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BackgroundNatural selection and genetic drift are major forces responsible for temporal genetic changes in populations. Furthermore, these evolutionary forces may interact with each other. Here we study the impact of an ongoing adaptive process at the molecular genetic level by analyzing the temporal genetic changes throughout 40 generations of adaptation to a common laboratory environment. Specifically, genetic variability, population differentiation and demographic structure were compared in two replicated groups of Drosophila subobscura populations recently sampled from different wild sources.ResultsWe found evidence for a decline in genetic variability through time, along with an increase in genetic differentiation between all populations studied. The observed decline in genetic variability was higher during the first 14 generations of laboratory adaptation. The two groups of replicated populations showed overall similarity in variability patterns. Our results also revealed changing demographic structure of the populations during laboratory evolution, with lower effective population sizes in the early phase of the adaptive process. One of the ten microsatellites analyzed showed a clearly distinct temporal pattern of allele frequency change, suggesting the occurrence of positive selection affecting the region around that particular locus.ConclusionGenetic drift was responsible for most of the divergence and loss of variability between and within replicates, with most changes occurring during the first generations of laboratory adaptation. We also found evidence suggesting a selective sweep, despite the low number of molecular markers analyzed. Overall, there was a similarity of evolutionary dynamics at the molecular level in our laboratory populations, despite distinct genetic backgrounds and some differences in phenotypic evolution.

Immunosuppressive tumor microenvironment (TME) limits the response to immunotherapy based on programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blockade. Here, pH-sensitive metal-organic framework nanoparticles (MOF NPs) which efficiently co-encapsulate hemoglobin (Hb) and catalase (CAT) and preserve their activities in physiological conditions are fabricated, embedded in liposome to improve water dispersity, and conjugated with PD-1 antibody (aPD-1) for binding PD-1+ T cells. The nanodrug (C&H@MOF/PL-A) thus prepared hitchhikes on circulating PD-1+ T cells for efficient protein delivery to tumor sites. The tumor weak acidity may detach the functionalized MOF from T cells while still leaving aPD-1 to bind T cells for immune checkpoint blockade (ICB). Finally, the MOF NPs release CAT and Hb which catalyzes oxygen production and stores oxygen in situ, respectively, for a long-term hypoxia relief. Consequently, the immunosuppression in TME is reversed to boost an ICB-based immunotherapy against colorectal carcinoma. [Display omitted] • Proteins were loaded into the defects of MOF nanoparticles to protect their activity during blood circulation. • Nanodrug hitchhikes on circulating PD-1+ T cells for efficient protein delivery to tumor sites. • CAT and Hb which catalyzes oxygen production and stores oxygen, respectively, were applied for long-term hypoxia relief. [ABSTRACT FROM AUTHOR]

Tumor resection is usually associated with tumor recurrence due to the residual tumor cells. Improving the localized accumulation of therapeutics at the surgical sites is a promising approach for the inhibition of tumor recurrence and metastasis. Herein, we report an in situ hitchhiking strategy for postsurgical tumor therapy via targeting of therapeutics-loaded liposomes to neutrophils (NEs). Anticancer drug doxorubicin (DOX) and non-nucleotide stimulator of interferon genes (STING) agonist SR-717 are encapsulated into liposomes followed by surface modification with anti-Ly6G antibodies, which can target NEs in situ in blood stream for hitchhiking delivery to the postsurgical inflamed tumor sites. The delivered DOX can inhibit the growth of residual tumor cells and trigger the tumor immunogenic cell death (ICD) for tumor-specific immunity, while SR-717 can facilitate dendritic cell maturation and enhance antitumor immunity. Consequently, the in situ NE-hitchhiking delivery of therapeutics can efficiently suppress tumor recurrence and metastatic melanoma growth after tumor resection, which circumvents the complex ex vivo processes of separation, engineering, and refusion of leukocytes and represents a targeted delivery strategy for postsurgical cancer chemo-immunotherapy. [Display omitted] • In situ hitchhiking strategy in blood stream can overcome the drawbacks of ex situ hitchhiking strategy. • NE-hitchhiking of therapeutics can improve the targeted delivery efficacy at postsurgical sites. • SR-717 together with the DOX can synergistically elicit the tumor-specific T-cell immunity for improved immunotherapy. • The combination of anticancer drugs and STING agonists result in a significant decrease in tumor recurrence and metastasis. [ABSTRACT FROM AUTHOR]

