To truly distinguish whether a streptomycin-resistant mutant is i

To truly distinguish whether a streptomycin-resistant mutant is introduced by transformation

via electroporation or generated by spontaneous mutation, we created two silent mutations flanking the missense mutation of codon 43 of rpsL-SR1 (Fig. 1). PCR amplicon was generated from this mutation, named rpsL-WM, and used to transform V. parvula PK1910. Obeticholic Acid chemical structure In five independent experiments, we obtained similar results: when equal amounts of DNA was used, rpsL-WM transformation always gave two to three times more streptomycin-resistant colonies than rpsL-WT transformation. The result of one transformation was shown in Fig. 2a. The rpsL gene from all these streptomycin-resistant colonies was then sequenced. Of the 19 colonies from rpsL-WM transformation, 11 contained the rpsL-WM sequence (Fig. 2b), three had the rpsL-SR1 sequence, and five had the rpsL-SR2 sequence. In contrast, of the nine colonies from the rpsL-WT transformation, five had the rpsL-SR1 sequence, four had the rpsL-SR2, and no colony had the rpsL-WM sequence. This result unequivocally demonstrates that V. parvula PK1910 is transformable. Veillonellae bacteria have so far remained as one of the most prevalent yet least studied microorganisms

in the human oral microbiome, largely due to our inability to genetically transform them. In this study, we set forth to test the transformability of Dinaciclib V. parvula strain PK1910, inspired by the finding of multiple competence-related genes on its genome. To this end, we have generated a ‘watermarked’rpsL gene conferring streptomycin resistance and shown that V. parvula PK1910 is transformable by electroporation. To our knowledge, this is the first report of genetic transformation in veillonellae. Electroporation has been successfully

used for DNA transformation in a large number of bacteria, such as Lactococcus lactis, Clostridium perfringens, Propionibacterium acnes, and Fusobacterium nucleatum, with varying optimal conditions for each bacterium (McIntyre & Harlander, 1989; Jiraskova et al., 2005; Kinder Haake et al., 2006; Cheong et al., 2008). In our efforts to optimize the procedure for transformation, we identified several parameters important to V. parvula transformation. First, the culturing media and Phosphatidylinositol diacylglycerol-lyase cell growth stage are important. Veillonella parvula could be reproducibly transformed only when cells were grown in ASSPL medium and harvested at the early exponential phase. Another parameter important to transformation is MgCl2 in the electroporation buffer. The incorporation of 1 mM MgCl2 in the electroporation buffer is required for the success of transformation. The pulse length and voltage of electroporation are also important. Success was repeatedly achieved with field strength of 20 kV cm−1, capacitance of 25 μF, and resistance setting of 200 Ω. Because our goal in this study was to examine the possibility of using electroporation to introduce DNA into V.

5 ms Electric shocks were administered by a Grass Instruments S-

5 ms. Electric shocks were administered by a Grass Instruments S-88 dual-channel square-pulse stimulator with an Isolation Unit SIU7 (all by Grass Instrument Division, Astro-Med Inc., West Warwick, RI, USA). The electrodes were placed on the radial side of the most distal phalanges of the left and right index fingers. Individual shock strength threshold determination was performed before conditioning and, to account for habituation effects, after half

of the total number of 80 shock presentations, separately for shocks administered to the left and right hands. Participants RG7204 price were asked to rate their sensation of shock intensity on a six-point scale ranging from one (‘not perceptible at all’) to six (‘painful’). Current levels started off at 1 mA and were gradually increased until a subjective rating of five was reached; this corresponded to an ‘unpleasant but

not painful’ sensation from the shock. The mean UCS intensity level was 5.02 ± 3.52 mA. Differential emotional significance was assigned to the click-like tones by means of MultiCS conditioning (Bröckelmann et al., 2011; Steinberg et al., 2012b). Affective conditioning BAY 80-6946 molecular weight paradigms typically involve one neutral stimulus (CS) that becomes associated with a UCS after repeated contingent CS–UCS pairings and acquires the power to elicit the CR previously evoked by UCS presentation alone (e.g., Quirk et al., 1995; Dolan et al., 2006; Stolarova et al., 2006; Keil et al., 2007; Moses et al., 2010; Kluge et al., 2011). MultiCS conditioning extends this classical approach by assigning behavioural Astemizole relevance to multiple CS per affective category and with only few contingent CS–UCS pairings. This procedure therefore challenges the brain’s capacity to process emotional stimuli in terms of speed and resolving power. In addition, for investigations

