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The West Virginia University (WVU) Personal Rapid Transit (PRT) system was built between 1971 and 1975 in Morgantown, West Virginia to be a prototype transportation system of the future. Envisioned as a hybrid of public and automotive transportation, the fully automated cars deliver passengers directly to their destinations without stopping at intervening stations. The PRT concept may be familiar to STS scholars through Latour's study of Aramis, a PRT in Paris that was never completed. This article recounts a history with the opposite ending: the successful realization of a PRT in West Virginia. Our account supplements existing ones, which explain the construction of the WVUPRT primarily as the product of geography and politics. While not denying these factors, we carve out an explanatory role for another influence: a public narrative about the dangers of hitchhiking and crimes that might ensue from that practice. In weaving together that narrative with the history of the WVUPRT, we show how public narratives of crime authorize technological infrastructure.

Human evolution is intricately linked with culture, which permeates almost all facets of human life from health and reproduction, to the environments in which we live. Nevertheless, our understanding of the ways in which stably transmitted, evolutionarily relevant human cultural traits might interact with the human genome is incomplete, and methods to detect such interactions are limited. Here, we describe some rules of cultural transmission which could pertain to both humans and cultural nonhuman animals that could lead to the formation and maintenance of stable associations between cultural and genetic traits. Next, we show that, in the presence of such associations, a process analogous to genetic hitchhiking is possible in gene–culture systems. These could leave signatures in the human genome similar to, and perhaps indistinguishable from, those left by selection on genetic traits. Finally, we model selective interference between cultural and genetic traits. We show that selective interference between a cultural trait under selection and a genetic trait under selection can reduce the efficacy of natural selection in the human genome, both in terms of the probability of fixation of beneficial alleles and the dynamics of selective sweeps. We then show that the efficiency of selection at genetic loci can, however, be increased in the presence of strong cultural transmission biases. This implies that the signatures of gene–culture interactions in genetic data may be complex and wide-ranging in gene–culture coevolutionary systems. [ABSTRACT FROM AUTHOR]

When nutrient starvation sets in, the tubular endoplasmic reticulum (ER) within the morphological domain transforms into sheet-like ER structures. Motile early endosomes and lysosomes, which establish membrane contact sites (MCS) with the tubular ER, exert force to organize the tubular ER network in fed cells at steady-state, a phenomenon known as hitchhiking. During early stages of starvation, MCS are reconfigured, leading to conversion of the tubular ER network into sheet-like ER. Lipid metabolism involving phosphatidylinositol 3-phosphate [PI(3)P] at MCS between the tubular ER and motile endolysosomes has an important role in early starvation-induced ER remodeling. ER-phagy is activated during prolonged starvation and may selectively remove specific ER subdomains enriched in (oxidized) polyunsaturated fatty acid phospholipids. Unlike most other organelles found in multiple copies, the endoplasmic reticulum (ER) is a unique singular organelle within eukaryotic cells. Despite its continuous membrane structure, encompassing more than half of the cellular endomembrane system, the ER is subdivided into specialized sub-compartments, including morphological, membrane contact site (MCS), and de novo organelle biogenesis domains. In this review, we discuss recent emerging evidence indicating that, in response to nutrient stress, cells undergo a reorganization of these sub-compartmental ER domains through two main mechanisms: non-destructive remodeling of morphological ER domains via regulation of MCS and organelle hitchhiking, and destructive remodeling of specialized domains by ER-phagy. We further highlight and propose a critical role of membrane lipid metabolism in this ER remodeling during starvation. [ABSTRACT FROM AUTHOR]

Copyright of Tourism Tribune / Lvyou Xuekan is the property of Tourism Institute of Beijing Union University 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.)

Overall, the cultural and artistic practices that continue to surround hitchhiking subcultures are largely untapped by serious scholastic research. This paper, deliberately non-linear, explores the haptic dimensions of hitchhiking. We use this mode of travel to make certain observations about our late-modern, or cosmopolitan age, as well as about some of the subcultures surrounding adventurous, competitive, and alternative transport. The piece is grounded in a form of duo-auto-ethnography, inspired by the experiences of two authors who are well-versed in this practice, but who have still not met in person. The paper argues that one of the main lessons to arise from the era of mass hitchhiking during the mid-twentieth century is that the types of sensory knowledge acquired and passed on by hitchhikers themselves are unique in their spatio-temporal potential for being imaginatively transformed into tools for shaping wider socio-political projects. [ABSTRACT FROM AUTHOR]

Phoresy is an interspecies interaction that facilitates spatial dispersal by attaching to a more mobile species. Hitchhiking species have evolved specific traits for physical contact and successful phoresy, but the regulatory mechanisms involved in such traits and their evolution are largely unexplored. The nematode Caenorhabditis elegans displays a hitchhiking behavior known as nictation during its stress-induced developmental stage. Dauer-specific nictation behavior has an important role in natural C. elegans populations, which experience boom-and-bust population dynamics. In this study, we investigated the nictation behavior of 137 wild C. elegans strains sampled throughout the world. We identified species-wide natural variation in nictation and performed a genome-wide association mapping. We show that the variants in the promoter of nta-1, encoding a putative steroidogenic enzyme, underlie differences in nictation. This difference is due to the changes in nta-1 expression in glial cells, which implies that glial steroid metabolism regulates phoretic behavior. Population genetic analysis and geographic distribution patterns suggest that balancing selection maintained two nta-1 haplotypes that existed in ancestral C. elegans populations. Our findings contribute to further understanding of the molecular mechanism of species interaction and the maintenance of genetic diversity within natural populations. [ABSTRACT FROM AUTHOR]

