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Key Clinical Message: Stenotrophomonas maltophilia can cause rare odontogenic brain abscesses in immunocompetent patients, highlighting the importance of considering uncommon pathogens in central nervous system infections. With only three reported cases of cerebral abscesses and one pituitary abscess caused by this microorganism, tailored diagnostic methods and individualized treatment regimens are crucial for accurate management. Brain abscesses present diagnostic and therapeutic challenges, with Stenotrophomonas maltophilia infections being exceptionally rare in the central nervous system. We present a case of odontogenic brain abscesses caused by S. maltophilia in an immunocompetent patient, highlighting the rarity and complexity of such infections. A 66‐year‐old male presented with spatial–temporal disorientation and left‐sided weakness. Radiological investigations revealed an expansive lesion in the right posterior frontal region. A craniotomy and drainage were performed, identifying S. maltophilia in the purulent material. The patient responded well to tailored antibiotic therapy. S. maltophilia‐related central nervous system infections are infrequent, emphasizing the need for a heightened clinical suspicion in atypical cases. This case contributes to the literature, emphasizing the importance of a multidisciplinary approach for successful diagnosis and management. [ABSTRACT FROM AUTHOR]

Background: Deficiency of Conserved Oligomeric Golgi (COG) subunits (COG1–8) is characterized by both N‐ and O‐protein glycosylation defects associated with destabilization and mislocalization of Golgi glycosylation machinery components (COG‐CDG). Patients with COG defects present with neurological and multisystem involvement and possible malformation occurrence. Eighteen patients with COG6‐CDG (COG6 mutations) were reported to date. We describe a patient with COG6‐CDG with novel variants and a novel clinical feature namely a congenital recto‐vaginal fistula. Methods: In‐depth serum N‐ and O‐glycosylation structural analyses were conducted by MALDI‐TOF mass spectrometry. COG6 variants were identified by a gene panel and confirmed by Sanger sequencing. Results: This female newborn presented with facial dysmorphism, distal arthrogryposis and recurrent stool discharges per vaginam. A double‐contrast barium‐enema X‐ray study revealed a dehiscence (approximately 5 mm) at the anterior wall of the rectal ampoule communicating with the vagina consistent with a recto‐vaginal fistula. She had developmental delay, corpus callosum dysgenesis, liver and gastrointestinal involvement, hyperthermia episodes and early demise. Serum N‐ and O‐glycosylation analyses pointed to a profound Golgi disarrangement. We identified two novel variants in COG6: a deletion of 1 bp mutation c.823delA creating a shift in the reading frame and a premature stop codon and a 3 bp deletion (c.1141_1143delCTC) producing an in‐frame deletion of 1 amino acid. Conclusion: The congenital recto‐vaginal fistula is a rare type of anorectal malformation that, to our knowledge, has not been reported in patients with a COG6 defect nor in patients with other COG defects. This study broadens COG6‐CDG genetic landscape and spectrum of malformations. [ABSTRACT FROM AUTHOR]

Purpose: Tear fluid N‐Glycome from patients affected with vernal (VKC) and atopic keratoconjunctivitis (AKC) was investigated to identify specific changes in tears and to recognize possible glyco‐biomarkers. Methods: The analysis of the N‐glycans was performed using matrix‐assisted laser desorption ionization mass spectrometry on single tear samples. Tears from control normal subjects (CTRL), VKC and AKC patients were processed and treated with peptide N‐glycosidase F (PNGase F) to deglycosylate N‐glycoproteins. Released N‐glycans were purified, permethylated, and analyzed by matrix‐assisted laser desorption/ionization‐time of flight mass spectrometry and tandem mass spectrometry (MALDI‐TOF MS and MALDI‐TOF MS/MS). Results: More than 150 complex N‐glycans, including highly fucosylated biantennary, triantennary, tetra‐antennary, and bisecting species, were observed in our spectra. Three distinct patterns for CTRL, VKC, and AKC patients were identified in terms of relative intensities for some N‐glycans structures. Major variations involved bisecting and hyperfucosylated glycoforms. The most intense ions were associated with species at m/z 1907.0 (asialo, agalacto, bisected, biantennary structure—NGA2B) in CTRL MS profiles, at m/z 2605.3 and 2966.5 in VKC, and at m/z 2792.4 in AKC corresponding to a well‐known biantennary, disialylated N‐glycan. Several peaks were associated with structures bearing one or two Lewis X epitopes. Structures were confirmed by MS/MS analysis. Quantitative differences among the three groups were statistically significant. Conclusions: Tear MS profiles are rich in specific glycoforms, particularly those with a high fucosylation degree, indicating both core and peripheral decoration. Tear N‐glycome analysis provided important information for a better comprehension of VKC and AKC alterations at the molecular level. [ABSTRACT FROM AUTHOR]

