Molecular Biological Properties Research Articles

Modeling the structural and reactivity properties of hydrazono methyl-4H-chromen-4-one derivatives—wavefunction-dependent properties, molecular docking, and dynamics simulation studies

This study explains the vibration and interaction of three pharmaceutically active hydrazine derivatives, (E)-3-((2-(2,5-difluorophenyl)hydrazono)methyl)-4H-chromen-4-one (DFH), (E)-3-((2-(4-(trifluoromethyl)phenyl)hydrazono)methyl)-4H-chromen-4-one (TMH), and (E)-3-((2-(3,5-bis(trifluoromethyl)phenyl)hydrazono)methyl)-4H-chromen-4-one (BPH) using theoretical approach. The trend in chemical reactivity and stability of the studied compounds was observed to show increasing stability and decreasing reactivity and this was obtained from orbital energies. The effect of bromine and chlorine atoms, instead of fluorine atoms, is also noted. Surface analysis on the covalent bond was attained by ELF and LOL analysis. Biological activities were predicted using molecular docking studies. Docking results were analyzed with standard drugs, 5-fluorouracil/piperine. Antitumor activity of hydrazine derivatives was found to be higher than reference ones. Molecular dynamics (MD) simulation was performed for 100ns to validate the stability behavior of hydrazine derivatives with the dual specificity threonine tyrosine kinase (TTK) protein. RMSD, RMSF, Rg, SASA, and intermolecular analysis of DFH, TMH, and BPH with threonine tyrosine kinase forms stable ligand-protein interactions. The molecular and predictive biological properties of three pharmaceutically active hydrazine derivatives which can be helpful to researchers in future experimental validation through in vitro and in vivo studies.

Molecular correlates of clinical benefit in previously treated patients (pts) with BRAF V600E-mutant metastatic colorectal cancer (mCRC) from the BEACON study.

3513 Background: Encorafenib + binimetinib + cetuximab (enco/bini/cetux; triplet) and enco + cetux (doublet) regimens improved overall survival and objective response rate vs standard of care in pts with previously treated BRAF V600E-mutant mCRC in the randomized phase 3 BEACON study. To identify molecular correlates of clinical outcome, we performed molecular profiling in tumors from pts in the study. Methods: Baseline tumor samples were retrospectively analyzed by whole-exome sequencing (WES) and whole transcriptome sequencing (WTS) using ImmunoID NeXT (Personalis, Menlo Park, CA, USA). BRAF-mutant (BM) and consensus molecular subtypes (CMS) were determined using published classifiers. Pathway activities were evaluated with gene set variation analysis. Objective tumor response was evaluated according to each subtype. Additional association and interaction analyses between molecular features and clinical outcomes by treatments are ongoing and will be presented. Results: Baseline tumor samples were analyzed by WES and/or WTS from 527 of 665 (79.2%) randomized pts. The biomarker analyses set is representative of the total pt population and had similar clinical outcomes. Of the 460 pts analyzed by WTS (165/224 [73.7%] in the triplet arm, 146/220 [66.4%] in the doublet arm, and 149/221 [67.4%] in the control arm), 84.6% were classified as either CMS1 (n = 225) or CMS4 (n = 164). The proportion of pts classified as BM1 was 32.2% (n = 148) and the majority (84.5%) of these were CMS4, whereas many of those classified as BM2 (67.8%, n = 312) were CMS1 (64.7%). In the BM1 and CMS4 tumors, expression of inflammatory response and epithelial mesenchymal transition genes were elevated, and expression of cell cycle genes was reduced. The response rate in pts with CMS4 and/or BM1 tumors was higher in the triplet arm (CMS4: 33.3% [95% CI: 21.7–46.7]; BM1: 33.3% [95% CI: 21.4–47.1]) compared with the doublet arm (CMS4: 19.2% [95% CI: 9.6–32.5]; BM1: 14.9% [95% CI: 6.2–28.3]). Conclusions: Molecular characteristics and biological properties observed in BRAF V600E-mutant mCRC suggest that a subset of pts with specific molecular features may derive greater clinical benefit from triplet than doublet therapy. Additionally, these findings support the utility of gaining further understanding of the biological landscape in BRAF-mutant mCRC to enable potential hypotheses for pt selection to improve clinical outcome in future studies. Clinical trial information: NCT02928224.

