Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire

2021 ◽  
Vol 219 (2) ◽  
Author(s):  
Danielle J. Dauphars ◽  
Ariana Mihai ◽  
Liuyang Wang ◽  
Yuan Zhuang ◽  
Michael S. Krangel
Keyword(s):  
Regulatory Elements ◽  
V Gene

The Tcra repertoire is generated by multiple rounds of Vα-Jα rearrangement. However, Tcrd recombination precedes Tcra recombination within the complex Tcra-Tcrd locus. Here, by ablating Tcrd recombination, we report that Tcrd rearrangement broadens primary Vα use to diversify the Tcra repertoire in mice. We reveal that use of Trav15-dv6 family V gene segments in Tcrd recombination imparts diversity in the Tcra repertoire by instigating use of central and distal Vα segments. Moreover, disruption of the regions containing these genes and their cis-regulatory elements identifies the Trav15-dv6 family as being responsible for driving central and distal Vα recombinations beyond their roles as substrates for Tcrd recombination. Our study demonstrates an indispensable role for Tcrd recombination in general, and the Trav15-dv6 family in particular, in the generation of a combinatorially diverse Tcra repertoire.

Elevated Levels of Prothrombin Activation Fragment 1+2 in Plasma from Patients with Heterozygous Arg506 to Gin Mutation in the Factor V Gene (APC-Resistance) and/or Inherited Protein S Deficiency

1996 ◽  
Vol 75 (02) ◽  
pp. 270-274 ◽  
Author(s):  
Benget Zöller ◽  
Johan Holm ◽  
Peter Svensson ◽  
Björn Dahlbäck
Keyword(s):  
Plasma Concentration ◽  
Protein C ◽  
Protein S ◽  
Factor V ◽  
Protein S Deficiency ◽  
Apc Resistance ◽  
S Deficiency ◽  
Increased Risk ◽  
Factor V Gene ◽  
V Gene

SummaryInherited resistance to activated protein C (APC-resistance), caused by a point mutation in the factor V gene leading to replacement of Arg(R)506 with a Gin (Q), and inherited protein S deficiency are associated with functional impairment of the protein C anticoagulant system, yielding lifelong hypercoagulability and increased risk of thrombosis. APC-resistance is often an additional genetic risk factor in thrombosis-prone protein S deficient families. The plasma concentration of prothrombin fragment 1+2 (F1+2), which is a marker of hyper-coagulable states, was measured in 205 members of 34 thrombosis-prone families harbouring the Arg506 to Gin mutation (APC-resistance) and/or inherited protein S deficiency. The plasma concentration of F1+2 was significantly higher both in 38 individuals carrying the FV:Q506 mutation in heterozygous state (1.7 ± 0.7 nM; mean ± SD) and in 48 protein S deficient cases (1.9 ± 0.9 nM), than in 100 unaffected relatives (1.3 ±0.5 nM). Warfarin therapy decreased the F1+2 levels, even in those four patients who had combined defects (0.5 ± 0.3 nM). Our results agree with the hypothesis that individuals with APC-resistance or protein S deficiency have an imbalance between pro- and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state.

A Novel Polymorphism in Exon 10 of the Factor V Gene Inducing an Amino Acid Replacement of Arginine to Lysine at Codon 485

1997 ◽  
Vol 78 (05) ◽  
pp. 1419-1420 ◽  
Author(s):  
Tetsuo Ozawa ◽  
Kenji Niiya ◽  
Naoko Ejiri ◽  
Nobuo Sakuragawa
Keyword(s):  
Amino Acid ◽  
Amino Acid Replacement ◽  
Factor V ◽  
Factor V Gene ◽  
V Gene ◽  
Exon 10

Hungarian small business tax and possibilities to minimize distortions from capital income taxation

2015 ◽  
Vol 37 (s1) ◽  
pp. 87-105
Author(s):  
Benedek Nobilis ◽  
András Svraka
Keyword(s):  
Small Business ◽  
Cash Flow ◽  
Capital Accumulation ◽  
Value Added ◽  
Regulatory Elements ◽  
Capital Income ◽  
Potential Growth ◽  
Elegant Method ◽  
Business Tax ◽  
Working Out

Governments throughout the EU and OECD countries rely on revenues raised on capital income. Albeit several arguments can be made for keeping these taxes, in their widespread form they hinder capital accumulation and significantly lower potential growth due to their savings and investment distorting nature. At the same time, the actual economic impact of tax types is largely influenced by their structure. An elegant method, which is also simple in its concept, for eliminating the economic distortions of profit taxes is cash-flow taxation which moves income taxes closer to the more growth-friendly value-added taxes. The small business tax, which was introduced in Hungary in 2013, was designed along these principles. In this paper we review the theoretical literature on cash-flow taxation and discuss the main regulatory elements of the small business tax, as well as the solutions elaborated for working out the challenges related to its implementation.

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