Dubinsky et al.[22] demonstrated a correlation between 6TGN levels and remission, as well as a correlation between higher 6TGN levels and leucopenia. This correlation has also been documented in pediatric acute lymphoblastic leukemia[35] as well as heart and renal transplantation literature.[36, 37] High 6TGN

levels have also been associated with an increased risk of any adverse event. In a retrospective Epacadostat solubility dmso Swedish study of 364 IBD patients, 41% of patients with a 6TGN above 400 experienced an adverse event (P = 0.005), including myelotoxicity and gastrointestinal disturbances.[38] Prior to the advent of thiopurine metabolite testing, standard clinical practice suggested that, if a patient on thiopurine therapy develops hepatotoxicity

(as evidenced by elevated transaminases and/or cholestatic enzymes with or without a rise in bilirubin), the offending agent should be withdrawn and a patient should be labelled as having an ‘allergy’ to thiopurines. As such, thiopurines could no longer be considered as a potential therapeutic option again for that patient. The Canadian group that originally discovered the minimum therapeutic threshold for 6TGN found that high levels of 6MMP were associated with hepatotoxicity in the form of elevated levels of hepatic transaminases. In total, 16 of 92 patients (17%) developed hepatotoxicity. Median 6MMP levels in patients with hepatotoxicity were 5463, compared with 2213 for those with normal liver enzymes. If 6MMP levels were above 5700, the risk of hepatotoxicity SRT1720 cost increased by a factor of three (18% vs. 6%). There was no correlation with 6MMP levels and therapeutic response or 6MP dose. There was also no correlation between 6TGN levels and hepatotoxicity.[22] PAK6 Patients who preferentially

produce 6MMP rather than 6TGN are known as ‘thiopurine shunters’ (see below). This group, characterized by having a 6MMP to 6TGN ratio > 20, is at risk for hepatotoxicity and possibly refractoriness to standard thiopurine therapy. There are two major drug interactions with thiopurines with direct relevance to metabolite testing. The first is with allopurinol, a potent inhibitor of XO, one of the critical enzymes involved in thiopurine metabolism. Allopurinol has been the mainstay of treatment for gout for many years.[39] Traditional teaching has dictated that because the combination of full dose allopurinol and thiopurines causes profound myelosuppression, the two drugs should never be given in combination.[38] More recently, the effect of allopurinol on thiopurine metabolism is being used to advantage (see below). The second interaction is with 5-aminosalicylates (balsalazide, mesalasine, olsalazine or sulphasalazine), used frequently in IBD patients and sometimes in rheumatological conditions. Studies in vitro have shown that sulphasalazine and olsalazine can inhibit TPMT,[40, 41] suggesting that concomitant 5ASA may increase 6TGN levels and potentially lead to myelosuppression.

Dubinsky et al.[22] demonstrated a correlation between 6TGN levels and remission, as well as a correlation between higher 6TGN levels and leucopenia. This correlation has also been documented in pediatric acute lymphoblastic leukemia[35] as well as heart and renal transplantation literature.[36, 37] High 6TGN

levels have also been associated with an increased risk of any adverse event. In a retrospective PS-341 nmr Swedish study of 364 IBD patients, 41% of patients with a 6TGN above 400 experienced an adverse event (P = 0.005), including myelotoxicity and gastrointestinal disturbances.[38] Prior to the advent of thiopurine metabolite testing, standard clinical practice suggested that, if a patient on thiopurine therapy develops hepatotoxicity

(as evidenced by elevated transaminases and/or cholestatic enzymes with or without a rise in bilirubin), the offending agent should be withdrawn and a patient should be labelled as having an ‘allergy’ to thiopurines. As such, thiopurines could no longer be considered as a potential therapeutic option again for that patient. The Canadian group that originally discovered the minimum therapeutic threshold for 6TGN found that high levels of 6MMP were associated with hepatotoxicity in the form of elevated levels of hepatic transaminases. In total, 16 of 92 patients (17%) developed hepatotoxicity. Median 6MMP levels in patients with hepatotoxicity were 5463, compared with 2213 for those with normal liver enzymes. If 6MMP levels were above 5700, the risk of hepatotoxicity selleck kinase inhibitor increased by a factor of three (18% vs. 6%). There was no correlation with 6MMP levels and therapeutic response or 6MP dose. There was also no correlation between 6TGN levels and hepatotoxicity.[22] Protirelin Patients who preferentially

