Migration Events Research Articles

S91 Management of Biliary Complications in Liver Transplant Recipients Using a Fully Covered Self-expandable Metal Stent With Antimigration Features

Introduction: Following liver transplant (LT) with duct-to-duct anastomosis, biliary strictures and leaks are typically managed with endoscopic retrograde cholangiopancreatography (ERCP) and stenting. While multiple plastic stents are typically used for strictures, self-expandable metal stents (SEMS) can be used to decrease the number of ERCPS with longer periods of stent patency. However, their use is limited by stent migration. The use of fully covered SEMS (FCSEMS), with antimigration fins to manage benign biliary complications following LT may provide stricture resolution with limited adverse events. As such we aimed to describe clinical outcomes of FCSEMS in LT recipients using one type of FCSEMS. Methods: This was a single center retrospective study of consecutive adult LT patients undergoing FCSEMS from January 2014 to April 2022. Primary outcomes were stricture resolution and recurrence. Secondary outcomes included rates of stent migration, stent occlusion, and number of ERCPs required. Results: 46 LT patients with anastomotic strictures (n=40), bile leaks (n=4) or both (n=2) (average age 55.8 years, 33% women) were treated with a FCSEMS with antimigration features (Viabil, W.L. Gore, Flagstaff, AZ) approved for malignant strictures. The median time from LT to FCSEMS placement was 132.5 days. Within one year of LT, 32 patients (69.5%) required intervention; early intervention at less than 30 and 90 days was needed in 7 and 20 patients, respectively. At the time of study conclusion there were 3 patients with stents in situ. Stricture resolution was seen in 34 patients (74%) after an average stent dwell time of 134.5 ± 71 days; recurrence was observed in 8 patients (17%). There were three instances of partial proximal stent migration that did not require reintervention or interfere with removability. Procedural details are listed in Table: The total mean number of ERCPS required was 2.48 (range 1-5). Conclusion: The use of a FCSEMS with antimigration features offers an opportunity to enhance stricture resolution with longer stent dwell times and fewer ERCPs. In our cohort there were no instances of clinically significant stent migration, dysfunction, or procedure related adverse events. Furthermore, these stents provide an opportunity reduce procedure related costs. Additional studies are needed to identify suitable patients for FCSEMS placement. Table 1. - Procedure related details and stent outcomes Stent Dwell Time +/- Standard Deviation (days) 134.5 +/- 71.8 Stent Placement transpapillary vs intraductally, n (%) 36 (78.3%) vs 10 (21.7%) Prior Sphincterotomy, n (%) 17 (40%) Stricture Recurrence, n (%) 8 (17%) Average Number ERCPs, n (range) 2.48 (1-5) Stent Migration, n (%) 3 (6.5 %) Stent Occlusion, n (%) 8 (17%)

The genetics of bird migration

Bird migration is one of the most amazing biological phenomena exhibited by organisms today, with birds as small as three grams travelling thousands of kilometers twice each year. Most people are familiar with this behaviour; they likely recognize the seasonal movements of birds each year and may have even witnessed specific migratory events (e.g., geese flying in their characteristic V-formations). What many people may not know is that bird migration has a strong genetic basis, especially in groups like songbirds who migrate alone and at night, preventing juveniles from following more experienced adult birds on their first migration. Successful migration also requires the coordinated function of many traits, not only behavioural traits like timing and orientation but also morphological and physiological traits to permit these long distance treks. Together, these traits comprise what has been called the 'migratory syndrome'. In this primer, we provide a broad overview of research on the genetics of migratory traits, from early experimental work to future functional assays and their importance for bird conservation. We focus primarily on songbirds as most work on the genetics of migration has been conducted with this group.

