bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ovulation sources coagulation protease cascade and hepatocyte growth factor to support physiological growth and malignant transformation
Authors: Huang Hsuan-Shun , Chen Pao-Chu , Chu Sung-Chao , Lee Ming-Hsun , Huang Chi-Ya , Chu Tang-Yuan 
Published: June 2021

ABSTRACTThe fallopian tube fimbrial epithelium (FTE), which is exposed to the follicular fluid (FF) contents of ovulation, is regarded as the main origin of ovarian high-grade serous carcinoma (HGSC). Previously, we found that growth factors in FF, such as IGF2, are responsible for the malignant transformation of FTE. However, ovulation is a monthly transient event, whereas carcinogenesis requires continuous, long-term exposure. Here, we found the transformation activity of FF sustained for more than 30 days after drainage into the peritoneal fluid (PF). Hepatocyte growth factor (HGF), activated through the ovulation injury-tissue factor–thrombin–HGFA–HGF cleavage cascade confers a sustained transformation activity to FTE, HGSC. Physiologically, the high reserve of the coagulation-HGF cascade sources a sustained level of HGF in PF, then to the blood circulation. This HGF axis promotes the growth of the corpus luteum and repair of tissue injury after ovulation.Graphical AbstractThe fluid content of the ovulating ovarian follicle (follicular fluid [FF]) exerts a long-lasting transformation effect that is sustained after mixing with peritoneal fluid (PF). The coagulation protease cascade and hepatocyte growth factor (HGF) are responsible for the sustained activity. The high abundance of cascade proteins and pro-form HGF activator and HGF in FF/PF supports the constant supply of active-form HGF lasting for a whole month, covering the entire ovulation cycle. This sustained HGF activity promotes the proliferative repair of the ovarian surface and fallopian tube fimbrial epithelia as well as the growth of the corpus luteum. The same activity also inadvertently promotes the malignant transformation of the fimbrial epithelium, high-grade serous carcinoma, and epithelial ovarian cancer. In addition to the peritoneal cavity, ovulation sources HGF to blood circulation, which may serve an endocrine role.HIGHLIGHTOvulatory follicular fluid (FF) exerts a long-lasting transformation activity covering throughout the ovulation cycle.The ovulation injury-coagulation proteases-hepatocyte growth factor (HGF) cascade is responsible for the sustained activity.Ovulation sources HGF into the peritoneal cavity, then into the blood circulation.This coagulation-HGF cascade promotes the transformation of fallopian tube epithelial cells and ovarian cancer cells.Physiologically, it promotes the growth of the corpus luteum and injured epithelium after ovulation.
Decline in constitutive proliferative activity in the zebrafish retina with ageing
Authors: Hernández-Núñez Ismael , Quelle-Regaldie Ana , Sánchez Laura , Adrio Fátima , Candal Eva , Barreiro-Iglesias Antón 
Published: June 2021

AbstractIt is largely assumed that the teleost retina shows continuous and active proliferative and neurogenic activity throughout life. But when deepening in the teleost literature one finds that assumptions about a highly active and continuous proliferation in the adult retina are based on studies in which proliferation was not quantified in a comparative way at the different life stages or was mainly studied in juveniles/young adults. Here, we performed a systematic and comparative study of the constitutive proliferative activity of the retina from early developing (2 days post-fertilization) to aged (up to 3-4 years post-fertilization) zebrafish. Mitotic activity and cell cycle progression were analyzed by using immunofluorescence against pH3 and PCNA, respectively. We observed a decline in cell proliferation in the retina with ageing, even despite the occurrence of a wave of secondary proliferation during sexual maturation. During this wave of secondary proliferation the distribution of proliferating and mitotic cells changes from the inner to the outer nuclear layer in the central retina. Importantly, in aged zebrafish there is a virtual disappearance of mitotic activity. Our results showing a decline in proliferative activity of the zebrafish retina with ageing are of crucial importance since it is generally assumed that the fish retina has continuous proliferative activity throughout life.
Modulation of RecFORQ- and RecA-mediated homologous recombination inEscherichia coliby isoforms of translation initiation factor IF2
Authors: Mallikarjun Jillella , SaiSree L , Himabindu P , Anupama K , Reddy Manjula , Gowrishankar J 
Published: June 2021