produce 6MMP rather than 6TGN are known as ‘thiopurine shunters’ (see below). This group, characterized by having a 6MMP to 6TGN ratio > 20, is at risk for hepatotoxicity and possibly refractoriness to standard thiopurine therapy. There are two major drug interactions with thiopurines with direct relevance to metabolite testing. The first is with allopurinol, a potent inhibitor of XO, one of the critical enzymes involved in thiopurine metabolism. Allopurinol has been the mainstay of treatment for gout for many years.[39] Traditional teaching has dictated that because the combination of full dose allopurinol and thiopurines causes profound myelosuppression, the two drugs should never be given in combination.[38] More recently, the effect of allopurinol on thiopurine metabolism is being used to advantage (see below). The second interaction is with 5-aminosalicylates (balsalazide, mesalasine, olsalazine or sulphasalazine), used frequently in IBD patients and sometimes in rheumatological conditions. Studies in vitro have shown that sulphasalazine and olsalazine can inhibit TPMT,[40, 41] suggesting that concomitant 5ASA may increase 6TGN levels and potentially lead to myelosuppression.

It was piloted with three practising pharmacists before use and required no changes. Pharmacist respondents were asked to estimate the number of times per

week they supplied both over-the-counter (OTC) weight-loss products and prescriptions for weight-loss medicines, using the options none, one to three, four to six, seven to nine, or 10 or more. They were asked to list the weight-loss products they stocked and to indicate the facilities available in the pharmacy which could be useful in supporting weight management, by use of closed Omipalisib questions. This method was used to minimise completion time and maximise response rates; however; open questions were to obtain information about any weight-management services provided. Initially all 66 community pharmacies within Sefton PCT were contacted by telephone to inform them of the study and to arrange a convenient time for a researcher to personally visit those willing to participate. During this visit, all conducted by the same researcher, the questionnaire was completed via a face-to-face interview with the community

pharmacist. The level of deprivation of all pharmacies within the PCT was assessed using Index of Multiple Deprivation (IMD) and the pharmacy postcode. These were categorised as high (IMD 15 or greater), moderate (IMD 9–14) or low (IMD below 9).[20,21] The average estimated frequency of OTC sales and prescriptions was calculated using the frequencies of each option, taking the mid-points where a range was identified and 10 for the learn more highest option. Data were analysed using SPSS version 14. Associations between responses and demographic variables were tested for statistical

significance using Chi-squared tests. In total 177 members of the public completed the face-to-face interview, 69.5% of whom were female. 4��8C Difficulties were experienced in recording accurately the total number of people approached, many of whom refused to consider being interviewed. However, it was estimated that approximately one in every eight people approached actively considered participating. A high proportion of these, having listened to the standardised introduction and been offered the information leaflet, then agreed to the interview, but we were unable to calculate an actual response rate. Attaining the desired quota sample also proved difficult, since fewer older people and males agreed to be interviewed. Therefore the age distribution of the respondents did not reflect that of the Sefton population: people aged 65 or over were under-represented, whereas younger people were over-represented (Table 1). Fewer respondents viewed their overall health as good or very good compared to health ratings obtained in the 2001 Census for Sefton, while more rated it as fair or poor (Table 2).

Any queries (other than missing material) should be directed to the corresponding author for the article. “
“Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA Department of Life Science, Hiroshima Institute of Technology, Saeki-ku, Hiroshima, Japan Streptomyces linear chromosomes selleckchem frequently cause deletions at both ends spontaneously or by various mutagenic treatments, leading to chromosomal circularization and arm replacement. However, chromosomal circularization has not been confirmed at a sequence level

in the model species, Streptomyces coelicolor A3(2). In this work, we have cloned and sequenced a fusion junction of a circularized chromosome in an S. coelicolor A3(2) mutant and found a 6-bp overlap between the left and right deletion ends. This result shows that chromosomal circularization occurred by nonhomologous

