suis 2 of 110 kDa (Fig 2b), confirming that HtpS is a cell surfa

suis 2 of 110 kDa (Fig. 2b), confirming that HtpS is a cell surface-associated protein of S. suis 2. To determine whether rHtpS-elicited antibodies could affect C3 deposition on the surface of S. suis 2, 05ZYH33 binding of C3 was detected by FCM after incubation with different concentrations of rabbit anti-HtpS sera. C3 deposition on S. suis 2 was low (41.9±2.01%) in the absence of rabbit anti-HtpS sera. When S. suis 2 was incubated with increasing concentrations of rabbit anti-HtpS sera, the C3 deposition on the bacterial surface was increased significantly in a rabbit anti-HtpS sera concentration-dependent manner, with up to 62.9±4.20% bacteria positive

with 50% rabbit anti-HtpS Dasatinib in vivo sera (Fig. 4). Normal human sera and preimmune rabbit sera

were used as controls and induced only weak changes in C3 deposition compared with rabbit anti-HtpS sera (data not shown). The bactericidal experiment was adopted to evaluate the bactericidal activity of the rabbit anti-HtpS antibody. As shown in Fig. 5, 72.9±3.88% of S. suis 2 bacteria could survive after incubation with whole blood not containing rabbit anti-HtpS antibody. In the presence of 5% rabbit anti-HtpS antibody, the survival of the bacteria in whole blood was significantly reduced to 51±7.74%. To determine Talazoparib clinical trial whether rHtpS can protect mice against S. suis 2 infection, mice were immunized with rHtpS and challenged with a lethal dose of S. suis 2 05ZYH33. ELISA test results revealed that titers of rHtpS-specific antibody of the group immunized with rHtpS ranged from 204 800 to 819 200 before challenge with S. suis 2. After the challenge, all 10 mice of the negative control group died

within 24 h postinoculation, while only two out of 10 mice immunized with rHtpS died in the same period. The remaining eight mice only exhibited rough hair in the first 24 h postinoculation, and then recovered and survived (Fig. 6). The mortality rate was significantly reduced in mice immunized with rHtpS (P<0.001), indicating that rHtpS confers protection in mice. So far, histidine triad family proteins have been documented in group A, B, C, G streptococcal species, S. pneumoniae, as well as S. suis 2 (Adamou et al., 2001; Kunitomo et al., 2008; Aranda et al., 2009). Mirabegron Although the function of this family is not clear, histidine triad protein family members, Pht proteins of S. pneumoniae and HtpA of S. pyogenes, have proved to be good candidates for subunit vaccines due to their strong ability to protect mice against bacterial infection (Adamou et al., 2001; Zhang et al., 2001; Kunitomo et al., 2008). Crystal structure analysis of PhtA revealed that the histidine triad domain of histidine triad protein family members was a zinc-binding fold (Riboldi-Tunnicliffe et al., 2004, 2005). Recently, Ogunniyi et al.

Genes coding for MtrF, MtrC, and OmcA were deleted in one step T

Genes coding for MtrF, MtrC, and OmcA were deleted in one step. This deletion led to further excision of mtrD and mtrE from the chromosome. The genes for the decaheme c-type cytochrome SO_1659 and the diheme cytochrome SO_2931 were deleted subsequently. The presence of MtrA and MtrB this website was shown to be a requirement for metal reduction by S. oneidensis (Bretschger et al., 2007). Hence, possible effects of the removal of genes ranging from mtrF to mtrC on the expression of mtrA and mtrB were circumvented by the concomitant introduction of an arabinose-inducible promoter

and the araC repressor. Genes coding for OM cytochromes from S. oneidensis were cloned separately into plasmid pBAD202 to assign specific functions to these proteins in further experiments. The sequence information for a C-terminal strep-tag was added to allow for the specific detection of the proteins produced. The relative amounts of the produced OM cytochromes were quantified via immunodetection of the added strep-tag epitope (Fig. 1a). OmcA production resulted in the strongest strep-tag derived signal compared with all other OM cytochromes produced (Fig. 1c). Signals resulting from MtrCstrep and MtrFstrep production were detected in similar quantities, which indicates similar production levels. In contrast, the production of SO_1659strep

and SO_2931strep seems to be strongly reduced compared with the other three OM cytochromes. Proteinase K assays according to Myers & Myers (2003a) were performed to investigate whether the proteins are oriented toward the periplasm or the surrounding media (Fig. 2). Detection was based selleck screening library on the added strep-tag epitope. IMP dehydrogenase A control reaction using production of a strep-tagged MtrA protein that is localized to the periplasm was performed, to ensure that the assay conditions did not interfere with cell integrity. Localization of OmcA and MtrC to the cell surface was already shown by other research groups (Myers & Myers,

