MODY 2: Mutation identification and molecular ancestry in a Brazilian family

Maturity Onset Diabetes of the Young (MODY) is a heterogeneous group of genetic diseases characterized by a primary defect in insulin secretion and hyperglycemia, non-ketotic disease, monogenic autosomal dominant mode of inheritance, age at onset less than 25 years, and lack of auto-antibodies. It accounts for 2–5% of all cases of non-type 1 diabetes. MODY subtype 2 is caused by mutations in the glucokinase (GCK) gene. In this study, we sequenced the GCK gene of two volunteers with clinical diagnosis for MODY2 and we were able to identify four mutations including one for a premature stop codon (c.76C>T). Based on these results, we have developed a specific PCR-RFLP assay to detect this mutation and tested 122 related volunteers from the same family. This mutation in the GCK gene was detected in 21 additional subjects who also had the clinical features of this genetic disease. In conclusion, we identified new GCK gene mutations in a Brazilian family of Italian descendance, with one due to a premature stop codon located in the second exon of the gene. We also developed a specific assay that is fast, cheap and reliable to detect this mutation. Finally, we built a molecular ancestry model based on our results for the migration of individuals carrying this genetic mutation from Northern Italy to Brazil.     

Phosphoproteome Profiling of the Receptor Tyrosine Kinase MuSK Identifies Tyrosine Phosphorylation of Rab GTPases

Muscle-specific receptor tyrosine kinase (MuSK) agonist antibodies were developed 2 decades ago to explore the benefits of receptor activation at the neuromuscular junction. Unlike agrin, the endogenous agonist of MuSK, agonist antibodies function independently of its coreceptor low-density lipoprotein receptor–related protein 4 to delay the onset of muscle denervation in mouse models of ALS. Here, we performed dose–response and time-course experiments on myotubes to systematically compare site-specific phosphorylation downstream of each agonist. Remarkably, both agonists elicited similar intracellular responses at known and newly identified MuSK signaling components. Among these was inducible tyrosine phosphorylation of multiple Rab GTPases that was blocked by MuSK inhibition. Importantly, mutation of this site in Rab10 disrupts association with its effector proteins, molecule interacting with CasL 1/3. Together, these data provide in-depth characterization of MuSK signaling, describe two novel MuSK inhibitors, and expose phosphorylation of Rab GTPases downstream of receptor tyrosine kinase activation in myotubes.     

Accumulation of agmatine in chayote (Sechium edule) leaves during development

Arginine, agmatine, putrescine and spermidine were found in the apical parts and leaves of chayote ( Sechium edule Swartz ) at various stages of development. The concentration of agmatine, the immediate decarboxylation product of L-arginine, increased considerably in young leaves at the first emergence of floral buds. Young leaves always had a relatively higher content of agmatine than older ones. There was a decrease in the concentration of agmatine from the apical part to the basal leaves. Agmatine was the predominant amine in young leaves at every stage of development (50–90% of the whole amine pool). It was also predominant in mature leaves when the floral buds appeared (70% of the total amine content). An accumulation of agmatine could not be found in other Cucurbitaceae species.     

Hepatic DNAJB9 Drives Anabolic Biasing to Reduce Steatosis and Obesity

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Albino inflorescence proliferation of Dendrocalamus latiflorus

Summary Inflorescence proliferation is a plant tissue culture technique that, can be used to obtain in vitro inflorescences year-round without the intervening development of vegetative organs. In this study, we used albino mutant inflorescences of Dendrocalamus latiflorus as the original explant material to investigate, the effect of plant growth regulators on long-term inflorescence proliferation. The albino inflorescences proliferated on solidified Murashige and Skoog (MS) basal medium supplemented with thidiazuron (TDZ), and the optimal concentration for successful long-term inflorescence proliferation was 0.45 μM TDZ. A combination of α-naphthaleneacetic acid (NAA) with 0.45 μM TDZ inhibited the inflorescence proliferation. Inflorescences cultured on a TDZ-free medium supplemented with 26.82 μM NAA rooted in 21 d, vegetative shoots formed by 42 d and, in one case, flowering occurred after 63 d. The auxins 2,4-dichlorophenoxyacetic acid (2,4-D, 4.52 μM) and pieloram (4.14 μM) induced shoot formation. The protocol described can be used to produce large numbers of mutant inflorescences within a relatively short period of time.     

Glycoalkaloids of Solanum Series Megistacrolobum and related potato cultigens

Glycoalkaloids were used as evidence of the affinities of nine taxa of Solanum Series Megistacrolobum and related potato cultigens from western Bolivia. S. boliviense, S. sanctae-rosae and S. toralapanum contain the commertetraose sugar moiety and appear to represent a relatively wild group within the Series. S. megistacrolobum, S. sogarandinum and S. raphanifolium show anomolous glycoalkaloid profiles that probably reflect hybridization associated with human disturbance. Primitive forms of the S. χ ajanhuiri cultigen are indistinguishable chemicaliy from conspecific weeds that were previously classified as S. megistacrolobum. Variation in total glycoalkaloid content within Series Megistacrolobum likely reflects direct selection by humans for reduced glycoalkaloid levels during the domestication process.     

Alkylphenol hydroxylases in the oxidation of p-cresol, 4-ethylphenol and 4-n-propylphenol by Pseudomonas putida JD1

Abstract Growth of Pseudomonas putida JD1 on 4-ethylphenol results in the production of the flavocytochrome c, 4-ethylphenol methylenehydroxylase. Both p -cresol and 4- n -propylphenol are substrates for this enzyme. 4-Ethylphenol methylenehydroxylase is also produced by the organism when grown with 4- n -propylphenol. However, when grown with p -cresol, a different hydroxylase is produced which shows greater activity towards p -cresol than towards 4-ethylphenol, and is not active towards 4- n -propylphenol.     

Allogibberic acid: An inhibitor of flowering in Lemna perpusilla

Allogibberic acid (I) has been identified as the compound responsible for the inhibition of flowering, increase in frond multiplication rate and decrease in frond size produced in Lemna perpusilla 6746 by autoclaved, unbuffered aqueous solutions of gibberellic acid (VII). 13-Deoxyallogibberic acid (IV), a product of autoclaving aq. GA₇ (VIII) solutions, also inhibits flowering in L. perpusilla and is about 10 times more active than allogibberic acid.     

Abundance of mRNAs encoding HMG1/HMG2 class high-mobility-group DNA-binding proteins are differentially regulated in cotyledons of Pharbitis nil

The abundance of an mRNA encoding an HMG1/2 protein from Pharbitis nil (HMG1) has been previously shown to be regulated by light and an endogenous rhythm in cotyledons. A second Pharbitis nil HMG cDNA (HMG2) was characterized. The sequence of HMG2 was 82% and 86% identical to HMG1 at the nucleotide and amino acid level, respectively. As with HMG1, HMG2 mRNA was detected in all vegetative tissues and was most abundant in roots. However, unlike HMG1, HMG2 mRNA abundance did not increase upon transfer of cotyledons to darkness and did not exhibit regulation by an endogenous circadian rhythm when maintained in continuous darkness over a 68 h period. Similarly, while the abundance of HMG1 mRNA during a dark period that induced photoperiodically controlled flowering was dramatically affected by brief light exposure (night break), this treatment had no effect on HMG2 mRNA abundance. Collectively, these data are consistent with a role of HMG1 in contributing to the circadian-regulated and/or dark-regulated gene expression with constitutive expression of HMG2 playing a housekeeping role in the general regulation of gene expression in Pharbitis nil cotyledons.