Extensive Migration Research Articles

Angiotropism, pericytic mimicry and extravascular migratory metastasis: an embryogenesis-derived program of tumor spread.

Intravascular dissemination of tumor cells is the accepted mechanism of cancer metastasis. However, the phenomenon of angiotropism, pericyte mimicry (PM), and extravascular migratory metastasis (EVMM) has questioned the concept that tumor cells metastasize exclusively via circulation within vascular channels. This new paradigm of cancer spread and metastasis suggests that metastatic cells employ embryonic mechanisms for attachment to the abluminal surfaces of blood vessels (angiotropism) and spread via continuous migration, competing with and replacing pericytes, i.e., pericyte mimicry (PM). This is an entirely extravascular phenomenon (i.e., extravascular migratory metastasis or EVMM) without entry (intravasation) into vascular channels. PM and EVMM have mainly been studied in melanoma but also occur in other cancer types. PM and EVMM appear to be a reversion to an embryogenesis-derived program. There are many analogies between embryogenesis and cancer progression, including the important role of laminins, epithelial-mesenchymal transition, and the re-activation of embryonic signals by cancer cells. Furthermore, there is no circulation of blood during the first trimester of embryogenesis, despite the fact that there is extensive migration of cells to distant sites and formation of organs and tissues during this period. Embryonic migration therefore is a continuous extravascular migration as are PM and EVMM, supporting the concept that these embryonic migratory events appear to recur abnormally during the metastatic process. Finally, the perivascular location of tumor cells intrinsically links PM to vascular co-option. Taken together, these two new paradigms may greatly influence the development of new effective therapeutics for metastasis. In particular, targeting embryonic factors linked to migration that are detected during cancer metastasis may be particularly relevant to PM/EVMM.

Daily growth of young-of-the-year largehead hairtail (Trichiurus japonicus) in relation to environmental variables in the East China Sea

Abstract Largehead hairtail (Trichiurus japonicus) is an important fish species in China Sea, characterized by wide distribution, extensive migration, long spawning period and high economic value. The East China Sea is one of the typical over-exploited ecosystems in the world where most of the fish populations are overfished. In spite of high fishing pressure over an extended period, the catch of largehead hairtail showed an increasing trend in recent years. In this study, using otolith microstructure analysis for daily ageing, we explored spawning seasonality of largehead hairtail and daily growth of young-of-the-year (YoY) largehead hairtail in the East China Sea. Spawning seasonality of largehead hairtail was found to be nearly year round with two dominant seasons: autumn and spring. The gradient forest method was used to identify the relative importance of various environmental variables in relation to daily growth of YoY largehead hairtail; the first six most important environmental variables were subsequently analyzed using generalized additive models for their specific associations with daily growth of YoY largehead hairtail. Results show that sea surface temperature (SST), sea bottom temperature (SBT), temperature difference (TD) between surface and bottom water, and mixed layer depth (MLD) are the most important variables for daily growth of almost all month cohorts. In addition, the consistent interactive effects of water temperature (SST and SBT) and MLD suggest that daily growth of YoY largehead hairtail is influenced by the interactive effects of water temperature and nutrient supplies. This study highlights the importance of understanding the reproductive process and early growth of largehead hairtail in relation to environmental variables, which has important implications for the sustainable management and utilization of largehead hairtail in the over-exploited China Seas.

Network architecture and regulatory logic in neural crest development.

The neural crest is an ectodermal cell population that gives rise to over 30 cell types during vertebrate embryogenesis. These stem cells are formed at the border of the developing central nervous system and undergo extensive migration before differentiating into components of multiple tissues and organs. Neural crest formation and differentiation is a multistep process, as these cells transition through sequential regulatory states before adopting their adult phenotype. Such changes are governed by a complex gene regulatory network (GRN) that integrates environmental and cell-intrinsic inputs to regulate cell identity. Studies of neural crest cells in a variety of vertebrate models have elucidated the function and regulation of dozens of the molecular players that are part of this network. The neural crest GRN has served as a platform to explore the molecular control of multipotency, cell differentiation, and the evolution of vertebrates. In this review, we employ this genetic program as a stepping-stone to explore the architecture and the regulatory principles of developmental GRNs. We also discuss how modern genomic approaches can further expand our understanding of genetic networks in this system and others. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Biological Mechanisms > Cell Fates Developmental Biology > Lineages Models of Systems Properties and Processes > Cellular Models.