2003a; Shi et al., 2008). Hence, MtrCstrep and OmcAstrep were used as proteinase K-degradable control proteins. As Fig. 2 shows, OmcAstrep, MtrCstrep, MtrFstrep, and the decaheme cytochrome SO_1659strep are clearly hydrolyzed by the proteinase. Diheme SO_2931strep does not seem to be surface exposed or is not available for proteinase activity. Cell suspension assays showed that only the production of MtrCstrep and MtrFstrep could partly rescue the mutant phenotype for ferric citrate reduction (Fig. 3a and b). MtrFstrep production resulted in a 1.2-fold accelerated ferric citrate reduction rate compared with the MtrCstrep-producing strain. Surprisingly, the presence of OmcAstrep did not lead to increased ferric iron reduction rates compared with the ΔOMC mutant. To exclude the possible effects of the strep-tag epitope on protein activity, control experiments with the native form of omcA in the same vector backbone were performed. Production of the native form of OmcA was shown via heme activity staining (Fig. 1b).

, 1996) As described above, this domain contains a ‘Walker-type’

, 1996). As described above, this domain contains a ‘Walker-type’ ATP-binding site (Jung & Altendorf, 1998b). Truncated forms of KdpD lacking this site (KdpD/Δ12–228, KdpD/Δ12–395) were characterized Z-VAD-FMK in vivo by a deregulated phosphatase activity. In contrast, the sole N-terminal cytoplasmic domain (KdpD/1–395)

caused constitutive expression of kdpFABC in vivo (Heermann et al., 2003a). Detailed biochemical studies revealed a stabilizing function of the N-terminal domain of KdpD in complex with phospho-KdpE and the corresponding DNA-binding site (Heermann et al., 2003a, 2009a). Many bacteria, for example the cyanobacterium Anabaena sp., have a KdpD homologue that comprises only the N-terminal domain without the C-terminal transmitter domain and the transmembrane helices (Ballal et al., 2005). selleck chemicals llc Replacement of the N-terminal domain of E. coli KdpD with the short KdpD version of Anabaena resulted in a chimera that was functional in E. coli in vivo and in vitro (Ballal et al., 2002). This result suggested that Anabaena KdpD functions in a manner similar to the N-terminal domain of E. coli KdpD. The Usp domain within the N-terminal domain functions as a binding surface for the universal stress protein UspC, and it was shown to be important for internal protein dynamics, allowing structural alterations within

KdpD upon stimulus perception (Heermann et al., 2009b). Using a ‘domain-swapping’ approach, the Usp domain within KdpD was replaced by KdpD-Usp domains of various bacteria and the six soluble universal stress proteins of E. coli, respectively. In vivo and in vitro analyses of these KdpD chimeras revealed that signaling within KdpD involves alterations of electrostatic interactions.

Chimeras containing UspF or UspG not only prevented kdpFABC expression under salt stress but also under K+ limitation, although these hybrid proteins exhibited kinase and phosphatase activities in vitro (Heermann et al., 2009a). Analysis of the predicted wild-type KdpD-Usp tertiary structure revealed that this domain has a net positively charged surface, while both UspF and UspG are characterized by net negatively charged surfaces (Heermann et al., 2009a). It is proposed that the positively O-methylated flavonoid charged Usp domain interacts with other positively charged residues in KdpD shifting the histidine kinase into the ‘ON’ state by electrostatic repulsion (Fig. 2a). Chimeras containing the negatively charged UspF or UspG remain in the ‘OFF’ state due to electrostatic attraction. A possible explanation as to why KdpD-UspF and KdpD-UspG are active in vitro, but block kdpFABC expression in vivo might be that the stabilization of the phospho-KdpE/DNA complex by the N-terminal domain of KdpD is prevented in the ‘OFF’ state (Fig. 2a) (Heermann et al., 2003a). KdpE belongs to the OmpR/PhoB response regulator family.

