Size Of Subpopulation Research Articles

Nucleoid‐associated Rok differentially affects chromosomal transformation on Bacillus subtilis recombination‐deficient cells

Rok, a Bacillus subtilis nucleoid-associated protein (NAP), negatively regulates competence development and silences xenogeneic genes. We show that rok inactivation increases rpoB482 natural intraspecies chromosomal transformation (CT) and plasmid transformation to a different extent. In ΔaddAB, ΔrecO, recF15, ΔrecU, ΔruvAB or rec+ cells intraspecies CT significantly increases, but the ΔrecD2 mutation reduces, and the ΔrecX, ΔradA or ΔdprA mutation further decreases CT in the Δrok context when compared to rok+ cells. These observations support the idea that rok inactivation, by altering the topology of the recipient DNA, differentially affects the integration of homologous DNA in rec-deficient strains, and in minor extent the competent subpopulation size. The impairment of other NAP (Hbsu or LrpC) also increased intra- and interspecies CT (nonself-DNA, ~8% nucleotide sequence divergence) in rec+ cells, but differentially reduced both types of CTs in certain rec-deficient strains. We describe that rok inactivation significantly stimulates intra and interspecies CT but differentially reduces them in transformation-deficient cells, perhaps by altering the nucleoid architecture. We extend the observation to other NAPs (Hbsu, LrpC).

Glomerular Macrophages in Human Auto- and Allo-Immune Nephritis.

Macrophages are involved in tissue homeostasis. They participate in inflammatory episodes and are involved in tissue repair. Macrophages are characterized by a phenotypic heterogeneity and a profound cell plasticity. In the kidney, and more particularly within glomeruli, macrophages are thought to play a maintenance role that is potentially critical for preserving a normal glomerular structure. Literature on the glomerular macrophage role in human crescentic glomerulonephritis and renal transplantation rejection with glomerulitis, is sparse. Evidence from preclinical models indicates that macrophages profoundly modulate disease progression, both in terms of number—where depletion has resulted in a reduced glomerular lesion—and sub-phenotype—M1 being more profoundly detrimental than M2. This evidence is corroborated by better outcomes in patients with a lower number of glomerular macrophages. However, due to the very limited biopsy sample size, the type and role of macrophage subpopulations involved in human proliferative lesions is more difficult to precisely define and synthesize. Therefore, specific biomarkers of macrophage activation may enhance our ability to assess their role, potentially enabling improved monitoring of drug activity and ultimately allowing the development of novel therapeutic strategies to target these elusive cellular players.

Sonoporation generates downstream cellular impact after membrane resealing

Sonoporation via microbubble-mediated ultrasound exposure has shown potential in drug and gene delivery. However, there is a general lack of mechanistic knowledge on sonoporation-induced cellular impact after membrane resealing, and this issue has made it challenging to apply sonoporation efficiently in practice. Here, we present new evidence on how sonoporation, without endangering immediate cell viability, may disrupt downstream cellular hemostasis in ways that are distinguished from the bioeffects observed in other sonicated and unsonoporated cells. Sonoporation was realized on HL-60 leukemia cells by delivering pulsed ultrasound (1 MHz frequency, 0.50 MPa peak negative pressure; 10% duty cycle; 30 s exposure period; 29.1 J/cm2 acoustic energy density) in the presence of lipid-shelled microbubbles (1:1 cell-to-bubble ratio). Results showed that 54.6% of sonoporated cells, despite remaining initially viable, underwent apoptosis or necrosis at 24 h after sonoporation. Anti-proliferation behavior was also observed in sonoporated cells as their subpopulation size was reduced by 43.8% over 24 h. Preceding these cytotoxic events, the percentages of sonoporated cells in different cell cycle phases were found to be altered by 12 h after exposure. As well, for sonoporated cells, their expressions of cytoprotective genes in the heat shock protein-70 (HSP-70) family were upregulated by at least 4.1 fold at 3 h after exposure. Taken altogether, these findings indicate that sonoporated cells attempted to restore homeostasis after membrane resealing, but many of them ultimately failed to recover. Such mechanistic knowledge should be taken into account to devise more efficient sonoporation-mediated therapeutic protocols.

