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Efficient homing of infused hematopoietic stem and progenitor cells (HSPCs) into the bone marrow (BM) is the prerequisite for successful hematopoietic stem cell transplantation. However, only a small part of infused HSPCs find their way to the BM niche. A better understanding of the mechanisms that facilitate HSPC homing will help to develop strategies to improve the initial HSPC engraftment and subsequent hematopoietic regeneration. Here, we show that irradiation upregulates the endomucin expression of endothelial cells in vivo and in vitro. Furthermore, depletion of endomucin in irradiated endothelial cells with short-interfering RNA (siRNA) increases the HSPC-endothelial cell adhesion in vitro. To abrogate the endomucin of BM sinusoidal endothelial cells (BM-SECs) in vivo, we develop a siRNA-loaded bovine serum albumin nanoparticle for targeted delivery. Nanoparticle-mediated siRNA delivery successfully silences endomucin expression in BM-SECs and improves HSPC homing during transplantation. These results reveal that endomucin plays a critical role in HSPC homing during transplantation and that gene-based manipulation of BM-SEC endomucin in vivo can be exploited to improve the efficacy of HSPC transplantation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Stem cell therapy is an alternative treatment strategy for restoring damaged myocardial tissue after acute myocardial infarction. Exercise preconditioning can induce endogenous cardioprotective effects in the body. However, the efficacy and mechanism of the combined application are still unclear. OBJECTIVE: To explore the effect and possible mechanism of exercise preconditioning combined with bone marrow mesenchymal stem cells on the therapeutic effect in rats with acute myocardial infarction. METHODS: Seventy male SD rats were randomly divided into sham operation group, model group, stem cell therapy group, exercise preconditioning group, and combined intervention group. Rats in the exercise preconditioning group and combined intervention group underwent 8-week aerobic exercise on the treadmill before modeling. The animal model of acute myocardial infarction was made by ligating the anterior descending coronary artery. The stem cell therapy group and the combined intervention group were injected with bone marrow mesenchymal stem cells (1×109 L-1, 1 mL) through the tail vein the next day after modeling. After 4 weeks of treatment, the exercise performance was evaluated by a graded treadmill exercise test. The cardiac structure and function were detected by echocardiography. The left ventricle was isolated. 2,3,5-Triphenyltetrazolium chloride staining was used to evaluate myocardial infarct size. Masson staining was used to obtain collagen volume fraction. CD31 immunohistochemical staining was used to detect myocardial capillary density. TUNEL staining was used to detect myocardial cell apoptosis. Immunoblotting was used to detect protein expression levels of stromal cell-derived factor 1, CXC chemokine receptor protein 4, tumor necrosis factor-α, interleukin-10, and vascular endothelial growth factor. RESULTS AND CONCLUSION: (1) Intervention efficacy: Compared with the sham operation group, exercise performance, left ventricular ejection fraction, left ventricular fractional shortening, and CD31 positive cell rate decreased (P < 0.05); myocardial infarct size, collagen volume fraction, and myocardial apoptotic rate increased (P < 0.05) in the model group. Compared with the model group, exercise performance was not statistically significant (P > 0.05) in the stem cell therapy group, and the exercise performance improved (P < 0.05) in the exercise preconditioning and combined intervention groups; left ventricular ejection fraction, left ventricular fractional shortening, and CD31 positive cell rate increased (P < 0.05), and the myocardial infarct size, collagen volume fraction, and cardiomyocyte apoptosis rate decreased (P < 0.05) in the stem cell therapy, exercise preconditioning, and combined intervention groups. Compared with the stem cell therapy group, exercise performance, left ventricular ejection fraction, left ventricular shortening fraction, and CD31 positive cell rate increased (P < 0.05), myocardial infarct size, collagen volume fraction, and myocardial cell apoptosis rate decreased (P < 0.05) in the combined intervention group. (2) Protein expression: Compared with the sham operation group, the expression of tumor necrosis factor-α increased (P < 0.05), while interleukin-10 and vascular endothelial growth factor expression decreased (P < 0.05) in the model group. Compared with the model group, the expression of CXC chemokine receptor protein 4 increased (P < 0.05) in the stem cell therapy group and combined intervention group, and the expression of tumor necrosis factor-α decreased (P < 0.05) while interleukin-10 and vascular endothelial growth factor increased (P < 0.05) in the stem cell therapy group, exercise preconditioning group, and combined intervention group. Compared with the stem cell therapy group, the expression of tumor necrosis factor-α decreased (P < 0.05), while CXC chemokine receptor protein 4, interleukin-10, and vascular endothelial growth factor increased (P < 0.05) in the combined intervention group. To conclude, exercise preconditioning can enhance the therapeutic effect of bone marrow mesenchymal stem cells in rats with acute myocardial infarction, which can inhibit cardiac remodeling, improve cardiac function, and delay the progress of heart failure. Its mechanism is related to the promotion of stem cell homing, inhibition of inflammatory response, and promotion of angiogenesis. [ABSTRACT FROM AUTHOR]

Genetic biocontrol aims to suppress or modify populations of species to protect public health, agriculture, and biodiversity. Advancements in genome engineering technologies have fueled a surge in research in this field, with one gene editing technology, CRISPR, leading the charge. This review focuses on the current state of CRISPR technologies for genetic biocontrol of pests and highlights the progress and ongoing challenges of using these approaches.

A disbalance between immune regulatory cells and inflammatory cells is known to drive atherosclerosis. However, the exact mechanism is not clear. Here, we investigated the homing of immune regulatory cells, mainly, regulatory T cells (Tregs) and myeloid‐derived suppressor cells (MDSCs) subsets in asymptomatic coronary artery disease (CAD) risk factor‐exposed young individuals (dyslipidemia [DLP] group) and stable CAD patients (CAD group). Compared with healthy controls (HCs), Tregs frequency was reduced in both DLP and CAD groups but expressed high levels of CCR5 in both groups. The frequency of monocytic‐myeloid‐derived suppressor cells (M‐MDSCs) was increased while polymorphonuclear myeloid‐derived suppressor cells (PMN‐MDSCs) were decreased in CAD patients only. Interestingly, although unchanged in frequency, M‐MDSCs of the DLP group expressed high levels of CCR5. Serum levels of chemokines (CCL5, CX3CL1, CCL26) and inflammatory cytokines (IL‐6, IL‐1β, IFN‐γ, TNF‐α) were higher in the DLP group. Stimulation with inflammatory cytokines augmented CCR5 expression in Tregs and M‐MDSCs isolated from HCs. Activated endothelial cells showed elevated levels of CX3CL1 and CCL5 in vitro. Blocking CCR5 with D‐Ala‐peptide T‐amide (DAPTA) increased Treg and M‐MDSC frequency in C57Bl6 mice fed a high‐fat diet. In accelerated atherosclerosis model, DAPTA treatment led to the formation of smooth muscle‐rich plaque with less macrophages. Thus, we show that CCR5‐CCL5 axis is instrumental in recruiting Tregs and M‐MDSCs to dysfunctional endothelium in the asymptomatic phase of atherosclerosis contributing to atherosclerosis progression. Drugs targeting CCR5 in asymptomatic and CAD risk‐factor/s‐exposed individuals might be a novel therapeutic regime to diminish atherogenesis. [ABSTRACT FROM AUTHOR]

