Small Population Size Research Articles

Survival in nunatak and peripheral glacial refugia of three alpine plant species is partly predicted by altitudinal segregation.

Mountain biota survived the Quaternary cold stages most probably in peripheral refugia and/or ice-free peaks within ice-sheets (nunataks). While survival in peripheral refugia has been broadly demonstrated, evidence for nunatak refugia is still scarce. We generated RADseq data from three mountain plant species occurring at different elevations in the southeastern European Alps to investigate the role of different glacial refugia during the Last Glacial Maximum (LGM). We tested the following hypotheses. (i) The deep Piave Valley forms the deepest genetic split in the species distributed across it, delimiting two peripheral refugia. (ii) The montane to alpine species Campanula morettiana and Primula tyrolensis survived the LGM in peripheral refugia, while high-alpine to subnival Saxifraga facchinii likely survived in several nunatak refugia. (iii) The lower elevation species suffered a strong population decline during the LGM. By contrast, the higher elevation species shows long-term stability of population sizes due to survival on permanently ice-free peaks and small population sizes at present. We found peripheral refugia on both sides of the Piave Valley, which acted as a major genetic barrier. Demographic modelling confirmed nunatak survival not only for S. facchinii but also for montane to alpine C. morettiana. Altitudinal segregation influenced the species' demographic fluctuations, with the lower elevation species showing a significant population increase at the end of the LGM, and the higher elevation species either showing decrease towards the present or stable population sizes with a short bottleneck. Our results highlight the role of nunatak survival and species ecology in the demographic history of mountain species.

The influence of gene flow on population viability in an isolated urban caracal population.

Wildlife populations are becoming increasingly fragmented by anthropogenic development. Small and isolated populations often face an elevated risk of extinction, in part due to inbreeding depression. Here, we examine the genomic consequences of urbanization in a caracal (Caracal caracal) population that has become isolated in the Cape Peninsula region of the City of Cape Town, South Africa, and is thought to number ~50 individuals. We document low levels of migration into the population over the past ~75 years, with an estimated rate of 1.3 effective migrants per generation. As a consequence of this isolation and small population size, levels of inbreeding are elevated in the contemporary Cape Peninsula population (mean FROH = 0.20). Inbreeding primarily manifests as long runs of homozygosity >10 Mb, consistent with the effects of isolation due to the rapid recent growth of Cape Town. To explore how reduced migration and elevated inbreeding may impact future population dynamics, we parameterized an eco-evolutionary simulation model. We find that if migration rates do not change in the future, the population is expected to decline, though with a low projected risk of extinction. However, if migration rates decline or anthropogenic mortality rates increase, the potential risk of extinction is greatly elevated. To avert a population decline, we suggest that translocating migrants into the Cape Peninsula to initiate a genetic rescue may be warranted in the near future. Our analysis highlights the utility of genomic datasets coupled with computational simulation models for investigating the influence of gene flow on population viability.

Effects of Melissa officinalis (lemon balm) consumption on serum lipid profile: a meta-analysis of randomized controlled trials