Sedimentary System of Ash Deposits from Long-Term Vulcanian Activity at Sakurajima Volcano, Japan

Ash deposits from short-lived vulcanian eruptions are ubiquitous at active volcanoes and are important for understanding the development of a volcanic edifice. In this study, we investigated the sedimentary system of ash deposits produced by long-term vulcanian activity from Showa crater of Sakurajima volcano, Japan, based on the grain size characteristics of ash from individual eruptions. We collected falling ash samples from 20 individual vulcanian eruptions between March 3 and 11, 2010. The grain size distributions of the ash samples were unimodal, bimodal, and trimodal, depending on the event. The median particle size of the main subpopulation decreases with distance from vent. The low standard deviation of the grain size of the main subpopulation implies deposition from transient volcanic plumes. For the finest subpopulation in the polymodal samples, the median grain size is very fine ash (<30 μm), indicating that this subpopulation was derived from ash aggregates. Overall, the sedimentary system of the long-term vulcanian activity at Sakurajima volcano is explained by accumulation of ash particles from repeated transient plumes and ash aggregation, and the latter controlled the behavior of the very fine ash.

Harnessing peak transmission around symptom onset for non-pharmaceutical intervention and containment of the COVID-19 pandemic

Within a short period of time, COVID-19 grew into a world-wide pandemic. Transmission by pre-symptomatic and asymptomatic viral carriers rendered intervention and containment of the disease extremely challenging. Based on reported infection case studies, we construct an epidemiological model that focuses on transmission around the symptom onset. The model is calibrated against incubation period and pairwise transmission statistics during the initial outbreaks of the pandemic outside Wuhan with minimal non-pharmaceutical interventions. Mathematical treatment of the model yields explicit expressions for the size of latent and pre-symptomatic subpopulations during the exponential growth phase, with the local epidemic growth rate as input. We then explore reduction of the basic reproduction number R0 through specific transmission control measures such as contact tracing, testing, social distancing, wearing masks and sheltering in place. When these measures are implemented in combination, their effects on R0 multiply. We also compare our model behaviour to the first wave of the COVID-19 spreading in various affected regions and highlight generic and less generic features of the pandemic development.

Adaptive Granularity Learning Distributed Particle Swarm Optimization for Large-Scale Optimization.

Large-scale optimization has become a significant and challenging research topic in the evolutionary computation (EC) community. Although many improved EC algorithms have been proposed for large-scale optimization, the slow convergence in the huge search space and the trap into local optima among massive suboptima are still the challenges. Targeted to these two issues, this article proposes an adaptive granularity learning distributed particle swarm optimization (AGLDPSO) with the help of machine-learning techniques, including clustering analysis based on locality-sensitive hashing (LSH) and adaptive granularity control based on logistic regression (LR). In AGLDPSO, a master-slave multisubpopulation distributed model is adopted, where the entire population is divided into multiple subpopulations, and these subpopulations are co-evolved. Compared with other large-scale optimization algorithms with single population evolution or centralized mechanism, the multisubpopulation distributed co-evolution mechanism will fully exchange the evolutionary information among different subpopulations to further enhance the population diversity. Furthermore, we propose an adaptive granularity learning strategy (AGLS) based on LSH and LR. The AGLS is helpful to determine an appropriate subpopulation size to control the learning granularity of the distributed subpopulations in different evolutionary states to balance the exploration ability for escaping from massive suboptima and the exploitation ability for converging in the huge search space. The experimental results show that AGLDPSO performs better than or at least comparable with some other state-of-the-art large-scale optimization algorithms, even the winner of the competition on large-scale optimization, on all the 35 benchmark functions from both IEEE Congress on Evolutionary Computation (IEEE CEC2010) and IEEE CEC2013 large-scale optimization test suites.

A new estimator and approach for estimating the subpopulation parameters

Based on some theoretical results, we recommend a new algorithm for estimating the total and mean of a subpopulation variable for the case of a known subpopulation size, which is different from the algorithm recommended by most of sampling books. The latter usually recommend the multiplication of the subpopulation sample mean by the subpopulation size rather than the subpopulation total estimator for the unknown subpopulation size. We present a criterion to determine which estimator is more efficient. The criterion shows that the traditional total subpopulation estimator for unknown subpopulation size will be more efficient if the subpopulation mean is close to zero. Using an innovative procedure, we develop a new estimator, and we study its properties using real data. The new estimator is potentially an appropriate direct estimator in a composite estimator for small area estimation.