Alcaligenes faecalis is the predominant Gram‐negative bacterium inhabiting gut‐associated lymphoid tissues, Peyer's patches. We previously reported that an A. faecalis lipopolysaccharide (LPS) acted as a weak agonist for Toll‐like receptor 4 (TLR4)/myeloid differentiation factor‐2 (MD‐2) receptor as well as a potent inducer of IgA without excessive inflammation, thus suggesting that A. faecalis LPS might be used as a safe adjuvant. In this study, we characterized the structure of both the lipooligosaccharide (LOS) and LPS from A. faecalis. We synthesized three lipid A molecules with different degrees of acylation by an efficient route involving the simultaneous introduction of 1‐ and 4′‐phosphates. Hexaacylated A. faecalis lipid A showed moderate agonistic activity towards TLR4‐mediated signaling and the ability to elicit a discrete interleukin‐6 release in human cell lines and mice. It was thus found to be the active principle of the LOS/LPS and a promising vaccine adjuvant candidate. [ABSTRACT FROM AUTHOR]

Aim: Long‐term ecological data provide a stepped frame of island ecosystem transformation after successive waves of human colonization, essential to determine conservation and management baselines. However, the timing and ecological impact of initial human settlement on many islands is still poorly known. Here, we report analyses from a 4800‐year sedimentary sequence from Gran Canaria (Canary Islands), with the goal of disentangling forest responses to natural fire from early human pressure on the island. Location: La Calderilla, a volcanic maar caldera at 1,770 m a.s.l. on Gran Canaria. Taxon: Plants and fungi. Methods: A core from the caldera infill was analysed for sediment properties, pollen, micro‐ and macrocharcoal, with radiocarbon and biochronology dating. Fossil data were statistically zoned and interpreted with the help of cross‐correlation and ordination analyses. Surface samples and a pollen–vegetation training set were used as modern analogues for vegetation reconstruction. Results: Before human settlement (4,800–2,000 cal. yr bp), pine (Pinus canariensis) pollen dominated. Extensive dry pine forests characterized the highlands, although with temporary declining phases, followed by prompt (sub‐centennial scale) recovery. Towards 2,280 cal. yr bp there was a shift to open vegetation, marked by an increase in coprophilous spores. Coincidental with independent evidence of human settlement in the pine belt (2,000–470 cal. yr bp) there was a decline of pine and a peak in charcoal. Following historic settlement (470–0 cal. yr bp), pollen producers from anthropogenic habitats, secondary vegetation and coprophilous fungi increased in abundance, reflecting higher pressure of animal husbandry and farming. Modern moss polsters reflect extensive reforestation since 1950 ce (Common Era). Main conclusions: From 4,800 cal. yr bp, the pristine vegetation covering the Gran Canaria highlands was a mosaic of dry pine forests and open vegetation. The pine forests sustained intense fires, which may well have promoted habitat diversity. Human interference was initiated around 2,280 cal. yr bp probably by recurrent cultural firing and animal husbandry, triggering a steady trend of forest withdrawal and expansion of grasses and scrubs, until the final disappearance of the pine forest locally in the 20th century. Grasslands were found to be of ancient cultural origin in the summit areas of Gran Canaria, although they underwent an expansion after the Castilian Conquest. [ABSTRACT FROM AUTHOR]

The literature shows an increased risk for post‐traumatic stress disorder (PTSD) among illegal migrants. We aimed to estimate the prevalence of PTSD, subthreshold PTSD, the degree of disability, and differences in sociodemographic and anamnestic characteristics associated with these clinical conditions in a sample of newly arrived migrants. Two hundred male asylum seekers from West sub‐Saharan Africa were evaluated for traumatic life events, PTSD symptoms, and disability through the Life Events Checklist for DSM‐5 (LEC‐5), the Primary Care PTSD Screen, the PTSD Checklist for DSM‐5, and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). The current prevalence of PTSD and subthreshold PTSD was 9.5% and 12.0%, respectively. PTSD and subthreshold PTSD subgroups presented higher WHODAS 2.0 scores and LEC‐5 events, an over‐representation of individuals with childhood adversities and an excess of premigration psychiatric contacts unrelated to PTSD spectrum disorders and peri‐migration offences. Witnessing a traumatic event and disability in understanding and communication predicted both the presence of PTSD symptoms and PTSD status. PTSD spectrum disorders should be considered among the clinical emergencies associated with asylum seeker condition, and targeted interventions also involving the host citizens should be predisposed. [ABSTRACT FROM AUTHOR]

