Search

Planetary sustainability is in trouble, heading towards what pioneer of evolutionary biology, E.O Wilson, twenty-two years ago called a "bottleneck". Created through the actions of humanity this is an increasingly narrow passage through which only some species can pass, and on which humans depend to provide the sources of re-radiation. What is lost is hard to impossible to restore. Keeping this passage as wide as possible is crucial, but the trends are not yet promising. At a time when those trends appear to be converging to a human and ecological crisis of planetary but finite duration, changed priorities are required whilst at the same time providing opportunity. In particular, strategies, such as experimental governance devised to act in the face of unknowns and uncertain knowledge provide a basis for action to hold open and successfully pass through the bottleneck, a goal which is of the highest importance for humans as we seek to achieve a sustainable future. [ABSTRACT FROM AUTHOR]

Theoretical Biology and the Organism After the clear historical break of the First World War, and driven not least by an empirically and conceptually opaque situation - a I Krise i as Schaxel and others labeled it - we find a period in which new attempts of scientists and philosophers to build theoretical biology increasingly flourished. How does the trend towards theoretical biology resemble recent calls to renew the conceptual foundations of biology? In 1919, the German zoologist Julius Schaxel began his book I Grundzüge der Theoriebildung in der Biologie i (Foundations of Theory Construction in Biology) with the following statement: Physics and chemistry have maintained method and theory with increasing factual enrichment .... At the same time, biology loses its own reasoning, wants to be physics and chemistry of the living, collects immeasurable individual knowledge [Einzelwissen], hypotheses proliferate uncontrolled, self-reflection, methodology remains undone. [Extracted from the article]

Genome wide patterns of nucleotide diversity and recombination reveal considerable variation including hotspots. Some studies suggest that these patterns are primarily dictated by individual locus history related at a broader scale to the population demographic history. Because bottlenecks have occurred in the history of numerous species, we undertook a simulation approach to investigate their impact on the patterns of aggregation of polymorphic sites and linkage disequilibrium (LD). We developed a new index (Polymorphism Aggregation Index) to characterize this aggregation and showed that variation in the density of polymorphic sites results from an interplay between the bottleneck scenario and the recombination rate. Under particular conditions, aggregation is maximized and apparent mutation hotspots resulting in a 50-fold increase in polymorphic sites density can occur. In similar conditions, long distance LD can be detected. [ABSTRACT FROM AUTHOR]

Arabidopsis halleri is a hyperaccumulating pseudo-metallophyte and an emerging model to explore molecular basis of metal tolerance and hyperaccumulation. In this regard, understanding of interacting genes can be a crucial aspect as these interactions regulate several biological functions at molecular level in response to multiple signals. In this current study, we applied a weighted gene co-expression network analysis (WGCNA) on root and shoot RNA-seq data of A. halleri to predict the related scale-free organ specific co-expression networks, for the first time. A total of 19,653 genes of root and 18,081 genes of shoot were grouped into 14 modules and subjected to GO and KEGG enrichment analysis. "Photosynthesis" and "photosynthesis–antenna proteins" were identified as the most enriched and common pathway to both root and shoot. Whereas "glucosinolate biosynthesis," "autophagy," and "SNARE interactions in vesicular transport" were specific to root, and "circadian rhythm" was found to be enriched only in shoot. Later, hub and bottleneck genes were identified in each module by using cytoHubba plugin based on Cytoscape and scoring the relevance of each gene to the topology of the network. The modules with the most significant differential expression pattern across control and treatment (Cd-Zn treatment) were selected and their hub and bottleneck genes were screened to validate their possible involvement in heavy metal stress. Moreover, we combined the analysis of co-expression modules together with protein–protein interactions (PPIs), confirming some genes as potential candidates in plant heavy metal stress and as biomarkers. The results from this analysis shed the light on the pivotal functions to the hyperaccumulative trait of A. halleri, giving perspective to new paths for future research on this species. [ABSTRACT FROM AUTHOR]

The pathogenesis of bacteraemia after challenge with one million pneumococci of three isogenic variants was investigated. Sequential analyses of blood samples indicated that most episodes of bacteraemia were monoclonal events providing compelling evidence for a single bacterial cell bottleneck at the origin of invasive disease. With respect to host determinants, results identified novel properties of splenic macrophages and a role for neutrophils in early clearance of pneumococci. Concerning microbial factors, whole genome sequencing provided genetic evidence for the clonal origin of the bacteraemia and identified SNPs in distinct sub-units of F0/F1 ATPase in the majority of the ex vivo isolates. When compared to parental organisms of the inoculum, ex-vivo pneumococci with mutant alleles of the F0/F1 ATPase had acquired the capacity to grow at low pH at the cost of the capacity to grow at high pH. Although founded by a single cell, the genotypes of pneumococci in septicaemic mice indicate strong selective pressure for fitness, emphasising the within-host complexity of the pathogenesis of invasive disease. [ABSTRACT FROM AUTHOR]

The 3′ untranslated genome region (UTR) of arthropod-borne viruses is characterized by enriched direct repeats (DRs) and stem-loop structures. Despite many years of theoretical and experimental study, on-going positive selection on the 3′UTR had never been observed in ‘real-time,’ and the role of the arbovirus 3′UTR remains poorly understood. We observed a lineage-specific 3′UTR sequence pattern in all available Asian lineage of the mosquito-borne alphavirus, chikungunya virus (CHIKV) (1958–2009), including complicated mutation and duplication patterns of the long DRs. Given that a longer genome is usually associated with less efficient replication, we hypothesized that the fixation of these genetic changes in the Asian lineage 3′UTR was due to their beneficial effects on adaptation to vectors or hosts. Using reverse genetic methods, we examined the functional importance of each direct repeat. Our results suggest that adaptation to mosquitoes, rather than to mammalian hosts, is a major evolutionary force on the CHIKV 3′UTR. Surprisingly, the Asian 3′UTR appeared to be inferior to its predicted ancestral sequence for replication in both mammals and mosquitoes, suggesting that its fixation in Asia was not a result of directional selection. Rather, it may have resulted from a population bottleneck during its introduction from Africa to Asia. We propose that this introduction of a 3′UTR with deletions led to genetic drift and compensatory mutations associated with the loss of structural/functional constraints, followed by two independent beneficial duplications and fixation due to positive selection. Our results provide further evidence that the limited epidemic potential of the Asian CHIKV strains resulted from founder effects that reduced its fitness for efficient transmission by mosquitoes there. [ABSTRACT FROM AUTHOR]