[Display omitted] Since the inception of the concept of "magic bullet", nanoparticles have evolved to be one of the most effective carriers in drug delivery. Nanoparticles improve the therapeutic efficacy of drugs offering benefits to treating various diseases. Unlike free drugs which freely diffuse and distribute through the body, nanoparticles protect the body from the drug by reducing non-specific interactions while also improving the drug's pharmacokinetics. Despite acquiring some FDA approvals, further clinical application of nanoparticles is majorly hindered by its limited ability to overcome biological barriers resulting in uncontrolled biodistribution and high clearance. The use of cell-inspired systems has emerged as a promising approach to overcome this challenge as cells are biocompatible and have improved access to tissues and organs. One of such is the hitchhiking of nanoparticles to circulating cells such that they are recognized as 'self' components evading clearance and resulting in site-specific drug delivery. In this review, we discuss the concept of nanoparticle cellular hitchhiking, highlighting its advantages, the principles governing the process and the challenges currently limiting its clinical translation. We also discuss in situ hitchhiking as a tool for overcoming these challenges and the considerations to be taken to guide research efforts in advancing this promising technology. [ABSTRACT FROM AUTHOR]

Insects harbor a variety of maternally inherited bacterial symbionts. As such, variation in symbiont presence/absence, in the combinations of harbored symbionts, and in the genotypes of harbored symbiont species provide heritable genetic variation of potential use in the insects’ adaptive repertoires. Understanding the natural importance of symbionts is challenging but studying their dynamics over time can help to elucidate the potential for such symbiont-driven insect adaptation. Toward this end, we studied the seasonal dynamics of six maternally transferred bacterial symbiont species in the multivoltine pea aphid (Acyrthosiphon pisum). Our sampling focused on six alfalfa fields in southeastern Pennsylvania, and spanned 14 timepoints within the 2012 growing season, in addition to two overwintering periods. To test and generate hypotheses on the natural relevance of these non-essential symbionts, we examined whether symbiont dynamics correlated with any of ten measured environmental variables from the 2012 growing season, including some of known importance in the lab. We found that five symbionts changed prevalence across one or both overwintering periods, and that the same five species underwent such frequency shifts across the 2012 growing season. Intriguingly, the frequencies of these dynamic symbionts showed robust correlations with a subset of our measured environmental variables. Several of these trends supported the natural relevance of lab-discovered symbiont roles, including anti-pathogen defense. For a seventh symbiont—Hamiltonella defensa—studied previously across the same study periods, we tested whether a reported correlation between prevalence and temperature stemmed not from thermally varying host-level fitness effects, but from selection on co-infecting symbionts or on aphid-encoded alleles associated with this bacterium. In general, such “hitchhiking” effects were not evident during times with strongly correlated Hamiltonella and temperature shifts. However, we did identify at least one time period in which Hamiltonella spread was likely driven by selection on a co-infecting symbiont—Rickettsiella viridis. Recognizing the broader potential for such hitchhiking, we explored selection on co-infecting symbionts as a possible driver behind the dynamics of the remaining six species. Out of twelve examined instances of symbiont dynamics unfolding across 2-week periods or overwintering spans, we found eight in which the focal symbiont underwent parallel frequency shifts under single infection and one or more co-infection contexts. This supported the idea that phenotypic variation created by the presence/absence of individual symbionts is a direct target for selection, and that symbiont effects can be robust under co-habitation with other symbionts. Contrastingly, in two cases, we found that selection may target phenotypes emerging from symbiont co-infections, with specific species combinations driving overall trends for the focal dynamic symbionts, without correlated change under single infection. Finally, in three cases—including the one described above for Hamiltonella—our data suggested that incidental co-infection with a (dis)favored symbiont could lead to large frequency shifts for “passenger” symbionts, conferring no apparent cost or benefit. Such hitchhiking has rarely been studied in heritable symbiont systems. We propose that it is more common than appreciated, given the widespread nature of maternally inherited bacteria, and the frequency of multi-species symbiotic communities across insects.