BackgroundAccording to traditional medicine, Melissa officinalis L., (lemon balm) has been known to remove harmful substances from the blood and is considered a cardiac tonic. Therefore, its use as a cardiovascular remedy may explain the lipid-lowering effects of lemon balm. Dyslipidemia can be considered as a significant preventable risk factor for atherosclerosis, coronary heart disease and type 2 diabetes. The present study is the first meta-analysis to investigate the effects of M. officinalis administration on serum levels of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride (TG) and total cholesterol (TC).MethodsFrom inception to October 2023, a thorough search through literature was conducted using PubMed, Scopus, and Web of Science. The inclusion criteria of this study were randomized controlled trials, with or without blinding which provided adequate data for each group at the beginning and end of the follow-up period. Meta-analysis was performed on randomized controlled trials using Comprehensive Meta-Analysis (CMA) V4 software. Risk of bias in the selected studies was examined according to the revised Cochrane risk-of-bias tool for randomized trials. Begg’s funnel plot symmetry status, Begg’s rank correlation, and Egger’s weighted regression tests were employed to evaluate potential publication bias.ResultsThe meta-analysis comprised of 5 randomized controlled trials with a total of 302 patients. The findings of the meta-analysis indicated that the consumption of lemon balm had a significant decrease in TG (SMD (95% CI): -0.396(-0.620, -0.173), p-value = 0.001), TC (SMD (95% CI): -0.416 (-0.641, -0.192), p-value < 0.001) and LDL (SMD (95% CI): -0.23(-0.45, -0.008), p < 0.05) levels compared to the placebo group. While it had no statistically significant effect on HDL level (SMD (95% CI): 0.336(-0.091, 0.767), p-value = 0.123). No significant and detectable publication bias was found in the meta-analysis. Additionally, all included clinical studies demonstrated a low risk of bias for missing outcome data and selection of the reported results. The robustness of the results was demonstrated by a sensitivity analysis using the one-study remove method.ConclusionsThe findings of this meta-analysis provide evidence that lemon balm may be administered as a safe and beneficial herbal medicine for reducing TC, TG and LDL levels. According to the pooled results of 5 studies with a total of 302 patients, lemon balm intake had no significant effect on HDL level. This study reinforces the notion that lemon balm may have a substantial impact on serum lipid profile as a potential remedy in cases of dyslipidemia. The main concern of our research is the limited number of eligible studies and the relatively small population size of each individual study. The patients of these studies had different types of diseases and metabolic syndromes. However, the meta-analysis was sufficiently powered to detect the considerable effects of lemon balm in the combined population regardless of type of diseases.

Strain-specific and sensitive monitoring of the biocontrol agent Trichoderma asperellum T34 in growing medium via real-time PCR

ABSTRACT Trichoderma asperellum Samuels, Lieckf. & Nirenberg is one of several Trichoderma species comprising effective biocontrol strains. One of these, Trichoderma asperellum T34, shows activity against soilborne pathogens such as Rhizoctonia, Fusarium, and Pythium. The activity of biocontrol strains such as T34 depends on their establishment in the rhizosphere. Monitoring of the population of T34 and other strains in the rhizosphere and the growing medium is therefore important for evaluating their potential in different crops and different growing systems. Until now, strain-specific monitoring has been very difficult as the main quantification methods, i.e. traditional dilution plating or standard molecular detection methods, are specific only at genus or species level, respectively. Genotyping-by-sequencing was used to identify genomic loci specific to T34. These were used to develop strain-specific Taqman real-time (qPCR) assays. After testing for specificity and sensitivity, two assays were combined in duplex format. The duplicate assay provided an internal control to avoid a false positive signal in case one of the target loci would be present in an as yet unidentified non-target organism. An optional enrichment step in semi-selective medium was included for increased sensitivity in cases of small T34 population size, theoretically allowing detection down to 0.1 spore equivalent per mL growing medium. The techniques were applied to 200 mL samples of growing medium analyzed 0, 19, and 112 days after spiking with different numbers and combinations of spores from target and non-target Trichoderma isolates. This technique shows potential for developing other strain-specific detection assays using an affordable genotyping tool.

Niche partitioning and individual specialisation in resources and space use of sympatric fur seals at their range margin

Ecological theory predicts niche partitioning between high-level predators living in sympatry as a mechanism to minimise the selective pressure of competition. Accordingly, male Australian fur seals Arctocephalus pusillus doriferus and New Zealand fur seals A. forsteri that live in sympatry should exhibit partitioning in their broad niches (in habitat and trophic dimensions) in order to coexist. However, at the northern end of their distributions in Australia, both are recolonising their historic range after a long absence due to over-exploitation, and their small population sizes suggest competition should be weak and may allow overlap in niche space. We found some niche overlap, yet clear partitioning in diet trophic level (δ15N values from vibrissae), spatial niche space (horizontal and vertical telemetry data) and circadian activity patterns (timing of dives) between males of each species, suggesting competition may remain an active driver of niche partitioning amongst individuals even in small, peripheral populations. Consistent with individual specialisation theory, broad niches of populations were associated with high levels of individual specialisation for both species, despite putative low competition. Specialists in isotopic space were not necessarily specialists in spatial niche space, further emphasising their diverse individual strategies for niche partitioning. Males of each species displayed distinct foraging modes, with Australian fur seals primarily benthic and New Zealand fur seals primarily epipelagic, though unexpectedly high individual specialisation for New Zealand fur seals might suggest marginal populations provide exceptions to the pattern generally observed amongst other fur seals.