Retroviral insertional mutagenesis (RIM) is a powerful tool for cancer genomics that was combined in this study with deep sequencing (RIM/DS) to facilitate a comprehensive analysis of lymphoma progression. Transgenic mice expressing two potent collaborating oncogenes in the germ line (CD2-MYC, -Runx2) develop rapid onset tumours that can be accelerated and rendered polyclonal by neonatal Moloney murine leukaemia virus (MoMLV) infection. RIM/DS analysis of 28 polyclonal lymphomas identified 771 common insertion sites (CISs) defining a ‘progression network’ that encompassed a remarkably large fraction of known MoMLV target genes, with further strong indications of oncogenic selection above the background of MoMLV integration preference. Progression driven by RIM was characterised as a Darwinian process of clonal competition engaging proliferation control networks downstream of cytokine and T-cell receptor signalling. Enhancer mode activation accounted for the most efficiently selected CIS target genes, including Ccr7 as the most prominent of a set of chemokine receptors driving paracrine growth stimulation and lymphoma dissemination. Another large target gene subset including candidate tumour suppressors was disrupted by intragenic insertions. A second RIM/DS screen comparing lymphomas of wild-type and parental transgenics showed that CD2-MYC tumours are virtually dependent on activation of Runx family genes in strong preference to other potent Myc collaborating genes (Gfi1, Notch1). Ikzf1 was identified as a novel collaborating gene for Runx2 and illustrated the interface between integration preference and oncogenic selection. Lymphoma target genes for MoMLV can be classified into (a) a small set of master regulators that confer self-renewal; overcoming p53 and other failsafe pathways and (b) a large group of progression genes that control autonomous proliferation in transformed cells. These findings provide insights into retroviral biology, human cancer genetics and the safety of vector-mediated gene therapy. [ABSTRACT FROM AUTHOR]

In the absence of long-term monitoring data, inferences about extinctions of species and populations are generally based on past observations about the presence of a particular species at specified places and times (sightings). Several methods have been developed to estimate the probability and timing of extinctions from records of such sightings, but they differ in their computational complexity and assumptions about the nature of the sighting record. Here we use simulations to evaluate the performance of seven methods proposed to estimate the upper confidence limit on extinction times under different extinction and sampling scenarios. Our results show that the ability of existing methods to correctly estimate the timing of extinctions varies with the type of extinction (sudden vs. gradual) and the nature of sampling effort over time. When the probability of sampling a species declines over time, many of the methods perform poorly. On the other hand, the simulation results also suggest that as long as the choice of the method is determined by the nature of the underlying sighting data, existing methods should provide reliable inferences about the timing of past extinctions. [ABSTRACT FROM AUTHOR]

Copyright of Applications in Plant Sciences is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: Analysis reconstruction networks from two diseases, IBD and NASH and their relationship, based on systems biology methods. Background: IBD and NASH are two complex diseases, with progressive prevalence and high cost for countries. There are some reports on co-existence of these two diseases. In addition, they have some similar risk factors such as age, obesity, and insulin resistance. Therefore, systems biology approach can help to discover their relationship. Methods: DisGeNET and STRING databases were sources of disease genes and constructing networks. Three plugins of Cytoscape software, including ClusterONE, ClueGO and CluePedia, were used to analyze and cluster networks and enrichment of pathways. Based on degree and Betweenness, hubs and bottleneck nodes were defined. Results: Common genes between IBD and NASH construct a network with 99 nodes. Common genes between IBD and NASH were extracted and imported to STRING database to construct PPI network. The resulting network contained 99 nodes and 333 edges. Five genes were selected as hubs: JAK2, TLR2, TP53, TLR4 and STAT3 and five genes were selected as bottleneck including: JAK2, TP53, AGT, CYP3A4 and TLR4. These genes were hubs in analysis network that was constructed from hubs of NASH and IBD networks. Conclusion: Systems biology methods, specifically PPI networks, can be useful for analyzing complicated related diseases. Finding Hub and bottleneck proteins should be the goal of drug designing and introducing disease markers. [ABSTRACT FROM AUTHOR]

Background: The IAEA colony is the only one available for mass rearing of Glossina pallidipes, a vector of human and animal African trypanosomiasis in eastern Africa. This colony is the source for Sterile Insect Technique (SIT) programs in East Africa. The source population of this colony is unclear and its genetic diversity has not previously been evaluated and compared to field populations. Methodology/Principal Findings: We examined the genetic variation within and between the IAEA colony and its potential source populations in north Zimbabwe and the Kenya/Uganda border at 9 microsatellites loci to retrace the demographic history of the IAEA colony. We performed classical population genetics analyses and also combined historical and genetic data in a quantitative analysis using Approximate Bayesian Computation (ABC). There is no evidence of introgression from the north Zimbabwean population into the IAEA colony. Moreover, the ABC analyses revealed that the foundation and establishment of the colony was associated with a genetic bottleneck that has resulted in a loss of 35.7% of alleles and 54% of expected heterozygosity compared to its source population. Also, we show that tsetse control carried out in the 1990's is likely reduced the effective population size of the Kenya/Uganda border population. Conclusions/Significance: All the analyses indicate that the area of origin of the IAEA colony is the Kenya/Uganda border and that a genetic bottleneck was associated with the foundation and establishment of the colony. Genetic diversity associated with traits that are important for SIT may potentially have been lost during this genetic bottleneck which could lead to a suboptimal competitiveness of the colony males in the field. The genetic diversity of the colony is lower than that of field populations and so, studies using colony flies should be interpreted with caution when drawing general conclusions about G. pallidipes biology. [ABSTRACT FROM AUTHOR]

Sperm marking provides a key tool for reproductive biology studies, but it also represents a valuable monitoring tool for genetic pest control strategies such as the sterile insect technique. Sperm-marked lines can be generated by introducing transgenes that mediate the expression of fluorescent proteins during spermatogenesis. The homozygous lines established by transgenesis approaches are going through a genetic bottleneck that can lead to reduced fitness. Transgenic SIT approaches have mostly focused on Dipteran and Lepidopteran pests so far. With this study, we provide sperm-marked lines for the Coleopteran pest model organism, the red flour beetle Tribolium castaneum, based on the β2-tubulin promoter/enhancer driving red (DsRed) or green (EGFP) fluorescence. The obtained lines are reasonably competitive and were thus used for our studies on reproductive biology, confirming the phenomenon of 'last-male sperm precedence' and that the spermathecae are deployed for long-term sperm storage, enabling the use of sperm from first mating events even after secondary mating events for a long period of time. The homozygosity and competitiveness of the lines will enable future studies to analyze the controlled process of sperm movement into the long-term storage organ as part of a post-mating cryptic female choice mechanism of this extremely promiscuous species. [ABSTRACT FROM AUTHOR]

Rhynchaenus maculosus is an emerging insect pest with an increasingly serious tendency. Lack of biology information results in the bottleneck of integrated management of this pest. To facilitate an available design of integrated pest management strategy, biology of R. maculosus, including voltinism, life cycle, distribution, and damage has been investigated. Results reveal that R. maculosus is oligophagous and distributes in Heilongjiang, Jilin, and Liaoning provinces, China. This pest produces one generation per year (univoltinism) and overwinters as adults in leaf litter. From mid-April to late-April, active overwintering adults emerge from overwintering sites. The next generation of adult R. maculosus appears from mid-May to early June until mid-August to early September when the beetles move into the overwintering places. The entire time span of adult occurrence ranges from 315.6 ± 3.6 to 336.4 ± 3.2 days (Mean ± SD). Larvae undergo 3 instars with a total duration of 20 to 23 days. R. maculosus larvae feed on Q. wutaishanica and Q. mongolica without host-specific preference between the two host species, but do not harm Q. acutissim. Three species of larval parasites were collected and identified as Braconidae sp., Eulophidae sp., and Ceraphronidae sp. Biological information of R. maculosus provides essential insights for design and implementation of integrated management of this pest. [ABSTRACT FROM AUTHOR]