Biopsy is the clinical standard for diagnosing lymph node (LN) metastasis, but it is invasive and poses significant risk to patient health. Magnetic resonance imaging (MRI) has been utilized as a noninvasive alternative but is limited by low sensitivity, with only ∼35% of LN metastases detected, as clinical contrast agents cannot discriminate between healthy and metastatic LNs due to nonspecific accumulation. Nanoparticles targeted to the C-C chemokine receptor 2 (CCR2), a biomarker highly expressed in metastatic LNs, have the potential to guide the delivery of contrast agents, improving the sensitivity of MRI. Additionally, cancer cells in metastatic LNs produce monocyte chemotactic protein 1 (MCP1), which binds to CCR2 + inflammatory monocytes and stimulates their migration. Thus, the molecular targeting of CCR2 may enable nanoparticle hitchhiking onto monocytes, providing an additional mechanism for metastatic LN targeting and early detection. Hence, we developed micelles incorporating gadolinium (Gd) and peptides derived from the CCR2-binding motif of MCP1 (MCP1-Gd) and evaluated the potential of MCP1-Gd to detect LN metastasis. When incubated with migrating monocytes in vitro , MCP1-Gd transport across lymphatic endothelium increased 2-fold relative to nontargeting controls. After administration into mouse models with initial LN metastasis and recurrent LN metastasis, MCP1-Gd detected metastatic LNs by increasing MRI signal by 30-50% relative to healthy LNs. Furthermore, LN targeting was dependent on monocyte hitchhiking, as monocyte depletion decreased accumulation by >70%. Herein, we present a nanoparticle contrast agent for MRI detection of LN metastasis mediated by CCR2-targeting and demonstrate the potential of monocyte hitchhiking for enhanced nanoparticle delivery.

Mutator alleles that elevate the genomic mutation rate may invade nonrecombining populations by hitchhiking with beneficial mutations. Mutators have been repeatedly observed to take over adapting laboratory populations and have been found at high frequencies in both microbial pathogen and cancer populations in nature. Recently, we have shown that mutators are only favored by selection in sufficiently large populations and transition to being disfavored as population size decreases. This population size‐dependent sign inversion in selective effect suggests that population structure may also be an important determinant of mutation rate evolution. Although large populations may favor mutators, subdividing such populations into sufficiently small subpopulations (demes) might effectively inhibit them. On the other hand, migration between small demes that otherwise inhibit hitchhiking may promote mutator fixation in the whole metapopulation. Here, we use stochastic, agent‐based simulations and evolution experiments with the yeast Saccharomyces cerevisiae to show that mutators can, indeed, be favored by selection in subdivided metapopulations composed of small demes connected by sufficient migration. In fact, we show that population structure plays a previously unsuspected role in promoting mutator success in subdivided metapopulations when migration is rare. [ABSTRACT FROM AUTHOR]

Population differentiation and diversification depend in large part on the ability and propensity of organisms to successfully disperse. However, our understanding of these processes in organisms with high dispersal ability is biased by the limited genetic resolution offered by traditional genotypic markers. Many neustonic animals disperse not only as pelagic larvae, but also as juveniles and adults while drifting or rafting at the surface of the open ocean. In theory, the heightened dispersal ability of these animals should limit opportunities for species diversification and population differentiation. To test these predictions, we used next‐generation sequencing of genomewide restriction‐site‐associated DNA tags (RADseq) and traditional mitochondrial DNA sequencing, to investigate the species‐level relationships and global population structure of Planes crabs collected from oceanic flotsam and sea turtles. Our results indicate that species diversity in this clade is low—likely three closely related species—with no evidence of cryptic or undescribed species. Moreover, our results indicate weak population differentiation among widely separated aggregations with genetic indices showing only subtle genetic discontinuities across all oceans of the world (RADseq FST = 0.08–0.16). The results of this study provide unprecedented resolution of the systematics and global biogeography of this group and contribute valuable information to our understanding of how theoretical dispersal potential relates to actual population differentiation and diversification among marine organisms. Moreover, these results demonstrate the limitations of single gene analyses and the value of genomic‐level resolution for estimating contemporary population structure in organisms with large, highly connected populations. Next‐generation sequencing of genomewide restriction‐site‐associated DNA tags (RADseq) and traditional mitochondrial DNA sequencing were used to investigate the species‐level relationships and global population structure of Planes crabs collected from oceanic flotsam and sea turtles. Our results indicate that species diversity in this clade is low—only three species—with no evidence of cryptic or undescribed species. Moreover, our results indicate weak population differentiation among widely separated aggregations with genetic indices showing only subtle genetic discontinuities across all oceans of the world. [ABSTRACT FROM AUTHOR]