Phylogeography and colonization pattern of subendemic round-leaved oxeye daisy from the Dinarides to the Carpathians

The Carpathians are an important biodiversity hotspot and a link between mountain ranges on the European continent. This study investigated the phylogeography of one the Carpathian subendemics, Leucanthemum rotundifolium, which is distributed throughout the range and in one isolated population outside it. Range-wide sampling was used to examine phylogeographic patterns by sequencing uniparentally inherited chloroplast markers that exemplify seed dispersal. Reconstruct Ancestral State in Phylogenies (RASP) software, Bayesian binary Markov Chain Monte Carlo (BBM) analysis, and ecological niche modeling based on concatenated results of five algorithms were used to infer migration routes and examine links with other species through phylogeny. The round-leaved oxeye daisy is an example of organisms that reached the Carpathians through a southern “Dacian” migration route, most probably through long-distance dispersal. Dating placed the events in the Pleistocene and supported migrations during cooler periods and stasis/isolation followed by separation in the interglacials. Haplotype diversification indicated that after L. rotundifolium reached the area around the Fagaras Mountains, several migration events occurred leading to colonization of the Southern Carpathians followed by migration to the Apuseni Mountains, the Eastern Carpathians, and finally the Western Carpathians. The results are consistent with previous phylogeographic studies in this region and indicate several novel patterns.

Characterizing the river migration process based on migration events of individual bends: a case study of the lower Yellow River, China

Frequent channel shifts in the Lower Yellow River easily leads to embankment collapse causing geomorphological processes necessary to characterize. This paper segmented the river centreline from its component unit-bends and established a migration event model to characterize the migration process of rivers. The inflection points on the river centreline can be used to segment individual bends. Three types of migration events, disappearance, lateral migration and decomposition, are defined for the first time to categorize river migration. Furthermore, these migration events can be rapidly detected using the Meander Migration Index. The four-tuple BMModel (Bend Migration Model), including events, spatial positions, bend types and migration attributes, systematically quantifies the river migration process. In addition, these results can be implemented with an integrated PyBend (Python-Bend migarition) package, providing promising technical support for the studies of river migration and evolution over long time series.

The impact of sampling bias on viral phylogeographic reconstruction.

Genomic epidemiology plays an ever-increasing role in our understanding of and response to the spread of infectious pathogens. Phylogeography, the reconstruction of the historical location and movement of pathogens from the evolutionary relationships among sampled pathogen sequences, can inform policy decisions related to viral movement among jurisdictions. However, phylogeographic reconstruction is impacted by the fact that the sampling and virus sequencing policies differ among jurisdictions, and these differences can cause bias in phylogeographic reconstructions. Here we assess the potential impacts of geographic-based sampling bias on estimated viral locations in the past, and on whether key viral movements can be detected. We quantify the effect of bias using simulated phylogenies with known geographic histories, and determine the impact of the biased sampling and of the underlying migration rate on the accuracy of estimated past viral locations. We find that overall, the accuracy of phylogeographic reconstruction is high, particularly when the migration rate is low. However, results depend on sampling, and sampling bias can have a large impact on the numbers and nature of estimated migration events. We apply these insights to the geographic spread of Ebolavirus in the 2014-2016 West Africa epidemic. This work highlights how sampling policy can both impact geographic inference and be optimized to best ensure the accuracy of specific features of geographic spread.

Crime and the Mariel Boatlift

We describe crime attributable to the Mariel Boatlift, the 1980 Cuban refugee crisis that increased Miami’s population by nearly 10%. Using synthetic control methods to match Miami with cities that exhibit similar pre-intervention crime patterns, we find the phenomenon comparatively increased property crime and murder rates; we also document weaker but suggestive relative growth in violent crime. Compositional features of the newcomers partially drive results; the disproportionately young, male Cubans’ characteristics highly correlate with illicit activity. However, the degree of prior incarceration and psychiatric institutionalization likely explains the majority of the observed effects. Given the group’s unique composition and the absence of rigorous screening, it likely constitutes the worst observed migration event in terms of public safety in US history. The Marielitos bear little resemblance to other groups of newcomers. Hence, it would be imprudent to use crime connected with the 1980 event we study to inform immigration policy.

