Changes in individuals’ working practice,

and departmental or trust policies or procedures at NHS trusts across England were also identified. Copyright © 2012 John Wiley & Sons. “
“RP Raghavan, et al. Consultant delivered seven-day health care: results from a medical model on a diabetes base ward. Pages 58–61. “
“A 36-year-old female diabetic patient with genetically confirmed Prader–Willi syndrome had developed weight increase and severe symptomatic hyperglycaemia despite triple oral hypoglycaemic therapies. Main meals were supervised at home and when working in day care. The addition of insulin therapy induced further weight increase and hypertension with only a small improvement in glycaemia. She suffered from a thrombotic stroke. During rehabilitation her hyperphagia persisted and she was commenced on exenatide in addition to insulin and oral hypoglycaemic agents. Incretin analogue therapy NVP-AUY922 price was well tolerated after brief initial nausea. Improved glycaemia allowed insulin to be phased out after six months. General well-being,

weight, blood pressure, microalbuminuria, glycosylated haemoglobin, and serum lipids all showed sustained improvement. Despite concerns about hyperphagia and resultant severe vomiting in Prader–Willi syndrome, our patient responded safely to incretin analogue therapy. Weight loss and metabolic improvements have been sustained for four years. Copyright © 2011 John Wiley & Sons. “
“The Quality and Outcomes Framework for diabetes mellitus has led to an improvement in diabetes management since its introduction in 2004. However, see more the focus on reduction of HbA1c must not detract from a holistic approach to patient care. We present the case

of a patient whose unexpected decline in HbA1c levels culminated in an emergency presentation to hospital, where Addison’s disease was diagnosed. Features of adrenal insufficiency were present prior to acute admission. We review the presenting features of Addison’s disease and discuss the differential diagnosis of reduced HbA1c in diabetic patients. Copyright © 2013 John Wiley & Sons. “
“As all aspiring young diabetologists are now acutely aware, yet another educational training requirement has been introduced along the demanding pathway towards achieving consultant competency. Complementing traditional workplace-based Thymidine kinase assessments, the Federation of Royal Colleges of Physicians has introduced Specialty Certificate Examinations (SCEs), including Diabetes & Endocrinology, to ensure that trainees (SpRs/StRs) have demonstrated a sound knowledge of their specialty topic within the context of safe and competent clinical practice at consultant level. Satisfactory completion of the SCE is now mandatory for trainees who have entered a training programme since 2007 and needs to be obtained prior to being awarded a Certificate of Completion of Training (CCT).

To determine whether PsspB expression was indeed forespore-specific, the PsspB fragment was released from pPERM580 by digestion with EcoRI and BamHI and cloned upstream of the gfpmut3a gene in plasmid pAD123. The resulting construct, pPERM750, was

cloned in E. coli Ivacaftor mw DH5α and transformed into B. subtilis PS832, yielding strain PERM751, in which the location(s) of green fluorescent protein (GFP) expression in sporulating cells could be determined by fluorescence microscopy. To this end, cells sporulating in liquid Difco sporulation medium (Schaeffer et al., 1965) at 37 °C were harvested 7 h after the start of sporulation. The cells were viewed and photographed by fluorescence microscopy on an Axioscop-40 Carl Zeiss fluorescence microscope with an Aplan × 100 filter, using excitation from 450 to 490 nm and emission >515 nm. Eighty sporangia were analyzed to determine the cell compartment (namely, mother cell and/or forespore) where signaling pathway synthesis of GFP took place. Two milliliters of purified spores of B. subtilis strains at an OD600 nm of 1 were lyophilized. The dry spores plus 0.2 mL of 0.45–0.6-mm-diameter glass beads in 1.5-mL Eppendorf tubes with a small magnetic stirrer were disrupted by twenty 30-s periods of shaking in a vortex mixer adjusted to the maximum speed; this procedure gave >80% spore breakage

as determined by microscopy. The dry powder was suspended at 4 °C in 50 mM Tris-HCl (pH 7.5)–100 mM NaCl supplemented with a protease inhibitor cocktail (Roche, Mannheim, Germany) and mixed 1 : 1 with 2 × sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) sample buffer. The mixtures were boiled for 5 min, centrifuged for 5 min at