AbstractHomologous recombination (HR) is critically important for chromosomal replication as well as DNA damage repair in all life forms. InEscherichia coli, the process of HR is comprised of (i) two parallel pre-synaptic pathways that are mediated, respectively, by proteins RecB/C/D and RecF/O/R/Q; (ii) a synaptic step mediated by RecA that leads to generation of Holliday junctions (HJs); and (iii) post-synaptic steps mediated sequentially by HJ-acting proteins RuvA/B/C followed by proteins PriA/B/C of replication restart. Combined loss of RuvA/B/C and a DNA helicase UvrD is synthetically lethal, which is attributed to toxicity caused by accumulated HJs since viability in these double mutant strains is restored by removal of the pre-synaptic or synaptic proteins RecF/O/R/Q or RecA, respectively. Here we show that, as in ΔuvrDstrains,ruvmutations confer synthetic lethality in cells deficient for transcription termination factor Rho, and that loss of RecFORQ pre-synaptic pathway proteins or of RecA suppresses this lethality. Furthermore, loss of IF2-1 (which is one of three isoforms [IF2-1, IF2-2, and IF2-3] of the essential translation initiation factor IF2 that are synthesized from three in-frame initiation codons ininfB) also suppresseduvrD-ruvandrho-ruvlethalities, whereas deficiency of IF2-2 and IF2-3 exacerbated the synthetic defects. Our results suggest that Rho deficiency is associated with an increased frequency of HR that is mediated by the RecFORQ pathway along with RecA. They also lend support to earlier reports that IF2 isoforms participate in DNA transactions, and we propose that they do so by modulation of HR functions.ImportanceThe process of homologous recombination (HR) is important for maintenance of genome integrity in all cells. InEscherichia coli, the RecA protein is a critical participant in HR, which acts at a step common to and downstream of two HR pathways mediated by the RecBCD and RecFOR proteins, respectively. In this study, an isoform (IF2-1) of the translation initiation factor IF2 has been identified as a novel facilitator of RecA’s function in vivo during HR.
CHD4 conceals aberrant CTCF-binding sites at TAD interiors by regulating chromatin accessibility in mESCs
Authors: Han Sungwook , Lee Hosuk , Lee Andrew J. , Kim Seung-Kyoon , Jung Inkyung , Koh Gou Young , Kim Tae-Kyung , Lee Daeyoup 
Published: June 2021

AbstractCTCF plays a critical role in the 3D chromatin organization by determining the TAD borders. Although CTCF primarily binds at the TAD borders, there also exist putative CTCF-binding sites within TADs, which are spread throughout the genome by retrotransposition. However, the detailed mechanism responsible for masking these putative CTCF-binding sites remains elusive. Here, we show that the ATP-dependent chromatin remodeler, CHD4, regulates chromatin accessibility to conceal aberrant CTCF-binding sites embedded in H3K9me3-enriched heterochromatic B2 SINEs in mouse embryonic stem cells (mESCs). Upon CHD4 depletion, these aberrant CTCF-binding sites become accessible, and aberrant CTCF recruitment occurs at the TAD interiors, resulting in disorganization of the local TADs. Furthermore, RNA-binding intrinsically disordered domains of CHD4 is required to prevent the aberrant CTCF bindings. Lastly, CHD4 is required for the repression of B2 SINE transcripts. These results highlight the CHD4-mediated mechanism that safeguards the appropriate CTCF bindings and associated TAD organizations in mESCs.
High-speed multifocus phase imaging in thick tissue
Authors: Xiao Sheng , Zheng Shuqi , Mertz Jerome 
Published: June 2021