1D Strong recommendation Very low-quality evidence Benefits app

1D Strong recommendation. Very low-quality evidence. Benefits appear to outweigh risk and burdens, or vice versa. Evidence limited to case studies. Strong recommendation based mainly on case studies and expert judgment. 2A Weak recommendation. High-quality evidence. Benefits www.selleckchem.com/products/BKM-120.html closely balanced with risks and burdens. Consistent evidence from well-performed randomized, controlled trials or overwhelming

evidence of some other form. Further research is unlikely to change our confidence in the estimate of benefit and risk. Weak recommendation, best action may differ depending on circumstances or patients or societal values. 2B Weak recommendation. Moderate-quality evidence. Benefits closely balanced with risks

and burdens, some uncertainly in the estimates of benefits, risks and burdens. Evidence from randomized, controlled trials with important limitations (inconsistent results, methods flaws, indirect or imprecise). Further research may change the estimate of benefit and risk. Weak recommendation, alternative approaches likely to be better for some patients under some circumstances. 2C Weak recommendation. Low-quality evidence. Uncertainty in the estimates of benefits, risks, and burdens; benefits may be closely balanced with risks and burdens. Evidence from observational studies, unsystematic clinical experience, or from randomized, controlled trials with serious flaws. Any estimate of effect is uncertain. Weak recommendation; other alternatives may be reasonable. 2D Weak recommendation. Ku-0059436 in vivo Very low-quality evidence. Uncertainty in the estimates of benefits, risks, and burdens; benefits may be closely balanced with risks and burdens. Evidence limited to case studies and expert judgment. Very weak recommendation; other alternatives may be equally not reasonable. Databases: Medline, Embase, Cochrane Library Conference

abstracts: -  IAS Conference on HIV Pathogenesis and Treatment Date parameters: -  Databases: July 2013 Five systemic literature searches were undertaken from published work and conference abstracts up until July 2011 as described in the BHIVA guidelines development manual. The population was defined as HIV-positive women covering five areas. Search questions were set by the Writing Group within each search as listed below Study design: Systematic reviews (SRs), randomized control trials (RCTs), observational, risk, economic Population: HIV-positive women Intervention: starting antiretroviral therapy during pregnancy Comparator: none Outcomes: death, AIDS, non-AIDS co-morbidities, maternal obstetric morbidity, infant mortality and morbidity, mother-to-child HIV transmission, drug resistance.

1 plasmid containing hygromycin resistance gene was used as the s

1 plasmid containing hygromycin resistance gene was used as the second plasmid in co-transformation reaction. A positive transformant was selected and tested on minimal medium. The expression of AfuNce102 driven by its own promoter resulted in normal sporulation and growth phenotype (data not shown). To investigate the intracellular localization of AfuNce102,

a C-terminal fusion construct, driven by the glaA inducible promoter, was prepared and transformed into the A. fumigatus AF293 parent strain. A positive transformant was isolated and grown in inducing medium containing maltodextrin 1% as the sole carbon source. This transformant was directly analyzed by fluorescent microscopy. In young mycelia, Nce102 tagged with EGFP was primarily detected in ER with a tip-high gradient (Fig. 3d). The fluorescence was also detectable at selleck compound the Akt inhibitor septum (Fig. 3a and e). In old hyphae, the ER localization of EGFP-tagged protein was more clear, and the EGFP fluorescence was frequently observed in ring-like structures (Figs 3e and 4b). DAPI staining of mycelia demonstrated that these ring structures are nuclei (Fig. 4b and c). During the conidiophore formation,

a faint and diffused fluorescence was detected in the vesicle, and later, a strong signal was observed in phialides and mature conidia (Fig. 5). A variable intensity of EGFP fluorescence was observed among phialides. As the expression of AfuNce102 under the control of glaA promoter may result in a nonphysiological level of the tagged protein, we tested the growth phenotype of AfuNce102-GFP transformant in the inducing medium. The results showed that overexpression of AfuNce102-GFP did not affect the growth phenotype of the A. fumigatus, including the radial growth rate or sporulation (data not shown). To test whether the deletion of AfuNce102 can affect the virulence of A. fumigatus in an animal model, the survival of infected, temporarily immunocompromised mice was monitored for 4 weeks. Figure 6

illustrates the survival curves during the experiment. In statistical analysis of survival percentages using Mann–Whitney ADP ribosylation factor test, a significant survival difference was observed between the group infected with wild type spores and the control group, which only received cyclophosphamide (P = 0.029). The difference of survival between the group infected by AfuNce102 deletant spores and the control group was also significant (P = 0.04). However, the difference of survival between two infected groups was not statistically significant (P = 0.34). These comparisons support the conclusion that the virulence of fungus has not been affected by AfuNce102 gene deletion. So far, several studies have documented the role of Nce102 in membrane organization, eisosome assembly, and endocytosis in yeast (Grossmann et al., 2008; Frohlich et al., 2009).