Wortmannin molecular weight recombination of the deletion ends in this species, too. At the end of the study, we discuss on stability and evolution of Streptomyces chromosomes. “
“Lactobacilli occupy specific ecological niches, where they represent a major component of foods, human and animal microbial communities. Employing these bacteria in industrial fermentations or for human health benefits exposes them to certain life-threatening conditions where their ability to adapt plays a key role in their survival and continued microbial activity. Since the postgenomic era began, proteomics has become the first choice among research approaches available for environmental adaptation and stress response investigators. The latest developments in the applications of proteomics to understand physiological changes in Lactobacillus species under harsh conditions are remarkable. Niclosamide “
“Lactobacillus acidophilus is a commercially significant bacterial probiotic, originally isolated from the human gastrointestinal tract and designated Bacillus acidophilus in 1900. Throughout the development of methods to identify and characterise bacteria, L. acidophilus has undergone multiple

taxonomic revisions and is now the type species of a phylogenetic subgroup in the highly diverse and heterogeneous Lactobacillus genus. As a result of the limitations of differentiating phenotypically similar species by morphological and biochemical means and revisionary nature of Lactobacillus taxonomy, the characterisation of L. acidophilus has struggled with misidentification and misrepresentation. In contrast, due to its global use as a probiotic supplement in functional foods, L. acidophilus sensu stricto is now one of the most well-characterised Lactobacillus species. Here, we establish the provenance of L. acidophilus strains, unpicking historical and current misidentifications of L. acidophilus, and reviewing the probiotic, genomic and physiological characteristics of this important Lactobacillus species.

Any queries (other than missing material) should be directed to the corresponding author for the article. “
“Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA Department of Life Science, Hiroshima Institute of Technology, Saeki-ku, Hiroshima, Japan Streptomyces linear chromosomes www.selleckchem.com/products/byl719.html frequently cause deletions at both ends spontaneously or by various mutagenic treatments, leading to chromosomal circularization and arm replacement. However, chromosomal circularization has not been confirmed at a sequence level

in the model species, Streptomyces coelicolor A3(2). In this work, we have cloned and sequenced a fusion junction of a circularized chromosome in an S. coelicolor A3(2) mutant and found a 6-bp overlap between the left and right deletion ends. This result shows that chromosomal circularization occurred by nonhomologous

selleck chemicals llc recombination of the deletion ends in this species, too. At the end of the study, we discuss on stability and evolution of Streptomyces chromosomes. “
“Lactobacilli occupy specific ecological niches, where they represent a major component of foods, human and animal microbial communities. Employing these bacteria in industrial fermentations or for human health benefits exposes them to certain life-threatening conditions where their ability to adapt plays a key role in their survival and continued microbial activity. Since the postgenomic era began, proteomics has become the first choice among research approaches available for environmental adaptation and stress response investigators. The latest developments in the applications of proteomics to understand physiological changes in Lactobacillus species under harsh conditions are remarkable. Ribonucleotide reductase “
“Lactobacillus acidophilus is a commercially significant bacterial probiotic, originally isolated from the human gastrointestinal tract and designated Bacillus acidophilus in 1900. Throughout the development of methods to identify and characterise bacteria, L. acidophilus has undergone multiple

taxonomic revisions and is now the type species of a phylogenetic subgroup in the highly diverse and heterogeneous Lactobacillus genus. As a result of the limitations of differentiating phenotypically similar species by morphological and biochemical means and revisionary nature of Lactobacillus taxonomy, the characterisation of L. acidophilus has struggled with misidentification and misrepresentation. In contrast, due to its global use as a probiotic supplement in functional foods, L. acidophilus sensu stricto is now one of the most well-characterised Lactobacillus species. Here, we establish the provenance of L. acidophilus strains, unpicking historical and current misidentifications of L. acidophilus, and reviewing the probiotic, genomic and physiological characteristics of this important Lactobacillus species.

9A and C from the present data set obtained before SC inactivation). Despite this difference between the two monkeys, we found that SC inactivation again strongly disrupted microsaccade directions in monkey J during the attention task. Moreover, such disruption was consistent with a repulsion of microsaccades away from the inactivated region, as we observed in monkey M. To illustrate this, Fig. 9A and B plots the results from monkey J for the pre-injection (A) and post-injection (B) cases when the cue was placed in the affected region of SC inactivation, and Fig. 9C and D shows the results for when the foil was in the affected region. As just

mentioned, INNO-406 price pre-injection data in this monkey revealed that the initial cue-induced bias in microsaccade directions was first towards the foil (Fig. 9A and C, red curve) and then towards