Several stages are determined in the early run of sockeye salmon into tributaries of Lake Nachikinskoye: i) maturation of adults at depth, ii) concentration of adults in the mouths of the main tributaries, iii) entry of small flocks of the spawners into tributaries over a short distance, iv) upstream movement of lager flocks, v) thinning of flocks and formation of pairs, vi) spawning, and vii) death of spawned fish. In the large, stable accumulations formed in the mouths of tributaries, salmon choose paths for onward movement in the process of homing, by decoding imprinting information. There, aggregations of spawners are differentiated into separate flocks going to spawn on different spawning grounds. A peculiarity of this population of sockeye salmon is the retention of individuals not ready for spawning in many pits and catches of the rivers, with formation of well-visible compact schools, which dissipate as the fish mature. Filling of the spawning grounds in tributaries is determined by their characteristics, and typically occurs with a dome-shaped dynamics of intensity. The upward long-term trend in filling of the spawning grounds is observed in the lower Taburetka River (before its tributaries), while the downward trend — in the tributaries. Data on the filling for the last 5 years are presented. The greatest contribution to reproduction of the early sockeye salmon in Lake Nachikinskoye is provided by the lower reaches of the Taburetka River (41 %), whereas its tributary, the Verkhnyaya River, contributes 20 % and inputs of other tributaries are noticeably lower. In conditions of degradation for a part of the spawning grounds due to increased anthropogenic impact, all existing subpopulations should be preserved as productive as possible.

This article explores the experiences of young people navigating an evolving system of housing and homelessness services in Vancouver, Canada. Despite recent shifts toward Housing First policies and calls for prevention-oriented initiatives, many young people continue to rely on temporary emergency accommodations. Amid a surge in youth homelessness and unstable housing in Vancouver, our study examines young people’s “homing” strategies across time and place and temporary and more permanent living environments. We draw from an ongoing ethnographic study that began in 2021 and has involved over 70 interviews and 100 h of fieldwork with 54 young people aged 19 to 29. Our findings emphasize that feeling at home extends beyond having a roof over one’s head for an extended period of time. A focus on homing strategies—that is, the day-to-day practices, routines, and forms of sociality that generate a sense of stability and care even in un-homelike places—highlights how young people can be better supported in making themselves at home in the places where they live, potentially preventing returns to street-based homelessness. This study contributes insights to youth homelessness prevention policies, urging a strengths-based approach that aligns with young people’s needs, priorities, and desires for homemaking.

Mesenchymal stem cells (MSCs) have shown great potential for the treatment of liver injuries, and the therapeutic efficacy greatly depends on their homing to the site of injury. In the present study, we detected significant upregulation of hepatocyte growth factor (HGF) in the serum and liver in mice with acute or chronic liver injury. In vitro study revealed that upregulation of miR-9-5p or miR-221-3p promoted the migration of human MSCs (hMSCs) toward HGF. Moreover, overexpression of miR-9-5p or miR-221-3p promoted hMSC homing to the injured liver and resulted in significantly higher engraftment upon peripheral infusion. hMSCs reduced hepatic necrosis and inflammatory infiltration but showed little effect on extracellular matrix (ECM) deposition. By contrast, hMSCs overexpressing miR-9-5p or miR-221-3p resulted in not only less centrilobular necrosis and venous congestion but also a significant reduction of ECM deposition, leading to obvious improvement of hepatocyte morphology and alleviation of fibrosis around central vein and portal triads. Further studies showed that hMSCs inhibited the activation of hepatic stellate cells (HSCs) but could not decrease the expression of TIMP-1 upon acute injury and the expression of MCP-1 and TIMP-1 upon chronic injury, while hMSCs overexpressing miR-9-5p or miR-221-3p led to further inactivation of HSCs and downregulation of all three fibrogenic and proinflammatory factors TGF-β, MCP-1, and TIMP-1 upon both acute and chronic injuries. Overexpression of miR-9-5p or miR-221-3p significantly downregulated the expression of α-SMA and Col-1α1 in activated human hepatic stellate cell line LX-2, suggesting that miR-9-5p and miR-221-3p may partially contribute to the alleviation of liver injury by preventing HSC activation and collagen expression, shedding light on improving the therapeutic efficacy of hMSCs via microRNA modification. [ABSTRACT FROM AUTHOR]

Architectural anthropology offers a way to critically analyse spaces through the social life that happens around them. It is a qualitative approach that relies on ethnography to connect larger systems and subjective dimensions, self-reflexivity, and the use of visualisations as a key analytical tool. This paper reflects on the possible contribution of architectural anthropology to housing studies. More specifically, it looks at homing processes in social housing, interrogating how non-domestic spaces perform through tenants' inhabitation practices. It tests ways to visualise ethnographic data gathered during immersive fieldwork that involved participant observation and informal interactions in a high-rise estate in Brussels. Three types of visualisations (subjective map, annotated photograph, lived-in axonometry) are presented to articulate the paper's discussion of homing, un-homing and de-homing processes at the level of a district, urban interstices, and beyond social housing. Ultimately, the paper concludes that architectural anthropology may contribute further to housing studies by exploring the relationship between home(making) and urban contexts. [ABSTRACT FROM AUTHOR]

Autoimmune liver diseases include primary biliary cholangitis, primary sclerosing cholangitis, and autoimmune hepatitis, a family of chronic immune-mediated disorders that target hepatocytes and cholangiocytes. Treatments remain nonspecific, variably effective, and noncurative, and the need for liver transplantation is disproportionate to their rarity. Development of effective therapies requires better knowledge of pathogenic mechanisms, including the roles of genetic risk, and how the environment and gut dysbiosis cause immune cell dysfunction and aberrant bile acid signaling. This review summarizes key etiologic and pathogenic concepts and themes relevant for clinical practice and how such learning can guide the development of new therapies for people living with autoimmune liver diseases. [ABSTRACT FROM AUTHOR]

Introduction: In order to successfully move from place to place, our brain often combines sensory inputs from various sources by dynamically weighting spatial cues according to their reliability and relevance for a given task. Two of the most important cues in navigation are the spatial arrangement of landmarks in the environment, and the continuous path integration of travelled distances and changes in direction. Several studies have shown that Bayesian integration of cues provides a good explanation for navigation in environments dominated by small numbers of easily identifiable landmarks. However, it remains largely unclear how cues are combined in more complex environments. Methods: To investigate how humans process and combine landmarks and path integration in complex environments, we conducted a series of triangle completion experiments in virtual reality, in which we varied the number of landmarks froman open steppe to a dense forest, thus going beyond the spatially simple environments that have been studied in the past. We analysed spatial behaviour at both the population and individual level with linear regression models and developed a computational model, based on maximum likelihood estimation (MLE), to infer the underlying combination of cues. Results: Overall homing performance was optimal in an environment containing three landmarks arranged around the goal location. With more than three landmarks, individual differences between participants in the use of cues are striking. For some, the addition of landmarks does not worsen their performance, whereas for others it seems to impair their use of landmark information. Discussion: It appears that navigation success in complex environments depends on the ability to identify the correct clearing around the goal location, suggesting that some participants may not be able to see the forest for the trees. [ABSTRACT FROM AUTHOR]