Adélie penguins’ extensive seasonal migration supports dynamic Marine Protected Area planning in Antarctica

Spatiotemporal dynamics of ecosystems can challenge the pertinence of Marine Protected Area (MPA) planning. Seasonal environmental changes are extreme in polar regions, however MPA planning in East Antarctica relies mostly on species' summer distribution only. Thirteen Adélie penguins were tracked from Ile des Pétrels (Terre Adélie), and their seasonal distribution and behaviour were compared to the proposed “D'Urville Sea-Mertz” MPA. During the phase of high food-demand preceding moult, penguins used mostly (68.4%) this proposed area. However, following autumnal sea ice extension, penguins migrated north-westwards: overall, 73% of their locations were outside the MPA proposal, and this was up to >99% during winter (in July), the season when penguins maximized their dive depth and time (August and September, respectively). This study thus supports the proposal of implementing a “krill no-take zone” policy in this MPA, in line with the pre-moult foraging of these krill predators in this area. Further protection of the year-round habitats of migratory Adélie penguins could be achieved by inter-connecting the East Antarctic MPA proposals along the ice edge during winter, thereby mirroring the ecosystem's seasonal dynamics.

Gerontological Issues in Bengali Film Dekha

In the Indian context modernization, industrialization, urbanization, and westernization—‘the four horsemen of the modern apocalypse’ (Laurence Cohen, 1998:p.17) have a significant predicament in recent dimensions of gerontology. The problem relates to population ageing, controlled fertility, mortality rates and eventually the increase of life expectancy. The proliferation of old age home, extensive overseas migration, transnational dispersal of families, dissociation of the traditional multigenerational joint family, and simultaneous rise up of the nuclear family etc., are also some major causes behind the problems. These multidimensional interrelated challenges have been artistically shown in case of some old characters in Gautam Ghosh’s national award-winning Bengali film Dekha (2001). Particularly in the life of the protagonist, Sashibhusan Sanyal the problems have found differently added significance because of his disability (blindness).But his positive attitude to fight against the oddities of life contextualizes the film with a projection to highlight the old age problems from three main foci—biological, psychological, and social, to justify the relevance of the problematic. This paper argues the necessity of a consolidated progressive action by social scientists, policy makers and the elderly community to promote healthy and fruitful ageing at all spheres to counter the old age hazards.

Bar, stripe and spot development in sand-dwelling cichlids from Lake Malawi

BackgroundMelanic patterns such as horizontal stripes, vertical bars and spots are common among teleost fishes and often serve roles in camouflage or mimicry. Extensive research in the zebrafish model has shown that the development of horizontal stripes depends on complex cellular interactions between melanophores, xanthophores and iridophores. Little is known about the development of horizontal stripes in other teleosts, and even less is known about bar or spot development. Here, we compare chromatophore composition and development of stripes, bars and spots in two cichlid species of sand-dwellers from Lake Malawi—Copadichromis azureus and Dimidiochromis compressiceps.Results(1) In D. compressiceps, stripes are made of dense melanophores underlaid by xanthophores and overlaid by iridophores. Melanophores and xanthophores are either loose or absent in interstripes, and iridophores are dense. In C. azureus, spots and bars are composed of a chromatophore arrangement similar to that of stripes but are separated by interbars where density of melanophores and xanthophores is only slightly lower than in stripes and iridophore density appears slightly greater. (2) Stripe, bar and spot chromatophores appear in the skin at metamorphosis. Stripe melanophores directly differentiate along horizontal myosepta into the adult pattern. In contrast, bar number and position are dynamic throughout development. As body length increases, new bars appear between old ones or by splitting of old ones through new melanophore appearance, not migration. Xanthophore and iridophore distributions follow melanophore patterns. (3) Metamorphic pigmentation arises in cichlids in a fashion similar to that described in zebrafish: melanophore progenitors derived from the medial route of neural crest migration migrate from the vicinity of the neural tube to the skin during metamorphosis.ConclusionThe three pigment cell types forming stripes, bars and spots arise in the skin at metamorphosis. Stripes develop by differentiation of melanophores along horizontal myosepta, while bars do not develop along patent anatomical boundaries and increase in number in relation with body size. We propose that metamorphic melanophore differentiation and migratory arrest upon arrival to the skin lead to stripe formation, while bar formation must be supported by extensive migration of undifferentiated melanophores in the skin.

