Molecular musings in microbial ecology and evolution

<p>Abstract</p> <p/> <p>A few major discoveries have influenced how ecologists and evolutionists study microbes. Here, in the format of an interview, we answer questions that directly relate to how these discoveries are perceived in these two branches of microbiology, and how they have impacted on both scientific thinking and methodology.</p> <p>The first question is "<it>What has been the influence of the 'Universal Tree of Life' based on molecular markers?" </it>For evolutionists, the tree was a tool to understand the past of known (cultured) organisms, mapping the invention of various physiologies on the evolutionary history of microbes. For ecologists the tree was a guide to discover the current diversity of unknown (uncultured) organisms, without much knowledge of their physiology.</p> <p>The second question we ask is "<it>What was the impact of discovering frequent lateral gene transfer among microbes?" </it>In evolutionary microbiology, frequent lateral gene transfer (LGT) made a simple description of relationships between organisms impossible, and for microbial ecologists, functions could not be easily linked to specific genotypes. Both fields initially resisted LGT, but methods or topics of inquiry were eventually changed in one to incorporate LGT in its theoretical models (evolution) and in the other to achieve its goals despite that phenomenon (ecology).</p> <p>The third and last question we ask is "<it>What are the implications of the unexpected extent of diversity?" </it>The variation in the extent of diversity between organisms invalidated the universality of species definitions based on molecular criteria, a major obstacle to the adaptation of models developed for the study of macroscopic eukaryotes to evolutionary microbiology. This issue has not overtly affected microbial ecology, as it had already abandoned species in favor of the more flexible operational taxonomic units. This field is nonetheless moving away from traditional methods to measure diversity, as they do not provide enough resolution to uncover what lies below the species level.</p> <p>The answers of the evolutionary microbiologist and microbial ecologist to these three questions illustrate differences in their theoretical frameworks. These differences mean that both fields can react quite distinctly to the same discovery, incorporating it with more or less difficulty in their scientific practice.</p> <p>Reviewers</p> <p>This article was reviewed by W. Ford Doolittle, Eugene V. Koonin and Maureen A. O'Malley.</p

<i>Plasmodium </i>Condensin Core Subunits SMC2/SMC4 Mediate Atypical Mitosis and Are Essential for Parasite Proliferation and Transmission

Condensin is a multi-subunit protein complex regulating chromosome condensation and segregation during cell division. In Plasmodium spp., the causative agent of malaria, cell division is atypical and the role of condensin is unclear. Here we examine the role of SMC2 and SMC4, the core subunits of condensin, during endomitosis in schizogony and endoreduplication in male gametogenesis. During early schizogony, SMC2/SMC4 localize to a distinct focus, identified as the centromeres by NDC80 fluorescence and chromatin immunoprecipitation sequencing (ChIP-seq) analyses, but do not form condensin I or II complexes. In mature schizonts and during male gametogenesis, there is a diffuse SMC2/SMC4 distribution on chromosomes and in the nucleus, and both condensin I and condensin II complexes form at these stages. Knockdown of smc2 and smc4 gene expression reveals essential roles in parasite proliferation and transmission. The condensin core subunits (SMC2/SMC4) form different complexes and may have distinct functions at various stages of the parasite life cycle

Reflections and Considerations on Running Creative Visualization Learning Activities

This paper draws together nine strategies for creative visualization activities. Teaching visualization often involves running learning activities where students perform tasks that directly support one or more topics that the teacher wishes to address in the lesson. As a group of educators and researchers in visualization, we reflect on our learning experiences. Our activities and experiences range from dividing the tasks into smaller parts, considering different learning materials, to encouraging debate. With this paper, our hope is that we can encourage, inspire, and guide other educators with visualization activities. Our reflections provide an initial starting point of methods and strategies to craft creative visualisation learning activities, and provide a foundation for developing best practices in visualization education

Reflections and Considerations on Running Creative Visualization Learning Activities

This paper draws together nine strategies for creative visualization activities. Teaching visualization often involves running learning activities where students perform tasks that directly support one or more topics that the teacher wishes to address in the lesson. As a group of educators and researchers in visualization, we reflect on our learning experiences. Our activities and experiences range from dividing the tasks into smaller parts, considering different learning materials, to encouraging debate. With this paper, our hope is that we can encourage, inspire, and guide other educators with visualization activities. Our reflections provide an initial starting point of methods and strategies to craft creative visualisation learning activities, and provide a foundation for developing best practices in visualization education.Comment: 8 pages, 3 figures. Accepted at 4th IEEE Workshop on Visualization Guidelines in Research, Design, and Education (VisGuides 2022), at IEEE VIS 202

Ibrutinib Plus Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia: The CLARITY Study.