His legs are screaming pins and needles and his hands cannot feel if anything is broken. Blood drips from somewhere onto the snow, but not for long. [ABSTRACT FROM AUTHOR]

Background: Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies. Results: In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-β/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats. Conclusion: In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation. [ABSTRACT FROM AUTHOR]

Neutrophils are a crucial component of the innate immune system and play a pivotal role in various physiological processes. From a physical perspective, hitchhiking is considered a phenomenon of efficient transportation. The combination of neutrophils and hitchhikers has given rise to effective delivery systems both in vivo and in vitro, thus neutrophils hitchhiking become a novel approach to disease treatment. This article provides an overview of the innovative and feasible application of neutrophils as drug carriers. It explores the mechanisms underlying neutrophil function, elucidates the mechanism of drug delivery mediated by neutrophil‐hitchhiking, and discusses the potential applications of this strategy in the treatment of cancer, immune diseases, inflammatory diseases, and other medical conditions. [ABSTRACT FROM AUTHOR]

B cell-targeted cancer vaccines are receiving increasing attention in immunotherapy due to the combined antibody-secreting and antigen-presenting functions. In this study, we propose a natural IgM-hitchhiking delivery strategy to co-deliver tumor antigens and adjuvants to splenic marginal zone B (MZB) cells. We constructed nanovaccines (FA-sLip/OVA/MPLA) consisting of classical folic acid (FA)-conjugated liposomes co-loaded with ovalbumin (OVA) and toll-like receptor 4 agonists, MPLA. We found that natural IgM absorption could be manipulated at the bio-nano interface on FA-sLip/OVA/MPLA, enabling targeted delivery to splenic MZB cells. Systemic administration of FA-sLip/OVA/MPLA effectively activated splenic MZB cells via IgM-mediated multiplex pathways, eliciting antigen-specific humoral and cytotoxic T lymphocyte responses, and ultimately retarding E.G7-OVA tumor growth. In addition, combining FA-sLip/OVA/MPLA immunization with anti-PD-1 treatments showed improved antitumor efficiency. Overall, this natural IgM-hitchhiking delivery strategy holds great promise for efficient, splenic MZB cell-targeted delivery of cancer vaccines in future applications. Splenic MZB cells-selective co-delivery of cancer antigens and TLR4 agonists was realized via a natural IgM-hitchhiking delivery strategy. The nanovaccines could capture natural IgM in the circulation and led to the accumulation in splenic MZB cells, eliciting lasting tumor antigen-specific antibodies production and cytotoxic T lymphocyte responses. [Display omitted] • Proposing a natural IgM-hitchhiking delivery strategy to deliver nanovaccines to splenic MZB cells • Utilizing the combined antigen-specific humoral and cellular immune of splenic MZB cells for cancer immunotherapy • Improving antitumor efficiency through combination with nanovaccines and anti-PD-1 treatments [ABSTRACT FROM AUTHOR]

Mutator alleles, which confer increased mutation rates, are known to spontaneously emerge and "hitchhike" to fixation in evolving asexual populations. Theory predicts that in an evolving asexual mutator population, a second mutator allele may spontaneously arise and hitchhike to fixation. Here, we describe an empirical test of the hypothesis of repeated hitchhiking. The starting population was a clonal strain of mutL − Escherichia coli whose mutation rate was 100-fold higher than wild type. We exposed the mutL − strain to a series of three antibiotics in increasing order of selective strength: fosfomycin, rifampicin, and streptomycin. Two independent replicates of the experiment were performed. As predicted, elevated mutation rates and enrichment for multilocus mutators (which bear more than one mutator allele) were observed in the end point populations of both experiments. DNA sequencing revealed an identical spontaneous 1-bp insertion in the mutator gene mutT in both end point populations. In the multilocus mutators, the causal relationship between the mutT − mutations and the increase in mutation rate was supported with mutT + plasmid complementation tests. Surprisingly, when the experiment was repeated with the antibiotics deployed in decreasing order of selective strength, enrichment for multilocus mutators was not observed. Our data support the likelihood that the mutT − mutations rose to fixation in both populations, consistent with the hypothesis of repeated mutator hitchhiking. The escalation of mutation rates in asexual populations is relevant to multiple biological scenarios, including antibiotic resistance, host–pathogen interactions, and carcinogenesis. [ABSTRACT FROM AUTHOR]

Bacteria have shown great potential in anti-tumor treatment, and an attenuated strain of Salmonella named VNP20009 has been shown to be safe in clinical trials. However, colonized bacteria recruit neutrophils into the tumor, which release NETs to capture and eliminate bacteria, compromising bacterial-based tumor treatment. In this study, we report a neutrophil hitchhiking nanoparticles (SPPS) that block the formation of NET to enhance bacteria-mediated tumor therapy. In the 4 T1 tumor-bearing mouse model, following 24 h of bacterial therapy, there was an approximately 3.0-fold increase in the number of neutrophils in the bloodstream, while the amount of SPPS homing to tumor tissue through neutrophil hitchhiking increased approximately 2.0-fold. It is worth noting that the NETs in tumors significantly decreased by approximately 2.0-fold through an intracellular ROS scavenging-mediated NETosis reprogramming, thereby increasing bacterial vitality by 1.9-fold in tumors. More importantly, the gene drug (siBcl-2) loaded in SPPS can be re-encapsulated in apoptotic bodies by reprogramming neutrophils from NETosis to apoptosis, and enable the redelivery of drugs to tumor cells, further boosting the antitumor efficacy with a synergistic effect, resulting in about 98% tumor inhibition rate and 90% survival rate. [Display omitted] [ABSTRACT FROM AUTHOR]