AbstractPhase microscopy is widely used to image unstained biological samples. However, most phase imaging techniques require transmission geometries, making them unsuited for thick sample applications. Moreover, when applied to volumetric imaging, phase imaging generally requires large numbers of measurements, often making it too slow to capture live biological processes with fast 3D index-of-refraction variations. By combining oblique back-illumination microscopy and a z-splitter prism, we perform phase imaging that is both epi-mode and multifocus, enabling high-speed 3D phase imaging in thick, scattering tissues with a single camera. We demonstrate here 3D qualitative phase imaging of blood flow in chick embryos over a field of view of 546 × 546 × 137 μm3 at speeds up to 47 Hz.
Dopamine enhanced auditory perceptual learning in humans via long-term memory consolidation
Authors: Tang Ding-lan , Zhang Jun-Yun , Li Xiaoli , Zhang Yu-Xuan 
Published: June 2021

AbstractDopamine is known to modulate sensory plasticity in animal brain, but how it impacts perceptual learning in humans remains largely unknown. In a placebo-controlled, double-blinded training experiment with young healthy adults (both male and female), oral administration of Madopar, a dopamine precursor, during each of multiple training sessions was shown to enhance auditory perceptual learning, particularly in late training sessions. Madopar also enhanced learning and transfer to working memory when tested outside the time widow of drug effect, which appeared to retain for at least 20 days. To test whether such learning modulation was mediated by the dopaminergic working memory network, the same dopamine manipulation was applied to working memory training, but to little influence on learning or transfer. Further, a neural network model of auditory perceptual learning revealed distinctive behavioural modulation patterns for proposed dopaminergic functions in the auditory cortex: trial-by-trial reinforcement signals (reward/reward prediction error and expected reward) and across-session memory consolidation. Only the memory consolidation simulations matched experimental observations. The results thus demonstrate that dopamine modulates human perceptual learning, mostly likely via enhancing memory consolidation over extended time scales.
From collocations to call-ocations: using linguistic methods to quantify animal call combinations
Authors: Bosshard Alexandra B. , Leroux Maël , Lester Nicholas A. , Bickel Balthasar , Stoll Sabine , Townsend Simon W. 
Published: June 2021

AbstractEmerging data in a range of non-human animal species have highlighted a latent ability to combine certain pre-existing calls together into larger structures. Currently, however, there exists no objective quantification of call combinations. This is problematic because animal calls can co-occur with one another simply through chance alone. One common approach applied in language sciences to identify recurrent word combinations is collocation analysis. Through comparing the co-occurrence of two words with how each word combines with other words within a corpus, collocation analysis can highlight above chance, two-word combinations. Here, we demonstrate how this approach can also be applied to non-human animal communication systems by implementing it on a pseudo dataset. We argue collocation analysis represents a promising tool for identifying non-random, communicatively relevant call combinations in animals.
The water-soluble chitosan derivative, N-methylene phosphonic chitosan, is an effective fungicide against the phytopathogen Fusarium eumartii
Authors: Mesas Florencia Anabel , Terrile María Cecilia , Silveyra María Ximena , Zuñiga Adriana , Rodriguez María Susana , Casalongué Claudia Anahí , Mendieta Julieta Renée 
Published: June 2021

AbstractChitosan has been considered an environmental-friendly polymer. However, its use in agriculture has not been extended yet due to its relatively low solubility in water. In an attempt to improve such chemical characteristics, a chitosan-derivative prepared by adding a phosphonic group to chitosan N-methylene phosphonic chitosan, NMPC, was obtained from shrimp fishing industry waste from Argentinean Patagonia. This study showed that NMPC had a fungicidal effect on the phytopathogenic fungus Fusarium solani f. sp. eumartii (F. eumartii). NMPC inhibited F. eumartti mycelial growth and spore germination with low IC50 values. In vivo studies showed that NMPC affected fungal membrane permeability, ROS production, and cell death. NMPC also exerted antifungal effects against two other phytopathogens, Botrytis cinerea, and Phytophthora infestans. NMPC did not affect tomato cell viability at the same doses applied to these phytopathogens. Furthermore, the selective cytotoxicity of NMPC could give it added value in its application as an antimicrobial agent in agriculture.
Destructive and constructive cheater suppression through quorum sensing
Authors: Moffett Alexander S. , Thomas Peter J. , Hinczewski Michael , Eckford Andrew W. 
Published: June 2021