The threat by the invasive African tulip tree,

Expert knowledge is widely used for assessing the conservation status of little-known species. Pterocymbium oceanicum is a large, emergent tree endemic to Fiji. Experts classified the species as ‘Critically Endangered’ (IUCN Red List) in 2016 and estimated the population size at &lt;250 mature individuals with the largest subpopulation consisting of a single stand of 100 individuals. We surveyed this stand and counted 133 individuals, which validated the expert estimate. However, we discovered an additional three stands nearby, increasing the total subpopulation size to 433 individuals. Therefore, the expert estimate reliably and conservatively estimated population size but missed important information. Field surveys suggest that P. oceanicum has a narrow ecological niche as a long-lived early pioneer at mid-elevations (400–800 m) in seasonally dry forests, one of Fiji’s most degraded ecosystems. The introduced African Tulip Tree, Spathodea campanulata, is invading the sampled subpopulation and shares the characteristics of being a large, fast-growing and early successional tree. Therefore, the narrow niche of P. oceanicum may now be threatened by S. campanulata. Our study highlights that expert knowledge can provide valuable information about threatened species but also has limitations. IUCN Red List assessments based solely on expert assessments should therefore be cautiously interpreted. The invasion by S. campanulata poses a serious threat to P. oceanicum and needs to be carefully monitored, with the impacts of S. campanulata on the establishment and growth of P. oceanicum requiring urgent investigation.

Integrated conservation of important plant taxa through the improvement of the original plant micro-reserve (PMR) approach: The intensive PMR monitoring case of Ophrys kotschyi

Developing a monitoring system and a conservation strategy against the negative impact of global change on threatened plant species, is nowadays the challenge for conservation experts. The Plant Micro-Reserve (PMR) approach became a highly effective approach in protecting plant species, since mild active management of vegetation plots and protection of plant populations takes place. The PMR has greatly evolved since its initial concept of managing a large network of PMRs, to having fewer protected areas subject to intensive scientific monitoring (e.g. Intensive Monitoring PMR; IM-PMR). This study further improved the IM-PMR approach by focusing on the threatened plant species of Ophrys kotschyi in Cyprus. The proposed IM-PMR enhances the available knowledge on the biology, physiology and ecology of the targeted plant species, through implementing an intensive monitoring system and assessing its genetic diversity. Within the framework of IM-PMR, the population size of O. kotschyi recorded statistically significant differentiation during the monitoring period, most likely due to the vegetative dormancy of the species. The subpopulation size and dormancy in O. kotschyi was correlated with precipitation and air temperature for specific months. In addition, the different local climatic conditions and the species dormancy between years seem to influence the flowers production among individuals, in the four monitoring years. Nevertheless, the low natural fecundity compared to the artificially pollinated plants and the absent correlation with any of the climatic parameters, might be closely related to the lack of pollinators at this site. The genetic diversity (HT = 0.456) is higher compared to other endemic and short-lived perennial species, while the genetic differentiation among the subpopulations of O. kotschyi showed significant substructure (FSTFIS=0.5 = 0.097*). The subpopulation within IM-PMR showed relatively lower genetic diversity among the largest subpopulations of O. kotschyi, and the highest percentage of linked loci. Such observations support the non-random association of different loci in this subpopulation, and the ineffective pollen flow within this single subpopulation. The improvement of the original PMR approach in the current IM-PMR proposal denotes that different ecological aspects are taken into account towards gaining a holistic knowledge on a target species. The IM-PMR approach as implemented for O. kotschyi, could lead to the development of an integrated conservation approach for rare, threatened, or endangered species.