In the field of bioinformatics, understanding protein secondary structure is very important for exploring diseases and finding new treatments. Considering that the physical experiment-based protein secondary structure prediction methods are time-consuming and expensive, some pattern recognition and machine learning methods are proposed. However, most of the methods achieve quite similar performance, which seems to reach a model capacity bottleneck. As both model design and learning process can affect the model learning capacity, we pay attention to the latter part. To this end, a framework called Multistage Combination Classifier Augmented Model (MCCM) is proposed to solve the protein secondary structure prediction task. Specifically, first, a feature extraction module is introduced to extract features with different levels of learning difficulties. Second, multistage combination classifiers are proposed to learn decision boundaries for easy and hard samples, respectively, with the latter penalizing the loss value of the hard samples and finally improving the prediction performance of hard samples. Third, based on the Dirichlet distribution and information entropy measurement, a sample difficulty discrimination module is designed to assign samples with different learning difficulty levels to the aforementioned classifiers. The experimental results on the publicly available benchmark CB513 dataset show that our method outperforms most state-of-the-art models. [ABSTRACT FROM AUTHOR]

To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we generated high-quality genome sequences from three gray wolves, one from each of the three putative centers of dog domestication, two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. Analysis of these sequences supports a demographic model in which dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow. In dogs, the domestication bottleneck involved at least a 16-fold reduction in population size, a much more severe bottleneck than estimated previously. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was substantially larger than represented by modern wolf populations. We narrow the plausible range for the date of initial dog domestication to an interval spanning 11–16 thousand years ago, predating the rise of agriculture. In light of this finding, we expand upon previous work regarding the increase in copy number of the amylase gene (AMY2B) in dogs, which is believed to have aided digestion of starch in agricultural refuse. We find standing variation for amylase copy number variation in wolves and little or no copy number increase in the Dingo and Husky lineages. In conjunction with the estimated timing of dog origins, these results provide additional support to archaeological finds, suggesting the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that, surprisingly, none of the extant wolf lineages from putative domestication centers is more closely related to dogs, and, instead, the sampled wolves form a sister monophyletic clade. This result, in combination with dog-wolf admixture during the process of domestication, suggests that a re-evaluation of past hypotheses regarding dog origins is necessary. [ABSTRACT FROM AUTHOR]

We investigated potential drivers of interest in topic–context and topic–activity combinations, as well as interactions between the different elements of situational interest in evolutionary biology. High school students (n = 982, age 17 years) were asked to rate their interest in two sets of items consisting of topic–context and topic–activity combinations. Rasch modeling, analyses of variance, and descriptive statistics revealed that topics are the dominant dimension and moderate the general level of interest that students express in both topic–context and topic–activity combinations. Qualitative findings from interviews with high school students (n = 6, age 16 years) support this finding. Thus, choice of a particular context, as well as choice of a particular activity, may be less important than previously assumed, since topics are the bottleneck and drive situational interest in topic–context combinations and topic–activity combinations. Implications for evolution education are discussed. [ABSTRACT FROM AUTHOR]

Copyright of Crustaceana is the property of Brill Academic Publishers and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Where do the bottlenecks for information and attention lie when our visual system processes incoming stimuli? The human visual system encodes the incoming stimulus and transfers its contents into three major memory systems with increasing time scales, viz., sensory (or iconic) memory, visual short-term memory (VSTM), and long-term memory (LTM). It is commonly believed that the major bottleneck of information processing resides in VSTM. In contrast to this view, we show major bottlenecks for motion processing prior to VSTM. In the first experiment, we examined bottlenecks at the stimulus encoding stage through a partial-report technique by delivering the cue immediately at the end of the stimulus presentation. In the second experiment, we varied the cue delay to investigate sensory memory and VSTM. Performance decayed exponentially as a function of cue delay and we used the time-constant of the exponential-decay to demarcate sensory memory from VSTM. We then decomposed performance in terms of quality and quantity measures to analyze bottlenecks along these dimensions. In terms of the quality of information, two thirds to three quarters of the motion-processing bottleneck occurs in stimulus encoding rather than memory stages. In terms of the quantity of information, the motion-processing bottleneck is distributed, with the stimulus-encoding stage accounting for one third of the bottleneck. The bottleneck for the stimulus-encoding stage is dominated by the selection compared to the filtering function of attention. We also found that the filtering function of attention is operating mainly at the sensory memory stage in a specific manner, i.e., influencing only quantity and sparing quality. These results provide a novel and more complete understanding of information processing and storage bottlenecks for motion processing. [ABSTRACT FROM AUTHOR]

Background: The origin of extraordinarily rich biodiversity in tropical forests is often attributed to evolution under stable climatic conditions over a long period or to climatic fluctuations during the recent Quaternary period. Here, we test these two hypotheses using Dracaena cambodiana, a plant species distributed in paleotropical forests. Methods: We analyzed nucleotide sequence data of two chloroplast DNA (cpDNA: atpB-rbcL and trnD-trnT) regions and genotype data of six nuclear microsatellites from 15 populations (140 and 363 individuals, respectively) distributed in Indochina Peninsular and Hainan Island to infer the patterns of genetic diversity and phylogeographic structure. The population bottleneck and genetic drift were estimated based upon nuclear microsatellites data using the software programs BOTTLENECK and 2MOD. The lineage divergence times and past population dynamics based on cpDNA data were estimated using coalescent-based isolation-with-migration (IMa) and BEAST software programs. Results: A significant phylogeographic structure (NST = 0.876, GST = 0.796, FST-SSR = 0.329, RST = 0.449; NST>GST, RST>FST-SSR, P<0.05) and genetic differentiation among populations were detected. Bottleneck analyses and Bayesian skyline plot suggested recent population reduction. The cpDNA haplotype network revealed the ancestral populations from the southern Indochina region expanded to northward. The most recent ancestor divergence time of D. cambodiana dated back to the Tertiary era and rapid diversification of terminal lineages corresponded to the Quaternary period. Conclusions: The results indicated that the present distribution of genetic diversity in D. cambodiana was an outcome of Tertiary dispersal and rapid divergence during the Quaternary period under limited gene flow influenced by the uplift of Himalayan-Tibetan Plateau and Quaternary climatic fluctuations respectively. Evolutionary processes, such as extinction-recolonization during the Pleistocene may have contributed to the fast diversification in D. cambodiana. [ABSTRACT FROM AUTHOR]

Background: Domestication generally implies a loss of diversity in crop species relative to their wild ancestors because of genetic drift through bottleneck effects. Compared to native Mediterranean fruit species like olive and grape, the loss of genetic diversity is expected to be more substantial for fruit species introduced into Mediterranean areas such as apricot (Prunus armeniaca L.), which was probably primarily domesticated in China. By comparing genetic diversity among regional apricot gene pools in several Mediterranean areas, we investigated the loss of genetic diversity associated with apricot selection and diffusion into the Mediterranean Basin. Results: According to the geographic origin of apricots and using Bayesian clustering of genotypes, Mediterranean apricot (207 genotypes) was structured into three main gene pools: 'Irano-Caucasian', 'North Mediterranean Basin' and 'South Mediterranean Basin'. Among the 25 microsatellite markers used, only one displayed deviations from the frequencies expected under neutrality. Similar genetic diversity parameters were obtained within each of the three main clusters using both all SSR loci and only 24 SSR loci based on the assumption of neutrality. A significant loss of genetic diversity, as assessed by the allelic richness and private allelic richness, was revealed from the 'Irano-Caucasian' gene pool, considered as a secondary centre of diversification, to the northern and southwestern Mediterranean Basin. A substantial proportion of shared alleles was specifically detected when comparing gene pools from the 'North Mediterranean Basin' and 'South Mediterranean Basin' to the secondary centre of diversification. Conclusions: A marked domestication bottleneck was detected with microsatellite markers in the Mediterranean apricot material, depicting a global image of two diffusion routes from the 'Irano-Caucasian' gene pool: North Mediterranean and Southwest Mediterranean. This study generated genetic insight that will be useful for management of Mediterranean apricot germplasm as well as genetic selection programs related to adaptive traits. [ABSTRACT FROM AUTHOR]