Reservoir and development characteristics of the Da'anzhai tight oil in Sichuan Basin, SW China

The oil in the Jurassic Da'anzhai reservoirs in the Sichuan Basin is unconventional tight oil, which accumulated in or near source rocks, and did not experience extensive migration in a large-scale long distance. The first submember, second submember and third submember of Da'anzhai Member are dominated by shell limestone which is widely and continuously distributed, and are typical near-source lacustrine shell limestone tight reservoirs. Complex lithology, multiple types of reservoir space and complicated pore structure are developed in these reservoirs. The effective reservoir space mainly includes micro-pores and micro-fractures with strong fabric selectivity. The petrophysics experiment reveals that the average connected matrix porosity of tight oil reservoir in Jurassic Da'anzhai Member is about 2.13%, lower than that of other tight oil reservoirs but higher than the average effective porosity (0.97%) from previous single alcohol-saturated method. According to production performance data, the Da'anzhai shell limestone reservoir is not a simple porous or fractured reservoir, but has complex pore-throat-fracture association or storage-seepage mode. Because the development of fossil shells controls the development of micro-fractures, fluids are difficult to enter into but easy to escape from the reservoirs. Although the pore-throat is fine, the sorting is poor and the displacement pressure is high, the movable fluid saturation and mercury ejection efficiency of the reservoir in the Da'anzhai Member is only slightly lower than that of some storage-seepage modes, and higher than that of Oil-bearing Group 7 of Yanchang Formation in the Ordos Basin. The reservoir in the Da'anzhai Member is one of the few tight oil reservoirs with high natural productivity. The tight oil in the shell limestone of the Da'anzhai Member has great development potential, but its extensive and effective development also has some challenges, such as high seepage resistance of matrix and ineffective single development mode. The development mode of the Da'anzhai tight oil should draw lessons from the Bakken Formation in North America and Oil-bearing Gourp 7 of Yanchang Formation in the Ordos Basin, and thus, effective development technologies based on volume fracturing and fine operation for shell limestone tight oil in the Da'anzhai Member in Sichuan Basin are developed to realize the development of profit and scale.

Abstract LB-134: The olfactory bulb provides a radioresistant niche for GBM cells