14 550 g, 30-μL aliquots of the supernatant were run on 10% SDS-PAGE and the gel was stained with Coomassie blue (Laemmli, 1970). Quantification of protein expression was accomplished by densitometry using quantity one 1-d software from Bio-Rad Laboratories (Hercules, CA). For measurement of spore killing by wet heat, spores at an OD600 nm of 1 (108 spores mL−1) in water were incubated Selleckchem Fluorouracil at 90 °C. For dry heat treatment, 1-mL spores at an OD600 nm of 1 (108 spores mL−1) in water were lyophilized in glass tubes and the dry spores were heated at 90 or 120 °C in an oil bath. The heated tubes were cooled and spores were rehydrated with 1 mL sterile water. For UV-C treatment, 5 mL spores at an OD600 nm of 0.5 (107 spores mL−1) in phosphate buffered-saline (0.7% Na2HPO4, 0.3% KH2PO4, 0.4% NaCl; pH 7.5) were continuously stirred and irradiated at room temperature with a short-wave UV lamp (maximum output 254 nm; UV products, Upland, CA) (energy output=75 W m−2) at various fluences. Spore survival during these treatments was measured by plating aliquots of dilutions in water on Luria–Bertani medium (Miller, 1972) agar plates, and counting colonies after 24–48 h of incubation at 37 °C.

Travel destinations were Africa (n = 32; 57.2%), Europe (n = 11; 19.5%), Asia (n = 7; 12.5%), the Caribbean (n = 2; 3.6%), Indian Ocean (n = 2; 3.6%), Pacific Ocean (n = 1; 1.8%), and Latin America (n = 1; 1.8%). Median duration of travel, for the 49 non-expatriates, was 21 days (25–75 IQ: 12–60 d). Table 1 shows the demographics and travel characteristics according to destination. Among the 31 travelers (55%) who stayed in endemic regions of malaria, only 9 (29%) had an optimal compliance with malaria chemoprophylaxis. Symptoms began during

travel in 20 patients (35.71%). As for the remaining 36 travelers, the median interval between return and clinical onset was 10 days (25–75 IQ: 4–14 d). Among the 20 patients who developed symptoms abroad, 15 (75%) consulted a local doctor of whom 11 buy HM781-36B (55%) required a medical evacuation. The median

interval between clinical onset and hospitalization, for all patients, was 4 days Ensartinib (25–75 IQ: 1.5–7 d). Due to initial wrong diagnosis (Table 2), a late management occurred in 20 cases with an average delay of 6.9 days (range: 1–50 d). Fever, headaches, and neck stiffness were the most common clinical features (Table 3) and all three were present in 50% of cases. The patients presented with a meningeal syndrome in 24 cases, whereas 20 others had an encephalitic presentation. The remaining 12 (21%) patients had an incomplete clinical presentation (headaches or fever). By comparing cerebral malaria with the other 44 diagnoses, it was noted that jaundice, Florfenicol dyspnea, and splenomegaly were significantly more

likely in malaria (p < 0.05). However, there was neither neck stiffness, rash, focal neurological findings nor lymphadenopathies in malaria. The analysis of full blood count showed that lymphocytopenia and thrombocytopenia were significantly lower (p < 0.05) in malaria-related CMI. In addition, we observed one case of eosinophilia (neurocysticercosis). As for biochemistry tests, CRP and total bilirubinemia were significantly higher in malaria cases (p < 0.05 and p < 0.005, respectively). Regarding the other etiologies, CRP was not discriminating; it was high in 42% of the confirmed viral CMI. The diagnosis of meningitis or encephalitis was confirmed in 43 patients by a pleiocytosis on lumbar puncture. The cytological analysis and CSF biochemical markers (protein and glucose concentrations) did not seem discriminating between etiologies. Thus, 25% (n = 6) of the confirmed viral CMI had a neutrophilic or mixed CSF formula, 46% (n = 11) had a protein concentration >1 g/L, and 12.5% (n = 3) had a low glucose concentration. Seventeen patients underwent a brain CT scan, 18 a brain MRI, and one a lumbar spine MRI. Among them, nine patients had a brain CT scan followed by a MRI. In all, seven morphological investigations were abnormal.

