Structural and biochemical analysis of the unique interactions of the Campylobacter jejuni CorA channel protein with divalent cations.

CorA is a Mg2+ channel that plays a key role in the homeostasis of intracellular Mg2+ in bacteria and archaea. CorA consists of a cytoplasmic domain and a transmembrane domain and generates a Mg2+ pathway by forming a pentamer in the cell membrane. CorA gating is regulated via negative feedback by Mg2+, which is accommodated by the pentamerization interface of the CorA cytoplasmic domain (CorACD). The Mg2+-binding sites of CorACD differ depending on the species, suggesting that the Mg2+-binding modes and Mg2+-mediated gating mechanisms of CorA vary across prokaryotes. To define the Mg2+-binding mechanism of CorA in the Campylobacter jejuni pathogen, we structurally and biochemically characterized C. jejuni CorACD (cjCorACD). cjCorACD adopts a three-layered α/ß/α structure as observed in other CorA orthologs. Interestingly, cjCorACD exhibited enhanced thermostability in the presence of Ca2+, Ni2+, Zn2+, or Mn2+ in addition to Mg2+, indicating that cjCorACD interacts with diverse divalent cations. This cjCorACD stabilization is mediated by divalent cation accommodation by negatively charged residues located at the bottom of the cjCorACD structure away from the pentamerization interface. Consistently, cjCorACD exists as a monomer irrespective of the presence of divalent cations. We concluded that cjCorACD binds divalent cations in a unique pentamerization-independent manner.

Transcatheter pulmonary valve replacement in surgically-created double-barrel right ventricular outflow tracts: A single center case-series.

This manuscript describes the feasibility and approach to the assessment and performance of transcatheter pulmonary valve replacement (tPVR) in patients with surgically-created "double-barrel" right ventricular outflow tracts (RVOT). Patients with tetralogy of Fallot may have coronary anomalies which prohibit the performance of traditional tetralogy of Fallot repair. In certain cases, this may necessitate the placement of a right ventricle to pulmonary artery conduit in addition to the native RVOT, which is left in situ, creating so-called "double-barrel" RVOTs. When these patients develop RVOT dysfunction later in life, they would typically be referred for reoperation due to concerns for risk of coronary compression associated with a transcatheter approach. However, whether a transcatheter approach with valve replacement in the native RVOT is feasible or safe is unknown. This was a retrospective review of patients with a surgically created "double-barrel" RVOTs who underwent cardiac catheterization for assessment of tPVR at Boston Children's Hospital. From July 2012 to July 2022, there were four patients with "double-barrel" RVOTs who underwent assessment for tPVR. The age at catheterization ranged between 22 and 39 years. In three out of four patients, coronary compression testing was negative. These three patients had successful tPVR in the native RVOT. At follow up, all three patients were free of greater than mild regurgitation by echocardiogram and had a maximum instantaneous gradient across the RVOT ranging between 20 and 33 mmHg. Performance of tPVR in patients with surgically created "double-barrel" RVOTs is feasible. The safety of this procedure depends crucially on coronary artery assessment at all stages.

Soft Tissue Structures at Risk With a Percutaneous Focal Dome Osteotomy: A Cadaver Study.

The focal dome osteotomy allows deformity correction through frontal plane rotation, and if needed, anterior or posterior translation. This percutaneous technique allows extracapsular ankle realignment with minimal soft tissue dissection. While circumventing a standard anterior incision, this technique encounters soft tissue structures that must be considered. Focal dome osteotomies were simulated on 10 fresh-frozen below the knee cadavers. Centered proximal to the tibial plafond at the physeal scar, a radial arm using a 4-hole Rancho cube was used to map the dome. Medial, lateral, and central incisions were made to allow access for drilling and measured to nearby anatomic structures. Among 10 cadavers, the age and weight were 70 ± 7.96 years and 134.7 ± 30.8 pounds, respectively. In all cadavers, the hole below the most proximal posthole provided the ideal position for the creation of the osteotomy. The medial and central incisions were closest to the tibialis anterior tendon measuring 3.37 ± 2.48 mm and 0.43 ± 0.9 mm, respectively. The lateral incision and half-pin used to create the distal axis of rotation were closest to the extensor hallucis longus tendon, measuring 1.97 ± 1.92 mm and 1.27 ± 1.5 mm, respectively. Drilling the second hole from the top on a 4-hole Rancho cube, forming a 2.50 cm radial arm, created the ideal osteotomy arc. Though neurovascular structures were further away from respective incision and half-pin sites compared to tendons, in several specimens, anatomic variations held them closer, warranting preoperative handheld Doppler and mapping. Care should be taken to protect anterior ankle anatomy during dissection, drilling, and completing the osteotomy.

