bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression
Authors: Franke Martin , De la Calle-Mustienes Elisa , Neto Ana , Almuedo-Castillo María , Irastorza-Azcarate Ibai , Acemel Rafael D. , Tena Juan J. , Santos-Pereira José M. , Gómez-Skarmeta José L. 
Published: September 2021

AbstractCoordinated chromatin interactions between enhancers and promoters are critical for gene regulation. The architectural protein CTCF mediates chromatin looping and is enriched at the boundaries of topologically associating domains (TADs), which are sub-megabase chromatin structures. In vitro CTCF depletion leads to a loss of TADs but has only limited effects over gene expression, challenging the concept that CTCF-mediated chromatin structures are a fundamental requirement for gene regulation. However, how CTCF and a perturbed chromatin structure impacts gene expression during development remains poorly understood. Here we link the loss of CTCF and gene regulation during patterning and organogenesis in a ctcf knockout zebrafish model. CTCF absence leads to loss of chromatin structure and affects the expression of thousands of genes, including many developmental regulators. Our results demonstrate the essential role of CTCF in providing the structural context for enhancer-promoter interactions, thus regulating developmental genes.
The Warburg effect is necessary to promote glycosylation in the blastema during zebrafish tail regeneration
Authors: Sinclair Jason W. , Hoying David R. , Bresciani Erica , Nogare Damian Dalle , Needle Carli D. , Berger Alexandra , Wu Weiwei , Bishop Kevin , Elkahloun Abdel G. , Chitnis Ajay , Liu Paul , Burgess Shawn M. 
Published: September 2021

AbstractThroughout their lifetime, fish maintain a high capacity for regenerating complex tissues after injury. We utilized a larval tail regeneration assay in the zebrafish Danio rerio, which serves as an ideal model of appendage regeneration due to its easy manipulation, relatively simple mixture of cell types, and superior imaging properties. Regeneration of the embryonic zebrafish tail requires development of a blastema, a mass of dedifferentiated cells capable of replacing lost tissue, a crucial step in all known examples of appendage regeneration. Using this model, we show that tail amputation triggers an obligate metabolic shift to promote glucose metabolism during early regeneration similar to the Warburg effect observed in tumor forming cells. Inhibition of glucose metabolism did not affect the overall health of the embryo but completely blocked the tail from regenerating after amputation due to the failure to form a functional blastema. We performed a time series of single-cell RNA sequencing on regenerating tails with and without inhibition of glucose metabolism. We demonstrated that metabolic reprogramming is required for sustained TGF-β signaling and blocking glucose metabolism largely mimicked inhibition of TGF-β receptors, both resulting in an aberrant blastema. Finally, we showed using genetic ablation of three possible metabolic pathways for glucose, that metabolic reprogramming is required to provide glucose specifically to the hexosamine biosynthetic pathway while neither glycolysis nor the pentose phosphate pathway were necessary for regeneration.
Development and testing of a novel image analysis algorithm for descriptive evaluation of shape change of a shrinkable soft material
Authors: Stienkijumpai Pinpinat , Jinorose Maturada , Devahastin Sakamon 
Published: September 2021

AbstractSoft material can undergo non-uniform deformation or change of shape upon processing. Identifying shape and its change is nevertheless not straightforward. In this study, novel image-based algorithm that can be used to identify shapes of input images and at the same time classify non-uniform deformation into various patterns, i.e., swelling/shrinkage, horizontal and vertical elongations/contractions as well as convexity and concavity, is proposed. The algorithm was first tested with computer-generated images and later applied to agar cubes, which were used as model shrinkable soft material, undergoing drying at different temperatures. Shape parameters and shape-parameter based algorithm as well as convolutional neural networks (CNNs) either incorrectly identified some complicated shapes or could only identify the point where non-uniform deformation started to take place; CNNs lacked ability to describe non-uniform deformation evolution. Shape identification accuracy of the newly developed algorithm against computer-generated images was 65.88%, while those of the other tested algorithms ranged from 34.76 to 97.88%. However, when being applied to the deformation of agar cubes, the developed algorithm performed superiorly to the others. The proposed algorithm could both identify the shapes and describe their changes. The interpretation agreed well with that via visual observation.
Analysis of the signal cross talk via CCL26 in the tumor microenvironment in osteosarcoma
Authors: Kawano Masanori , Iwasaki Tatsuya , Itonaga Ichiro , Kubota Yuta , Tanaka Kazuhiro , Tsumura Hiroshi 
Published: September 2021