with time-sensitive neurophysiological measures such as MEG or EEG, the procedure provides a sufficiently high number of trials within each experimental condition assuring good signal-to-noise ratio for data analysis while every single stimulus is repeated only a few times, reducing extinction of the acquired emotional meaning due to repeated non-reinforced CS presentations after conditioning (Rogan et al., 1997). Upon arrival in the laboratory, participants were informed about the experimental procedure and the electric shock administration, and gave written informed consent to the protocol. The affective associative learning procedure in the MEG comprised one pre-conditioning MEG measurement, two interspersed conditioning sessions and one post-conditioning MEG measurement (Fig. 1), as well as three behavioural tasks administered after MEG data acquisition.

“The aim of the study was to compare prospectively indicat

“The aim of the study was to compare prospectively indicator-condition (IC)-guided testing versus testing of those with non-indicator conditions (NICs) in four primary care centres (PCCs) in Barcelona, Spain. From October 2009 to February 2011, patients aged from 18 to 65

years old who attended a PCC for a new herpes zoster infection, seborrhoeic eczema, mononucleosis syndrome or leucopenia/thrombopenia were included in the IC group, and one in every 10 randomly selected patients consulting for other reasons were included in the NIC group. A proportion of patients in each group were offered an HIV test; those who agreed to be tested were given a rapid finger-stick HIV test (€6 per test). Epidemiological and clinical

data were collected and analysed. During the study period, 775 patients attended with one of the four selected ICs, while 66 043 patients presented with an NIC. HIV screening was offered to 89 patients with ICs (offer rate Poziotinib supplier 11.5%), of whom 85 agreed to and completed testing (94.4 and 100% acceptance and completion rates, respectively). In the NIC Selleckchem R788 group, an HIV test was offered to 344 persons (offer rate 5.2%), of whom 313 accepted (90.9%) and 304 completed (97.1%) testing. HIV tests were positive in four persons [prevalence 4.7%; 95% confidence interval (CI) 1.3–11.6%] in the IC group and in one person in the NIC group (prevalence 0.3%; 95% CI 0.01–1.82%; P < 0.009). If every eligible person had taken an HIV test, we would have spent €4650 in the IC group and €396 258 in the NIC group, and an estimated 36 (95% CI 25–49) and 198 persons (95% CI 171–227), respectively, would have been diagnosed with HIV infection. The estimated cost per new HIV diagnosis would Montelukast Sodium have

been €129 (95% CI €107–153) in the IC group and €2001 (95% CI €1913–2088) in the NIC group. Although the number of patients included in the study was small and the results should be treated with caution, IC-guided HIV testing, based on four selected ICs, in PCCs seems to be a more feasible and less expensive strategy to improve diagnosis of HIV infection in Spain than a nontargeted HIV testing strategy. The large majority of sexually transmitted infection (STI) prevention, diagnosis, and treatment occurs in primary care centres (PCCs) [1, 2]. In Spain, access to the health service is universal and free, and PCCs are the settings most frequently visited in order to take an HIV test (approximately 30% of all HIV tests are carried out in PCCs) [3, 4], and where 72% of people receive health care at least once a year [5]. As such, they appear to be suitable settings for HIV screening strategies [6]. Moreover, as a consequence of the reduction in morbidity and mortality in HIV-infected patients associated with highly active antiretroviral therapy, an increased number of patients have stable, chronic HIV infection, and this health care challenge may require new approaches.

In 1996, a correlation between 6TGN

and clinical remissio

In 1996, a correlation between 6TGN

and clinical remission was demonstrated for the first time in a cohort of 25 Canadian adolescent patients receiving 6MP for more than 4 months. The investigators found a significant inverse relationship between disease activity as measured by the Harvey–Bradshaw index and 6TGN levels, with a Spearman rank correlation co-efficient of –0.457 (P < 0.05). 6MMP levels did not correlate with disease activity.[18] The landmark follow-up study from the same group in 2000 included 92 patients (79 Crohn's, eight ulcerative colitis and five indeterminate colitis patients) and provided further insight into 6TGN thresholds. Overall, higher 6TGN levels NVP-AUY922 cost were observed in responders versus non-responders (median 312 vs. 199, P < 0.0001). A secondary analysis found that if 6TGN levels were > 235 pmol/8 × 108 RBCs, then patients had an odds ratio (OR) of 5.0 (95% confidence interval [CI] 2.6–9.7, P < 0.001) of being a responder. Again, no correlation with 6MMP levels was seen. There was also no difference in the weight-based dose for responders versus non-responders with median dosage of 6MP in both groups being 1.25 mg/kg. The dose of 6MMP correlated poorly with 6TGN levels (r = 0.0009).[22] In a 2006

