibility of data obtained using two different commercial software for perfusion maps calculation and analysis, as one of the potential sources of variability can be the software itself.

Methods: DSC and DCE analyses from 20 patients with gliomas were tested for both the intrasoftware (as intraobserver and interobserver reproducibility) and the intersoftware reproducibility, as well as the impact of different postprocessing choices [vascular input function (VIF) selection and deconvolution algorithms] on the quantification of perfusion biomarkers plasma volume (Vp), volume transfer constant (K ) and rCBV.

Neural Stem Cell Transplantation Induces Stroke Recovery by Upregulating Glutamate Transporter GLT-1 in Astrocytes.

Unlabelled: Ischemic stroke is the leading cause of disability, but effective therapies are currently widely lacking. Recovery from stroke is very much dependent on the possibility to develop treatments able to both halt the neurodegenerative process as well as to foster adaptive tissue plasticity. Here we show that ischemic mice treated with neural precursor cell (NPC) transplantation had on neurophysiological analysis, early after treatment, reduced presynaptic release of glutamate within the ipsilesional corticospinal tract (CST), and an enhanced NMDA-mediated excitatory transmission in the contralesional CST.

Longitudinal MRI quantification of muscle degeneration in Duchenne muscular dystrophy.

Objective: The aim of this study was to evaluate the usefulness of magnetic resonance imaging (MRI) in detecting the progression of Duchenne muscular dystrophy (DMD) by quantification of fat infiltration (FI) and muscle volume index (MVI, a residual-to-total muscle volume ratio).

Methods: Twenty-six patients (baseline age: 5-12 years) with genetically proven DMD were longitudinally analyzed with lower limb 3T MRI, force measurements, and functional tests (Gowers, 10-m time, North Star Ambulatory Assessment, 6-min walking test). Five age-matched controls were also examined, with a total of 85 MRI studies.

Long-Term Survival Rate in Patients With Acute Respiratory Failure Treated With Noninvasive Ventilation in Ordinary Wards.

Objective: Noninvasive ventilation is a life-saving technique increasingly used to treat acute respiratory failure. Noninvasive ventilation has been applied mostly in ICUs, but several reasons brought to an increasing application of noninvasive ventilation in ordinary wards. Few articles evaluated the outcomes of patients receiving noninvasive ventilation including long-term follow-up.

Dynamic contrast-enhanced and dynamic susceptibility contrast perfusion MR imaging for glioma grading: Preliminary comparison of vessel compartment and permeability parameters using hotspot and histogram analysis.

Introduction: Dynamic susceptibility contrast (DSC)-MRI is a perfusion technique with high diagnostic accuracy for glioma grading, despite limitations due to inherent susceptibility effects. Dynamic contrast-enhanced (DCE)-MRI has been proposed as an alternative technique able to overcome the DSC-MRI shortcomings. This pilot study aimed at comparing the diagnostic accuracy of DSC and DCE-MRI for glioma grading by evaluating two estimates of blood volume, the DCE-derived plasma volume (Vp) and the DSC-derived relative cerebral blood volume (rCBV), and a measure of vessel permeability, the DCE-derived volume transfer constant K(trans).

Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis.

Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc). The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis.

Quantitative MRI of the spinal cord and brain in adrenomyeloneuropathy: in vivo assessment of structural changes.

Adrenomyeloneuropathy is the late-onset form of X-linked adrenoleukodystrophy, and is considered the most frequent metabolic hereditary spastic paraplegia. In adrenomyeloneuropathy the spinal cord is the main site of pathology. Differently from quantitative magnetic resonance imaging of the brain, little is known about the feasibility and utility of advanced neuroimaging in quantifying the spinal cord abnormalities in hereditary diseases.