AbstractInteraction with surrounding healthy cells plays a major role in the growth and metastasis of osteosarcoma. In this study, we hypothesized that humoral factors, which do not require direct contact with cells, are involved in the interaction between osteosarcoma and the surrounding cells. We identified the humoral factor involved in the association between tumor cells and surrounding normal cells using a co-culture model and investigated the significance of our findings. When human osteosarcoma cells (MG63) and human mesenchymal stem cells (hMSCs) were co-cultured and comprehensively analyzed for changes in each culture group, we found that the expression of chemokine (CC motif) ligand 26 (CCL26) was significantly enhanced. We also analyzed the changes in cell proliferation in co-culture, enhanced interaction with administration of recombinant CCL26 (rCCL26), reduced interaction with administration of anti-CCL26 antibodies, changes in invasive and metastatic abilities. CCL26 levels, motility, and invasive capability increased in the co-culture group and the group with added rCCL26, compared to the corresponding values in the MG63 single culture group. In the group with added CCL26 neutralizing antibodies, CCL26 level decreased in both the single and co-culture groups, and motility and invasive ability were also reduced. In a nude mice lung metastasis model, the number of lung metastases increased in the co-culture group and the group with added rCCL26, whereas the number of tumors were suppressed in the group with added neutralizing antibodies compared to those in the MG63 alone. This study identified a possible mechanism by which osteosarcoma cells altered the properties of normal cells to favorably change the microenvironment proximal to tumors and to promote distant metastasis.
The time course of molecular acclimation to seawater in a euryhaline fish
Authors: Bonzi Lucrezia C. , Monroe Alison A. , Lehmann Robert , Berumen Michael L. , Ravasi Timothy , Schunter Celia 
Published: September 2021

AbstractThe Arabian pupfish, Aphanius dispar, is a euryhaline fish inhabiting both inland nearly-freshwater desert ponds and highly saline Red Sea coastal lagoons of the Arabian Peninsula. Desert ponds and coastal lagoons, located respectively upstream and at the mouths of dry riverbeds (“wadies”), have been found to potentially become connected during periods of intense rainfall, which could allow the fish to migrate between these different habitats. Flash floods would therefore flush Arabian pupfish out to sea, requiring a rapid acclimation to a greater than 40 ppt change in salinity. To investigate the molecular pathways of salinity acclimation during such events, a Red Sea coastal lagoon and a desert pond population were sampled, with the latter exposed to a rapid increase in water salinity. Changes in branchial gene expression were investigated via genome-wide transcriptome measurements over time from 6 h to 21 days. The two natural populations displayed basal differences in genes related to ion transport, osmoregulation and immune system functions. These mechanisms were also differentially regulated in seawater transferred fish, revealing their crucial role in long-term adaptation. Other processes were only transiently activated shortly after the salinity exposure, including cellular stress response mechanisms, such as molecular chaperone synthesis and apoptosis. Tissue remodelling processes were also identified as transient, but took place later in the timeline, suggesting their importance to long-term acclimation as they likely equip the fish with lasting adaptations to their new environment. The alterations in branchial functional pathways displayed by Arabian pupfish in response to salinity increases are diverse. These reveal a large toolkit of molecular processes important for adaptation to hyperosmolarity that allow for successful colonization to a wide variety of different habitats.
Genetic predisposition to tinnitus in the UK Biobank population
Authors: Urbanek Madeleine E. , Zuo Jian 
Published: September 2021