International trade and movement of people are largely responsible for increasing numbers of non-native insect introductions to new environments. For forest insects, trade in live plants and transport of wood packaging material (WPM) are considered the most important pathways facilitating long-distance invasions. These two pathways as well as trade in firewood, logs, and processed wood are commonly associated with insect infestations, while "hitchhiking" insects can be moved on cargo, in the conveyances used for transport (e.g., containers, ships), or associated with international movement of passengers and mail. Once established in a new country, insects can spread domestically through all of the above pathways. Considerable national and international efforts have been made in recent years to reduce the risk of international movement of plant pests. International Standards for Phytosanitary Measures (ISPMs) No. 15 (WPM), 36 (plants for planting), and 39 (wood) are examples of phytosanitary standards that have been adopted by the International Plant Protection Convention to reduce risks of invasions of forest pests. The implementation of ISPMs by exporting countries is expected to reduce the arrival rate and establishments of new forest pests. However, many challenges remain to reduce pest transportation through international trade, given the ever-increasing volume of traded goods, variations in quarantine procedures between countries, and rapid changes in distribution networks. It is therefore likely that many more human-assisted invasions of forest insects will take place. New geographic expansions by natural modes are also made possible due to changes in host distribution and/or climate. [ABSTRACT FROM AUTHOR]

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Mitochondrial dysfunction plays a major role in driving acute kidney injury (AKI) via alteration in energy and oxygen supply, which creates further ROS and inflammatory responses. However, mitochondrial targeting medicine in recovering AKI is challenging. Herein, we conjugated SS31, a mitochondria-targeted antioxidant tetrapeptide connecting a cleavable linker to rapamycin (Rapa), which provided specific interaction with FK506-binding protein (FKBP) in the RBCs. Once entering the bloodstream, SS31-Rapa could be directed to the intracellular space of RBCs, allowing the slow diffusion of the conjugate to tissues via the concentration gradient. The new RBC hitchhiking strategy enables the encapsulation of conjugate into RBC via a less traumatic and more natural and permissive manner, resulting in prolonging the t 1/2 of SS31 by 6.9 folds. SS31-Rapa underwent the direct cellular uptake, instead of the lysosomal pathway, released SS31 in response to activated caspase-3 stimulation in apoptotic cells, favoring the mitochondrial accumulation of SS31. Combined with autophagy induction associated with Rapa, a single dose of SS31-Rapa can effectively reverse cisplatin and ischemia reperfusion-induced AKI. This work thus highlights a simple and effective RBC hitchhiking strategy and a clinically translatable platform technology to improve the outcome of other mitochondrial dysfunctional related diseases. • SS31-Rapa hitchhikes RBCs by binding erythrocytic FKBP and extends SS31's circulation. • SS31-DVED-Rapa can release free SS31 by caspase-3, to fulfill mitochondrial targeting. • Rapa domain enhances autophagy and works with SS31 to reduce ROS after AKI. • SS31-DVED-Rapa significantly improves the outcome of SS31 in AKI. [ABSTRACT FROM AUTHOR]

