bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicellular dynamics on structured surfaces: Stress concentration is a key to controlling complex microtissue morphology on engineered scaffolds
Authors: Matsuzawa Ryosuke , Matsuo Akira , Fukamachi Shuya , Shimada Sho , Takeuchi Midori , Nishina Takuya , Kollmannsberger Philip , Sudo Ryo , Okuda Satoru , Yamashita Tadahiro 
Published: March 2023

AbstractTissue engineers have utilized a variety of three-dimensional (3D) scaffolds for controlling multicellular dynamics and the resulting tissue microstructures. In particular, cutting-edge microfabrication technologies, such as 3D bioprinting, provide increasingly complex structures. However, unpredictable microtissue detachment from scaffolds, which ruins desired tissue structures, is becoming an evident problem. To overcome this issue, we elucidated the mechanism underlying collective cellular detachment by combining a new computational simulation method with quantitative tissue-culture experiments. We first quantified the stochastic processes of cellular detachment shown by vascular smooth muscle cells on model curved scaffolds and found that microtissue morphologies vary drastically depending on cell contractility, substrate curvature, and cell-substrate adhesion strength. To explore this mechanism, we developed a new particle-based model that explicitly describes stochastic processes of multicellular dynamics, such as adhesion, rupture, and large deformation of microtissues on structured surfaces. Computational simulations using the developed model successfully reproduced characteristic detachment processes observed in experiments. Crucially, simulations revealed that cellular contractility-induced stress is locally concentrated at the cell-substrate interface, subsequently inducing a catastrophic process of collective cellular detachment, which can be suppressed by modulating cell contractility, substrate curvature, and cell-substrate adhesion. These results show that the developed computational method is useful for predicting engineered tissue dynamics as a platform for prediction-guided scaffold design.
Laser-based killing of a macroparasite inside its live invertebrate host
Authors: Musset Olivier , Balourdet Aude , Perrot-Minnot Marie-Jeanne 
Published: March 2023

AbstractWhether host phenotypic alterations induced by parasites are reversible or not is a core issue to understand underlying mechanisms as well as the fitness costs of infection and recovery to the host. Clearing infection is an essential step to address this issue, which turns out to be challenging with endoparasites of large size relative to that of their host. Here, we took advantage of the lethality, contactless and versatility of high-energy laser beam to design such tool, using thorny-headed worms and their amphipod intermediate host as a model system. We show that laser-based de-parasitization can be achieved using blue laser targeting carotenoid pigments inPolymorphus minutusbut not in the larger and less pigmentedPomphorhynchus tereticollis. Using DNA degradation to establish parasite death, we found that 80%P. minutusdied from within-host exposure to 5 pulses of 50 ms duration, 1.4W power and 450 nm wavelength. Survival rate of infected gammarids to laser treatment was higher than uninfected ones (62% and 33% at 11 days after exposure, respectively). The failure to killP. tereticolliswas also observed with nanosecond-green laser, an alternative laser source targeting lipid. We discuss the possible causes of amphipod death following parasite treatment and highlight the perspectives that this technology offers.
Continued dysfunction of capillary pericytes promotes no-reflow after experimental strokein vivo
Authors: Shrouder J , Filser S , Varga DP , Besson-Girard S , Mamrak U , Bulut B , Seker FB , Geserich B , Laredo F , Wehn A , Khalin I , Bayer P , Liesz A , Gökce O , Plesnila N 
Published: March 2023

AbstractIncomplete reperfusion of the microvasculature (“no-reflow”) after ischemic stroke damages salvageable brain tissue. Previous ex-vivo studies suggest pericytes are vulnerable to ischemia and may exacerbate no-reflow, but the viability of pericytes and their association with no-reflow remains underexplored in vivo. Using longitudinalin vivo2-photon single-cell imaging over seven days we show 87% of pericytes constrict during cerebral ischemia, remain constricted post-reperfusion and 50% of the pericyte population are acutely damaged. Moreover, we reveal ischemic pericytes are fundamentally implicated in capillary no-reflow by limiting and arresting blood flow within the first 24 hours post-stroke. Despite sustaining acute membrane damage, we observe up to 80% of cortical pericytes survive ischemia, upregulate unique transcriptomic profiles and replicate. Finally, we demonstrate delayed recovery of capillary diameter by ischemic pericytes after reperfusion predicts vessel reconstriction in the sub-acute phase of stroke. Cumulatively, these findings demonstrate surviving cortical pericytes remain both viable and promising therapeutic targets to counteract no-reflow after ischemic stroke.
Hyperactive Ras disrupts cell size control and a key step in cell cycle entry in budding yeast
Authors: DeWitt Jerry T. , Chinwuba Jennifer C. , Kellogg Douglas R. 
Published: March 2023