Pathogenic de novo variants in the X‐linked gene SLC35A2 encoding the major Golgi‐localized UDP‐galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2‐congenital disorders of glycosylation (CDG; formerly CDG‐IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin N‐glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2‐CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2‐dependent UDP‐galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wild‐type to mutant alleles in fibroblasts from affected individuals. [ABSTRACT FROM AUTHOR]

The structural elucidation of lipopolysaccharides (LPSs) from Gram‐negative marine bacteria, along with the assessment of their immunological properties, is a fascinating and active research field. Such studies can aid understanding of adaptation phenomena that occur in the marine environment, but they can also open up new perspectives on the design and development of new immunoregulatory drugs. In this paper, we report the structural characterization of the lipid A component of the LPS isolated from the marine bacterium Cobetia pacifica KMM 3879T, which is characterized by a family of structures differing in their acylation patterns. The structural assignment was achieved through extensive chemical analysis and matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry. Moreover, cellular immunology studies on the LPS highlighted its low immunostimulatory impact, as well as a very interesting and promising inhibitory activity of the toxic effects of Escherichia coli LPS. [ABSTRACT FROM AUTHOR]

The importance of the outer membrane and of its main constituent, lipopolysaccharide, in the symbiosis between rhizobia and leguminous host plants has been well studied. Here, the first complete structural characterization of the entire lipopolysaccharide from an O-chain-deficient Bradyrhizobium ORS285 rfaL mutant is achieved by a combination of chemical analysis, NMR spectroscopy, MALDI MS and MS/MS. The lipid A structure is shown to be consistent with previously reported Bradyrhizobium lipid A, that is, a heterogeneous blend of penta- to hepta-acylated species carrying a nonstoichiometric hopanoid unit and possessing very-long-chain fatty acids ranging from 26:0(25-OH) to 32:0(31-OH). The structure of the core oligosaccharide region, fully characterized for the first time here, is revealed to be a nonphosphorylated linear chain with methylated sugar residues, with a heptose residue exclusively present in the outer core region, and with the presence of two singly substituted 3-deoxy- d- manno-oct-2-ulosonic acid (Kdo) residues, one of which is located in the outer core region. The lipid A moiety is linked to the core moiety through an uncommon 4-substituted Kdo unit. [ABSTRACT FROM AUTHOR]

We describe the clinical and whole genome sequencing (WGS) study of a non-consanguineous Italian family in which two siblings, a boy and a girl, manifesting a severe epileptic encephalopathy (EE) with skeletal abnormalities, carried novel SLC35A3 compound heterozygous mutations. Both siblings exhibited infantile spasms, associated with focal, and tonic vibratory seizures from early infancy. EEG recordings showed a suppression-burst (SB) pattern and multifocal paroxysmal activity in both. In addition both had quadriplegia, acquired microcephaly, and severe intellectual disability. General examination showed distal arthrogryposis predominant in the hands in both siblings and severe left dorso-lumbar convex scoliosis in one. WGS of the siblings-parents quartet identified novel compound heterozygous mutations in SLC35A3 in both children. SLC35A3 encodes the major Golgi uridine diphosphate N-acetylglucosamine transporter. With this study, we add SLC35A3 to the gene list of epilepsies. Neurological symptoms and skeletal abnormalities might result from impaired glycosylation of proteins involved in normal development and function of the central nervous system and skeletal apparatus. [ABSTRACT FROM AUTHOR]

The search for novel lipid A analogues from any biological source that can act as antagonists, displaying inhibitory activity towards the production of pro-inflammatory cytokines, or as immunomodulators in mammals, is a very topical issue. To this aim, the structure and immunological properties of the lipopolysaccharide lipid A from the purple nonsulfur bacterium Rhodopseudomonas palustris strain BisA53 have been determined. This lipid A displays a unique structural feature, with a non-phosphorylated skeleton made up of the tetrasaccharide Man p-α-(1→4)-Glc pN3N-β-1→6-Glc pN3N-α-(1→1)-α-Gal pA, and four primary amide-linked 14:0(3-OH) and, as secondary O-acyl substituents, a 16:0 and the very long-chain fatty acid 26:0(25-OAc), appended on the Glc pN3N units. This lipid A architecture is definitely rare, so far identified only in the genus Bradyrhizobium. Immunological tests on both murine bone-marrow-derived and human monocyte-derived macrophages revealed an extremely low immunostimulant capability of this LPS lipid A. [ABSTRACT FROM AUTHOR]