Abstract Brain tumor xenografts initiated from human GBM stem-like cells (GSCs) mimic many of the characteristics of GBM in situ including extensive invasiveness and migration. Using a GSC orthotopic brain tumor model, we show that the CD133+ NSC11 cells, a well-documented GSC line, display extensive migration and invasion along white matter tracts in the right hemisphere (RH) towards the olfactory bulb (OB) by day 35 post-implantation into the right striatum of nude mice. Radioresponse of tumor cells in the right hemisphere and olfactory bulb was assessed by a series of three daily injections of the halogenated thymidine analog CldU (5-chloro-2’-deoxyuridine), which is incorporated into DNA during S-phase and allows for the identification of proliferating cells. The CldU injections delivered to untreated mice resulted in 54% and 56% CldU positive tumor cells in the RH and the OB, respectively. CldU injections initiated 4 days post-10Gy resulted in 2.4% of tumor cells in the RH and 35% in the OB being positive for CldU. CldU injections initiated 12 days post-10Gy resulted in 5.5% of tumor cells in the RH and 50% in the OB being positive for CldU. These data indicate preferential radioresistance of GBM cells located in the olfactory bulb. These proliferation analyses were followed up with digital droplet PCR (ddPCR) analysis to determine the percentage of human cells remaining in the right hemisphere and olfactory bulb following irradiation. Specifically, NSC11 brain tumor xenografts received a single dose of 10Gy and the right hemisphere and olfactory bulb were collected at day 7 and 14 post-10Gy. Analyses of MKL2 (human specific) and Tfrc (mouse specific) gene sequences revealed that by day 14 post-10Gy, 32% of tumor cells are detectable in the OB and 5% in the RH. This can be compared to sham irradiated controls with 28% of tumor cells in the OB and 25% in the RH detected at the initial time of radiation and 76% in the OB and 73% in the RH following an additional 14 days of growth. These data indicate that following IR, the number of tumor cells in the olfactory bulb remains the same while the number in the right hemisphere decreases, consistent with decreased radiosensitivity of GBM cells in the olfactory bulb. Finally, RNA was extracted from NSC11 cells located in the right hemisphere and OB taken from formalin-fixed, paraffin embedded (FFPE) tumor cores at day 35 after-implantation. Gene expression profiles were run using Nanostring technology. Analyses revealed that NSC11 cells located in the OB were enriched in cellular processes involved in growth factor signaling, neurotransmitter signaling (i.e. glutamate and calcium), and various cancer-related pathways (i.e., RAS, MAPK, PI3K). These findings suggest intrinsic gene expression differences of GBM cells that have migrated from the right hemisphere to the olfactory bulb and provide a framework for further investigations into the mechanisms and processes mediating the GBM radioresistance. Citation Format: Cindy R. Timme, Barbara H. Rath, Kevin A. Camphausen, Philip J. Tofilon. The olfactory bulb provides a radioresistant niche for GBM cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-134.

Non-canonical Wnt signaling regulates junctional mechanocoupling during angiogenic collective cell migration.

Morphogenesis of hierarchical vascular networks depends on the integration of multiple biomechanical signals by endothelial cells, the cells lining the interior of blood vessels. Expansion of vascular networks arises through sprouting angiogenesis, a process involving extensive cell rearrangements and collective cell migration. Yet, the mechanisms controlling angiogenic collective behavior remain poorly understood. Here, we show this collective cell behavior is regulated by non-canonical Wnt signaling. We identify that Wnt5a specifically activates Cdc42 at cell junctions downstream of ROR2 to reinforce coupling between adherens junctions and the actin cytoskeleton. We show that Wnt5a signaling stabilizes vinculin binding to alpha-catenin, and abrogation of vinculin in vivo and in vitro leads to uncoordinated polarity and deficient sprouting angiogenesis in Mus musculus. Our findings highlight how non-canonical Wnt signaling coordinates collective cell behavior during vascular morphogenesis by fine-tuning junctional mechanocoupling between endothelial cells.

Assessing land surface temperature and land use change through spatio-temporal analysis: a case study of select major cities of India

Globalisation and opening up of markets has seen large-scale unplanned urbanisation in previous decade especially in developing countries like India. Dynamic changing policies influenced by global entities to set up profitable, industry-oriented cities have powered extensive migration with population upwelling contributing to the fast-growing urban expansion that needs monitoring and planning to design urban cities of the future. Research agenda here is to understand the change in land use (LU) temporally and model the land use change based on cellular automata through slope, land use, excluded, urban, transport and hillshade (SLEUTH) approach. Scientific studies carried out to address LU, its linkage with rising surface temperature and prediction of urban growth are limited or conducted only for smaller geographical extents and lack study especially in the most active and diverse country like India. This paper proposes implementation of integrated method of LU, land surface temperature dynamics, and urban modelling for four major cities: Delhi, Mumbai, Kolkata and Hyderabad. Of the four cities, Delhi, the capital of India, has shown enormous change in terms of increasing paved surface from 21.63% in 2003 to 31.56% in 2017 with corresponding mean surface temperature surge of 25.93 °C and 36.51 °C, respectively, suggesting one of the worst affected cities. Predicted LU envisions the possibility of a spurt in unplanned growth across the city boundary that would hinder developing basic amenities and would cause increased thermal discomfort amongst residents. This was understood through analysis of land surface temperature in relation to changing land use, indicating a need for sustainable development strategies to be implemented to avoid business-as-usual scenario. The analysis aims to help planners and city managers to understand region-specific issues in urban growth and to improve the cityscape with specific interventions.

