Familial hypomagnesaemia, Hypercalciuria and Nephrocalcinosis associated with a novel mutation of the highly conserved leucine residue 116 of Claudin 16 in a Chinese patient with a delayed diagnosis: A case report

Background: Sixty mutations of claudin 16 coding gene have been reported in familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) patients. Recent investigations revealed that a highly conserved glycine-leucine-tryptophan (115G-L-W117) motif in the first extracellular segment (ESC1) of claudin 16 might be essential for stabilization of the appropriately folded ECS1 structure and conservation of normal claudin 16 function. However, neither missense nor nonsense mutation has ever been described in this motif. Our study aimed at identifying mutations in a Chinese patient with FHHNC and exploring the association between genotype and phenotype. Case presentation: A 33-year-old female presented with 4 years history of recurrent acute pyelonephritis without other notable past medical history. Her healthy parents, who aged 56 and 53 respectively, were second cousins, and her only sibling died from renal failure without definite cause at age 25. Renal ultrasound imaging demonstrated atrophic kidneys and bilateral nephrocalcinosis. The laboratory workup revealed impaired renal function (Stage CKD IV), hypocalcemia and mild hypomagnesemia, accompanied with marked renal loss of magnesium and hypercalciuria. During the follow-up, treatment with calcitriol and calcium but not with magnesium was difficult to achieve normal serum calcium levels, whereas her serum magnesium concentration fluctuated within normal ranges. In the end, the patient unavoidably reached ESRD at 36 years old. The clinical features and family history suggested the diagnosis of FHHNC. To make a definite diagnosis, we use whole-exome sequencing to identify the disease-causing mutations and Sanger sequencing to confirm the mutation co-segregation in the family. As a result, a novel homozygous mutation (c.346C > G, p.Leu116Val) in115G-L-W117motif of claudin 16 was identified. Her parents, grandmother and one of her cousins carried heterozygous p.Leu116Val, whereas 200 unrelated controls did not carry this mutation. Conclusions: We described a delayed diagnosis patient with FHHNC in the Chinese population and identified a novel missense mutation in the highly conserved115G-L-W117motif of claudin 16 for the first time. According to the reported data and the information deduced from 3D modeling, we speculate that this mutation probably reserve partial residual function which might be related to the slight phenotype of the patient

Identification of a novel TSC2 c.3610G > A, p.G1204R mutation contribute to aberrant splicing in a patient with classical tuberous sclerosis complex: a case report

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in any organ systems. Mutations in the TSC1 or TSC2 gene lead to the dysfunction of hamartin or tuberin proteins, which cause tuberous sclerosis complex. Case presentation: We describe the clinical characteristics of patients from a Chinese family with tuberous sclerosis complex and analyze the functional consequences of their causal genetic mutations. A novel heterozygous mutation (c.3610G > A) at the last nucleotide of exon 29 in TSC2 was identified. On the protein level, this variant was presumed to be a missense mutation (p.Gly1204Arg). However, the splicing assay revealed that this mutation also leads to the whole TSC2 exon 29 skipping, besides the wild-type transcript. The mutated transcript results in an in-frame deletion of 71 amino acids (p.Gly1133_Thr1203del) and its ratio with the normal splice product is of about 44:56. Conclusions: The novel c.3610G > A TSC2 mutation was identified in association with tuberous sclerosis complex. And it was proven to code both for a missense-carrying transcript (56%), and for an isoform lacking exon 29 (44%)

Effect of solid solution treatment on microstructure and mechanical properties of extruded MgY12Zn2,5 magnesium alloys

The microstructural evolution of MgY12Zn2,5 magnesium alloys was observed, and the strengthening and toughening mechanism of the alloys were studied. The results showed that the MgY12Zn2,5 alloy after solution treatment with higher content of 14H - LPSO (long - period stacking - ordered structures) could more effectively inhibit the recrystallization and growth of recrystallized grains, and the microstructure was more fine and uniform. And its tensile strength (Rm), yield strength (Rv) were 395 MPa, 308 MPa and elongation (A) 17,5 %, respectively. In contrast, the MgY12Zn2,5 alloy treated at 470 °C for 24 h, whose Rm, Rv, were only 376 MPa, 282 MPa and A 15,5 %, respectively

Universal behavior of giant electroresistance in epitaxial La0.67Ca0.33MnO3 thin films

We report a giant resistance drop induced by dc electrical currents in La0.67Ca0.33MnO3 epitaxial thin films. Resistance of the patterned thin films decreases exponentially with increasing current and a maximum drop shows at the temperature of resistance peak Tp. Variation of resistance with current densities can be scaled below and above Tp, respectively. This work can be useful for the future applications of electroresistance.Comment: 13 pages, 4 figure

Rapid and high capacity methane storage in clathrate hydrates using surfactant dry solution

Surfactant dry solution (DS) was prepared by mixing sodium dodecyl sulfate (SDS) solution, hydrophobic silica nanoparticles and air in a high speed blender. Flour-like SDS-DS combines the advantages of dispersed dry water and active SDS solution. Methane storage in clathrate hydrates using SDS-DS was investigated in a stainless steel vessel without stirring under the condition of 5.0MPa and 273.2K. The results demonstrated that highly dispersed SDS-DS could significantly enhance formation kinetics and storage capacity of methane hydrate. SDS-DS exhibited about the same methane storage capacity (172.96m3 m-3) as dry water, but faster storage rates than dry water. Compared to SDS solution, SDS-DS had similar storage rates (7.44m3 m-3 min-1) and higher methane storage capacity under the relative low pressure. However, the aggregation of partial SDS-DS powders destroyed its original dispersive property after hydrate dissociation

Inelastic current-voltage characteristics of atomic and molecular junctions

We report first-principles calculations of the inelastic current-voltage (I-V) characteristics of a gold point contact and a molecular junction in the nonresonant regime. Discontinuities in the I-V curves appear in correspondence to the normal modes of the structures. Due to the quasi-one-dimensional nature of these systems, specific modes with large longitudinal component dominate the inelastic I-V curves. In the case of the gold point contact, our results are in good agreement with recent experimental data. For the molecular junction, we find that the inelastic I-V curves are quite sensitive to the structure of the contact between the molecule and the electrodes thus providing a powerful tool to extract the bonding geometry in molecular wires.Comment: 4 pages, 3 figure

Efficiency of Energy Conversion in Thermoelectric Nanojunctions

Using first-principles approaches, this study investigated the efficiency of energy conversion in nanojunctions, described by the thermoelectric figure of merit $ZT$. We obtained the qualitative and quantitative descriptions for the dependence of $ZT$ on temperatures and lengths. A characteristic temperature: $T_{0}= \sqrt{\beta/\gamma(l)}$ was observed. When $T\ll T_{0}$, $ZT\propto T^{2}$. When $T\gg T_{0}$, $ZT$ tends to a saturation value. The dependence of $ZT$ on the wire length for the metallic atomic chains is opposite to that for the insulating molecules: for aluminum atomic (conducting) wires, the saturation value of $ZT$ increases as the length increases; while for alkanethiol (insulating) chains, the saturation value of $ZT$ decreases as the length increases. $ZT$ can also be enhanced by choosing low-elasticity bridging materials or creating poor thermal contacts in nanojunctions. The results of this study may be of interest to research attempting to increase the efficiency of energy conversion in nano thermoelectric devices.Comment: 2 figure