Метапневмовірусна інфекція птиці: розробка вітчизняного методу діагностики та епізоотологічний моніторинг у птахівничих господарствах України

The main biological (cultural) properties of field isolates of metapneumovirus (MPV) were studied, normal and hyperimmune sera to metapneumovirus for IHR-diagnosticum (erythrocyte diagnosticum based on indirect hemagglutination reaction) were obtained, and a set of M-component components was developed. A diagnostic system of IHR (indirect hemagglutination reaction) was developed, with the help of which epizootological monitoring was carried out in poultry farms and the spread of a new infectious disease of poultry (metapneumovirus infection) among turkeys and chickens in poultry farms of Ukraine was studied. The purpose of the research is to develop a domestic diagnostic test system (erythrocyte diagnosticum for IHR) for metapneumovirus infection (MPVI) or infectious avian rhinotracheitis (IRT). As a result of the conducted researches metapneumovirus infection or infectious rhinotracheitis was established in poultry farms of 4 regions of Ukraine. The pathogen was isolated, its molecular-biological properties were studied by PCR (polymerase chain reaction), and it was established that it belongs to the genus Metapneumovirus (MPV), subtype B. The results of the epidemiological monitoring indicate that the developed erythrocyte MPV (IRT) antigen based on IHR is sensitive and specific and can be used to control the spread of metapneumovirus infection and the intensity of immunity in birds vaccinated against this disease. The production inspection in poultry farms in the western regions of Ukraine established the possibility of using IHR-diagnosticum for control of MPVI. As a result of the performed work the new domestic method of diagnostics, forecasting and protection of poultry against a metapneumovirus infection is offered. Prospects for further research are to use this erythrocyte diagnosticum based on the indirect hemagglutination reaction to monitor metapneumovirus infection of birds in poultry farms in Ukraine and determine the epizootic situation for this disease.

Experimental and theoretical analysis of molecular structure, vibrational spectra and biological properties of the new Co(II), Ni(II) and Cu(II) Schiff base metal complexes

A new novel Cobalt, Nickel and Copper metal complexes were synthesized from Schiff base ligand of 2,2′-((1E,1′E)-((4-nitro-1,2-phenylene) bis(azanylylidene)) bis(methanylylidene)) diphenol. The structures of all the synthesised compounds have been analysed using Fourier-Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR) spectroscopy, Ultraviolet-Visible (UV-Vis) spectrum, elemental analysis and Powder X-ray diffraction (PXRD). The experimental spectral frequencies of ligand and metal complexes are correlated with theoretically computed vibrational frequencies. The molecular structure of the ligand and its metal complexes has been optimized using B3LYP-6-311G(d,p)/LANL2DZ basis set and their parameters have been discussed. Natural bond orbital and Frontier Molecular Orbital analysis have assessed the presence of a metal-ligand bond in complexes. Further, biological activity studies such as antioxidant, anti-inflammatory, antidiabetic have also been analyzed using various methods. In addition, molecular docking studies have also been performed on all complexes using the α-amylase enzyme structure to calculate the possible binding energy of inhibitors.

Molecular-Biological Properties of the Attenuated Strain of Salmonella Abortus-Equi E-841, used in the Creation of a Vaccine against Abortion of Mares

Molecular-Biological Properties of the Attenuated Strain of <i>Salmonella Abortus-</i>Equi E-841, used in the Creation of a Vaccine against Abortion of Mares

Intrahepatic Cholangiocarcinoma: Evolving Concepts and Medical Treatment

Cholangiocarcinoma (bile duct cancer) is classified into intrahepatic and extrahepatic cholangiocarcinoma (perihilar and distal cholangiocarcinoma) according to the anatomical location of the lesion. The incidence of extrahepatic cholangiocarcinoma has been relatively stagnant in recent decades, but intrahepatic cholangiocarcinoma is steadily increasing worldwide, requiring attention. Various classification systems based on gross growth patterns, histological findings, and tumor-derived cells, as well as classification based on existing anatomical location, have been proposed, however, the consensus has not been established yet. Intrahepatic cholangiocarcinoma is a carcinoma with an extremely poor prognosis. Complete tumor resection is the only curative treatment. The overall survival rate for 5 years after surgery is 15% to 40%, but recurrence after surgery is observed in 2/3 patients. Therefore, determining the right stage before surgery and selecting an appropriate treatment method through a multidisciplinary approach is a very important process in determining proper treatment. Systemic therapy may be used for locally advanced biliary tract cancer or metastatic biliary tract cancer where surgery is not possible. However, the effectiveness of traditional anticancer chemotherapeutic agents is rather pessimistic, therefore treatments using molecular biological properties have recently been attempted. Finding a way to increase the number of resectable cases through early diagnosis is one of the main challenges. In addition, it is also hoped that the selection of new therapeutic targets and therapeutics will be possible as a result of advanced research on gene expression profiles and mutations in cholangiocarcinoma.