PRO94 Outcomes of Benefit Reassessments of Orphan Drugs in Germany after Exceedance of the 50-Million-EURO Revenue Threshold

For orphan drugs in Germany, an added benefit is granted by law within the early benefit assessment. However, this privilege no longer applies if the drug’s turnovers exceed 50 million euro within 12 months, leading to a benefit reassessment based on a comparison against an appropriate comparative therapy. The objective of the current study is to evaluate the development of an orphan drug’s added benefit as well as the negotiated price rebate after reassessment. Outcomes of all early benefit assessments of orphan drugs that were reassessed by April 2020 due to the exceedance of the 50-million-euro revenue threshold were analyzed. The number and size of subpopulations and the respective granted added benefit as well as the resulting negotiated rebate were determined across assessments. In 6 out of 9 cases, an orphan drug was granted an added benefit for at least one subpopulation after reassessment. However, the mean proportion of patients with an added benefit among the total population shrunk from 100% to 43%. In the first assessment, the added benefit had been considered non-quantifiable for an average of 56% of the total patient population. This proportion amounted to only 3% in the reassessment, while the added benefit of 40% of the total population was quantified as considerable. Nevertheless, the rebate after reassessment maintained identical for only one drug. In all other cases the rebate increased by additional 3% to 14%. The reassessment of an orphan drug due to exceedance of the 50-million-euro threshold in Germany is associated with a high risk of a reduction of the proportion of patients with a granted added benefit resulting in an increased rebate on the drug’s price. Therefore, a careful evaluation of potential risks and benefits of exceeding the 50-million-euro threshold is crucial to prevent harmful outcomes of the reassessment.

Evaluating extinction debt in fragmented forests: the rapid recovery of a critically endangered primate

AbstractFragmented tropical forests can be highly dynamic, with the spatial configuration of forest patches changing through time. Yet, the lack of longitudinal studies limits our understanding of how patch dynamics affect biodiversity, especially when there is a time lag in species extinctions (extinction debt). We assessed how temporal changes in patch size, shape complexity and isolation affect populations of the Mexican howler monkey (Alouatta palliata mexicana), hypothesizing that we would find an extinction debt in this relatively long‐lived species. We assessed patch occupancy, subpopulation size and immature‐to‐female ratio in 39 forest patches from Los Tuxtlas, Mexico, in both 2001 and 2013. To identify time‐lag responses to habitat disturbance, we related demographic attributes in 2013 to patch metrics in 2001 and 2013 and tested whether primate subpopulations were better predicted by current or historical patch characteristics. We also assessed how changes in patch metrics affected each demographic attribute between 2001 and 2013. Patch size and shape complexity increased over time, whereas isolation decreased. These positive spatial changes were accompanied by a 1.6‐fold increase in mean subpopulation size over the same period. In addition, occupancy and immature‐to‐female ratio were similarly related to patch attributes in both years, suggesting that there is no extinction debt. Our findings are ‘good news’, suggesting that forest recovery over a relatively short period can promote the recovery of this Critically Endangered taxon. They also highlight the importance of preventing forest loss and promoting forest regeneration in human‐modified tropical landscapes.

Variations of the Escherichia coli population in the digestive tract of broilers

ABSTRACT We explored the between-group and temporal variations in the intestinal Escherichia coli populations of broilers under experimental conditions, taking both antimicrobial resistance and virulence into consideration. Four replicates of 45 commercial chicks were reared in four animal facilities. On their first day of life (Day 0), they were orally inoculated with two extended-spectrum-cephalosporin-resistant (ESCR) E. coli (2.72 log10 CFU of a bla CMY-2- and 2.55 log10 CFU of a bla CTX-M-carrying E. coli). Faecal samples were then collected weekly and caecal samples were obtained from birds sacrificed on Days 21 or 42. The total, ESC-, ciprofloxacin- and gentamicin-resistant E. coli populations were enumerated on MacConkey (MC) and MC-supplemented media, and eight virulence-associated genes (VAGs) (iroN, iutA, iss, ompT, hlyF, vat, frzorf4 , and fyuA) were sought by PCR on isolates obtained on MC agar. The results showed significant between-group differences in the size of the resistant sub-populations and the presence of VAGs. Contrary to bla CTX-M-positive strains, bla CMY-positive strains persisted up to Day 42, but represented only a minor fraction of the total E. coli population. The ESC-, gentamicin- and ciprofloxacin-resistant populations decreased over time. Isolates obtained during the first week contained a mean of 5.1 VAGs. The percentages of some VAG profiles differed between faecal isolates on Day 41 and caecal isolates on Day 42. The fluctuations or differences between E. coli isolates according to group, age, and faecal or caecal origin need to be considered when designing experimental protocols and seeking to improve colibacillosis control. RESEARCH HIGHLIGHTS Temporal variations in the intestinal E. coli populations of broilers was studied. The antibiotic-resistant populations decreased over time. Virulence profiles differed between faecal isolates on Day 41 and caecal isolates on Day 42. Strains with the highest numbers of virulence genes were present during the first days.