AbstractThe evolutionary consequences of quorum sensing in regulating bacterial cooperation are not fully understood. In this study, we reveal unexpected consequences of regulating public good production through quorum sensing on bacterial population dynamics, showing that quorum sensing can be a collectively harmful alternative to unregulated production. We analyze a birth-death model of bacterial population dynamics accounting for public good production and the presence of non-producing cheaters. Our model demonstrates that when demographic noise is a factor, the consequences of controlling public good production according to quorum sensing depend on the cost of public good production and the presence of non-public fitness benefits. When public good production is inexpensive, quorum sensing is a destructive alternative to unconditional production, in terms of the mean population extinction time. When costs are higher, quorum sensing becomes a constructive strategy for the producing strain, both stabilizing cooperation and decreasing the risk of population extinction.
Neural event segmentation of continuous experience in human infants
Authors: Yates Tristan S. , Skalaban Lena J. , Ellis Cameron T. , Bracher Angelika J. , Baldassano Christopher , Turk-Browne Nicholas B. 
Published: June 2021

AbstractHow infants experience the world is fundamental to understanding their cognition and development. A key principle of adult experience is that, despite receiving continuous sensory input, we perceive this input as discrete events. Here we investigate such event segmentation in infants and how it differs from adults. Research on event cognition in infants often uses simplified tasks in which (adult) experimenters help solve the segmentation problem for infants by defining event boundaries or presenting discrete actions/vignettes. This presupposes which events are experienced by infants and leaves open questions about the principles governing infant segmentation. We take a different, data-driven approach by studying infant event segmentation of continuous input. We collected whole-brain fMRI data from awake infants (and adults, for comparison) watching a cartoon and used a hidden Markov model to identify event states in the brain. We quantified the existence, timescale, and organization of multiple event representations across brain regions. The adult brain exhibited a known hierarchical gradient of event timescales, from shorter events in early visual regions to longer events in later visual and associative regions. In contrast, the infant brain only represented longer events, even in early visual regions, with no timescale hierarchy. The boundaries defining these infant events only partially overlapped with boundaries defined from adult brain activity and behavioral judgments. These findings suggest that events are organized differently in infants, with longer timescales and more stable neural patterns, even in sensory regions. This may indicate greater temporal integration and reduced temporal precision during dynamic, naturalistic perception.Significance StatementSensory input is continuous and yet humans perceive discrete events. This event segmentation has been studied in adults by asking them to indicate natural breaks in continuous input. This classic parsing task is impossible in infants who cannot understand or follow instructions. We circumvent this barrier by testing how the infant brain parses. We applied a computational model to rare awake fMRI data from infants to identify how their brains transitioned between stable states during a cartoon. Whereas adults showed a gradient in event timescales, from shorter events in sensory regions to longer events in associative regions, infants persistently segmented fewer, longer events across the cortical hierarchy. These findings provide new neuroscientific insight into how infants represent their environment.
Enrichment of SARM1 alleles encoding variants with constitutively hyperactive NADase in patients with ALS and other motor nerve disorders
Authors: Gilley Jonathan , Jackson Oscar , Pipis Menelaos , Estiar Mehrdad A. , Al-Chalabi Ammar , Danzi Matt C. , van Eijk Kristel R. , Goutman Stephen A. , Harms Matthew B. , Houlden Henry , Iacoangeli Alfredo , Kaye Julia , Lima Leandro ,   Queen Square Genomics, Ravits John , Rouleau Guy A. , Schüle Rebecca , Xu Jishu , Züchner Stephan , Cooper-Knock Johnathan , Gan-Or Ziv , Reilly Mary M. , Coleman Michael P. 
Published: June 2021

