The effects of age and ganglioside composition on the rate of motor nerve terminal regeneration following antibody-mediated injury in mice

Gangliosides are glycosphingolipids highly enriched in neural plasma membranes, where they mediate a diverse range of functions and can act as targets for auto-antibodies present in human immune-mediated neuropathy sera. The ensuing autoimmune injury results in axonal and motor nerve terminal (mNT) degeneration. Both aging and ganglioside-deficiency have been linked to impaired axonal regeneration. To assess the effects of age and ganglioside expression on mNT regeneration in an autoimmune injury paradigm, anti-ganglioside antibodies and complement were applied to young adult and aged mice wildtype (WT) mice, mice deficient in either b- and c-series (GD3sKO) or mice deficient in all complex gangliosides (GM2sKO). The extent of mNT injury and regeneration was assessed immediately or after 5 days, respectively. Depending on ganglioside expression and antibody-specificity, either a selective mNT injury or a combined injury of mNTs and neuromuscular glial cells was elicited. Immediately after induction of the injury, between 1.5% and 11.8% of neuromuscular junctions (NMJs) in the young adult groups exhibited healthy mNTs. Five days later, most NMJs, regardless of age and strain, had recovered their mNTs. No significant differences could be observed between young and aged WT and GM2sKO mice; aged GD3sKO showed a mildly impaired rate of mNT regeneration when compared with their younger counterparts. Comparable rates were observed between all strains in the young and the aged mice. In summary, the rate of mNT regeneration following anti-ganglioside antibody and complement-mediated injury does not differ majorly between young adult and aged mice irrespective of the expression of particular gangliosides

Fatal Clostridium sordellii-mediated hemorrhagic and necrotizing gastroenteropathy in a dog: case report

Background: Canine hemorrhagic gastroenteritis (also canine gastrointestinal hemorrhagic syndrome) is commonly associated with Clostridium perfringens, although in some cases the etiology remains unclear. This report describes a fatal acute hemorrhagic and necrotizing gastroenteropathy in a dog associated with Clostridium sordellii, a bacterial species never before identified as the etiological agent of hemorrhagic and necrotizing gastroenteropathy in dogs. Case presentation: A fully vaccinated, eight-year-old, female neutered Labrador presented with a history of vomiting without diarrhea. Clinical examination revealed pink mucous membranes, adequate hydration, normothermia, and normocardia. The dog was discovered deceased the following day. Post-mortem examination showed moderate amounts of dark red, non-clotted fluid within the stomach that extended into the jejunum. Discoloration was noted in the gastric mucosa, liver, lungs, and kidneys, with small petechial hemorrhages present in the endocardium over the right heart base and thymic remnants. Histological analysis demonstrated that the gastric fundic mucosa, the pyloric region, small intestine, and large intestine exhibited superficial coagulative necrosis and were lined with a layer of short Gram-positive rods. Anaerobic culture of the gastric content revealed C. sordellii as the dominant bacterial species and neither Salmonella spp., Campylobacter spp., C. perfringens, nor C. difficile were isolated. Unexpectedly, whole genome sequencing of the C. sordellii isolate showed that it lacked the main plasmid-encoded virulence factors typical of the species, indicating that the genetic determinants of pathogenicity of this strain must be chromosomally encoded. Further phylogenetic analysis revealed it to be genetically similar to C. sordellii isolates associated with gastroenteric disease in livestock, indicating that the infection may have been acquired from the environment. Conclusions: This case demonstrates that C. sordellii can associate with a canine hemorrhagic and necrotizing gastroenteropathy in the absence of C. perfringens and illustrates the benefits of using bacterial whole genome sequencing to support pathological investigations in veterinary diagnostics. These data also update the molecular phylogeny of C. sordellii, indicating a possible pathogenic clade in the environment that is distinct from currently identified clades

Canceling the Big Deal: Three R1 Libraries Compare Data, Communication, and Strategies