AbstractSevere defects in cell size are a nearly universal feature of cancer cells. However, the underlying causes are unknown. A previous study suggested that a hyperactive mutant of yeast Ras (ras2G19V) that is analogous to the human Ras oncogene causes cell size defects, which could provide clues to how oncogenes influence cell size. However, the mechanisms by whichras2G19Vinfluences cell size are unknown. Here, we found thatras2G19Vinhibits a critical step in cell cycle entry, in which an early G1 phase cyclin induces transcription of late G1 phase cyclins. Thus,ras2G19Vdrives overexpression of the early G1 phase cyclin Cln3, yet Cln3 fails to induce normal transcription of late G1 phase cyclins, leading to delayed cell cycle entry and increased cell size.ras2G19Vinfluences transcription of late G1 cyclins via a poorly understood step in which Cln3 inactivates the Whi5 transcriptional repressor. Previous studies found that Ras relays signals via protein kinase A (PKA) in yeast; however,ras2G19Vappears to influence G1 phase cyclin expression via novel PKA-independent signaling mechanisms. Together, the data define new mechanisms by which hyperactive Ras influences cell cycle entry and cell size in yeast. Expression of G1 phase cyclins is also strongly influenced by mammalian Ras via mechanisms that remain unclear. Therefore, further analysis of PKA-independent Ras signaling in yeast could lead to discovery of conserved mechanisms by which Ras family members control expression of G1 phase cyclins.
Stochasticity explains non-genetic inheritance of lifespan and apparent trade-offs between reproduction and ageing
Authors: Drake Elizabeth D , Simons Mirre J P 
Published: March 2023

AbstractStochastic effects are central to the biology and demography of ageing. Genetically identical individuals do not all die at the exact same time but show a distribution of lifespan. Although such effects are appreciated, any cascading effects from stochastic effects of ageing are underappreciated. We show here that genetically identical female flies (Drosophila melanogaster) that live long, produce longer lived daughters. In line with previous work, we also find that daughters born to older mothers are shorter lived, also termed the Lansing effect. We further show that longer-lived flies produce less offspring, suggesting an apparent trade-off due to stochastic effects alone. We explain these effects using an extension of the reliability theory of ageing by dichotomising ageing physiology in reproduction and lifespan supporting units. These simple models reproduce non-genetic inheritance of lifespan, the Lansing effect and trade-offs between reproduction and lifespan. Our work implies that if non-genetic inheritance of lifespan is widespread it explains the generally low heritability of this trait. Furthermore, trade-offs between performance, e.g. reproduction, and lifespan may be less widespread than predicted by evolutionary biology of ageing, stemming from stochasticity rather than differential investment. Anti-ageing treatments therefore come without any unintended costs to other physiology, a perceived risk that limits translation of these treatments to humans.
Photothermally Detected Stimulated Raman Microscopy towards Ultrasensitive Chemical Imaging
Authors: Zhu Yifan , Ge Xiaowei , Ni Hongli , Yin Jiaze , Lin Haonan , Wang Le , Tan Yuying , Prabhu Dessai Chinmayee V. , Cheng Ji-Xin 
Published: March 2023