Acute coronary syndrome in an anomalous mid-LAD right coronary artery: Don't forget to look twice before turning left.

A 68-year-old female with past medical history of hypertension, hyperlipidemia, multiple sclerosis, diverticulitis, and tobacco use presented with 1 day of atypical chest pain after a recent diverticulitis flare. Initial workup was notable for a normal electrocardiogram but elevated high sensitivity troponin T (616 ng/L). Due to persistent symptoms, the patient was given antiplatelet therapy and taken urgently to the catheterization lab where she was found to have complete occlusion of an anomalous right coronary artery branching off the mid-left anterior descending artery. Angioplasty was performed with a drug-eluting stent and her symptoms resolved. The patient recovered well and was discharged on appropriate medical therapy. This case demonstrates a case of acute coronary syndrome in an extremely rare coronary congenital abnormality. Further research is needed on when to be suspicious for coronary anomalies on patients presenting with myocardial infarction.

Grape juice reduces the effects of amyloid ß aggregation phenotype and extends the longevity in Caenorhabditis elegans.

OBJECTIVES: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence of aggregated amyloid-ß (Aß) peptides. Several natural compounds have been proposed against this disease and grape products are among these. However, little is known about grape juice potential. Transgenic Caenorhabditis elegans (C. elegans) strains that express human Aß have been used as an in vivo model for AD. METHODS: In this study, we have exposed CL2006 worms to nine different juices obtained from different cultivars. RESULTS: Cora, Bordo, Isabel, Isabel Precoce, BRS-Magna, BRS-Rubea and BRS-Violeta juices improved the behavioral phenotype (paralysis) that is caused by Aß aggregation in the transgenic animals at the concentrations tested and no toxic effects were found. Some juices were also able to increase the worm's lifespan. We could not attribute lifespan increase and paralysis reduction with any specific compound found in the phytochemical analysis. DISCUSSION: Our data indicate that the rich constitution of the juices is responsible for attenuating the phenotype caused by Aß aggregation in C. elegans.

Combinational Regularity Analysis (CORA) - a new method for uncovering complex causation in medical and health research.

BACKGROUND: Modern configurational comparative methods (CCMs) of causal inference, such as Qualitative Comparative Analysis (QCA) and Coincidence Analysis (CNA), have started to make inroads into medical and health research over the last decade. At the same time, these methods remain unable to process data on multi-morbidity, a situation in which at least two chronic conditions are simultaneously present. Such data require the capability to analyze complex effects. Against a background of fast-growing numbers of patients with multi-morbid diagnoses, we present a new member of the family of CCMs with which multiple conditions and their complex conjunctions can be analyzed: Combinational Regularity Analysis (CORA). METHODS: The technical heart of CORA consists of algorithms that have originally been developed in electrical engineering for the analysis of multi-output switching circuits. We have adapted these algorithms for purposes of configurational data analysis. To demonstrate CORA, we provide several example applications, both with simulated and empirical data, by means of the eponymous software package CORA. Also included in CORA is the possibility to mine configurational data and to visualize results via logic diagrams. RESULTS: For simple single-condition analyses, CORA's solution is identical with that of QCA or CNA. However, analyses of multiple conditions with CORA differ in important respects from analyses with QCA or CNA. Most importantly, CORA is presently the only configurational method able to simultaneously explain individual conditions as well as complex conjunctions of conditions. CONCLUSIONS: Through CORA, problems of multi-morbidity in particular, and configurational analyses of complex effects in general, come into the analytical reach of CCMs. Future research aims to further broaden and enhance CORA's capabilities for refining such analyses.