Protein N-glycosylation consists in the synthesis and processing of the oligosaccharide moiety (N-glycan) linked to a protein and it serves several functions for the proper central nervous system (CNS) development and function. Previous experimental and clinical studies have shown the importance of proper glycoprotein sialylation for the synaptic function and the occurrence of autism spectrum disorders (ASD) in the presence of sialylation deficiency in the CNS. Late-onset Tay Sachs disease (LOTSD) is a lysosomal disorder caused by mutations in the HEXA gene resulting in GM2-ganglioside storage in the CNS. It is characterized by progressive neurological impairment and high co-occurrence of psychiatric disturbances. We studied the N-glycome profile of the cerebrospinal fluid (CSF) in a 14 year-old patient with GM2-gangliosidosis (LOTSD). At the age of 4, the patient presented regressive autism fulfilling criteria for childhood disintegrative disorder (CDD). A CSF sample was obtained in the course of diagnostic work-up for the suspicion of an underlying neurodegenerative disorder. We found definite changes of CSF N-glycans due to a dramatic decrease of sialylated biantennary and triantennary structures and an increase of asialo-core fucosylated bisected N-glycans. No changes of total plasma N-glycans were found. Herein findings highlight possible relationships between the early onset psychiatric disturbance featuring CDD in the patient and defective protein sialylation in the CNS. In conclusion, the study first shows aberrant N-glycan structures of CSF proteins in LOTSD; unveils possible pathomechanisms of GM2-gangliosidosis; supports existing relationships between neuropsychiatric disorders and unproper protein glycosylation in the CNS. Autism Res 2016, 9: 423-428. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We report the first complete structural characterization of the lipopolysaccharide (LPS) from a cystic fibrosis (CF) clinical isolate of Prevotella denticola (B003V1S1X). Chemical, spectroscopic, and spectrometric analyses revealed a unique rough-type LPS (LOS) structure. The structure has a highly negatively charged heptasaccharide core region containing hexoses, with the first two sugars, 3-deoxy- D- manno-oct-2-ulosonic acid (Kdo) and mannose, highly phosphorylated. Furthermore, the lipid A moiety has the typical structure for the genus Prevotella, and was also highly phosphorylated. [ABSTRACT FROM AUTHOR]

N-glycosylation is a fundamental modification of proteins and exists in the three domains of life and in some viruses, including the chloroviruses, for which a new type of core N-glycan is herein described. This N-glycan core structure, common to all chloroviruses, is a pentasaccharide with a b-glucose linked to an asparagine residue which is not located in the typical sequon N-X-T/S. The glucose is linked to a terminal xylose unit and a hyperbranched fucose, which is in turn substituted with a terminal galactose and a second xylose residue. The third position of the fucose unit is always linked to a rhamnose, which is a semiconserved element because its absolute configuration is virus-dependent. Additional decorations occur on this core N-glycan and represent a molecular signature for each chlorovirus. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to verify CD44sol levels in the saliva of patients during follow-up after surgery for laryngeal cancer, to compare them with those registered at the time of diagnosis (pre-intervention) in the same patients, and to assess the reliability of the test as a prognostic indicator.Methods: This prospective study was performed on 21 patients having laryngeal cancer who underwent surgery at the Division of Otolaryngology, University of Catanzaro; twelve adults with head and neck benign disease were recruited to form a control group. For each patient, the clinical–anamnestic data were collected and entered into a database. The sampling of undiluted saliva was performed the day before surgery and during the follow-up, every 3 months. Salivary CD44sol levels were determined using the ELISA method.Results: Mean salivary CD44sol levels in the patients group before surgery (pre-intervention) were significantly higher than those in the control group (70.75 ± 33.8 vs. 12.4 ± 8.7 ng/ml). At follow-up performed 3 months after surgery, 18 of 21 (85.71%) patients had a reduction in salivary CD44sol levels, with a mean value of 50.1 ng/ml; the difference between these and pre-intervention CD44sol levels was statistically significant (P < 0.04). Mean CD44sol levels of 31.1 ng/ml at 6 months post-intervention have been determined in 19 of 21 enrolled patients; none of the 19 patients have actual signs of recurrence.Conclusions: These data seem to show that the determination of salivary CD44sol levels can represent a promising prognostic test in laryngeal carcinomas. [ABSTRACT FROM AUTHOR]

