COMPUTATIONAL METHODOLOGY TO ANALYZE THE EFFECT OF MASS TRANSFER RATE ON ATTENUATION OF LEAKED CARBON DIOXIDE IN SHALLOW AQUIFERS

Exsolution and re-dissolution of CO2 gas within heterogeneous porous media are investigated using experimental data and mathematical modeling. In a set of bench-scale experiments, water saturated with CO2 under a given pressure is injected into a 2-D water-saturated porous media system, causing CO2 gas to exsolve and migrate upwards. A layer of fine sand mimicking a heterogeneity within a shallow aquifer is present in the tank to study accumulation and trapping of exsolved CO2. Then, clean water is injected into the system and the accumulated CO2 dissolves back into the flowing water. Simulated exsolution and dissolution mass transfer processes are studied using both nearequilibrium and kinetic approaches and compared to experimental data under conditions that do and do not include lateral background water flow. The mathematical model is based on the mixed hybrid finite element method that allows for accurate simulation of both advection- and diffusion- dominated processes

Gentamicin induces LAMB3 nonsense mutation readthrough and restores functional laminin 332 in junctional epidermolysis bullosa

Herlitz junctional epidermolysis bullosa (H-JEB) is an incurable, devastating, and mostly fatal inherited skin disease for which there is only supportive care. H-JEB is caused by loss-of-function mutations in LAMA3, LAMB3, or LAMC2, leading to complete loss of laminin 332, the major component of anchoring filaments, which mediate epidermal-dermal adherence. LAMB3 (laminin \u3b23) mutations account for 80% of patients with H-JEB, and 3c95% of H-JEB\u2013associated LAMB3 mutations are nonsense mutations leading to premature termination codons (PTCs). In this study, we evaluated the ability of gentamicin to induce PTC readthrough in H-JEB laminin \u3b23-null keratinocytes transfected with expression vectors encoding eight different LAMB3 nonsense mutations. We found that gentamicin induced PTC readthrough in all eight nonsense mutations tested. We next used lentiviral vectors to generate stably transduced H-JEB cells with the R635X and C290X nonsense mutations. Incubation of these cell lines with various concentrations of gentamicin resulted in the synthesis and secretion of full-length laminin \u3b23 in a dose-dependent and sustained manner. Importantly, the gentamicin-induced laminin \u3b23 led to the restoration of laminin 332 assembly, secretion, and deposition within the dermal/epidermal junction, as well as proper polarization of \u3b16\u3b24 integrin in basal keratinocytes, as assessed by immunoblot analysis, immunofluorescent microscopy, and an in vitro 3D skin equivalent model. Finally, newly restored laminin 332 corrected the abnormal cellular phenotype of H-JEB cells by reversing abnormal cell morphology, poor growth potential, poor cell-substratum adhesion, and hypermotility. Therefore, gentamicin may offer a therapy for H-JEB and other inherited skin diseases caused by PTC mutations

The genome of the largest bony fish, ocean sunfish (<i>Mola mola</i>), provides insights into its fast growth rate

BACKGROUND: The ocean sunfish (Mola mola), which can grow up to a length of 2.7 m and weigh 2.3 tons, is the world’s largest bony fish. It has an extremely fast growth rate and its endoskeleton is mainly composed of cartilage. Another unique feature of the sunfish is its lack of a caudal fin, which is replaced by a broad and stiff lobe that results in the characteristic truncated appearance of the fish. RESULTS: To gain insights into the genomic basis of these phenotypic traits, we sequenced the sunfish genome and performed a comparative analysis with other teleost genomes. Several sunfish genes involved in the growth hormone and insulin-like growth factor 1 (GH/IGF1) axis signalling pathway were found to be under positive selection or accelerated evolution, which might explain its fast growth rate and large body size. A number of genes associated with the extracellular matrix, some of which are involved in the regulation of bone and cartilage development, have also undergone positive selection or accelerated evolution. A comparison of the sunfish genome with that of the pufferfish (fugu), which has a caudal fin, revealed that the sunfish contains more homeobox (Hox) genes although both genomes contain seven Hox clusters. Thus, caudal fin loss in sunfish is not associated with the loss of a specific Hox gene. CONCLUSIONS: Our analyses provide insights into the molecular basis of the fast growth rate and large size of the ocean sunfish. The high-quality genome assembly generated in this study should facilitate further studies of this ‘natural mutant’. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13742-016-0144-3) contains supplementary material, which is available to authorized users