Zinc, ω-3 polyunsaturated fatty acids and vitamin D: An essential combination for prevention and treatment of cancers

Zinc, ω-3 polyunsaturated fatty acids (PUFAs) and vitamin D are essential nutrients for health, maturation and general wellbeing. Extensive literature searches have revealed the widespread similarity in molecular biological properties of zinc, ω-3 PUFAs and vitamin D, and their similar anti-cancer properties, even though they have different modes of action. These three nutrients are separately essential for good health, especially in the aged. Zinc, ω-3 PUFAs and vitamin D are inexpensive and safe as they are fundamentally natural and have the properties of correcting and inhibiting undesirable actions without disturbing the normal functions of cells or their extracellular environment. This review of the anticancer properties of zinc, ω-3 PUFAs and vitamin D is made in the context of the hallmarks of cancer. The anticancer properties of zinc, ω-3 PUFAs and vitamin D can therefore be used beneficially through combined treatment or supplementation. It is proposed that sufficiency of zinc, ω-3 PUFAs and vitamin D is a necessary requirement during chemotherapy treatment and that clinical trials can have questionable integrity if this sufficiency is not checked and maintained during efficacy trials.

Properties and Therapeutic Implications of an Enigmatic D477G RPE65 Variant Associated with Autosomal Dominant Retinitis Pigmentosa.

RPE65 isomerase, expressed in the retinal pigmented epithelium (RPE), is an enzymatic component of the retinoid cycle, converting all-trans retinyl ester into 11-cis retinol, and it is essential for vision, because it replenishes the photon capturing 11-cis retinal. To date, almost 200 loss-of-function mutations have been identified within the RPE65 gene causing inherited retinal dystrophies, most notably Leber congenital amaurosis (LCA) and autosomal recessive retinitis pigmentosa (arRP), which are both severe and early onset disease entities. We previously reported a mutation, D477G, co-segregating with the disease in a late-onset form of autosomal dominant RP (adRP) with choroidal involvement; uniquely, it is the only RPE65 variant to be described with a dominant component. Families or individuals with this variant have been encountered in five countries, and a number of subsequent studies have been reported in which the molecular biological and physiological properties of the variant have been studied in further detail, including observations of possible novel functions in addition to reduced RPE65 enzymatic activity. With regard to the latter, a human phase 1b proof-of-concept study has recently been reported in which aspects of remaining vision were improved for up to one year in four of five patients with advanced disease receiving a single one-week oral dose of 9-cis retinaldehyde, which is the first report showing efficacy and safety of an oral therapy for a dominant form of RP. Here, we review data accrued from published studies investigating molecular mechanisms of this unique variant and include hitherto unpublished material on the clinical spectrum of disease encountered in patients with the D477G variant, which, in many cases bears striking similarities to choroideremia.

Synthetic Approaches to the Anticancer Agent Fredericamycin A

AbstractIn this minireview, we have highlighted various developments related to the total synthesis of an anticancer agent, fredericamycin A (NSC‐305263). The presence of a unique molecular architecture and significant biological properties associated with fredericamycin A have greatly enhanced the research activity, and we cover the total synthesis of this molecule since its isolation. Different methodologies adopted for the construction of the stereogenic spiro centre are radical spirocyclization, Diels−Alder (DA) reaction, [3+2] annulation, photochemical approach, ring‐closing metathesis (RCM), palladium‐catalyzed cross‐coupling reaction, rearrangement approach, benzannulation etc. This minireview provides an overview of the contribution of different research groups in the total synthesis of fredericamycin A. We also cover various model studies related to the synthesis of this molecule.