Global change biology has been entering a big data era due to the vast increase in availability of both environmental and biological data. Big data refers to large data volume, complex data sets, and multiple data sources. The recent use of such big data is improving our understanding of interactions between biological systems and global environmental changes. In this review, we first explore how big data has been analyzed to identify the general patterns of biological responses to global changes at scales from gene to ecosystem. After that, we investigate how observational networks and space‐based big data have facilitated the discovery of emergent mechanisms and phenomena on the regional and global scales. Then, we evaluate the predictions of terrestrial biosphere under global changes by big modeling data. Finally, we introduce some methods to extract knowledge from big data, such as meta‐analysis, machine learning, traceability analysis, and data assimilation. The big data has opened new research opportunities, especially for developing new data‐driven theories for improving biological predictions in Earth system models, tracing global change impacts across different organismic levels, and constructing cyberinfrastructure tools to accelerate the pace of model‐data integrations. These efforts will uncork the bottleneck of using big data to understand biological responses and adaptations to future global changes. [ABSTRACT FROM AUTHOR]

Spiroplasmas are cell-wall-deficient helical bacteria belonging to the class Mollicutes. Their ability to maintain a helical shape in the absence of cell wall and their motility in the absence of external appendages have attracted attention from the scientific community for a long time. In this review we compare and contrast motility, shape determination and cytokinesis mechanisms of Spiroplasma with those of other Mollicutes and cell-walled bacteria. The current models for rod-shape determination and cytokinesis in cell-walled bacteria propose a prominent role for the cell wall synthesis machinery. These models also involve the cooperation of the actin-like protein MreB and FtsZ, the bacterial homolog of tubulin. However the exact role of the cytoskeletal proteins is still under much debate. Spiroplasma possess MreBs, exhibit a rod-shape dependent helical morphology, and divide by an FtsZ-dependent mechanism. Hence, spiroplasmas represent model organisms for deciphering the roles of MreBs and FtsZ in fundamental mechanisms of non-spherical shape determination and cytokinesis in bacteria, in the absence of a cell wall. Identification of components implicated in these processes and deciphering their functions would require genetic experiments. Challenges in genetic manipulations in spiroplasmas are a major bottleneck in understanding their biology. We discuss advancements in genome sequencing, gene editing technologies, super-resolution microscopy and electron cryomicroscopy and tomography, which can be employed for addressing long-standing questions related to Spiroplasma biology. [ABSTRACT FROM AUTHOR]

Modern biology produces data at a staggering rate. Yet, much of these biological data is still isolated in the text, figures, tables and supplementary materials of articles. As a result, biological information created at great expense is significantly underutilised. The protein motif biology field does not have sufficient resources to curate the corpus of motif-related literature and, to date, only a fraction of the available articles have been curated. In this study, we develop a set of tools and a web resource, 'articles.ELM', to rapidly identify the motif literature articles pertinent to a researcher's interest. At the core of the resource is a manually curated set of about 8000 motif-related articles. These articles are automatically annotated with a range of relevant biological data allowing in-depth search functionality. Machine-learning article classification is used to group articles based on their similarity to manually curated motif classes in the Eukaryotic Linear Motif resource. Articles can also be manually classified within the resource. The 'articles.ELM' resource permits the rapid and accurate discovery of relevant motif articles thereby improving the visibility of motif literature and simplifying the recovery of valuable biological insights sequestered within scientific articles. Consequently, this web resource removes a critical bottleneck in scientific productivity for the motif biology field. Database URL: http://slim.icr.ac.uk/articles/ [ABSTRACT FROM AUTHOR]

Aerobiology is a branch of biology that studies microorganisms passively transferred by the air. Bacteria, viruses, fungal spores, tiny insects, and pollen grains are samples of microorganisms. Pollen grains classification is essential in medicine, agronomy, economy, etc. It is performed traditionally (manually) and automatically. The automated approach is faster, more accurate, cost-effective, and with less human intervention than the manual method. In this paper, we introduce a Residual Cognitive Attention Network (RCANet) for the automated classification of pollen grains microscopic images. The suggested attention block, Ventral-Dorsal Ateetntion Block (VDAB), is designed based on the ventral (temporal) and dorsal (parietal) pathways of the occipital lobe. It is embedded in each Basic Block of the architecture of ResNet18. The VDAB is composed of ventral and dorsal attention blocks. The ventral and dorsal streams detect the structure and location of the pollen grain, respectively. According to the mentioned pathways, the Ventral Attention Block (VAB) extracts the channels related to the shape of the pollen grain, and the Dorsal Attention Block (DAB) is focused on its position. Three publicly pollen grains datasets including the Cretan Pollen Dataset (CPD), Pollen13K, and Pollen23E are employed for experiments. The ResNet18 and the proposed method (RCANet) are trained on the datasets and the proposed RCANet obtained higher performance metrics than the ResNet18 in the test step. It achieved weighted F1-score values of 98.69%, 97.83%, and 98.24% with CPD, Pollen13K, and Pollen23E datasets, respectively. [ABSTRACT FROM AUTHOR]

The hallmarks of aging have been influential in guiding the biology of aging research, with more recent and growing recognition of the interdependence of these hallmarks on age‐related health outcomes. However, a current challenge is personalizing aging trajectories to promote healthy aging, given the diversity of genotypes and lived experience. We suggest that incorporating heterogeneity—including intrinsic (e.g., genetic and structural) and extrinsic (e.g., environmental and exposome) factors and their interdependence of hallmarks—may move the dial. This editorial perspective will focus on one hallmark, namely mitochondrial dysfunction, to exemplify how consideration of heterogeneity and interdependence or crosstalk may reveal new perspectives and opportunities for personalizing aging research. To this end, we highlight heterogeneity within mitochondria as a model. [ABSTRACT FROM AUTHOR]

In recent years, the fields of evolutionary biomechanics and morphology have developed into a deeply quantitative and integrative science, resulting in a much richer understanding of how structural relationships shape macroevolutionary patterns. This issue highlights new research at the conceptual and experimental cutting edge, with a special focus on applying big data approaches to classic questions in form–function evolution. As this issue illustrates, new technologies and analytical tools are facilitating the integration of biomechanics, functional morphology, and phylogenetic comparative methods to catalyze a new, more integrative discipline. Although we are at the cusp of the big data generation of organismal biology, the field is nonetheless still data-limited. This data bottleneck is primarily due to the rate-limiting steps of digitizing specimens, recording and tracking organismal movements, and extracting patterns from massive datasets. Automation and machine-learning approaches hold great promise to help data generation keep pace with ideas. As a final and important note, almost all the research presented in this issue relied on specimens—totaling the tens of thousands—provided by museum collections. Without collection, curation, and conservation of museum specimens, the future of the field is much less bright. [ABSTRACT FROM AUTHOR]