Realignment Midfoot Osteotomy: A Preoperative Planning Method and Intraoperative Surgical Technique.

Deformities of the midfoot are often treated with midfoot osteotomies. The goal of the midfoot osteotomy is to create a plantigrade forefoot to hindfoot relationship. Many different techniques are described for performing midfoot osteotomies. Our goal is to present an objective pre-operative planning method and an intra-operative technique for accurate multiplanar realignment and discuss our short-term results. We retrospectively reviewed 18 patients, 10 female (56%) and 8 male (44%), that underwent realignment midfoot osteotomies. The mean follow-up was 25 months (range, 4-120). The mean age at the time of surgery was 53 years (range, 21-76). Statistically significant improvement in radiographic alignment was found in the anteroposterior talo-first metatarsal angle (p = .002) and the mechanical axis deviation of the foot (p = .02). This study proved that our pre-operative and intra-operative planning technique provides accurate multiplanar radiographic realignment with good clinical results.

Functional analysis of whether the glycine residue of the GMN motif of the Arabidopsis MRS2/MGT/CorA-type Mg2+ channel protein AtMRS2-11 is critical for Mg2+ transport activity.

Magnesium (Mg2+) plays a critical role in many physiological processes. The AtMRS2/MGT family, which contains nine Arabidopsis genes (and two pseudogenes), belongs to a eukaryotic subset of the CorA superfamily of divalent cation transporters. AtMRS2-11/MGT10 possesses the signature GlyMetAsn sequence (the GMN motif) conserved in the CorA superfamily; however, little is known about the role of the GMN motif in AtMRS2. Direct measurement using the fluorescent dye mag-fura-2 revealed that reconstituted AtMRS2-11 mediated rapid Mg2+ uptake into proteoliposomes at extraliposomal Mg2+ concentrations of 10 and 20 mM. Mutations in the GMN motif, G417 to A, S or V, did not show a significant change in Mg2+ uptake relative to the wild-type protein. The G417W mutant exhibited a significant increase in Mg2+ uptake. The functional complementation assay in Escherichia coli strain TM2 showed that E. coli cells expressing AtMRS2-11 with mutations in G of the GMN motif did not grow in LB medium without Mg2+ supplementation, while growth was observed in LB medium supplemented with 0.5 mM Mg2+; no difference was observed between the growth of TM2 cells expressing the AtMRS2-11 G417W mutant and that of cells expressing wild-type AtMRS2-11. These results suggested that the Mg2+ transport activity of the AtMRS2-11 GMN-motif mutants was low at low physiological Mg2+ concentrations; thus, the Gly residue is critical for Mg2+ transport, and the Mg2+ transport activity of the GMN-motif mutants was increased at high Mg2+ concentrations.

Effectiveness of an Avatar application for teaching heart attack recognition and response: A pragmatic randomized control trial.

AIMS: To evaluate the effectiveness of an Avatar application for educating people with acute coronary syndrome (heart attack). BACKGROUND: A lack of understanding of Acute Coronary Syndrome symptoms and appropriate responses often contribute to delay in seeking medical treatment. DESIGN: A single-centre, non-blinded, pragmatic randomized controlled trial. METHODS: Seventy Acute Coronary Syndrome patients were randomly assigned to the intervention (Avatar application) or usual care groups. Participants were followed up at 0, 1, and 6 months. Tobit Growth Curve Model was used to analyse the primary outcome-symptom knowledge; and the secondary outcomes-attitudes and beliefs. Heart attack action plan implementation and health care utilisation were analysed using Chi-square and Mann-Whitney U test. RESULTS: Of the 70 participants, 63% were male and the mean age of the participants was 64.7 (SD 11.7) years. Sixty-six (94.2%) participants completed follow-up. Between group differences on acute coronary syndrome (ACS) Response Index scores were statistically significant at 1-month and 6-month follow-ups (p < .01). The intervention group had a significant improvement in symptom knowledge, attitudes, and beliefs over the 6-month period (p < .001, p = .009, p < .001 respectively); and no significant improvement in the usual care group participants (p = .152, p = .068, p = .228). For healthcare use, at follow-up, there was a significant difference in ambulance use, between the intervention group and the usual care group (33.33% vs. 18.18%, p = .008; cardiac: 88.89% vs. 42.86%; p = .049); 85.14% of participants reported that the application helped them to feel more confident in recognizing and responding to symptoms in the future. CONCLUSION: The education app was effective in improving individuals' ACS knowledge, attitudes, and beliefs. A large multi-centre trial with a longer follow-up to evaluate the intervention's effectiveness on clinical outcomes will be our next step in evaluation. IMPACT: The content of AVATARS (Nurse Cora) app can be translated into different languages and evaluated for patients from different health settings and linguistic backgrounds. TRIAL REGISTRATION: This study has been registered with Australian New Zealand Clinical Trials Registry (ANZCTR). The trial registration number is ACTRN12616000803493.

