The Saanen goat as an animal model for post-laryngectomy research: practical implications

A modern way of voice rehabilitation after total laryngectomy includes the use of shunt valves and tracheostoma valves. Problems of fixation to the surrounding tissue are a major drawback in the use of the shunt valve, heat and moisture exchange (HME) filters and, especially, the tracheostoma valve. To solve these problems different tissue connectors were developed. The main objective was to test the feasibility of these prototypes in a new animal model. Here we discuss the results, problems and complications of the selected Saanen goat model. In this prospective laboratory study, 19 healthy adult female Saanen goats (Capra hircus) were used and observed post-surgically for 12 weeks. Selection criteria such as comparable anatomy to humans and easy handling were used for animal model development. Also a literature search using the Medline and the ISI Web of Science databases was performed. The anatomy of the Saanen goat was investigated in a separate postmortem study. Surgery consisted of a laryngotracheal separation and implantation of a tracheo-oesophageal and tracheostoma tissue connector with fibrin tissue glue. Postoperative care consisted of frequent stoma care, monitoring appetite, weight, vital signs and administration of antibiotics, analgesics and mucolytic agents. All animals survived the surgical procedure. However, postoperative care was extensive, labour intensive and was accompanied by several complications. Eleven animals died spontaneously before the end of the experiment. The tracheostoma tissue connector caused signs of local infection in all cases. There was no evidence of infection around the tracheo-oesophageal tissue connector in 18 cases. It was concluded that the use of goats in this tracheostoma model was associated with major complications and should, therefore, only be used for short-term experiments with intensive care. Additional research is needed to see if clinical application of the tissue connectors is possible in the future.     

Selective expression rather than specific function of Txk and Itk regulate Th1 and Th2 responses

Itk and Txk/Rlk are Tec family kinases expressed in T cells. Itk is expressed in both Th1 and Th2 cells. By contrast, Txk is preferentially expressed in Th1 cells. Although Itk is required for Th2 responses in vivo and Txk is suggested to regulate IFN-gamma expression and Th1 responses, it remains unclear whether these kinases have distinct roles in Th cell differentiation/function. We demonstrate here that Txk-null CD4(+) T cells are capable of producing both Th1 and Th2 cytokines similar to those produced by wild-type CD4(+) T cells. To further examine whether Itk and Txk play distinct roles in Th cell differentiation and function, we examined Itk-null mice carrying a transgene that expresses Txk at levels similar to the expression of Itk in Th2 cells. Using two Th2 model systems, allergic asthma and schistosome egg-induced lung granulomas, we found that the Txk transgene rescued Th2 cytokine production and all Th2 symptoms without notable enhancement of IFN-gamma expression. These results suggest that Txk is not a specific regulator of Th1 responses. Importantly, they suggest that Itk and Txk exert their effects on Th cell differentiation/function at the level of expression.     

Microbial biogeochemistry and phosphorus limitation in cryoconite holes on glaciers across the Taylor Valley,McMurdo Dry Valleys,Antarctica

Biogeochemistry - Zooplankton communities are important components of aquatic food webs in part because they recycle nutrients and carbon. Lacking a complete understanding of the composition of...     

Rats go genomic

A report on the meeting 'Rat Genomics and Models', Cold Spring Harbor, USA, 8-11 December 2005.     

DNA Sequences Proximal to Human Mitochondrial DNA Deletion Breakpoints Prevalent in Human Disease Form G-quadruplexes,a Class of DNA Structures Inefficiently Unwound by the Mitochondrial Replicative Twinkle Helicase

Mitochondrial DNA deletions are prominent in human genetic disorders, cancer, and aging. It is thought that stalling of the mitochondrial replication machinery during DNA synthesis is a prominent source of mitochondrial genome instability; however, the precise molecular determinants of defective mitochondrial replication are not well understood. In this work, we performed a computational analysis of the human mitochondrial genome using the “Pattern Finder” G-quadruplex (G4) predictor algorithm to assess whether G4-forming sequences reside in close proximity (within 20 base pairs) to known mitochondrial DNA deletion breakpoints. We then used this information to map G4P sequences with deletions characteristic of representative mitochondrial genetic disorders and also those identified in various cancers and aging. Circular dichroism and UV spectral analysis demonstrated that mitochondrial G-rich sequences near deletion breakpoints prevalent in human disease form G-quadruplex DNA structures. A biochemical analysis of purified recombinant human Twinkle protein (gene product of c10orf2) showed that the mitochondrial replicative helicase inefficiently unwinds well characterized intermolecular and intramolecular G-quadruplex DNA substrates, as well as a unimolecular G4 substrate derived from a mitochondrial sequence that nests a deletion breakpoint described in human renal cell carcinoma. Although G4 has been implicated in the initiation of mitochondrial DNA replication, our current findings suggest that mitochondrial G-quadruplexes are also likely to be a source of instability for the mitochondrial genome by perturbing the normal progression of the mitochondrial replication machinery, including DNA unwinding by Twinkle helicase.     

A Dutch guideline for the treatment of scoliosis in neuromuscular disorders

Background

Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care.

Methods

The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence.

Results

For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands.

Conclusion

In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders.     

产β—葡萄糖苷酶真菌诱变菌株快速筛选方法

报道了一种快速筛选产β-葡萄糖管酶真菌诱变菌株的方法。该法利用ρNPG经β-葡萄糖苷酶水解,水解产物ρNP在碱性条件下显色的原理。采用自制的特殊初筛平皿.经一年多的实践应用表明此法具有简便、灵敏、筛子消耗量小、筛选效率高等优点。