Methane gas transport in unconfined aquifers: A numerical sensitivity study of a controlled release experiment at CFB Borden

Subsurface leakage of natural gas from petroleum wells can impact freshwater aquifers. Accurate prediction of gas migration in the subsurface will depend on knowledge of permeability, porosity, and flow system conditions. A series of two-dimensional numerical multi-phase flow simulations (CFbio) were conducted to investigate the role of multi-phase parameters (relative permeability and air entry pressure), flow system conditions (intrinsic permeability, anisotropy, and groundwater velocity), and geometric properties (layer thickness and layer lateral continuity) on the flow of gas-phase methane emanating from two variable-rate point sources in an unconfined sandy aquifer. Numerical simulations showed that for a homogeneous, weakly anisotropic aquifer, gas migrates almost exclusively vertically due to buoyancy, before venting to the vadose zone and atmosphere. As vertical migration became restricted through increased anisotropy, inclusion of lower-permeable layers, or increased horizontal groundwater velocity, an increase in the lateral component of gas migration was observed. This led to the formation of a broader lateral migration of the gas-phase plume and establishment of variably distributed vertical preferential flow paths, ultimately resulting in increased gas retention in the aquifer with relatively less methane reaching the vadose zone or atmosphere. The inclusion of a thin layer with moderately lower permeability (1–2 orders of magnitude) and increased air entry pressure was used to depict a fine-grained sand lens within a uniform aquifer. This subtle feature led to the formation of thin gas pools extending up- and down-gradient beneath the lens, allowing methane to travel much farther and faster than by groundwater advection alone, which is consistent with field observations during the experiment. In all scenarios investigated gas-phase methane was shown to migrate predominantly vertically due to buoyancy, until the aquitard permeability was <30% of the aquifer permeability. Our modelling demonstrates that even subtle permeability contrasts, together with capillary pressure changes demarcating grain-scale bedding, will lead to extensive lateral free-phase gas migration, and development of a more extensive and complex zone of impacted aquifer than presupposed.

Vertical distribution and diel migration of mesopelagic fishes on the northern slope of the South China sea

Mesopelagic fishes are major components contributing to deep-sea scattering layers in the open ocean. They have the potential to support a substantial higher trophic level harvest, but knowledge about this possible resource is still rudimentary. Some of the mesopelagic fishes undertake diel vertical migration (DVM) over large depths by feeding in shallow water during darkness and migrating to depth to avoid visual predators during daylight. The vertical distribution and diel migration pattern of the mesopelagic fishes on the northern slope of the South China Sea were investigated during two multidisciplinary surveys carried out in October 2014 and June 2015. Based on acoustic and biological sampling, a distinct deep scattering layer (DSL) consisting mainly of mesopelagic fishes was identified in deep water (>300 m). Extensive diel vertical migration for hundreds of meters to form dense aggregations in the epipelagic zone (0–150 m) at night was observed in both seasons, but the migration was highly species dependent. While most of the Myctophiformes and the Perciformes undertook DVM, most of the Salmoniformes and Beryciformes remained in deep water both day and night. Based on paired day-night differences of acoustic density in the DSL, the migrating proportion of mesopelagic backscatter varied markedly in different locations, ranging from 28% to 63%, with a mean of 48% in two seasons. The extensive vertical migration occurred in separate groups at different periods during sunset and sunrise hours. Additional analysis showed that the center of gravity of the mesopelagic backscatters (200–1000 m) and their night distribution in the subsurface layer (10–150 m) were positively correlated with the mean temperature in respective zones. Moreover, some of the mesopelagic communities on the slope were found to undertake pronounced diel horizontal migration in a pattern of towards the shore in the evening and away from the shore after midnight. The horizontal migrant species were mainly Myctophidae, in particular Diaphus chrysorhynchus and Diaphus garmani. Simultaneous analysis on typical tidal currents indicated that the horizontal migration, over a large distance with high speed and biomass, could not be explained by passive transport due to tidal currents alone, and the active swimming of the mesopelagic fishes may also play an important role.

