Explore the vast range of titles available.

Background:Hereditary spastic paraparesis (HPS) linked to mutations in the spastin gene (SPG4) is considered to be a pure form of spastic hereditary paraparesis. However, in this disease also other signs of central nervous system involvement are frequently found.Methods:Clinical, genetical and neuroradiological investigations were carried out in a large family with autosomal dominant spastic paraparesis and in a sporadic case with spastic paraparesis.Results:Additional clinical and molecular data are provided, studying other members of the same pedigree, as already described, with a five-base deletion in exon 9 of the SPG4 gene (1215–1219delTATAA) whose members show MRI anomalies that fall within the Dandy–Walker continuum. Furthermore, an unrelated female patient with hypoplasia of the cerebellar vermis is indicated, carrying a de novo previously reported mutation of the SPG4 gene (c.1741C>T p.R581X).Conclusions:Spastin may play an important role in the development of the central nervous system and in particular in the development of the structures of posterior fossa.

A broad range of Nuclear Physics research activities have been carried out at INFN-LNS until the summer 2020, when the accelerators were stopped for the upgrade. The upgrade of LNS is a project mainly funded by a PON-FESR (National Program for Research and Innovation) strategic line for boosting the research infrastructures, having its own goals, time-schedule and deadlines. In addition to such an action promoted by the Italian Ministry of Research, further funds have been made available from INFN budget. The end of the phase supported by the PON for procurement and tenders is currently set for the end of 2023. A series of actions will therefore be implemented to improve scientific opportunities for users. In particular, the focus is on the commissioning of the Tandem and Superconducting Cyclotron with the new set-up, completed by the renewal of the experimental areas and the commissioning of the new fragment separator FRAISE, also financed under the PON. The high-intensity program, including the determination of the nuclear matrix elements (NME) for the double beta decay and the study of EOS for nuclear matter with large neutron content, will be made feasible by these improvements to accelerators, beamlines and detectors. Some highlights of the whole activity as well as of the Applied Physics perspectives and the Astroparticle Physics multi-messenger program, strictly connected to the Nuclear Physics program, are given.

Human chitotriosidase (Chit) is a member of the chitinase family and it is synthesized by activated macrophages. Recently, a genetic polymorphism was found to be responsible for the common deficiency in Chit activity, frequently encountered in different populations. We analyzed the Chit gene in some ethnic groups from the Mediterranean and African areas, to evaluate whether the Chit gene polymorphism correlates with the changes in environmental features and the disappearance of parasitic diseases. We found a heterozygote frequency for the duplication of 24 bp in exon 10 of 44% in Sicily and 32.71% in Sardinia, whereas those homozygous Chit deficient were 5.45 and 3.73%, respectively. In contrast, in Benin and Burkina Faso, both mesoendemic regions for Plasmodium falciparum malaria and other infections due to intestinal parasites, a low incidence of Chit mutation was found (heterozygous 0 and 2%, respectively) and no subject was homozygous for Chit deficiency. Our results provide evidence of the fact that the low frequency or the absence of mutant Chit gene may represent a protective factor in the population still living in disadvantaged environmental conditions. The present study suggests that the disappearance of parasitic diseases and the improved environmental conditions may have ensued the occurrence of a high percentage of 24-bp mutation in Sicily, in Sardinia and in other Mediterranean countries, whereas in the sub-Saharan regions (Benin and Burkina Faso), the widespread parasitic diseases and the poor social status have contributed to maintenance of the wild-type Chit gene.

Chitinases have been identified in a variety of organisms ranging from prokaryotes to eukaryotes, known to specifically degrade chitin, an abundant polymer of N-acetylglucosamine. Recently a human chitinolytic enzyme called CHIT1 was discovered. CHIT1 is expressed by activated macrophages and hydrolyzes artificial chitotrioside substrates, but its specific function in humans is unknown, since it is generally believed that man completely lacks endogenous chitin and endogenous substrates for chitinases. An intriguing question is whether the chitotriosidase activity is just an evolutionary remnant or it has a physiological function in man. To test these hypotheses we utilized a “phylogenomic” approach performing accurate sequence analyses of this gene, coding for CHIT1, in rodents and primates. Inspecting the sequences available in public databases, we determined that this gene is conserved in rodents (mouse and rat) and primates (chimpanzee, gorilla, orangutan, gibbon, baboon, a common marmoset and black macaque). Moreover we found that a 24-base pair duplication that determines an enzymatically inactive human protein is not present in primates, suggesting that this polymorphism was created during human evolution. These results indicate that chitotriosidase is conserved across the evolutionary scale. Such conservation of the CHIT1 gene argues in favour of an important biological role.   