Highlights • Frequency of hitchhikers increased along narrow trails, and also due to outbound workers in both trail widths. Regardless of outbound foraging flow being comparable in both trail widths, the narrower ones had high density of workers leading to a presumed increase in head-on encounters. • Head-on encounter rates cause a reduction in travel speed and, furthermore, are regulatory factors of task-allocation. • High density trails lead to an increase in the rate of head-on encounters which could constitute as a stimulus to task-allocation of very small workers to the function of hitchhiker to avoid traffic jams. Abstract During foraging, thousands of leaf-cutting ant workers travel along high traffic foraging trails which, when narrow, reduce the leaf delivery rate due to the reduction in workers' travel-speed. On the other hand, high worker traffic promotes head-on encounters which are supposed to mediate worker task allocation and so could constitute a cue which induces traffic reduction. Very small workers along trails, for example, could change their task between marking the trail chemically to hitchhiking. Since they assume the hitchhiker function even in the absence of phorid parasitoids, one can suppose that hitchhiker behavior could be a strategy mediated by head-on encounters to avoid the high density of workers. Thus, we studied how the variation of worker density on the trail influences the hitchhiker frequency, testing the hypothesis that very small workers climb on the transported leaves to reduce trail traffic. Therefore, five Acromyrmex subterraneus colonies were linked to a foraging area by trails of different width (1.5 or 3 cm). We counted the number of hitchhikers and the outbound worker flow. The frequency of hitchhikers increased along narrow trails, and also due to outbound workers in both trail widths. Regardless of outbound foraging flow being comparable in both trail widths, the narrower ones had high density of workers leading to a presumed increase in head-on encounters. Head-on encounter rates cause a reduction in travel speed and, furthermore, are regulatory factors of task-allocation. Thus, high density trails lead to an increase in the rate of head-on encounters which could constitute as a stimulus to task-allocation of very small workers to the function of hitchhiker to avoid traffic jams. [ABSTRACT FROM AUTHOR]

Under the nearly neutral theory of molecular evolution, the proportion of effectively neutral mutations is expected to depend upon the effective population size (N e). Here, we investigate whether this is the case across the genome of Drosophila melanogaster using polymorphism data from North American and African lines. We show that the ratio of the number of nonsynonymous and synonymous polymorphisms is negatively correlated to the number of synonymous polymorphisms, even when the nonindependence is accounted for. The relationship is such that the proportion of effectively neutral nonsynonymous mutations increases by ∼45% as N eis halved. However, we also show that this relationship is steeper than expected from an independent estimate of the distribution of fitness effects from the site frequency spectrum. We investigate a number of potential explanations for this and show, using simulation, that this is consistent with a model of genetic hitchhiking: Genetic hitchhiking depresses diversity at neutral and weakly selected sites, but has little effect on the diversity of strongly selected sites. [ABSTRACT FROM AUTHOR]

The anticancer efficacy of chemotherapy is greatly limited by short blood circulation and poor tumor selectivity. Thus, anticancer prodrugs with prolonged systemic circulation, tumor-specific distribution and bioactivation, could significantly strengthen the chemotherapy efficacy. Herein, we design two novel tumor cell reduction/oxidation-responsive docetaxel (DTX) prodrugs, DTX-maleimide conjugates with disulfide bond (DSSM) or thioether bond (DSM) linkages, to evaluate the roles of different sensitive linkages in drug release, pharmacokinetics and therapeutic efficacy. An ester bond-linkage prodrug (DM) is utilized as a non-sensitive control. DSSM and DSM show reduction- or oxidation-sensitive release behavior, respectively, and exhibit hyperselective bioactivation and cytotoxicities between cancerous and normal cells. They could instantly hitchhike blood circulating albumin after i.v. administration with albumin-binding half-lives as short as 1 min, resulting in prolonged systemic circulation, increased tumor accumulation. In response to the upregulated reduction/oxidation environment within tumor cells, DSSM and DSM exhibit selectively release capacity in tumor tissues, their TAI Tumor/Liver values are over 30-fold greater than DM. Combining the above delivery advantages into one, DSSM and DSM achieve enhanced antitumor efficacy of DTX. Such a uniquely developed strategy, integrating high albumin-binding capability and reduction/oxidation-sensitive drug superselective release in tumors, has great potential to be applied in clinical cancer therapy. [ABSTRACT FROM AUTHOR]

Evolutionary dynamics in laboratory microbial evolution experiments can be surprisingly complex. In the past two decades, observations of these dynamics have challenged simple models of adaptation and have shown that clonal interference, hitchhiking, ecological diversification, and contingency are widespread. In recent years, advances in high-throughput strain maintenance and phenotypic assays, the dramatically reduced cost of genome sequencing, and emerging methods for lineage barcoding have made it possible to observe evolutionary dynamics at unprecedented resolution. These new methods can now begin to provide detailed measurements of key aspects of fitness landscapes and of evolutionary outcomes across a range of systems. These measurements can highlight challenges to existing theoretical models and guide new theoretical work towards the complications that are most widely important. [ABSTRACT FROM AUTHOR]