AbstractTinnitus, the phantom perception of noise originating from the inner ear, has been reported by 15% of the world’s population, with many patients reporting major deficits to cognition and mood. However, both objective diagnostic tools and targeted therapeutic strategies have yet to be established. To better understand the underlying genes that may preclude tinnitus, we performed a genome-wide association study of the UK Biobank’s 49,960 whole exome sequencing participants to identify any loci strongly associated with tinnitus. We identified 17 suggestive single nucleotide polymorphisms (p < 1e−5) spanning 13 genes in two sex-separated cohorts reporting chronic, bothersome tinnitus (control males n = 7,315, tinnitus males n = 226, control females n = 11,732, tinnitus females n = 300). We also found a significant missense mutation in WDPCP (p = 3.959e−10) in the female cohort, a mutation which has been previously implicated in typical neuronal functioning through axonal migration and structural reinforcement, as well as in Bardet-Biedl syndrome-15, a ciliopathy. Additionally, in situ hybridization in the embryonic and P56 mouse brain demonstrated that the majority of these genes are expressed within the dorsal cochlear nucleus, the region of the brain theorized to initially induce tinnitus. Further RT-qPCR and RNAScope data also reveals this expression pattern. The results of this study indicate that predisposition to tinnitus may span across multiple genomic loci and be established by weakened neuronal circuitry and maladaptive cytoskeletal modifications within the dorsal cochlear nucleus.
Microbial transfers from permanent grassland ecosystems to milk in dairy farms in the Comté cheese area
Authors: Chemidlin Prévost-Bouré N. , Karimi B. , Sadet-Bourgeteau S. , Djemiel C. , Brie M. , Dumont J. , Campedelli M. , Nowak V. , Guyot P. , Letourneur C. , Manneville V. , Gillet F. , Bouton Y. 
Published: September 2021

AbstractThe specificity of dairy Protected Designation of Origin (PDO) products is related to their “terroir” of production. This relationship needs better understanding for efficient and sustainable productions preserving the agroecological equilibrium of agroecosystems, especially grasslands. Specificity of PDO Comté cheese was related to the diversity of natural raw milk bacterial communities, but their sources need to be determined. It is hypothesized that raw milk indigenous microbial communities may originate from permanent grazed grasslands by the intermediate of dairy cows according to the sequence soil–phyllosphere–teat–milk. This hypothesis was evaluated on a 44 dairy farms network across PDO Comté cheese area by characterizing prokaryotic and fungal communities of these compartments by metabarcoding analysis (16S rRNA gene: V3–V4 region, 18S rRNA gene: V7–V8 region). Strong and significant links were highlighted between the four compartments through a network analysis (0.34 < r < 0.58), and were modulated by soil pH, plant diversity and elevation; but also by farming practices: organic fertilization levels, cattle intensity and cow-teat care. This causal relationship suggests that microbial diversity of agroecosystems is a key player in relating a PDO product to its “terroir”; this under the dependency of farming practices. Altogether, this makes the “terroir” even more local and needs to be considered for production sustainability.
A microfluidic approach to rescue ALS motor neuron degeneration using rapamycin
Authors: Chennampally Phaneendra , Sayed-Zahid Ambreen , Soundararajan Prabakaran , Sharp Jocelyn , Cox Gregory A. , Collins Scott D. , Smith Rosemary L. 
Published: September 2021

AbstractTAR DNA-binding protein-43 (TDP-43) is known to accumulate in ubiquitinated inclusions of amyotrophic lateral sclerosis affected motor neurons, resulting in motor neuron degeneration, loss of motor functions, and eventually death. Rapamycin, an mTOR inhibitor and a commonly used immunosuppressive drug, has been shown to increase the survivability of Amyotrophic Lateral Sclerosis (ALS) affected motor neurons. Here we present a transgenic, TDP-43-A315T, mouse model expressing an ALS phenotype and demonstrate the presence of ubiquitinated cytoplasmic TDP-43 aggregates with > 80% cell death by 28 days post differentiation in vitro. Embryonic stem cells from this mouse model were used to study the onset, progression, and therapeutic remediation of TDP-43 aggregates using a novel microfluidic rapamycin concentration gradient generator. Results using a microfluidic device show that ALS affected motor neuron survival can be increased by 40.44% in a rapamycin dosage range between 0.4-1.0 µM.
Green synthesis of carbamates and amides via Cu@Sal-Cs catalyzed C–O and C–N oxidative coupling accelerated by microwave irradiation
Authors: Asadi Mahboubeh , Naimi-Jamal M. Reza , Panahi Leila 
Published: September 2021