How and under what situations populations adapt to local conditions remains a key question in evolutionary biology. This study tests if the particular morphology of a population of Tree lizards, Urosaurus ornatus, located in a canyon on the margin of the species range represents an adaptation to canyon habitat. Morphology was compared across 40 populations showing that relative hind limb length, tail length, and mass were all outliers for this population. The function of the relatively longer hind limbs, tail, and lower mass was proposed to be for better sprinting ability on the sheer canyon walls that provide the only available habitat structure for this population. Partial least squares regression found significant effects of tail length on top speed on a broad, steep surface. Partial least squares logistic regression identified significant effects of tail length on survival as well in males but not females of this population. Another canyon population of Tree lizards with access to alternative substrates (trees) showed no evidence of selection on the same morphological features. Ancestral state reconstruction using a phylogeny inferred for 21 populations found that the unique morphology of the focal population was evolutionarily derived compared to closely related populations and so likely arose under the present environmental conditions. Population genetic structure also supported the process of adaptive divergence as there was no evidence for migration and/or a recent genetic bottleneck in the focal population. Lizards in this population appear to have responded to selection allowing them to become specialists for running on canyon walls while other canyon populations with access to a greater variety of habitat structure have not. [ABSTRACT FROM AUTHOR]

The Antarctic-South American bank-forming moss Chorisodontium aciphyllum is known for having the oldest sub-fossils of any extant plant in Antarctica as well as extreme survival abilities, making it a candidate species for possible long-term survival in Antarctica. Applying phylogeographic and population genetic methods using the plastid markers trnL-F and rps4 and the nuclear internal transcribed spacer, we investigated the genetic diversity within C. aciphyllum throughout its range. Low genetic variation was found in all loci, both between and within Antarctic and southern South American populations, suggesting a relatively recent (likely within the last million years) colonization of this moss to the Antarctic, as well as a likely severe bottleneck during Pleistocene glaciations in southern South America. We also performed a simple atmospheric transfer modeling approach to study potential colonization rates of small (microscopic/microbial) or spore-dispersed organisms (such as many mosses and lichens). These suggested that the northern Antarctic Peninsula shows potentially regular connectivity from southern South America, with air masses transferring, particularly southbound, between the two regions. We found elevated genetic variation of C. aciphyllum in Elephant Island, also the location of the oldest known moss banks (> 5500 years), suggesting this location to be a genetic hotspot for this species in the Antarctic. [ABSTRACT FROM AUTHOR]

Immunohistochemistry is a crucial method for detecting specific proteins within tissue samples, yet constrained to one biomarker per tissue section. Multiplexed immunofluorescence, while allowing simultaneous visualization of multiple proteins, faces limitations in the number of simultaneous fluorescent labels due to spectral overlap. Although cyclic immunofluorescence techniques have successfully broadened antibody staining capacities in a single tissue sample, they are plagued by time-consuming and labor-intensive procedures, sample degradation risks, and inability to scale beyond thin sections. In this study, we introduce the use of 3D confocal Fluorescence Lifetime Imaging Microscopy as a high-throughput, multiplexed immunofluorescence platform that can differentiate 11 or more biomarkers in 3D tissue volumes. Leveraging both spectral and lifetime information, this approach allows for practical spatial biology in thin sections that can readily scale to larger volumes of tissue. We believe that this highly multiplexed and versatile biomarker imaging platform will significantly expedite cancer research and enable new translational approaches in the future. Confocal Fluorescence Lifetime Imaging Microscopy is introduced for highly multiplexed immunofluorescence, enabling the differentiation of 11+ biomarkers in 3D tissue, a technique with potential for interpreting the spatial heterogeneity of thick tumor samples. [ABSTRACT FROM AUTHOR]

The use of neutron methods in environmental and biological sciences is rapidly emerging and accelerating with the development of new instruments at neutron user facilities. This article, based on a workshop held at Oak Ridge National Laboratory (ORNL), offers insights into the application of neutron techniques in environmental and biological sciences. We highlight recent advances and identify key challenges and potential future research areas. These include soil and rhizosphere processes, root water dynamics, plant-microbe interactions, structure and dynamics of biological systems, applications in synthetic biology and enzyme engineering, next-generation bioproducts, biomaterials and bioenergy, nanoscale structure, and fluid dynamics of porous materials in geochemistry. We provide an outlook on emerging opportunities with an emphasis on new capabilities that will be enabled at the Spallation Neutron Source Second Target Station currently under design at ORNL. The mission of scientific neutron user facilities worldwide is to enable science using state-of-the-art neutron capabilities. We aim to encourage researchers in the environmental and biological research community to explore the unique capability afforded by neutrons at these facilities. [ABSTRACT FROM AUTHOR]

There is a growing interest in empirically exploring the biological underpinnings of political attitudes and behavior. Heritability studies are a primary vehicle for conducting such investigations and data sets rich in political phenotypes are becoming broadly accessible. A bottleneck exists, however, in exploiting these opportunities because they involve a statistical re-tooling for political scientists and require a conceptual shift that has substantial implications for the field's traditional theoretical models. Methodologically, most twin studies rely on structural equation models unfamiliar to political scientists. We show this methodological bottleneck is easily navigable; it is the lesser discussed shift in theoretical assumptions poses the larger problem to integrating biological elements into the study of political attitudes and behavior. To address these issues we provide a detailed introduction to a regression-based method for analyzing genetic influence on political attitudes and behaviors that will be methodologically intuitive to political scientists with even minimum quantitative training. In doing so, we provide a platform for bridging important conceptual divides between political science and behavioral genetics. [ABSTRACT FROM AUTHOR]

This study elucidates the genomic basis of the evolution of pathogens alongside free-living organisms within the family Alcaligenaceae of Betaproteobacteria. Towards that end, the complete genome sequence of the sulfur-chemolithoautotroph Tetrathiobacter kashmirensis WT001T was determined and compared with the soil isolate Achromobacter xylosoxidans A8 and the two pathogens Bordetella bronchiseptica RB50 and Taylorella equigenitalis MCE9. All analyses comprehensively indicated that the RB50 and MCE9 genomes were almost the subsets of A8 and WT001T, respectively. In the immediate evolutionary past Achromobacter and Bordetella shared a common ancestor, which was distinct from the other contemporary stock that gave rise to Tetrathiobacter and Taylorella. The Achromobacter-Bordetella precursor, after diverging from the family ancestor, evolved through extensive genome inflation, subsequent to which the two genera separated via differential gene losses and acquisitions. Tetrathiobacter, meanwhile, retained the core characteristics of the family ancestor, and Taylorella underwent massive genome degeneration to reach an evolutionary dead-end. Interestingly, the WT001T genome, despite its conserved architecture, had only 85% coding density, besides which 578 out of its 4452 protein-coding sequences were found to be pseudogenized. Translational impairment of several DNA repair-recombination genes in the first place seemed to have ushered the rampant and indiscriminate frame-shift mutations across the WT001T genome. Presumably, this strain has just come out of a recent evolutionary bottleneck, representing a unique transition state where genome self-degeneration has started comprehensively but selective host-confinement has not yet set in. In the light of this evolutionary link, host-adaptation of Taylorella clearly appears to be the aftereffect of genome implosion in another member of the same bottleneck. Remarkably again, potent virulence factors were found widespread in Alcaligenaceae, corroborating which hemolytic and mammalian cell-adhering abilities were discovered in WT001T. So, while WT001T relatives/derivatives in nature could be going the Taylorella way, the lineage as such was well-prepared for imminent host-confinement. [ABSTRACT FROM AUTHOR]

