Genetic diversity and population structure of Caragana microphylla Lam. based on analysis of inter-simple sequence repeat markers

Caragana microphylla Lam. is a long-lived shrub species in the semi-arid, arid and desert regions. To determine the genetic diversity and population structure of C. microphylla Lam., 17 wild populations from the central and eastern part of Inner Mongolia were analyzed by inter-simple sequence repeat. 18 primers  produced 296 bands across a total of 510 individuals. A high percentage of polymorphic loci was observed at species level (PPB = 81.4%). Based on analysis of molecular variance, 74.99% of the genetic variation of C. microphylla Lam. was found within population, 7% difference between regions and 15.2% among collection  sites within regions. Cluster analyses showed that 17 populations are most arranged in the same cluster by  geographic location. An indirect estimate of the GST-derived Nm value (Nm = 1.8921) indicate that gene flow is high among 17 populations. No significant correlation (r2 = 0.13) between genetic and geographic distance was detected. Results of this study suggest that C. microphylla Lam. has a high genetic variability and potential as a source of variation for breeding programs.Key words: Inter-simple sequence repeat (ISSR), Caragana microphylla Lam., genetic structure

Analysis of genetic diversity in Arrhenatherum elatius Germplasm using inter-simple sequence repeat (ISSR) markers

The genetic diversity of 19 Arrhenatherum elatius accessions was analyzed using 100 inter-simple sequence repeat (ISSR) primers, out of which 11 generated distinct amplification products. Out of the 152 total bands detected, 107 were polymorphic. The percentage of polymorphic bands (PPB) was 68.9% with an average of 9.73 polymorphic bands per primer. The ISSR-based genetic similarity (GS) coefficients among the 19 accessions ranged from 0.4821 to 0.7411, revealing high genetic diversity. Based on the UPGMA cluster analysis and the principal components analysis (PCA), the 19 A. elatius accessions were divided into three groups with similar situations. We found that the genetic distance was related to the geographical distance among the 19 A. elatius accessions studied. These results confirm the potential value of genetic diversity preservation for future breeding programs.Key words: Arrhenatherum elatius, genetic diversity, inter-simple sequence repeat (ISSR) markers

Transcriptomic Analysis of Laribacter hongkongensis Reveals Adaptive Response Coupled with Temperature

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Tricyclic heterocycles display diverse sensitivity to the A147T TSPO polymorphism

The 18 kDa translocator protein (TSPO) is a target for the development of imaging agents to detect neuroinflammation. The clinical utility of second-generation TSPO ligands has been hindered by the presence of a polymorphism, rs6971, which causes a non-conservative substitution of alanine for threonine at amino acid residue 147 (TSPO A147T). Given the complex nature of TSPO binding, and the lack of non-discriminating high-affinity ligands at both wild type and A147T forms of TSPO, a series of novel TSPO ligands containing various heterocyclic scaffolds was developed to explore the pharmacophoric drivers of affinity loss at TSPO A147T. In general, N-benzyl-N-methyl-substituted amide ligands showed increased affinity at TSPO A147T, and a pyrazolopyrimidine acetamide containing this motif displayed low nanomolar binding affinities to both TSPO forms

Linear approaches to intramolecular Förster Resonance Energy Transfer probe measurements for quantitative modeling

Numerous unimolecular, genetically-encoded Forster Resonance Energy Transfer (FRET) probes for monitoring biochemical activities in live cells have been developed over the past decade. As these probes allow for collection of high frequency, spatially resolved data on signaling events in live cells and tissues, they are an attractive technology for obtaining data to develop quantitative, mathematical models of spatiotemporal signaling dynamics. However, to be useful for such purposes the observed FRET from such probes should be related to a biological quantity of interest through a defined mathematical relationship, which is straightforward when this relationship is linear, and can be difficult otherwise. First, we show that only in rare circumstances is the observed FRET linearly proportional to a biochemical activity. Therefore in most cases FRET measurements should only be compared either to explicitly modeled probes or to concentrations of products of the biochemical activity, but not to activities themselves. Importantly, we find that FRET measured by standard intensity-based, ratiometric methods is inherently non-linear with respect to the fraction of probes undergoing FRET. Alternatively, we find that quantifying FRET either via (1) fluorescence lifetime imaging (FLIM) or (2) ratiometric methods where the donor emission intensity is divided by the directly-excited acceptor emission intensity (denoted R<sub>alt</sub>) is linear with respect to the fraction of probes undergoing FRET. This linearity property allows one to calculate the fraction of active probes based on the FRET measurement. Thus, our results suggest that either FLIM or ratiometric methods based on R<sub>alt</sub> are the preferred techniques for obtaining quantitative data from FRET probe experiments for mathematical modeling purpose