Background Understanding and treating vernal keratoconjunctivitis ( VKC) has been a challenge because the pathogenesis is unclear and antiallergic therapy often unsuccessful. The aim of the study was to analyze peptide profiles in human tears using mass spectrometry to elucidate compositional differences between healthy subjects and patients affected by VKC. Methods Tears were collected from healthy subjects and VKC patients. Digested samples were treated with iTRAQ (isobaric tag for relative and absolute quantitation). Separation of tryptic peptides was realized using a Micro HPLC interfaced with a microfraction collector. MS and MS/ MS mass spectra were performed using a MALDI TOF/ TOF 4800 Applied Biosystem spectrometer. Protein Pilot™ software with Paragon™ algorithm v4.1.46 or GPS™ with Mascot engine was used as search engines with Swiss Prot or IPI human as the databases. Results A significant number of peptides were examined, and 78 proteins were successfully identified. In all VKC samples, levels of serum albumin, transferrin, and hemopexin were found up to 100 times higher than control tear levels and correlated to the severity of disease. Hemopexin, transferrin, mammaglobin B, and secretoglobin 1 D were found significantly over-expressed in VKC samples compared with the control samples. Tear samples from patients treated with topical cyclosporine or corticosteroids showed a dramatic reduction in these protein levels. Conclusions LC MALDI MS and isobaric tag for relative and absolute quantitation technique may be useful in the quantitative and qualitative characterization of the peptidoma of human tears. These techniques may identify target proteins to be used in the diagnosis and management of VKC and other inflammatory ocular surface conditions. [ABSTRACT FROM AUTHOR]

Introduction. Clinical staging is the most important time in management of glottic cancer in early stage (I-II).We have conducted a prospective study to evaluate if magnetic resonance imaging (MRI) is more accurate than computed tomography (CT) about tumoral extension, to exactly choose themost appropriate surgical approach, from organ preservation surgery to demolitive surgery. Materials and Methods. This prospective study was conducted on 26 male patients, with suspected laryngeal neoplasia of glottic region. The images of MRI and CT were analyzed to define the expansion of glottic lesion to anterior commissure, laryngeal cartilages, subglottic and/or supraglottic site, and paraglottic space. The results of MRI and CT were compared with each other and with the pathology report. Results. CT accuracy was 70% with low sensitivity but with high specific value. MRI showed a diagnostic accuracy in 80% of cases, with a sensitivity of 100% and high specificity. Statistical analysis showed that MRI has higher correlation than CT with the pathology report. Conclusion. Our study showed that MRI is more sensitive than CT in the preoperative staging of early glottic cancer, to select exactly the eligible patients in conservative surgery of the larynx, as supracricoid laryngectomy and cordectomy by CO2 laser. [ABSTRACT FROM AUTHOR]

The ability to form ordered nanostructures at the wafer level with low cost methodologies has represented a challenge in the last decade in many research fields spanning from nanoelectronics to photovoltaics (PVs). For the latter application the nanostructures have demonstrated interesting capabilities for exploiting the quantum effects in terms of efficient visible light absorption. To fabricate ordered nanostructures many solutions have been proposed but they provide feature densities lower than 109 cm−2 or present high fabrication costs. We propose a wafer level and low-cost Lithography based on block CoPolymers self-assembling (LCP), which allows the formation of nanofeatures controlled down to 10 nm and density higher than 5 × 1010 cm−2. We propose to use this technique to form radial junctions in nanoholes for solar cells. The approach is similar to that of the nanowires, i.e., it decouples the optical path of the visible photons from the electrical path of the carriers, but since the one-dimensional (1D) structures are embedded inside the bulk of the wafer the structure is more robust and allows easier implementation. To form the junction inside the nanoholes a novel strategy based on the deposition of monolayers of dopant-containing molecules is proposed. This technique allows to obtain shallow and controlled junction depths with peak carrier concentrations of about 1019 cm−3 for both n- and p-type doping. [ABSTRACT FROM AUTHOR]