AbstractStimulated Raman scattering (SRS) microscopy has shown enormous potential in revealing molecular structures, dynamics and couplings in complex systems. However, the sensitivity of SRS is fundamentally limited to milli-molar level due to the shot noise and the small modulation depth. To overcome this barrier, we revisit SRS from the perspective of energy deposition. The SRS process pumps molecules to their vibrationally excited states. The thereafter relaxation heats up the surrounding and induces refractive index changes. By probing the refractive index changes with a laser beam, we introduce stimulated Raman photothermal (SRP) microscopy, where a >500-fold boost of modulation depth is achieved. Versatile applications of SRP microscopy on viral particles, cells, and tissues are demonstrated. SRP microscopy opens a new way to perform vibrational spectroscopic imaging with ultrahigh sensitivity.One-Sentence SummaryWe demonstrate a new spectroscopic imaging method that improves the signal intensity by >500-fold.
Zebrahub – Multimodal Zebrafish Developmental Atlas Reveals the State-Transition Dynamics of Late-Vertebrate Pluripotent Axial Progenitors
Authors: Lange Merlin , Granados Alejandro , VijayKumar Shruthi , Bragantini Jordão , Ancheta Sarah , Santhosh Sreejith , Borja Michael , Kobayashi Hirofumi , McGeever Erin , Solak Ahmet Can , Yang Bin , Zhao Xiang , Liu Yang , Detweiler Angela M. , Paul Sheryl , Mekonen Honey , Lao Tiger , Banks Rachel , Kim Yang-Joon , Jacobo Adrian , Balla Keir , Awayan Kyle , D’Souza Samuel , Haase Robert , Dizeux Alexandre , Pourquie Olivier , Gómez-Sjöberg Rafael , Huber Greg , Serra Mattia , Neff Norma , Pisco Angela Oliveira , Royer Loïc A. 
Published: March 2023

ABSTRACTElucidating the developmental processes of organisms requires a comprehensive understanding of cellular lineages in the spatial, temporal, and molecular domains. In this study, we introduce Zebrahub, a dynamic atlas of zebrafish embryonic development that integrates single-cell sequencing time course data with lineage reconstructions facilitated by light-sheet microscopy. This atlas offers high-resolution and in-depth molecular insights into zebrafish development, achieved through the sequencing of individual embryos across ten developmental stages, complemented by trajectory reconstructions. Zebrahub also incorporates an interactive tool to navigate the complex cellular flows and lineages derived from light-sheet microscopy data, enablingin silicofate mapping experiments. To demonstrate the versatility of our multi-modal resource, we utilize Zebrahub to provide fresh insights into the pluripotency of Neuro-Mesodermal Progenitors (NMPs). Our publicly accessible web-based platform, Zebrahub, is a foundational resource for studying developmental processes at both transcriptional and spatiotemporal levels, providing researchers with an integrated approach to exploring and analyzing the complexities of cellular lineages during zebrafish embryogenesis.
The novel coronary artery disease risk factor ADAMTS-7 modulates atherosclerotic plaque formation by degradation of TIMP-1
Authors: Sharifi M. Amin , Wierer Michael , Dang Tan An , Milic Jelena , Moggio Aldo , Sachs Nadja , von Scheidt Moritz , Hinterdobler Julia , Müller Philipp , Werner Julia , Stiller Barbara , Aherrahrou Zouhair , Erdmann Jeanette , Zaliani Andrea , Graettinger Mira , Reinshagen Jeanette , Gul Sheraz , Gribbon Philip , Maegdefessel Lars , Bernhagen Jürgen , Sager Hendrik B. , Mann Matthias , Schunkert Heribert , Kessler Thorsten 
Published: March 2023

AbstractBackgroundTheADAMTS7locus was genome-wide significantly associated with coronary artery disease (CAD). Lack of the extracellular matrix (ECM) protease ADAMTS-7 was shown to reduce atherosclerotic plaque formation.ObjectiveTo identify molecular mechanisms and downstream targets of ADAMTS-7 mediating risk of atherosclerosis.MethodsTargets of ADAMTS-7 were identified by high-resolution mass spectrometry of atherosclerotic plaques from Apoe-/- and Apoe-/-Adamts7-/- mice. ECM proteins were identified using solubility profiling. Putative targets were validated using immunofluorescence,in vitrodegradation assays, co-immunoprecipitation, and Förster resonance energy transfer (FRET)-based protein-protein interaction assays.ADAMTS7expression was measured in fibrous caps of human carotid artery plaques.ResultsIn humans,ADAMTS7expression was higher in caps of unstable as compared to stable carotid plaques. Compared to Apoe-/- mice, atherosclerotic aortas of Apoe-/- mice lacking Adamts-7 (Apoe-/-Adamts7-/-) contained higher protein levels of tissue inhibitor of metalloproteases 1 (Timp-1). In co-immunoprecipitation experiments, the catalytic domain of ADAMTS-7 bound to TIMP-1, which was degraded in the presence of ADAMTS-7in vitro.ADAMTS-7 reduced the inhibitory capacity of TIMP-1 at its canonical target matrix metalloprotease 9 (MMP-9) As a downstream mechanism, we investigated collagen content in plaques of Apoe-/- and Apoe-/-Adamts7-/- mice after Western diet. Picrosirius red staining of the aortic root revealed less collagen as a readout of higher MMP-9 activity in Apoe-/- as compared to Apoe-/- Adamts7-/- mice. In order to facilitate high-throughput screening for ADAMTS-7 inhibitors with the aim to decrease TIMP-1 degradation, we designed a FRET-based assay targeting the ADAMTS-7 catalytic site.ConclusionADAMTS-7,which is induced in unstable atherosclerotic plaques, decreases TIMP-1 stability reducing its inhibitory effect on MMP-9, which is known to promote collagen degradation and is likewise genome-wide significantly associated with CAD. Disrupting the interaction of ADAMTS-7 and TIMP-1 might be a strategy to increase collagen content and plaque stability for reduction of atherosclerosis-related events.
High Maternal Adiposity During Pregnancy Programs an Imbalance in the Lipidome and Predisposes to Diet-induced Hepatosteatosis in the Offspring
Authors: Scheidl Taylor B. , Wager Jessica L. , Baker Larissa G. , Brightwell Amy L. , Melan Katrina M. , Larion Sebastian , Sarr Ousseynou , Regnault Timothy RH. , Urbanski Stefan J , Thompson Jennifer A. 
Published: March 2023