Global Transmission of Human Immunodeficiency Virus 1 Subtype C and Its Impact on the Circulation of B/C Recombination Strains in China

Abstract This study aimed to reconstruct the origin and worldwide epidemic history of human immunodeficiency virus (HIV) 1 subtype C and comprehend how HIV-1 subtype C was introduced into and spread throughout China in the form of B/C recombinant strains. Envelope sequences of HIV-1 subtype C and some other subtypes deposited before December 31, 2020 were downloaded from the Los Alamos HIV Database and the Chinese National Center for AIDS/STD Control and Prevention Database. The available sequences were screened for quality, and Bayesian analysis was used to build the maximum clade credibility evolutionary tree to analyze and judge the origin and spread of HIV-1 subtype C. HIV-1 subtype C originated in central Africa around 1952, then spread to southern Africa around 1969 and to eastern Africa around 1973. HIV-1 subtype C from southern Africa was introduced into India in 1977. HIV-1 subtype C of eastern Africa was introduced into Brazil in 1987. Indian HIV-1 subtype C was exported to China in three migration events during the period from 1986 to 1989. The two predominant recombinants in China (CRF07_BC and CRF08_BC) emerged in 1988 and 1990, respectively. Other B/C recombinants, namely, CRF64_BC, CRF61_BC and CRF62_BC, originated in 1993, 2002 and 2000, respectively. Our study has reconstructed the global origin and evolutionary history of HIV-1 subtype C. In addition, our study demonstrated that the Chinese HIV-1 subtype C originated from three related Indian lineages around the mid to late 1980s and, since then, has formed some B/C recombinants with subtype B that caused a widespread epidemic in China.

Aldehyde dehydrogenase 2 and arrhythmogenesis.

Cardiac arrhythmia is a common cardiovascular disease that leads to considerable economic burdens and significant global public health challenges. Despite the remarkable progress made in recent decades, antiarrhythmic therapy remains suboptimal. Aldehyde dehydrogenase 2 (ALDH2), a critical detoxifying enzyme, catalyzes toxic aldehydes and protects individuals from damage caused by oxidative stress. Accumulating evidence has demonstrated that ALDH2 activation has potential antiarrhythmic benefits. The correlation between ALDH2 deficiency and arrhythmogenesis has been widely recognized. In this review, we summarize recent research on the potential role of ALDH2 activation and antiarrhythmic protection, as well as the role played by the ALDH2∗2 polymorphism (rs671) in promoting arrhythmic risk. Additionally, we discuss important new findings illustrating the use of ALDH2 activators, which may prove to be promising antiarrhythmic therapy agents.

Historical Evolutionary Dynamics and Phylogeography Analysis of Transmissible Gastroenteritis Virus and Porcine Deltacoronavirus: Findings from 59 Suspected Swine Viral Samples from China.

Since the beginning of the 21st century, humans have experienced three coronavirus pandemics, all of which were transmitted to humans via animals. Recent studies have found that porcine deltacoronavirus (PDCoV) can infect humans, so swine enteric coronavirus (SeCoV) may cause harm through cross-species transmission. Transmissible gastroenteritis virus (TGEV) and PDCoV have caused tremendous damage and loss to the pig industry around the world. Therefore, we analyzed the genome sequence data of these two SeCoVs by evolutionary dynamics and phylogeography, revealing the genetic diversity and spatiotemporal distribution characteristics. Maximum likelihood and Bayesian inference analysis showed that TGEV could be divided into two different genotypes, and PDCoV could be divided into four main lineages. Based on the analysis results inferred by phylogeography, we inferred that TGEV might originate from America, PDCoV might originate from Asia, and different migration events had different migration rates. In addition, we also identified positive selection sites of spike protein in TGEV and PDCoV, indicating that the above sites play an essential role in promoting membrane fusion to achieve adaptive evolution. In a word, TGEV and PDCoV are the past and future of SeCoV, and the relatively smooth transmission rate of TGEV and the increasing transmission events of PDCoV are their respective transmission characteristics. Our results provide new insights into the evolutionary characteristics and transmission diversity of these SeCoVs, highlighting the potential for cross-species transmission of SeCoV and the importance of enhanced surveillance and biosecurity measures for SeCoV in the context of the COVID-19 epidemic.