Contribution of DNA adenine methylation to gene expression heterogeneity in Salmonella enterica.

Expression of Salmonella enterica loci harboring undermethylated GATC sites at promoters or regulatory regions was monitored by single cell analysis. Cell-to-cell differences in expression were detected in ten such loci (carA, dgoR, holA, nanA, ssaN, STM1290, STM3276, STM5308, gtr and opvAB), with concomitant formation of ON and OFF subpopulations. The ON and OFF subpopulation sizes varied depending on the growth conditions, suggesting that the population structure can be modulated by environmental control. All the loci under study except STM5308 displayed altered patterns of expression in strains lacking or overproducing Dam methylase, thereby confirming control by Dam methylation. Bioinformatic analysis identified potential binding sites for transcription factors OxyR, CRP and Fur, and analysis of expression in mutant backgrounds confirmed transcriptional control by one or more of such factors. Surveys of gene expression in pairwise combinations of Dam methylation-dependent loci revealed independent switching, thus predicting the formation of a high number of cell variants. This study expands the list of S. enterica loci under transcriptional control by Dam methylation, and underscores the relevance of the DNA adenine methylome as a source of phenotypic heterogeneity.

New data on the genetic diversity of European bison Bison bonasus (Linnaeus, 1758) in Belarus

The paper presents data on the assessment of the genetic diversity of five subpopulations of the European bison (Bison bonasus) in Belarus — from the National Park “Belovezhskaya Pushcha”, the National Park “Pripyatsky”, the Osipovichi district (Mogilev area), SEI “Berezinsky Biosphere Reserve” and the Grodno region. In general, the work includes 30 samples of muscle tissue from the collection of Gene bank of wild fauna in SSPA “SPC NAS of Belarus on Bioresources” (Minsk, Belarus). Microsatellites were used as markers to assess genetic diversity, structure, and search for signs of a sharp decline in the size of bison subpopulations in the past. A total of 11 microsatellite markers were used, recommended by the Food and Agriculture Organization of the United Nations for cattle research. The analysis of B. bonasus subpopulation from the NP “Pripyatsky” showed signs of passing through the genetic bottleneck. All studied subpopulations are characterized by a similarly low genetic diversity level in all analyzed indicators (mean number of alleles, allelic diversity, observed and expected heterozygosity). The expected heterozygosity (He) for the three subpopulations from the NP “Belovezhskaya Pushcha”, the NP “Pripyatsky” and from the Osipovichi district ranged from 0.37 to 0.39. For the studied subpopulations, the values of the fixation index were negative. The assessment of the presence of genetic structuring between the subpopulations of bison from the NP “Belovezhskaya Pushcha”, the NP “Pripyatsky” and from the Osipovichi district based on the values of such indexes as Fst and DJost which showed no signs of genetic differentiation, which is also confirmed by principal coordinates analysis (PCoA). The European bison conservation in Belarus has required tremendous efforts in the past. So far, even though the impressively large population size reached in Belarus, B. bonasus status still should not be considered as stable, which is closely linked to aspects of its overall low genetic diversity. Our research confirmed the low genetic variability of Belarusian subpopulations. Therefore, the more extensive research concentrated on identifying genetic diversity is necessary to ensure the beneficial control of gene flow and register a potential correlation of unfavorable gene variants with possible inbreeding depression. These attempts are required to lay the groundwork for the management and protection of the European bison in Belarus.

Partitioning heterozygosity in subdivided populations: Some misuses of Nei's decomposition and an alternative probabilistic approach.