pooled analysis of 12 studies (including these two), a 6TGN level above 230–260 pmol/8 × 108 RBCs had this website a pooled OR for remission of 3.27 (1.71–6.27, P < 0.001).[23] A Spanish observational study of 113 adult patients is the only study published since then that did not find a correlation between 6TGN levels and clinical response. However, there was a positive predictive value of response of 87% in patients with 6TGN levels above 260.[24] Using a 6TGN threshold of 230, an updated meta-analysis published in 2013 including 20 studies of 2234 IBD patients, found the pooled OR was 2.09 (95% CI, 1.53–2.87, P < 0.00001) for remission.[25] The other way that 6TGN levels have been shown to relate

to clinical efficacy has been in dose-escalation studies. Examples include a French study of 55 IBD patients with either steroid-dependent or active IBD for the last 6 months while on stable doses of AZA. Escalation of the dose of AZA achieved clinical remission in 77% of patients with a baseline Amylase 6TGN in the range of 100–200 compared to only 24% of patients with a baseline 6TGN in the 300–400 range and none of the patients with a 6TGN of > 400 at baseline (P = 0.041).[26] Even though this paper was subsequently withdrawn due to authorship disagreement, similar findings have been subsequently reported. Two studies evaluating outcomes of thiopurine optimization found that in patients with subtherapeutic 6TGN levels, clinical improvement and/or remission were noted in 88%[27] and 78%[28] after thiopurine dose escalation.

Managing drug interactions (see above) Where the HIV drug has th

Managing drug interactions (see above). Where the HIV drug has the potential to be adversely affected by another drug, and the combination is unavoidable, TDM may be used either to manage that interaction, or else discount a significant interaction in a particular patient.

Other situations. Knowledge of plasma–drug concentrations may be clinically useful when evaluating whether there is scope for treatment simplification, or else confirming or refuting impaired drug absorption YAP-TEAD Inhibitor 1 supplier as a reason for virological failure. More detailed recommendations for the use of TDM are available in the BHIVA guidelines for the routine investigation and monitoring of adult JAK2 inhibitor drug HIV-1-infected

individuals 2011 [52]. As for all other investigations, it is essential that TDM is undertaken correctly, especially with regard to timing (undertaken when steady state has been achieved). A consensus has been achieved for defining targets [53] for many ARVs. With many newer agents, evidence for a defined minimum target for efficacy is either weak or lacking, and evidence for an upper toxicity cut-off for most ARVs is lacking. We recommend patients stopping ART containing an NNRTI in combination with an NRTI backbone replace all drugs with a PI (LPV/r) for 4 weeks (1C). We recommend patients stopping a PI-containing regimen stop all drugs simultaneously and no replacement is required (1C). Proportion of patients with an undetectable VL on ART who, PLEK2 on stopping a regimen containing an NNRTI in combination with a NRTI backbone,

are switched to PI/r for 4 weeks. In general, treatment interruptions are not recommended for most patients. Whatever the reason for stopping ART (e.g. drug toxicity, intercurrent illness, after pregnancy or patient choice), pharmacological issues must be considered for a clinician to give guidance. The half-life of each drug included in the regimen is critical. There is the potential for monotherapy or dual therapy if ARV drugs with different half-lives are stopped simultaneously. NNRTI and NRTI resistance mutations have been detected following discontinuation of previously suppressive regimens [54] and may have the potential to affect the likelihood of viral re-suppression on restarting an NNRTI-based ART regimen. There are limited data on which to base recommendations for how to protect against development of resistance in the period immediately following treatment cessation. Several discontinuation strategies have been proposed [55], and choice is influenced by clinical considerations, patient wishes and pharmacological principles.