Relatively few studies have extensively analysed the genetic diversity of the runner bean through molecular markers. Here, we used six chloroplast microsatellites (cpSSRs) to investigate the cytoplasmic diversity of 331 European domesticated accessions of the scarlet runner bean (Phaseolus coccineus L.), including the botanical varieties albiflorus, bicolor and coccineus, and a sample of 49 domesticated and wild accessions from Mesoamerica. We further explored the pattern of diversity of the European landraces using 12 phenotypic traits on 262 individuals. For 158 European accessions, we studied the relationships between cpSSR polymorphisms and phenotypic traits. Additionally, to gain insights into the role of gene flow and migration, for a subset of 115 accessions, we compared and contrasted the results obtained by cpSSRs and phenotypic traits with those obtained in a previous study with 12 nuclear microsatellites (nuSSRs). Our results suggest that both demographic and selective factors have roles in the shaping of the population genetic structure of the European runner bean. In particular, we infer the existence of a moderate-to-strong cytoplasmic bottleneck that followed the expansion of the crop into Europe, and we deduce multiple domestication events for this species. We also observe an adaptive population differentiation in the phenology across a latitudinal gradient, which suggests that selection led to the diversification of the runner bean in Europe. The botanical varieties albiflorus, bicolor and coccineus, which are based solely on flower colour, cannot be distinguished based on these cpSSRs and nuSSRs, nor according to the 12 quantitative traits. [ABSTRACT FROM AUTHOR]

Landscape genetic approaches offer the promise of increasing our understanding of the influence of habitat features on genetic structure. We assessed the genetic diversity of the endangered golden-cheeked warbler ( Dendroica chrysoparia) across their breeding range in central Texas and evaluated the role of habitat loss and fragmentation in shaping the population structure of the species. We determined genotypes across nine microsatellite loci of 109 individuals from seven sites representing the major breeding concentrations of the species. No evidence of a recent population bottleneck was found. Differences in allele frequencies were highly significant among sites. The sampled sites do not appear to represent isolated lineages requiring protection as separate management units, although the amount of current gene flow is insufficient to prevent genetic differentiation. Measures of genetic differentiation were negatively associated with habitat connectivity and the percentage of forest cover between sites, and positively associated with geographic distance and the percentage of agricultural land between sites. The northernmost site was the most genetically differentiated and was isolated from other sites by agricultural lands. Fragmentation of breeding habitat may represent barriers to dispersal of birds which would pose no barrier to movement during other activities such as migration. [ABSTRACT FROM AUTHOR]

Since its immigration in the Pacific island of New Caledonia in 1942 (i.e. about 240 tick-generations ago), the cattle tick Boophilus microplus has experienced a remarkable adaptive diversification there. In order to better understand the population factors involved, we have investigated the B. microplus population structure on that main host-species, Bos taurus. This study was based microsatellite loci and confirmed that the island colonization came along with a significant bottleneck. Knowledge on B. microplus biology led us to expect B. microplus populations to be composed of highly inbred lineages irregularly dispatched among the individual hosts belonging to the same herds. Instead, this study evidenced a weak inbreeding level and an absence of genetic differentiation within herds. Complementarily, a significant signal of isolation by distance exhibited that human-traffic of cattle does not promote high tick dispersal within the island. Finally, the tick density was found to be about a few hundreds of reproducing adults per squared kilometre, for a gene dispersal range of about a few hundred metres per tick generation. Results are discussed with regard to the evolution of new adaptive changes. [ABSTRACT FROM AUTHOR]

We apply new analytical methods to understand the consequences of population bottlenecks for expected additive genetic variance. We analyze essentially all models for multilocus epistasis that have been numerically simulated to demonstrate increased additive variance. We conclude that for biologically plausible models, large increases in expected additive variance--attributable to epistasis rather than dominance--are unlikely. Naciri-Graven and Goudet (2003) found that as the number of epistatically interacting loci increases, additive variance tends to be inflated more after a bottleneck. We argue that this result reflects biologically unrealistic aspects of their models. Specifically, as the number of loci increases, higher-order epistatic interactions become increasingly important in these models, with an increasing fraction of the genetic variance becoming nonadditive, contrary to empirical observations. As shown by Barton and Turelli (2004), without dominance, conversion of nonadditive to additive variance depends only on the variance components and not on the number of loci per se. Numerical results indicating that more inbreeding is needed to produce maximal release of additive variance with more loci follow directly from our analytical results. which show that high levels of inbreeding (F > 0.5) are needed for significant conversion of higher-order components. We discuss alternative approaches to modeling multilocus epistasis and understanding its consequences. [ABSTRACT FROM AUTHOR]

Polymerase chain reaction (PCR) restriction fragment length polymorphism analysis of mitochondrial DNA was applied to the genetic structure and evolutionary history of the more ancestral Pangasianodon hypophthalmus ( n = 82), and the recently speciated catfish Pangasius bocourti ( n = 90) from the Cambodian Mekong River. Both pangasiids were characterized by a lack of genetic population structure that may result from high levels of contemporary gene flow. Genetic diversity was lower in P. hypophthalmus than in P. bocourti. However, a different evolutionary history was inferred for both species based on genealogical and demographic analyses (mismatch analysis, Tajima’s D- and Fu’s FS-tests). The genetic profile of the more ancestral P. hypophthalmus shows indications of a recent population bottleneck, whereas the recently speciated P. bocourti shows signatures of historical population expansion. This study stresses the importance of preserving the migration routes in the Cambodian Mekong basin in order to maintain the genetic diversity and long-term integrity of both species. [ABSTRACT FROM AUTHOR]

Evolutionary biology was previously considered a historical science with predictions about evolutionary trajectories believed to be near impossible. The development of high throughput sequencing and data analysis technologies has challenged this belief, and provided an abundance of data that yields novel insights into evolutionary processes. Evolutionary predictions are now increasingly being used to develop fundamental knowledge of evolving systems and/or to demonstrate evolutionary control. Here we investigate the factors that make evolutionary repeatability more or less likely to increase the accuracy of evolutionary predictions. We identify outstanding questions and provide a potential starting point to determine how evolutionary repeatability is affected by genetic relatedness. [ABSTRACT FROM AUTHOR]

