Genomic characterization of γ-terpinene synthase from Thymus caespititius

Planta Medica ◽  
2011 ◽  
Vol 77 (12) ◽  
Author(s):  
AS Lima ◽  
B Lukas ◽  
J Novak ◽  
AC Figueiredo ◽  
LG Pedro ◽  
...  
2020 ◽  
Vol 20 (7) ◽  
pp. 490-500 ◽  
Author(s):  
Justin S. Becker ◽  
Amir T. Fathi

The genomic characterization of acute myeloid leukemia (AML) by DNA sequencing has illuminated subclasses of the disease, with distinct driver mutations, that might be responsive to targeted therapies. Approximately 15-23% of AML genomes harbor mutations in one of two isoforms of isocitrate dehydrogenase (IDH1 or IDH2). These enzymes are constitutive mediators of basic cellular metabolism, but their mutated forms in cancer synthesize an abnormal metabolite, 2- hydroxyglutarate, that in turn acts as a competitive inhibitor of multiple gene regulatory enzymes. As a result, leukemic IDH mutations cause changes in genome structure and gene activity, culminating in an arrest of normal myeloid differentiation. These discoveries have motivated the development of a new class of selective small molecules with the ability to inhibit the mutant IDH enzymes while sparing normal cellular metabolism. These agents have shown promising anti-leukemic activity in animal models and early clinical trials, and are now entering Phase 3 study. This review will focus on the growing preclinical and clinical data evaluating IDH inhibitors for the treatment of IDH-mutated AML. These data suggest that inducing cellular differentiation is central to the mechanism of clinical efficacy for IDH inhibitors, while also mediating toxicity for patients who experience IDH Differentiation Syndrome. Ongoing trials are studying the efficacy of IDH inhibitors in combination with other AML therapies, both to evaluate potential synergistic combinations as well as to identify the appropriate place for IDH inhibitors within existing standard-of-care regimens.


2021 ◽  
pp. 198465
Author(s):  
Pengjun Han ◽  
Yunjia Hu ◽  
Xiaoping An ◽  
Lihua Song ◽  
Huahao Fan ◽  
...  

2021 ◽  
Vol 13 (4) ◽  
pp. 2289
Author(s):  
Mateja Janeš ◽  
Minja Zorc ◽  
Maja Ferenčaković ◽  
Ino Curik ◽  
Peter Dovč ◽  
...  

Balkan Livestock Guardian Dogs (LGD) were bred to help protect sheep flocks in sparsely populated, remote mountainous areas in the Balkans. The aim of this study was genomic characterization (107,403 autosomal SNPs) of the three LGD breeds from the Balkans (Karst Shepherd, Sharplanina Dog, and Tornjak). Our analyses were performed on 44 dogs representing three Balkan LGD breeds, as well as on 79 publicly available genotypes representing eight other LGD breeds, 70 individuals representing seven popular breeds, and 18 gray wolves. The results of multivariate, phylogenetic, clustering (STRUCTURE), and FST differentiation analyses showed that the three Balkan LGD breeds are genetically distinct populations. While the Sharplanina Dog and Tornjak are closely related to other LGD breeds, the Karst Shepherd is a slightly genetically distinct population with estimated influence from German Shepard (Treemix analysis). Estimated genomic diversity was high with low inbreeding in Sharplanina Dog (Ho = 0.315, He = 0.315, and FROH>2Mb = 0.020) and Tornjak (Ho = 0.301, He = 0.301, and FROH>2Mb = 0.033) breeds. Low diversity and high inbreeding were estimated in Karst Shepherds (Ho = 0.241, He = 0.222, and FROH>2Mb = 0.087), indicating the need for proper diversity management. The obtained results will help in the conservation management of Balkan LGD dogs as an essential part of the specific grazing biocultural system and its sustainable maintenance.


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