(2001) showed that the reaction is dependent on the presence of m

(2001) showed that the reaction is dependent on the presence of membrane

fractions of recombinant E. coli carrying B. subtilis pgsBCA genes. No γ-PGA was produced if cytosolic or other extracellular fractions were used in the in vitro assay, indicating that a membrane this website association was required. The enzyme complex remains attached to the cell membrane while γ-PGA is secreted by the cell. The PgsA protein can function as a γ-PGA transporter, indicating an important role in the elongation of the γ-PGA polymer (Ashiuchi et al., 2001). The production of γ-PGA was repressed by the sporulation-specific transcription factor Spo0A. Even though the pgsBCA operon is highly regulated, γ-PGA is not essential for cell growth and biofilm formation (Branda et al., 2006). The sequences of pgsBCA genes have been found to be similar to those of the ywsC and ywtAB genes of B. subtilis 168 (Urushibata et al., 2002). As described, the synthesis of γ-PGA requires energy, posing an interesting

question: what is the advantage to the cell? Stanley & Lazazzera (2005) proposed that γ-PGA is involved in biofilm formation to enhance cell–surface interactions through salt bridges (e.g. Ca2+ or Mg2+) as intermediaries between negative-charged cell surfaces. The in vitro production of γ-PGA could also be activated during biofilm formation in response to an increase in the salinity and osmolarity of the medium resulting from evaporation of Proteasome inhibition water during a long duration of incubation. In B. anthracis the production of γ-PGA results in the formation of a capsule and is correlated to the virulence of the strain (Candela & Fouet, 2006). However, in spite of some detailed studies, the specific role of γ-PGA in natural environments needs to be further clarified and investigations are needed to assess the presence of other sorptive EPS. The third category of EPS includes surface-active lipopeptides, such as surfactin, which are among the most-studied molecules produced by B. subtilis (Flemming et al., 2007). On the basis of the structural relationships,

lipopeptides have been classified into three groups: the surfactin group, the iturin group and the plipastatin–fengycin group (Tsuge et al., 2001) (Fig. 1). Although these surfactants are not large polymeric compounds, they play a very important also role in solubilizing substrates that otherwise would be inaccessible to the bacteria (Neu, 1996; Sutherland, 2001b). Synthesis of lipopeptides does not occur on ribosomes, but is catalyzed by large complex peptide synthetases protein structures (Lin et al., 1999). Even though surfactants exist in nature in both low- and high-molecular-weight forms, only the low-molecular-weight forms are found in B. subtilis (Ron & Rosenberg, 2001). The lipopeptide surfactins are the most important surfactants studied in B. subtilis (Fig. 1).

Now that, we have a bigger editorial team, it will hasten the tur

Now that, we have a bigger editorial team, it will hasten the turnaround time of a manuscript, as prompt decision is often the priority in the minds of the authors. We have also created a panel of experts as reviewers to realise this process. Any more eager experts are still welcome to join. The new team intends to incorporate new features in the journal to improve quality, readership and visibility. New content and features that you will see introduced over the coming months include: Editorial review”

on top articles in the current issue as well as a “Letter from the Editor in chief” on issues relevant to the Sotrastaurin mw journal and the speciality of Rheumatology, “State of the Art Reviews” and “original articles” on clinical and basic science topics, novel hypotheses (Theoretical or Conceptual) with a strong biological basis featured as “Futuristic Rheumatology”, “APLAR Grand Round” – in-depth discussion of an exceptional case with powerful message, “Postgraduate Quiz” on rare or classical clinical or radiological images, “Rheumatology News & Views from APLAR Region” featuring social, economic, and cultural issues relevant to Rheumatology including Vemurafenib cost announcements, “Expert Comments”

on top, recent publications from all journals with relevant learning points, “Milestones in Science, Art and Commerce of Rheumatology” including write ups on exemplary Patients, “Correspondence” including case reports as Letters to the Editor, comments and reply on recent publications

