The Role of Arp2/3 in Ring Canal Development in Drosophila melanogaster

Infertility and impaired fecundity affect 8.2 million women in the United States. Intercellular bridges are essential to the proper formation of germ cells in many organisms; therefore, learning more about how they are formed and regulated during the formation of sperm and eggs could provide insight into how defects in their structure can impact fertility. Intercellular bridges are actin-rich structures that connect developing germ cells to each other and allow the transfer of materials. I used the development of the fruit fly egg as a model system to study formation and regulation of intercellular bridges. Specifically, I investigated the role of an actin nucleating protein complex located at the ring canals, Arp2/3, in the formation and expansion of these structures. The objective of this work is to characterize the effect of depletion, mutation, or inhibition of the Arp2/3 complex on the structure and growth of these intercellular bridges, called ring canals. Because ring canals are rich in actin and actin-binding proteins, I predicted that if Arp2/3 levels are altered, then ring canal formation and/or growth will be affected. When levels of Arp2/3 complex proteins were reduced or if the complex was chemically inhibited, ring canals are significantly smaller than in controls; this difference was more pronounced in later stages of oogenesis (stages 7-10b), suggesting Arp2/3 plays a role in ring canal structure and stability in later stages of oogenesis. Because these structures are found in organisms from insects to humans, research on the Arp2/3 complex provides valuable understanding of intercellular bridge structure and function that can be applied to higher organisms and our understanding of infertility

Development of learning objectives for neurology in a veterinary curriculum: part I: undergraduates

Background With an increasing caseload of veterinary neurology patients in first opinion practice, there is a requirement to establish relevant learning objectives for veterinary neurology encompassing knowledge, skills and attitudes for veterinary undergraduate students in Europe. With help of experts in veterinary neurology from the European College of Veterinary Neurology (ECVN) and the European Society of Veterinary Neurology (ESVN) a survey of veterinary neurologic learning objectives using a modified Delphi method was conducted. The first phase comprised the development of a draft job description and learning objectives by a working group established by the ECVN. In the second phase, a quantitative questionnaire (multiple choice, Likert scale and free text) covering 140 learning objectives and subdivided into 8 categories was sent to 341 ESVN and ECVN members and a return rate of 62% (n = 213/341) was achieved. Results Of these 140 learning objectives ECVN Diplomates and ESVN members considered 42 (30%) objectives as not necessary for standard clinical veterinary neurology training, 94 (67%) were graded to be learned at a beginner level and 4 (3%) at an advanced level. The following objectives were interpreted as the most important day one skills: interpret laboratory tests, perform a neurological examination and establish a neuroanatomical localization. In this survey the three most important diseases of the central nervous system included epilepsy, intervertebral disc disease and inflammatory diseases. The three most important diseases of the peripheral nervous system included polyradiculoneuritis, myasthenia gravis and toxic neuropathies. Conclusions The results of this study should help to reform the veterinary curriculum regarding neurology and may reduce the phenomenon of “Neurophobia”.</p

Toll-like receptors 4 and 9 are responsible for the maintenance of the inflammatory reaction in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis

BACKGROUND: Steroid-responsive meningitis-arteritis (SRMA) is a systemic inflammatory disease affecting young adult dogs and a potential large animal model for neutrophilic meningitis. Similarities between SRMA and infectious central nervous system (CNS) diseases in lymphocyte subsets suggest an infectious origin. Toll-like receptors (TLRs) are pattern recognition receptors playing an important role in innate immunity. Due to their ability to recognize both self and non-self antigens, we hypothesize that TLRs are among the key factors for the induction of the inflammatory process in SRMA and provide an indirect hint on the etiology of the disease. METHODS: The expression profile of cell surface TLRs (TLR2, TLR4 and TLR5) and intracellular TLRs (TLR3 and TLR9) of canine leukocytes was analyzed by immunophenotyping and subsequent flow cytometric measurements. Experiments were performed on cerebrospinal fluid (CSF) and peripheral blood (PB) samples of dogs affected with SRMA during the acute phase (n = 14) as well as during treatment (n = 23) and compared with those of dogs with bacterial meningitis (n = 3), meningoencephalitis of unknown etiology (n = 6), neoplasia of the central nervous system (n = 6) and a group of dogs with miscellaneous neurological diseases (n = 9). Two additional control groups consisted of dogs with pyogenic infections (n = 13) and of healthy dogs (n = 6). RESULTS: All examined groups showed a high percentage of TLR2, TLR4 and TLR5 positive PB polymorphonuclear cells (PMNs) in comparison to healthy dogs. Very high values of TLR9 positive PB PMNs were detected in acute SRMA. Only a few similarities were found between SRMA patients and dogs with pyogenic infections, both groups were characterized by high expression of TLR4 positive PB monocytes. Glucocorticosteroid therapy reduced TLR2, TLR4 and TLR9 expression in PB monocytes. CONCLUSIONS: A relatively high expression of TLR4 and TLR9 in acute SRMA suggests that these two receptors might be involved in the inflammatory process in SRMA, enhancing the autoimmune reaction. Systematic CSF cell analysis for TLRs can be performed in future treatment studies in larger animals, such as dogs

Clinical presentation, diagnostic findings and outcome of dogs with presumptive spinal-only meningoencephalomyelitis of unknown origin

Objectives: To summarise clinical presentation, diagnostic findings and long-term outcome for dogs clinically diagnosed with meningoencephalomyelitis of unknown origin affecting the spinal cord alone. Methods: Medical records were reviewed for dogs diagnosed with presumptive spinal-only meningoencephalomyelitis of unknown origin between 2006 and 2015. Results: 21 dogs were included; the majority presented with an acute (43%) or chronic (52%) onset of neurological signs. Ambulatory paresis was the most common neurological presentation (67%). Neurological examination most commonly revealed a T3-L3 myelopathy, and spinal hyperaesthesia was a common finding (71%). A spinal cord lesion was visible in 90% of cases on magnetic resonance imaging. Eighteen lesions (86%) showed parenchymal contrast enhancement and 17 lesions (81%) showed contrast enhancement of overlying meninges. All dogs were treated with immunosuppressive doses of glucocorticosteroids, sometimes combined with cytosine arabinoside. At time of data capture, 10/21 dogs (48%) had died or been euthanased because of the condition. Overall median survival time was 669 days. Clinical Significance: Meningoencephalomyelitis of unknown origin should be considered in the differential diagnosis of dogs presenting with a progressive myelopathy. Magnetic resonance imaging features can possibly help to distinguish presumptive meningoencephalomyelitis of unknown origin from other more common spinal diseases. Overall, long-term survival is guarded, approximately 50% of dogs will die or be euthanased despite appropriate therapy

Compliance als Schutz vor Verbandsverantwortlichkeit?

Compliance bedeutet nicht nur Einhaltung und Beachtung von Vorschriften, sondern betrifft auch Maßnahmen, die die Einhaltung der Rechtsnormen absichern sollen und läuft somit auf eine Übererfüllung von Verpflichtungen hinaus. Wenn es keinen klaren Maßstab für Kontroll- und Überwachungspflichten gibt, besteht die Gefahr, dass Strafverfolgungsbehörden die Compliance-Maßnahmen als Maßstab heranziehen und so eine Verschärfung der Pflichten erzeugen. Nach den Regeln des Verbandsverantwortlichkeitsgesetzes schließt im Übrigen das beste Compliance-System nicht zwingend die Verbandsverantwortlichkeit aus, steht aber unter Umständen einem Verfahren gegen den Verband entgegen. “Compliance” does not only mean the compliance with norms but also comprises measures which shall ensure compliance and, thus, implies the over-implementation of duties. Where there is no clear yardstick for duties of control and surveillance, the danger that criminal law enforcement authorities use compliance measures as a benchmark and thus cause a tightening of the respective duties is present. According to the rules of the (Austrian) statute for the criminal responsibility of legal entities, the best of all compliance systems does not necessarily bar the responsibility of a legal entity, but – under certain circumstances – excludes a procedure against the legal entity