Despite being a new promising tool for cancer therapy, intravenous delivery of oncolytic viruses (OVs) is greatly limited by poor tumor targeting, rapid clearance in the blood, severe organ toxicity, and cytokine release syndrome. Herein, a simple and efficient strategy of erythrocyte‐leveraged oncolytic virotherapy (ELeOVt) is reported, which for the first time assembled OVs on the surface of erythrocytes with up to near 100% efficiency and allowed targeted delivery of OVs to the lung after intravenous injection to achieve excellent treatment of pulmonary metastases while greatly improving the biocompatibility of OVs as a drug. Polyethyleneimine (PEI) as a bridge to assemble OVs on erythrocytes also played an important role in promoting the transfection of OVs. It is found that ELeOVt approach significantly prolonged the circulation time of OVs and increased the OVs distribution in the lung by more than tenfold, thereby significantly improving the treatment of lung metastases while reducing organ and systemic toxicity. Taken together, these findings suggest that the ELeOVt provides a biocompatible, efficient, and widely available approach to empower OVs to combat lung metastasis. [ABSTRACT FROM AUTHOR]

Overall, the cultural and artistic practices that continue to surround hitchhiking subcultures are largely untapped by serious scholastic research. This paper, deliberately non-linear, explores the haptic dimensions of hitchhiking. We use this mode of travel to make certain observations about our late-modern, or cosmopolitan age, as well as about some of the subcultures surrounding adventurous, competitive, and alternative transport. The piece is grounded in a form of duo-auto-ethnography, inspired by the experiences of two authors who are well-versed in this practice, but who have still not met in person. The paper argues that one of the main lessons to arise from the era of mass hitchhiking during the mid-twentieth century is that the types of sensory knowledge acquired and passed on by hitchhikers themselves are unique in their spatio-temporal potential for being imaginatively transformed into tools for shaping wider socio-political projects.

For many rural communities in lower-income countries, paratransit services are commonly used. Their service quality is widely debated. There are limited alternative modes, while on-demand mobilities are an option. Some travelers hitchhike and are seen via social media, despite its widely constructed contentiousness. Hitchhiking is, generally, understudied, while social media is also an emerging research field. This paper aims to explore rural (long-distance) hitchhiking demand in South Africa (SA) and compare hitching supply with the commonly used paratransit service, i.e., minibus taxis. Ultimately, probe and encourage assessments of (rural) Mobility-as-a-Service (MaaS), in the context of lower-income countries. The chosen case study is the Waterberg District Municipality in Limpopo Province (SA). Quantitatively described primary data includes the random one-on-one hitcher interviews (m = 429), social media hitcher (n = 418) and driver (o = 93) posts, and a full day observation of all paratransit services from each of the six rural towns in the case study. The results yield ride characteristics, travel arrangements, waiting times, travelling period and mobility satisfactory factors. More empirical evidence is needed to inform policymakers regarding the establishment of or investment in institutions to develop strategies and enforce the transit-competitions and multimodal information technology system that is user-centric – (rural) MaaS. This study makes a valuable contribution to lower-income community traveler’s needs and challenges, with potential political and technological interventions.

Abstract Despite being a new promising tool for cancer therapy, intravenous delivery of oncolytic viruses (OVs) is greatly limited by poor tumor targeting, rapid clearance in the blood, severe organ toxicity, and cytokine release syndrome. Herein, a simple and efficient strategy of erythrocyte‐leveraged oncolytic virotherapy (ELeOVt) is reported, which for the first time assembled OVs on the surface of erythrocytes with up to near 100% efficiency and allowed targeted delivery of OVs to the lung after intravenous injection to achieve excellent treatment of pulmonary metastases while greatly improving the biocompatibility of OVs as a drug. Polyethyleneimine (PEI) as a bridge to assemble OVs on erythrocytes also played an important role in promoting the transfection of OVs. It is found that ELeOVt approach significantly prolonged the circulation time of OVs and increased the OVs distribution in the lung by more than tenfold, thereby significantly improving the treatment of lung metastases while reducing organ and systemic toxicity. Taken together, these findings suggest that the ELeOVt provides a biocompatible, efficient, and widely available approach to empower OVs to combat lung metastasis.

During the Middle and Late Woodland periods in the American Midwest some small-scale societies transitioned from grit to limestone as the primary clay temper. Limestone offers experimentally demonstrated benefits to vessel manufacture, including decreased wall thickness, but given the society-wide changes in mobility and exchange that also occurred, we investigated whether the use of limestone temper resulted in a different vessel weight relative to an analogous grit-tempered vessel. Our analyses demonstrated a significant difference: post-firing, limestone-tempered vessels were 4.5% lighter than grit-tempered ones. The combination of reduced weight and other benefits could help explain why limestone became the predominant temper type throughout much of the Midwest. These issues have direct analogs in the biological realm, and we use three concepts from evolutionary biology – modularity, mosaic evolution, and constraint – to investigate the role limestone temper played not only in vessel weight but also in other aspects of vessel production and use. [ABSTRACT FROM AUTHOR]

A drug-delivery system consisting of an inorganic host—layered double hydroxide (LDH)—and an anticancer drug—methotrexate (MTX)—was prepared via the intercalation route (MTX-LDH), and its hematocompatibility was investigated. Hemolysis, a red blood cell counting assay, and optical microscopy revealed that the MTX-LDH had no harmful toxic effect on blood cells. Both scanning electron microscopy and atomic force microscopy exhibited that the MTX-LDH particles softly landed on the concave part inred blood cells without serious morphological changes of the cells. The time-dependent change in the surface charge and hydrodynamic radius of MTX-LDH in the plasma condition demonstrated that the proteins can be gently adsorbed on the MTX-LDH particles, possibly through protein corona, giving rise to good colloidal stability. The fluorescence quenching assay was carried out to monitor the interaction between MTX-LDH and plasma protein, and the result showed that the MTX-LDH had less dynamic interaction with protein compared with MTX alone, due to the capsule moiety of the LDH host. It was verified by a quartz crystal microbalance assay that the surface interaction between MTX-LDH and protein was reversible and reproducible, and the type of protein corona was a soft one, having flexibility toward the biological environment. [ABSTRACT FROM AUTHOR]

Copyright of Sport & Tourism Central European Journal / Sport i Turystyka Srodkowoeuropejskie Czasopismo Naukowe is the property of Jan Dlugosz University in Czestochowa 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.)