3). The putative disruptants were further characterized by PCR and Southern blot analyses, which confirmed the homologous recombination events. As shown in Fig. 2b, a primer pair (primers 1/2) designed to amplify a fragment internal to the Mga1 coding region yielded no products when DNA

from the homologous recombinants was used as a template, whereas a fragment of the hph gene could be amplified from the same sample (primers 3/4). Meanwhile, amplicons of wild type (2.9 kb) selleck and deletion (3.7 kb) alleles of Mga1 differed in size when primers contained in homologous arms (primers 5/6) were used. For T-DNA random-insertion mutagenesis, amplicons both in wild-type strains and in disruptants were amplified. A probe corresponding to the Mga1 coding region and the 3′ homologous arm (probe 1) yielded

a single hybridizing band in a Southern blot of XbaI-digested genomic DNA of Mga1 deletion mutants, compared with two bands in the wild-type strain and three bands in the T-DNA random-insertion mutant (Fig. 2c). A single Selleckchem PI3K Inhibitor Library hybridizing band detected with the hph marker cassette (probe 2) in the mutants, but none in the wild type, revealed that the deletion mutants carried a single integrated copy of the Mga1 disruption construct (Fig. 2c). As shown in Fig. 4, the Mga1 target deletion mutant GKmga1 produced significantly more citrinin and pigments than the wild-type strain M7 in YES media. After 14 days of cultivation, the wild-type strain M7 produced 53.19±14.58 μg mL−1 citrinin and 9.21±0.05 U mL−1 pigments (OD485 nm), whereas the GKmga1 produced 540.90±121.62 μg mL−1 citrinin (approximately ninefold higher) and 15.78±0.33 U mL−1 pigments (OD485 nm) (approximately 71% higher). Intensive Adenosine triphosphate investigation of

heterotrimeric G-protein signalling pathways in model filamentous fungi and pathogenic fungi revealed that, despite considerable sequence similarity among Group I Gα-subunits, their functions, in some cases, show distinct variations between species. In general, deletion of Group I Gα-subunits in different fungi results in similar defects in vegetative growth as well as sexual and asexual sporulation (Gao & Nuss, 1996; Ivey et al., 1996; Yu et al., 2008; Mehrabi et al., 2009), which were also observed in this study. However, the influences of the same mutation of the genes on secondary metabolites vary substantially within and across fungal genera. For instance, a dominant activating fadA allele inhibited sterigmatocystin and aflatoxin biosynthesis in Aspergillus spp., but stimulated T-2 toxin biosynthesis in Fusarium sporotrichioides (Hicks et al., 1997; Tag et al., 2000). Furthermore, in A.

These examples represent very dissimilar areas, and the only common factor is hubris on the part of experienced

researchers. Secondarily, failure of peer review sometimes happens, and journal editors do not step in, sometimes even when alerted before publication. These failures of the publishing process teach us that unnecessary mistakes occur and should warn us all to watch our own enthusiasms. This is a commentary on the publishing of science, beyond the fringe from what is recognized as the innovative results and hypotheses leading from them (Kuhn, 1962), and not on the scientific results themselves. In this Selleck Alpelisib time of open-access online publishing, sometimes reports are altered after publication online, at the option of the editor (sometimes without or sometimes with authors’ agreement). This new process is also open to beyond the fringe problems concerning what publication now means. The topic here is that creative and experienced experimentalists frequently overly Galunisertib supplier interpret their

results, going from far more than mere hypothesis to what is quickly recognized by the peer community as snake oil. This phenomenon is not new. Two useful monographs cover the processes by which one can judge innovative real science from beyond the fringe ideas, with examples mostly from physics. Park (2000) has a long interest in this problem, especially with regard to flying saucers and claims of governmental cover-up of beyond the fringe physical science. Friedlander’s (1995) book is titled ‘At the fringe ….’, so we move here to ‘Beyond the fringe’, recognizing that this phrase was used 50 years ago for a British stage comedy that had strong academic roots. Irving Langmuir (a Nobel laureate physical chemist) perhaps started

modern consideration selleck screening library of these problems, when he called this ‘pathological science’ in an unpublished 1953 lecture at General Electric Company (where he worked). That lecture was recorded and later transcribed and published (Langmuir & Hall, 1989). Langmuir considered it pathological when the excess enthusiasm by scientists (often distinguished and experienced) ran beyond reason. Langmuir himself, however, was victim to this situation in his unwarranted defense of a model for protein structure. The model (Senechal, 2012) might be described as heterocyclic polyatomic rings assembled into a lace doily-like flat structure that could then fold over on itself, leaving amino acid side chains either internal or sticking out.

