Alternative Sites Research Articles

Comparison Between Distal Trans-radial Access and Conventional Trans-radial Access for Coronary Angiography.

Background Compared with a conventional wrist puncture for radial artery catheterization, a distal radial artery puncture has the advantage of reducing the incidence of radial artery occlusion (RAO). Aim The present study was designed to evaluate the feasibility of distal trans-radial access compared with conventional trans-radial access for coronary angiography. Methods A prospective, randomized, single-blinded, comparative study was conducted at a tertiary care center in India between December 2018 and November 2020. A total of 420 patients (aged >18 years) with signs and symptoms suggestive of coronary artery disease (CAD) and with a palpable radial artery in anatomical snuffbox were randomized into two groups. Group A comprised patients accessed at the distal trans-radial site, and Group B consisted of patients accessed at the conventional trans-radial site for coronary angiography. Baseline demographics, clinical history, and risk factors for CAD were documented. Procedural-related parameters and complications were compared between the two groups. Results The procedural success rate was non-significant between Group A and Group B (96% vs. 98%; p=0.38). Puncture in a single attempt was higher in Group B compared to Group A (92% vs. 78%; p<0.001). There was no significant difference between Group A and Group B for operation time (p=0.207), fluoroscopy time (p=0.183), and contrast volume (p=0.345). The rate of RAO was higher in Group B compared to Group A (13% vs. 2%; p<0.001). Radial artery hematoma/swelling at the puncture site between Group A (10%) and Group B (8%) was not significant (p=0.61). Post-procedural hemostasis time in Group A was 28 ± 7.86 minutes, and in Group B was 24 ± 6.23 minutes. Both post-procedural persistence of pain (p<0.001) and hand clumsiness (p<0.001) were significantly higher in Group B compared to Group A. Conclusion For coronary angiography, the distal trans-radial access site is a reliable and secure alternate access site.

Categorizing Patient Selection, Outcomes, and Indications in a Decade of 405 Profunda Artery Perforator Flaps.

Autologous tissue is the only permanent option for breast reconstruction. Whereas abdominal tissue remains popular, considering alternative donor sites ensures comprehensive care tailored to a patient. The thigh has been established as an excellent choice in autologous reconstruction. The authors present a 10-year experience with 405 profunda artery perforator (PAP) flaps. An institutional review board-approved 10-year retrospective review of all patients treated with PAP flaps for breast reconstruction was performed. Procedures were carried out by 2 surgeons at the same institution. PAP flaps were divided into 4 consecutive groups with approximately 100 flaps in each group. Demographics, indications, intraoperative data, postoperative complications, revisions, and patient-reported outcomes were recorded and analyzed. A total of 207 patients (405 PAP flaps) were included. This accounted for 17.2% of all breast reconstruction flaps. A total of 55% of patients underwent a multiflap procedure. The average flap weight was 354.3 g (±117.2), which decreased significantly over time ( P < 0.001). Rates of major complications were 9.6% wounds, 4.4% seromas, 4.7% hematomas, and 3.5% infections. Total flap loss was 2%, 67% of which were in stacked cases. Satisfaction routinely improved from before to after surgery. As available flap donor sites continue to evolve, tailoring breast reconstruction to the individual patient is standard in centers of excellence. The PAP flap has emerged as an excellent choice for autologous-based breast reconstruction through use of proper patient selection and surgical technique. Therapeutic, IV.

Assignment of product ions produced from ciguatoxin-3C provides a deep insight into the fragmentation mechanism of polycyclic ether compounds.