ABSTRACTBackgroundExposure to high maternal adiposityin uterois a significant risk factor for the later-life development of metabolic syndrome (MetS), including non-alcoholic fatty liver disease (NAFLD). We have previously shown that high pre-pregnancy adiposity programs adipose tissue dysfunction in the offspring, leading to spillover of fatty acids into the circulation, a key pathogenic event in obesity-associated MetS. Herein, we hypothesized that programming of adipose tissue dysfunction in offspring born to overweight dams increases the risk for developing NAFLD.ResultsFemales heterozygous for leptin receptor deficiency (Hetdb) were used as a model of high pre-pregnancy adiposity. Wild-type (Wt) offspring born to Hetdbpregnancies gained significantly more body fat following high fat/fructose diet (HFFD) compared to Wt offspring born to Wt dams. HFFD increased circulating free fatty acids (FFA) in male offspring of control dams, while FFA levels were similar in HFFD-fed offspring from Wt dams compared to CD or HFFD-Wt offspring from Hetdbdams. Despite female-specific protection from diet-induced FFA spillover, both male and female offspring from Hetdb. dams were more susceptible to diet-induced hepatosteatosis. Lipidomic analysis revealed that CD-offspring of overweight dams had decreased hepatic PUFA levels compared to control offspring. Changes to saturated fatty acids (SFA) and thede novolipogenic (DNL) index were diet driven; however, there was a significant effect of the intrauterine environment on FA elongation and Δ9 desaturase activity.ConclusionHigh maternal adiposity during pregnancy programs a susceptibility to diet-induced hepatosteatosis.
Cryo-EM of α-tubulin isotype containing microtubules revealed a contracted structure of α4A/β2A microtubules
Authors: Diao Lei , Zheng Wei , Zhao Qiaoyu , Liu Mingyi , Fu Zhenglin , Zhang Xu , Bao Lan , Cong Yao 
Published: March 2023

AbstractMicrotubules are hollow α/β-tubulin heterodimeric polymers playing critical roles in cells. In vertebrates, both α- and β-tubulin have multiple isotypes encoded by different genes, which are intrinsic factors in regulating microtubule functions. However, structures of microtubules composed of different tubulin isotypes, especially α-tubulin isotypes, remain largely unknown. Here, we purified recombinant tubulin heterodimers composed of different mouse α-tubulin isotypes, including α1A, α1C and α4A, with β-tubulin isotype β2A. We further assembled and determined the cryo-electron microscopy (cryo-EM) structures of α1A/β2A, α1C/β2A, and α4A/β2A microtubules. Our structural analysis demonstrated that α4A/β2A microtubules exhibit a longitudinal contraction between tubulin interdimers compared with α1A/β2A and α1C/β2A microtubules. Collectively, our findings reveal that α-tubulin isotype composition could tune microtubule structures, and also provide evidence for the “tubulin code” hypothesis.
PERK-mediated induction of miR-5p and miR-3p arms of miR-616 regulates cell growth by targeting c-MYC
Authors: Arabkari Vahid , Sultana Afrin , Barua David , Webber Mark , Smith Terry , Gupta Ananya , Gupta Sanjeev 
Published: March 2023

