Method C: Absorption corrected method The value of ��max of EM and TE was determined by scanning the drug solution in the range 200- 400 nm at 0.5 band width and 600 nm/min scan speed and was found to be at 293.38 and 270.29 nm, respectively. Wortmannin ATM EM also showed absorbance at 270.29 nm, while TE did not show any interference at 293.38 nm [Figure 4]. To construct Beer’s plot for EM and TE, stock solutions of 1000 ��g/ml of both the drugs were prepared in 0.1N HCl and working standard dilutions were made in 0.1N HCl using stock solution of 1000 ��g/ml. Also Beer’s plot was constructed for EM and TE in solution mixture at different concentration (4:6, 8:12, 12:18, 16:24, 20:30 ��g/ml) levels. Both the drugs followed linearity individually and in mixture within the concentration range 4-20 ��g/ml and 6-30 ��g/ml for EM and TE, respectively.

Figure 4 Simple overlay spectra of EM (4-20 ��g/ml) and TE (6-30 ��g/ml) in 0.1N HCl with formulation (12 + 18 ��g/ml) of EM and TE, respectively. Determination of absorption factor at selected wavelengths EM and TE solution in 0.1N HCl of known concentrations were scanned against blank on spectrophotometer. The value of absorption factor was found to be 0.52. Quantitative estimation of EM and TE was carried out using following equations: Corrected Absorbance of TE at 270.29 nm = Abs270.29 (TE + EM) �C [(abs270.29 (EM)/ abs293.38 (EM)] �� abs293.38 (EM) or Corrected Absorbance of TE at 270.29 nm = abs270.29 (TE + EM) �C 0.52 �� abs293.38 (EM) where; abs: Absorption value at given wavelengths.

Preparation of standard stock solutions and calibration curve Standard stock solutions of pure drug containing 1000 ��g/ml of TE and EM were prepared separately by dissolving 100 mg of pure TE and EM in a 100 ml volumetric flask and volume was made up to the mark with methanol for method A and B and with 0.1N HCl for method C. The working standard solutions of these drugs were obtained by dilution of the respective stock solution in methanol and 0.1N HCl for proposed methods. Derivative amplitudes of spectrum, by using the above mentioned procedures, were used to prepare calibration curves for both the drugs. Beer’s law obeyed in the concentration range of 3-21 ��g/ml for TE and 2-14 ��g/ml for EM by method A and B whereas 6-30 ��g/ml for TE and 4-20 ��g/ml for EM by method C.

Preparation of sample stock solution and formulation analysis To assay by using method A and B, 20 tablets were weighed accurately and a quantity of tablet powder equivalent to 100 mg of TE (66.66 mg of EM) was weighed and dissolved in the 80 ml of methanol with the aid of ultrasonication for 5 min and solution was filtered through Whatman paper No. 41 into a 100 ml Cilengitide volumetric flask. Filter paper was washed with methanol, adding washings to the volumetric flask and volume was made up to the mark with methanol.

The relative standard deviation (RSD) and assay values obtained by two analysts were 0.28, 99.67, and 0.26, 99.68, respectively selleck screening library [Table 4]. Table 4 Determination of precision Accuracy (recovery test) Accuracy of the method was studied by recovery experiments. The recovery experiments were performed by adding known amounts of the drugs in powdered tablets. The recovery was performed at three levels, 80, 100, and 120% of lafutidine standard concentration. The recovery samples were prepared in afore mentioned procedure. Three samples were prepared for each recovery level. The solutions were then analyzed, and the percentage recoveries were calculated from the calibration curve. The recovery values for lafutidine ranged from 100.1 �� 0.07611% [Table 2, Figure 4].

Figure 4 Overlay UV spectra of lafutidine standard and test tablet from 200-400 nm Limit of detection and limit of quantification The Limit of detection (LOD) and limit of quantification (LOQ) of lafutidine were determined by using standard deviation of the response and slope approach as defined in ICH guidelines. The LOD and LOQ for lafutidine are described in Table 3. Determination of active ingredients in tablets The validated method was applied for the determination of lafutidine in tablets (six tablets were assayed and the results in Table 2 indicate that the amount of drug in tablet samples met with requirements (98%�C102% of the label claim). CONCLUSION The developed UV spectrophotometric method was found to be rapid, simple, inexpensive, reproducible, and applicable over a wide concentration range with high precision and accuracy.