AbstractA new nano-scale Cu@salicylaldehyde-modified-chitosan (Cu@Sal-CS) was synthesized through a green, eco-friendly and cost-effective technique. The prepared catalyst was characterized using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), Energy-dispersive X-ray spectroscopy (EDXS), and inductively coupled plasma (ICP) analysis. The synthesized Cu@Sal-CS catalyst indicated its performance in the C–O and C–N oxidative coupling using the reaction of 1,3-dicarbonyl derivatives/2- substituted phenols with amides for the preparation of carbamates, as well as in the reaction of aldehydes and various amines in the synthesis of amides. The significant features of this work are operational simplicity of catalyst synthesis, in situ and new modification method, use of an efficient, recoverable, frequently reused and stable catalyst without any loss of catalytic activity, and high yields of the products in short times.
Trait gradients inform predictions of seagrass meadows changes to future warming
Authors: Pansini Arianna , La Manna Gabriella , Pinna Federico , Stipcich Patrizia , Ceccherelli Giulia 
Published: September 2021

AbstractComparing populations across temperature gradients can inform how global warming will impact the structure and function of ecosystems. Shoot density, morphometry and productivity of the seagrass Posidonia oceanica to temperature variation was quantified at eight locations in Sardinia (western Mediterranean Sea) along a natural sea surface temperature (SST) gradient. The locations are spanned for a narrow range of latitude (1.5°), allowing the minimization of the effect of eventual photoperiod variability. Mean SST predicted P. oceanica meadow structure, with increased temperature correlated with higher shoot density, but lower leaf and rhizome width, and rhizome biomass. Chlorophyll a (Chl-a) strongly impacted seagrass traits independent of SST. Disentangling the effects of SST and Chl-a on seagrass meadow shoot density revealed that they work independently, but in the same direction with potential synergism. Space-for-time substitution predicts that global warming will trigger denser seagrass meadows with slender shoots, fewer leaves, and strongly impact seagrass ecosystem. Future investigations should evaluate if global warming will erode the ecosystem services provided by seagrass meadows.
Long term monitoring of the reproductive behavior of wild Chinese pangolin (Manis pentadactyla)
Authors: Sun Nick Ching-Min , Pei Kurtis Jai-Chyi , Wu Li-Yue 
Published: September 2021

AbstractObservations of Chinese pangolin (Manis pentadactyla) in the wild are extremely rare and challenging because of their nocturnal and cryptic activity patterns and low population density. The present article reported the first field observation in eastern Taiwan, from October 4, 2012 to June 16, 2016, on the reproductive behavior of the Chinese pangolin based on the monitoring of a female (LF28) using radiotelemetry and camera traps. During this period, LF28 aged from 1–4.5 years old and gave two single-births, both took place in early December, at 3 and 4 years old, respectively. We recorded the entire 157 days of the first nursing period from parturition to maternal separation. For the second infant, the gestation period was estimated to be around 150 days based on the evidence that the pregnancy started in early Jul. 2015 and the offspring was born on Dec. 9, 2015. During the entire nursing period, LF28 frequently moved the offspring from one nursing burrow to another staying various durations ranging from 1 day to more than 35 days, and almost all (= 15/16) of these burrows were located in the core (MCP75) of LF28’s home range. Started from the month of parturition and lasting throughout the whole nursing period, different adult males constantly visiting the nursing burrows were recorded. Mating behavior was recorded once outside the burrow in March, which provided evidence of the occurrence of post-partum estrus in this species. Delayed implantation was proposed based on the observation of a several months lag between copulation and the estimated pregnancy initiation date. The present study demonstrated the advantage of using remote technologies to learn the life history of resting fossorial species.
School environment and physical activity in adolescents from São Paulo city
Authors: Ferrari Gerson , Rezende Leandro F. M. , Florindo Alex A. , Mielke Grégore I. , Peres Maria Fernanda Tourinho 
Published: September 2021