Canceling the Big Deal is becoming more common, but there are still many unanswered questions about the impact of this change and the fundamental shift in the library collections model that it represents. Institutions like Southern Illinois University Carbondale and the University of Oregon were some of the first institutions to have written about their own experience with canceling the Big Deal several years ago, but are those experiences the norm in terms of changes in budgets, collection development, and interlibrary loan activity? Within the context of the University of California system’s move to cancel a system-wide contract with Elsevier, how are libraries managing the communication about Big Deals both internally with library personnel as well as externally with campus stakeholders? Three R1 libraries (University of Maryland, University of Oklahoma, and Kansas State University) will compare their data, discuss both internal and external communication strategies, and examine the impact these decisions have had on their collections in terms of interlibrary loan and collection development strategies. The results of a brief survey measuring the status of the audience members with respect to Big Deals, communication efforts with campus stakeholders, and impacts on collections will also be discussed

Mitochondrial fission factor (MFF) frameshift variant in Bullmastiffs with mitochondrial fission encephalopathy.

Familial cerebellar ataxia with hydrocephalus in Bullmastiffs was described almost 40 years ago as a monogenic autosomal recessive trait. We investigated two young Bullmastiffs showing similar clinical signs. They developed progressive gait and behavioural abnormalities with an onset at around 6 months of age. Neurological assessment was consistent with a multifocal brain disease. Magnetic resonance imaging of the brain showed intra-axial bilateral symmetrical focal lesions localised to the cerebellar nuclei. Based on the juvenile age, nature of neurological deficits and imaging findings, an inherited disorder of the brain was suspected. We sequenced the genome of one affected Bullmastiff. The data were compared with 782 control genomes of dogs from diverse breeds. This search revealed a private homozygous frameshift variant in the MFF gene in the affected dog, XM_038574000.1:c.471_475delinsCGCTCT, that is predicted to truncate 55% of the wild type MFF open reading frame, XP_038429928.1: p.(Glu158Alafs*14). Human patients with pathogenic MFF variants suffer from 'encephalopathy due to defective mitochondrial and peroxisomal fission 2'. Archived samples from two additional affected Bullmastiffs related to the originally described cases were obtained. Genotypes in a cohort of four affected and 70 unaffected Bullmastiffs showed perfect segregation with the disease phenotype. The available data together with information from previous disease reports allow classification of the investigated MFF frameshift variant as pathogenic and probably causative defect of the observed neurological phenotype. In analogy to the human phenotype, we propose to rename this disease 'mitochondrial fission encephalopathy (MFE)'

NDUFS7 variant in dogs with Leigh syndrome and its functional validation in a Drosophila melanogaster model

Two Jack-Russell Terrier × Chihuahua mixed-breed littermates with Leigh syndrome were investigated. The dogs presented with progressive ataxia, dystonia, and increased lactate levels. Brain MRI showed characteristic bilateral symmetrical T2 hyperintense lesions, histologically representing encephalomalacia. Muscle histopathology revealed accumulation of mitochondria. Whole genome sequencing identified a missense variant in a gene associated with human Leigh syndrome, NDUFS7:c.535G > A or p.(Val179Met). The genotypes at the variant co-segregated with the phenotype in the investigated litter as expected for a monogenic autosomal recessive mode of inheritance. We investigated the functional consequences of the missense variant in a Drosophila melanogaster model by expressing recombinant wildtype or mutant canine NDUFS7 in a ubiquitous knockdown model of the fly ortholog ND-20. Neither of the investigated overexpression lines completely rescued the lethality upon knockdown of the endogenous ND-20. However, a partial rescue was found upon overexpression of wildtype NDUFS7, where pupal lethality was moved to later developmental stages, which was not seen upon canine mutant overexpression, thus providing additional evidence for the pathogenicity of the identified variant. Our results show the potential of the fruit fly as a model for canine disease allele validation and establish NDUFS7:p.(Val179Met) as causative variant for the investigated canine Leigh syndrome

Serum anti‐GM2 and anti‐GalNAc‐GD1a ganglioside IgG antibodies are biomarkers for immune‐mediated polyneuropathies in cats