We have defined the complete structure and assessed the biological activity of the lipopolysaccharide (LPS) from Alkalimonas delamerensis, an alkaliphilic bacterium isolated from soda lakes in China and East Africa. The structural determination, which was achieved by the use of chemical, spectroscopic and spectrometric approaches, indicates a novel Rough type lipopolysaccharide that is rich in negatively charged groups in the lipid A inner core region. The proinflammatory activity of the pure lipopolysaccharide has also been defined by testing the LPS as a stimulant in human HEK293 cells, which express the CD14/MD2/TLR4 complex (HEK293-hTLR4), and in bone marrow-derived macrophages. [ABSTRACT FROM AUTHOR]

Background The clinical evolution of laryngeal squamous cell carcinoma (SCC) is undetectable with the current staging criteria. To more completely understand the biology of laryngeal SCC, we assessed the expression of the proteins B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) and p16. Methods We assessed immunohistochemically the expression of BMI1 and p16 in 25 laryngeal SCCs at different stages. Results High BMI1 expression was detected in 11.7% of glottic tumors and in 50% of supraglottic tumors. No significant differences were observed in the patients' clinical data after they were stratified by the tumor expression of p16. The expression of nuclear BMI1 in the absence of p16 immunoreactivity correlated significantly with the pN status of the primary tumors. Conclusion Nuclear BMI1 expression in the absence of p16 expression seems to characterize a subset of patients with a high risk of developing lymph node metastasis. © 2012 Wiley Periodicals, Inc. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

We present a study on the morphological evolution of hydrogenated amorphous silicon layers obtained by plasma enhanced chemical vapor deposition at different H dilutions in the regime close to the formation of the nanocrystalline (nc-Si) phase. The role of hydrogen in the transition from the amorphous to the crystalline phase is investigated by accurate structural and chemical characterisation, from the early stages of nucleation, where the nuclei present a size slightly larger than the critical nucleus, i.e. about 0.8 nm in radius, up to the formation of crystalline grains larger than 30 nm in radius. Hydrogen is found to have a crucial role in the transition from a-Si:H to nc-Si:H, since it forms an intermediate bond-centred Si-H-Si configuration, and when the H moves away from the bond-centred location, the strained Si-Si bonds either break or relax, undergoing local structural rearrangements closer to those of c-Si. During this phase transition a part of H bonds at grain boundaries. A correlation between the structural characteristics of the crystalline phase and the bonding mechanism of Si with H through multiple hydrides, such as Si-H2 and Si-H3 is found. Particularly the SiH3 are found to be directly correlated to the shape and the size of the nanocrystallites present in the films (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Objective: Congenital disorders of glycosylation (CDG) are a group of metabolic diseases due to defects in protein and lipid glycosylation. We searched for the primary defect in 3 children from 2 families with a severe neurological phenotype, including profound developmental delay, intractable epilepsy, progressive microcephaly, severe hypotonia with elevated blood creatine kinase levels, and early fatal outcome. There was clinical evidence of a muscular dystrophy-dystroglycanopathy syndrome, supported by deficient O-mannosylation by muscle immunohistochemistry. Methods: Biochemical and molecular methods were combined to pinpoint the defect in the glycosylation pathway in the endoplasmic reticulum. Results: Metabolic investigations revealed CDG-I, pointing to a defect in protein N-glycosylation in the endoplasmic reticulum. Analysis of lipid-linked oligosaccharides in fibroblasts showed accumulation of Dol-PP-GlcNAc2-Man5. DNA analysis revealed mutations in DPM2, 1 of the subunits of the dolichol-phosphate-mannose (DPM) synthase; the patient in the first family is compound heterozygous for 2 mutations (c.68A>G, predicting a missense mutation p.Y23C and c.4-1G>C, a splice mutation), whereas the patients in the second family are homozygous for the same missense mutation (c.68A>G, p.Y23C). Interpretation: We describe a new CDG, due to a deficiency of DPM2. Hence, mutations have now been described in the genes for the 3 subunits of DPM: DPM1, DPM2, and DPM3, whereby DPM2-CDG links the congenital disorders of glycosylation to the congenital muscular dystrophies. ANN NEUROL 2012;72:550-558 [ABSTRACT FROM AUTHOR]