ABSTRACTSARM1, a protein with critical NADase activity, is a central executioner in a conserved programme of axon degeneration. We report seven rare missense or in-frame microdeletion human SARM1 variant alleles in patients with amyotrophic lateral sclerosis (ALS) or other motor nerve disorders that alter the SARM1 auto-inhibitory ARM domain and constitutively hyperactivate SARM1 NADase activity. The constitutive NADase activity of these seven variants is similar to that of SARM1 lacking the entire ARM domain and greatly exceeds the activity of wild-type SARM1, even in the presence of nicotinamide mononucleotide (NMN), its physiological activator. This rise in constitutive activity alone is enough to promote neuronal degeneration in response to otherwise non-harmful, mild stress. Importantly, these strong gain-of-function alleles are completely patient-specific in the cohorts studied and show a highly significant association with disease at the single gene level. These findings of disease-associated coding variants that alter SARM1 function build on previously reported genome-wide significant association with ALS for a neighbouring, more common SARM1 intragenic single nucleotide polymorphism (SNP) to support a contributory role of SARM1 in these disorders. A broad phenotypic heterogeneity and variable age-of-onset of disease among patients with these alleles also raises intriguing questions about the pathogenic mechanism of hyperactive SARM1 variants.
Cellular electron tomography of the apical complex in the apicomplexan parasite Eimeria tenella shows a highly organised gateway for regulated secretion
Authors: Burrell Alana , Marugan-Hernandez Virginia , Moreira-Leite Flavia , Ferguson David J P , Tomley Fiona M , Vaughan Sue 
Published: June 2021

AbstractThe apical complex of apicomplexan parasites is essential for host cell invasion and intracellular survival and as the site of regulated exocytosis from specialised secretory organelles called rhoptries and micronemes. Despite its importance, there is little data on the three-dimensional organisation and quantification of these organelles within the apical complex or how they are trafficked to this specialised region of plasma membrane for exocytosis. In coccidian apicomplexans there is an additional tubulin-containing hollow barrel structure, the conoid, which provides a structural gateway for this specialised secretion. Using a combination of cellular electron tomography and serial block face-scanning electron microscopy (SBF-SEM) we have reconstructed the entire apical end of Eimeria tenella sporozoites. We discovered that conoid fibre number varied, but there was a fixed spacing between fibres, leading to conoids of different sizes. Associated apical structures varied in size to accommodate a larger or smaller conoid diameter. However, the number of subpellicular microtubules on the apical polar ring surrounding the conoid did not vary, suggesting a control of apical complex size. We quantified the number and location of rhoptries and micronemes within cells and show a highly organised gateway for trafficking and docking of rhoptries, micronemes and vesicles within the conoid around a set of intra-conoidal microtubules. Finally, we provide ultrastructural evidence for fusion of rhoptries directly through the parasite plasma membrane early in infection and the presence of a pore in the parasitophorous vacuole membrane, providing a structural explanation for how rhoptry proteins (ROPs) may be trafficked between the parasite and the host cytoplasm.SignificanceApicomplexan parasites cause a wide range of human and animal diseases. The apical complex is essential for motility, host cell invasion and intracellular survival within a specialised vacuole called the parasitophorous vacuole. We know that molecules important for all of these processes are secreted from the apical complex via a set of secretory organelles and there is even evidence that some parasite molecules can enter the host cell from the parasitohorous vacuole, but there is little understanding of exactly how this occurs. Here we have used three dimensional electron microscopy to reconstruct the entire apical end of the parasite and whole individual parasites. Our results provide important insights into the structural organisation and mechanisms for delivery of parasite molecules via this important area of the cell.