Marine polycyclic ethers have drawn attention owing to their unique chemical structures and involvement in food poisoning and fish killing. To study structural diversity, we performed a structural assignment of product ions produced from a representative ladder-shaped polycyclic ether, ciguatoxin-3C, and elucidated the mechanism of generation. The product ions used for the structural assignment were produced from a precursor ion [M + H]+ using liquid chromatography/quadrupole time-of-flight mass spectrometry, by employing an atmospheric pressure chemical ionization source. Three charged sites were considered at both terminals of a molecule. Typical charge-remote fragmentation was produced at the respective charge sites, yielding a hybrid spectrum. C-C bonds bordering two ethers could cleave and trigger the fission of two other bonds. Prominent ions indicating the serial loss of water molecules resulted from the simultaneous deprivation of ethereal oxygen and hydrogen atoms. The resultant double bonds formed long chains of conjugated polyenes, which stabilized charge via resonance. Three alternative charge sites produce a hybrid spectrum. The simultaneous fission of three bonds was explained. For the first time, intense ions due to serial dehydration were explained by the elimination of ether oxygen atoms and the subsequent conjugation of double bonds. All product ions were considered by the structural features of polycyclic ether that facilitates the formation of conjugated polyenes.

Efektivitas Monitoring Glukosa Darah dengan Pengambilan Sampel di Telapak Tangan Terhadap Penurunan Nyeri Akibat Tusukan Jarum pada Pasien Diabetes Mellitus

This literature study aims to determine Effectiveness of Blood Glucose Monitoring by Sampling on the Palm of the Hand in Reducing Needlestick Pain in Diabetes Mellitus Patients. The research design is a systematic review, using 6 databases, ProQuest, EMBASE, SpringerLink, Sage Journals, Scopus and Taylor and Francis. A total of 10 articles were reviewed from 2010 to 2022. The keywords used in the literature search were Diabetes Mellitus AND Blood Glucose AND pain AND palm site AND fingertip. The protocol and literature review evaluation used the Critical Appraisal Skills Program issued by the JBI Guideline. The results of the study showed that the palms of the hands as blood glucose sampling sites were effective in reducing pain due to needle pricks in patients with diabetes mellitus. In addition, pain can also be minimized by adjusting the diameter of the lancet and the depth of the puncture and using the latest technology/method for testing blood glucose. In conclusion, palms as an alternative site for blood glucose sampling are effective in reducing pain due to needle pricks in patients with diabetes mellitus.&#x0D; &#x0D; Keywords: Diabetes Mellitus, Blood Glucose, Pain, Palms, Fingertips

Comprehensive Genetic Analysis Unraveled the Missing Heritability and a Founder Variant of BEST1 in a Chinese Cohort With Autosomal Recessive Bestrophinopathy.

To describe the genetic landscape of BEST1 for a large Chinese cohort with autosomal recessive bestrophinopathy (ARB), identify the missing heritability, and report a common Chinese founder variant. We recruited 65 patients from 63 families with a clinical diagnosis of ARB. All patients underwent ophthalmic examinations and comprehensive genetic analyses, including Sanger DNA sequencing of BEST1 and whole genome sequencing (WGS). The effects of deep intronic variants (DIVs) on splicing were assessed using in vitro splicing assays in HEK293T cells and patient-derived peripheral blood mononuclear cells. Haplotype mapping was performed for 17 unrelated patients harboring variant c.867+97G>A. We identified 54 distinct disease-causing variants of BEST1 in 63 pedigrees, 62probands with biallelic variants, and one family with monoallelic variants. Sanger DNA sequencing of BEST1 initially detected 51 variants in 61 pedigrees, including 19probands with one heterozygous variant. Subsequent WGS, combined with supplementary Sanger sequencing, revealed three missing DIVs (c.1101-491A>G, c.867+97G>A, and c.867+97G>T) in 20 families. The novel DIV c.1101-491A>G caused an abnormal splicing resulting in a 204-nt pseudoexon (PE) insertion, whereas c.867+97G>A/T relatively strengthened an alternative donor site, resulting in a 203-nt intron retention (IR). The PE and IR generated a premature termination codon downstream. Haplotype analysis identified c.867+97G>A as a common founder variant with an allele frequency of 16%. Our results expand the pathogenic variant spectrum of BEST1, and DIVs can explain almost all of the missing heritability. The c.867+97G>A DIV is a common founder variant for Chinese patients with ARB.