Diel timing of migration is not plastic in a migratory ungulate

The temporal windows during which animals complete essential life processes (i.e. temporal niche) allow animals to match their actions to a given environmental context. When completing seasonal migrations, some migrants switch their activity patterns (e.g. from diurnal to nocturnal in multiple species of migratory birds) to take advantage of better conditions. We tested the temporal niche-switch hypothesis by comparing activity patterns before and during migration for four populations of migratory mule deer, Odocoileus hemionus , in western Wyoming, U.S.A. (2007–2019). We predicted that the physically taxing and risky event of terrestrial migration would prompt shifts in diel activity patterns. In contrast to the niche-switch hypothesis, mule deer did not drastically change their activity patterns during migration. Both before and during migration, mule deer were crepuscular (i.e. most active during twilight hours). When migrating in the spring, however, mule deer tended to concentrate activity near dawn, although they did not concentrate activity near dawn in the autumn, when less snow was present. By moving in the morning during spring migration, mule deer moved when snow was hardest, potentially allowing them to avoid the energetic costs of sinking into deep snow. Mule deer overall maintained a consistent pattern of crepuscular activity, but fine-tuned their activity patterns during migration, which may allow them to better match their behaviours with environmental conditions while completing an important life event. Rather than abandoning activity patterns, animals instead may make subtle alterations in their activity patterns to take advantage of present conditions. • Mule deer did not switch the time of day that they were most active when migrating. • Instead, migratory mule deer fine-tuned their migratory behaviour. • Shifts in temporal niches may be underappreciated behavioural strategies.

Analysis of Common SNPs across Continents Reveals Major Genomic Differences between Human Populations.

Common alleles tend to be more ancient than rare alleles. These common SNPs appeared thousands of years ago and reflect intricate human evolution including various adaptations, admixtures, and migration events. Eighty-four thousand abundant region-specific alleles (ARSAs) that are common in one continent but absent in the rest of the world have been characterized by processing 3100 genomes from 230 populations. Also computed were 17,446 polymorphic sites with regional absence of common alleles (RACAs), which are widespread globally but absent in one region. A majority of these region-specific SNPs were found in Africa. America has the second greatest number of ARSAs (3348) and is even ahead of Europe (1911). Surprisingly, East Asia has the highest number of RACAs (10,524) and the lowest number of ARSAs (362). ARSAs and RACAs have distinct compositions of ancestral versus derived alleles in different geographical regions, reflecting their unique evolution. Genes associated with ARSA and RACA SNPs were identified and their functions were analyzed. The core 100 genes shared by multiple populations and associated with region-specific natural selection were examined. The largest part of them (42%) are related to the nervous system. ARSA and RACA SNPs are important for both association and human evolution studies.

A Chemically Fuelled Molecular Automaton Displaying Programmed Migration of Zn2+ Between Alternative Binding Sites.

A molecular system comprising a cationic zinc complex and an amino acid-derived ambident ligand having phosphate and carboxylate binding sites undergoes a series of rearrangements in which the metal cation migrates autonomously from one site to another. The location of the metal is identified by the circular dichroism spectrum of a ligated bis(2-quinolylmethyl)-(2-pyridylmethyl)amine (BQPA) chromophore, which takes a characteristic shape at each binding site. Migration is fuelled by the decomposition of trichloroacetic acid to CO2 and CHCl3 , which progressively neutralises the acidity of the system as a function of time, revealing in sequence binding sites of increasing basicity. The migration rate responds to control by variation of the temperature, water content and triethylamine concentration, while an excess of fuel controls the duration of an induction period before the migration event.

Multicenter retrospective evaluation of transmural migration of subcutaneous ureteral bypass devices within the digestive tract in cats.