, 2011) This enhances the acquisition and retention of motor lea

, 2011). This enhances the acquisition and retention of motor learning when applied over motor cortex (Nitsche et al., 2003b; Antal et al., 2004a; Reis et al., 2009), probably by increasing GPCR & G Protein inhibitor the associated long-term potentiation which underlies cortical plasticity (Stagg & Nitsche, 2011). These effects have been extended by research showing that anodal tDCS over Wernicke’s or Broca’s areas can enhance artificial language learning (Floel et al., 2008; Vries et al., 2010). Only one study has so far examined the effects of tDCS on perceptual learning, finding only a transient enhancement of visual learning by anodal stimulation before the effect dissipated with more training (Fertonani et al.,

2011). Our initial aim was to determine whether auditory perceptual learning, like motor learning, is enhanced by increasing excitability of its primary cortical representation, as it is underpinned by similar use-dependent plasticity, which anodal tDCS is thought

to enhance. We instead found that anodal tDCS did not enhance frequency discrimination learning but unexpectedly degraded frequency discrimination. We conducted two further experiments examining the effects of anodal tDCS on the Selleckchem LEE011 place and temporal coding processes that underlie auditory frequency discrimination to determine the cause of this degradation. Cumulative evidence suggests the auditory system uses duplex coding, with temporal processes dominant at lower frequencies (Moore, 1973; Moore & Glasberg, 1989) and place processes dominant at higher frequencies (Johnson, 1980). We took psychophysical Amino acid measurements of place and temporal coding and showed that the degradation of frequency discrimination was probably due to interference with temporal coding. Twenty adult volunteers (14 females) aged between 18 and 27 years (median = 23 years), all of whom reported normal hearing, participated in the three experiments. This sample size is consistent with previous psychophysical studies (Demany & Semal, 2002; Mathys et al., 2010). Fifteen subjects completed the frequency discrimination learning task reported in Experiment 1. As learning

was being examined, subjects with extensive psychoacoustic experience or with more than 1 year’s musical experience were not recruited. Seven subjects (four of whom participated in Experiment 1) were recruited for Experiment 2A. Six subjects (two of whom competed both Experiments 1 and 2A and two who completed only Experiment 2A) participated in Experiment 2B. Author M.F.T. completed Experiments 2A and 2B but was blind to stimulation condition with the procedure being performed by another experimenter and was not informed of stimulation condition until after testing was completed. All other subjects were blind to the stimulation condition and Naïve to the experimental aims. No formal audiometric assessment was performed; instead stimulus levels were tailored to each subject’s sensitivity.

This was a 4-week, prospective, observational study that was cond

This was a 4-week, prospective, observational study that was conducted in the MICU of an academic medical centre. Lexi-Interact and Micromedex interaction databases were utilized daily to screen patients’ medication profiles for DDIs, and severity was assessed using each database’s severity rating scale. Of 240 patient medication profiles evaluated, 457 DDIs were identified. The rate of DDIs this website was 190.4 DDIs/100 patient days with 297 of these interactions being unique

drug pairs. About 25% (114/457) were considered major DDIs. The most commonly involved medications were antihypertensive medications (106/457) and anticoagulants/antiplatelet agents (80/457). DDIs occur frequently in the MICU. Severity and drug combinations related to DDIs in the MICU differ from DDIs published in other ICU settings. When developing a DDI alerting system, patient characteristics and location should be considered. “

standardisation Aloxistatin involves promoting the prescribing of pre-selected products within a particular category across a healthcare region and is designed to improve patient safety by promoting continuity of medicine use across the primary/secondary care interface, in addition to cost containment without compromising clinical care (i.e. maintaining safety and efficacy). To examine the impact of product standardisation on the prescribing of compound alginate preparations within primary care in Northern Ireland. Data were obtained on alginate prescribing from the Northern Ireland Central Services Agency (Prescription Pricing Branch), covering a period of 43 months. Two standardisation promotion interventions were carried out at months 18 and 33. In addition to conventional statistical analyses, a simple interrupted time MRIP series analysis approach, using graphical

interpretation, was used to facilitate interpretation of the data. There was a significant increase in the prescribed share of the preferred alginate product in each of the four health boards in Northern Ireland and a decrease in the cost per Defined Daily Dose for alginate liquid preparations overall. Compliance with the standardisation policy was, however, incomplete and was influenced to a marked degree by the activities of the pharmaceutical industry. The overall economic impact of the prescribing changes during the study was small (3.1%). The findings suggested that product standardisation significantly influenced the prescribing pattern for compound alginate liquid preparations within primary care across Northern Ireland. “
“Context  Electronic prescribing (EP) systems are advocated as a solution to minimise medication errors. Benefits in patient safety are often as a result of some clinical decision support (CDS) within the system.