Activated macrophages are major effectors at all stages of lesion formation in multiple sclerosis (MS) brain. Here, we report that the macrophage enzyme chitotriosidase (Chit) is significantly elevated both in plasma and cerebrospinal fluid (CSF) of patients with MS as compared to healthy controls and other neurological patients (P< 0.001). Furthermore, the Chit activity in blood significantly associates with the MS clinical course (higher in secondary progressive relative to relapsing remitting, P = 0.01) and the clinical severity as measured by Kurtkze’s Expanded Disability Status Scale (P<0.001). Also, we found that Chit activity is compartmentalized in the central nervous system of early MS patients and that its CSF/plasma quotient, in the presence of a preserved albumin quotient, correlates with the extent of future clinical deterioration (r = 0.91; P<0.001). These findings confirm that innate immunity, here represented by Chit, is clinically relevant in MS and allows, if confirmed, reconsidering novel MS therapeutic strategies specifically aimed at this branch of the immune response.

High levels of plasma chitotriosidase are a marker of macrophage activation in several pathologies and, in particular, in human malaria. Plasmodium falciparum, during its maturative cycle in the midgut of the Anopheles mosquito, secretes a chitinase to disrupt the peritrophic membrane, a necessary step in the migration of the parasite from the midgut to the salivary glands of malaria’s vector. The cooperation between human chitotriosidase (Chit) and the chitinase from P. falciparum in attacking the peritrophic membranes in the Anopheles midgut has been recently demonstrated by in vivo experiments. The present study confirms, by computational methods, this functional homology. A simple sequence analysis method, potentially useful to assess fine textual closeness in families of homologous proteins, is reported here and applied to a set of chitinases from mammals and plasmodia. This analysis confirms the clustering and the phylogenetic relationships obtained with well-known alignment methods, but also shows that the sequences of chitinases from malaria hosts and malaria parasites are correlated. This correlation, a sign of functional homology, is discussed as a condition for the spreading of different forms of malaria. From this perspective, one can get insight into the origins of malaria and its genetic or pharmacological control.

In the Anopheles midgut, Plasmodium falciparum produces a specific chitinase able to penetrate the blood meal surrounding the chitin-containing peritrophic membrane (PM). High levels of an analogous chitinase, chitotriosidase (CHIT), may be found in human blood, being the markers of macrophage activation. To verify the hypothesis that CHIT present in malaria patient blood could help parasite to overcome PM, we carried out a bioassay by feeding Anopheles stephensi females on an artificial apparatus that contained human blood from four different sources and with different chitinase concentrations: (1) healthy donors, as negative controls; (2) patients with malaria; (3) patients with Gaucher disease; and (4) whole blood enriched with commercial P. falciparum chitinase, as positive controls. After 16, 20 and 24 h of bloodfeeding, mosquitoes were dissected to extract the midgut and assess the effect of the different chitinases on membrane structure. Optical microscopy showed that formation of PM was clearly complete after 16 h in the posterior midgut from Anopheles already fed with healthy donor bloods. By contrast, PM formation was visible after 16 h in the posterior midgut of mosquitoes fed with malaria and Gaucher patient bloods but appeared clearly damaged at 20 and 24 h. At the same time, the PM formation was almost completely inhibited in the midgut of Anopheles fed with P. falciparum chitinase-enriched bloods. These alterations were clearly confirmed by transmission electronic microscopy. In the present paper, we demonstrate that human CHIT from different sources is active on anophelines’ PM.

Numerous neuropathologic and imaging studies have reported different structural abnormalities in the brains of autistic subjects. However, whether or not the degree of brain abnormality is correlated with the severity of developmental impairment in autistic disorder is still unknown. The midsagittal area of the cerebrum, corpus callosum, midbrain, cerebellar vermis, and vermal lobules VI and VII was measured by means of magnetic resonance imaging in 22 boys with low-functioning autistic disorder and in 11 age-matched normal controls. Morphometric measures were statistically compared between groups and correlated with age and scores on the Psychoeducational Profile-Revised and the Childhood Autism Rating Scale. A significant negative correlation was found between midsagittal area of the cerebrum and age in patients with autistic disorder, and a positive correlation was found between the midsagittal area of the midbrain and some sub-scales of the Psychoeducational Profile—Revised. (J Child Neurol 2000;15:504—508).

Malaria is still a major cause of severe disease which is responsible for millions of deaths, mostly in children under 5 years old, in tropical countries, especially sub-Saharan Africa. Complications of severe anaemia and cerebral malaria are thought to be the major cause of morbidity and mortality but recent evidence suggests that the host's immunological response could also contribute to the pathophysiology of the disease in human beings. Intensive studies of the immune response to malaria parasites in human beings have provided a wealth of information about the cells and cytokines implicated in the pathophysiology of survival and fatal outcome in severe infections. This review focuses on the pivotal role of macrophages and other important cellular effectors, molecules, and cytokines involved in the activation of the immune response at the different stages of human falciparum malaria. Our understanding of the putative mechanisms by which cytokines may mediate beneficial and harmful effects, through activation of phagocytic cells, could help to develop new treatment strategies, regardless of the emergence of parasite multidrug resistance.

Crossing of the antigens through a damaged small intestinal mucosa, deposition of immune complexes in target organs, a reduction in immune surveillance, mechanism of molecular mimicry, and activated T cell response may contribute to the pathogenesis of the diseases associated with celiac disease. [...]this case shows two major issues: an acute polyneuropathy can be a complication of celiac disease in childhood and its benign course could help in the understanding of the underlying pathogenic mechanisms.