Botulinum neurotoxin is shielded by NTNHA in an interlocked complex     

Gu S  Rumpel S  Zhou J  Strotmeier J  Bigalke H  Perry K  Shoemaker CB  Rummel A  Jin R 《Science (New York, N.Y.)》2012,335(6071):977-981

Botulinum neurotoxins (BoNTs) are highly poisonous substances that are also effective medicines. Accidental BoNT poisoning often occurs through ingestion of Clostridium botulinum-contaminated food. Here, we present the crystal structure of a BoNT in complex with a clostridial nontoxic nonhemagglutinin (NTNHA) protein at 2.7 angstroms. Biochemical and functional studies show that NTNHA provides large and multivalent binding interfaces to protect BoNT from gastrointestinal degradation. Moreover, the structure highlights key residues in BoNT that regulate complex assembly in a pH-dependent manner. Collectively, our findings define the molecular mechanisms by which NTNHA shields BoNT in the hostile gastrointestinal environment and releases it upon entry into the circulation. These results will assist in the design of small molecules for inhibiting oral BoNT intoxication and of delivery vehicles for oral administration of biologics.  相似文献   

Identification of small molecule activators of cryptochrome   总被引：1，自引：0，他引：1  

T Hirota  JW Lee  PC St John  M Sawa  K Iwaisako  T Noguchi  PY Pongsawakul  T Sonntag  DK Welsh  DA Brenner  FJ Doyle  PG Schultz  SA Kay 《Science (New York, N.Y.)》2012,337(6098):1094-1097

Impairment of the circadian clock has been associated with numerous disorders, including metabolic disease. Although small molecules that modulate clock function might offer therapeutic approaches to such diseases, only a few compounds have been identified that selectively target core clock proteins. From an unbiased cell-based circadian phenotypic screen, we identified KL001, a small molecule that specifically interacts with cryptochrome (CRY). KL001 prevented ubiquitin-dependent degradation of CRY, resulting in lengthening of the circadian period. In combination with mathematical modeling, our studies using KL001 revealed that CRY1 and CRY2 share a similar functional role in the period regulation. Furthermore, KL001-mediated CRY stabilization inhibited glucagon-induced gluconeogenesis in primary hepatocytes. KL001 thus provides a tool to study the regulation of CRY-dependent physiology and aid development of clock-based therapeutics of diabetes.  相似文献   

Adverse reactions from essential oil‐containing natural flea products exempted from Environmental Protection Agency regulations in dogs and cats     

Allison G. Genovese DVM  Mary Kay McLean MS  Safdar A. Khan DVM  MS  PhD  DABVT 《Journal of Veterinary Emergency and Critical Care》2012,22(4):470-475

  相似文献   

Single screw transphyseal bridging of the distal metacarpus and metatarsus for correction of angular limb deformity in the foal     

A. T. Kay  R. J. Hunt 《Equine Veterinary Education》2009,21(12):671-672

  相似文献   

Leaching-bed reactor for producing stabilised plant growing media from dairy manure     

Wei Liao  Craig Frear  Kay Oakley  Shulin Chen 《Biosystems Engineering》2010,106(3):278-285

  相似文献   

Detection and isolation of a herpesvirus from a spur-thighed tortoise (Testudo graeca) in the UK     

Drury SE  Gough RE  Kay AV  McArthur SD 《The Veterinary record》1999,145(20):586-588

  相似文献   

Correction of angular limb deformity in two subspecies of flamingo (Phoenicopterus ruber) utilizing a transphyseal bridging technique.     

Tawnia J Zollinger  Kay A Backues  Armando G Burgos-Rodriguez 《Journal of zoo and wildlife medicine》2005,36(4):689-697

Three hand-raised American flamingo (Phoenicopterus ruber ruber) chicks and one hand-raised Chilean flamingo (Phoenicopterus ruber chilensis) developed valgus angular limb deformities of the proximal tarsometatarsal bone. All flamingos underwent surgical correction to unequally retard the growth plate using transphyseal bridging. Positive profile pins were placed in the proximal epiphysis and distal to the growth plate in the metaphysis on the convex side of the affected tarsometatarsus. Various banding techniques were used in each flamingo to create tension. Three of the four flamingos responded in 7-14 days with correction or slight overcorrection of the valgus limb deformity. The fourth flamingo's leg deformity did not improve for reasons thought to be related to improper implant placement. Growth plate retardation by transphyseal bridging proved successful in correcting valgus limb deformity of the proximal tarsometatarsus. This technique may be considered as an option for correction of angular limb deformities of the proximal tarsometatarsus in flamingos less than 90-120 days of age.  相似文献   