The method was validated as per the guidelines laid by ICH. The results of the validated tests were found to be satisfactory and therefore this method can be applied successfully for routine quality control analysis of lafutidine in bulk and pharmaceutical formulation. ACKNOWLEDGMENT We would like to thank Mr. Rambhau Moze Hon��ble President, Genba Sopanrao Moze trust for his kind support. Footnotes Source of Support: Nil Conflict of Interest: None declared.
In this edition of Pharmaceutical Methods, I am impressed by the number of articles that use as their means of analysis Liquid Chromatography with UV/Diode Array Detection (DAD). Five or more years ago, the predictions were that all such UV/DAD would be by now replaced by Liquid Chromatography�CMass Spectrometry (LC�CMS) technologies.

LC�CMS technologies were heralded as infallible as they are highly sensitive and selective even in the presence of multiple compounds within very complex matrices, are capable of finding related analogues and isomers, Cilengitide are high mass accuracy technologies that could discern between isobaric compounds or between co-eluting compounds, and their ability is seemingly endless.

caeruleus (Caer_4537, Caer_1186, Caer_4536, Caer_1187, Belinostat Caer_4538, Caer_1188, Caer_4539, Caer_4530, Caer_4535). But only one gene, encoding a phosphopantetheinyl transferase component of a siderophore synthetase, is associated with siderophore biosynthesis (Caer_3105). As it was isolated from a biofilm and a siderophore-transport associated genes were present, we presume that P. caeruleus DSM 24564T is utilizing siderophores, which are produced by other ambient bacteria [65]. The phylogenetic tree of the 16S rRNA gene analysis (Figure 1) with intermingled Phaeobacter and Leisingera species indicates that the classification of P. caeruleus DSM 24564T might need to be reconsidered. Hence, we conducted a preliminary phylogenomic analysis using GGDC [66-68] and the draft genomes of the type strains of the other Leisingera and Phaeobacter species.

The results shown in Table 7 indicate that the DNA-DNA hybridization (DDH) similarities calculated in silico for P. caeruleus DSM 24564T compared to other Phaeobacter species are, in general, not higher than those to Leisingera species. Although, the highest value by far was obtained for P. daeponensis, it was immediately followed by L. aquimarina and L. methylohalidivorans, which is in accordance with Figure 1. Table 7 DDH similarities between P. caeruleus DSM 24564T and the other Phaeobacter and Leisingera species (with genome-sequenced type strains) calculated in silico with the GGDC server version 2.0 [66]*. Acknowledgements The authors would like to gratefully acknowledge the assistance of Iliana Schr?der for growing P.

caeruleus cultures and Evelyne-Marie Brambilla for DNA extraction and quality control (both at the DSMZ). The work conducted by the U.S. Department of Energy Joint Genome Institute was supported by the Office of Science of the U.S. Department of Energy under contract No. DE-AC02-05CH11231; the work conducted by the members of the Roseobacter consortium was supported by the German Research Foundation (DFG) Transregio-SFB 51. We also thank the European Commission which supported phenotyping via the Microme project 222886 within the Framework 7 program.
Dehalobacter restrictus strain PER-K23 (DSM 9455), is the type strain of the species Dehalobacter restrictus [1]. Currently two pure cultures of D. restrictus have been described, namely D. restrictus strains PER-K23 and TEA [1,2].

We publish here the first full genome of a pure culture within the genus Dehalobacter and a preliminary comparison with a previously obtained metagenome from a co-culture containing Dehalobacter sp. strain E1 and Sedimentibacter sp [3]. Organohalide respiration GSK-3 (OHR) is considered as a key process in bioremediation of sites contaminated with organohalides such as tetrachloroethene (PCE) and trichloroethene (TCE), leading to a great interest in understanding the physiology and metabolism of organohalide respiring bacteria (OHRB).

The utilization of laparoscopic modalities has demonstrated to result in diminished selleck Pazopanib surgical trauma, lower conversion rates, reduced complication rates, and quicker recovery with shorter length of hospital stay compared with open surgery [5�C7]. Four main mechanisms have been hypothesized in the pathogenesis of colonoscopic perforation: direct penetration of the bowel wall, barotrauma, thermal abrasion, and traction injury [3, 13, 14]. The selection of an appropriate approach for the management of a colonoscopic perforation must be individualized on a case-by-case basis. A history of previous colonic pathology requiring partial colectomy, such as recurrent diverticulitis or neoplastic disease, may preclude consideration of primary repair.

