The connection matrix of the human brain (the human “connectome”) represents an indispensable foundation for basic and applied neurobiological research. However, the network of anatomical connections linking the neuronal elements of the human brain is still largely unknown. While some databases or collations of large-scale anatomical connection patterns exist for other mammalian species, there is currently no connection matrix of the human brain, nor is there a coordinated research effort to collect, archive, and disseminate this important information. We propose a research strategy to achieve this goal, and discuss its potential impact.

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The Human Connectome: A Structural Description of the Human Brain

Multicellular animals detect pathogens via a set of receptors that recognize pathogen-associated molecular patterns (PAMPs). However, pathogens are not the only causative agents of tissue and cell damage: trauma is another one. Evidence is accumulating that trauma and its associated tissue damage are recognized at the cell level via receptor-mediated detection of intracellular proteins released by the dead cells. The term "alarmin" is proposed to categorize such endogenous molecules that signal tissue and cell damage. Intriguingly, effector cells of innate and adaptive immunity can secrete alarmins via nonclassical pathways and often do so when they are activated by PAMPs or other alarmins. Endogenous alarmins and exogenous PAMPs therefore convey a similar message and elicit similar responses; they can be considered subgroups of a larger set, the damage-associated molecular patterns (DAMPs).

https://jlb.onlinelibrary.wiley.com/doi/epdf/10.1189/jlb.0306164

DAMPs, PAMPs and alarmins: all we need to know about danger

Stem cells are defined as cells able to both extensively self-renew and differentiate into progenitors. Research data show that more resistant stem cells than common cancer cells exist in cancer patients.To identify unrecognized differences between cancer stem cells and cancer cells might be able to develope effective classification,diagnose and treat ment for cancer.

Stem Cells,Cancer and Cancer Stem Cells

Annexins are Ca2+ and phospholipid binding proteins forming an evolutionary conserved multigene family with members of the family being expressed throughout animal and plant kingdoms. Structurally,...

/pdf/annexins-from-structure-to-function-4sosiwfhgs.pdf

Annexins: from structure to function.

Although it was thought that apoptotic cells, when rapidly phagocytosed, underwent a silent death that did not trigger an immune response, in recent years a new concept of immunogenic cell death (ICD) has emerged. The immunogenic characteristics of ICD are mainly mediated by damage-associated molecular patterns (DAMPs), which include surface-exposed calreticulin (CRT), secreted ATP and released high mobility group protein B1 (HMGB1). Most DAMPs can be recognized by pattern recognition receptors (PRRs). In this Review, we discuss the role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in regulating the immunogenicity of dying cancer cells and the effect of therapy-resistant cancer microevolution on ICD.

Immunogenic cell death and DAMPs in cancer therapy.

Immunocytochemical detection of the calcium-regulated proteins, S100B and S100A1, in bovine retina: their calcium-dependent stimulation of a membrane-bound guanylate cyclase activity as investigated by ultracytochemistry

Interaction of S-100 protein with liposomes of cardiolipin

We have further characterized the effect of the acidic Ca 2+ -binding S-100 protein on the physical state of brain membranes using purified synaptic plasma membranes (SPM). S-100-induced changes in the fluidity of the lipid bilayer of SPM were monitored using membranes labeled with either 5-NS or 16-NS. The electron spin resonance spectra indicate that S-100 reduces the fluidity of both the polar surface and the hydrophobic core of SPM in the presence of micro-molar amounts of Ca 2+ , the effect reaching the maximum at about 25-50 nM S-100 after about 10-30 min of incubation of the protein with membranes at room temperature.

S-100 Protein Decreases the Fluidity of the Lipid Bilayer of Purified Synaptic Plasma Membranes

Artesunate induces ROS-mediated apoptosis and counteracts tumor growth in vivo in embryonal rhabdomyosarcoma cells.

Sertoli cells (SeC) are responsible for the immunoprivileged status of the testis thanks to which allogeneic or xenogeneic engraftments can survive without pharmacological immune suppression if co-injected with SeC. This peculiar ability of SeC is dependent on secretion of a plethora of factors including maturation factors, hormones, growth factors, cytokines and immunomodulatory factors. The anti-inflammatory and trophic properties of SeC have been largely exploited in several experimental models of diseases, diabetes being the most studied. Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive pathology in which lack of functional dystrophin leads to progressive muscle degeneration culminating in loss of locomotion and premature death. Despite a huge effort to find a cure, DMD patients are currently treated with anti-inflammatory steroids. Recently, encapsulated porcine SeC (MC-SeC) have been injected ip in the absence of immunosuppression in an animal model of DMD resulting in reduction of muscle inflammation and amelioration of muscle morphology and functionality, thus opening an additional avenue in the treatment of DMD. The novel protocol is endowed with the advantage of being potentially applicable to all the cohort of DMD patients regardless of the mutation. This mini-review addresses several issues linked to the possible use of MC-SeC injected ip in dystrophic people.

Rosario Donato

Papers

Immunocytochemical detection of the calcium-regulated proteins, S100B and S100A1, in bovine retina: their calcium-dependent stimulation of a membrane-bound guanylate cyclase activity as investigated by ultracytochemistry

Interaction of S-100 protein with liposomes of cardiolipin

S-100 Protein Decreases the Fluidity of the Lipid Bilayer of Purified Synaptic Plasma Membranes

Artesunate induces ROS-mediated apoptosis and counteracts tumor growth in vivo in embryonal rhabdomyosarcoma cells.

Do Porcine Sertoli Cells Represent an Opportunity for Duchenne Muscular Dystrophy