Often times we have some data and want to test if a particular statistical model (or model class) is a good fit. For instance, it is common to make normality assumptions about certain kinds of data for simplicity. Nevertheless one must check if these assumptions are reasonable. In Goodness-of-Fit (GoF) testing we strive to check the compatibility of the data with a fixed single model (simple Go...

Notch signaling plays a critical role during development by directing the binary cell fate decision between progenitors and differentiated cells. Previous studies have shown sustained Notch activation in cartilage leads to chondrodysplasia. Genetic evidence indicates that Notch regulates limb bud mesenchymal stem cell differentiation into chondrocytes via an Rbpj-dependent Notch pathway. Howeve...

Missense mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase SHP-2, cause clinically similar but distinctive disorders, LEOPARD (LS) and Noonan (NS) syndromes. The LS is an autosomal dominant disorder with pleomorphic developmental abnormalities including lentigines, cardiac defects, short stature and deafness. Biochemical analyses indicated that LS alleles engender los...

Troponin C (TnC) is implicated in the initiation of myocyte contraction via binding of cytosolic Ca²⁺ and subsequent recognition of the Troponin I switch peptide. Mutations of the cardiac TnC N-terminal regulatory domain have been shown to alter both calcium binding and myofilament force generation. We have performed molecular dynamics simulations of engineered TnC variants that increase or dec...

Gain-of-function (GOF) mutations in the pore-forming (Kir6.2) and regulatory (SUR1) subunits of KATP channels have been identified as the most common cause of human neonatal diabetes mellitus. The critical effect of these mutations is confirmed in mice expressing Kir6.2-GOF mutations in pancreatic β cells. A second KATP channel pore-forming subunit, Kir6.1, was originally cloned from the pancre...

TRPV4 is a polymodal cation channel gain-of-function (GOF) allele which causes skeletal dysplasia in humans. To better understand its gating, we screened for additional GOF alleles based on their ability to block yeast proliferation. Repeatedly, only a limited number of such growth-blocking mutations were isolated. Expressed in oocytes, wild-type channels can be strongly activated by either hyp...

The common symbiosis pathway is at the core of symbiosis signaling between plants and soil microbes. In this pathway, calcium- and calmodulin-dependent protein kinase (CCaMK) plays a crucial role in integrating the signals both in arbuscular mycorrhizal symbiosis (AMS) and in root nodule symbiosis (RNS). However, the molecular mechanism by which CCaMK coordinates AMS and RNS is largely unknown....

OBJECTIVE The molecular basis of the mutations in the PCSK9 gene that produces familial hypercholesterolemia (FH) in the Turkish population is unknown. This study was conducted to determine the presence of four different PCSK9 gain-of-function (GOF) mutations (F216L, R496W, S127R, and D374Y) in a group of patients with FH. METHODS A total of 80 consecutive patients with FH (mean age: 56±11 ye...

PURPOSE To examine the developmental pathobiology of the eyelid and the cornea caused by epithelial β-catenin gain-of-function (gof) during mouse embryogenesis. METHODS Compound mutant mice (Ctnnb1(GOFOSE) , gof of β-catenin in the epidermis and the ocular surface epithelium) were generated by time-mating keratin 5-promoter-Cre recombinase (Krt5-Cre) and Ctnnb1(fE3/WT) (floxed exon 3 of Ctnnb...

Motivation toward physical exercise (MPE) and trait self-control (TSC) were identified as key predictors of subjective wellbeing (SWB). However, there has not been any research designed to examine the mediating role of TSC in the relationship between MPE and SWB. The present study utilizes self-determination theory, control-process theory of self-regulation, and theory of multiple pathways of T...