This article explores the experiences of young people navigating an evolving system of housing and homelessness services in Vancouver, Canada. Despite recent shifts toward Housing First policies and calls for prevention-oriented initiatives, many young people continue to rely on temporary emergency accommodations. Amid a surge in youth homelessness and unstable housing in Vancouver, our study examines young people's "homing" strategies across time and place and temporary and more permanent living environments. We draw from an ongoing ethnographic study that began in 2021 and has involved over 70 interviews and 100 h of fieldwork with 54 young people aged 19 to 29. Our findings emphasize that feeling at home extends beyond having a roof over one's head for an extended period of time. A focus on homing strategies—that is, the day-to-day practices, routines, and forms of sociality that generate a sense of stability and care even in un-homelike places—highlights how young people can be better supported in making themselves at home in the places where they live, potentially preventing returns to street-based homelessness. This study contributes insights to youth homelessness prevention policies, urging a strengths-based approach that aligns with young people's needs, priorities, and desires for homemaking. [ABSTRACT FROM AUTHOR]

In response to an everlasting housing crisis, cities worldwide have witnessed a surge in alternative housing initiatives (AHIs) driven by third‐sector organisations. In Brussels, a network of third‐sector organisations has been developing strategies with each other and local authorities, resulting in a plethora of initiatives focusing on various critical situations. Drawing on ethnographic research in a Brussels AHI, this article investigates how its complex multi‐actor structure affects the daily life of its inhabitants both within their dwellings and the wider neighbourhood. By capturing the tactics employed by third‐sector actors on the ground, which often deviate from their initial strategy for reclaiming the right to housing, as well as the homing practices of the inhabitants, the article focuses on tracing how and why such a housing configuration does or does not address its inhabitants’ interplaying vulnerabilities related with the housing crisis as well as their relationship with the local urban fabric.

We conducted an acoustic telemetry study of native golden perch (Macquaria ambigua) to examine movement behaviour in areas affected by methane seeps and hypoxia in the intermittent Condamine River, Murray‐Darling Basin (MDB), Australia.Fish were collected during periods of no flow and hypoxia (dissolved oxygen [DO] <1 mg/L). Despite these conditions, 38 of 43 fish tagged with acoustic transmitters were detected for >3 months post‐tagging in the study reach and 27 fish were being detected after 14 months. During periods of elevated river flow and relatively high DO, 30 fish moved away from their original tagging locations, with three undertaking movements (>7 km) outside the study reach and not returning.Generalised additive mixed models showed a significant increase in the probability of movement as soon as flow commenced and when water temperatures exceeded 19°C. As flows receded, most fish that had moved exhibited accurate homing behaviour to their original tagging location.The patterns of movement and site fidelity exhibited by golden perch correspond with previous studies of the species in intermittent rivers not affected by methane seeps and severe hypoxia, suggesting that the methane seeps and hypoxia did not inhibit fish movement nor render the affected habitats unsuitable for habitation.Golden perch can survive and remain active in water with much lower DO (<1 mg/L) than previously described for large‐bodied native fishes in the MDB. However, fish condition in the study reach was slightly lower than other regions of the MDB, providing preliminary evidence that fish residing in habitats affected by chronic hypoxia and methane seepage may experience sub‐lethal stress.Our results demonstrate the importance of field‐based data on the behavioural and physiological responses of fish to chronic hypoxia and methane exposure to guide appropriate management responses. [ABSTRACT FROM AUTHOR]

This paper studies Gooneratne's A change of Skies from diasporic perspective. Globalization, colonization and global flow of labour have led people to shift to different parts of the world. This dispersion from the homeland and re-rootedness in the diaspora space is a complex phenomenon. It involves intersection of multiple spatio-temporal and personal factors that shape and reshape the diasporic subjects. Keeping this in view, the selected novel reflects upon the diasporic journey of a young Sri-Lankan couple who shifts to Australia initially for a period of five years but later on decides to reside there permanently. Bharat and Navaranjini's experiences as immigrants in the host country and their struggle for homing of diaspora are representative of the efforts of all the immigrants who shift abroad for some reason or the other. Brah's notions of diaspora journey, the formation of the diasporas, relational positioning, the homing of diaspora and Berry's ideas related to plural societies and acculturation strategies have been used as theoretical framework for this research. The study is qualitative in nature and uses Belsey's textual analysis as a method to interpret the selected text. The paper concludes that though the immigrants are treated differently on the basis of relational positioning in the host country, making diaspora composite formation due to distinctive historical experiences and multiple modalities of race, gender, class, religion, generation and language, they negotiate these differences and finally succeed in their efforts of homing diaspora space. [ABSTRACT FROM AUTHOR]

Poison frogs of the superfamily Dendrobatoidea have fascinated researchers since the 19th century, which is reflected in multiple studies on their natural history, taxonomy, toxicity, colour pattern diversity, and elaborate territorial, reproductive and parental care behaviours. Broadly speaking, however, the term "poison frogs" may apply as well to other taxa which also possess skin toxins. Hereon, we refer to poison frogs as this extended group involving, besides Dendrobatoidea (Dendrobatidae + Aromobatidae), a few genera in families such as Bufonidae and Mantellidae (among others). Most studies on poison frogs have focused on species considered charismatic due to their bright and flashy colours, limiting possible generalisations of patterns and mechanisms explaining the high morphological, ecological, and behavioural differentiation, but also convergence, among these groups. Furthering our understanding of the evolutionary ecology of poison frogs requires increasing not only the scope and depth of our own questions, but also the number and diversity of study systems. Inspired by the special issue on dendrobatid and aromobatid poison frogs published ten years ago in this same journal, we have put together the present special issue aiming to broaden both the topics and the coverage of poison frog clades. This first part consists of 15 manuscripts covering topics ranging from larval behavioural ecology and parental care to space use and its environmental determinants, along with conservation implications. [ABSTRACT FROM AUTHOR]

Context: Translocation is a common management strategy for wildlife populations, yet hard-release of reptiles, including box turtles (Terrapene spp.), has often proven ineffective due to homing attempts and wandering. Soft-release translocation has been presented as a possible method for mitigation of the negative effects of hard-release translocation, but studies incorporating standard soft-release strategies have produced mixed results and often see persistent homing attempts by soft-released study animals. Aims: The aim of this study was to examine long-term holding (>1 year) of box turtles at an off-site location prior to translocation as a means to reduce homing attempts and wandering commonly observed in immediate-release box turtles. Methods: We radiotracked translocated Terrapene carolina triunguis to compare movements of nine immediate-release box turtles and nine box turtles that had been maintained for >1 year at a nearby off-site holding facility (long-term holding) prior to a 750–1000 m translocation. Key results: Box turtles held long-term before a short-distance translocation moved significantly shorter distances each day post-release than immediate-release turtles. Turtles held long-term moved in non-directional, random orientations, whereas immediate-release turtles exhibited consistent directionality in movements back towards their initial capture (home) locations. Conclusions: Our results demonstrated that turtles held off-site remained within the translocation site more reliably than the immediate-release turtles, which had a higher tendency to home. Implications: Long-term holding of turtles prior to translocation could significantly reduce homing responses and wandering, thus increasing translocation efficacy while reducing intensity of post-translocation management. Wildlife translocation is often necessary to mitigate negative effects of habitat loss or degradation as a result of urbanisation. This study investigated post-translocation movements of immediately released Terrapene carolina triunguis (three-toed box turtle) and box turtles held long-term (>1 year) at an off-site location prior to translocation. Turtles held long-term remained within the translocation site more reliably and had reduced homing attempts compared with immediate-release turtles. We make recommendations for mitigating homing attempts of translocated turtles. Photograph by Elizabeth D. Hays. [ABSTRACT FROM AUTHOR]