Tongue and tail necrosis in an atypical case of acute steroid responsive meningitis-arteritis in a dog

Acute steroid responsive meningitis-arteritis (SRMA) is a common neurological disorder in young dogs. Typical clinical symptoms of the acute form of SRMA are neck pain, depression and fever. This case report describes a 1.5-year-old Pointer with uncommon neurological deficits (unilateral multiple cranial nerve deficits and Homer's syndrome) and an exceptional necrosis of the tongue. This was believed to be part of the systemic vasculitis accompanying SRMA. The patient also developed tail necrosis and iatrogenic calcinosis cutis, which complicated further treatment of the dog

Clinical reasoning in canine spinal disease: what combination of clinical information is useful?

Spinal disease in dogs is commonly encountered in veterinary practice. Numerous diseases may cause similar clinical signs and presenting histories. The study objective was to use statistical models to identify combinations of discrete parameters from the patient signalment, history and neurological examination that could suggest the most likely diagnoses with statistical significance. A retrospective study of 500 dogs referred to the Queen Mother Hospital for Animals before June 2012 for the investigation of spinal disease was performed. Details regarding signalment, history, physical and neurological examinations, neuroanatomical localisation and imaging data were obtained. Univariate analyses of variables (breed, age, weight, onset, deterioration, pain, asymmetry, neuroanatomical localisation) were performed, and variables were retained in a multivariate logistic regression model if P<0.05. Leading diagnoses were intervertebral disc extrusion (IVDE, n=149), intervertebral disc protrusion (n=149), ischaemic myelopathy (IM, n=48) and neoplasms (n=44). Multivariate logistic regression characterised IM and acute non-compressive nucleus pulposus extrusions as the only peracute onset, non-progressive, non-painful and asymmetrical T3-L3 myelopathies. IVDE was most commonly characterised as acute onset, often deteriorating, painful and largely symmetrical T3-L3 myelopathy. This study suggests that most spinal diseases cause distinctive combinations of presenting clinical parameters (signalment, onset, deterioration, pain, asymmetry, neuroanatomical localisation). Taking particular account of these parameters may aid decision making in a clinical setting

Current Approaches to the Management of Acute Thoracolumbar Disc Extrusion in Dogs

Intervertebral disc extrusion (IVDE) is one of the most common neurologic problems encountered in veterinary clinical practice. The purpose of this manuscript is to provide an overview of the literature related to treatment of acute canine thoracolumbar IVDE to help construct a framework for standard care of acute canine thoracolumbar IVDE where sufficient evidence exists and to highlight opportunities for future prospective veterinary clinical research useful to strengthen care recommendations in areas where evidence is low or non-existent. While there exist a number of gaps in the veterinary literature with respect to standards of care for dogs with acute thoracolumbar IVDE, recommendations for standard care can be made in some areas, particularly with respect to surgical decompression where the currently available evidence supports that surgery should be recommended for dogs with nonambulatory paraparesis or worse. While additional information is needed about the influence on timing of decompression on outcome in dogs that are deep pain negative for longer than 48 h duration, there is no evidence to support treatment of the 48 h time point as a cut off beyond which it becomes impossible for dogs to achieve locomotor recovery. Surgical decompression is best accomplished by either hemilaminectomy or mini-hemilaminectomy and fenestration of, at a minimum, the acutely ruptured disc. Adjacent discs easily accessed by way of the same approach should be considered for fenestration given the evidence that this substantially reduces future herniation at fenestrated sites. Currently available neuroprotective strategies such as high does MPSS and PEG are not recommended due to lack of demonstrated treatment effect in randomized controlled trials, although the role of anti-inflammatory steroids as a protective strategy against progressive myelomalacia and the question of whether anti-inflammatory steroids or NSAIDs provide superior medical therapy require further evaluation