scholarly journals Frequent Recombination Events in Leishmania donovani: Mining Population Data

Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 572 ◽  
Author(s):  
Igor B. Rogozin ◽  
Arzuv Charyyeva ◽  
Ivan A. Sidorenko ◽  
Vladimir N. Babenko ◽  
Vyacheslav Yurchenko

The Leishmania donovani species complex consists of all L. donovani and L. infantum strains mainly responsible for visceral leishmaniasis (VL). It was suggested that genome rearrangements in Leishmania spp. occur very often, thus enabling parasites to adapt to the different environmental conditions. Some of these rearrangements may be directly linked to the virulence or explain the reduced efficacy of antimonial drugs in some isolates. In the current study, we focused on a large-scale analysis of putative gene conversion events using publicly available datasets. Previous population study of L. donovani suggested that population variability of L. donovani is relatively low, however the authors used masking procedures and strict read selection criteria. We decided to re-analyze DNA-seq data without masking sequences, because we were interested in the most dynamic fraction of the genome. The majority of samples have an excess of putative gene conversion/recombination events in the noncoding regions, however we found an overall excess of putative intrachromosomal gene conversion/recombination in the protein coding genes, compared to putative interchromosomal gene conversion/recombination events.

2018 ◽  
Vol 115 (50) ◽  
pp. 12775-12780 ◽  
Author(s):  
Kevin P. Johnson ◽  
Christopher H. Dietrich ◽  
Frank Friedrich ◽  
Rolf G. Beutel ◽  
Benjamin Wipfler ◽  
...  

Hemipteroid insects (Paraneoptera), with over 10% of all known insect diversity, are a major component of terrestrial and aquatic ecosystems. Previous phylogenetic analyses have not consistently resolved the relationships among major hemipteroid lineages. We provide maximum likelihood-based phylogenomic analyses of a taxonomically comprehensive dataset comprising sequences of 2,395 single-copy, protein-coding genes for 193 samples of hemipteroid insects and outgroups. These analyses yield a well-supported phylogeny for hemipteroid insects. Monophyly of each of the three hemipteroid orders (Psocodea, Thysanoptera, and Hemiptera) is strongly supported, as are most relationships among suborders and families. Thysanoptera (thrips) is strongly supported as sister to Hemiptera. However, as in a recent large-scale analysis sampling all insect orders, trees from our data matrices support Psocodea (bark lice and parasitic lice) as the sister group to the holometabolous insects (those with complete metamorphosis). In contrast, four-cluster likelihood mapping of these data does not support this result. A molecular dating analysis using 23 fossil calibration points suggests hemipteroid insects began diversifying before the Carboniferous, over 365 million years ago. We also explore implications for understanding the timing of diversification, the evolution of morphological traits, and the evolution of mitochondrial genome organization. These results provide a phylogenetic framework for future studies of the group.


2020 ◽  
Vol 26 ◽  
Author(s):  
Luíza Dantas-Pereira ◽  
Edézio F. Cunha-Junior ◽  
Valter V. Andrade-Neto ◽  
John F. Bower ◽  
Guilherme A. M. Jardim ◽  
...  

: Chagas disease, Sleeping sickness and Leishmaniasis, caused by trypanosomatids Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp., respectively, are considered neglected tropical diseases, and they especially affect impoverished populations in the developing world. The available chemotherapies are very limited and a search for alternatives is still necessary. In folk medicine, natural naphthoquinones have been employed for the treatment of a great variety of illnesses, including parasitic infections. This review is focused on the anti-trypanosomatid activity and mechanistic analysis of naphthoquinones and derivatives. Among all the series of derivatives tested in vitro, naphthoquinone-derived 1,2,3-triazoles were very active on T. cruzi infective forms in blood bank conditions, as well as in amastigotes of Leishmania spp. naphthoquinones containing a CF3 on a phenyl amine ring inhibited T. brucei proliferation in the nanomolar range, and naphthopterocarpanquinones stood out for their activity on a range of Leishmania species. Some of these compounds showed a promising selectivity index (SI) (30 to 1900), supporting further analysis in animal models. Indeed, high toxicity to the host and inactivation by blood components are crucial obstacles to be overcome to use naphthoquinones and/or their derivatives for chemotherapy. Multidisciplinary initiatives embracing medicinal chemistry, bioinformatics, biochemistry, and molecular and cellular biology need to be encouraged to allow the optimization of these compounds. Large scale automated tests are pivotal for the efficiency of the screening step, and subsequent evaluation of both the mechanism of action in vitro and pharmacokinetics in vivo are essential for the development of a novel, specific and safe derivative, minimizing adverse effects.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shumaila Sayyab ◽  
Anders Lundmark ◽  
Malin Larsson ◽  
Markus Ringnér ◽  
Sara Nystedt ◽  
...  