Fecal genotyping to estimate small mammal population size, with a comparison to live mark-recapture estimates

Live capture-recapture is often considered the gold standard for estimating wildlife population size or density, but the approach can be limited by permitting requirements, required labor, welfare concerns, and biased estimates resulting from heterogeneity in individual behavior. Noninvasive genetic sampling (e.g., from fecal pellets) offers a powerful alternative approach, but this method’s success varies among taxa, with little research available on its use in rodents. Here, we addressed a series of questions to develop a noninvasive genetic sampling approach for the endangered giant kangaroo rat (Dipodomys ingens): (1) how quickly does DNA degrade in natural conditions, (2) how many pellets are required to recover a genotype, (3) how often do multiple individuals contaminate a pooled sample from a single sampling location, and (4) how do variable and parameter estimates from noninvasive genetic sampling compare to live-trapping mark-recapture estimates? We found that fecal pellets were successfully genotyped up to 9 days (estimated probability of recovery = 0.78) after exposure to hot, arid conditions, but that rate fell precipitously soon after. Although giant kangaroo rats are territorial, multiple individuals deposited fecal pellets at the same sampling locations; however, single pellets contained sufficient DNA to recover genotypes and to identify individuals, so contamination was not a problem for this approach. Capture probabilities were lower using noninvasive genetic sampling ( = 0.26, SE = 0.01) than live trapping ( = 0.40, SE = 0.06). Population estimates were generally similar using noninvasive genetic sampling, although they were quite a bit higher ( = 64 , = 38) on one grid. Noninvasive genetic sampling can overcome many of the limitations of live-trapping for small mammals, but the approach should be tested in additional taxa and systems to provide more generalizable recommendations for sampling schemes.

A new species of Passiflora (Passifloraceae, subgenus Passiflora) in the flora of Colombia discovered in uncharted Andean territory

A new species of Passiflora belonging to the subgenus Passiflora (supersection Stipulata, section Kermesinae) is described and illustrated from living material and herbarium specimens. Passiflora pitalensis is similar to P. lehmannii, and it can be recognized primarily by its petiole green, leaves with broader lobes, peduncle green, bract lanceolate, corona filaments in 5 series with outer filaments in 2 series, fruit ovoid, and seed margin dentate. This species is rare and endemic to Colombia in the Andean region at elevations ranging from 1,749–2,027 m and should be considered Endangered (EN) due to its restricted occurrence with a small population size of no more than 90 individuals.

Founder populations of Stuckenia pectinata in restored ponds originate from genetically diverse propagule pool: A case study of urban ponds in Brussels, Belgium

Eutrophication and cyanobacteria blooms are considered major problems for the biodiversity and water quality of urban ponds. While biomanipulation techniques such as drawdown with fish removal have great potential to restore turbid ponds to a clearwater status, it remains difficult to predict if and how macrophytes will recover naturally. Here, we used individual genotyping and population genetics based on 20 nuclear microsatellite loci to investigate the recruitment and recolonization strategies of the submerged macrophyte Stuckenia pectinata (L.) Börner. More specifically, we compared the founder genetic diversity of recovering populations just after biomanipulation to the genetic diversity of spontaneous, contiguous populations that settled over an extended period of time and were within the same catchment. Our results showed that turbid ponds may contain a persistent propagule bank that allows for an immediate re-establishment of genetically diverse populations of S. pectinata once a desired clearwater state is restored. Therefore, biomanipulation without sediment removal proved to be successful for founding populations to become immediately integrated with their established populations, thus maintaining the overall diversity of this species within local areas. Additionally, our results demonstrated an excess of heterozygotes in established populations that may be caused by substantial drift in albeit small effective population sizes of this predominantly outbreeding species.