Hitchhiking has a long history as a form of alternative tourism and has experienced significant transformations in recent years due to the overall digitalisation of travel and culture. Similarly to other forms of mobilities, it was disrupted by the COVID-19 pandemic and non-pharmaceutical interventions aiming to stop the disease. The paper first defines hitchhiking as a social phenomenon and outlines its history from global and Polish perspectives. Then, it discusses the current developments and possible futures of hitchhiking culture. It is based first on the outline of the location of hitchhiking in contemporary popular culture, particularly Internet culture, and second on in-depth interviews with five young yet experienced lifestyle hitchhikers, performed during strict pandemic restrictions. The interviews focus on three major topics: modern challenges in hitchhiking, ITC (information and communication technologies) use, and hitchhiking during the pandemic. The results indicate the evolution of hitchhiking as a social phenomenon, where the cultural heritage of alternative lifestyles intertwines with the increasing role of the Internet and mobile communication. In conclusion, we postulate further studies, including applying new methodological approaches and asking research questions regarding, e.g. the commodification of tourism, the importance of web reputation, and interactions between hitchhikers, residents and drivers.

ABSTRACTDuring the Middle and Late Woodland periods in the American Midwest some small-scale societies transitioned from grit to limestone as the primary clay temper. Limestone offers experimentally demonstrated benefits to vessel manufacture, including decreased wall thickness, but given the society-wide changes in mobility and exchange that also occurred, we investigated whether the use of limestone temper resulted in a different vessel weight relative to an analogous grit-tempered vessel. Our analyses demonstrated a significant difference: post-firing, limestone-tempered vessels were 4.5% lighter than grit-tempered ones. The combination of reduced weight and other benefits could help explain why limestone became the predominant temper type throughout much of the Midwest. These issues have direct analogs in the biological realm, and we use three concepts from evolutionary biology – modularity, mosaic evolution, and constraint – to investigate the role limestone temper played not only in vessel weight but also in other aspects of vessel production and use.

Copyright of Culture & Communication / Kültür ve İletişim is the property of Imge Publishing House 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.)

Myocardial infarction (MI) is the leading cause of death worldwide. However, current therapies are unable to restore the function of the injured myocardium. Advanced approaches, such as stimulation of cardiomyocyte (CM) proliferation are promising, but suffer from poor pharmacokinetics and possible systemic adverse effects. Nanomedicines can be a solution to the above‐mentioned drawbacks. However, targeting the cardiac tissue still represents a challenge. Herein, a MI‐selective precision nanosystem is developed, that relies on the heart targeting properties of atrial natriuretic peptide (ANP) and lin‐TT1 peptide‐mediated hitchhiking on M2‐like macrophages. The system based on pH‐responsive putrescine‐modified acetalated dextran (Putre‐AcDEX) nanoparticles, shows biocompatibility with cultured cardiac cells, and ANP receptor‐dependent interaction with CMs. Moreover, treatment with nanoparticles (NPs) loaded with two pleiotropic cellular self‐renewal promoting compounds, CHIR99021 and SB203580, induces a 4‐fold increase in bromodeoxyuridine (BrdU) incorporation in primary cardiomyocytes compared to control. In vivo studies confirm that M2‐like macrophages targeting by lin‐TT1 peptide enhances the heart targeting of ANP. In addition, NP administration does not alter the immunological profile of blood and spleen, showing the short‐term safety of the developed system in vivo. Overall, the study results in the development of a peptide‐guided precision nanosystem for delivery of therapeutic compounds to the infarcted heart. [ABSTRACT FROM AUTHOR]

Privacy-preserving task assignment is vital to assign a task to appropriate workers and protect workers' privacy or task privacy for spatial crowdsourcing (SC). Existing solutions usually require each worker to travel to the task location on purpose to perform this task, which fails to consider that workers have specific trajectories and carry out the task on their way in a hitchhiking manner. To this end, this paper proposes a privacy-preserving hitchhiking task assignment scheme for SC, named PKGS. Specifically, we formulate the privacy-preserving hitchhiking task assignment as a decision problem of the relationship between dot and line under privacy protection. In particular, we present a privacy-preserving travel distance calculation protocol and a privacy-preserving comparison protocol through the Paillier cryptosystem and the SC framework. Results of theoretical analysis and experimental evaluation show that PKGS can not only protect the location privacy of both each worker and the task simultaneously but also assign the task to the worker holding a minimum travel distance. In contrast to prior solutions, PKGS outperforms in the computation of travel distance and task assignment. [ABSTRACT FROM AUTHOR]