BackgroundPlacement of a subcutaneous ureteral bypass (SUB) device is an effective method to relieve all causes of ureteral obstruction in cats. Complications involving migration within the gastrointestinal tract have been seldomly described.ObjectivesTo characterize transmural migration of SUB devices within the digestive tract in cats.AnimalsEleven migrated SUB catheters identified in 8 cats between 2017 and 2021.MethodsRetrospective review of medical records of cats with a SUB device in which migration into the gastrointestinal tract was identified.ResultsThe median time from SUB device placement to implant migration was 928 days (201‐2298 days). Seven cats had obstruction of the SUB device and a positive urine culture at diagnosis. The migration was identified by ultrasound in 6/11, pre‐operative contrast radiography in 2/2, and only at time of surgery in 3 SUB devices. All cats underwent surgical correction. Four nephrostomy and 7 cystotomy catheters migrated. Migration occurred into the duodenum (3/11), jejunum (7/11), and colon (1/11). SUB devices were removed in 7 cats and replaced in 2 cats, with 1 cat diagnosed with 2 migration events. Gastrointestinal resection and anastomosis were performed in 7/8 cats and an enterotomy in 2 cats. Six cats survived to discharge. The median follow‐up time after migration diagnosis was 365 days (range, 0‐1114 days) and 2 cats are still alive.Conclusions and Clinical ImportanceAlthough a rare complication, migration of SUB device should be considered in cats with SUB device obstruction and a positive urine culture.

Phylogeography of Sub-Saharan Mitochondrial Lineages Outside Africa Highlights the Roles of the Holocene Climate Changes and the Atlantic Slave Trade.

Despite the importance of ancient DNA for understanding human prehistoric dispersals, poor survival means that data remain sparse for many areas in the tropics, including in Africa. In such instances, analysis of contemporary genomes remains invaluable. One promising approach is founder analysis, which identifies and dates migration events in non-recombining systems. However, it has yet to be fully exploited as its application remains controversial. Here, we test the approach by evaluating the age of sub-Saharan mitogenome lineages sampled outside Africa. The analysis confirms that such lineages in the Americas date to recent centuries—the time of the Atlantic slave trade—thereby validating the approach. By contrast, in North Africa, Southwestern Asia and Europe, roughly half of the dispersal signal dates to the early Holocene, during the “greening” of the Sahara. We elaborate these results by showing that the main source regions for the two main dispersal episodes are distinct. For the recent dispersal, the major source was West Africa, but with two exceptions: South America, where the fraction from Southern Africa was greater, and Southwest Asia, where Eastern Africa was the primary source. These observations show the potential of founder analysis as both a supplement and complement to ancient DNA studies.

1,2-Radical Shifts in Photoinduced Synthetic Organic Transformations: A Guide to the Reactivity of Useful Radical Synthons.

The exploration of 1,2-radical shift (RS) mechanisms in photoinduced organic reactions has provided efficient routes for the generation of important radical synthons in many chemical transformations. In this Review, the basic concepts involved in the traditional 1,2-spin-center shift (SCS) mechanisms in recently reported studies are discussed. In addition, other useful 1,2-RSs are addressed, such as those proceeding through 1,2-group migrations in carbohydrate chemistry, via 1,2-boron shifts, and by the generation of α-amino radicals. The discussion begins with a general overview of the basic aspects of 1,2-RS mechanisms, followed by a demonstration of their applicability in photoinduced transformations. The sections that follow are organized according to the mechanisms operating in combination with the 1,2-radical migration event. This contribution is not a comprehensive review but rather aims to provide an understanding of the topic, focused on the more recent advances in the field, and establishes a definition for the nomenclature that has been used to describe such mechanisms.

Evolutionary Genomics of a Subdivided Species.