Abstract 4845: Evaluating racial disparities in immune checkpoint inhibitor survival and autoimmunity

Abstract Introduction: In recent years, immune checkpoint inhibitors (ICI) have revolutionized the landscape of treatment across a variety of cancers. Potential concerns regarding racial disparities in ICI access and therapeutic efficacy have been well documented. Recent studies have indicated improved ICI access and response outcomes in White patients compared to minority groups with head and neck cancer (HNC) and melanoma patients. In contrast, patients diagnosed with lung cancer have been mixed, with some research suggesting black patients may fare better with ICI therapy. Existing literature is largely limited to retrospective studies with small population sizes, and lacks comparisons of racial disparities across malignancies. We aim to describe and compare racial inequities in ICI outcomes in HNC, melanoma, and lung cancer. Methods: The TriNetX US Collaborative Network database was queried for patients &amp;gt;18 years-old with a diagnosis of head and neck cancer, melanoma or lung cancer that were treated with ICIs. Malignancy cohorts were defined by race: non-Hispanic White (NHW) and Black. Race cohorts were 1:1 propensity score matched (PSM) for comorbidities, oncologic stage, and chemoradiation treatment. Demographic differences in cohorts were evaluated prior to matching. Following PSM, overall survival and rates of autoimmunity were assessed at 5 years. Results: 19,443 NHW and 2,827 Black patients treated with ICI were identified. At a baseline, the Black patient cohorts had significantly higher rates of comorbidies (p&amp;lt;0.02). Across all malignancies, the geographic distribution of NHW patients was more equally distributed compared to Black patients (majority south). With PSM, black HNC patients had significantly lower survival rates compared to NHW [HR: 1.4 (1.2, 1.6), p=0.0002]. In melanoma, the same trend was present, though not significant [HR: 1.3 (0.95, 1.7), p=0.1]. In contrast, in lung cancer, Black patients had significantly higher survival rates compared to NHW patients [HR 0.78 (0.70, 0.86), p&amp;lt;0.0001]. In HN and lung cancer, NHW patients had significantly higher rates of autoimmune conditions after ICI therapy compared to Black [OR: 2.0 (1.4,2.8), 1.2 (1.0, 1.4), respectively]. Conclusion: This study represents the most extensive analysis of racial disparities on ICI outcomes across malignancies. This study found that black patients treated with ICIs had decreased survival rates at 5 years compared to NHW patients in HNC and melanoma, but increased survival rate in lung cancer. This disparity persisted following PSM, matching cohorts for comorbidities, oncologic stage and adjuvant therapy. Black patients also had significantly lower rates of autoimmunity in HN and lung cancer. Noted differences in survival may be a reflection of geographic practice differences, access to care and/or socioeconomic status. Further investigation is required to elucidate the underlying etiologies of these trends. Citation Format: Kathryn L. Nunes, Pablo Llerena, Praneet Kaki, Shreya Mandloi, Annie Moroco, Eric Mastrolonardo, David M. Cognetti, Adam J. Luginbuhl, Joseph M. Curry. Evaluating racial disparities in immune checkpoint inhibitor survival and autoimmunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4845.

Transcriptome data analysis provides insights into the conservation of Michelia lacei, a plant species with extremely small populations distributed in Yunnan province, China.