Objective To evaluate response to therapy over a 24-month period in a large prospective international cohort of patients with juvenile dermatomyositis (DM). Methods The study included 145 patients with recent-onset juvenile DM and 130 juvenile DM patients experiencing disease flare, all of whom were <18 years old. Disease activity parameters and therapeutic approaches in 4 geographic areas were analyzed at baseline and at 6, 12, and 24 months. Response was assessed according to the Pediatric Rheumatology International Trials Organization (PRINTO) juvenile DM response criteria, and data were reported 'as observed' and in the intent-to-treat (ITT) population. Results Patients with recent-onset juvenile DM at baseline had higher baseline disease activity and greater improvement over 24 months when compared to juvenile DM patients experiencing disease flare at baseline. Methotrexate (MTX) or high-dose corticosteroids were administered more frequently to patients with recent-onset juvenile DM, compared to juvenile DM patients experiencing disease flare, who were more likely to receive cyclosporine. Compared to patients from Western and Eastern Europe, a higher proportion of patients from South and Central America and North America received pulse steroids, and the average steroid dosage was higher in the North American and South and Central American patients. The use of MTX was similar in all 4 regions, while cyclosporin A was more frequently used in Western Europe. In the 'as observed' analysis, 57.9% of the patients with recent-onset juvenile DM and 36.4% of the patients experiencing disease flare ( P < 0.001) reached at least a 70% response by PRINTO criteria at 6 months; these proportions had increased at month 24 to 78.4% and 51.2%, respectively ( P < 0.001). Corresponding results of the ITT analysis were much lower, with only one-third of the patients able to maintain the initial assigned therapy over 24 months. Conclusion Patients with recent-onset juvenile DM are more likely to achieve significant clinical improvement over 24 months, when compared to patients experiencing flares of juvenile DM. Internationally, various therapeutic approaches are used to treat this disease. [ABSTRACT FROM AUTHOR]

Contribution of mass spectrometry (MS) in the diagnosis and characterization of congenital disorders of glycosylation (CDG) has long been known. CDG type I diseases are characterized by the under-occupancy of protein N-glycosylation sites. Electrospray (ESI) MS and matrix assisted laser desorption ionization (MALDI) MS are effective for underglycosylation analyses of intact serum Transferrin (Tf) in CDG-I patients by mass determination of individual component glycoforms. Thus, high-throughput methods developed to speed-up analytical times found increasing application in clinical testing for CDG detection. ESI MS recognizable glycoform profiles of serum Tf have been reported in CDG-I different from PMM2-CDG and in individual CDG-II defects. MALDI MS analysis of acidic and neutral N-linked glycans released from total plasma or targeted glycoproteins, is the mainstream tool to explore abnormal oligosaccharide structure and changes in the relative amount of individual oligosaccharides in CDG-II patients. Here we briefly review state-of-the-art and updates of MS-based applications for the diagnosis of CDG with special emphasis to detectable glycosylation profiles reported in different CDG types. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2010) 114, 761–771. The possibility to selectively remove noradrenergic neurons in the locus coeruleus/subcoeruleus (LC/SubC) complex by the immunotoxin anti-dopamine-β-hydroxylase (DBH)-saporin has offered a powerful tool to study the functional role of this projection system. In the present study, the anatomical consequences of selective lesions of the LC/SubC on descending noradrenergic projections during early postnatal development have been investigated following bilateral intraventricular injections of anti-DBH-saporin or 6-hydroxydopamine to immature (4 day old) rats. Administration of increasing doses (0.25–1.0 μg) of the immunotoxin produced, about 5 weeks later, a dose-dependent loss of DBH-immunoreactive neurons in the LC/SubC complex (≈ 45–90%) paralleled by a similar reduction of noradrenergic innervation in the terminal territories in the lumbar spinal cord. Even at the highest dose used (1.0 μg) the immunotoxin did not produce any detectable effects on dopaminergic, adrenergic, serotonergic or cholinergic neuronal populations, which, by contrast, were markedly reduced after administration of 6-hydroxydopamine. The ≈ 90% noradrenergic depletion induced by 0.5 and 1.0 μg of anti-DBH-saporin remained virtually unchanged at 40 weeks post-lesion. Conversely, the ≈ 45% reduction of spinal innervation density estimated at 5 weeks in animals injected with the lowest dose (0.25 μg) of the immunotoxin was seen recovered up to near-normal levels at 40 weeks, possibly as a result of the intrinsic plasticity of the developing noradrenergic system. A similar reinnervation in the lumbar spinal cord was also seen promoted by grafts of fetal LC tissue implanted at the postnatal day 8 (i.e. 4 days after the lesion with 0.5 μg of anti-DBH-saporin). In these animals, the number of surviving neurons in the grafts and the magnitude of the reinnervation, with fibers extending in both the grey and white matter for considerable distances, were seen higher than those reported in previous studies using adult recipients. This would suggest that the functional interactions between the grafted tissue and the host may recapitulate the events normally occurring during the ontogenesis of the coeruleo-spinal projection system, and can therefore be developmentally regulated. Thus, the neonatal anti-DBH-saporin lesion model, with the possibility to produce graded noradrenergic depletions, holds promises as a most valuable tool to address issues of compensatory reinnervation and functional recovery in the severed CNS as well as to elucidate the mechanisms governing long-distance axon growth from transplanted neural precursors. [ABSTRACT FROM AUTHOR]