Therefore, self-reported depressive symptoms did not improve the SVM prediction accuracy. Including data on CART CPE also failed to improve the prediction. For the scenario where log10 HIV RNA was included, the accuracy of the prediction was 75% for impairment and 72% for NP nonimpairment. These same accuracies were also achieved for the scenario where detectable vs. undetectable HIV RNA was used. Hence inclusion of CPE did not improve

prediction accuracy. Our study was conducted with the intention of generating an extra-brief tool to assist HIV physicians in referring HIV-positive persons at risk for NP impairment. We believe that our study provides a preliminary but robust solution to this first objective. Indeed, we found that our SVM-derived check details models yielded adequate prediction accuracy for NP impairment (sensitivity 78%; n=28/36) and NP nonimpairment (specificity 70%; n=43/61). These figures are certainly adequate for use of the algorithm as an adjunct clinical tool. Moreover, we believe that the predictions were quite good in comparison with predictions of HAND provided by brief paper-and-pencil NP instruments. Davis et al. [28] reported

70% sensitivity and 71% specificity for the HIV-dementia scale. Carey et al. [29] showed 78% sensitivity, 85% specificity and 83% overall prediction accuracy using two selected NP tests. The California Computerised Assessment Package (Calcap), a brief cognitive computerized test, yielded 68% sensitivity and 77% specificity [30]. Lastly, the brief computerized battery CogState demonstrated 81% sensitivity, MI-503 in vivo 70% specificity, and an overall prediction accuracy of 77% [31]. These accuracy rates provide preliminary support for application of these models in a clinical setting. In addition, this algorithm can be easily implemented on a web-interface platform (under construction) for which the HIV physician will only have to input

the necessary characteristics [for example when using the model determined from detectable levels of HIV RNA the required characteristics are: age in years; current CD4 T-cell count; presence or absence of past CNS HIV-related diseases (yes or no); and current CART duration in months]. The expected duration of the screening (computation Akt inhibitor of the algorithm including data entry with interactive instructions) is about 3 min. Here we have shown that it is the inclusion of easily ascertainable clinical factors that makes the algorithm practical. However, while the inclusion of the factors might be obvious, the relative weighting of each is certainly not. This study also contributes to the body of evidence on the use of SVM as a robust tool for data classification problems [18]. SVM methods have been increasingly used in a wide variety of medical classification problems.

thuringiensis; and (3) pKESX is lost at 42 °C. A 0.9-kb SalI/BamHI fragment containing calY and its promoter was ligated into the corresponding site of pKSV7 to generate complementation plasmid pKPC. The plasmid pKESX was electroporated into strain KCTF12. After selection on the LB plate containing chloramphenicol at 30 °C, the transformants were incubated at 42 °C for 12 h without antibiotics and spread onto LB agar plates containing erythromycin. Colonies were replicated on LB agar plates containing erythromycin or chloramphenicol. Transformants

conferring both chloramphenicol sensitivity and erythromycin resistance were selected as strain KCTF; these were STA-9090 molecular weight the calY replacement mutants. The plasmid pKPC was electroporated into strain KCTF and transformants conferring chloramphenicol resistance were selected as strain KCTFC; these were the calY complementation mutants. All of the replacement and complementation mutants were further confirmed by PCR, sequencing, Western blot and MS. Strains KCTF12, KCTF and KCTFC were

grown in 50 mL LB medium until stationary phase and pelleted by centrifugation at 10 000 r.p.m. for 10 min. Pellets were washed twice with washing buffer [10 mmol L−1 EDTA (pH 8.0), 1 mmol L−1 NaCl, 1 mmol L−1 phenylmethylsulfonyl fluoride (Sigma)] and resuspended in 2 mL distilled water. Suspensions of 50 μL were mixed with 50 μL 2 × sample loading buffer and boiled for 5 min. Proteins of 10 μg were separated by 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and then transferred to polyvinylidene difluoride (PVDF) membranes (Sigma) using a tank Galunisertib chemical structure blot apparatus (Toyo, Tokyo, Japan). The PVDF membranes were incubated with primary rabbit antichitinase antiserum