Interactions between environmental stressors may contribute to ongoing pollinator declines, but have not been extensively studied. Here, we examined the interaction between the agricultural fungicide Pristine (active ingredients: 25.2% boscalid, 12.8% pyraclostrobin) and high temperatures on critical honeybee behaviours. We have previously shown that consumption of field-realistic levels of this fungicide shortens worker lifespan in the field and impairs associative learning performance in a laboratory-based assay. We hypothesized that Pristine would also impair homing and foraging behaviours in the field, and that an interaction with hot weather would exacerbate this effect. Both field-relevant Pristine exposure and higher air temperatures reduced the probability of successful return on their own. Together, the two factors synergistically reduced the probability of return and increased the time required for bees to return to the hive. Pristine did not affect the masses of pollen or volumes of nectar or water brought back to the hive by foragers, and it did not affect the ratio of forager types in a colony. However, Pristine-fed bees brought more concentrated nectar back to the hive. As both agrochemical usage and heat waves increase, additive and synergistic negative effects may pose major threats to pollinators and sustainable agriculture. [ABSTRACT FROM AUTHOR]

Violence in the intimate sphere can send women and children out of their homes and onto journeys over vast geographical distances and into various forms of temporary accommodation. When women and children are displaced like this, they have to settle and re-settle on their complex journeys away from intimate partner violence. This article shows that not all these places will be or become home and that the absence of home can entail different forms of distress, such as fear, alienation and despondency. The concept of home is (re)emerging in social work. By employing a threefold understanding of home as a physical place, a feeling and a practice, this article offers new insights into the role of home in the recovery process of women and children subjected to violence. Home is an essential place for adults and children. Therefore, this article argues that home is an important concept for social workers working with families subjected to violence, as finding home can be a central part of the recovery process. This article is based on data from two studies on families experiencing intimate partner violence, drawing on fieldwork at a women's shelter and on semi-structured interviews with women and children. [ABSTRACT FROM AUTHOR]

Abstract Objective To investigate the mechanism of ultrasound microbubbles (UTMB) promoting stem cells homing to fibrotic liver. Methods Bone marrow derived mesenchymal stem cells (BMSCs) were divided into 5 groups with or without ultrasound microbubbles and continuously irradiated with ultrasound conditions of frequency 1 MHZ and output power 0.6 W/cm2 for different times, and then injected into a mouse model of liver fibrosis through the tail vein with or without ultrasound microbubbles, with sound intensity. The effect of ultrasound microbubbles on MSC expression of CXC chemokine receptor 4 (CXCR4) and homing fibrotic liver was evaluated by flow cytometry (FCM), western blot (WB) and immunohistochemistry (IHC) analysis. Results The level of CXCR4 expression was significantly higher in the ultrasound microbubble group than in the non-intervention group (P

Hematopoietic stem-cell (HSC) transplantation (HSCT) is used to treat various hematologic disorders. Use of genetically modified mouse models of hematopoietic cell transplantation has been critical in our fundamental understanding of HSC biology and in developing approaches for human patients. Pre-clinical studies in animal models provide insight into the journey of transplanted HSCs from infusion to engraftment in bone-marrow (BM) niches. Various signaling molecules and growth factors secreted by HSCs and the niche microenvironment play critical roles in homing and engraftment of the transplanted cells. The sustained equilibrium of these chemical and biologic factors ensures that engrafted HSCs generate healthy and durable hematopoiesis. Transplanted healthy HSCs compete with residual host cells to repopulate stem-cell niches in the marrow. Stem-cell niches, in particular, can be altered by the effects of previous treatments, aging, and the paracrine effects of leukemic cells, which create inhospitable bone-marrow niches that are unfavorable for healthy hematopoiesis. More work to understand how stem-cell niches can be restored to favor normal hematopoiesis may be key to reducing leukemic relapses following transplant.

Objective: To investigate the mechanism of ultrasound microbubbles (UTMB) promoting stem cells homing to fibrotic liver. Methods: Bone marrow derived mesenchymal stem cells (BMSCs) were divided into 5 groups with or without ultrasound microbubbles and continuously irradiated with ultrasound conditions of frequency 1 MHZ and output power 0.6 W/cm2 for different times, and then injected into a mouse model of liver fibrosis through the tail vein with or without ultrasound microbubbles, with sound intensity. The effect of ultrasound microbubbles on MSC expression of CXC chemokine receptor 4 (CXCR4) and homing fibrotic liver was evaluated by flow cytometry (FCM), western blot (WB) and immunohistochemistry (IHC) analysis. Results: The level of CXCR4 expression was significantly higher in the ultrasound microbubble group than in the non-intervention group (P < 0.05), and the number of MSC and the rate of CXCR4 receptor positivity in the ultrasound microbubble-treated liver tissues were significantly higher than in the non-intervention group (P < 0.01). Conclusion: Ultrasonic microbubbles can promote the expression of CXCR4 on the surface of MSCs, thus improving the homing rate of MSCs in fibrotic liver. [ABSTRACT FROM AUTHOR]

This study investigates how China’s COVID-19 prevention policy during the pandemic affected the physical and mental well-being of Chinese students overseas returning home, and how their perceptions of ‘home’ were both challenged and reinforced through their interactions with China’s virus prevention and control measures. We first review the literature on the vulnerability of transnational students during the pandemic, with a focus on transnational Chinese students. Then we explore the concept of ‘homing’ within the context of China’s cultural definition of ‘roots’ (gen, 根). Drawing from participant narratives, we identified three interwoven themes highlighting challenges faced during their journey home – reconnecting with cultural roots, negotiating with critical institutions, and struggling with in-between identities, and analysed their relationships with their health identity and the concept of home. Our findings offer practical insights for improving the well-being of these transnational migrants during times of crisis. [ABSTRACT FROM AUTHOR]

Species translocation is a common tool to reverse biodiversity loss, but it has a high failure rate. One factor that contributes to failure is postrelease hyperdispersal, which we define as the long‐distance movement of individuals resulting in their failure to contribute to population establishment. We reviewed reported incidences of hyperdispersal and compared rates of hyperdispersal among taxa, population demographics, release cohorts, and success of mitigation techniques. Of 151 conservation translocations (reinforcements and reintroductions) in which animals were tracked, hyperdispersal was confirmed in 52.1% of programs. The prevalence of hyperdispersal (percentage of studies) was relatively consistent across taxa (42.9–60%), but hyperdispersal rates in birds were likely underestimated because 76.9% of bird translocations showed incidences in which birds could not be located after release, but hyperdispersal was unable to be confirmed. Eutherians exhibited a higher average incidence of hyperdispersal (percentage of hyperdispersing individuals in a cohort) of 20.2% than birds, reptiles, and marsupials (10.4%, 15.7%, and 10.3%, respectively). No significant trends were observed for sex, source population, or translocation type, but there were nonsignificant trends for males to hyperdisperse more than females and for higher incidences of hyperdispersal in reinforcements relative to reintroduction programs. Mitigation techniques included temporary confinement, supplementation of resources, and releasing animals in social groups, but only half of studies examining mitigation techniques found them useful. Hyperdispersal incidence was variable within taxa, and we advise against forming translocations strategies based on results from other species. Hyperdispersal is a significant welfare, economic, and conservation issue in translocations, and we suggest definitions, reporting, and experimental strategies to address it. [ABSTRACT FROM AUTHOR]