Michelia lacei W.W.Smith (Magnoliaceae), was classified as a Plant Species with Extremely Small Populations (PSESP) by the Yunnan Provincial Government in both action plans of 2012 and 2021. This evergreen tree is known for its high ornamental and scientific value, but it faces significant threats due to its extremely small population size and narrow geographical distribution. The study aims to understand the genetic structure, diversity, and demographic history of this species to inform its conservation strategies. The analysis of transcriptome data from 64 individuals across seven populations of M. lacei identified three distinct genetic clusters and generated 104,616 single-nucleotide polymorphisms (SNPs). The KM ex-situ population, originating from Longling County, exhibited unique genetic features, suggesting limited gene flow. The genetic diversity was substantial, with significant differences between populations, particularly between the KM lineage and the OTHER lineage. Demographic history inferred from the data indicated population experienced three significant population declines during glaciations, followed by periods of recovery. We estimated the effective population size (Ne) of the KM and OTHER lineages 1,000 years ago were 85,851 and 416,622, respectively. Gene flow analysis suggested past gene flow between populations, but the KM ex-situ population showed no recent gene flow. A total of 805 outlier SNPs, associated with four environmental factors, suggest potential local adaptation and showcase the species' adaptive potential. Particularly, the BZ displayed 515 adaptive loci, highlighting its strong potential for adaptation within this group. The comprehensive genomic analysis of M. lacei provides valuable insights into its genetic background and highlights the urgent need for conservation efforts. The study underscores the importance of ex-situ conservation methods, such as seed collection and vegetative propagation, to safeguard genetic diversity and promote population restoration. The preservation of populations like MC and BZ is crucial for maintaining the species' genetic diversity. In-situ conservation measures, including the establishment of in-situ conservation sites and community engagement, are essential to enhance protection awareness and ensure the long-term survival of this threatened plant species.

Proof of concept of physiologically based pharmacokinetic modelling in paediatric acute lymphoblastic leukaemia.

Physiologically based pharmacokinetic (PBPK) modelling is an alternative modelling technique that is increasingly used in pharmacokinetics. Due to its nature, it can be complementarily employed to population pharmacokinetics, especially when it comes to small population size. Here, we report the proof of concept of its application to accurately describe the pharmacokinetics of a recombinant L-asparaginase in paediatric patients with acute lymphoblastic leukaemia. Data from two randomized, double-blind, phase II/III clinical studies (MC-ASP.4/ALL; MC-ASP.5/ALL) were included to setup and evaluate the final model, respectively. Final population values for basic pharmacokinetic parameters were calculated (clearance: 0.0569 L/h/19.5 kg, volume of distribution: 1.251 L, half-life: 18.5 h, trough concentration: 140.9 IU/L). Pharmacokinetic parameter prediction as well as predictive performance of the model proofed to be comparable to a separately developed population pharmacokinetic model with 13% deviation in predicted median L-asparaginase trough levels. To the best of our knowledge, this is the first whole-body PBPK model of a non-antibody therapeutic protein.

Genetic diversities in wild and cultivated populations of the two closely-related medical plants species, Tripterygium Wilfordii and T. Hypoglaucum (Celastraceae)

BackgroundThe sustainable supply of medicinal plants is important, and cultivating and domesticating them has been suggested as an optimal strategy. However, this can lead to a loss of genetic diversity. Tripterygium wilfordii Hook. f. is a medicinal plant commonly used in traditional Chinese medicine, but its wild populations are dwindling due to excessive harvesting. To protect the species and meet the increasing demand, it is urgent to cultivate it on a large scale. However, distinguishing between T. wilfordii and T. hypoglaucum, two similar species with different medicinal properties, is challenging. Therefore, it is crucial to understand the genetic diversity and population structure of these species for their sustainable utilization.ResultsIn this study, we investigated the genetic diversity and population structure of the two traditional medicinal semiwoody vines plant species, Tripterygium wilfordii and T. hypoglaucum, including wild and cultivated populations using chloroplast DNA (cpDNA) sequences and microsatellite loci. Our results indicated that the two species maintain a high level of genetic divergence, indicating possible genetic bases for the different contents of bioactive compounds of the two species. T. wilfordii showed lower genetic diversity and less subdivided population structures of both markers than T. hypoglaucum. The potential factors in shaping these interesting differences might be differentiated pollen-to-seed migration rates, interbreeding, and history of population divergence. Analyses of cpDNA and microsatellite loci supported that the two species are genetically distinct entities. In addition, a significant reduction of genetic diversity was observed for cultivated populations of the two species, which mainly resulted from the small initial population size and propagated vegetative practice during their cultivation.ConclusionOur findings indicate significant genetic divergence between T. wilfordii and T. hypoglaucum. The genetic diversity and population structure analyses provide important insights into the sustainable cultivation and utilization of these medicinal plants. Accurate identification and conservation efforts are necessary for both species to ensure the safety and effectiveness of crude drug use. Our study also highlighted the importance of combined analyses of different DNA markers in addressing population genetics of medicinal plants because of the contrasts of inheritance and rates of gene flow. Large-scale cultivation programs should consider preserving genetic diversity to enhance the long-term sustainability of T. wilfordii and T. hypoglaucum. Our study proposed that some populations showed higher genetic diversity and distinctness, which can be considered with priority for conservation and as the sources for future breeding and genetic improvement.