Lack of optimal bowel preparation prior to colonoscopy or a prolonged interval between perforation and intervention may increase the risk of fecal contamination of the peritoneal cavity. In such cases, resection with diversion may be considered [6, 13]. However, preservation of a minimally invasive platform may be accomplished through laparoscopic segmental resection [6]. Furthermore, some colonoscopic perforations may be managed with endoscopic clipping or with conservative measures [11, 15�C17]. When identified during the index colonoscopy, endoscopic clipping may be successfully accomplished, avoiding any further intervention and its potential complications [11, 17]. Delayed colonoscopic perforations are typically due to thermal injury, which are in most cases small perforations.

These minor perforations represent the main indication for conservative treatment, which consists of intravenous hydration, antibiotics, and bowel rest [16]. Laparoscopic surgery represents an efficient technique for primary colonic repair. During this MIS technique, laparoscopic exploration is performed to visualize the perforation and assess the bowel GSK-3 content spillage into the peritoneal cavity. It is important to examine the entire large bowel in order to identify and repair secondary perforations. Occasionally, the proper identification of the perforation is not readily achieved; in such cases, colonoscopic assistance may be required. In this scenario, colonoscopic insufflation withCO2 is preferred over air insufflation, as the former is avidly absorbed through the colonic mucosa, avoiding substantial increment in the intraluminal pressure. Minimization of spillage is achieved by clamping the proximal bowel and using steep Trendelenburg for right colon perforations or reverse-Trendelenburg for left colon perforations. Once the colonic wall injury is identified, the edges of the perforation must be debrided if necrotic.

The surgeon then places a retractor in the patient’s mouth to gain surgical exposure, selleck chemical and the 3 sterilely draped robotic arms are placed in surgical position (Figures (Figures22 and and33). Figure 2 Patient-side cart and robotic arms positioning. (Courtesy of Intuitive Surgical Inc., 2010.) Figure 3 Robotic arms positioning in the oral cavity. Laryngeal reconstruction in pediatric patient. (Courtesy of Dr. Rahbar, 2007.) 7. Clinical Applications of Robotic Surgery in the Otolaryngology and Head and Neck Surgery 7.1. Head and Neck Oncology (TORS) O’Malley Jr. et al. initiated the TORS studies in canine and cadaveric models [13, 22�C27] and applied the technique to clinical practice. In 2006, three patients underwent robot-assisted transoral tongue base resection in a prospective clinical trial [13].

In this study, the robot enabled the surgeons to easily identify the glossopharyngeal, hypoglossal and lingual nerves, as well as the lingual artery. One T1 and one T2 squamous cell (AJCC cancer staging [29]): two instances of squamous cell carcinoma (one T1 and one T2) were adequately resected with negative margins, good hemostasis, and no postoperative complications. The different retractor types were assessed first during the cadaveric part of the study, and then at the beginning of each procedure performed in patients. The FK retractor achieved the best (versus Crowe Davis and Dingman retractors) tissue exposure and retraction. The same group published another study in which robot-assisted tonsillectomy was performed on 27 patients with squamous cell carcinoma.

25 of the 27 patients had negative cancer margins and 26 of the 27 patients were able to swallow postoperatively [27]. In 2007, Solares and Strome [30] described transoral carbon dioxide (CO2) laser robotic-assisted supraglottic laryngectomy in a 74-year-old woman with a large supraglottic tumor. Postoperatively, the patient was able to swallow by day five. The use of the carbon dioxide laser linked to the surgical robotic system allows more maneuverability of the instrument’s tips and improves beyond ��sight of beam�� limitations. In addition to tumor resection, robotic surgery can be used in the reconstruction of postresection defects. Mukhija et al. reported two cases of robotic-assisted free flap reconstruction in the oral cavity and oropharynx.

These studies highlight the improved visualization provided by RAS, avoiding the need to perform a mandibulotomy for access, thereby reducing morbidity and operative time [31]. After preliminary studies assessing the feasibility of TORS for oncologic resection, a series of studies were performed to examine the functional outcomes of these procedures [8, 15, 32�C39]. Most GSK-3 studies primarily report on oropharyngeal and oral cavity cancer, however, there are also case series on hypopharyngeal and laryngeal malignancy treated with TORS. Failure due to suboptimal access has been reported.