Development of a pooled probe method for locating small gene families in a physical map of soybean using stress related paralogues and a BAC minimum tile path     

Kay L Shopinski  Muhammad J Iqbal  Jeffry L Shultz  Dheepakkumaran Jayaraman  David A Lightfoot 《Plant methods》2006,2(1):20-13

Background  

Genome analysis of soybean (Glycine max L.) has been complicated by its paleo-autopolyploid nature and conserved homeologous regions. Landmarks of expressed sequence tags (ESTs) located within a minimum tile path (MTP) of contiguous (contig) bacterial artificial chromosome (BAC) clones or radiation hybrid set can identify stress and defense related gene rich regions in the genome. A physical map of about 2,800 contigs and MTPs of 8,064 BAC clones encompass the soybean genome. That genome is being sequenced by whole genome shotgun methods so that reliable estimates of gene family size and gene locations will provide a useful tool for finishing. The aims here were to develop methods to anchor plant defense- and stress-related gene paralogues on the MTP derived from the soybean physical map, to identify gene rich regions and to correlate those with QTL for disease resistance.  相似文献   

Physiological Responses of Men and Women to Barley and Oat Extracts (Nu‐trimX). II. Comparison of Glucose and Insulin Responses     

Judith Hallfrisch  Daniel J. Scholfield  Kay M. Behall 《Cereal Chemistry》2003,80(1):80-83

This study was designed to compare the glucose, insulin, and glucagon responses to consumption of high‐soluble β‐glucan compounds from oats and barley. After an initial medical evaluation that included blood and urine testing, 11 men and 11 women, nondiabetics, 35–57 years, were selected. Subjects consumed a controlled diet for three days. On the third day of five successive periods, subjects consumed 1 g/kg of body weight of carbohydrate as glucose or 0.66 g/kg of body weight pudding (predominantly sucrose) and 0.33 g/kg of body weight as oat bran, barley flour, oat or barley extract (Nu‐trimX) in a Latin square design. Order of treatment was randomly assigned. Glycemic responses were calculated using the trapezoid method. Data were analyzed using mixed procedure analysis of variance program. Glucose responses to oats, barley, and both extracts, and areas under the curve were significantly lower than responses to the glucose solution (P < 0.0001). Insulin responses for the barley extract were lowest and were significantly lower than for glucose solution. Oat and barley extracts retain the beneficial effects of the grains from which they are extracted. High‐soluble fiber barley is more effective than standard oats. Oat and barley carbohydrate‐based fat substitutes can provide a useful addition to menus to control plasma glucose responses.  相似文献   

Compressive myelopathy due to intervertebral disk extrusion in a llama (Lama glama).     

Beth A Valentine  Montague N Saulez  Christopher K Cebra  Kay A Fischer 《Journal of veterinary diagnostic investigation》2006,18(1):126-129

A 12-year-old intact female llama was euthanized following acute onset of spastic tetraparesis and recumbency with inability to rise. Postmortem examination revealed caudal cervical spinal cord compression due to a mass within the ventral spinal canal arising from the C6-C7 intervertebral disk space and attached to an irregularly thickened annulus fibrosis. On histopathologic examination, the mass was composed of amorphous acellular basophilic to amphophilic material admixed with irregularly arranged collagen bundles. The amorphous material was metachromatic and contained multiple small foci of markedly vacuolated round cells, characteristic of origin from the nucleus pulposus. Severe necrosis of all white matter tracts with astrocytic reaction was present in the overlying spinal cord segment. Ascending and descending Wallerian degeneration and dissecting interstitial astrogliosis were present within white matter tracts above and below the lesion, respectively. The diagnosis was compressive myelopathy due to chronic extrusion of the nucleus pulposus of the C6-C7 intervertebral disk. To the authors' knowledge, this is the first report of intervertebral disk disease in a camelid.  相似文献