How does population size influence administrative performance? Evidence from Malta, Samoa, and Suriname

Public administration scholars pay increasing attention to the role of context as a pathway to genuinely comparative analysis. Specifically, they focus on the economic, institutional and socio-cultural conditions in which administration takes place. Population size is an overlooked contextual factor despite the fact that existing studies often make implicit, positive assumptions about the effects of smallness on administrative performance. We investigate these assumptions by focusing on small, rather than large states across three dimensions: representativeness, transparency and service delivery. Drawing on unique qualitative data from three small states from different continents, Malta, Samoa and Suriname, we find that contra implicit assumptions, small population size does not have the overwhelmingly positive effects that much of the literature assumes. Rather, smallness tends to undermine legal-rational decision making and to facilitate patronage-based service delivery. These findings indicate that the contextual turn in public administration needs to pay more attention to the way population size shapes bureaucratic practice in all states, large and small.

Feasibility of wastewater-based detection of emergent pandemics through a global network of airports.

Wastewater-based surveillance has been put into practice during the pandemic. Persistence of SARS-CoV-2 in faeces of infected individuals, and high volume of passengers travelling by air, make it possible to detect virus from aircraft wastewater, lending itself to the potential identification of a novel pathogen prior to clinical diagnosis. In this study, we estimated the likelihood of detecting the virus through aircraft wastewater from the probabilities of air travel, viral shedding, defecation, testing sensitivity, and sampling. We considered various hypothetical scenarios, with diverse sampling proportions of inbound flights, surveillance airports, and sources of outbreaks. Our calculations showed that the probability of detecting SARS-CoV-2 would increase exponentially against time in the early phase of the pandemic, and would be much higher if the 20 major airports in Asia, Europe, and North America cooperated to perform aircraft wastewater surveillance. We also found other contributors to early detection, including high sampling proportion of inbound flight at destination airports, small population size of the epicentre relative to the travel volume, and large volume of outbound travelers to major airports around the globe. We concluded that routine aircraft wastewater monitoring could be a feasible approach for early identification and tracking of an emerging pathogen with high faecal shedding rates, particularly when implemented through a global surveillance network of major airports.

Random genetic drift sets an upper limit on mRNA splicing accuracy in metazoans

Most eukaryotic genes undergo alternative splicing (AS), but the overall functional significance of this process remains a controversial issue. It has been noticed that the complexity of organisms (assayed by the number of distinct cell types) correlates positively with their genome-wide AS rate. This has been interpreted as evidence that AS plays an important role in adaptive evolution by increasing the functional repertoires of genomes. However, this observation also fits with a totally opposite interpretation: given that ‘complex’ organisms tend to have small effective population sizes (Ne), they are expected to be more affected by genetic drift, and hence more prone to accumulate deleterious mutations that decrease splicing accuracy. Thus, according to this ‘drift barrier’ theory, the elevated AS rate in complex organisms might simply result from a higher splicing error rate. To test this hypothesis, we analyzed 3496 transcriptome sequencing samples to quantify AS in 53 metazoan species spanning a wide range of Ne values. Our results show a negative correlation between Ne proxies and the genome-wide AS rates among species, consistent with the drift barrier hypothesis. This pattern is dominated by low abundance isoforms, which represent the vast majority of the splice variant repertoire. We show that these low abundance isoforms are depleted in functional AS events, and most likely correspond to errors. Conversely, the AS rate of abundant isoforms, which are relatively enriched in functional AS events, tends to be lower in more complex species. All these observations are consistent with the hypothesis that variation in AS rates across metazoans reflects the limits set by drift on the capacity of selection to prevent gene expression errors.