AbstractThe mechanisms driving clonal heterogeneity and evolution in relapsed pediatric acute lymphoblastic leukemia (ALL) are not fully understood. We performed whole genome sequencing of samples collected at diagnosis, relapse(s) and remission from 29 Nordic patients. Somatic point mutations and large-scale structural variants were called using individually matched remission samples as controls, and allelic expression of the mutations was assessed in ALL cells using RNA-sequencing. We observed an increased burden of somatic mutations at relapse, compared to diagnosis, and at second relapse compared to first relapse. In addition to 29 known ALL driver genes, of which nine genes carried recurrent protein-coding mutations in our sample set, we identified putative non-protein coding mutations in regulatory regions of seven additional genes that have not previously been described in ALL. Cluster analysis of hundreds of somatic mutations per sample revealed three distinct evolutionary trajectories during ALL progression from diagnosis to relapse. The evolutionary trajectories provide insight into the mutational mechanisms leading relapse in ALL and could offer biomarkers for improved risk prediction in individual patients.


2020 ◽  
pp. 1-26
Author(s):  
Qinwen Hu ◽  
Muhammad Rizwan Asghar ◽  
Nevil Brownlee

HTTPS refers to an application-specific implementation that runs HyperText Transfer Protocol (HTTP) on top of Secure Socket Layer (SSL) or Transport Layer Security (TLS). HTTPS is used to provide encrypted communication and secure identification of web servers and clients, for different purposes such as online banking and e-commerce. However, many HTTPS vulnerabilities have been disclosed in recent years. Although many studies have pointed out that these vulnerabilities can lead to serious consequences, domain administrators seem to ignore them. In this study, we evaluate the HTTPS security level of Alexa’s top 1 million domains from two perspectives. First, we explore which popular sites are still affected by those well-known security issues. Our results show that less than 0.1% of HTTPS-enabled servers in the measured domains are still vulnerable to known attacks including Rivest Cipher 4 (RC4), Compression Ratio Info-Leak Mass Exploitation (CRIME), Padding Oracle On Downgraded Legacy Encryption (POODLE), Factoring RSA Export Keys (FREAK), Logjam, and Decrypting Rivest–Shamir–Adleman (RSA) using Obsolete and Weakened eNcryption (DROWN). Second, we assess the security level of the digital certificates used by each measured HTTPS domain. Our results highlight that less than 0.52% domains use the expired certificate, 0.42% HTTPS certificates contain different hostnames, and 2.59% HTTPS domains use a self-signed certificate. The domains we investigate in our study cover 5 regions (including ARIN, RIPE NCC, APNIC, LACNIC, and AFRINIC) and 61 different categories such as online shopping websites, banking websites, educational websites, and government websites. Although our results show that the problem still exists, we find that changes have been taking place when HTTPS vulnerabilities were discovered. Through this three-year study, we found that more attention has been paid to the use and configuration of HTTPS. For example, more and more domains begin to enable the HTTPS protocol to ensure a secure communication channel between users and websites. From the first measurement, we observed that many domains are still using TLS 1.0 and 1.1, SSL 2.0, and SSL 3.0 protocols to support user clients that use outdated systems. As the previous studies revealed security risks of using these protocols, in the subsequent studies, we found that the majority of domains updated their TLS protocol on time. Our 2020 results suggest that most HTTPS domains use the TLS 1.2 protocol and show that some HTTPS domains are still vulnerable to the existing known attacks. As academics and industry professionals continue to disclose attacks against HTTPS and recommend the secure configuration of HTTPS, we found that the number of vulnerable domain is gradually decreasing every year.


Genetics ◽  
2002 ◽  
Vol 162 (4) ◽  
pp. 1805-1810 ◽  
Author(s):  
Martin J Lercher ◽  
Nick G C Smith ◽  
Adam Eyre-Walker ◽  
Laurence D Hurst

AbstractThe large-scale systematic variation in nucleotide composition along mammalian and avian genomes has been a focus of the debate between neutralist and selectionist views of molecular evolution. Here we test whether the compositional variation is due to mutation bias using two new tests, which do not assume compositional equilibrium. In the first test we assume a standard population genetics model, but in the second we make no assumptions about the underlying population genetics. We apply the tests to single-nucleotide polymorphism data from noncoding regions of the human genome. Both models of neutral mutation bias fit the frequency distributions of SNPs segregating in low- and medium-GC-content regions of the genome adequately, although both suggest compositional nonequilibrium. However, neither model fits the frequency distribution of SNPs from the high-GC-content regions. In contrast, a simple population genetics model that incorporates selection or biased gene conversion cannot be rejected. The results suggest that mutation biases are not solely responsible for the compositional biases found in noncoding regions.


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