Background and Aims: Recent work identified anti-GM2 and anti-GalNAc-GD1a IgG ganglioside antibodies as biomarkers in dogs clinically diagnosed with acute canine polyradiculoneuritis, in turn considered a canine equivalent of Guillain-Barré syndrome. This study aims to investigate the serum prevalence of similar antibodies in cats clinically diagnosed with immune-mediated polyneuropathies. Methods: The sera from 41 cats clinically diagnosed with immune-mediated polyneuropathies (IPN), 9 cats with other neurological or neuromuscular disorders (ONM) and 46 neurologically normal cats (CTRL) were examined for the presence of IgG antibodies against glycolipids GM1, GM2, GD1a, GD1b, GalNAc-GD1a, GA1, SGPG, LM1, galactocerebroside and sulphatide. Results: A total of 29/41 IPN-cats had either anti-GM2 or anti-GalNAc-GD1a IgG antibodies, with 24/29 cats having both. Direct comparison of anti-GM2 (sensitivity: 70.7%; specificity: 78.2%) and anti-GalNAc-GD1a (sensitivity: 70.7%; specificity: 70.9%) antibodies narrowly showed anti-GM2 IgG antibodies to be the better marker for identifying IPN-cats when compared to the combined ONM and CTRL groups (p=0.049). Anti-GA1 and/or anti-sulphatide IgG antibodies were ubiquitously present across all sample groups, whereas antibodies against GM1, GD1a, GD1b, SGPG, LM1 and galactocerebroside were overall only rarely observed. Interpretation: Anti-GM2 and anti-GalNAc-GD1a IgG antibodies may serve as serum biomarkers for immune-mediated polyneuropathies in cats, as previously observed in dogs and humans

Rapid Injury and Steady Recovery of the Neuromuscular Nerve Terminal Integrity After Application of Anti-ganglioside Antibody in a Murine Model of Guillain-Barré Syndrome

No abstract available

Rapid Injury and Steady Recovery of the Neuromuscular Nerve Terminal Integrity After Application of Anti-ganglioside Antibody in a Murine Model of Guillain-Barré Syndrome

No abstract available

Institut fuer Materialforschung. Ergebnisbericht ueber Forschung und Entwicklung 1994

The IMF consists of three institutes with different tasks: IMF I works mainly on the development of metals, nonmetals and composite materials and on problems concerning the structure and properties of interfaces and protective layers. IMF II works on component reliablility, failure mechanisms and damage analysis. IMF III works on problems of process engineering in the production of ceramic powders and ceramic, metallic and polymeric microstructures, as well as on the design of nuclear components and the optimisation of corrosive materials. The IMF supports the research activities of Karlsruhe Research Center, especially in nuclear fusion research, microsystems engineering, nuclear safety, superconductivity, and low-pollution and low-waste processes. Materials and strength problems are investigated for future fusion reactors, high-performance microsystems, and safety problems in nuclear engineering. (orig./MM)Das Institut besteht aus den drei Teilinstituten IMF I, IMF II und IMF III. Die Aufgabengebiete gliedern sich in Angewandte Werkstoffphysik (IMF I), Werkstoff- und Strukturmechanik (IMF II) und Werkstoff-Prozesstechnik (IMF III). Das IMF I arbeitet hierbei bevorzugt an der Entwicklung von metallischen, nichtmetallischen und Verbundwerkstoffen sowie an Fragen zu Struktur und Eigenschaften von Grenzflaechen und Oberflaechenschutzschichten. Das IMF II behandelt schwerpunktmaessig die Zuverlaessigkeit von Komponenten, Versagenmechanik und Schadenskunde. Das IMF III bearbeitet prozesstechnische Fragestellungen bei der Herstellung keramischer Pulver und keramischer, metallischer und polymerer Mikrostrukturen. Daneben befasst es sich mit der Auslegung kerntechnischer Komponenten und der Optimierung korrosionsbelasteter Materialien. An den verschiedenen Arbeitsschwerpunkten des Kernforschungszentrums wirkt das Institut mit seinen Forschungsarbeiten besonders in der Kernfusion, Mikrosystemtechnik, Nuklearen Sicherheitsforschung, der Supraleitung sowie bei den schadstoff- und abfallarmen Verfahren mit. Es werden Material- und Festigkeitsprobleme fuer zukuenftige Fusionsreaktoren, in hochleistungsfaehigen Mikrosystemen und sicherheitsrelevante Fragen der Kerntechnik untersucht. (orig./MM)Available from TIB Hannover: ZA 5141(5534) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Age-related Changes to the Distribution of Perisynaptic Schwann Cells at the Murine Neuromuscular Junction

No abstract available