Random genetic drift sets an upper limit on mRNA splicing accuracy in metazoans.

Most eukaryotic genes undergo alternative splicing (AS), but the overall functional significance of this process remains a controversial issue. It has been noticed that the complexity of organisms (assayed by the number of distinct cell types) correlates positively with their genome-wide AS rate. This has been interpreted as evidence that AS plays an important role in adaptive evolution by increasing the functional repertoires of genomes. However, this observation also fits with a totally opposite interpretation: given that 'complex' organisms tend to have small effective population sizes (Ne), they are expected to be more affected by genetic drift, and hence more prone to accumulate deleterious mutations that decrease splicing accuracy. Thus, according to this 'drift barrier' theory, the elevated AS rate in complex organisms might simply result from a higher splicing error rate. To test this hypothesis, we analyzed 3496 transcriptome sequencing samples to quantify AS in 53 metazoan species spanning a wide range of Ne values. Our results show a negative correlation between Ne proxies and the genome-wide AS rates among species, consistent with the drift barrier hypothesis. This pattern is dominated by low abundance isoforms, which represent the vast majority of the splice variant repertoire. We show that these low abundance isoforms are depleted in functional AS events, and most likely correspond to errors. Conversely, the AS rate of abundant isoforms, which are relatively enriched in functional AS events, tends to be lower in more complex species. All these observations are consistent with the hypothesis that variation in AS rates across metazoans reflects the limits set by drift on the capacity of selection to prevent gene expression errors.

Too simple, too complex, or just right? Advantages, challenges, and guidance for indicators of genetic diversity

Abstract Measuring genetic diversity of wild species using DNA-based data remains resource intensive and time consuming for nearly all species. However, genetic assessments are needed for global conservation commitments, including the Convention on Biological Diversity, and for governments and managers to evaluate conservation progress, as well as prioritizing species and populations to preserve and recover genetic diversity (e.g., via genetic rescue). Recently, indicators were developed for tracking and reporting genetic diversity status and trends for hundreds of species. The indicators quantify two simple proxies of within-population and among-population genetic diversity and adaptive potential: small effective population size (Ne &amp;lt; 500) and the loss of genetically distinct populations. The indicators must balance scientific credibility, practicality, and simplicity. In the present article, we summarize the advantages of these pragmatic indicators, address critiques by scientists for simplifying assumptions and by policymakers for complexity, and propose potential solutions and next steps. We aim to support practitioners putting indicators into policy, action, legislation, and reporting.

Management of neurogenic bladder in patients with spinal cord injuries/disorders and end stage renal disease: a case series

IntroductionPatients with spinal cord injuries/disorders (SCI/D) often suffer from bladder dysfunction, commonly referred to as neurogenic bladder or neurogenic lower urinary tract dysfunction (NLUTD). Standard urologic evaluation and management help to minimize complications such as vesicoureteral reflux, urinary tract infection, and nephrolithiasis. However, we have further encountered patients with more complex issues, such as chronic kidney disease (CKD), end-stage renal disease (ESRD), bilateral nephrectomies, and urinary diversion/augmentation surgeries. Of particular interest, there is a lack of standardized guidance for bladder management in SCI/D patients with ESRD. These patients are at high risk for urological complications and would benefit from codified bladder management strategies.Case presentationIn this article, we present eleven unique cases of NLUTD with associated ESRD and discuss recommendations utilizing simple and commonly available clinical interventions.DiscussionThe inherently small population size of SCI/D patients with NLUTD and ESRD makes detailing a large sample size case series difficult. Future studies must aim to include a larger sample size as able, however, to better determine standardized protocols for chronic bladder management in SCI/D patients with NLUTD and ESRD. Experiences from this small case series are offered for consideration.