We used the European Consensus

We used the European Consensus NVP-LDE225 concentration Definition to assess trends in late presentation (CD4 count < 350 cells/μL or AIDS-defining illness) and AHD (CD4 count < 200 cells/μL or AIDS-defining illness) and evaluated associated risk factors using logistic regression methods. Among 14 487 eligible patients, 12 401 (85.6%) were late presenters and 9127 (63.0%) presented with AHD. Late

presentation decreased from 88.9% in 2005 to 80.1% in 2010 (P < 0.001). Similarly, AHD decreased from 67.8% in 2005 to 53.6% in 2010 (P < 0.001). In logistic regression models adjusting for sociodemographic and biological variables, male sex [adjusted odds ratio (aOR) = 1.80; 95% confidence interval

(CI) 1.60–2.04], older age (aOR = 1.37; 95% CI 1.22–1.54), civil service employment (aOR = 1.48; 95% CI 1.00–2.21), referral from out-patient (aOR = 2.18; 95% CI 1.53–3.08) and in-patient (aOR = 1.55; 95% CI 1.11–2.17) services, and hepatitis B virus (aOR = 1.43; 95% CI 1.26–1.63) and hepatitis C virus (aOR = 1.18; 95% CI 1.02–1.37) coinfections were associated with late presentation. Predictors of AHD were male sex (aOR = 1.67; 95% CI 1.54–1.82), older age (aOR = 1.26; 95% CI 1.16–1.36), unemployment (aOR = 1.34; 95% CI 1.00–1.79), referral from out-patient (aOR = 2.40; 95% CI 1.84–3.14) Rucaparib solubility dmso and in-patient (aOR = 1.97; 95% CI 1.51–2.57) services and hepatitis B virus coinfection (aOR = 1.30; 95% CI 1.19–1.42). Efforts to reduce the proportion of patients who first

seek care at late stages of disease are needed. The identified risk factors should be utilized in formulating targeted public health interventions to improve early diagnosis and presentation for HIV care. “
“The objective of this systematic review was to evaluate the effectiveness Afatinib nmr of adherence-enhancing interventions for highly active antiretroviral therapy (HAART) in HIV-infected patients in developed countries. A systematic literature search was performed (January 2001 to May 2012) in EMBASE, including MEDLINE records, CENTRAL and PsycInfo. Trials meeting the following predefined inclusion criteria were included: adult patients with an HIV infection treated with HAART, an intervention to enhance patient adherence, adherence as the outcome, clinical outcomes, randomized controlled trial (RCT), article written in English or German, patient enrolment after 2001, and trial conducted in World Health Organization (WHO) stratum A. Selection was performed by two reviewers independently. All relevant data on patient characteristics, interventions, adherence measures and results were extracted in standardized tables. The methodological trial quality was evaluated by two reviewers independently.

piricola and Rhizoctonia solani– indicating that it does not lyse

piricola and Rhizoctonia solani– indicating that it does not lyse fungal cells (Ngai &

Ng, 2006). Similarly, schizolysin does not have a lytic action on fungal cells. Hemolysin production is related to virulence of microorganisms like bacteria, resulting in septicemia and diarrhea (Raimondi et al., 2000). Hemolysin causes lysis in various kinds of cells including erythrocytes, mast cells, neutrophils and polymorphonuclear cells, and increases virulence by inflicting tissue damage or by dissolving materials that would inhibit pathogens from spreading throughout the tissue. The expression of ostreolysin is undetectable during mycelial growth; it proceeds during formation of primordia and fruiting bodies, but declines during maturation Buparlisib (Vidic et al., 2005). Schizolysin probably regulates fruiting initiation in the split gill mushroom, as suggested for the