Nanoscale ultrasound contrast agents, or nanobubbles, are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in cancer. These sub-micron particles are approximately 10x smaller than clinically available microbubbles. This allows them to effectively traverse compromised physiological barriers and circulate for extended periods of time. While various aspects of nanobubble behavior have been previously examined, their behavior in human whole blood has not yet been explored. Accordingly, herein we examined, for the first time, the short and long-term effects of blood components on nanobubble acoustic response. We observed differences in the kinetics of backscatter from nanobubble suspensions in whole blood compared to bubbles in phosphate buffered saline (PBS), plasma, or red blood cell solutions (RBCs). Specifically, after introducing nanobubbles to fresh human whole blood, signal enhancement, or the magnitude of nonlinear ultrasound signal, gradually increased by 22.8 ± 13.1% throughout our experiment, with peak intensity reached within 145 s. In contrast, nanobubbles in PBS had a stable signal with negligible change in intensity (−1.7 ± 3.2%) over 8 min. Under the same conditions, microbubbles made with the same lipid formulation showed a −56.8 ± 6.1% decrease in enhancement in whole blood. Subsequent confocal, fluorescent, and scanning electron microscopy analysis revealed attachment of the nanobubbles to the surface of RBCs, suggesting that direct interactions, or hitchhiking, of nanobubbles on RBCs in the presence of plasma may be a possible mechanism for the observed effects. This phenomenon could be key to extending nanobubble circulation time and has broad implications in drug delivery, where RBC interaction with nanoparticles could be exploited to improve delivery efficiency.

Adoptive T cells and immunotherapy suppress the most destructive metastatic tumors and prevent tumor recurrence by inducing T lymphocytes. However, the heterogeneity and immune privilege of invasive metastatic clusters often reduce immune cell infiltration and therapeutic efficacy. Here, the red blood cells (RBC)-hitchhiking mediated lung metastasis delivery of multi-grained iron oxide nanostructures (MIO) programming the antigen capture, dendritic cell harnessing, and T cell recruitment is developed. MIO is assembled to the surface of RBCs by osmotic shock-mediated fusion, and reversible interactions enable the transfer of MIO to pulmonary capillary endothelial cells by intravenous injection by squeezing RBCs at the pulmonary microvessels. RBC-hitchhiking delivery revealed that >65% of MIOs co-localized in tumors rather than normal tissues. In alternating magnetic field (AMF)-mediated magnetic lysis, MIO leads to the release of tumor-associated antigens, namely neoantigens and damage-associated molecular patterns. It also acted as an antigen capture agent-harnessed dendritic cells delivers these antigens to lymph nodes. By utilizing site-specific targeting, erythrocyte hitchhiker-mediated delivery of MIO to lung metastases improves survival and immune responses in mice with metastatic lung tumors. [Display omitted] [ABSTRACT FROM AUTHOR]

We investigated, for the first time, the hitchhiker‐host fidelity of deep‐diving whale sharks and Chilean devil rays. We found that two of the most ubiquitous oceanic hitchhikers, the common remora and the pilot fish, are able to follow their hosts to bathypelagic depths, where they are exposed to extreme gradients of light, dissolved oxygen, temperature, and pressure. We documented a deep dive of a large whale shark hosting remoras and pilot fish. Common remora was observed at the deepest section of the dive, at 1460 m, where the water temperature was 3.6°C. A pilot fish was recorded at 900 m, during the ascent phase, with the water temperature of 7.5°C. Although the adaptations that allow these hitchhikers to mitigate the impacts of such extreme environmental conditions remain unknown, we discuss these findings in the framework of the ecophysiology of deep diving and the hitchhiker‐host fidelity. [ABSTRACT FROM AUTHOR]

Natural selection not only affects the actual loci under selection but also leaves “footprints” in patterns of genetic variation in linked genetic regions. This offers exciting opportunities for inferring selection and for understanding the processes shaping levels of genetic variation in natural populations. Here, we develop analytical approximations based on coalescent theory to characterize the genetic footprint of a complex, but potentially common type of natural selection: balancing selection with seasonally fluctuating allele frequencies. As we show analytically and confirm with stochastic simulations, seasonal allele frequency fluctuations can have important (and partly unexpected) consequences for the genetic footprint of balancing selection. Fluctuating balancing selection generally leads to an increase in genetic diversity close to the selected site, the effect of balancing selection, but reduces diversity further away from the selected site, which is a consequence of the allele-frequency fluctuations effectively producing recurrent bottlenecks of allelic backgrounds. This medium- and long-range reduction usually outweighs the short-range increase when averaging diversity levels across the entire chromosome. Strong fluctuating balancing selection even induces a loss of genetic variation in unlinked regions, e.g. on different chromosomes. If many loci in the genome are simultaneously under fluctuating balancing selection this can lead to substantial genome-wide reductions in genetic diversity, even when allele-frequency fluctuations are small and local footprints are difficult to detect. Thus, together with genetic drift, selective sweeps and background selection, fluctuating selection could be a major force shaping levels of genetic diversity in natural populations. [ABSTRACT FROM AUTHOR]

Plant gravitropism has fascinated scientists for centuries. A new study provides a major mechanistic update of the so-called starch/statolith hypothesis, revealing how gravity perception is converted into a physiological response. [ABSTRACT FROM AUTHOR]

Predictions about the effect of natural selection on patterns of linked neutral variation are largely based on models involving the rapid fixation of unconditionally beneficial mutations. However, when phenotypes adapt to a new optimum trait value, the strength of selection on individual mutations decreases as the population adapts. Here, I use explicit forward simulations of a single trait with additive-effect mutations adapting to an "optimum shift." Detectable "hitchhiking" patterns are only apparent if (i) the optimum shifts are large with respect to equilibrium variation for the trait, (ii) mutation rates to large-effect mutations are low, and (iii) large-effect mutations rapidly increase in frequency and eventually reach fixation, which typically occurs after the population reaches the new optimum. For the parameters simulated here, partial sweeps do not appreciably affect patterns of linked variation, even when the mutations are strongly selected. The contribution of new mutations vs. standing variation to fixation depends on the mutation rate affecting trait values. Given the fixation of a strongly selected variant, patterns of hitchhiking are similar on average for the two classes of sweeps because sweeps from standing variation involving large-effect mutations are rare when the optimum shifts. The distribution of effect sizes of new mutations has little effect on the time to reach the new optimum, but reducing the mutational variance increases the magnitude of hitchhiking patterns. In general, populations reach the new optimum prior to the completion of any sweeps, and the times to fixation are longer for this model than for standard models of directional selection. The long fixation times are due to a combination of declining selection pressures during adaptation and the possibility of interference among weakly selected sites for traits with high mutation rates.