Heuristic control of power consumption by up to 1000 V electrical loads at mining enterprises

Purpose. To develop a method for synthesizing the structure and algorithm of the system for automated control of power consumption by up to 1000 V electrical receivers at mining enterprises with iron ore underground mining methods. This enables direct control of the load connection to the industrial power grid to ensure minimum power costs depending on its cost per day ahead. Methodology. The problem of controlling power consumption of electrical receivers at iron ore underground mines is formalized as a binary form of mixed integer programming. To solve it, a binary implementation of the heuristic genetic algorithm is used. The mathematical modeling method analyzes the impact of genetic algorithm settings, such as the number of phenotypes in the population, the number of elite phenotypes that pass unchanged to the next generation, and the method of phenotype crossover on its quality. Findings. As a result of the research, it is found that the most effective way to control the process of power consumption based on an evolutionary genetic algorithm is to use the Laplace crossover function and keep the percentage of elite phenotypes in the population at 10 %. Moreover, at the smallest population size, the best accuracy is observed when using the Laplace function, while at one- and two-point crossover functions, it worsens, but not significantly (no more than 0.2 %). However, as the number of elite phenotypes increases, the duration of the evolutionary search in the control process is reduced by almost a factor of two in the case of one- and two-point crossovers. Originality. For the first time, the structure of a heuristic system for automated control of power consumption by underground electrical receivers with a supply voltage of up to 1000 V at iron ore underground mines has been developed on the basis of an evolutionary genetic algorithm. Depending on the designed volumes of ore production and the daily power cost per day, this allows determining the optimal power load schedule of underground distribution substations in advance, which, subject to the accepted limits on hourly and daily power, minimizes the cost of purchasing power, and thus reduces the cost of the final product. Practical value. The architecture of a heuristic system for controlling power consumption by electrical receivers with a voltage of up to 1000 V based on an evolutionary genetic algorithm is developed and recommended when optimizing the power load schedule of transformer substations of mining and metallurgical enterprises, in particular, of iron ore underground mines operating in this voltage class.

Genomic ancestry and social dynamics of the last hunter-gatherers of Atlantic France

Since the early Holocene, western and central Europe was inhabited by a genetically distinct group of Western Hunter-Gatherers (WHGs). This group was eventually replaced and assimilated by the incoming Neolithic farmers. The western Atlantic façade was home to some of the last Mesolithic sites of mainland Europe, represented by the iconic open-air sites at Hoedic and Téviec in southern Brittany, France. These sites are known for the unusually well-preserved and rich burials. Genomic studies of Mesolithic European hunter-gatherers have been limited to single or a few individuals per site and our understanding of the social dynamics of the last Mesolithic hunter-gatherers of Europe and their interactions with incoming farmers is limited. We sequenced and analyzed the complete genomes of 10 individuals from the Late Mesolithic sites of Hoedic, Téviec, and Champigny, in France, four of which sequenced to between 23- and 8-times genome coverage. The analysis of genomic, chronological and dietary data revealed that the Late Mesolithic populations in Brittany maintained distinct social units within a network of exchanging mates. This resulted in low intra-group biological relatedness that prevented consanguineous mating, despite the small population size of the Late Mesolithic groups. We found no genetic ancestry from Neolithic farmers in the analyzed hunter-gatherers, even though some of them may have coexisted with the first farming groups in neighboring regions. Hence, contrary to previous conclusions based on stable isotope data from the same sites, the Late Mesolithic forager community was limited in mate-exchange to neighboring hunter-gatherer groups, to the exclusion of Neolithic farmers.