ABSTRACTC/EBP homologous protein (CHOP), also known as DNA damage-inducible transcript 3 (DDIT3), is a member of CCAAT/enhancer-binding protein (C/EBP) family. The expression of CHOP is upregulated during unfolded protein response (UPR), and sustained CHOP activity plays an important role in UPR-induced apoptosis. MicroRNA-616 is localized in an intron of the CHOP gene. However, regulation of miR-616 expression during UPR and its function in breast cancer is not clearly understood. We show that miR-5p/-3p arms of miR-616 are expressed with levels of 5p arm higher than 3p arm. During conditions of UPR, the expression of miR-5p and miR-3p arms of miR-616 and its host gene (CHOP) was concordantly increased primarily in a PERK-dependent manner. We show that ectopic expression of miR-616 significantly suppressed cell growth and colony formation, whereas knockout of miR-616 increased it. We identified that MYC proto-oncogene (c-MYC) gene is repressed during the UPR and targeted by miR-616. Further, we show that expression of miR-616 and CHOP is downregulated in human breast cancer, where expression of miR-616 was associated with poor overall survival (OS) in luminal A subtype and better OS HER2 subtype of breast cancer. In summary, our results suggest a dual function for the DDIT3 locus, where CHOP protein and miR-616 can co-operate to regulate cancer progression.
Hydrogen sulfide small intestinal bacterial overgrowth case registry
Authors: Goldenberg Joshua Z , Nevitt Britta , Wentz Anna E , Bradley Ryan , Siebecker Allison 
Published: March 2023

SummaryBackgroundThere is growing interest in hydrogen sulfide small intestinal bacterial overgrowth (H2S SIBO). However, basic questions including how clinicians are making the diagnosis, what symptoms are present, and what clinicians are using for treatment, remain unanswered.AimsTo address this, we created an online, survey-based, clinical registry of H2S SIBO cases.MethodsParticipants in this study were clinicians diagnosing and treating patients with H2S SIBO and input data on patient presentation, diagnosis, treatment, and treatment response. We describe the population and summarize our results using descriptive statistics. We use Pearson’s chi-squared test and modified Poisson regression in exploratory analyses.Results131 total cases were submitted by 99 providers across a spectrum of health disciplines. The mean patient age was 45.6 (71.4% female). The most common symptoms were bloating (77.0%), constipation (50.8%) and abdominal pain (50.8%). Diagnosis was made based on flatline hydrogen in the 3rd hour of a lactulose breath test (42.5%), symptom presentation (empiric) (31.9%), or H2S levels (25.7%). The most common treatments used were a low sulfur diet (46.6%), oregano (44.0%), and bismuth (39.7%). Fifty-eight percent of cases were responders. Of the most common interventions used, only a low sulfur diet (73% responder; p=0.01) and bismuth (76% responder; p=0.01) were significantly associated with treatment response. Interestingly, response rates differed based on how H2S SIBO was diagnosed, with empiric underperforming flatline diagnoses (relative risk 0.60; p=0.04).ConclusionsThis case registry represents the largest collection of H2S SIBO cases to-date, providing important early descriptive information on this emerging diagnosis.
Gentrification and Food Environments: A Rapid Evidence Assessment
Authors: Gie Simone , Borthwick Fiona 
Published: March 2023

AbstractGentrification is a complex and controversial process, where the influx of new, wealthier residents to previously run-down neighbourhoods brings change such as economic development, infrastructure investments and lower crime rates, but can be to the detriment of the original lower-income residents, who are either displaced, or stay but cannot take advantage of the new opportunities. Understanding how neighbourhood change affects food environments can shed light on the possible causal pathways between gentrification and urban health inequalities. This rapid evidence assessment reviewed evidence on the impact of gentrification on the healthfulness of food environments globally. Ten studies were identified through a systematic keyword search and assessed. We found limited evidence of an effect, with a small, albeit consistent, body of evidence mostly comprised of low- to medium-quality observational studies, all from high-income countries. Most studies examined effects on availability or affordability of food, finding an association between gentrification and increased availability of unhealthy foods, or reduced affordability for original low-income residents.