The ways in which genetic variation is distributed within and among populations is a key determinant of the evolutionary features of a species. However, most comprehensive studies of these features have been restricted to studies of subdivision in settings known to have been driven by local adaptation, leaving our understanding of the natural dispersion of allelic variation less than ideal. Here, we present a geographic population-genomic analysis of 10 populations of the freshwater microcrustacean Daphnia pulex, an emerging model system in evolutionary genomics. These populations exhibit a pattern of moderate isolation-by-distance, with an average migration rate of 0.6 individuals per generation, and average effective population sizes of ∼650,000 individuals. Most populations contain numerous private alleles, and genomic scans highlight the presence of islands of excessively high population subdivision for more common alleles. A large fraction of such islands of population divergence likely reflect historical neutral changes, including rare stochastic migration and hybridization events. The data do point to local adaptive divergence, although the precise nature of the relevant variation is diffuse and cannot be associated with particular loci, despite the very large sample sizes involved in this study. In contrast, an analysis of between-species divergence highlights positive selection operating on a large set of genes with functions nearly nonoverlapping with those involved in local adaptation, in particular ribosome structure, mitochondrial bioenergetics, light reception and response, detoxification, and gene regulation. These results set the stage for using D. pulex as a model for understanding the relationship between molecular and cellular evolution in the context of natural environments.

Distribution and phylogeography of the genus Mattirolomyces with a focus on the Asian M. terfezioides haplotypes.

Mattirolomyces is an edible commercial sequestrate genus that is globally distributed. From the five described taxa of this genus, Mattirolomyces terfezioides is the most common species in Asia. Our recent attempts to locate M. terfezioides outside its current distribution area in China documented its first records in areas of poplar trees with the lowest known temperature and precipitation averages ever recorded for this species. This peculiar ecology was not reflected on the species-morphological features nor on its phylogenetic position in the genus. The first attempt to apply the phylogenetic network approach to Mattirolomyces revealed its geographic origin in the Asian-Pacific areas prior to frequent long-distance migration events. Based on data from recent study areas, we found that the collections from Inner Mongolia and the Shanxi province were similar to European collections. Asian haplotypes were less distant from the outgroup comparing to collections from Europe, supporting the hypothesis that M. terfezioides was originated from this Chinese area and was subsequently transported to Europe. Exploring M. terfezioides ecology and its mycorrhiza potential to grow in association with poplars would be of great importance for planning cultivation projects of this valuable desert truffle species in Central and Eastern China, a currently underexploited economic sector that deserves further ecological and M. terfezioides mycorrhizal synthesis investigations.

Evolutionary patterns of plastome resolve multiple origins of the Ns-containing polyploid species in Triticeae

Tracing evolutionary history proves challenging for polyploid groups that have evolved rapidly, especially if an ancestor of a polyploid is extinct. The Ns-containing polyploids are recognized as the NsXm and StHNsXm genomic constitutions in Triticeae. The Ns originated from Psathyrostachys, while the Xm represented a genome of unknown origin. Here, we use genetic information in plastome to trace the complex lineage history of the Ns-containing polyploid species by sampling 26 polyploids and 90 diploid taxa representing 23 basic genomes in Triticeae. Phylogenetic reconstruction, cluster plot of genetic distance matrix, and migration event demonstrated that (1) the Ns plastome originated from different Psathyrostachys species, and the Xm plastome may originate from an ancestral lineage of Henrardia, Agropyron, and Eremopyrum; (2) the Ns, Xm, and St genome donors separately served as the maternal parents during the speciation of the Ns-containing polyploid species, resulting in a maternal haplotype polymorphism; (3) North AmericanLeymusspecies might originate from colonization during late Miocene via the Bering land bridge and were the paternal donor of the StHNsXm genome Pascopyrum species. Our results shed new light on our understanding of the rich diversity and ecological adaptation of the Ns-containing polyploid species.

Identification of the prognostic signature based on genomic instability-related alternative splicing in colorectal cancer and its regulatory network.