Here, we expand our analysis to the murine colon carcinoma cell line CT-26 cells and use CT-26 cells in syngeneic Balb/c mice as an in vivo model of colorectal cancer. LCL-30 was cytotoxic for CT-26 cells in a dose- and time-dependent fashion, in analogy to other cell lines previously tested (Dindo et al, 2006). Cellular fractionation and mass spectrometric analyses showed the following site LCL-30 to be enriched in the mitochondrial fraction, in line with published data on cationic ��-pyridinium analogues of C6 and C16 ceramide (Novgorodov et al, 2005; Dindo et al, 2006; Senkal et al, 2006). Incubation with LCL-30 led to a dose- and time-dependent decrease of cellular ATP-levels, pointing to a breakdown of mitochondrial respiration, as already described for the ��-pyridinium C6 analogue LCL-29 (Novgorodov et al, 2005).

Yet to our surprise, hallmarks of mitochondrially mediated apoptotic cell death, such as cytochrome c release or caspase activation, could not be detected. The mechanism of LCL-30-mediated cell death in CT-26 remains unclear, although ceramide has been implicated as an endogenous mediator of caspase-independent programmed cell death (Thon et al, 2005). Delineating the differences between cell lines that show caspase activation (SW403) and those without (CT-26) might help define the different mechanisms involved. Exposure to LCL-30 led to a transient depression of whole-cell ceramide levels, whereas mitochondrial ceramide levels showed a transient rise. This ceramide response is somewhat different from SW403, which show a mitochondrial decrease of ceramide levels (Dindo et al, 2006).

Importantly, the rapid and pronounced rise of mitochondrial S1P levels is comparable between both cell lines, raising the possibility of the presence of a mitochondrial sphingosine kinase (SphK). Additional experiments with isomers of LCL-30 have revealed S1P to be derived from endogenous sources and not from the breakdown of LCL-30 (Bielawska A, unpublished). S1P has been primarily regarded as a counter player of ceramide activity, although the intracellular compartmentalisation and the biological context (Ikeda et al, 2003) are important for its biological effects. Future experiments should take intracellular distribution of sphingosine kinase proteins into account.

While the activation of SphK1 leads to reduced apoptosis and improved proliferation, activation of SphK2 has been associated with enhanced cell death (Liu et al, 2003), which has been attributed to differential localisation in ER vs cytosol (Wattenberg et al, 2006). Neither SphK1 nor SphK2 has been detected in mitochondria. Nevertheless, there is evidence for additional sphingosine kinase activity Cilengitide (Fukuda et al, 2003), which might be responsible for the rise in mitochondrial levels of S1P in response to LCL-30.

It has been shown Sunitinib clinical that reactive oxygen and nitrogen species (ROS and RNS) contribute to the acinar cell damage during the early phases of pancreatitis [6]. ROS can act as a molecular trigger to activate oxidant-sensitive nuclear transcription factor kappa B (NF-��B) and thus induces cytokine expression, participating in various inflammatory processes. Moreover, an important link between ROS generation and apoptosis has been shown in both human and experimental pancreatitis. Numerous studies have shown many anti-oxidant treatments significantly reduce pancreatic injury and inflammation [7]. In AP, cytokines and other mediators derived from the inflamed pancreas activate the production of the inducible nitric oxide synthase (iNOS).

An enhanced formation of nitric oxide (NO) due to the induction of iNOS may be an important factor in the systemic and local haemodynamic disturbances and regulation of pancreatic exocrine secretion associated with AP. Excess of NO cause hypotension and decrease blood perfusion of various organs, including the pancreas and lung, correlating with apoptotic changes [8]. Therefore, treatments that could regulate free radicals ROS or RNS may directly contribute to the modality of acinar cell death and the degree of inflammation. Dachengqi Decoction (DCQD) composed of Radix et Rhizoma Rhei (Dahuang), Cortex Magnoliae Officinalis (Houpu), Fructus Aurantii Immaturus (Zhishi) and Natrii Sulphas (Mangxiao) is traditionally used as the representative prescription purgative for the treatment of constipation and for clearing internal heat in the stomach and intestine [9].