oyster mushroom by Vidic et al. (2005). Aspergillus hemolysin (Sakaguchi et al., 1975) is expressed during sporulation. Whether hemolysin plays similar roles in bacteria, ascomycete fungi such as Aspergillus species, and basidiomycete fungi, including mushrooms, awaits clarification. This work was financially supported by National Grants of China (nyhyzx07-008, 2007BAD89B00 and 2010CB732202). Fig. S1. Ion-exchange chromatography of fraction C3 derived from fraction D3 adsorbed on DEAE-cellulose column, which was subsequently fractionated on CM-cellulose to yield C3 on a Q-Sepharose column (1×10 cm) in 10 mM phosphate buffer (pH 7.0). Fig. S2. FPLC-gel filtration of fraction Q2 adsorbed on Q-Sepharose on Superdex 75 in 10 mM phosphate buffer (pH 7.5) containing 0.15 M NaCl in the buffer. Table S1. Purification of hemolysin from 100 g fresh fruiting bodies of Schizophyllum commune. Table S2. Effects of compounds on hemolytic activity of Schizophyllum commune hemolysin (schizolysin).

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. “
“Resistance to carbapenems in enterobacteria is mediated Isotretinoin by the production of several types of carbapenemases or by the decreased permeability of the outer membrane, combined with the expression of extended-spectrum β-lactamases (ESBLs) or AmpC-like cephalosporinases. The objective of this study was to characterize carbapenem-nonsusceptible (C-NS) isolates of Klebsiella pneumoniae in the University Hospital in Plzeň (Czech Republic) and compare them with carbapenem-susceptible (C-S) K. pneumoniae isolates from the same patients. Six C-NS K pneumoniae isolates from different patients were collected between January 2007 and June 2008, and from three of these patients, C-S isolates were available for the study as well. The isolates were typed by pulsed-field gel electrophoresis and multilocus sequence typing.

columnare at 5 min postexposure to the mucus However, when F co

columnare at 5 min postexposure to the mucus. However, when F. columnare cells were pretreated with 50 mM d-mannose, the catfish skin mucus failed to induce the upregulation of gldH, suggesting that gldH might play an important role in the chemotactic

response of F. columnare to catfish skin mucus and that pretreatment of F. columnare with d-mannose might be able to block the chemotactic response of F. columnare to catfish. Whether pretreatment of F. columnare with d-mannose will affect the virulence of F. columnare to catfish merits further study. In summary, using a different pretreatment of F. columnare cells and an in vitro chemotaxis assay, we found selleck products that at least two major components were involved in the chemotactic responses of F. columnare

to catfish skin mucus. Firstly, the capsule of F. columnare plays an important role in recognizing the extracellular chemoattractants from the catfish mucus through lectin-like receptors. Secondly, one or more gliding motility proteins are involved in the chemotactic response of F. columnare to catfish skin mucus. These components might play important roles in the cell-to-cell communication necessary for gliding the chemotaxis of F. columnare toward catfish skin mucus. However, the exact roles of F. columnare gliding motility proteins in chemotaxis and the identities of the lectin-like receptors on the capsule of F. columnare receptors and the chemoattractants of the catfish skin mucus remain to be further studied. We thank Drs Benjamin LaFrentz (USDA-ARS) and Victor Panangala (USDA collaborator) for critical reviews of the manuscript. learn more We thank Beth Peterman and Stacey LaFrentz (USDA-ARS) for their excellent technical support. We also thank the management team of the Aquatic Animal Health Research Unit for daily care and management of the fish. This study Hydroxychloroquine was supported by the USDA/ARS CRIS project #6420-32000-024-00D. The use of trade, firm or corporate names in this publication is for the information and convenience of the reader. Such use does

not constitute an official endorsement or approval by the United States Department of Agriculture or the Agricultural Research Service of any product or service to the exclusion of others that may be suitable. “
“National Institute of Vegetable and Tea Science, Mie, Japan University of Tsukuba, Tsukuba, Japan Fusarium oxysporum produces three kinds of asexual spores: microconidia, macroconidia and chlamydospores. We previously analysed expressed sequence tags during vegetative growth and conidiation in F. oxysporum and found 42 genes that were markedly upregulated during conidiation compared to vegetative growth. One of the genes, FVS1, encodes a protein with a sterile alpha motif (SAM) domain, which functions in protein–protein interactions that are involved in transcriptional or post-transcriptional regulation and signal transduction.