RNA binding motif protein 45-mediated phosphorylation enhances protein stability of ASCT2 to promote hepatocellular carcinoma progression.

Targeting metabolic remodeling represents a potentially promising strategy for hepatocellular carcinoma (HCC) therapy. In-depth understanding on the regulation of the glutamine transporter alanine-serine-cysteine transporter 2 (ASCT2) contributes to the development of novel promising therapeutics. As a developmentally regulated RNA binding protein, RBM45 is capable to shuttle between nucleus and cytoplasm, and directly interacts with proteins. By bioinformatics analysis, we screened out that RBM45 was elevated in the HCC patient specimens and positively correlated with poor prognosis. RBM45 promoted cell proliferation, boosted xenograft tumorigenicity and accelerated HCC progression. Using untargeted metabolomics, it was found that RBM45 interfered with glutamine metabolism. Further results demonstrated that RBM45 positively associated with ASCT2 in human and mouse specimens. Moreover, RBM45 enhanced ASCT2 protein stability by counteracting autophagy-independent lysosomal degradation. Significantly, wild-type ASCT2, instead of phospho-defective mutants, rescued siRBM45-suppressed HCC cell proliferation. Using molecular docking approaches, we found AG-221, a mutant isocitrate dehydrogenase 2 (mIDH2) inhibitor for acute myeloid leukemia therapy, pharmacologically perturbed RBM45-ASCT2 interaction, decreased ASCT2 stability and suppressed HCC progression. These findings provide evidence that RBM45 plays a crucial role in HCC progression via interacting with and counteracting the degradation of ASCT2. Our findings suggest a novel alternative structural sites for the design of ASCT2 inhibitors and the agents interfering with RBM45-ASCT2 interaction may be a potential direction for HCC drug development.

Alternative Chromophore Binding Sites in Non-Covalent Fluorescent Complexes of Bacterial Lipocalin

The three-dimensional structure of DiB3, a fluorescent non-covalent complex of a genetically engineered variant of the bacterial protein lipocalin Blc with a synthetic GFP-like chromophore M739, was determined by the calculation method of molecular mechanics. Compared to the crystal structure of the related DiB1 complex, an alternative binding site for the M739 chromophore was found in the structure of the DiB3 complex.

Bone Shell Technique with Relocated Crestal Ridge Segment for Anterior Horizontal Mandibular Ridge Atrophy: A Case Series.

Horizontal and vertical ridge augmentation via the bone shell technique provides predictable outcomes. The external oblique ridge is the most-used donor site for bone plate harvesting, followed by the mandibular symphysis. The lateral sinus wall and the palate have also been described as alternative donor sites. This preliminary case series reports a bone shell technique that used the coronal segment of the knife-edge ridge as a bone shell in five consecutive edentulous patients (20 sites) with severe mandibular horizontal ridge atrophy and adequate ridge height. The follow-up period was 1 to 4 years. The average horizontal bone gains at 1 mm and 5 mm below the newly formed ridge crest were 3.6 ± 0.76 mm and 3.4 ± 0.92 mm, respectively. Ridge volume was sufficiently restored in all patients to enable implant placement in a staged approach. In 2 of the 20 sites, additional hard tissue grafts were required at implant placement. The advantages of utilizing the relocated crestal ridge segment are as follows: The donor and recipient sites are the same, no major anatomical structures are compromised, periosteal releasing incisions and flap advancement are not required for primary wound closure, and the risk of wound dehiscence is minimized due to reduced muscle tension.