Aims: Infection with specific pathogens may lead to increased adiposity. The human adenovirus 36 (Ad36) is a relatively new factor in promoting adipogenesis. It seems to improve the metabolic profile, expanding adipose tissue and enhancing insulin sensitivity in animal models. The aim of this study was to investigate whether any association or predictor effect of Ad36 seropositivity is present in non-alcoholic fatty liver disease (NAFLD), a condition associated with obesity and insulin resistance (IR). Methods: Sixty-five NAFLD patients and 114 controls were investigated. Ultrasound bright liver score (BLS), body composition, IR evaluated by homeostasis model assessment of insulin resistance index (HOMA or HOMA-IR) and serum neutralization assay for antibodies to Ad36 were assessed. Results: Ad36-seropositive patients have a lower risk of bright liver [OR 0.505 (95% confidence interval (CI) 0.265–0.962)]; greater IR leads to a higher risk of bright liver [OR 9.673 (95% CI 4.443–21.058)]. Among NAFLD, Ad36-seropositive vs. Ad36-seronegative patients did not show a significant IR difference. Ad36-seropositive NAFLD patients, with the same levels of HOMA and BLS, had greater body mass index and body fat mass, in comparison with seronegative NAFLD patients. By a multiple linear regression model, BLS was explained by HOMA (β 0.513; P<0.0001), high density lipoprotein cholesterol (β−0.219, P<0.006) and Ad36 seropositivity (β−0.202, P<0.005); Ad36 seropositivity did not explain HOMA in the other multiple logistic regression model. Conclusions: Ad36 seropositivity is not associated with a significant difference of IR in NAFLD patients, but is associated with a greater adiposity. Ad36 seropositivity is associated with a lower occurrence of NAFLD and bright liver, which, conceivably, is not directly mediated by IR. [ABSTRACT FROM AUTHOR]

A 32 year-old asymptomatic male came to our attention with a 21-year history, documented elsewhere, of puzzling increases in his serum transaminase level. At first, very low serum ceruloplasmin level suggested Wilson disease. Two liver biopsies showed mild portal inflammation, steatosis and mild fibrosis. Further investigation revealed low levels of the glycoproteins AT III and clotting factor XI, leading to a diagnosis of congenital disorder of glycosylation (CDG) type II. Further studies as to the cause of this 'apparently new' CDG, are ongoing. On the basis of our data and a literature review, we suggest that subjects with asymptomatic hypertransaminasaemia be screened for CDG. [ABSTRACT FROM AUTHOR]

Pseudomonas stutzeri OXI is a Gram-negative microorganism able to grow in media containing aromatic hydrocarbons. A novel lipo-oligosaccharide from P. stutzeri OX1 was isolated and characterized. For the first time, the presence of two moieties of 4,6- O-(1-carboxy)-ethylidene residues (pyruvic acid) was identified in a core region; these two residues were found to possess different absolute configuration. The structure of the oligosaccharide backbone was determined using either alkaline or acid hydrolysis. Alkaline treatment, aimed at recovering the complete carbohydrate backbone, was carried out by mild hydrazinolysis (de-O-acylation) followed by de-N-acylation using hot KOH. The lipo-oligosaccharide was also analyzed after acid treatment, attained by mild hydrolysis with acetic acid, to obtain information on the nature of the phosphate and acyl groups. The two resulting oligosaccharides were isolated by gel permeation chromatography, and investigated by compositional and methylation analyses, by MALDI mass spectrometry, and by 1H-, 31P- and 13C-NMR spectroscopy. These experiments led to the identification of the major oligosaccharide structure representative of core region-lipid A. All sugars are d-pyranoses and α-linked, if not stated otherwise. Based on the structure found, the hypothesis can be advanced that pyruvate residues are used to block elongation of the oligosaccharide chain. This would lead to a less hydrophilic cellular surface, indicating an adaptive response of P. sutzeri OX1 to a hydrocarbon-containing environment. [ABSTRACT FROM AUTHOR]