Inhibition of CorA-Dependent Magnesium Homeostasis Is Cidal in Mycobacterium tuberculosis.

Mechanisms of magnesium homeostasis in Mycobacterium tuberculosis are poorly understood. Here, we describe the characterization of a pyrimidinetrione amide scaffold that disrupts magnesium homeostasis in the pathogen by direct binding to the CorA Mg2+/Co2+ transporter. Mutations in domains of CorA that are predicted to regulate the pore opening in response to Mg2+ ions conferred resistance to this scaffold. The pyrimidinetrione amides were cidal against the pathogen under both actively replicating and nonreplicating conditions in vitro and were efficacious against the organism during macrophage infection. However, the compound lacked efficacy in infected mice, possibly due to limited exposure. Our results indicate that inhibition of Mg2+ homeostasis by CorA is an attractive target for tuberculosis drug discovery and encourage identification of improved CorA inhibitors.

Mg2+ homeostasis and transport in cyanobacteria - at the crossroads of bacterial and chloroplast Mg2+ import.

Magnesium cation (Mg2+) is the most abundant divalent cation in living cells, where it is required for various intracellular functions. In chloroplasts and cyanobacteria, established photosynthetic model systems, Mg2+ is the central ion in chlorophylls, and Mg2+ flux across the thylakoid membrane is required for counterbalancing the light-induced generation of a ΔpH across the thylakoid membrane. Yet, not much is known about Mg2+ homoeostasis, transport and distribution within cyanobacteria. However, Mg2+ transport across membranes has been studied in non-photosynthetic bacteria, and first observations and findings are reported for chloroplasts. Cyanobacterial cytoplasmic membranes appear to contain the well-characterized Mg2+ channels CorA and/or MgtE, which both facilitate transmembrane Mg2+ flux down the electrochemical gradient. Both Mg2+ channels are typical for non-photosynthetic bacteria. Furthermore, Mg2+ transporters of the MgtA/B family are also present in the cytoplasmic membrane to mediate active Mg2+ import into the bacterial cell. While the cytoplasmic membrane of cyanobacteria resembles a 'classical' bacterial membrane, essentially nothing is known about Mg2+ channels and/or transporters in thylakoid membranes of cyanobacteria or chloroplasts. As discussed here, at least one Mg2+ channelling protein must be localized within thylakoid membranes. Thus, either one of the 'typical' bacterial Mg2+ channels has a dual localization in the cytoplasmic plus the thylakoid membrane, or another, yet unidentified channel is present in cyanobacterial thylakoid membranes.

Magnesium uptake characteristics in Arabidopsis revealed by 28Mg tracer studies.