Hematopoietic stem-cell (HSC) transplantation (HSCT) is used to treat various hematologic disorders. Use of genetically modified mouse models of hematopoietic cell transplantation has been critical in our fundamental understanding of HSC biology and in developing approaches for human patients. Pre-clinical studies in animal models provide insight into the journey of transplanted HSCs from infusion to engraftment in bone-marrow (BM) niches. Various signaling molecules and growth factors secreted by HSCs and the niche microenvironment play critical roles in homing and engraftment of the transplanted cells. The sustained equilibrium of these chemical and biologic factors ensures that engrafted HSCs generate healthy and durable hematopoiesis. Transplanted healthy HSCs compete with residual host cells to repopulate stem-cell niches in the marrow. Stem-cell niches, in particular, can be altered by the effects of previous treatments, aging, and the paracrine effects of leukemic cells, which create inhospitable bone-marrow niches that are unfavorable for healthy hematopoiesis. More work to understand how stem-cell niches can be restored to favor normal hematopoiesis may be key to reducing leukemic relapses following transplant. [ABSTRACT FROM AUTHOR]

Purpose: About 25% of patients with common variable immunodeficiency disease (CVID) have splenomegaly, necessitating sometimes splenectomy whom consequences on the immunological profile of CVID patients have never been studied. We analyzed 11 CVID patients' comprehensive blood immune cell phenotypes pre- and post-splenectomy. Methods: Flow cytometry analyses of immune cell populations. Results: Among 89 CVID cohort patients, 41 with splenomegaly, splenomegaly was strongly associated with granulomatous disease, autoimmune disorders, lymphoid hyperplasia, and/or portal hypertension. CVID patients with splenomegaly have significant peripheral lymphopenia (p = 0.001), and significantly fewer peripheral class-switched memory B cells (smBs) (p = 0.001), CD4+ T lymphocytes (p = 0.001), NK (p = 0.0001) and dendritic cells (p ≤ 0.01), and significantly more circulating CD4+ and CD8+ (p = 0.00001) T cell subset activation (p = 0.00005), than CVID patients without splenomegaly. Examination of splenectomy impact on circulating lymphocyte subset distributions demonstrated the drastically enhanced total circulating lymphocyte count post-splenectomy, predominantly B lymphocytes and CD8+ T cells. However, splenectomy did not change B cell distribution, with smBs remaining persistently low, in contrast to complete inversion of the circulating T cell composition, with reversal of the CD4+/CD8+ ratio suggesting that amplification of the CD8+ T cell compartment is a CVID characteristic in patients with splenomegaly. Our results highlight this CD8+ amplification in CVID–splenomegaly patients that might be explained by a homing effect to the spleen and/or possible chronic virus replication, which in turn could induce T cell expansions. Conclusion: Splenectomizing CVID patients with splenomegaly restores the absolute circulating lymphocyte count, suggesting that the decreased T cell count in the presence of splenomegaly cannot be used as an exclusive criterion for combined immunodeficiency. [ABSTRACT FROM AUTHOR]

Stem cells have self-renewal, replication, and multidirectional differentiation potential, while progenitor cells are undifferentiated, pluripotent or specialized stem cells. Stem/progenitor cells secrete various factors, such as cytokines, exosomes, non-coding RNAs, and proteins, and have a wide range of applications in regenerative medicine. However, therapies based on stem cells and their secreted exosomes present limitations, such as insufficient source materials, mature differentiation, and low transplantation success rates, and methods addressing these problems are urgently required. Ultrasound is gaining increasing attention as an emerging technology. Low-intensity pulsed ultrasound (LIPUS) has mechanical, thermal, and cavitation effects and produces vibrational stimuli that can lead to a series of biochemical changes in organs, tissues, and cells, such as the release of extracellular bodies, cytokines, and other signals. These changes can alter the cellular microenvironment and affect biological behaviors, such as cell differentiation and proliferation. Here, we discuss the effects of LIPUS on the biological functions of stem/progenitor cells, exosomes, and non-coding RNAs, alterations involved in related pathways, various emerging applications, and future perspectives. We review the roles and mechanisms of LIPUS in stem/progenitor cells and exosomes with the aim of providing a deeper understanding of LIPUS and promoting research and development in this field. [ABSTRACT FROM AUTHOR]

During an escape from predators, many animals need to evaluate and choose a refuge within seconds. We investigated refuge choice in the amphibious blackspotted rockskipper, Entomacrodus striatus, in Moorea, French Polynesia. Rockskippers are small combtooth blennies that inhabit rocky beaches and jetties at the aquatic/terrestrial interface. They are conspicuous for their eponymous jumping to/from refugia among rocks when threatened. We have observed refugia with both multiple conspecifics and solitary fish in the field, and here tested whether fish choose refugia that are occupied by conspecifics in the laboratory. E. striatus chose unoccupied refugia on the opposite side of the experimental tank in 11/14 trials, a significantly greater number of times than they chose occupied refugia. In 3/14 trials, fish chose occupied refugia, indicating that refuge occupation does not prohibit their use by conspecifics. We hypothesize that chemical stress signals from the occupying fish deter most fish from choosing the same refuge. [ABSTRACT FROM AUTHOR]

Animal movement and feeding studies shed light on ecological roles and can inform management strategies for fished species. However, the feeding and movement of nocturnal sea cucumbers have been rarely studied. We determined the movement dynamics, feeding ecology and sheltering behaviour of the nocturnal Stichopus cf. monotuberculatus (dragonfish) at One Tree Reef and Heron Island Reef on the southern Great Barrier Reef. The short-term movement of individual sea cucumbers were tracked, and sediment defecation rates were measured. Displacement rates averaged 3–33 cm h−1 across the four sites, with the sea cucumbers moving more slowly approaching sunrise and within patches of organically rich sediment. The movement paths were moderately tortuous, with larger sea cucumbers moving along straighter paths. Rates of sediment turnover averaged 7.8 g h−1 and were greatest for larger individuals. The faecal casts were organically richer and composed of finer grains than the ambient surface sediments, implying that S. cf. monotuberculatus avoids consuming coarse sediments and feeds on nutritionally rich particles. The sea cucumbers sheltered under hard reef substrata and moved non-directionally on the seascape, with a few individuals homing back to their original refuges. The affinity to reef substrata and short nightly net displacements of S. cf. monotuberculatus have implications for the spatial management of this and other similar species. Larger individuals occupied deeper refuges, implying that projected declines in substratum rugosity on coral reefs due to climate change could impact the size structure of sea cucumber populations, with implications for fisheries. [ABSTRACT FROM AUTHOR]

IntroductionIn order to successfully move from place to place, our brain often combines sensory inputs from various sources by dynamically weighting spatial cues according to their reliability and relevance for a given task. Two of the most important cues in navigation are the spatial arrangement of landmarks in the environment, and the continuous path integration of travelled distances and changes in direction. Several studies have shown that Bayesian integration of cues provides a good explanation for navigation in environments dominated by small numbers of easily identifiable landmarks. However, it remains largely unclear how cues are combined in more complex environments.MethodsTo investigate how humans process and combine landmarks and path integration in complex environments, we conducted a series of triangle completion experiments in virtual reality, in which we varied the number of landmarks from an open steppe to a dense forest, thus going beyond the spatially simple environments that have been studied in the past. We analysed spatial behaviour at both the population and individual level with linear regression models and developed a computational model, based on maximum likelihood estimation (MLE), to infer the underlying combination of cues.ResultsOverall homing performance was optimal in an environment containing three landmarks arranged around the goal location. With more than three landmarks, individual differences between participants in the use of cues are striking. For some, the addition of landmarks does not worsen their performance, whereas for others it seems to impair their use of landmark information.DiscussionIt appears that navigation success in complex environments depends on the ability to identify the correct clearing around the goal location, suggesting that some participants may not be able to see the forest for the trees.