in IJRD. Today, high quality clinical and basic rheumatology research is being carried out by scientists from APLAR countries either at their own home country or elsewhere in the world. Our International Journal of Rheumatic Diseases is an ideal vehicle for the transmission of your labour into the medical literature biosphere. Currently we have six regular issues and up to two special issues a year. With your support, my team will strive with determination to make it a monthly, high quality international journal sooner than later. “
“Joint diseases in antiquity and the Renaissance were generally known by the all-encompassing term, gout (podagra or gotta). Only in later centuries was there a differentiation in the types of joint diseases, distinguishing gout in the modern sense from other arthritic and rheumatic disorders. The present article illustrates one pictorial representation Rolziracetam of joint disease from the early sixteenth century, a case that seems typical of gouty tophi. “
“To determine the prevalence of symptomatic osteoarthritis (OA) in rural regions of Shanxi Province, China, and to identify factors increasing the prevalence of OA. Residents over 16 years of age of targeted towns and villages in rural regions of Shanxi Province were sampled using a stratified multi-stage cluster method. Those exhibiting symptoms of rheumatism were referred to rheumatologists and those in whom rheumatism was suspected were X-rayed within 10 days of interview.

The link between DNA methylation

and ribosome biosynthesi

The link between DNA methylation

and ribosome biosynthesis could be at the heart of the interaction between a Bleomycin solubility dmso host and a parasitic R-M system. As a large number of DNA methyltransferases found in REBASE modify 5′CCWGG3′sites, it is possible that R-M systems influence expression of ribosomal protein genes and/or other genes to promote their maintenance. The effect of Dcm and other DNA methyltransferases on the entire E. coli transcriptome is currently under investigation. We thank Dr John Crane (SUNY Buffalo) and Dr Martin Marinus (University of Massachusetts Medical School) for providing E. coli strains. We thank Dr Ashok Bhagwat (Wayne State University) for providing the pDcm-9 and pDcm-21 plasmids.

We thank Ping Wang and Joshua Prey at the Roswell Park Cancer Institute for the LC MS/MS analysis. Support for this work was provided by the Geneseo Foundation and NIH Grant R15AI074035-01 (K.T.M). K.T.M. and R.D.S. contributed equally to the work. Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. “
“The type III secretion system (T3SS) is a sophisticated protein secretion machinery that delivers bacterial virulence proteins into host Trichostatin A cost cells. A needle-tip protein, Bsp22, is one of the secreted substrates of the T3SS and plays an essential role in the full function of the T3SS in Bordetella bronchiseptica. In this study, we found that BB1618 functions as a chaperone for Bsp22. The deletion of BB1618 resulted in a dramatic impairment of Bsp22 secretion into the culture supernatants and Bsp22 stability in the bacterial cytosol. In contrast, the secretion of other type III secreted proteins was not affected by the BB1618 mutation. Furthermore, the BB1618 mutant strain could not induce cytotoxicity

and displayed the same phenotypes as the Bsp22 mutant strain. An immunoprecipitation assay demonstrated that BB1618 interacts with Bsp22, but not with BopB and BopD. Thus, we identified BB1618 as a specific type III chaperone for Bsp22. Therefore, we PI-1840 propose that BB1618 be renamed Btc22 for the Bordetella type III chaperone for Bsp22. Bordetella bronchiseptica is thought to be an evolutionary progenitor of Bordetella pertussis and Bordetella parapertussis, which are causative agents of whooping cough (pertussis) in humans (Mattoo & Cherry, 2005). Bordetella species produce and secrete many virulence factors, such as adhesins, toxins, and secreted proteins, via a type III secretion system (T3SS; Abe et al., 2008). The T3SS is a needle-like structure protruding from the bacterial surface and is required to exert full virulence in many Gram-negative pathogens, including Bordetella species (Abe et al., 2008).

Little is known about patient perception of paediatric oral medic

Little is known about patient perception of paediatric oral medicine services offered in relation to these conditions. The concept of a diary is increasingly recognised as a valuable way to capture patient events and perspective in healthcare research.