MAIN CONCLUSION: The Mg2+ uptake system in Arabidopsis roots is Gd3+- and Fe2+-sensitive, and responds to a changing Mg2+ concentration within 1 h with the participation of AtMRS2 transporters. Magnesium (Mg2+) absorption and the mechanism regulating its activity have not been clarified yet. To address these issues, it is necessary to reveal the characteristics of Mg2+ uptake in roots. Therefore, we first investigated the Mg2+ uptake characteristics in roots of 1-week-old Arabidopsis plants using 28Mg. The Mg2+ uptake system in roots was up-regulated within 1 h in response to the low Mg2+ condition. This induction was inhibited in Arabidopsis "mitochondrial RNA splicing 2/magnesium transport" mutants atmrs2-4/atmgt6 and atmrs2-7/atmgt7, while the expression of AtMRS2-4/AtMGT6 and AtMRS2-7/AtMGT7 genes in the Arabidopsis wild-type was not responsive to Mg2+ conditions. In addition, the Mg deficiency-induced Mg2+ uptake system was shut-down within 5 min when Mg2+ was resupplied to the environment. An inhibition study showed that the constitutive mechanism functioning in Mg2+ uptake under Mg2+ sufficient conditions was sensitive to a number of divalent and trivalent cations, particularly Gd3+ and Fe2+, but not to K+.

Anatomic spectrum of left coronary artery anomalies and associated mechanisms of coronary insufficiency.

This is a novel re-appraisal of an understudied and misunderstood group of important coronary anomalies. The general name of the group is "anomalous origin of the left coronary artery," but several additional details should be included in this group of anomalies and the explanation of their pathophysiology. The most lethal form in young athletes or military recruits features intramural aortic proximal course. This comprehensive review is based on a large experience at a dedicated center for coronary artery anomalies, using evolving knowledge (over 20 years) while employing prospective and disciplined programs of evaluation and treatment, according to the nature and severity of each anomaly. The most common pathogenic mechanism of coronary dysfunction relates to intramural coronary course, with or without ectopic origin, leading to variable lateral compression and stenosis inside the aortic tunica media; this compression is present at rest and worsens with exertion. We propose that such variable and dynamic stenoses can be best studied by examining their specific anatomy and clinical presentation, stress testing, and, most importantly, in vivo evaluation by intravascular ultrasonography. Such methods should be used to support individual risk evaluation and selection among treatment options.

Triplane Hallux Abducto Valgus Classification.

One of the most common procedures performed in the foot and ankle is correction of hallux abducto valgus deformity or "bunion surgery." Most foot and ankle surgeons recognize the challenges associated with defining each patient's individual deformity and selecting the optimal procedure for the best long-term results. Using current 2-dimensional algorithms that focus on the severity of the transverse plane deformity, surgical outcomes have varied. In the past 10 years, high recurrence and complication rates for popular procedures have been reported. In the same period, the reported data have elucidated an evolving anatomic understanding of the bunion deformity, with an expansion to 3 dimensions, including the frontal/coronal plane. We present a new classification and approach for the evaluation and procedure selection for bunion surgery. We hope this conceptual treatise on hallux abducto valgus based on clinical consensus and current data will stimulate academic discussion and further research. This anatomic classification is based on the 3-dimensional anatomy of the first ray.

The maize CorA/MRS2/MGT-type Mg transporter, ZmMGT10, responses to magnesium deficiency and confers low magnesium tolerance in transgenic Arabidopsis.

KEY MESSAGE: ZmMGT10 was specifically expressed in maize roots and induced by a deficiency of magnesium. Overexpression of ZmMGT10 restored growth deficiency of the Salmonella typhimurium MM281 strain and enhanced the tolerance in Arabidopsis to stress induced by low magnesium levels by increasing uptake of Mg2+ via roots. CorA/MRS2/MGT-type Mg2+ transporters play a significant role in maintaining magnesium (Mg) homeostasis in plants. Although the maize CorA/MRS2/MGT family comprises of 12 members, currently no member has been functionally characterized. Here, we report the isolation and functional characterization of ZmMGT10 from the maize MRS2/MGT gene family. ZmMGT10 has a typical structure feature which includes two conserved TMs near the C-terminal end and an altered AMN tripeptide motif. The high sequence similarity and close phylogenetic relationship indicates that ZmMGT10 is probably the counterpart of Arabidopsis AtMGT6. The complementation of the Salmonella typhimurium mutated MM281 strain indicates that ZmMGT10 possesses the ability to transport Mg2+. ZmMGT10 was specifically expressed in the plant roots and it can be stimulated by a deficiency of Mg. Transgenic Arabidopsis plants which overexpressed ZmMGT10 grew more vigorously than wild-type plants under low Mg conditions, exhibited by longer root length, higher plant fresh weight and chlorophyll content, suggesting ZmMGT10 was essential for plant growth and development under low Mg conditions. Further investigations found that high accumulation of Mg2+ occurred in transgenic plants attributed to improved Mg2+ uptake and thereby enhanced tolerance to Mg deficiency. Results from this investigation illustrate that ZmMGT10 is a Mg transporter of maize which can enhance the tolerance to Mg deficient conditions by improving Mg2+ uptake in the transgenic plants of Arabidopsis.