at a dilution of 1 : 1000 and subsequently with anti-rabbit secondary antibody conjugated to horseradish peroxidase (Sigma). Binding of the secondary antibody was detected with the Odyssey® Infrared Imaging System (Li-COR Biosciences, Lincoln, NE). To determine directly the differences in expression of the B. thuringiensis strains, the global proteins were dissolved Casein kinase 1 by loading buffer, and samples of about 20 μg solubilized proteins were separated by 10% SDS-PAGE. The different protein bands on the SDS-PAGE gel were excised, in-gel digested (Ranasinghe & Akhurst, 2002), and then analyzed by liquid chromatography–tandem MS (LC–MS/MS; Thermo Fisher) as described by Fu et al. (2008a, b) and Sun et al. (2008). The MS data were of good quality, with fragment ions clearly above the baseline noise and there were continuous y- and b-ion series (Wang & Yuan, 2005). LC-MS/MS data were acquired and processed automatically for subsequent protein identification by comparison against entries in the nonredundant NCBI database for gram-positive bacteria using Proteome discoverer 1.1 (Thermo Fisher) and the sequest algorithm. A 600-bp DNA fragment containing calY was amplified from B. thuringiensis by PCR and then sequenced.

thuringiensis; and (3) pKESX is lost at 42 °C. A 0.9-kb SalI/BamHI fragment containing calY and its promoter was ligated into the corresponding site of pKSV7 to generate complementation plasmid pKPC. The plasmid pKESX was electroporated into strain KCTF12. After selection on the LB plate containing chloramphenicol at 30 °C, the transformants were incubated at 42 °C for 12 h without antibiotics and spread onto LB agar plates containing erythromycin. Colonies were replicated on LB agar plates containing erythromycin or chloramphenicol. Transformants

conferring both chloramphenicol sensitivity and erythromycin resistance were selected as strain KCTF; these were Ceritinib nmr the calY replacement mutants. The plasmid pKPC was electroporated into strain KCTF and transformants conferring chloramphenicol resistance were selected as strain KCTFC; these were the calY complementation mutants. All of the replacement and complementation mutants were further confirmed by PCR, sequencing, Western blot and MS. Strains KCTF12, KCTF and KCTFC were

grown in 50 mL LB medium until stationary phase and pelleted by centrifugation at 10 000 r.p.m. for 10 min. Pellets were washed twice with washing buffer [10 mmol L−1 EDTA (pH 8.0), 1 mmol L−1 NaCl, 1 mmol L−1 phenylmethylsulfonyl fluoride (Sigma)] and resuspended in 2 mL distilled water. Suspensions of 50 μL were mixed with 50 μL 2 × sample loading buffer and boiled for 5 min. Proteins of 10 μg were separated by 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and then transferred to polyvinylidene difluoride (PVDF) membranes (Sigma) using a tank Navitoclax blot apparatus (Toyo, Tokyo, Japan). The PVDF membranes were incubated with primary rabbit antichitinase antiserum

at a dilution of 1 : 1000 and subsequently with anti-rabbit secondary antibody conjugated to horseradish peroxidase (Sigma). Binding of the secondary antibody was detected with the Odyssey® Infrared Imaging System (Li-COR Biosciences, Lincoln, NE). To determine directly the differences in expression of the B. thuringiensis strains, the global proteins were dissolved stiripentol by loading buffer, and samples of about 20 μg solubilized proteins were separated by 10% SDS-PAGE. The different protein bands on the SDS-PAGE gel were excised, in-gel digested (Ranasinghe & Akhurst, 2002), and then analyzed by liquid chromatography–tandem MS (LC–MS/MS; Thermo Fisher) as described by Fu et al. (2008a, b) and Sun et al. (2008). The MS data were of good quality, with fragment ions clearly above the baseline noise and there were continuous y- and b-ion series (Wang & Yuan, 2005). LC-MS/MS data were acquired and processed automatically for subsequent protein identification by comparison against entries in the nonredundant NCBI database for gram-positive bacteria using Proteome discoverer 1.1 (Thermo Fisher) and the sequest algorithm. A 600-bp DNA fragment containing calY was amplified from B. thuringiensis by PCR and then sequenced.

Rescued

plasmids were sequenced and analysed by restriction digestion to define the site of insertion in the genome. Insertion sites are shown in the cartoon in Fig. 2. In REMI-11, the insertion had occurred at a XhoI site 1820 bp downstream from the start codon of an ABC transporter family gene (AFUA_1G14330) and within the coding region. REMI-56 is an insertion upstream of a major facilitator superfamily (MFS) transporter. The insertional mutation has occurred in the 619 bp intergenic region between two tandemly transcribed genes, 203 bp downstream of a putative sulphate transporter (AFUA_1G05020) BMS-777607 in vitro and 416 bp upstream of a putative MFS transporter (AFUA_1G05010). The REMI insertion is close to the start codon of this ORF and to motifs associated with the core promoter in filamentous fungal genes.