Decreased influx of Calanus spp. into the south-western Norwegian Sea since 2003

The copepods Calanus hyperboreus and C. finmarchicus are the ecologically most important copepod species in the Nordic Seas. The larger C. hyperboreus, of polar origin, is advected into the south-western Norwegian Sea with the East Icelandic Current (EIC), and can therefore be considered an indicator species of these waters. Using large spatio-temporal hydrographic and zooplankton data sets, we show that an abrupt reduction in abundance of C. hyperboreus around the year 2003 in the south-western Norwegian Sea coincided with a reduction in the volume of Modified East Icelandic Water (MEIW) in the intermediate layers (R = 0.64, lagged one year). Abundance of C. hyperboreus and the volume of MEIW have since remained lower compared to the previous years (Mann-Whitney U tests, p < 0.05). The total zooplankton biomass in spring within the EIC, east of Iceland, was also much reduced around 2003 and has also since remained low. A comparable post-2003 reduction is observed in the abundance of overwintered stages of C. finmarchicus in May. Our results suggest that the reduction of zooplankton in the south-western Norwegian Sea around 2003 was caused by reduced influence of subarctic waters from the western region. This may in turn impact the extensive feeding migration of herring to this region.

Direct 3D bioprinted full-thickness skin constructs recapitulate regulatory signaling pathways and physiology of human skin

Currently available tissue engineered skin-equivalents fail to replicate anatomically relevant features, e.g. undulated morphology of the dermal-epidermal junction, resulting in inadequate recapitulation of biologically meaningful cellular signaling pathways. This study reports fabrication of 3D bioprinted, human cell-based full thickness skin model possessing anatomically relevant structural, mechanical and biochemical features akin to human skin. The unique undulated feature of the epidermis-dermis junction could be recapitulated in the 3D bioprinted skin-equivalents. Extensive migration of the keratinocytes within the construct along with differentiation events reminded reepithelialisation. Cell-cell interaction along with diffusible factors promoted expression of differentiation and cornification markers in region-specific manner. Architectural features and silk bioink microenvironment triggered deposition of basement membrane specific-proteins at the interface. Most interestingly, extensive transcriptomics and proteomics analysis accentuated striking similarity of the 3D bioprinted full thickness skin model to the native human skin, with involvement of a number of pathways related to skin development and physiology, such as skin development, extracellular matrix organization, keratinization/cornification and collagen fibril organization. Such bioprinted in vitro human skin models would offer tremendous potential for screening cosmetic products and drugs, as well as to understand the complex physiological processes relevant to human skin thereby bridging the gap between conventional monolayer or 3D cultures and animal models.

Natural diversity of CRISPR spacers of Thermus: evidence of local spacer acquisition and global spacer exchange.

We investigated the diversity of CRISPR spacers of Thermus communities from two locations in Italy, two in Chile and one location in Russia. Among the five sampling sites, a total of more than 7200 unique spacers belonging to different CRISPR-Cas systems types and subtypes were identified. Most of these spacers are not found in CRISPR arrays of sequenced Thermus strains. Comparison of spacer sets revealed that samples within the same area (separated by few to hundreds of metres) have similar spacer sets, which appear to be largely stable at least over the course of several years. While at further distances (hundreds of kilometres and more) the similarity of spacer sets is decreased, there are still multiple common spacers in Thermus communities from different continents. The common spacers can be reconstructed in identical or similar CRISPR arrays, excluding their independent appearance and suggesting an extensive migration of thermophilic bacteria over long distances. Several new Thermus phages were isolated in the sampling sites. Mapping of spacers to bacteriophage sequences revealed examples of local acquisition of spacers from some phages and distinct patterns of targeting of phage genomes by different CRISPR-Cas systems.This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.