Identification, and Functional and Expression Analyses of the CorA/MRS2/MGT-Type Magnesium Transporter Family in Maize.

Magnesium (Mg(2+)) is an essential macronutrient for plant growth and development, and the CorA/MRS2/MGT-type Mg(2+) transporters play important roles in maintaining Mg(2+) homeostasis in plants. Although the MRS2/MGT genes have been identified in two model plant species, Arabidopsis and rice, a comprehensive analysis of the MRS2/MGT gene family in other plants is lacking. In this work, 12 putative MRS2/MGT genes (ZmMGT1- ZmMGT12) were identified in maize and all of them were classified into five distinct subfamilies by phylogenetic analysis. A complementation assay in the Salmonella typhimurium MM281 strain showed that five representatives of the 12 members possess Mg(2+) transport abilities. Inhibition of ZmMGT protein activity using the hexaamminecobalt (III) (Co-Hex) inhibitor indicated that the ZmMGT protein mediated both low-affinity and high-affinity Mg(2+) transport in maize. A semi-quantitative reverse transcription-PCR (RT-PCR) analysis revealed that eight genes were constitutively expressed in all of the detected tissues, with one being specifically expressed in roots and three having no detectable expression signals. A quantitative RT-PCR analysis showed that some ZmMGT members displayed differential responses to Mg(2+) deficiency and aluminum (Al) stress. Furthermore, root growth inhibition and Mg(2+) accumulation analyses in two maize inbred lines, which conferred different levels of Al tolerance, revealed that ZmMGT proteins contributed to the Al resistance of the Al tolerance genotype. We hypothesize that ZmMGT family members function as Mg(2+) transporters and may play a role in linking Mg(2+) deficiency and Al stress responses. Our results will be valuable in a further analysis of the important biological functions of ZmMGT members in maize.

Bioactive compounds of juices from two Brazilian grape cultivars.

BACKGROUND: Grape juice consumption may prevent several chronic diseases owing to the presence of phenolic compounds, which have an important role in the reduction of oxidative stress. This study investigated the polyphenol content and antioxidant activities of grape juices from two cultivars: BRS-Cora and Isabella. Total polyphenol content (TPC), anthocyanins, antioxidant capacity (oxygen radical absorbance capacity, ferric reducing antioxidant power and 1,1-diphenyl-2-picrylhydrazyl), and phenolic profile (high-performance liquid chromatography with diode array and fluorescence detection--HPLC-DAD-FLD) were determined. RESULTS: BRS-Cora grape juice showed higher concentrations of total polyphenols and anthocyanins, as well as higher antioxidant potential, than those of Isabella grape juice. A significant positive correlation was found in TPC or anthocyanin contents when correlated with the remaining antioxidant assays. In addition, HPLC-DAD-FLD showed a higher total phenolic content in BRS-Cora grape juice compared to Isabella. CONCLUSION: The present results show BRS-Cora as a promising cultivar for grape juice production with an improved functional potential.

Focal dome osteotomy for correction of varus deformity at elbow in children.