Background: Colorectal cancer (CRC) is a heterogeneous disease with many somatic mutations defining its genomic instability. Alternative Splicing (AS) events, are essential for maintaining genomic instability. However, the role of genomic instability-related AS events in CRC has not been investigated. Methods: From The Cancer Genome Atlas (TCGA) program, we obtained the splicing profiles, the single nucleotide polymorphism, transcriptomics, and clinical information of CRC. Combining somatic mutation and AS events data, a genomic instability-related AS signature was constructed for CRC. Mutations analyses, clinical stratification analyses, and multivariate Cox regression analyses evaluated this signature in training set. Subsequently, we validated the sensitivity and specificity of this prognostic signature using a test set and the entire TCGA dataset. We constructed a nomogram for the prognosis prediction of CRC patients. Differentially infiltrating immune cells were screened by using CIBERSORT. Inmmunophenoscore (IPS) analysis was used to evaluate the response of immunotherapy. The AS events-related splicing factors (SF) were analyzed by Pearson’s correlation. The effects of SF regulating the prognostic AS events in proliferation and migration were validated in Caco2 cells. Results: A prognostic signature consisting of seven AS events (PDHA1-88633-ES, KIAA1522-1632-AP, TATDN1-85088-ES, PRMT1-51042-ES, VEZT-23786-ES, AIG1-77972-AT, and PHF11-25891-AP) was constructed. Patients in the high-risk score group showed a higher somatic mutation. The genomic instability risk score was an independent variable associated with overall survival (OS), with a hazard ratio of a risk score of 1.537. The area under the curve of receiver operator characteristic curve of the genomic instability risk score in predicting the OS of CRC patients was 0.733. Furthermore, a nomogram was established and could be used clinically to stratify patients to predict prognosis. Patients defined as high-risk by this signature showed a lower proportion of eosinophils than the low-risk group. Patients with low risk were more sensitive to anti-CTLA4 immunotherapy. Additionally, HSPA1A and FAM50B were two SF regulating the OS-related AS. Downregulation of HSPA1A and FAM50B inhibited the proliferation and migration of Caco2 cells. Conclusion: We constructed an ideal prognostic signature reflecting the genomic instability and OS of CRC patients. HSPA1A and FAM50B were verified as two important SF regulating the OS-related AS.

Microfluidic Invasion Chemotaxis Platform for 3D Neurovascular Co-Culture

Advances in microfabrication and biomaterials have enabled the development of microfluidic chips for studying tissue and organ models. While these platforms have been developed primarily for modeling human diseases, they are also used to uncover cellular and molecular mechanisms through in vitro studies, especially in the neurovascular system, where physiological mechanisms and three-dimensional (3D) architecture are difficult to reconstruct via conventional assays. An extracellular matrix (ECM) model with a stable structure possessing the ability to mimic the natural extracellular environment of the cell efficiently is useful for tissue engineering applications. Conventionally used techniques for this purpose, for example, Matrigels, have drawbacks of owning complex fabrication procedures, in some cases not efficient enough in terms of functionality and expenses. Here, we proposed a fabrication protocol for a GelMA hydrogel, which has shown structural stability and the ability to imitate the natural environment of the cell accurately, inside a microfluidic chip utilizing co-culturing of two human cell lines. The chemical composition of the synthesized GelMA was identified by Fourier transform infrared spectrophotometry (FTIR), its surface morphology was observed by field emission electron microscopy (FESEM), and the structural properties were analyzed by atomic force microscopy (AFM). The swelling behavior of the hydrogel in the microfluidic chip was imaged, and its porosity was examined for 72 h by tracking cell localization using immunofluorescence. GelMA exhibited the desired biomechanical properties, and the viability of cells in both platforms was more than 80% for seven days. Furthermore, GelMA was a viable platform for 3D cell culture studies and was structurally stable over long periods, even when prepared by photopolymerization in a microfluidic platform. This work demonstrated a viable strategy to conduct co-culturing experiments as well as modeling invasion and migration events. This microfluidic assay may have application in drug delivery and dosage optimization studies.