This article provides the background to the use of solicited diaries as a method of accessing the perspective of children and young people and describes a service evaluation that aimed to explore the experiences of young people with chronic oral ulcers attending the paediatric oral medicine clinic in a UK Dental Hospital. Chronic oral ulcers were found to significantly impact on a variety of physical and psychosocial aspects of young Trametinib manufacturer people’s lives. Overall, feedback regarding the specialist service was positive but suggestions were Lumacaftor made for

improvements. This article reviews the use of the solicited diary within healthcare research. It also illustrates the value of the diary in exploration of children and young people’s perspective on their chronic oral mucosal disease. In addition, a need for further research in this area has been highlighted. “
“International Journal of Paediatric Dentistry 2012; 22: 363–368 Background.  Effective caries control and management requires identification of susceptible children for timely intervention. Streptococcus mutans (S. mutans) is an important biomarker of caries risk. Aim.  This study aimed to comparatively evaluate the validities of a novel immunoassay and a conventional culture-based assay in detecting salivary S. mutans in a paediatric cohort. Methods.  190 children aged 3–4 years were recruited. The abundance of S. mutans in their saliva samples was analysed with three assay systems viz. a conventional culture-based assay (Dentocult SM), a novel immunoassay system (Saliva-Check MUTANS) based on monoclonal antibody technology and a Taqman

real-time PCR assay taken as a gold standard. Results.  The novel immunoassay accurately differentiated saliva samples with high (≥5 × 105 CFU/mL) and low (<5 × 105 CFU/mL) S. mutans levels. The sensitivity/specificity was 97.6%/90.6%. The conventional culture-based assay reached a reasonably high sensitivity/specificity (92.8%/81.3%) in identifying PD184352 (CI-1040) children with moderate (≥104 CFU/mL) S. mutans level. Its sensitivity/ specificity in selecting children with high (≥105 CFU/mL) and very high (>106 CFU/mL) S. mutans levels were not sufficient (78.7%/79.8% and 25.8%/91.8%, respectively). Conclusion.  The monoclonal antibody-based immunoassay accurately and rapidly determines S. mutans abundance in saliva and could be useful for chairside assessment of children’s caries risk. “
“Childhood obesity, dental caries, and periodontal disease are major public health problems due to their adverse impact on the growth and development of children. To examine the association between nutritional status, oral health, and lifestyle habits among schoolchildren in Serbia.

We thank for Ms Sato, Dr Ebihara and Dr Urushido for cell culture

We thank for Ms Sato, Dr Ebihara and Dr Urushido for cell culture, Ms Sato and Ms Morimoto for plasmid construction, and Dr Ito-Ishida for helpful comments on this manuscript. This

work was supported by Grants-in-Aid for Scientific Research (21220008 to S.O.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and a part of this study is the result of ‘Development of biomarker candidates for social behavior’ carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan (S.O.). K.O. was supported by the Graduate Program for Leaders in Life Innovation. The authors declare no conflict of interest. Abbreviations Antero anterogradely moving mitochondria/APP-containing vesicles PARP inhibitor APP amyloid precursor protein DIV days in vitro EGFP enhanced green fluorescent protein [M] moving periods/mobile state OMP C-terminal check details transmembrane region of mitochondrial outer membrane protein of 25 kDa Retro retrogradely moving mitochondria/APP-containing vesicles [SP] short-pause [SS] stationary state SV synaptic vesicle TTX tetrodotoxin “
“With in vivo confocal neuroimaging

(ICON), single retinal ganglion cells (RGCs) can be visualized non-invasively, repeatedly, in real-time and under natural conditions. Here we report the use of ICON to visualize dynamic changes in RGC morphology, connectivity and functional activation using calcium markers, and to visualize nanoparticle transport across the blood–retina barrier by fluorescent dyes. To document the versatility of ICON, we

studied the cellular response to optic nerve injury, and found evidence of reversible soma swelling, recovery of retrograde axonal transport and a difference in calcium activation dynamics between surviving and dying RGCs. This establishes ICON as a unique tool for studying CNS physiology and pathophysiology in real-time on a cellular level. ICON has potential applications in different research fields, such as neuroprotection/regeneration, degeneration, pharmacology, Glycogen branching enzyme toxicity and drug delivery. “
“Amyloid precursor protein (APP) and its paralogs, amyloid precursor-like protein-1 and amyloid precursor-like protein-2, appear to have redundant but essential role(s) during development. To gain insights into the physiological and possibly pathophysiological functions of APP, we used a functional proteomic approach to identify proteins that interact with the highly conserved C-terminal region of APP family proteins. Previously, we characterized an interaction between APP and ubiquitous mitochondrial creatine kinase. Here, we describe an interaction between APP and a novel protein, 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1). The interaction between APP and NIPSNAP1 was confirmed both in transiently transfected COS7 cells and in the mouse brain, where NIPSNAP1 is expressed at a high level.