A simple method was developed to detect signatures of ongoing selective sweeps in single nucleotide polymorphism (SNP) data. Based largely on the traditional site frequency spectrum (SFS), the method additionally incorporates linkage disequilibrium (LD) between pairs of SNP sites and uniquely represents both SFS and LD information as hierarchical "barcodes." This barcode representation allows the identification of a hitchhiking genomic region surrounding a putative target site of positive selection, or a core site. Sweep signals at linked neutral sites are then measured by the proportion (Fc) of derived alleles within the hitchhiking region that are linked in the derived allele group defined at the core site. In measuring Fc or intra-allelic variability in an informative way, certain conditions for derived allele frequencies are required, as illustrated with the human ST8SIA2 locus. Coalescent simulators with and without positive selection are used to assess the false-positive and false-negative rates of the Fc statistic. To demonstrate its power, the method was further applied to the LCT, OCA2, EDAR, SLC24A5 and ASPM loci, which are known to have undergone positive selection in human populations. Overall, the method is powerful and can be used to identify core sites responsible for ongoing selective sweeps. [ABSTRACT FROM AUTHOR]

In human populations, changes in genetic variation are driven not only by genetic processes, but can also arise from cultural or social changes. An abrupt population bottleneck specific to human males has been inferred across several Old World (Africa, Europe, Asia) populations 5000-7000 BP. Here, bringing together anthropological theory, recent population genomic studies and mathematical models, we propose a sociocultural hypothesis, involving the formation of patrilineal kin groups and intergroup competition among these groups. Our analysis shows that this sociocultural hypothesis can explain the inference of a population bottleneck. We also show that our hypothesis is consistent with current findings from the archaeogenetics of Old World Eurasia, and is important for conceptions of cultural and social evolution in prehistory. [ABSTRACT FROM AUTHOR]

How genome divergence eventually leads to speciation is a topic of prime evolutionary interest. Genomic islands of elevated divergence are frequently reported between diverging lineages, and their size is expected to increase with time and gene flow under the speciation-with-gene-flow model. However, such islands can also result from divergent sorting of ancient polymorphisms, recent ecological selection regardless of gene flow, and/or recurrent background selection and selective sweeps in low-recombination regions. It is challenging to disentangle these nonexclusive alternatives, but here we attempt to do this in an analysis of what drove genomic divergence between four lineages comprising a species complex of desert poplar trees. Within this complex we found that two morphologically delimited species, Populus euphratica and Populus pruinosa, were paraphyletic while the four lineages exhibited contrasting levels of gene flow and divergence times, providing a good system for testing hypotheses on the origin of divergence islands. We show that the size and number of genomic islands that distinguish lineages are not associated with either rate of recent gene flow or time of divergence. Instead, they are most likely derived from divergent sorting of ancient polymorphisms and divergence hitchhiking. We found that highly diverged genes under lineage-specific selection and putatively involved in ecological and morphological divergence occur both within and outside these islands. Our results highlight the need to incorporate demography, absolute divergence measurement, and gene flow rate to explain the formation of genomic islands and to identify potential genomic regions involved in speciation. [ABSTRACT FROM AUTHOR]

Plasmid families harbor different maintenances functions, depending on their size and copy number. Low copy number plasmids rely on active partition systems, organizing a partition complex at specific centromere sites that is actively positioned using NTPase proteins. Some low copy number plasmids lack an active partition system, but carry atypical intracellular positioning systems using a single protein that binds to the centromere site but without an associated NTPase. These systems have been studied in the case of the Escherichia coli R388 and of the Staphylococcus aureus pSK1 plasmids. Here we review these two systems, which appear to be unrelated but share common features, such as their distribution on plasmids of medium size and copy number, certain activities of their centromere-binding proteins, StbA and Par, respectively, as well as their mode of action, which may involve dynamic interactions with the nucleoid-packed chromosome of their hosts. • Single-protein segregation systems are widespread. • The two described single-protein segregation systems rely on association with the host nucleoid. • pSK1 Par and R388 StbA functions are well adapted to medium size and copy number plasmids. [ABSTRACT FROM AUTHOR]