Nei's decomposition of total expected heterozygosity in subdivided populations into within- and between-subpopulation components, HS and DST , respectively, is a classical tool in the conservation and management of genetic resources. Reviewing why this is not a decomposition into independent terms of within- and between-subpopulation gene diversity, we illustrate how this approach can be misleading because it overemphasizes the within-subpopulation component compared to Jost's nonadditive decomposition based on gene diversity indices. Using probabilistic partitioning of the total expected heterozygosity into independent within- and between-subpopulation contributions, we show that the contribution of the within-subpopulation expected heterozygosity to the total expected heterozygosity is not HS , as suggested by Nei's decomposition, but HS /s, with s being the number of subpopulations. Finally, we compare three possible approaches of decomposing total heterozygosity in subdivided populations (i.e., Nei's decomposition, Jost's approach, and probabilistic partitioning) with regard to independence between terms and sensitivity to unequal subpopulation sizes. For the conservation and management of genetic resources, we recommend using probabilistic partitioning and Jost's differentiation parameter rather than Nei's decomposition.

Modeling the 2014-2015 Ebola Virus Disease Outbreaks in Sierra Leone, Guinea, and Liberia with Effect of High- and Low-risk Susceptible Individuals.

Ebola virus disease (EVD) is a rare but fatal disease of humans and other primates caused by Ebola viruses. Study shows that the 2014-2015 EVD outbreak causes more than 10,000 deaths. In this paper, we propose and analyze a deterministic model to study the transmission dynamics of EVD in Sierra Leone, Guinea, and Liberia. Our analyses show that the model has two equilibria: (1) the disease-free equilibrium (DFE) which is locally asymptotically stable when the basic reproduction number ([Formula: see text]) is less than unity and unstable if it is greater than one, and (2) an endemic equilibrium (EE) which is globally asymptotically stable when [Formula: see text] is greater than unity. Furthermore, the backward bifurcation occurs, a coexistence between a stale DFE and a stable EE even if the [Formula: see text] is less than unity, which makes the disease control more strenuous and would depend on the initial size of subpopulation. By fitting to reported Ebola cases from Sierra Leone, Guinea, and Liberia in 2014-2015, our model has captured the epidemic patterns in all three countries and shed light on future Ebola control and prevention strategies.

Spheroid-Based Approach to Assess the Tissue Relevance of Analysis of Dispersed-Settled Tissue Cells by Cytometry of the Reaction Rate Constant.

Cytometry of Reaction Rate Constant (CRRC) uses time-lapse fluorescence microscopy to measure a rate constant of a catalytic reaction in individual cells and, thus, facilitate accurate size determination for cell subpopulations with distinct efficiencies of this reaction. Reliable CRRC requires uniform exposure of cells to the reaction substrate followed by their uniform imaging, which in turn, requires that a tissue sample be disintegrated into a suspension of dispersed cells, and these cells settle on the support surface before being analyzed by CRRC. We call such cells "dispersed-settled" to distinguish them from cells cultured as a monolayer. Studies of the dispersed-settled cells can be tissue-relevant only if the cells maintain their 3D tissue state during the multi-hour CRRC procedure. Here, we propose an approach for assessing tissue relevance of the CRRC-based analysis of the dispersed-settled cells. Our approach utilizes cultured multicellular spheroids as a 3D cell model and cultured cell monolayers as a 2D cell model. The CRRC results of the dispersed-settled cells derived from spheroids are compared to those of spheroids and monolayers in order to find if the dispersed-settled cells are representative of the spheroids. To demonstrate its practical use, we applied this approach to a cellular reaction of multidrug resistance (MDR) transport, which was followed by extrusion of a fluorescent substrate from the cells. The approach proved to be reliable and revealed long-term maintenance of MDR transport in the dispersed-settled cells obtained from cultured ovarian cancer spheroids. Accordingly, CRRC can be used to determine accurately the size of a cell subpopulation with an elevated level of MDR transport in tumor samples, which makes CRRC a suitable method for the development of MDR-based predictors of chemoresistance. The proposed spheroid-based approach for validation of CRRC is applicable to other types of cellular reactions and, thus, will be an indispensable tool for transforming CRRC from an experimental technique into a practical analytical tool.

Multi-population genetic algorithm with ER network for solving flexible job shop scheduling problems.