Results of surgical treatment of patients with stage IV colon cancer of older age groups and ways to improve them

The effectiveness of cytoreductive operations in geriatric patients with stage IV colon cancer was assessed. A comparative analysis of the results of surgical treatment of metastatic colon cancer in patients of various age groups was carried out. The molecular biological properties of colon adenocarcinoma in patients with metastatic colorectal cancer were studied. The clinical significance of immunohistochemical markers as the proliferative index of stem cancer cells (ALDH+Ki-67+) and the chemokine receptor CXCR4 was determined for predicting the long-term results of surgical treatment of patients with stage IV colon cancer has been determined. It was found that the survival rates of elderly and senile patients are not inferior to those in patients under 60 years of age. A comparative analysis of the immediate and long-term results of treatment indicates the effectiveness of cytoreductive interventions in elderly and senile patients suffering from stage IV colon cancer. It was found that the expression level of the receptor for CXCR4 chemokines and the proliferative activity of stem cancer cells correlate with the life expectancy of patients after cytoreductive interventions and can be used to clarify the indications for their implementation.

β-glucosidase from Hevea brasiliensis seeds: Purification, homology modeling, and insights into the substrate-binding model.

The isolation of β-glucosidase from Hevea brasiliensis (Hbglu) seeds was investigated and a homology model was built on the MODELLER software to understand the structure feature. The quality of the model was evaluated on PROCHEK. The refined model was used for molecular docking on AutoDock 4.2 to determine the substrate- binding sites and potential substrates based on their calculated binding affinities. The substrate specificity of Hbglu was verified through the kinetic measurement of hydrolytic activities. Molecular dynamic simulations of cyanogenic β-glucosidase and ligand-bound complex showed that the free energy (ΔG) for the binding of p-nitrophenyl-β-D-glucopyranoside and daidzein-7-O-β-D-glucoside were -8.6 and -7.92kcal/mol, respectively. Thus, daidzein-7-O-β-D-glucoside is a potential substrate. Future studies on the physicochemical properties and catalytic mechanisms will provide information on the molecular biological properties of Hbglu. PRACTICAL APPLICATIONS: This study reported the 3D structural simulation of β-glucosidase from Hbglu. The docking condition between Hbglu and various different substrates were assessed on Autodock. The results can be used as reference in designing enzymes, and improving the utilization of β-glucosidases for the hydrolysis of flavor precursors from fruits, teas, and wines and for the production of flavonoid compounds and cyanogenic glycoside degradation.

Molecular genetic characterisation and expression profiling of calpain 3 transcripts in red sea bream (Pagrus major)

Calpains (CAPNs) belong to the papain superfamily of cysteine proteases, and they are calcium-dependent cytoplasmic cysteine proteases that regulate a variety of physiological processes. We obtained the sequence of CAPN3 from an NGS-based analysis of Pagrus major (PmCAPN3) and confirmed the conserved molecular biological properties in the predicted amino acid sequence. The amino acid sequence and predicted domains of CAPN3 were found to be highly conserved in all of the examined species, and one catalytic domain and four calcium binding sites were identified. In healthy P. major, the PmCAPN3 mRNA was most abundantly expressed in the muscle and skin, and ubiquitously expressed in the other tissues used in the experiment. After artificial infections with fish pathogens, significant changes in its expression levels were found in immune-related tissues, most of showed upregulation. In particular, the highest level of expression was found in the liver, a tissue associated with protease activity. Taken together, these results suggest a physiological activity for PmCAPN3 in P. major and reveal functional possibilities that have not yet been reported in the immune system.

Rhysomania is a dangerous object the evaluating phytosanitary state of sugar beet seeds in Ukraine

The results of many years of research of beet necrotic yellow vein virus, which causes rhizomania, and is a quarantine object, are analyzed. The molecular-biological properties, features of its genome and dependence of pathogenesis on genetic variations of the virus are described. Diversity of virus pathotypes and disease circulation in the world and in Ukraine and ways of its spread are shown. Natural genes of sugar beet resistance to rhizomania were also analyzed.