Mitostasis, the process of mitochondrial maintenance by biogenesis and degradative mechanisms, is challenged by the extreme length of axons. PINK1 (PTEN induced putative kinase 1) is a mitochondrial protein that targets damaged mitochondria for mitophagy. In reconciling the short half-life of PINK1 with the need for mitophagy of damaged axonal mitochondria, we found that axonal mitophagy depends on local translation of the Pink1 mRNA. Using live-cell imaging, we detected co-transport of the Pink1 mRNA on mitochondria in neurons, which is crucial for mitophagy in distal parts of the cell. Here we discuss how the coupling of the transcript of a short-lived mitochondrial protein to the movement of its target organelles contributes to our understanding of mitostasis in neurons. [ABSTRACT FROM AUTHOR]

Genetic differentiation between divergent populations is often greater in chromosome centres than peripheries. Commonly overlooked, this broadscale differentiation pattern is sometimes ascribed to heterogeneity in crossover rate and hence linked selection within chromosomes, but the underlying mechanisms remain incompletely understood. A literature survey across 46 organisms reveals that most eukaryotes indeed exhibit a reduced crossover rate in chromosome centres relative to the peripheries. Using simulations of populations diverging into ecologically different habitats through sorting of standing genetic variation, we demonstrate that such chromosome-scale heterogeneity in crossover rate, combined with polygenic divergent selection, causes stronger hitchhiking and especially barriers to gene flow across chromosome centres. Without requiring selection on new mutations, this rapidly leads to elevated population differentiation in the low-crossover centres relative to the high-crossover peripheries of chromosomes ('Chromosome Centre-Biased Differentiation', CCBD). Using simulated and empirical data, we then show that strong CCBD between populations can provide evidence of polygenic adaptive divergence with a phase of gene flow. We further demonstrate that chromosome-scale heterogeneity in crossover rate impacts analyses beyond that of population differentiation, including the inference of phylogenies and parallel adaptive evolution among populations, the detection of genetic loci under selection, and the interpretation of the strength of selection on genomic regions. Overall, our results call for a greater appreciation of chromosome-scale heterogeneity in crossover rate in evolutionary genomics. [ABSTRACT FROM AUTHOR]

this essay introduces urban hitchhiking, a reflective practice of sharing a walk with strangers, and considers its relevance for research and artistic practice. Drawing from ethnography, psychogeography and performance studies, we frame urban hitchhiking as a score that has ethnographic potential akin to the ethnographic installation (Hartblay 2017) for exploring the complex relationships between people and cityscapes. We demonstrate this with the help of our own accounts of Urban Hitchhiking as two artists who developed the concept and a researcher who practiced it. The essay summarises four perspectives that emerged from our findings: spatiality, performativity, gender, and hospitality. It concludes that the key value of urban hitchhiking lies in its potential to create a setting that we define as an empathetic drift, which turns random encounters into shared acts of trust through which a variety of anthropological questions can be explored. [ABSTRACT FROM AUTHOR]

Hitchhiking is a means of transportation gained by asking other people for a (free) ride. We developed a multi-robot system which is the first of its kind to incorporate hitchhiking in robotics, and discuss its advantages. Our method allows the hitchhiker robot to skip redundant computations in navigation like path planning, localization, obstacle avoidance, and map update by completely relying on the driver robot. This allows the hitchhiker robot, which performs only visual servoing, to save computation while navigating on the common path with the driver robot. The driver robot, in the proposed system performs all the heavy computations in navigation and updates the hitchhiker about the current localized positions and new obstacle positions in the map. The proposed system is robust to recover from 'driver-lost' scenario which occurs due to visual servoing failure. We demonstrate robot hitchhiking in real environments considering factors like service-time and task priority with different start and goal configurations of the driver and hitchhiker robots. We also discuss the admissible characteristics of the hitchhiker, when hitchhiking should be allowed and when not, through experimental results. [ABSTRACT FROM AUTHOR]