The Effect Of Dıfferent Body Posıtıons On Calf Blood Pressure: A Cross-Sectional Study

The calf area is an alternative measurement site when blood pressure cannot be measured at the arm. To determine the effects of different body positions on calf blood pressure readings in healthy young students. A total of 100 healthy young students who agreed to participate in the study were randomly selected. The study was carried out in Aydın Adnan Menderes University Nursing Faculty. In all participants, blood pressure was measured in four positions: supine, prone, right lateral, and left lateral recumbent. All measurements were performed three times at 1-min intervals, and the results were compared. There was no statistically significant difference between the systolic and diastolic blood pressure measurements in the supine and prone positions (p&gt;0.05). The systolic blood pressure value was significantly lower in the left lateral recumbent position than in the other positions (p

Transcriptional diversity of the oxytocin receptor in prairie voles: mechanistic implications for behavioral neuroscience and maternal physiology.

The neurohormone oxytocin regulates many aspects of physiology primarily by binding to its receptor, the oxytocin receptor. The oxytocin receptor gene (Oxtr) has been shown to have alternative transcripts in the mouse brain which may each have different biological functions or be used in specific contexts. A popular animal model for studying oxytocin-dependent social behaviors is the prairie vole, a biparental and monogamous rodent. Alternative transcriptional capacity of Oxtr in prairie voles is unknown. We used 5' rapid amplification of cDNA ends to identify alternative Oxtr transcription start sites in prairie vole brain tissue and uterine tissue. We then validated expression of specific transcripts in fetal brains and assessed the impact of exogenous oxytocin administration in utero on offspring brain development. We identified seven distinct Oxtr transcripts, all of which are present in both brain and uterine tissue. We then demonstrated that maternal oxytocin administration alters expression of a specific subset of Oxtr transcripts and that these different transcripts are under unique epigenetic regulation, such that in the perinatal period only one of the alternative transcripts is associated with DNA methylation in the Oxtr promoter. These data establish the existence of multiple Oxtr transcripts in prairie vole brain and uterine tissue and implicate oxytocin in the regulation of alternative transcript expression. These data have significant implications for our understanding of null mutant models in both mice and voles and translation in human birth and behavior.

Yeast transcription factor Msn2 binds to G4 DNA.

Sequences capable of forming quadruplex or G4 DNA are prevalent in the promoter regions. The transformation from canonical to non-canonical secondary structure apparently regulates transcription of a number of human genes. In the budding yeast Saccharomyces cerevisiae, we identified 37 genes with a G4 motif in the promoters including 20 genes that contain stress response element (STRE) overlapping a G4 motif. STRE is the binding site of stress response regulators Msn2 and Msn4, transcription factors belonging to the C2H2 zinc-finger protein family. We show here that Msn2 binds directly to the G4 DNA structure through its zinc-finger domain with a dissociation constant similar to that of STRE-binding and that, in a stress condition, Msn2 is enriched at G4 DNA-forming loci in the yeast genome. For a large fraction of genes with G4/STRE-containing promoters, treating with G4-ligands led to significant elevations in transcription levels. Such transcriptional elevation was greatly diminished in a msn2Δ msn4Δ background and was partly muted when the G4 motif was disrupted. Taken together, our data suggest that G4 DNA could be an alternative binding site of Msn2 in addition to STRE, and that G4 DNA formation could be an important element of transcriptional regulation in yeast.

Calcium-Activated Big-Conductance (BK) Potassium Channels Traffic through Nuclear Envelopes into Kinocilia in Ray Electrosensory Cells.

Electroreception through ampullae of Lorenzini in the little skate, Leucoraja erinacea, involves functional coupling between voltage-activated calcium channels (CaV1.3, cacna1d) and calcium-activated big-conductance potassium (BK) channels (BK, kcnma1). Whole-mount confocal microscopy was used to characterize the pleiotropic expression of BK and CaV1.3 in intact ampullae. BK and CaV1.3 are co-expressed in electrosensory cell plasma membranes, nuclear envelopes and kinocilia. Nuclear localization sequences (NLS) were predicted in BK and CaV1.3 by bioinformatic sequence analyses. The BK NLS is bipartite, occurs at an alternative splice site for the mammalian STREX exon and contains sequence targets for post-translational phosphorylation. Nuclear localization of skate BK channels was characterized in heterologously transfected HEK293 cells. Double-point mutations in the bipartite NLS (KR to AA or SVLS to AVLA) independently attenuated BK channel nuclear localization. These findings support the concept that BK partitioning between the electrosensory cell plasma membrane, nucleus and kinocilium may be regulated through a newly identified bipartite NLS.