CD44 is a ubiquitous leukocyte adhesion molecule involved in cell-cell interaction, cell adhesion, migration, homing and differentiation. CD44 can mediate the interaction between leukemic stem cells and the surrounding extracellular matrix, thereby inducing a cascade of signaling pathways to regulate their various behaviors. In this review, we focus on the impact of CD44s/CD44v as biomarkers in leukemia development and discuss the current research and prospects for CD44-related interventions in clinical application.

Suppressive function of regulatory T cells (Treg) is dependent on signaling of their antigen receptors triggered by cognate self, dietary, or microbial peptides presented on MHC II. However, it remains largely unknown whether distinct or shared repertoires of Treg TCRs are mobilized in response to different challenges in the same tissue or the same challenge in different tissues. Here we use a fixed TCRβ chain FoxP3-GFP mouse model to analyze conventional (eCD4) and regulatory (eTreg) effector TCRα repertoires in response to six distinct antigenic challenges to the lung and skin. This model shows highly ‘digital’ repertoire behavior with easy-to-track challenge-specific TCRα CDR3 clusters. For both eCD4 and eTreg subsets, we observe challenge-specific clonal expansions yielding homologous TCRα clusters within and across animals and exposure sites, which are also reflected in the draining lymph nodes but not systemically. Some CDR3 clusters are shared across cancer challenges, suggesting a response to common tumor-associated antigens. For most challenges, eCD4 and eTreg clonal response does not overlap. Such overlap is exclusively observed at the sites of certain tumor challenges, and not systematically, suggesting transient and local tumor-induced eCD4=>eTreg plasticity. This transition includes a dominant tumor-responding eCD4 CDR3 motif, as well as characteristic iNKT TCRα CDR3. In addition, we examine the homeostatic tissue residency of clonal eTreg populations by excluding the site of challenge from our analysis. We demonstrate that distinct CDR3 motifs are characteristic of eTreg cells residing in particular lymphatic tissues, regardless of the challenge. This observation reveals the tissue-resident, antigen-specific clonal Treg populations.

Spermatogonial stem cells (SSCs) possess a unique ability to recolonize the seminiferous tubules. Upon microinjection into the adluminal compartment of the seminiferous tubules, SSCs transmigrate through the blood-testis barrier (BTB) to the basal compartment of the tubule and reinitiate spermatogenesis. It was recently discovered that inhibiting retinoic acid signaling with WIN18,446 enhances SSC colonization by transiently suppressing spermatogonia differentiation, thereby promoting fertility restoration. In this study, we report that WIN18,446 increases SSC colonization by disrupting the BTB. WIN18,446 altered the expression patterns of tight junction proteins (TJPs) and disrupted the BTB in busulfan-treated mice. WIN18,446 upregulated the expression of FGF2, one of the self-renewal factors for SSCs. While WIN18,446 enhanced SSC colonization in busulfan-treated wild-type mice, it did not increase colonization levels in busulfan-treated Cldn11-deficient mice, which lack the BTB, indicating that the enhancement of SSC colonization in wild-type testes depended on the loss of the BTB. Serial transplantation analysis revealed impaired self-renewal caused by WIN18,446, indicating that WIN18,446-mediated inhibition of retinoic acid signaling impaired SSC self-renewal. Strikingly, WIN18,446 administration resulted in the death of 45% of busulfan-treated recipient mice. These findings suggest that TJP modulation is the primary mechanism behind enhanced SSC homing by WIN18,446 and raise concerns regarding the use of WIN18,446 for human SSC transplantation.

Abstract Background As current therapies for canine osteoarthritis (OA) provide mainly symptomatic improvement and fail to address the complex pathology of the disease, mesenchymal stem cells (MSCs) offer a promising biological approach to address both aspects of OA through their immunomodulatory properties. Methods This study aimed to investigate the safety and efficacy of xenogeneic MSCs in dogs with OA at different dose levels after intravenous injection. OA was surgically induced in the right stifle joint. Thirty-two male and female dogs were divided into three treatment groups and a control group. Regular general physical examinations; lameness, joint, radiographic, and animal caretaker assessments; pressure plate analyses; and blood analyses were performed over 42 days. At study end, joint tissues were evaluated regarding gross pathology, histopathology, and immunohistochemistry. In a follow-up study, the biodistribution of intravenously injected 99mTc-labeled equine peripheral blood-derived MSCs was evaluated over 24h in three dogs after the cruciate ligament section. Results The dose determination study showed the systemic administration of ePB-MSCs in a canine OA model resulted in an analgesic, anti-inflammatory, and joint tissue protective effect associated with improved clinical signs and improved cartilage structure, as well as a good safety profile. Furthermore, a clear dose effect was found with 0.3 × 106 ePB-MSCs as the most effective dose. In addition, this treatment was demonstrated to home specifically towards the injury zone in a biodistribution study. Conclusion This model-based study is the first to confirm the efficacy and safety of systemically administered xenogeneic MSCs in dogs with OA. The systemic administration of a low dose of xenogeneic MSCs could offer a widely accessible, safe, and efficacious treatment to address the complex pathology of canine OA and potentially slow down the disease progression by its joint tissue protective effect.

Background Acute lymphoblastic leukaemia (ALL) is a common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL treatments but their effects on ALL malignancy remain unknown. Herein, we aim to study the effect of propofol and sevoflurane on the migration, homing and chemoresistance of ALL cells. Methods NALM-6 and Reh cells were treated with propofol (5 and 10 μg/ml) or sevoflurane (3.6%) in vitro for six hours. Then, cells were harvested for adhesion assay and migration assay in vitro. In in vivo experiments, GFP-NALM-6 cells were pre-treated with propofol (10 μg/ml) or sevoflurane (3.6%) for six hours. Then, cells were injected intravenously to C57BL/6 female mice followed by intravital microscopy. For chemoresistance study, cells were treated with rising concentrations of Ara-c (0.05-50 nM) plus 10μg/ml of propofol or Ara-C plus 3.6% of sevoflurane for 4 hours, followed by the assessment of cell viability via CCK-8 assay and detection of autophagy via flow cytometry. Results Both anaesthetics reduced in vivo migration and in vivo homing as exemplified by 1) the reduction in the number of cells entering the bone marrow and 2) the disturbance in homing location in relation to endosteal surface. Our results indicated that general anaesthetics reduced the surface CXCR4 expression and the adhesion of leukaemia cells to thrombin cleaved osteopontin (OPN) was reduced. Those changes might result in the alterations in migration and homing. In addition, both anaesthetics sensitised ALL cells to Ara-c possibly through CXCR4 mediated mechanisms. Propofol but not sevoflurane enhanced chemo-related cell death via inducing cytotoxic autophagy. Conclusion Together, our data suggest that both propofol and sevoflurane could reduce ALL migration, and homing in vivo and in vitro via CXCR4 and OPN mediated mechanisms. Both anaesthetics could sensitise ALL cells to chemotherapy possibly via CXCR4 mediated mechanisms.