REMI-14D is an insertion in the coding region of triose phosphate isomerase. Sequence analysis of rescued plasmid shows that REMI-14D contains an insertion within the coding region of AFUA_2G11020, the single-copy Angiogenesis inhibitor triose phosphate isomerase gene. The insertion is within the coding region, 452 bp from the start codon. REMI-85 and REMI-103 occur within the coding regions of two hypothetical genes (AFUA_5G07550 and AFUA_4G10880, respectively). These genes have no known function or homology with any gene of known function. AFUA_5G07550 is conserved in all Aspergillus species but poorly conserved in other fungi. The GNAT2 moderately azole-resistant strain REMI-101 has an insertion within the gene coding for the mitochondrial 29.9 KD ubiquinone NADH oxidoreductase subunit of respiratory complex I (AFUA_2G10600). The insertion was shown to occur at a genomic XhoI site, 534 bp downstream from the start codon of the gene. MICs for this strain were 1.0, 0.50 and 4.0 μg mL−1 for ITR, POS and RAV, respectively, versus 0.25, 0.12 and 1.0 μg mL−1 for AF210. REMI-102 was determined to contain an insertion in the promoter

region of the A. fumigatus cyc8 gene orthologue (AFUA_2G11840). The final REMI strain (REMI-116) was shown to have an insertion in the epsin 2 gene (AFUA_6G12570). However, Southern blot analysis suggests that there are at least two insertional events in this strain, and attempts to re-create the phenotype were unsuccessful. Therefore, it seems likely that the insertion in the epsin2 gene and the observed phenotype may be unlinked. As uncharacterised secondary mutations may arise during transformation or REMI, rescued plasmids were used to re-create the azole-resistant phenotype in the parental strain. Because the rescued plasmids contain flanking regions of the original insertion site, this procedure is functionally analogous to commonly used allele replacement methods and recombination between flanking regions and genomic DNA should regenerate the original REMI insertion in a new wild-type or parental strain (Fig. S1). Plasmids were termed p11, p85 etc.

“
“NMDA receptors (NMDARs) form glutamate-gated ion channels widely expressed in the central nervous system and highly permeable to calcium ions. NMDARs have always attracted much attention because of their central implications in numerous physiological and pathological processes including synaptic

plasticity and excitotoxicity. Ever since the discovery of NMDARs three decades ago, it has been acknowledged that native NMDARs do not form a homogeneous population of receptors but rather exist as multiple subpopulations that differ in their functional properties and, presumably, physiopathological roles. NMDARs are in fact large multi-subunit complexes arranged into heteromeric assemblies composed LDK378 solubility dmso see more of four homologous subunits within a repertoire of over 10 different subunits: eight GluN1 isoforms, four GluN2 subunits (A–D) and two GluN3 subunits (A and B). This review gives an overview of our current knowledge of the molecular basis underlying NMDAR functional heterogeneity. The modular architecture and expression profile of NMDAR subunits together with the basic principles of NMDAR operation are first introduced. The influence of subunit composition on receptor functional properties is then described, with emphasis put on the impact of differential incorporation of GluN1

and GluN2 subunits (the roles of GluN3 subunits being less well understood). The final part presents recent studies revealing the central, and largely unsuspected, role of the extracellular N-terminal Plasmin region in generating functional diversity of NMDARs. Indeed, the identity of this region, which is distal to the membrane and precedes the agonist-binding domains, determines key biophysical and pharmacological attributes of the various NMDAR subtypes. “
“Cranial motor neurons, which are divided into somatic motor (SM), branchiomotor (BM) and visceral motor (VM) neurons, form distinct axonal trajectories to innervate their synapse targets. Rho GTPase regulates various neuronal functions through one of the major effector proteins, Rho-kinase. Here, we addressed the in vivo role of the Rho/Rho-kinase

signaling pathway in axon patterning of cranial motor neurons. We performed conditional expression of a dominant-negative mutant for RhoA or Rho-kinase in transgenic mice by using the Cre-loxP system to suppress the activity of these molecules in developing cranial motor neurons. Blockade of the Rho/Rho-kinase signaling pathway caused defects in the patterning of SM axons but not in that of BM/VM axons, in which defects were accompanied by reduced muscle innervation and reduced synapse formation by SM neurons. In addition, blockade of the signaling pathway shifted the trajectory of growing SM axons in explant cultures, whereas it did not appear to affect the rate of spontaneous axonal outgrowth.