Alternative Chromophore Binding Sites in Noncovalent Fluorescent Complexes of Bacterial Lipocalin

Alternative Chromophore Binding Sites in Noncovalent Fluorescent Complexes of Bacterial Lipocalin

Feasibility of an endoscope-dominated side-to-end hypoglossal-facial anastomosis: an anatomical study.

A surgical simulation of an endoscope-dominated side-to-end hypoglossal-facial anastomosis was performed to evaluate the feasibility. Eight anatomical cadaver heads (16 sides) were recruited. The steps in conventional procedures were abbreviated or omitted. A facial nerve was first harvested near its external genu and was used for a side-to-end hypoglossal-facial anastomosis. The stump of the used facial nerve was truncated and recycled immediately caudal to the facial recess in another anastomosis and then recycled again at the stylomastoid foramen. As a recycled stump becomes too short to ensure a side-to-end anastomosis, the hypoglossal nerve was transected in situ, and an endoscopic end-to-end hypoglossal-facial anastomosis was attempted. Surgical simulation and quantitative measurement methods were used to analyze the anastomosis effects of different harvested sites of the facial nerve. Several steps in the conventional procedures provide little benefit in endoscopic surgery. A facial nerve stump recycled at the stylomastoid foramen is too short to ensure a tensionless side-to-end anastomosis. An endoscopic end-to-end hypoglossal-facial anastomosis was feasible, although it required more time than the classical microsurgical anastomosis. The greater agility of an endoscope enables the conventional surgical steps to be overlapped or interweaved into the procedure. The multiple surgical fields and ability to manipulate the viewpoint provided by an endoscope have brought about breakthroughs in classical surgical paradigms. In addition, it is best to choose the sites of the facial nerve harvested near the external genu. If unavailable, an alternative section site could be selected immediately caudal to the facial recess, but cannot be distal to the stylomastoid foramen. The length of the stump should be individualized and preferably optimized with a nerve stimulator.

Molecular characterization and expression patterns of a ryanodine receptor in soybean looper, Chrysodeixis includens.

Diamide insecticides, such as chlorantraniliprole, have been widely used to control insect pests by targeting the insect ryanodine receptor (RyR). Due to the efficacious insecticidal activity of diamides, as well as an increasing number of resistance cases, the molecular structure of RyR has been studied in many economically important insects. However, no research has been conducted on diamide resistance and RyR in the soybean looper, Chrysodeixis includens, a significant crop pest. In this study, we found moderate resistance to chlorantraniliprole in a field population from Puerto Rico and sequenced the full-length cDNA of the C. includens RyR gene, which encodes a 5124 amino acid-long protein. Genomic analysis revealed that the CincRyR gene consists of 113 exons, one of the largest exon numbers reported for RyR. Alternative splicing sites were detected in the cytosolic region. The protein sequence showed high similarity to other noctuid RyRs. Conserved structural features included the selectivity filter motif critical for ryanodine binding and ion conduction, as well as various domains involved in ion transport. Two mutation sites associated with diamide resistance in other insects were screened but not found in the Puerto Rico field populations or in the susceptible lab strain. Gene expression analysis indicated high expression of RyR in the third instar larval stage, particularly in muscle-containing tissues. Furthermore, exposure to a sublethal dose of chlorantraniliprole reduced RyR expression levels after 96 h. This study provides a molecular basis for understanding RyR structure and sheds light on potential mechanisms of diamide resistance in C. includens.

Optimal selection of suitable templates in protein interface prediction.