[Display omitted] • A concentration-dependent curve was determined using in vitro assays. • Copper chloride, copper sulfate, and nitroxynil were effective against nematodes. • A synergic effect was observed against Haemonchus spp. and Trichostrongylus spp. • Copper chloride had a better effect, even in combination, against nematode parasites. Infections caused by Haemonchus spp. and Trichostrongylus spp. are major health problems for sheep and cattle. The objective of this study was to determine the efficacy of copper chloride (CuCl 2), and copper sulphate (CuSO 4) at 2.0, 7.0, 30.0, 125.0, 500.0, and 2000.0 µM formulations, and nitroxynil 34% (NTX) at 0.235 mM against gastrointestinal nematodes (GINs) of ruminants. Hence, the in vitro egg hatch test (EHT), the larval development test (LDT), and the larval migration inhibition test (LMIT) were used. Haemonchus spp. (52%) and Trichostrongylus spp. (38%) were the most frequently found parasites. The data fitted a concentration-dependent shape with the highest efficacies of CuCl 2 and CuSO 4 at 95.2 and 97.3% for parasites collected from sheep, and 95.8 and 93.4% from cattle, respectively. The combination of the 50% inhibitory concentration (IC 50) of CuCl 2 and CuSO 4 and the IC 10 of NTX showed up to a 52% increase in efficacy above the expected additive results, demonstrating a synergic/drug enhancer interaction. NTX may retain Cu-II ions by complexation, in a hitchhiking mechanism carrying the salts across the parasite cell wall, causing oxidative stress as a consequence of free radical production and cell damage. Synergy data between NTX and CuCl 2 , and CuSO 4 represent a viable opportunity to develop new formulations for combating parasites of ruminants (i.e., Fasciola hepatica , Haemonchus spp., and Oesophagostomum spp.). [ABSTRACT FROM AUTHOR]

Purpose: This study explores the influence of partner innovation in board interlock networks on a firm's innovation tendency. Design/methodology/approach: This study collects a sample of publicly listed Chinese firms from 2008 to 2017 and uses fixed-effects ordinary least squares regressions to analyze the data. Findings: This study shows that interlocking partners with different innovation levels than that of the focal firm affect its innovation tendency in distinct ways. For more innovative partners, the innovation level has a U-shaped effect on the focal firm's innovation tendency. In the case of less innovative partners, the innovation level facilitates the focal firm's innovation tendency. Originality/value: Going beyond previous research that emphasized the role of interorganizational networks in facilitating firm innovation through a unitary learning effect, this study differentiates network partners into two categories based on their relative level of innovation compared with the focal firm and takes the hitchhiking effect into account to highlight potential obstacles in the learning process depending on the innovation conditions of partners. The study advances the literature on organizational learning, social networks and innovation. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus, which lacks pili and flagella, is nonmotile. However, it hitchhikes motile bacteria, such as Pseudomonas aeruginosa, to migrate in the environment. This study demonstrated that the hitchhiking motility of S. aureus SA113 was reduced after the tagO, which encodes an enzyme for wall teichoic acids (WTA) synthesis, was deleted. The hitchhiking motility was restored after the mutation was complemented by transforming a plasmid expressing TagO into the mutant. We also showed that adding purified lipopolysaccharide (LPS) to a culture that contains S. aureus SA113 and P. aeruginosa PAO1, reduced the movement of S. aureus, showing that WTA and LPS are involved in the hitchhiking motility of S. aureus. This study also found that P. aeruginosa promoted the movement of S. aureus in the digestive tract of Caenorhabditis elegans and in mice. In conclusion, this study reveals how S. aureus hitchhikes P. aeruginosa for translocation in an ecosystem. The results from this study improve our understanding on how a nonmotile pathogen moves in the environment and spreads in animals. [ABSTRACT FROM AUTHOR]