Background: High-throughput sequencing technologies are lifting major limitations to molecular-based ecological studies of eukaryotic microbial diversity, but analyses of the resulting millions of short sequences remain a major bottleneck for these approaches. Here, we introduce the analytical and statistical framework of sequence similarity networks, increasingly used in evolutionary studies and graph theory, into the field of ecology to analyze novel pyrosequenced V4 small subunit rDNA (SSU-rDNA) sequence data sets in the context of previous studies, including SSU-rDNA Sanger sequence data from cultured ciliates and from previous environmental diversity inventories. Results: Our broadly applicable protocol quantified the progress in the description of genetic diversity of ciliates by environmental SSU-rDNA surveys, detected a fundamental historical bias in the tendency to recover already known groups in these surveys, and revealed substantial amounts of hidden microbial diversity. Moreover, network measures demonstrated that ciliates are not globally dispersed, but are structured by habitat and geographical location at intermediate geographical scale, as observed for bacteria, plants, and animals. Conclusions: Currently available 'universal' primers used for local in-depth sequencing surveys provide little hope to exhaust the significantly higher ciliate (and most likely microbial) diversity than previously thought. Network analyses such as presented in this study offer a promising way to guide the design of novel primers and to further explore this vast and structured microbial diversity. [ABSTRACT FROM AUTHOR]

Shape is data and data is shape. Biologists are accustomed to thinking about how the shape of biomolecules, cells, tissues, and organisms arise from the effects of genetics, development, and the environment. Less often do we consider that data itself has shape and structure, or that it is possible to measure the shape of data and analyze it. Here, we review applications of topological data analysis (TDA) to biology in a way accessible to biologists and applied mathematicians alike. TDA uses principles from algebraic topology to comprehensively measure shape in data sets. Using a function that relates the similarity of data points to each other, we can monitor the evolution of topological features—connected components, loops, and voids. This evolution, a topological signature, concisely summarizes large, complex data sets. We first provide a TDA primer for biologists before exploring the use of TDA across biological sub‐disciplines, spanning structural biology, molecular biology, evolution, and development. We end by comparing and contrasting different TDA approaches and the potential for their use in biology. The vision of TDA, that data are shape and shape is data, will be relevant as biology transitions into a data‐driven era where the meaningful interpretation of large data sets is a limiting factor. [ABSTRACT FROM AUTHOR]

The development of Thrips tabaci was studied on transgenic BG I, BG II, non-Bt, and desi cotton cultivars. The oviposition period was minimum on desi cotton, FDK 124 (11.67 days) as compared to BG II (RCH 650) and non-Bt cotton (LH 2076). Female longevity was minimum on FDK 124 (17.50 days) followed by RCH 650 (23.17 days) and LH 2076 (21.83 days). Maximum female longevity was recorded on BGI cotton cultivar RCH 308 (26.83 days). Nymphal, pupal period, and total development period were minimum on FDK 124 (8.17, 2.33, and 34.00 days) as compared to Bt and non-Bt cotton cultivar, LH2076. Based on the higher oviposition period, female longevity, fecundity, and nymphal period, Bt cotton hybrids were found to be more favourable for thrips development in comparison to non-Bt cotton cultivars and desi cotton . The new generation insecticide, spinetoram 11.7SC @ 425g/ ha was most effective and also found to be safe to the predators. [ABSTRACT FROM AUTHOR]

Asteraceae are among the most abundant angiosperm families on oceanic islands. The reproductive biology of Asteraceae is reviewed and the attributes of the family contributing to their success on islands are discussed. Asteraceae are effective dispersers (the small, single-seeded fruits are moved great distances by wind and birds), and colonization is most likely limited by establishment. The pollinators of the colonizing ancestors rarely disperse with them to islands. Divorced from the pollinators of their ancestral habitats, the capitulum of aggregated small, shallow flowers typical of Asteraceae facilitates pollination of colonizers by various novel biotic visitors and by wind. Self-compatible (SC) colonizing ancestors are common, permitting establishment of sexual populations from one or few propagules. However, several large insular lineages of Asteraceae originated from functionally self-incompatible (SI) colonizers that may have also possessed the capacity to set some self-seed. Establishment may also be facilitated by dominance relationships among S-alleles in the sporophytic SI (SSI) system of Asteraceae, increasing cross-compatibility within small populations. Factors potentially promoting outcrossing in SC Asteraceae are: gynomonoecy, with temporal separation of receptive pistillate ray florets and pollen presentation in the hermaphroditic disc florets of a capitulum (interfloral protogyny); and intrafloral protandry where pollen presentation occurs before stigmata become receptive. Dioecy, gynodioecy, and monoecy are infrequent sexual systems in insular Asteraceae. Multiple paternity is similar in island composites to other Asteraceae, suggesting that neither compatible mates nor pollinators are typically limiting. Additional studies, particularly with genomic markers, are needed for more refined insights into mating systems and paternity in island Asteraceae as these results have important conservation implications. [ABSTRACT FROM AUTHOR]

Bioelectricity is the electrical activity that occurs within living cells and tissues. This activity is critical for regulating homeostatic cellular function and communication, and disruptions of the same can lead to a variety of conditions, including cancer. Cancer cells are known to exhibit abnormal electrical properties compared to their healthy counterparts, and this has driven researchers to investigate the potential of harnessing bioelectricity as a tool in cancer diagnosis, prognosis, and treatment. In parallel, bioelectricity represents one of the means to gain fundamental insights on how electrical signals and charges play a role in cancer insurgence, growth, and progression. This review provides a comprehensive analysis of the literature in this field, addressing the fundamentals of bioelectricity in single cancer cells, cancer cell cohorts, and cancerous tissues. The emerging role of bioelectricity in cancer proliferation and metastasis is introduced. Based on the acknowledgement that this biological information is still hard to access due to the existing gap between biological findings and translational medicine, the latest advancements in the field of nanotechnologies for cellular electrophysiology are examined, as well as the most recent developments in micro‐ and nano‐devices for cancer diagnostics and therapy targeting bioelectricity. [ABSTRACT FROM AUTHOR]

Here, high-throughput tomography (HiTT), a fast and versatile phase-contrast imaging platform for life-science samples on the EMBL beamline P14 at DESY in Hamburg, Germany, is presented. A high-photon-flux undulator beamline is used to perform tomographic phase-contrast acquisition in about two minutes which is linked to an automated data processing pipeline that delivers a 3D reconstructed data set less than a minute and a half after the completion of the X-ray scan. Combining this workflow with a sophisticated robotic sample changer enables the streamlined collection and reconstruction of X-ray imaging data from potentially hundreds of samples during a beam-time shift. HiTT permits optimal data collection for many different samples and makes possible the imaging of large sample cohorts thus allowing population studies to be attempted. The successful application of HiTT on various soft tissue samples in both liquid (hydrated and also dehydrated) and paraffin-embedded preparations is demonstrated. Furthermore, the feasibility of HiTT to be used as a targeting tool for volume electron microscopy, as well as using HiTT to study plant morphology, is demonstrated. It is also shown how the high-throughput nature of the work has allowed large numbers of 'identical' samples to be imaged to enable statistically relevant sample volumes to be studied. [ABSTRACT FROM AUTHOR]