Short Communication: Optimazing culture and differentiation L6 cell, C2C12 cell and primary myoblast cells culture

Abstract. Lesmana R, Goenawan H, Tarawan VM, Setiawan I, Hidayat A, Supratman U. 2018. Short Communication: Optimizing culture and differentiation of L6 cell, C2C12 cell, and primary myoblast cells culture. Cell Biol Dev 2: 51-54. Alteration in skeletal muscle function and structure could result from many chronic diseases, drug treatment, or physical activity. Therefore, understanding the molecular mechanism of skeletal muscle diseases or the adaptation process will be very important and beneficial. In most cases, for example, during aging, the imbalance between anabolic and catabolic processes could initiate a decreased muscle mass and change its fiber structure. Unfortunately, there is no suitable animal model for study, and animal model development is time-consuming at some point. Next, it is good to study and elaborate a model on disease mechanisms, drug targets, and hormonal effects in skeletal muscle, which is not easy and tricky. Finally, the promising methods to study molecular biology properties of muscle are using in vitro systems utilizing 2 cell lines derived from mouse (C2C12 myoblast cells) and rat (L6 myoblast. Another establishment technique is using mixed and isolated single fiber primary myocytes culture.

Label-free visualization of lignin deposition in loquats using complementary stimulated and spontaneous Raman microscopy

The lignification triggered by biotic or abiotic stresses hardens fruits and vegetables and eventually influences their consumer appeal. Extensive prior efforts have been made to unveil the underlying mechanism of flesh lignification, primarily focused on its physicochemical and molecular biological properties. Nevertheless, most of these studies used destroyed and homogenized bulk tissues as analytes; as a result, potentially valuable spatial information was lost. In this study, the deposition of lignin in loquat flesh during lignification was visualized from the tissue level to the single-cell level by combining the advantages of stimulated Raman scattering (SRS) and spontaneous Raman microscopy using label-free in situ molecular imaging. SRS has the advantages of being fast and providing large-area chemical imaging to reveal the spatial heterogeneity of lignin and cell wall polysaccharide distribution in loquat flesh. After 2 days of storage at 0 °C, increased lignins were observed by large-area SRS imaging. In addition, microscopic SRS images of the flesh cells indicated that the increased lignins were trapped in the cell corner (CC) and middle lamella (ML). Furthermore, the compositional and structural features of lignified cells (LCs), CC and ML of loquat flesh were investigated by spontaneous Raman microscopy, and the results showed that the LCs were a combination of lignin, cellulose, and hemicellulose, whereas CC and ML showed only deposited lignin and pectin without cross-linked cellulose and hemicellulose. This result further suggests that the lignins in the CC and ML regions of loquats were later synthesized alone during postharvest storage. This innovative combination of SRS and spontaneous Raman microscopy allows the label-free macroscale and fine chemical imaging of plant cell walls and will enhance our fundamental understanding of the structures and functions of the plant cell wall.

INFLUENCE OF THE AGE FACTOR AND TUMOR IMMUNOPHENOTYPE ON THE EFFECTIVENESS OF CYTOREDUCTIVE OPERATIONS IN METASTATIC COLORECTAL CANCER

Aim of the study. To analyze the effectiveness and safety of cytoreductive interventions in patients with IV stage colorectal cancer in account of the age factor and to assess the effect of the molecular biological properties of the tumor on long-term treatment results. Materials and methods. A comparative evaluation of the results of surgical treatment of metastatic colorectal cancer in patients of various age groups was carried out. The clinical significance of immunohistochemical markers for predicting long-term treatment outcomes has been studied. Results. The most significant risk factors for the development of postoperative complications were identified. The prognostic value of immunohistochemical markers such as the proliferative index of stem cancer cells (ALDH + Ki-67 +) and the chemokine receptor CXCR4 has been established. Conclusion. A comprehensive analysis of the molecular biological properties of the tumor, coupled with an assessment of the functional operability of patients, provides a personalized approach to the choice of surgical tactics in patients with stage IV colorectal cancer, which allows counting on the encouraging results of cytoreductive interventions.

Comprehensive approach to choosing surgical tactics for locally advanced forms of colorectal cancer in patients of older age groups

The objective is to improve the results of treatment of locally advanced colorectal cancer in patients of older age groups due to the personalized approach to choosing surgical tactics with a comprehensive assessment of the functional operability and molecular biological properties of the tumor.Material and methods. A comparative evaluation of the results of surgical treatment of locally advanced colorectal cancer in patients of different age groups was conducted on representative clinical material. We studied the molecular profile of tumors, taking into account the age factor, and the clinical significance of specific markers in predicting the results of treatment.Results. The most significant indicators of functional operability of patients that must be considered when choosing a surgical tactic were identified. . The features of the immunophenotype of tumors, taking into account the age factor, were determined; and the prognostic significance of specific immunohistochemical indicators was estimated.Conclusion. The use of a personalized approach to choosing surgical tactics allows to achieve encouraging results of treatment in geriatric patients with locally advanced colorectal cancer.