Mesenchymal stem cells (MSCs) have shown great potential for the treatment of liver injuries, and the therapeutic efficacy greatly depends on their homing to the site of injury. In the present study, we detected significant upregulation of hepatocyte growth factor (HGF) in the serum and liver in mice with acute or chronic liver injury. In vitro study revealed that upregulation of miR-9-5p or miR-221-3p promoted the migration of human MSCs (hMSCs) toward HGF. Moreover, overexpression of miR-9-5p or miR-221-3p promoted hMSC homing to the injured liver and resulted in significantly higher engraftment upon peripheral infusion. hMSCs reduced hepatic necrosis and inflammatory infiltration but showed little effect on extracellular matrix (ECM) deposition. By contrast, hMSCs overexpressing miR-9-5p or miR-221-3p resulted in not only less centrilobular necrosis and venous congestion but also a significant reduction of ECM deposition, leading to obvious improvement of hepatocyte morphology and alleviation of fibrosis around central vein and portal triads. Further studies showed that hMSCs inhibited the activation of hepatic stellate cells (HSCs) but could not decrease the expression of TIMP-1 upon acute injury and the expression of MCP-1 and TIMP-1 upon chronic injury, while hMSCs overexpressing miR-9-5p or miR-221-3p led to further inactivation of HSCs and downregulation of all three fibrogenic and proinflammatory factors TGF-β, MCP-1, and TIMP-1 upon both acute and chronic injuries. Overexpression of miR-9-5p or miR-221-3p significantly downregulated the expression of α-SMA and Col-1α1 in activated human hepatic stellate cell line LX-2, suggesting that miR-9-5p and miR-221-3p may partially contribute to the alleviation of liver injury by preventing HSC activation and collagen expression, shedding light on improving the therapeutic efficacy of hMSCs via microRNA modification.

Background Acute lymphoblastic leukaemia (ALL) is a common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL treatments but their effects on ALL malignancy remain unknown. Herein, we aim to study the effect of propofol and sevoflurane on the migration, homing and chemoresistance of ALL cells. Methods NALM-6 and Reh cells were treated with propofol (5 and 10 μg/ml) or sevoflurane (3.6%) in vitro for six hours. Then, cells were harvested for adhesion assay and migration assay in vitro. In in vivo experiments, GFP-NALM-6 cells were pre-treated with propofol (10 μg/ml) or sevoflurane (3.6%) for six hours. Then, cells were injected intravenously to C57BL/6 female mice followed by intravital microscopy. For chemoresistance study, cells were treated with rising concentrations of Ara-c (0.05-50 nM) plus 10μg/ml of propofol or Ara-C plus 3.6% of sevoflurane for 4 hours, followed by the assessment of cell viability via CCK-8 assay and detection of autophagy via flow cytometry. Results Both anaesthetics reduced in vivo migration and in vivo homing as exemplified by 1) the reduction in the number of cells entering the bone marrow and 2) the disturbance in homing location in relation to endosteal surface. Our results indicated that general anaesthetics reduced the surface CXCR4 expression and the adhesion of leukaemia cells to thrombin cleaved osteopontin (OPN) was reduced. Those changes might result in the alterations in migration and homing. In addition, both anaesthetics sensitised ALL cells to Ara-c possibly through CXCR4 mediated mechanisms. Propofol but not sevoflurane enhanced chemo-related cell death via inducing cytotoxic autophagy. Conclusion Together, our data suggest that both propofol and sevoflurane could reduce ALL migration, and homing in vivo and in vitro via CXCR4 and OPN mediated mechanisms. Both anaesthetics could sensitise ALL cells to chemotherapy possibly via CXCR4 mediated mechanisms.

Ras-related C3 botulinum toxin substrate 1 (Rac1) is a GTPase implicated in cell migration and homing of hematopoietic cells to the hematopoietic niche, and is commonly overexpressed in acute myeloid leukemia (AML). This can lead to quiescence of leukemic blasts in the niche and reduced response to therapy. We investigated the Rac1 inhibitor EHop-016 on AML by assessing its effects on MOLM-13 cells in vitro and in zebrafish larvae, regarding cell motility and therapeutic potential in combination with daunorubicin (DNR). In vitro assessment of proliferation and viability was by measurement of 3H-thymidine incorporation and detection of Annexin V/PI positive cells. Cell motility was evaluated by measurement of migration in a transwell system. Fluorescently stained MOLM-13 cells were injected into zebrafish larvae, and individual cells followed by confocal microscopy. Cell accumulation in the caudal hematopoietic tissue (CHT) was studied using a 12-hour timelapse, while in vivo efficacy of DNR, EHop-016 or a combination was investigated over 24 h.The in vitro results showed that EHop-016 acted synergistically in combination with DNR in reducing the viability of MOLM-13 cells (Bliss synergy score above 10 %). Non-toxic concentrations of EHop-016 reduced cell migration. These findings were reproduced in zebrafish larvae: larvae receiving both DNR and EHop-016 had significantly reduced tumor burden compared to the untreated control or single treatments. The accumulation of MOLM-13 cells in the CHT was reduced in larvae receiving EHop-016 treatment.Our findings demonstrate that targeting Rac1 in AML holds promise as a complementary treatment to established chemotherapy and should be further investigated.

This paper describes the main updates characterizing the new version of IONORT (IONOsperic Ray Tracing), a software tool developed at Istituto Nazionale di Geofisica e Vulcanologia to determine both the path of a high frequency (HF) radio wave propagating in the ionospheric medium, and the group time delay of the wave itself along the path. One of the main changes concerns the replacement of a regional three-dimensional electron density matrix, which was previously taken as input to represent the ionosphere, with a global one. Therefore, it is now possible to carry out different ray tracings from whatever point of the Earth's surface, simply by selecting suitable loop cycles thanks to the new ray tracing graphical user interface (GUI). At the same time, thanks to a homing GUI, it is also possible to generate synthetic oblique ionograms for whatever radio link chosen by the user. Both ray tracing and homing GUIs will be described in detail providing at the same time some practical examples of their use for different regions. IONORT software finds practical application in the planning of HF radio links, exploiting the sky wave, through an accurate and thorough knowledge of the ionospheric medium. HF radio waves users, including broadcasting and civil aviation, would benefit from the use of the IONORT software (version 2023.10). [ABSTRACT FROM AUTHOR]

Objective: Individual habitat preference can reduce intraspecific competition for resources and may differ between age groups, sexes, and adult phenotypes. The Channel Catfish Ictalurus punctatus is a widespread species occurring in diverse freshwater habitats. This species displays breeding philopatry, returning to nesting sites occupied in previous years. Larger Channel Catfish tend to nest in the main channels of large rivers, whereas smaller fish tend to prefer smaller tributaries. The purpose of our study was to determine whether this habitat segregation potentially associated with habitat preference affects the genetic structure of a population. We hypothesized that spatial segregation of breeding sites in the Ottawa River and its smaller tributaries at Lac des Chats reduced gene flow within the population, resulting in genetically differentiated demes associated with lacustrine‐like and fluvial habitats. Methods: Microsatellite allelic data was collected from 162 Channel Catfish. Result: We found little genetic variation between the Ottawa, Mississippi, and Madawaska rivers. Furthermore, our analyses suggested that the sampled specimens comprised one panmictic population. Fish from one site in the Ottawa River, however, were significantly differentiated from fish from a nearby site also in the Ottawa River as well as from fish from the Mississippi River tributary. Conclusion: Given that fish from sites further up the Ottawa River were not differentiated from fish from these sites, it is unlikely that geography can account for the differences observed; rather, assortative mating may explain the differentiation. We propose that panmixia within the population is caused by ontogenetic changes in habitat selection, straying individuals, or sex‐biased dispersal and philopatry. Impact statementHabitat segregation of breeding Channel Catfish populations does not translate into genetic isolation of lacustrine‐like and fluvial subpopulations, improving our understanding of gene flow. Ottawa River catfish are as genetically diverse as wild American populations and more diverse than domestic stocks. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have a high tropism for the hypoxic microenvironment of tumors. The combination of nanoparticles in MSCs decreases tumor growth in vitro as well as in rodent models of cancers in vivo. Covalent conjugation of nanoparticles with the surface of MSCs can significantly increase the drug load delivery in tumor sites. Nanoparticle-based anti-angiogenic systems (gold, silica and silicates, diamond, silver, and copper) prevented tumor growth in vitro. For example, glycolic acid polyconjugates enhance nanoparticle drug delivery and have been reported in human MSCs. Labeling with fluorescent particles (coumarin-6 dye) identified tumor cells using fluorescence emission in tissues; the conjugation of different types of nanoparticles in MSCs ensured success and feasibility by tracking the migration and its intratumor detection using non-invasive imaging techniques. However, the biosafety and efficacy; long-term stability of nanoparticles, and the capacity for drug release must be improved for clinical implementation. In fact, MSCs are vehicles for drug delivery with nanoparticles and also show low toxicity but inefficient accumulation in tumor sites by clearance of reticuloendothelial organs. To solve these problems, the internalization or conjugation of drug-loaded nanoparticles should be improved in MSCs. Finally, CXCR4 may prove to be a promising target for immunotherapy and cancer treatment since the delivery of siRNA to knock down this alpha chemokine receptor or CXCR4 antagonism has been shown to disrupt tumor–stromal interactions. [ABSTRACT FROM AUTHOR]