Majority of the existing works on network analysis study properties that are related to the global topology of a network. Examples of such properties include diameter, power-law exponent, and spectra of graph Laplacian. Such works enhance our understanding of real-life networks, or enable us to generate synthetic graphs with real-life graph properties. However, many of the existing problems on networks require the study of local topological structures of a network, which did not get the deserved attention in the existing works. In this work, we use graphlet frequency distribution (GFD) as an analysis tool for understanding the variance of local topological structure in a network; we also show that it can help in comparing, and characterizing real-life networks. The main bottleneck to obtain GFD is the excessive computation cost for obtaining the frequency of each of the graphlets in a large network. To overcome this, we propose a simple, yet powerful algorithm, called Graft , that obtains the approximate graphlet frequency for all graphlets that have up-to five vertices. Comparing to an exact counting algorithm, our algorithm achieves a speedup factor between 10 and 100 for a negligible counting error, which is, on average, less than 5 percent. [ABSTRACT FROM AUTHOR]

There is an increasingly pressing need, by several applications in diverse domains, for developing techniques able to index and mine very large collections of time series. Examples of such applications come from astronomy, biology, the web, and other domains. It is not unusual for these applications to involve numbers of time series in the order of hundreds of millions to billions. However, all relevant techniques that have been proposed in the literature so far have not considered any data collections much larger than one-million time series. In this paper, we describe $$i$$SAX 2.0 and its improvements, $$i$$SAX 2.0 Clustered and $$i$$SAX2+, three methods designed for indexing and mining truly massive collections of time series. We show that the main bottleneck in mining such massive datasets is the time taken to build the index, and we thus introduce a novel bulk loading mechanism, the first of this kind specifically tailored to a time series index. We show how our methods allows mining on datasets that would otherwise be completely untenable, including the first published experiments to index one billion time series, and experiments in mining massive data from domains as diverse as entomology, DNA and web-scale image collections. [ABSTRACT FROM AUTHOR]

The F508del-CFTR mutation, responsible for Cystic Fibrosis (CF), leads to the retention of the protein in the endoplasmic reticulum (ER). The mistrafficking of this mutant form can be corrected by pharmacological chaperones, but these molecules showed limitations in clinical trials. We therefore hypothesized that important factors in CF patients may have not been considered in the in vitro assays. CF has also been associated with an altered lipid homeostasis, i. e. a decrease in polyunsaturated fatty acid levels in plasma and tissues. However, the precise fatty acyl content of membrane phospholipids from human CF bronchial epithelial cells had not been studied to date. Since the saturation level of phospholipids can modulate crucial membrane properties, with potential impacts on membrane protein folding/trafficking, we analyzed this parameter for freshly isolated bronchial epithelial cells from CF patients. Interestingly, we could show that Palmitate, a saturated fatty acid, accumulates within Phosphatidylcholine (PC) in CF freshly isolated cells, in a process that could result from hypoxia. The observed PC pattern can be recapitulated in the CFBE41o− cell line by incubation with 100 µM Palmitate. At this concentration, Palmitate induces an ER stress, impacts calcium homeostasis and leads to a decrease in the activity of the corrected F508del-CFTR. Overall, these data suggest that bronchial epithelial cells are lipointoxicated by hypoxia-related Palmitate accumulation in CF patients. We propose that this phenomenon could be an important bottleneck for F508del-CFTR trafficking correction by pharmacological agents in clinical trials. [ABSTRACT FROM AUTHOR]

Dose addition, a commonly used concept in toxicology for the prediction of chemical mixture effects, cannot readily be applied to mixtures of partial agonists with differing maximal effects. Due to its mathematical features, effect levels that exceed the maximal effect of the least efficacious compound present in the mixture, cannot be calculated. This poses problems when dealing with mixtures likely to be encountered in realistic assessment situations where chemicals often show differing maximal effects. To overcome this limitation, we developed a pragmatic solution that extrapolates the toxic units of partial agonists to effect levels beyond their maximal efficacy. We extrapolated different additivity expectations that reflect theoretically possible extremes and validated this approach with a mixture of 21 estrogenic chemicals in the E-Screen. This assay measures the proliferation of human epithelial breast cancers. We found that the dose-response curves of the estrogenic agents exhibited widely varying shapes, slopes and maximal effects, which made it necessary to extrapolate mixture responses above 14% proliferation. Our toxic unit extrapolation approach predicted all mixture responses accurately. It extends the applicability of dose addition to combinations of agents with differing saturating effects and removes an important bottleneck that has severely hampered the use of dose addition in the past. [ABSTRACT FROM AUTHOR]

Modern computing architecture based on the separation of memory and processing leads to a well known problem called the von Neumann bottleneck, a restrictive limit on the data bandwidth between CPU and RAM. This paper introduces a new approach to computing we call AHaH computing where memory and processing are combined. The idea is based on the attractor dynamics of volatile dissipative electronics inspired by biological systems, presenting an attractive alternative architecture that is able to adapt, self-repair, and learn from interactions with the environment. We envision that both von Neumann and AHaH computing architectures will operate together on the same machine, but that the AHaH computing processor may reduce the power consumption and processing time for certain adaptive learning tasks by orders of magnitude. The paper begins by drawing a connection between the properties of volatility, thermodynamics, and Anti-Hebbian and Hebbian (AHaH) plasticity. We show how AHaH synaptic plasticity leads to attractor states that extract the independent components of applied data streams and how they form a computationally complete set of logic functions. After introducing a general memristive device model based on collections of metastable switches, we show how adaptive synaptic weights can be formed from differential pairs of incremental memristors. We also disclose how arrays of synaptic weights can be used to build a neural node circuit operating AHaH plasticity. By configuring the attractor states of the AHaH node in different ways, high level machine learning functions are demonstrated. This includes unsupervised clustering, supervised and unsupervised classification, complex signal prediction, unsupervised robotic actuation and combinatorial optimization of procedures–all key capabilities of biological nervous systems and modern machine learning algorithms with real world application. [ABSTRACT FROM AUTHOR]

To slow the inexorable rise of antibiotic resistance we must understand how drugs impact on pathogenesis and influence the selection of resistant clones. Staphylococcus aureus is an important human pathogen with populations of antibiotic-resistant bacteria in hospitals and the community. Host phagocytes play a crucial role in controlling S. aureus infection, which can lead to a population “bottleneck” whereby clonal expansion of a small fraction of the initial inoculum founds a systemic infection. Such population dynamics may have important consequences on the effect of antibiotic intervention. Low doses of antibiotics have been shown to affect in vitro growth and the generation of resistant mutants over the long term, however whether this has any in vivo relevance is unknown. In this work, the population dynamics of S. aureus pathogenesis were studied in vivo using antibiotic-resistant strains constructed in an isogenic background, coupled with systemic models of infection in both the mouse and zebrafish embryo. Murine experiments revealed unexpected and complex bacterial population kinetics arising from clonal expansion during infection in particular organs. We subsequently elucidated the effect of antibiotic intervention within the host using mixed inocula of resistant and sensitive bacteria. Sub-curative tetracycline doses support the preferential expansion of resistant microorganisms, importantly unrelated to effects on growth rate or de novo resistance acquisition. This novel phenomenon is generic, occurring with methicillin-resistant S. aureus (MRSA) in the presence of β-lactams and with the unrelated human pathogen Pseudomonas aeruginosa. The selection of resistant clones at low antibiotic levels can result in a rapid increase in their prevalence under conditions that would previously not be thought to favor them. Our results have key implications for the design of effective treatment regimes to limit the spread of antimicrobial resistance, where inappropriate usage leading to resistance may reduce the efficacy of life-saving drugs. [ABSTRACT FROM AUTHOR]