BACKGROUND: Cubitus varus is the most common complication of un-treated or mal-treated supracondylar fracture of humerus at elbow. Various osteotomies have been described to correct this deformity but each is associated with its own complications. In this study, focal dome osteotomy for correction of cubitus varus was performed to determine its functional and radiological outcome. MATERIALS AND METHOD: In this study, 35 children with cubitus varus deformity were admitted from Jan 2009- Jan 2013. Clinical assessment was done before the procedure by measuring the carrying angle at elbow joint. Radiographic assessment of deformity was done by anteroposterior (AP) radiographs of the elbow by measuring the humeral-ulnar angle (HUA) and metaphyseal-diaphyseal angle (MDA). Through anterolateral approach, supracondylar region of humerus was exposed and focal dome osteotomy was done at the center of rotation of angulation (CORA). Final assessment was done clinically for carrying angle and radiologically for HUA and MDA at 8 weeks to evaluate the functional and radiological outcome as good or poor. RESULTS: The mean age of 35 children at the time of surgery was (mean ± SD 8.03 ± 2.35) with range from 5 - 12 years, Male to female ratio was 1.50:1. The mean duration of injury was (170.26 ± 41.78) days. The functional outcome for carrying angle improved from 1.49 ± 5.95 to 14.46 ±1.44 with p value <0.05. Radiological outcome for humeral-ulnar and metaphyseal-diaphyseal angle improved from 27.71 ± 4.31 to 17.77 ± 1.23 and 103.66 ± 4.76 to 90.49 ± 1.96 with p value <0.05 respectively. The final Functional and Radiological outcome was good in 32 patients (91%) and poor in 3 patients (9%). CONCLUSIONS: Focal dome osteotomy is safe and stable method of correction of cubitus varus which avoids prominence of lateral condyle and is cosmetically acceptable.

The structure and regulation of magnesium selective ion channels.

The magnesium ion (Mg(2+)) is the most abundant divalent cation within cells. In man, Mg(2+)-deficiency is associated with diseases affecting the heart, muscle, bone, immune, and nervous systems. Despite its impact on human health, little is known about the molecular mechanisms that regulate magnesium transport and storage. Complete structural information on eukaryotic Mg(2+)-transport proteins is currently lacking due to associated technical challenges. The prokaryotic MgtE and CorA magnesium transport systems have recently succumbed to structure determination by X-ray crystallography, providing first views of these ubiquitous and essential Mg(2+)-channels. MgtE and CorA are unique among known membrane protein structures, each revealing a novel protein fold containing distinct arrangements of ten transmembrane-spanning α-helices. Structural and functional analyses have established that Mg(2+)-selectivity in MgtE and CorA occurs through distinct mechanisms. Conserved acidic side-chains appear to form the selectivity filter in MgtE, whereas conserved asparagines coordinate hydrated Mg(2+)-ions within the selectivity filter of CorA. Common structural themes have also emerged whereby MgtE and CorA sense and respond to physiologically relevant, intracellular Mg(2+)-levels through dedicated regulatory domains. Within these domains, multiple primary and secondary Mg(2+)-binding sites serve to staple these ion channels into their respective closed conformations, implying that Mg(2+)-transport is well guarded and very tightly regulated. The MgtE and CorA proteins represent valuable structural templates to better understand the related eukaryotic SLC41 and Mrs2-Alr1 magnesium channels. Herein, we review the structure, function and regulation of MgtE and CorA and consider these unique proteins within the expanding universe of ion channel and transporter structural biology.

Variability of Corylus avellana, L. CorA and profilin pollen allergens expression.

Corylus avellana is the source of inhalant allergies induced by hazel pollen as well as food allergies induced after ingestion of hazelnuts. In this study, real-time PCR approach was used to analyse expression of hazel pollen allergens on the molecular level. Relative quantity of hazelnut allergens Corylus avellana, L. CorA and Corylus avellana, L. pollen profiling in samples from different Ukraine areas were determining and comparing. Differences among the levels of both analysed allergen transcripts were found for hazel CorA and profillin. In both cases, the expression within the urbanized growth conditions was higher when compared to the sample from village area. The average expression for CorA was 0.84 times higher than for profilin and the results are very variable depending on the place of growth. Expression levels here were within the range of 2.957 up to the 52.936. Profilin expression was the highest in the sample from the polluted place of growth-cement plant area with the value of 52 times higher when compared to the sample from the village area. In this study, comparison of expression levels of hazel CorA and profiling pollen allergens was performed for the first time. Real-time PCR assay developed in this study proved the sensitivity for detection of the changes of the hazel pollen allergens expression levels and could benefit labs by fast and reproducible detection method of these allergens.