Small therapeutic proteins are receiving increased interest as therapeutic drugs; however, their clinical success has been limited due to their rapid elimination. Here, we report a half-life extension strategy via strategy via red blood cell red blood cell (RBC) hitch-hiking. This manuscript details the development and characterization of novel anti-RBC single-domain antibodies (sdAbs), their genetic fusion to therapeutic antibody fragments (TAF) as bispecific fusion constructs, and their influence on TAF pharmacokinetics and biodistribution. Several sdAbs specific to the band 3 antigen were generated via phage-display technology. Binding affinity to RBCs was assessed via flow cytometry. Affinity maturation via random mutagenesis was carried out to improve the binding affinity of the sdAbs. Bi-specific constructs were generated by fusing the anti-RBC sdAbs with anti-tissue necrosis factor alpha (TNF-α) TAF via the use of a glycine-serine flexible linker, and assessments for binding were performed via enzyme-linked immunosorbent assay and flow cytometry. Pharmacokinetics of anti-RBC sdAbs and fusion constructs were evaluated following intravenous bolus dosing in mice at a 1 mg/kg dose. Two RBC-binding sdAbs, RB12 and RE8, were developed. These two clones showed high binding affinity to human RBC with an estimated KD of 17.7 nM and 23.6 nM and low binding affinity to mouse RBC with an estimated KD of 335 nM and 528 nM for RB12 and RE8, respectively. Two derivative sdAbs, RMA1, and RMC1, with higher affinities against mouse RBC, were generated via affinity maturation (KD of 66.9 nM and 30.3 nM, respectively). Pharmacokinetic investigations in mice demonstrated prolonged circulation half-life of an anti-RBC-TNF-α bispecific construct (75 h) compared to a non-RBC binding control (1.3 h). In summary, the developed anti-RBC sdAbs and fusion constructs have demonstrated high affinity in vitro, and sufficient half-life extension in vivo. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) holds potential as an alternative approach for effective cancer treatment since it exerts minimal side effects on normal tissues. However, the photothermal stimulation increases the expression of heat shock protein (HSP) in tumor cells, rendering the tumor cells insensitive to heat and thus constraining the effects of PTT. In this study, biomimetic aggregation‐induced emission (AIE) photothermal agents with hitchhiking ability (DC@BPBBT dots) are developed by coating the nanoaggregates of the NIR AIE polymeric photothermal agents with dendritic cell (DC) membranes. Notably, the inner nanoaggregate (BPBBT dots) holds bright second‐window near infrared (NIR‐II) fluorescence (quantum yield of up to 3.47%) and a high photothermal conversion performance (photothermal conversion efficiency of up to 30.5%), and the outer cell membrane can facilitate the hitchhiking of DC@BPBBT dots on endogenous T cells and enhance the tumor delivery efficiency by about 1.2 times. Furthermore, DC@BPBBT dots can activate and stimulate T cells in vivo to secrete cytokine tumor necrosis factor α (TNF‐α), which can reduce the expression of heat shock protein 70 (HSP70) to render tumor cells more sensitive to heat. This study not only provides an alternative heat shock protein inhibition strategy based on immune cell interactions but also provides a hitchhike approach for drug delivery in cancer photothermal immunotherapy. [ABSTRACT FROM AUTHOR]

We conducted the monitoring of hitchhiker insect pests around the port area in Korea and reported the settlement of Melanoplus differentialis (Thomas, 1865) in Onsan Port, Ulsan, Korea. The occurrence pattern of the invasive species was determined using a line census method. Species identification was first performed with DNA barcoding, and then the DNA barcoded samples were morphologically re‐examined. Monitoring of the occurrence pattern revealed that the invasive populations of M. differentialis settled in a narrow artificial green area, and it occurred in large numbers (over 100 individuals per hour). Species identification of the invasive population using DNA barcoding indicated that the population showing high intraspecific divergence from null to 3.9% was difficult to identify as a separate species. However, in morphological re‐examination, the population was clearly identified as a single species, M. differentialis. In a haplotype analysis using DNA barcodes, the population included 45 haplotypes with polymorphism at 46 nucleotide sites. On the basis of these results, we considered that M. differentialis may have invaded into Onsan Port, Ulsan, Korea. Therefore, we provided the biological traits of the grasshopper for risk assessment and suggested the necessity of monitoring and controlling the dispersal of M. differentialis into the inlands of Korea in the early stages. [ABSTRACT FROM AUTHOR]

Eukaryotic cells across the tree of life organize their subcellular components via intracellular transport mechanisms. In canonical transport, myosin, kinesin, and dynein motor proteins interact with cargos via adaptor proteins and move along filamentous actin or microtubule tracks. In contrast to this canonical mode, hitchhiking is a newly discovered mode of intracellular transport in which a cargo attaches itself to an already-motile cargo rather than directly associating with a motor protein itself. Many cargos including messenger RNAs, protein complexes, and organelles hitchhike on membrane-bound cargos. Hitchhiking-like behaviors have been shown to impact cellular processes including local protein translation, long-distance signaling, and organelle network reorganization. Here, we review instances of cargo hitchhiking in fungal, animal, and plant cells and discuss the potential cellular and evolutionary importance of hitchhiking in these different contexts. [ABSTRACT FROM AUTHOR]

The 2-micron plasmid residing within the host budding yeast Saccharomyces cerevisiae nucleus serves as a model system for understanding the mechanism of segregation and stable maintenance of circular endogenously present extrachromosomal DNA in eukaryotic cells. The plasmid is maintained at a high average copy number (40-60 copies per yeast cell) through generations despite there is no apparent benefit to the host. Notably, the segregation mechanism of 2-micron plasmid shares significant similarities with those of bacterial low-copy-number plasmids and episomal forms of viral genomes in mammalian cells. These similarities include formation of a complex where the plasmid- or viral encoded proteins bind to a plasmid- or viral genome-borne locus, respectively and interaction of the complex with the host proteins. These together form a partitioning system that ensures stable symmetric inheritance of both these genomes from mother to daughter cells. Recent studies with substantial evidence showed that the 2-micron plasmid, like episomes of viruses such as Epstein-Barr virus, relies on tethering itself to the host chromosomes in a non-random fashion for equal segregation. This review delves into the probable chromosome hitchhiking mechanisms of 2-micron plasmid during its segregation, highlighting the roles of specific plasmid-encoded proteins and their interactions with host proteins and the chromosomes. Understanding these mechanisms provides broader insights into the genetic stability and inheritance of extrachromosomal genetic elements across diverse biological systems., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Sepsis is characterized by a dysregulated immune response and is very difficult to treat. In the cecal ligation and puncture (CLP) mouse model, we show that nanomedicines can effectively alleviate systemic and local septic events by targeting neutrophils. Specifically, by decorating the surface of clinical-stage dexamethasone liposomes with cyclic arginine-glycine-aspartic acid (cRGD) peptides, we promote their engagement with neutrophils in the systemic circulation, leading to their prominent accumulation at primary and secondary sepsis sites. cRGD-targeted dexamethasone liposomes potently reduce immature circulating neutrophils and neutrophil extracellular traps in intestinal sepsis induction sites and the liver. Additionally, they mitigate inflammatory cytokines systemically and locally while preserving systemic IL-10 levels, contributing to lower IFN-γ/IL-10 ratios as compared to control liposomes and free dexamethasone. Our strategy addresses sepsis at the cellular level, illustrating the use of neutrophils both as a therapeutic target and as a chariot for drug delivery.