AbstractWe examined the association of physical activity (PA) facilities and access to school with total PA and domain-specific PA in adolescents. We enrolled 2610 adolescents (mean: 14.9 years) from Sao Paulo city. The number and presence of sports courts, swimming pools, locker rooms, running/athletics tracks, entrance accessible for student cyclists, bike racks, speed limit signal around the school, and pedestrian crossing were assessed in each school. All participants responded to a questionnaire about frequency and duration of physical education classes, leisure time, and active commuting. Total PA was obtained by adding up all PA domains. Presence of three or more (OR: 1.62; 95% CI: 1.15 to 2.30) sports courts, swimming pool available in usable conditions (OR: 1.45; 95% CI: 1.01 to 2.10), running/athletics tracks (OR: 2.35; 95% CI: 1.07 to 5.18), and bike racks (OR: 1.38; 95% CI: 1.07 to 1.78) were positively associated with total PA. Number of sports courts, swimming pool available in usable conditions, speed limit signals around the school, and pedestrian crossings were positively associated with physical education classes. The bike racks, speed limit signs around the school, and pedestrian crossings were positively associated with active commuting. School environment was associated with increased PA. Our findings should be considered in future epidemiologic studies and for educational and health policy makers.
B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients
Authors: Tanaka Asuka , Ide Kentaro , Tanaka Yuka , Ohira Masahiro , Tahara Hiroyuki , Ohdan Hideki 
Published: September 2021

AbstractPretransplant desensitization with rituximab has been applied to preformed donor-specific anti-human leukocyte antigen antibody (DSA)-positive recipients for elimination of preformed DSA. We investigated the impact of pretransplant desensitization with rituximab on anti-donor T cell responses in DSA-positive transplant recipients. To monitor the patients’ immune status, mixed lymphocyte reaction (MLR) assays were performed before and after desensitization with rituximab. Two weeks after rituximab administration, the stimulation index (SI) of anti-donor CD4+T cells was significantly higher in the DSA-positive recipients than in the DSA-negative recipients. To investigate the mechanisms of anti-donor hyper responses of CD4+T cells after B cell depletion, highly sensitized mice models were injected with anti-CD20 mAb to eliminate B cells. Consistent with clinical observations, the SI values of anti-donor CD4+T cells were significantly increased after anti-CD20 mAb injection in the sensitized mice models. Adding B cells isolated from untreated sensitized mice to MLR significantly inhibited the enhancement of anti-donor CD4+T cell response. The depletion of the CD5+B cell subset, which exclusively included IL-10-positive cells, from the additive B cells abrogated such inhibitory effects. These findings demonstrate that IL-10+CD5+B cells suppress the excessive response of anti-donor CD4+T cells responses in sensitized recipients.
FBW7 couples structural integrity with functional output of primary cilia
Authors: Petsouki Eleni , Gerakopoulos Vasileios , Szeto Nicholas , Chang Wenhan , Humphrey Mary Beth , Tsiokas Leonidas 
Published: September 2021

AbstractStructural defects in primary cilia have robust effects in diverse tissues and systems. However, how disorders of ciliary length lead to functional outcomes are unknown. We examined the functional role of a ciliary length control mechanism of FBW7-mediated destruction of NDE1, in mesenchymal stem cell (MSC) differentiation. We show that FBW7 functions as a master regulator of both negative (NDE1) and positive (TALPID3) regulators of ciliogenesis, with an overall positive net effect on primary cilia formation, MSC differentiation to osteoblasts, and bone architecture. Deletion of Fbxw7 suppresses ciliation, Hedgehog activity, and differentiation, which are partially rescued in Fbxw7/Nde1-null cells. We also show that NDE1, despite suppressing ciliogenesis, promotes MSC differentiation by increasing the activity of the Hedgehog pathway by direct binding and enhancing GLI2 activity in a cilia-independent manner. We propose that FBW7 controls a protein-protein interaction network coupling ciliary structure and function, which is essential for stem cell differentiation.