Optimal interdependence between networks for the evolution of cooperation

Recent research has identified interactions between networks as crucial for the outcome of evolutionary games taking place on them. While the consensus is that interdependence does promote cooperation by means of organizational complexity and enhanced reciprocity that is out of reach on isolated networks, we here address the question just how much interdependence there should be. Intuitively, one might assume the more the better. However, we show that in fact only an intermediate density of sufficiently strong interactions between networks warrants an optimal resolution of social dilemmas. This is due to an intricate interplay between the heterogeneity that causes an asymmetric strategy flow because of the additional links between the networks, and the independent formation of cooperative patterns on each individual network. Presented results are robust to variations of the strategy updating rule, the topology of interdependent networks, and the governing social dilemma, thus suggesting a high degree of universality

Dissimilarity in the Folding of Human Cytosolic Creatine Kinase Isoenzymes

Creatine kinase (CK, EC 2.7.3.2) plays a key role in the energy homeostasis of excitable cells. The cytosolic human CK isoenzymes exist as homodimers (HMCK and HBCK) or a heterodimer (MBCK) formed by the muscle CK subunit (M) and/or brain CK subunit (B) with highly conserved three-dimensional structures composed of a small N-terminal domain (NTD) and a large C-terminal domain (CTD). The isoforms of CK provide a novel system to investigate the sequence/structural determinants of multimeric/multidomain protein folding. In this research, the role of NTD and CTD as well as the domain interactions in CK folding was investigated by comparing the equilibrium and kinetic folding parameters of HMCK, HBCK, MBCK and two domain-swapped chimeric forms (BnMc and MnBc). Spectroscopic results indicated that the five proteins had distinct structural features depending on the domain organizations. MBCK BnMc had the smallest CD signals and the lowest stability against guanidine chloride-induced denaturation. During the biphasic kinetic refolding, three proteins (HMCK, BnMc and MnBc), which contained either the NTD or CTD of the M subunit and similar microenvironments of the Trp fluorophores, refolded about 10-fold faster than HBCK for both the fast and slow phase. The fast folding of these three proteins led to an accumulation of the aggregation-prone intermediate and slowed down the reactivation rate thereby during the kinetic refolding. Our results suggested that the intra- and inter-subunit domain interactions modified the behavior of kinetic refolding. The alternation of domain interactions based on isoenzymes also provides a valuable strategy to improve the properties of multidomain enzymes in biotechnology

Personal radio use and cancer risks among 48,518 British police officers and staff from the Airwave Health Monitoring Study

Background: Radiofrequency electromagnetic fields (RF-EMF) from mobile phones have been classified as potentially carcinogenic. No study has investigated use of Terrestrial Trunked Radio (TETRA), a source of RF-EMF with wide occupational use, and cancer risks. Methods: We investigated association of monthly personal radio use and risk of cancer using Cox proportional hazards regression among 48,518 police officers and staff of the Airwave Health Monitoring Study in Great Britain. Results: During median follow-up of 5.9 years, 716 incident cancer cases were identified. Among users, the median of the average monthly duration of use in the year prior to enrolment was 30.5 min (inter-quartile range 8.1, 68.1). Overall, there was no association between personal radio use and risk of all cancers (hazard ratio [HR] = 0.98, 95% confidence interval [CI]: 0.93, 1.03). For head and neck cancers HR = 0.72 (95% CI: 0.30, 1.70) among personal radio users vs non-users, and among users it was 1.06 (95% CI: 0.91, 1.23) per doubling of minutes of personal radio use. Conclusions: With the limited follow-up to date, we found no evidence of association of personal radio use with cancer risk. Continued follow-up of the cohort is warranted