The West Virginia University (WVU) Personal Rapid Transit (PRT) system was built between 1971 and 1975 in Morgantown, West Virginia to be a prototype transportation system of the future. Envisioned as a hybrid of public and automotive transportation, the fully automated cars deliver passengers directly to their destinations without stopping at intervening stations. The PRT concept may be familiar to STS scholars through Latour's study of Aramis, a PRT in Paris that was never completed. This article recounts a history with the opposite ending: the successful realization of a PRT in West Virginia. Our account supplements existing ones, which explain the construction of the WVUPRT primarily as the product of geography and politics. While not denying these factors, we carve out an explanatory role for another influence: a public narrative about the dangers of hitchhiking and crimes that might ensue from that practice. In weaving together that narrative with the history of the WVUPRT, we show how public narratives of crime authorize technological infrastructure., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We recently published a paper quantifying the genome‐wide consequences of natural selection, including the effects of indirect selection due to the correlation of genetic regions (neutral or selected) with directly selected regions (Gompert et al., 2022). In their critique of our paper, Charlesworth and Jensen (2022) make two main points: (i) indirect selection is equivalent to hitchhiking and thus well documented (i.e., our results are not novel) and (ii) that we do not demonstrate the source of linkage disequilibrium (LD) between SNPs and the Mel‐Stripe locus in the Timema cristinae experiment we analyse. As we discuss in detail below, neither of these are substantial criticisms of our work. This is a reply to the commentary by Charlesworth and Jensen (2022); [ABSTRACT FROM AUTHOR]

We write to address recent claims by regarding the potentially important and underappreciated phenomena of "indirect selection," the observation that neutral regions may be affected by natural selection. We argue both that this phenomenon—generally known as genetic hitchhiking—is neither new nor poorly studied, and that the patterns described by the authors have multiple alternative explanations. [ABSTRACT FROM AUTHOR]

Hitchhiking bistatic radar system takes the direct wave signal that is transmitted by the non-cooperative radar emitter as the reference to detect and analyze the target echo signal, so as to realize the positioning and tracking of the target. This radar system has the advantages of low cost and strong survivability. Aiming at the problem of passive radar to covert the detection of maritime targets, this paper develops a hitchhiking bistatic radar system for maritime target detection, which uses the shore-based radar as the non-cooperative radar emitter. By continuously collecting the direct wave and target echo data of the non-cooperative radar, the direct wave reference signal reconstruction, pulse compression, interference suppression and synchronization processing, non-coherent integration, MTI (moving target indication), clutter map processing, and adaptive CFAR (constant false alarm rate) detection are completed to obtain the azimuth, bistatic range, and Doppler frequency of the target, and finally realize the positioning of non-cooperative maritime targets. This paper first introduces and demonstrates the composition principle of the system, introduces the signal processing implementation method of the system in detail, and tests and analyzes the key algorithms. The experimental results show that the system can realize the passive coherent detection of maritime moving targets and locate multiple targets at the same time. The experiment obtains a very clear PPI (plane position indicator) display picture of the hitchhiking bistatic radar system, and the radar detection data of the experimental system is in good agreement with the AIS (automatic identification system) data. [ABSTRACT FROM AUTHOR]

Unmanned aerial vehicle (UAV) has demonstrated its usefulness in goods delivery. However, the delivery distances are often restrained by the battery capacity of UAVs. This paper integrates UAVs into intelligent transportation systems for energy-efficient, delay-sensitive goods delivery. Dynamic programming (DP) is first applied to minimize the energy consumption of a UAV and ensure its timely arrival at its destination, by optimizing the control policy of the UAV. The control policy involves decisions including flight speed, hitchhiking (on collaborative ground vehicles), or recharging at roadside charging stations. Another key aspect is that we reveal the conditions of the remaining flight distance or the elapsed time, only under which the optimal action of the UAV changes. Accordingly, thresholds are derived, and the optimal control policy can be instantly made by comparing the remaining flight distance and the elapsed time with the thresholds. Simulations show that the proposed algorithms can improve the flight distance by 48%, as compared with existing alternatives. The proposed threshold-based technique can achieve the same performance as the DP-based solution, while significantly reducing the computational complexity. [ABSTRACT FROM AUTHOR]

Red blood cell (RBC) hitchhiking has great potential in enhancing drug therapy, by improving targeting and reducing rapid clearance of nanoparticles (NPs). However, to improve the potential for clinical translation of RBC hitchhiking, a more thorough understanding of the RBC-NP interface is needed. Here, we evaluate the effects of NP surface parameters on the success and biocompatibility of NP adsorption to extracted RBCs from various species. Major differences in RBC characteristics between rabbit, mouse and human were proven to significantly impact NP adsorption outcomes. Additionally, the effects of NP design parameters, including NP hydrophobicity, zeta potential, surfactant concentration and drug encapsulation, on RBC hitchhiking are investigated. Our studies demonstrate the importance of electrostatic interactions in balancing NP adsorption success and biocompatibility. We further investigated the effect of varying the anti-coagulant used for blood storage. The results presented here offer new insights into the parameters that impact NP adsorption on RBCs that will assist researchers in experimental design choices for using RBC hitchhiking as drug delivery strategy. [ABSTRACT FROM AUTHOR]