SCIENTIFIC PREDICTION OF MAGNESIUM OXIDE NANOPARTICLES TOXICITY AND ASSESSMENT OF ITS HAZARD FOR HUMAN HEALTH

Aim: To study biological effects of magnesium oxide nanoparticles on human health. Methods: Toxicity and potential hazards of magnesium oxide nanoparticles exposure was performed using mathematical models containing data on physical, chemical, molecular biological, biochemical, cytological and ecological properties with calculation of coefficients of hazard (D) and incompleteness of data evaluation (U) of magnesium nanoscale. Size and shape of the nanomaterial were defined using dynamic laser light scattering and scanning electron microscopy. Surface area was determined by the Brunauer, Emmet and Taylor method. Results: Magnesium oxide nanoparticles have a size of 5-100 nm and specific surface area of 64,5 m2/g. They are insoluble in water, can have hydrophobic or hydrophilic properties and have an effective positive charge. They can generate reactive oxygen species, damage DNA, interact with protein structures, destroying cell membrane, cause mitochondrial dysfunction, morphological changes and cell death, impact on proteomic and metabolic profiles, increasing the concentration digestive enzymes, carbohydrates, amino- acid and fatty acids. Besides, the material under investigation has such long-term effects of action: allergenicity, mutagenicity and embryotoxicity. D-coefficient was 1, 872. Conclusions: Magnesium oxide nanoparticles have a high degree of potential hazard for human health. The results warrant toxicological studies and assessment of toxicological-hygienic characteristics of magnesium oxide nanoparticles at various routes of intake for development of effective measures to prevent negative effect of magnesium oxide nanoparticles on human health.

Mycoplasma hafezii sp. nov., isolated from the trachea of a peregrine falcon (Falco peregrinus).

Mycoplasma species are well known pathogens in avian medicine, especially in poultry. However, several Mycoplasma species have been regularly found in the respiratory tract of birds of prey which seem to be commensals in these bird species. In previous studies, an unknown Mycoplasma species which caused false positive results in a Mycoplasma meleagridis-specific PCR, was isolated from a tracheal swab of a clinically healthy, captive, adult peregrine falcon (Falco peregrinus). The isolate appeared in typical fried-egg-shaped colonies on SP4 agar plates and was dependent on sterol for growth. Acid was produced from glucose, but no arginine or urea was hydrolysed. The temperature range for growth was 28-44 °C, with an optimum at 37 °C. Strain M26T was serologically distinct from all species of the genus Mycoplasma with 16S rRNA gene sequence similarity ≥94 %. Biochemical, serological and molecular biological properties demonstrate that this organism represents a novel species of the genus Mycoplasma, for which the name Mycoplasma hafezii sp. nov. is proposed; the type strain is M26T (NCTC 13928, DSM 27652).

Abnormal response of costal chondrocytes to acidosis in patients with chest wall deformity

Costal cartilage is much understudied compared to the load bearing cartilages. Abnormally grown costal cartilages are associated with the inherited chest wall deformities pectus excavatum and pectus carinatum resulting in sunken or pigeon chest respectively. A lack of understanding of the ultrastructural and molecular biology properties of costal cartilage is a major confounder in predicting causes and outcomes of these disorders. Due to the avascular nature of cartilage, chondrocytes metabolize glycolytically, producing an acidic environment. During physical activity hydrogen ions move within cartilage driven by compressive forces, thus at any one time, chondrocytes experience transient changes in pH. A variety of ion channels on chondrocytes plasma membrane equip them to function in the rapidly changing conditions they experience. In this paper we describe reduced expression of the ASIC2 gene encoding the acid sensing ion channel isoform 2 (previously referred to as ACCN1 or ACCN) in patients with chest wall deformities. We hypothesized that chondrocytes from these patients cannot respond normally to changes in pH that are an integral part of the biology of this tissue. Activation of ASICs indirectly creates a cascade ultimately dependent on intracellular calcium transients. The objective of this paper was to compare internal calcium signaling in response to external pH changes in costal chondrocytes from patients with chest wall deformities and healthy individuals. Although the molecular mechanism through which chondrocytes are regulated by acidosis remains unknown, we observed reduced amplitudes of calcium rise in patient chondrocytes exposed to low pH that become further impaired upon repeat exposure.