PURPOSE:The treatment of chronic lymphocytic leukemia (CLL) has been revolutionized by targeted therapies that either inhibit proliferation (ibrutinib) or reactivate apoptosis (venetoclax). Both significantly improve survival in CLL and replace chemoimmunotherapy for many patients. However, individually, they rarely lead to eradication of measurable residual disease (MRD) and usually are taken indefinitely or until progression. We present the CLARITY trial that combined ibrutinib with venetoclax to eradicate detectable CLL with the intention of stopping therapy. PATIENTS AND METHODS:CLARITY is a phase II trial that combined ibrutinib with venetoclax in patients with relapsed or refractory CLL. The primary end point was eradication of MRD after 12 months of combined therapy. Key secondary end points were response by International Workshop on CLL criteria, safety, and progression-free and overall survival. RESULTS:In 53 patients after 12 months of ibrutinib plus venetoclax, MRD negativity (fewer than one CLL cell in 10,000 leukocytes) was achieved in the blood of 28 (53%) and the marrow of 19 (36%). Forty-seven patients (89%) responded, and 27 (51%) achieved a complete remission. After a median follow-up of 21.1 months, one patient progressed, and all patients were alive. A single case of biochemical tumor lysis syndrome was observed. Other adverse effects were mild and/or manageable and most commonly were neutropenia or GI events. CONCLUSION:The combination of ibrutinib plus venetoclax was well tolerated in patients with relapsed or refractory CLL. There was a high rate of MRD eradication that led to the cessation of therapy in some patients. The progression-free and overall survival rates are encouraging for relapsed and refractory CLL

Combination romidepsin and azacitidine therapy is well tolerated and clinically active in adults with high‐risk acute myeloid leukaemia ineligible for intensive chemotherapy

Azacitidine (AZA) is important in the management of patients with acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy. Romidepsin (ROM) is a histone deacetylase inhibitor which synergises with AZA in vitro. The ROMAZA trial established the maximum tolerated dose (MTD) of combined ROM/AZA therapy in patients with AML, as ROM 12 mg/m2 on Days 8 and 15, with AZA 75 mg/m2 administered for 7/28 day cycle. Nine of the 38 (23·7%) patients treated at the MTD were classified as responders by Cycle 6 (best response: complete remission [CR]/incomplete CR n = 7, partial response n = 2). Correlative next‐generation sequencing studies demonstrated important insights into therapy resistance

ONeSAMP 3.0: Estimation of effective population size via SNP data from one population

The genetic effective size (Ne) is arguably one of the most important characteristics of a population as it impacts the rate of loss of genetic diversity. Methods that estimate Ne are important in population and conservation genetic studies as they quantify the risk of a population being inbred or lacking genetic diversity. Yet there are very few methods that can estimate the Ne from data from a single population and without extensive information about the genetics of the population, such as a linkage map, or a reference genome of the species of interest. We present ONeSAMP 3.0, an algorithm for estimating Ne from single nucleotide polymorphism (SNP) data collected from a single population sample using Approximate Bayesian Computation and local linear regression. We demonstrate the utility of this approach using simulated Wright-Fisher populations, and empirical data from five endangered Channel Island fox (Urocyon littoralis) populations to evaluate the performance of ONeSAMP 3.0 compared to a commonly used Ne estimator. Our results show that ONeSAMP 3.0 is is broadly applicable to natural populations and is flexible enough that future versions could easily include summary statistics appropriate for a suite of biological and sampling conditions. ONeSAMP 3.0 is publicly available under the GNU license at https://github.com/AaronHong1024/ONeSAMP_3.National Science FoundationAbstract -- Keywords -- Introduction -- Materials and methods -- Results -- Discussion -- Conclusion -- Data Availability -- Acknowledgements -- Funding -- Conflicts of interest -- Literature citedYe