the cue (Fig. 9A and C, blue curve). During SC inactivation and when the cue was in the affected region, this modulation was again abolished (Fig. 9B, left, blue curve); there was instead a strong and rapid (~140 ms after cue onset) initial bias away from the cued location (red arrow) and an Selleck Compound Library increase in movements towards neither the cue nor foil (Fig. 9B, right, black curve). This initial bias away from the cued location and towards neither location occurred ~110 ms earlier than the earliest directional modulation peak observed in any direction without SC inactivation in this monkey (referenced by the magenta lines). When the foil was in the affected region (Fig. 9D), microsaccade directions were very similar to those in the pre-injection case (Fig. 9C), as in monkey M, except that there was again a strong and rapid (~110 ms) bias away from the affected region, which, in this

case, corresponded to the foil location (Fig. 9D, middle, red arrow). In addition, unlike monkey M, monkey J showed stronger repulsion away from the affected region to the ‘neither’ stimulus locations than towards the diametrically opposite stimulus location, and he did so for both cue and foil in the affected region. Thus, the net effect of SC inactivation in this monkey SSR128129E was to reduce movements towards the affected region in favor of movements away from it (in this case, including the ‘neither’ locations, and not just the diametrically opposite location, as was the case in monkey M). The directional time course analyses of Figs 8 and 9 also revealed that, in both monkeys, microsaccades at other times relative to cue onset could still be directed towards the affected region of space after SC inactivation. In particular, microsaccades with longer latencies after cue onset, when the expected effects of attention shifts would have subsided, were not impaired. For example, as shown in in Fig.

, 2011). Our results

show that: (1) ApSHMT catalyzes THF-dependent and THF-independent reactions; (2) ApSHMT is a salt-inducible gene; and (3) overexpression of the ApSHMT gene increases the levels of not only glycine and serine, but also choline and glycine betaine, and conferred tolerance to salinity stress. Escherichia coli strains DH5α, BL21, BL21 (DE3), and BL21 (DE3) pLys were grown in the Luria–Bertani (LB) medium or in M9 minimal medium. Chloramphenicol, kanamycin, and ampicillin antibiotics were used at a concentration of 25, 25, and 50 mg L−1, LDK378 cell line respectively, as required. A. halophytica cells were grown photoautotrophically (70 μE m−2 s−1) in BG11 liquid medium containing 18 mM NaNO3 and Turk Island salt solution at 30 °C, as previously described (Waditee et al., 2003). The growth of E. coli and cyanobacterial cells was monitored by measuring absorbance at 620 and 730 nm, respectively, with a Shimadzu UV-160A spectrophotometer. The ApSHMT coding sequence was Lapatinib ic50 amplified from the genomic DNA of A. halophytica using the primer pair

ApSHMT-Nde 5′-CAACATATGGTGACGCAAACAAAC-3′ and ApSHMT-BamHI: 5′-AGGGATCCTTAT GCCATTGCGGG-3′, and thereby incorporating the 5′-NdeI and 3′-BamHI restriction sites. The PCR product was cloned into pCR2.1 vector and sequenced to exclude PCR errors. The full-length ApSHMT fragment was prepared by double digestion with NdeI and BamHI and ligated into the corresponding sites of pCold I vector (Takara, Tokyo, Japan). The expression construct was transformed first into E. coli strain DH5α and then strains BL21, BL21 (DE3), and

BL21 (DE3) pLys. Expression of recombinant ApSHMT was induced with 0.1 mM isopropyl β-d-thiogalactopyranoside at 16 °C. After 16 h, cells were harvested by centrifugation at 2300 g for 15 min. The bacterial pellets were resuspended Galeterone in buffer A (100 mM Tris-Cl, pH 8.0), sonicated, and centrifuged. Clear supernatant thus obtained was loaded onto the HisTrap FF column (GE Healthcare, Little Chalfont, UK). The column was washed extensively with buffer A containing 20 mM imidazole, followed by elution of the recombinant ApSHMT protein with buffer A containing 250 mM imidazole. Purified recombinant ApSHMT was used for biochemical characterization. For assay of THF-independent cleavage, the standard reaction mixture contained 10 μmol of dl-threo-3-phenylserine, 10 nmol of pyridoxal 5-phosphate (PLP), 100 μmol of Tris–HCl buffer (pH 8.5–9.0), and enzyme in a final volume of 0.5 mL. Incubation was performed at 30 °C for 10 min. The reaction was stopped by adding 0.5 mL of 1 M HCl. The benzaldehyde formed was determined by the 2,4-dinitrophenylhydrazine method (Misono et al., 2005). One unit of the enzyme was defined as the amount that catalyzed the formation of 1 μmol of benzaldehyde per minute in the reaction. Specific activity was expressed as units per milligram of protein. The THF-dependent cleavage was measured according to Simic et al.