Molecular-level classification of protein-protein interfaces can greatly assist in functional characterization and rational drug design. The most accurate protein interface predictions rely on finding homologous proteins with known interfaces since most interfaces are conserved within the same protein family. The accuracy of these template-based prediction approaches depends on the correct choice of suitable templates. Choosing the right templates in the immunoglobulin superfamily (IgSF) is challenging because its members share low sequence identity and display a wide range of alternative binding sites despite structural homology. We present a new approach to predict protein interfaces. First, template-specific, informative evolutionary profiles are established using a mutual information-based approach. Next, based on the similarity of residue level conservation scores derived from the evolutionary profiles, a query protein is hierarchically clustered with all available template proteins in its superfamily with known interface definitions. Once clustered, a subset of the most closely related templates is selected, and an interface prediction is made. These initial interface predictions are subsequently refined by extensive docking. This method was benchmarked on 51 IgSF proteins and can predict nontrivial interfaces of IgSF proteins with an average and median F-score of 0.64 and 0.78, respectively. We also provide a way to assess the confidence of the results. The average and median F-scores increase to 0.8 and 0.81, respectively, if 27% of low confidence cases and 17% of medium confidence cases are removed. Lastly, we provide residue level interface predictions, protein complexes, and confidence measurements for singletons in the IgSF. Source code is freely available at: https://gitlab.com/fiserlab.org/interdct_with_refinement.

Comparison of radial, dorsalis pedis, and posterior tibial arteries for ultrasound-guided arterial catheterisation with dynamic needle tip positioning in paediatric patients: a randomised controlled trial

BackgroundArterial catheterisation in children can be challenging and time-consuming. We aimed to compare the success rates of ultrasound-guided arterial catheterisation utilising the short-axis out-of-plane approach with dynamic needle tip positioning in the radial, dorsalis pedis, and posterior tibial arteries in paediatric patients. We also examined the factors influencing the catheterisation success using dynamic needle tip positioning. MethodsPaediatric patients (aged <3 yr) undergoing cardiac surgery were randomly assigned to three groups based on puncture sites: radial artery (Group R), dorsalis pedis artery (Group D), and posterior tibial artery (Group P). The first-attempt and overall success rates of arterial catheterisation were compared, followed by multiple logistic regression analysis (dependent variable: first-attempt success; independent variables: body weight, diameter and depth of the artery, targeted artery, and trisomy 21). ResultsThe study included 270 subjects (n=90 per group). There was no significant difference in the first-attempt (Group R: 82%, Group D: 76%, and Group P: 81%) and overall success rates (Group R: 94%, Group D: 93%, and Group P: 91%) among the three groups. The diameter of the artery (per 0.1 mm) (odds ratio: 1.32, 95% confidence interval: 1.09–1.60) and trisomy 21 (odds ratio: 0.43, 95% confidence interval: 0.20–0.92) were independent predictors of first-attempt success or failure. ConclusionThe first-attempt and overall success rates of arterial catheterisation of the dorsalis pedis and posterior tibial arteries were not inferior to those in the radial artery when using dynamic needle tip positioning. These two lower extremity peripheral arteries present viable alternative catheterisation sites in paediatric patients. Clinical trial registrationUMIN000042847.

Heimdall, an alternative protein issued from a ncRNA related to kappa light chain variable region of immunoglobulins from astrocytes: a new player in neural proteome