Genetic diversity and genetic structure of natural populations in an extremely narrowly distributed perennial species Glycine tabacina (Labill.) Benth. on the southeast islands in China

In China, Glycine tabacina (Labill.) Benth. is only distributed in the southeast coast and islands. In this study, 28 natural populations of G. tabacina species were sampled from 13 islands using 22 SSR markers. The Chinese G. tabacina was characterized by higher outcrossing rate and within-population genetic variation, extensive migration, greater population genetic differences and geographically weak-associated genetic differentiation, with higher level of heterogeneity within the natural populations along the southeast islands of China even though this species is a self-pollinating plant. The number of alleles per locus averaged 5.77 and ranged from 2 to 16. The expected heterozygosity (He) per locus averaged a value of 0.51, varying from 0.08 to 0.80. As an autogamous species, the Chinese G. tabacina unexpectedly showed a relatively high mean outcrossing rate in single locus (ts = 6.52%) and multilocus (tm = 6.75%), higher mean gene flow (Nm = 0.315), lower mean gene differentiation index (Gst = 0.436), and particularly, relatively lower among-population genetic variation (43.55%) and higher within-population genetic variation (49.66%) revealed by analysis of molecular variance. Spatial autocorrelation analysis revealed that populations within a radius of approximately 14.7 km would have a positive and significant genetic relationship to one another. However, the event of long-distance genetic background dispersal was revealed by individual assignment test and haplotype analysis (> 200 km dispersal was inferred, but > 56 km dispersal was observed). The north and middle-north islands of Fujian Province seemed to be the center of genetic diversity.

Ab initio modeling of oxygen ion migration in non-stoichiometric bismuth titanate pyrochlore Bi1.5Ti2O6.25

Ab initio investigation of the possibility of oxygen ion migration in non-stoichiometric bismuth titanate pyrochlore Bi1.5Ti2O6.25 has been performed. Density functional theory calculations together with the nudged elastic band method were used to estimate the O2– migration barriers. The migration energy barriers for the most favorable paths of oxygen migration related to O48f–O48f jumps are in the range 0.67–0.92 eV with the corresponding vacancy formation energy in the range 1.76–2.60 eV. These paths form extensive migration network in non-stoichiometric Bi1.5Ti2O6.25 which is sufficient for 3-dimensional O2– diffusion. The results show a good agreement with the experimentally obtained activation energy of oxygen diffusion in doped bismuth titanate pyrochlores with low dopant concentration.

Sociobehavioral and community predictors of unsuppressed HIV viral load: multilevel results from a hyperendemic rural South African population.

Extensive antiretroviral therapy scale-up is expected to prevent onward transmission of HIV by reducing the overall community viral load. Despite multiple studies about predictors of detectable viral load derived from clinical setting, to date, no study has established such predictors using a population-based viral load survey in a sub-Saharan African hyperendemic setting to inform interventions designed to halt HIV transmission. We used one of Africa's largest prospective cohorts in rural KwaZulu-Natal Province, South Africa, to establish the key sociodemographic, behavioral and community predictors of unsuppressed viral load at the population level. We collected 5454 viral load measurements from a population-based viral load survey of 3892 women living with HIV from a rural population during 2011, 2013 and 2014. Multilevel logistic regression models were fitted to examine the risk predictors of unsuppressed viral load. Among women living with HIV in this population, the prevalence of unsuppressed viral load was 69% in 2011, 58% in 2013 and 53% in 2014. Although time since HIV infection was associated with lower risk for virologic detection [adjusted odds ratio (aOR) = 0.91,0.87-0.94], young women (aOR = 2.59,1.47-4.55) with extensive external migration history (aOR = 1.25,1.02-1.54), greater number of sexual partners (aOR = 1.30,1.02-1.67), and longer history of residing in an HIV incidence hotspot community were more likely to experience unsuppressed viral load (aOR = 1.12,1.06-1.19). Young women, number of sexual partners, transiency and longer residence in an HIV hotspot community are important determinants of unsuppressed viral load in a hyperendemic rural African setting. To substantially reduce the persistently high transmission potential in these settings, targeted interventions to address these risk factors will be essential for both individual and population health gains.

