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In all domains of life, the nucleobases of tRNA can be methylated. These methylations are introduced either by enzymes or by the reaction of methylating agents with the nucleophilic centers of the nucleobases. Herein, we present a systematic approach to identify the methylation sites within RNA in vitro and in vivo. For discrimination between enzymatic tRNA methylation and tRNA methylation damage in bacteria, we used nucleic acid isotope labeling coupled mass spectrometry (NAIL‐MS). With NAIL‐MS, we clearly observed the formation of 7‐methylguanosine, 3‐methyluridine, and 6‐methyladenosine during exposure of bacteria to the alkylating agent methyl methanesulfonate (MMS) in vivo. These damage products were not reported to form in tRNA in vivo, as they were masked by the enzymatically formed modified nucleosides in previous studies. In addition, we found formation of the known damage products 1‐methyladenosine and 3‐methylcytidine in vivo. With a dynamic NAIL‐MS setup, we observed tRNA repair by demethylation of these two RNA modifications in vivo. Furthermore, we saw the potential repair of 6‐methyladenosine but not 7‐methylguanosine in bacterial tRNA.

Ribonucleic acid (RNA) is central to many life processes and, to fulfill its function, it has a substantial chemical variety in its building blocks. Enzymatic thiolation of uridine introduces 4‐thiouridine (s4U) into many bacterial transfer RNAs (tRNAs), which is used as a sensor for UV radiation. A similar modified nucleoside, 2‐thiocytidine, was recently found to be sulfur‐methylated especially in bacteria exposed to antibiotics and simple methylating reagents. Herein, we report the synthesis of 4‐methylthiouridine (ms4U) and confirm its presence and additional formation under stress in Escherichia coli. We used the synthetic ms4U for isotope dilution mass spectrometry and compared its abundance to other reported tRNA damage products. In addition, we applied sophisticated stable‐isotope pulse chase studies (NAIL‐MS) and showed its AlkB‐independent removal in vivo. Our findings reveal the complex nature of bacterial RNA damage repair., Through a combination of synthetic and analytical chemistry, the structure of the modified nucleoside 4‐methylthiouridine was confirmed in bacterial tRNA. The modification is of low abundance and forms after bacterial stress induced by methylating agents; this argues for its nature as a natural tRNA lesion. By pulse chase analysis, we show its repair through a dethiomethylation mechanism in vivo.

The post-2015 development agenda requires improved concepts to define and measure different forms of poverty and inequality. Building on the experiences made with the Millennium Development Goals, this paper gives an overview of several possible approaches by discussing their strengths and weaknesses. National, international, relative and multidimensional concepts are considered. Arguing that the discussions on the post-2015 agenda offer an opportunity to introduce new global measurements of progress that complement gross domestic product-based approaches, the authors make the case for a simple yet comprehensive index as a headline indicator that could help to better inform poverty and inequality reduction policies in the post-2015 world. Copyright © 2015 John Wiley & Sons, Ltd.

Kılıç, Fatma Arzu (Balikesir Author), Uncombable hair syndrome (UHS), also known as “spun glass hair syndrome,” “pili trianguli et canaliculi,” or “cheveux incoiffables” is a rare anomaly of the hair shaft which occurs in children and improves with age. UHS is characterized by dry, frizzy, spangly and often fair hair that is resistant to being combed flat.

Long-lived, sensitive, and specific biomarkers of particular mutagenic agents are much sought after and potentially have broad applications in the fields of cancer biology, epidemiology, and prevention. Many clastogens induce a spectrum of chromosome aberrations, and some of them can be exploited as biomarkers of exposure. Densely ionizing radiation, for example, alpha particle radiation (from radon or plutonium) and neutron radiation, preferentially induces complex chromosome aberrations, which can be detected by the 24-color multifluor fluorescence in situ hybridization (mFISH) technique. We report the detection and quantification of stable complex chromosome aberrations in lymphocytes of healthy former nuclear-weapons workers, who were exposed many years ago to plutonium, gamma rays, or both, at the Mayak weapons complex in Russia. We analyzed peripheral-blood lymphocytes from these individuals for the presence of persistent complex chromosome aberrations. A significantly elevated frequency of complex chromosome translocations was detected in the highly exposed plutonium workers but not in the group exposed only to high doses of gamma radiation. No such differences were found for simple chromosomal aberrations. The results suggest that stable complex chromosomal translocations represent a long-lived, quantitative, low-background biomarker of densely ionizing radiation for human populations exposed many years ago.

For a T × n matrix A = ‖ aij‖ in GF(2) we define a hypergraph GA with n vertices and T hyperedges et = {j: atj = 1}, t = 1,…, T. Denote at = (atn),t= 1,…, T. A set of row numbers {t1,…,tm} is called a critical set if the sum of vectors at1 + … + at m is the zero vector. In terms of hypergraph GA a critical set can be interpreted as a hypercycle. We can naturally definite the concept of independence for critical sets. Let s(A) be the maximal number of independent critical sets in A. The rank r(A) of the matrix A and s(A) are connected by the equality r(A) + s(A) = T. The total number of critical sets S(A) is equalt 2s(A) −1. Consider the folowing system of T random equations in GF(2): where i1(t.…,i(t), i = 1,…,T are indepndent identically distributed random variables which take values 1,…., n with equal probabilities. Denote Ar, n, T the matrix of this system. We prove that the number S(Ar,n,T) of critical sets in Ar, n, T or hypercycles in GAr,n,T has a threshold property. Let n, T→∞ and T/n→ α. Then for any fixed integer r ⩾ 3 there exists a constant α, such that MS(Ar,n,T)→0 if α α αr. © 1994 John Wiley & Sons, Inc.