Multi-level barriers are known to affect HAART compliance and may contribute to racial disparities in health outcomes and AIDS mortality [10]. The negative effects of poor HAART adherence on clinical outcomes have been documented consistently, Palbociclib mw and it is crucial to develop strategies to improve adherence [2]. The community health worker (CHW) model is emerging as an effective peer intervention to overcome barriers to adherence and thus improve medication compliance among people living with HIV/AIDS. Although there is no universal consensus about the most effective

way to improve or sustain HAART adherence, the United States Department of Health and Human Services (USDOH) did publish guidelines on this topic in 2009. This was a positive development responsive to prior research that reported that many health professionals provide minimal adherence interventions and counselling [11]. The USDOH recommendations advised providers to assess barriers to adherence at every visit, and, if needed, to pick an intervention from a list of those that had demonstrated effectiveness and would best suit individual patient needs [12]. However, these guidelines

do not promote a general standard of care regarding adherence strategies other Akt inhibitor than assessment, and are subjective because they are reliant upon the provider’s interpretation. The CHW model has been demonstrated to be an effective peer intervention to overcome barriers to HAART adherence in resource-poor settings, but is not currently utilized on a standard basis in the USA [13].

Considered ‘natural helpers’ by peers in local neighbourhoods, CHWs provide home-based support that focuses on patients’ health status in a multitude of ways. Examples include providing education on social support resources and personalized assistance with overcoming barriers to HAART adherence [14]. Barriers that may impact medication compliance include depression and other psychiatric illnesses [15,16], active drug Glutathione peroxidase or alcohol use [15–17], social stability [18] and degree of social support [19]. Several articles have described how the CHW model is currently and successfully implemented outside the USA to improve HAART adherence in disadvantaged areas, yet few have focused on the CHW model in the USA [13,14,20–23]. To enhance our understanding of the utility of CHWs in improving HAART adherence in the USA, we reviewed programmes that relied on this approach to improve biological HIV outcomes. We then used the strengths, limitations and results of the studies to make recommendations for employing the CHW model to reduce disparities in US communities. The CHW model aims to connect those who need medical care with payers and providers of health services [24]. Multiple terms are used interchangeably to describe CHWs, including lay health worker, community health promoter, outreach worker and peer health educator [24].

, 2009; Bendezúet al., 2009). The rodZ gene codes for an inner membrane protein that possesses a putative DNA-binding domain of a helix-turn-helix (HTH) motif. Furthermore, RodZ was shown to interact with bacterial actin MreB (Bendezúet al., 2009; van den Ent

find protocol et al., 2010), which may determine the place of cell wall synthesis (Alyahya et al., 2009; White et al., 2010). However, the exact role of RodZ in cell-shape determination remains to be elucidated. Mutants of rodZ were found to be growth deficient and exhibited a spherical form instead of the normal rod shape. In this work, we have further characterized the ΔrodZ mutant as well as its pseudorevertant and present evidence that strongly indicates the involvement of rodZ in the biosynthesis of peptidoglycans. All E. coli strains used were derivatives of KR0401 (Niba et al., 2007). Deletion mutations ΔrodZ∷kan and ΔsurA∷kan were introduced from mutants of each gene in the Keio collection (Baba et al., 2006) by P1kc-mediated transduction. lacZ fusions for promoter

analysis were constructed as follows: from approximately 500 bp upstream of the first gene of each operon together with approximately 12 bp from the translational start site inside the ORF was PCR-amplified and cloned into pJL28 or pJL30 protein-fusion vectors (Lucht et al., 1994). Copanlisib concentration In the case of the flhB gene, the region from nucleotide −7 to +5 was replaced with that of fliE, because, for unknown reasons, no β-galactosidase activity was obtained with its own initiator codon. pJL28-fliA (pMW198) and pJL29-flgB (pMW211) Nintedanib (BIBF 1120) have been described (Lehnen et al.,