Hierarchical Decoration of Eggshell Membrane with Polycaprolactone Nanofibers to fabricate a Bilayered Scaffold for Skin Tissue Engineering

ABSTRACTEggshell Membrane (ESM) is a naturally occurring proteinaceous microfibrous scaffold capable of mimicking the extracellular matrix (ECM). The extraction methodology deployed for its extraction process impedes its extensive application as a biomaterial in regenerative medicine. Herein, a unique route was deployed to decorate the surface of ESM with electrospun polycaprolactone (PCL) nanofiber in order to ameliorate the above problems and also fabricate a novel ECM mimicking bilayered scaffold for skin tissue engineering applications. Microstructural and surface topographic analysis confirms the formation of bilayered structure with smooth electrospun PCL nanofibers decorated on ESM. Carbodiimide chemistry was utilized to crosslink the two layers. Cytocompatibility evaluation of scaffolds was carried out with Human dermal fibroblast (HDF) cells. The biomimetic architecture and protein rich composition of as fabricated bilayered construct facilitated extensive cell adhesion, proliferation and migration in contrast the bare natural tissue led to impeded cell adhesion.

Astrocytes migrate from human neural stem cell grafts and functionally integrate into the injured rat spinal cord

Neural stem cells (NSCs) can differentiate into both neurons and glia after transplantation into spinal cord injury (SCI) sites. The neuronal component of stem cell grafts has the potential to form functional synaptic relays across the lesion site. The glial component may reform a blood-spinal cord barrier, support neuronal function, and contribute to remyelination. We performed a long-term, 1.5-year time course study focused on astrocyte migration, differentiation, integration, and safety following human NSC transplantation into C5 hemisection sites in immunodeficient rats. NSCs that adopted a neuronal fate did not migrate from the lesion site. In contrast, transplanted cells that adopted astrocyte fates exhibited long distance migration from the lesion site through host white matter in rostrocaudal directions. These cells migrated slowly at a mean rate of 2–3 mm/month, divided as they migrated, and gradually differentiated into astrocytes. After 1.5 years, human astrocytes migrated nine spinal cord segments, caudally to the mid-thoracic level, and rostrally into the brainstem. The migrated human astrocytes joined the endogenous population of astrocytes in the host spinal cord, extended perivascular endfeet towards host pericytes and endothelium, formed interspecies and intraspecies perivascular astrocytic networks connected by gap junctions, and expressed glutamate transporter proteins in perisynaptic processes, suggesting structural and functional integration. No adverse consequences of this extended glial migration were detected. Adjacent to the lesion site, chronic host astrocytic upregulation was significantly attenuated by NSC grafts. Thus, human astrocytes can migrate long distances from sites of SCI and safely integrate into the host central nervous system. Significance statementNeural stem cell (NSC) grafts are a candidate therapy for spinal cord injury (SCI). Here we report an 18-month study of astrocyte survival and migration from sites of SCI in immunodeficient rats. NSC grafts significantly attenuate host astrocyte reactivity at the lesion/host interface. Intra-graft astrocytes integrate into the host blood-spinal cord barrier (BSCB) and widely express glutamate transporter proteins characteristic of neurotransmitter regulation. Notably, astrocytic components of NSC grafts exhibit gradual yet extensive migration after implantation into the mid-cervical injury site; neurons do not migrate at all. This extensive astrocyte migration is not detectably associated with adverse outcomes anatomically or behaviorally.