BACKGROUND: There are still many problems to be solved or perfected in the treatment of ischemic heart disease by stem cell transplantation. Among them, the key of stem cell transplantation in the treatment of ischemic heart disease is that the transplanted cells can home to the damaged myocardium and survive there. OBJECTIVE: To evaluate the effect of tanshinone IIA on the survival and homing ability of myocardial precursor cells under hypoxia and investigate its related mechanism. METHODS: H9c2 cells were selected as the myocardial precursor cell model. The H9c2 cells were respectively intervened with cobalt chloride, tanshinone IIA+cobalt chloride and tanshinone IIA+cobalt chloride+AG126(ERK1/2 pathway inhibitor). Cell proliferation was detected with MTS method. Cell apoptosis was analyzed using flow cytometry. Cell migration was evaluated by scratch assay. The expression levels of ERK1/2 pathway related proteins (ERK1/2, p-ERK1/2, HIF- 1α, cleaved caspase-3, and MMP-9) were assessed using western blot assay. RESULTS AND CONCLUSION: (1) Compared with the cobalt chloride group, the proliferation of H9c2 cells treated with cobalt chloride combined with tanshinone IIA was accelerated; the apoptosis was reduced; and the homing ability was enhanced. During this process, the expression of ERK1/2 had no significant changes (P > 0.05), but the expression levels of p-ERK1/2, HIF-1α, and MMP-9 were significantly increased (P < 0.05), and the expression of cleaved caspase-3 was significantly decreased (P < 0.05). (2) Compared with the cobalt chloride + tanshinone IIA group, the ERK1/2 pathway in H9c2 cells treated with cobalt chloride + tanshinone IIA + AG126 was significantly inhibited, and the ability of cell survival and migration to the injured area was significantly decreased. (3) The results showed that tanshinone IIA could promote the survival and homing ability of myocardial precursor cells under hypoxia by regulating ERK1/2 pathway. [ABSTRACT FROM AUTHOR]

Objective: One of the biggest concerns of operating hatchery salmonid programs is high straying of returning adults into nontarget populations and the possible homogenization of genetic diversity among populations caused by spawning of stray fish. The composition of hatchery‐origin stray Chinook Salmon Oncorhynchus tshawytscha and steelhead O. mykiss relative to the natural spawning populations, termed "recipient population stray composition," was evaluated at three spatial scales in the upper Columbia River basin, where stray target limits were 5–10%. Methods: Chinook Salmon carcasses were collected from 1999 to 2018 in spawning areas shortly after spawning, and carcasses were examined to determine origin. Steelhead strays and spawning escapement were evaluated using passive integrated transponder tags between 2013 and 2018. We calculated mean stray compositions for 1999–2018 and for 2014–2018. Result: The mean recipient population stray compositions ranged between 0.02% and 87.35% and increased with decreasing spatial scale. Recipient stray compositions of all taxa at the basin scale were <3%, and summer and fall Chinook Salmon were <0.5%. Stray compositions in subbasins for all taxa ranged between 0.07% and 33.04%. Spring and summer Chinook Salmon exceeded 5% and 10% (summer Chinook Salmon) in some periods in the Entiat and Methow River subbasins, but stray compositions for all Chinook Salmon were <5% in the Wenatchee, Okanogan, and Hanford Reach subbasins for all periods. All steelhead stray compositions in subbasins exceeded 5%, except for those in the Wenatchee subbasin. Stray compositions of spring Chinook Salmon in tributaries ranged between 0.61% and 87.35%. Only the Chiwawa, Icicle, and Twisp rivers were consistently below 10%. Conclusion: In cases where recipient stray management targets were exceeded, some were the result of single hatchery contributions but others were the result of cumulative contributions from multiple hatcheries. Some solutions to reduce recipient stray compositions will likely involve a combination of changes to hatchery, harvest, and habitat management. Impact statementHatchery‐origin Chinook Salmon and steelhead stray compositions on the spawning grounds met management targets at the basin scale but in some cases exceeded management targets at finer spatial scales, often as a result of multiple hatchery programs contributing strays. [ABSTRACT FROM AUTHOR]

As animals execute essential behaviors like foraging, they must orient with respect to the space around them, requiring some neural/behavioral mechanism for spatial navigation. One such navigation mechanism is path integration, whereby animals recall their starting point by creating a memory-stored home vector. In some animals, this is stored in an egocentric frame of reference; however, it remains unclear what comprises this in animals' spatial memory. The fiddler crab Uca pugilator makes an excellent model to investigate the nature of the egocentric frame of reference because they appear to path integrate using self-motion cues to form an egocentric vector. We hypothesized that the home vector direction is governed by the optokinetic system, since the eye–body angle explicitly reflects the deviation of the body axis from home direction as optokinetic eye movements stabilize the eyes against body rotation. To test this hypothesis, we monitored eye and body movements during foraging excursions of crabs showing varying degrees of visual stabilization. We found that crabs with good eye stability had more accurate home vectors than those with poor eye stability, and the quantitative degree of stability accurately predicted the crabs' perception of home direction. These results suggest that eye movement reflexes may establish the homing direction in path integrating fiddler crabs. [ABSTRACT FROM AUTHOR]

Homing-based gene drives, engineered using CRISPR/Cas9, have been proposed to spread desirable genes throughout populations. However, invasion of such drives can be hindered by the accumulation of resistant alleles. To limit this obstacle, we engineer a confinable population modification home-and-rescue (HomeR) drive in Drosophila targeting an essential gene. In our experiments, resistant alleles that disrupt the target gene function were recessive lethal and therefore disadvantaged. We demonstrate that HomeR can achieve an increase in frequency in population cage experiments, but that fitness costs due to the Cas9 insertion limit drive efficacy. Finally, we conduct mathematical modeling comparing HomeR to contemporary gene drive architectures for population modification over wide ranges of fitness costs, transmission rates, and release regimens. HomeR could potentially be adapted to other species, as a means for safe, confinable, modification of wild populations.