Orofacial Cleft and Mandibular Prognathism-Human Genetics and Animal Models.

Many complex molecular interactions are involved in the process of craniofacial development. Consequently, the network is sensitive to genetic mutations that may result in congenital malformations of varying severity. The most common birth anomalies within the head and neck are orofacial clefts (OFCs) and prognathism. Orofacial clefts are disorders with a range of phenotypes such as the cleft of the lip with or without cleft palate and isolated form of cleft palate with unilateral and bilateral variations. They may occur as an isolated abnormality (nonsyndromic-NSCLP) or coexist with syndromic disorders. Another cause of malformations, prognathism or skeletal class III malocclusion, is characterized by the disproportionate overgrowth of the mandible with or without the hypoplasia of maxilla. Both syndromes may be caused by the presence of environmental factors, but the majority of them are hereditary. Several mutations are linked to those phenotypes. In this review, we summarize the current knowledge regarding the genetics of those phenotypes and describe genotype-phenotype correlations. We then present the animal models used to study these defects.

Unified Entrainment and Detrainment Closures for Extended Eddy-Diffusivity Mass-Flux Schemes.

We demonstrate that an extended eddy-diffusivity mass-flux (EDMF) scheme can be used as a unified parameterization of subgrid-scale turbulence and convection across a range of dynamical regimes, from dry convective boundary layers, through shallow convection, to deep convection. Central to achieving this unified representation of subgrid-scale motions are entrainment and detrainment closures. We model entrainment and detrainment rates as a combination of turbulent and dynamical processes. Turbulent entrainment/detrainment is represented as downgradient diffusion between plumes and their environment. Dynamical entrainment/detrainment is proportional to a ratio of a relative buoyancy of a plume and a vertical velocity scale, that is modulated by heuristic nondimensional functions which represent their relative magnitudes and the enhanced detrainment due to evaporation from clouds in drier environment. We first evaluate the closures off-line against entrainment and detrainment rates diagnosed from large eddy simulations (LESs) in which tracers are used to identify plumes, their turbulent environment, and mass and tracer exchanges between them. The LES are of canonical test cases of a dry convective boundary layer, shallow convection, and deep convection, thus spanning a broad rangeof regimes. We then compare the LES with the full EDMF scheme, including the new closures, in a single-column model (SCM). The results show good agreement between the SCM and LES in quantities that are key for climate models, including thermodynamic profiles, cloud liquid water profiles, and profiles of higher moments of turbulent statistics. The SCM also captures well the diurnal cycle of convection and the onset of precipitation.

H3K18Ac as a Marker of Cancer Progression and Potential Target of Anti-Cancer Therapy.

Acetylation and deacetylation are posttranslational modifications (PTMs) which affect the regulation of chromatin structure and its remodeling. Acetylation of histone 3 at lysine placed on position 18 (H3K18Ac) plays an important role in driving progression of many types of cancer, including breast, colon, lung, hepatocellular, pancreatic, prostate, and thyroid cancer. The aim of this review is to analyze and discuss the newest findings regarding the role of H3K18Ac and acetylation of other histones in carcinogenesis. We summarize the level of H3K18Ac in different cancer cell lines and analyze its association with patients' outcomes, including overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Finally, we describe future perspectives of cancer therapeutic strategies based on H3K18 modifications.

Novel Mutation of the RUNX2 Gene in Patients with Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder linked to mutations in the Runt-related transcription factor 2, encoded by the RUNX2 gene, which is essential for osteoblast differentiation and skeletal development. Here, we describe a novel nonsense mutation (c.532C>T; p.Q178X) in RUNX2 identified in 3 affected members of a Polish family with CCD. The localization and transcriptional transactivation studies show that the mutated form of the protein has altered the subcellular localization and significantly decreased transactivation properties, respectively. Consequently, our data show that the c.532C>T mutation generates a defective RUNX2 protein and is genetically linked to the CCD phenotype.