A genetic algorithm (GA) cannot always avoid premature convergence, and multi-population is usually used to overcome this limitation by dividing the population into several sub-populations (sub-population number) with the same number of individuals (sub-population size). In previous research, the questions of how a network structure composed of sub-populations affects the propagation rate of advantageous genes among sub-populations and how it affects the performance of GA have always been ignored. Therefore, we first propose a multi-population GA with an ER network (MPGA-ER). Then, by using the flexible job shop scheduling problem (FJSP) as an example and considering the total individual number (TIN), we study how the sub-population number and size and the propagation rate of advantageous genes affect the performance of MPGA-ER, wherein the performance is evaluated by the average optimal value and success rate based on TIN. The simulation results indicate the following regarding the performance of MPGA-ER: (i) performance shows considerable improvement compared with that of traditional GA; (ii) for an increase in the sub-population number for a certain TIN, the performance first increases slowly, and then decreases rapidly; (iii) for an increase in the sub-population size for a certain TIN, the performance of MPGA-ER first increases rapidly and then tends to remain stable; and (iv) with an increase in the propagation rate of advantageous genes, the performance first increases rapidly and then decreases slowly. Finally, we use a parameter-optimized MPGA-ER to solve for more FJSP instances and demonstrate its effectiveness by comparing it with that of other algorithms proposed in other studies.

Clinically relevant mutations in mycobacterial LepA cause rifampicin-specific phenotypic resistance

Although all wild-type bacterial populations exhibit antibiotic tolerance, bacterial mutants with higher or lower tolerant subpopulation sizes have been described. We recently showed that in mycobacteria, phenotypically-resistant subpopulations can grow in bulk-lethal concentrations of rifampicin, a first-line anti-tuberculous antibiotic targeting RNA polymerase. Phenotypic resistance was partly mediated by paradoxical upregulation of RNA polymerase in response to rifampicin. However, naturally occurring mutations that increase tolerance via this mechanism had not been previously described. Here, we used transposon insertional mutagenesis and deep sequencing (Tnseq) to investigate rifampicin-specific phenotypic resistance using two different in vitro models of rifampicin tolerance in Mycobacterium smegmatis. We identify multiple genetic factors that mediate susceptibility to rifampicin. Disruption of one gene, lepA, a translation-associated elongation factor, increased rifampicin tolerance in all experimental conditions. Deletion of lepA increased the subpopulation size that is able to grow in bulk-lethal rifampicin concentrations via upregulation of basal rpoB expression. Moreover, homologous mutations in lepA that are found in clinical Mycobacterium tuberculosis (Mtb) isolates phenocopy lepA deletion to varying degrees. Our study identifies multiple genetic factors associated with rifampicin tolerance in mycobacteria, and may allow correlation of genetic diversity of clinical Mtb isolates with clinically important phenotypes such as treatment regimen duration.

Single nucleotide polymorphism-based analysis of the genetic structure of Liangshan pig population.

ObjectiveTo conserve and utilize the genetic resources of a traditional Chinese indigenous pig breed, Liangshan pig, we assessed the genetic diversity, genetic structure, and genetic distance in this study.MethodsWe used 50K single nucleotide polymorphism (SNP) chip for SNP detection of 139 individuals in the Liangshan Pig Conservation Farm.ResultsThe genetically closed conserved population consisted of five overlapping generations, and the total effective content of the population (Ne) was 15. The whole population was divided into five boar families and one non-boar family. Among them, the effective size of each generation subpopulation continuously decreased. However, the proportion of polymorphic markers (PN) first decreased and then increased. The average genetic distance of these 139 Liangshan pigs was 0.2823±0.0259, and the average genetic distance of the 14 boars was 0.2723±0.0384. Thus, it can be deduced that the genetic distance changed from generation to generation. In the conserved population, 983 runs of homozygosity (ROH) were detected, and the majority of ROH (80%) were within 100 Mb. The inbreeding coefficient calculated based on ROH showed an average value of 0.026 for the whole population. In addition, the inbreeding coefficient of each generation subpopulation initially increased and then decreased. In the pedigree of the whole conserved population, the error rate of paternal information was more than 11.35% while the maternal information was more than 2.13%.ConclusionThis molecular study of the population genetic structure of Liangshan pig showed loss of genetic diversity during the closed cross-generation reproduction process. It is necessary to improve the mating plan or introduce new outside blood to ensure long-term preservation of Liangshan pig.