2002). Single-copy (chromosomal) lacZ fusion strains were subsequently obtained from plasmid-bearing strains via phage λInCh as described (Boyd et al., 2000). β-Galactosidase activity was measured according to Miller (1972). The plasmid vector for the expression of the cloned gene with the C-terminal S-tag, pBADs, was constructed based on pBAD322 (Cronan, 2006) by replacing the SphI–HindIII region with a 520-bp fragment amplified from pSHLeu (Gan et al., 2002). ΔHTH and Δ(30-133) deletions were introduced using a mutagenesis method of overlap extension reported by Warrens et al. (1997). Cells were grown in Luria–Bertani (LB) medium at 37 °C to the exponential growth phase. Formvar-carbon-coated copper grids were floated for 3 min onto a drop of cell culture, washed on drops of 0.9% NaCl and distilled water and then stained with 1% uranyl acetate. Images were obtained by a transmission electron microscope (H-7100, Hitachi, Tokyo, Japan) at an acceleration voltage of 75 kV. Peptidoglycan was isolated essentially as described (Hervéet al., 2007). Cells from 200-mL LB cultures grown at 37 °C to an OD600 nm of ca. 0.75 were used. After lysis of cells by the addition of hot 4% sodium dodecyl sulfate solution, followed by overnight incubation at room temperature, a cell wall fraction was obtained by centrifugation at 100 000 g for 1 h, washed with water and suspended in 0.

9% or greater). ATP hydrolysis by these domains is necessary for both secretion and phage assembly (Russel, 1995; Schoenhofen et al., 2005), suggesting they may be involved in priming the secretin for activity. The periplasmic portion of GspA, but not pI, is predicted to contain a three-helix-bundle-type

peptidoglycan (PG)-binding domain that is well modeled by Phyre2 (Kelley & Sternberg, 2009). Despite the resemblance of pI to GspA, the similarity is not maintained in the second accessory component in these systems, pXI and GspB, respectively. GspB is encoded separately from GspA, while pXI is formed by an alternate translation start site within the pI transcript and plays a different role (Haigh & Webster, 1999). The Erwinia Out system contains a GspB homolog, OutB, but oddly, lacks a GspA equivalent. Phyre2

buy Metformin (Kelley & Sternberg, 2009) is able to generate only partial models of ExeB, GspB, OutB, and pXI and all are of low confidence. Secondary structure predictions also show significant variations between the proteins. MxiJ is an accessory protein involved in S. flexneri T3S secretin formation (Schuch & Maurelli, 2001). A structure of MxiJ is not available but it can be well modeled on its homologs, S. typhimurium PrgH and E. coli EscJ. PrgH and EscJ are integral proteins involved in T3S and are thought to form 24-membered rings in the inner membrane (Yip et al., 2005; Schraidt & Marlovits, 2011). While the MxiJ homolog is a common component of T3S systems, find protocol the consequences

of mutating this protein are inconsistent across T3S systems. The presence of either MxiJ or the pilotin, MxiM, is sufficient for secretin assembly (Schuch & Maurelli, 2001). In the absence of YscJ in Y. enterocolitica, the secretin formed by YscC appears normal (Diepold et al., 2010). However, without E. coli EscJ or P. aeruginosa PscJ, secretion is abolished, although whether this PTK6 is attributable to a malformed secretin has not been demonstrated (Ogino et al., 2006; Burns et al., 2008). To date, these systems have not been shown to require a MxiM-like pilotin. Structures of T4bP accessory proteins TcpQ and BfpG have yet to be determined, but in both cases Phyre2 (Kelley & Sternberg, 2009) predicts the C-terminal half of the protein to adopt a VirB7-like fold. VirB7, together with VirB9 and VirB10, is involved in forming the outer membrane pore in type IV secretion systems and resembles the N0 domain found in secretins (Souza et al., 2011) although none of the Vir proteins contains a ‘secretin domain’. The presence of an N0-like domain in this non-secretin protein family suggests that Gram-negative bacteria have adopted a common protein fold to allow communication between components of membrane-spanning systems.