In China, DCQD has been used to treat AP for over 30 years [10]. Recent studies have shown that DCQD can promote gastrointestinal motility, inhibit cytokine activity and immune inflammatory response in AP [11]�C[13]. However, most of its biological activities have been studied individually on its ingredients. Studies designed to test the molecular mechanisms of the compound herb formula DCQD in the modality of pancreatic acinar cell death have not been elucidated to date. Thus, in our present work, we studied the effect of DCQD in regulating the inflammatory response via selective induction of pancreatic acinar cell apoptosis and explored the regulation mechanism of apoptosis/necrosis switch through its opposite effect in regulating ROS and NO in vitro and in vivo.

Materials and Methods 1. Materials 1.1. Drugs and reagents The spray-dried Radix et Rhizoma Rhei, Cortex Magnoliae Officinalis, Fructus Aurantii Immaturus and Natrii Sulphas powder were purchased from Chengdu Green Herbal Pharmaceutical Co. Ltd (Chengdu, China). The spray-dried powder was mixed of an equal amount and reconstituted Dacomitinib with sterile distilled water at concentrations for the crude drug of 2 g/mL DCQD in vivo study [14].

, 2008; Julvez et al., 2007; Mortensen, Michaelsen, Sanders, & Reinisch, 2004). selleck chem inhibitor A deficit in intellectual function on the Stanford�CBinet was noted (Olds et al., 1994), and the pre-school�Caged offspring of women that quit smoking during pregnancy, relative to those that persisted, had more difficulties on the verbal scale of the McCarthy assessment even after controlling for other prenatal and postnatal variables (Sexton et al., 1990). In contrast, nicotine-associated decrements in mathematics and reading on the Peabody Individual Achievement Test in children from the United States were nonsignificant when accounting for maternal education (Batty et al., 2006). Socioeconomic factors appear to be responsible for the nicotine group differences in reading but not mathematics or spelling in Dutch adolescents (Batstra et al.

, 2003). Children with a history of in utero smoking exposure had more problems with maternally rated executive function. The BRIEF findings were quite robust with significant mean elevations in the NIC groups on the GEC, both indices, and six of the eight scales. Most notably, the difference between unexposed and nicotine-exposed children on the GEC were retained after removal of the variance attributable to several other potential confounds. The proportion of children scoring in the clinical range was also more frequent among NIC-exposed children on the Inhibit, Emotional Control, Organization, and Monitor scales.

It should be reiterated that executive function is conceptualized by the BRIEF developers as a broad construct mediated by the frontal cortex with its associated cortical and subcortical connections that is responsible for intentional, goal-directed, problem-solving behaviors (Gioia et al., 2000). A fundamental strength of this instrument, unlike single laboratory executive function tests, is that this measure can be completed relatively quickly and can assess nonoverlapping aspects of executive functioning. Furthermore, although elevations in BRIEF ratings are well known among children with ADHD (Gioia et al., 2000; McCandless & O��Laughlin, 2007), abnormalities in executive function are certainly not unique to this condition and have also been identified in extremely low birth weight Entinostat (Anderson & Doyle, 2004), FAS (Chasnoff et al., 2010), and children that experienced a traumatic brain injury (Sesma et al., 2008). While this is the first report to examine maternally assessed executive function in the offspring of smokers, there are prior studies with laboratory-based measures (Fried et al., 2003; Huizink & Mulder, 2006; Kristjansson et al., 1989), and the present finding of abnormalities in the offspring of smokers are generally concordant.

Univariate Cox regression analyses including treatment as a covariable were performed, and identified a number of factors associated with reduced TTP. These Carfilzomib chemical structure included poor Karnofsky performance status (KPS; 70 vs 100%), liver metastases, multiple metastatic sites and younger age, with prognostic significance at a level of 15% (Table 4 ). Previous adjuvant treatment and gender did not appear to impact on disease progression. A multivariate Cox regression analysis using backward elimination of factors, with the first step including all factors identified in the univariate analyses, was then performed to assess the impact of independent prognostic factors on the treatment effect at a significance level of 5%. This analysis confirmed an increased risk of progression with lower age, liver metastases, poor KPS (70 or 80% at baseline) and multiple metastatic sites (Table 5 ).