The inefficient use of automobiles has long become dissonance-provoking for ecologists and financially disadvantaged travellers. Although there are now more than a dozen psychological studies examining hitch-hiking success this is the first meta-analytic summary of the base-rate of hitch-hiking and its moderators. Every study reporting sufficient data to calculate the proportion of cars stopping divided by the amount of cars in total was included regardless of the gender and age of the hitch-hiking confederates and drivers. A random effects approach was used to calculate study weights and resulted in an overall mean proportion of 9.00% (CI = [8.0, 11.0]). Hitch-hikers’ gender and publication type were significant moderators while controlling for country and year. Females, 12.57% CI[10.33, 14.81], had a higher base-rate than males, 5.71% CI[4.49, 6.92], while published studies, 10.30 CI [8.49, 12,11], had a higher base-rate than unpublished studies, 4.56 [2.96, 6.16]. All of the results were stable in the face of Trim and Fill as well as a leave-one-out analysis. Future research should continue to research the factors influencing hitch-hiking success (e.g. hitch-hiking mode: either standing at the side of the road signaling by thumbg/sign or requesting a ride by asking the drivers) while considering the base-rate to compute the necessary sample size. In practice the base-rate provides hitch-hikers a reasonable estimate of their average success, potentially limiting superstitious mannerisms. [ABSTRACT FROM AUTHOR]

The development of broiler chickens over the last 70 years has been accompanied by large phenotypic changes, so that the resulting genomic signatures of selection should be detectable by current statistical techniques with sufficiently dense genetic markers. Using two approaches, this study analysed high-density SNP data from a broiler chicken line to detect low-diversity genomic regions characteristic of past selection. Seven regions with zero diversity were identified across the genome. Most of these were very small and did not contain many genes. In addition, fifteen regions were identified with diversity increasing asymptotically from a low level. These regions were larger and thus generally included more genes. Several candidate genes for broiler traits were found within these 'regression regions', including IGF1, GPD2 and MTNR1 AI. The results suggest that the identification of zero-diversity regions is too restrictive for characterizing regions under selection, but that regions showing patterns of diversity along the chromosome that are consistent with selective sweeps contain a number of genes that are functional candidates for involvement in broiler development. Many regions identified in this study overlap or are close to regions identified in layer chicken populations, possibly due to their shared precommercialization history or to shared selection pressures between broilers and layers. [ABSTRACT FROM AUTHOR]

Great urban transformations are diffusing across the global South, removing the original landscape of urban margins to make of them a new urban frontier. These processes raise questions of both validity and legitimacy for ethnographic practice, requiring critical reflection on both spatiality and method in fieldwork at the urban margins. This paper draws on fieldwork experience in Beijing’s green belts, which could also be labelled the city’s urban margin or frontier, to reflect on the space-time of encounter in the field. I aim to demonstrate how space foregrounds not only our bodily experiences but also ethnographic investigations of the daily life, and hence becomes amethod. Beijing’s green belts symbolise a historical–geographical conjuncture (amoment) emerging in its urban metamorphosis. Traditional endeavours (immanent in various spatial metaphors) to identify field sites as reified entities are invalidated over the course of the space-time encounter, requiring a relational spatial ontology to register such dynamics. The use in fieldwork ofDiDi Hitch, a mobile app for taxi-hailing and hitchhiking, reveals the spatiotemporal construction of self–other relations needing recognition via the dialectics of the encounter. In this relational framework, an encounter is never a priori but a negotiation of ahere and nowbetween different trajectories and stories as individuals are thrown together in socially constructed space and time. [ABSTRACT FROM AUTHOR]

Hitchhiking, a recently developed bio-inspired cargo delivery system, has been harnessed for diverse applications. By leveraging the interactions between nanoparticles and circulatory cells or proteins, hitchhiking enables efficient navigation through the vasculature while evading immune system clearance. Moreover, it allows for targeted delivery of nutrients to tissues, surveillance of the immune system, and pathogen elimination. Various synthetic nanomaterials have been developed to facilitate hitchhiking with circulatory cells or proteins. By combining the advantages of synthetic nanomaterials and circulatory cells or proteins, hitchhiking nanomaterials demonstrate several advantages over conventional vectors, including enhanced circulatory stability and optimized therapeutic efficacy. This review provides an overview of general strategies for hitchhiking, choices of cells and proteins, and recent advances of hitchhiking nanomaterials for biomedical applications., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)