The dogma “One gene, one protein” is clearly obsolete since cells use alternative splicing and generate multiple transcripts which are translated into protein isoforms, but also use alternative translation initiation sites (TISs) and termination sites on a given transcript. Alternative open reading frames for individual transcripts give proteins originate from the 5′- and 3′-UTR mRNA regions, frameshifts of mRNA ORFs or from non-coding RNAs. Longtime considered as non-coding, recent in-silico translation prediction methods enriched the protein databases allowing the identification of new target structures that have not been identified previously. To gain insight into the role of these newly identified alternative proteins in the regulation of cellular functions, it is crucial to assess their dynamic modulation within a framework of altered physiological modifications such as experimental spinal cord injury (SCI). Here, we carried out a longitudinal proteomic study on rat SCI from 12 h to 10 days. Based on the alternative protein predictions, it was possible to identify a plethora of newly predicted protein hits. Among these proteins, some presented a special interest due to high homology with variable chain regions of immunoglobulins. We focus our interest on the one related to Kappa variable light chains which is similarly highly produced by B cells in the Bence jones disease, but here expressed in astrocytes. This protein, name Heimdall is an Intrinsically disordered protein which is secreted under inflammatory conditions. Immunoprecipitation experiments showed that the Heimdall interactome contained proteins related to astrocyte fate keepers such as “NOTCH1, EPHA3, IPO13” as well as membrane receptor protein including “CHRNA9; TGFBR, EPHB6, and TRAM”. However, when Heimdall protein was neutralized utilizing a specific antibody or its gene knocked out by CRISPR-Cas9, sprouting elongations were observed in the corresponding astrocytes. Interestingly, depolarization assays and intracellular calcium measurements in Heimdall KO, established a depolarization effect on astrocyte membranes KO cells were more likely that the one found in neuroprogenitors. Proteomic analyses performed under injury conditions or under lipopolysaccharides (LPS) stimulation, revealed the expression of neuronal factors, stem cell proteins, proliferation, and neurogenesis of astrocyte convertor factors such as EPHA4, NOTCH2, SLIT3, SEMA3F, suggesting a role of Heimdall could regulate astrocytic fate. Taken together, Heimdall could be a novel member of the gatekeeping astrocyte-to-neuroprogenitor conversion factors.

Early-Onset Aortic Dissection: Characterization of a New Pathogenic Splicing Variation in the MYH11 Gene with Several In-Frame Abnormal Transcripts

Rare pathogenic variants in the MYH11 gene are responsible for thoracic aortic aneurysms and dissections. They are usually heterozygous missense variants or in-frame deletions of several amino acids without alteration of the reading frame and mainly affect the coiled-coil domain of the protein. Variants leading to a premature stop codon have been described in patients with another phenotype, megacystis-microcolon-intestinal hypoperistalsis syndrome, with an autosomal recessive inheritance. The physiopathological mechanisms arising from the different genetic alterations affecting the MYH11 gene are still poorly understood. Consequently, variants of unknown significance are relatively frequent in this gene. We have identified a variant affecting the consensus donor splice site of exon 29 in the MYH11 gene in a patient who suddenly died from an aortic type A dissection at the age of 23 years old. A transcript analysis on cultured fibroblasts has highlighted several abnormal transcripts including two in-frame transcripts. The first one is a deletion of the last 78 nucleotides of exon 29, corresponding to the use of a cryptic alternative donor splice site; the second one corresponds to an exon 29 skipping. Familial screening has revealed that this molecular event occurred de novo in the proband. Taken together, these experiments allowed us to classify this variant as pathogenic. This case underlines the challenging aspect of the discovery of variations in the MYH11 gene for which the consequences on splicing should be systematically studied in detail.

Geophysical surveys in the Kashmir valley (J&K Himalayas) part II: Anomalous seismic site-effects and exploration of alternative site classification schemes

Extensive geophysical surveys (MHVSR and MASW) conducted for the microzonation of the Kashmir Valley, Himalayas, revealed unexpected dynamic characteristics at certain sites pointing out the weak relationship between fundamental frequency (f0) and time-averaged shear wave velocity over 30 m depth (VS,30). Unusual low-frequency amplification at stiff soil sites and high-frequency amplification at weathered rock sites was obtained. On the contrary, high-frequency amplification was attained at a soft soil site over shallow bedrock. Instances of topographic amplification on slopes, hills, and valleys were encountered. Consequently, the commonly used VS,30-based single-proxy site classification failed to explain these atypical site effects, thus underscoring the caution to be exercised for site classification in geologically complex regions. These findings motivated the documentation of the anomalies and the search for the most suitable site characterisation scheme for the geological deposits of the Kashmir Valley. The coupled MHVSR-VS,30 proxy approach accomplished the best results for the study region.