Of note, the analyses confirmed that risk of disease progression was independent of treatment, as indicated by the HR of 1.02 (95% CI 0.90�C1.15; P=0.79). Table 4 Results of univariate Cox regression analysis: TTP Table 5 Results of multivariate Cox regression analysis: TTP Overall survival Overall survival data, updated in June 2002 after 1147 events, confirm the integrated analysis results reported by Twelves (2002). In patients receiving capecitabine, overall survival was equivalent to that in patients treated with 5-FU/LV (HR 0.95, 95% CI 0.84?1.06, P=0.48). The median survival was 12.9 months (95% CI 11.8?14.0) in the capecitabine group and 12.8 months (95% CI 11.7?14.

0) in the 5-FU/LV group after 583 and 564 events, respectively (Figure 3). Univariate analyses identified nine prognostic factors for survival with a significance level of 15%. Multivariate Cox regression analysis confirmed that lower KPS (70 or 80 vs 100%), multiple metastatic sites and the presence of liver metastases were independent prognostic indicators for poor survival (Table 6 ). Patients with well-differentiated tumours had a slightly reduced risk of death compared with patients having less well-differentiated tumours. The data also suggest that previous surgery may have a prognostic effect, but the number of patients who did not have prior surgery was extremely small, as approximately 90% of patients had received prior surgery.

Similarly, multivariate Cox regression analysis suggested that risk of death was markedly reduced in patients defined as race ��other�� compared with the rest of the population (HR=0.64). However, this subgroup, comprising multiple ethnic groups (including Orientals and GSK-3 Hispanics), included only 35 patients in the capecitabine arm and 34 patients in the 5-FU/LV arm, and thus the results are difficult to interpret. Of note, the analyses confirmed that survival was independent of treatment.

This is consistent with the finding that FHL2 promotes invasive potential in colon cancer (Zhang et al, 2010). During cancer progression, advanced tumour cells frequently exhibit a conspicuous downregulation of epithelial markers and a loss of intercellular junctions, resulting in a loss of epithelial selleck chemicals CHIR99021 polarity and reduced intercellular adhesion. These alterations are often accompanied by nuclear accumulation of ��-catenin, increased cell motility and expression of mesenchymal-specific proteins such as vimentin (Vermeulen et al, 1995; Huber et al, 2005; Turley et al, 2008; Iwatsuki et al, 2010). This process called EMT can therefore promote invasion and metastasis (Bates and Mercurio, 2005; Huber et al, 2005; Turley et al, 2008). One of the decreased epithelial markers during EMT is E-cadherin (De Wever et al, 2008).

Four-and-a-half LIM domains protein 2 negatively regulates the transcription of E-cadherin through interaction with Snail 1 (Zhang et al, 2010, 2011). Moreover, FHL2 stimulates vimentin and matrix metalloproteinase-9 expressions (Zhang et al, 2010). Other arguments for a role of FHL2 in EMT come from a gain-of-function experiment in which the overexpression of FHL2 in a fish pre-osteoblastic cell line promoted cell dedifferentiation and altered gene expression profile in agreement with an EMT-like phenotype (Rafael et al, 2012). In contrast to others (Zhang et al, 2010), we did not detect nuclear FHL2 expression in CRC, using a well-defined and validated antibody; therefore, we suggest that FHL2 interacts via cytoplasmic/cell periphery protein interactions, rather than via direct transcriptional activation or repression, in the progression of CRC, including EMT.

Multiple functions have been ascribed to FHL2, and it is puzzling how a protein that consists of LIM domains only and that lacks any obvious enzymatic activity can exert such a functional diversity. Four-and-a-half LIM domains protein 2 can interact with >50 different proteins that belong to different functional classes, including receptors (Kurakula et al, 2011; Matulis and Mayo, 2012), structural proteins (Lange et al, 2002; Coghill et al, 2003), transcription factors and cofactors (Samson et al, 2004; Han et al, 2009; Hubbi et al, 2012), splicing factors (Dye and Patton, 2001; Ng et al, 2002), DNA replication and repair enzymes (Chan et al, 2000; Yan et al, 2003), and enzymes (Jiang et al, 2002; Lange et al, 2002; Wang et al, 2012).

The biological importance of many of these protein�Cprotein interactions has not been determined, but such information will contribute to further clarifying the roles of FHL2 in colorectal and other cancers. Cell-specific expression and cell-specific subcellular distribution of AV-951 FHL2, as well as the available concentrations of the interacting partners may partially favour certain interactions.