bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of repeated mammograms to evaluate risk of breast cancer: a systematic review of methods used in the literature
Authors: Anandarajah Akila , Chen Yongzhen , Stoll Carolyn , Hardi Angela , Jiang Shu , Colditz Graham A. 
Published: November 2021

AbstractObjectiveThis systematic review aimed to assess methods used to relate repeated mammographic images to breast cancer risk, including the time from mammogram to diagnosis of breast cancer, and methods for analysis of data from either one or both breasts (averaged or assessed individually).DesignA systematic review was performed.SettingThe databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov were searched through October 2021 to extract published articles in English describing the relationship of change in mammographic features with risk of breast cancer.ParticipantsWomen with mammogram images.Main outcome measureBreast cancer incidence.ResultsTwenty articles were included in the final review. We found that BIRADs and Cumulus were most commonly used for classifying mammographic density and automated assessment was used on more recent digital mammograms. Time between mammograms varied from 1 to median of 4.1 years, and only 9 of the studies used more than 2 mammograms to quantify features. One study used a prediction horizon of 5 and 10 years, one used 5 years only and another 10 years only, while in the others the prediction horizon was not clearly defined with investigators using the next screening mammogram.ConclusionThis review provided an updated overview of the state of the art and revealed research gaps; based on these, we provide recommendations for future studies using repeated measure methods for mammogram images to make the use of accumulating image data. By following these recommendations, we expect to improve risk classification and risk prediction for women to tailor screening and prevention strategies to level of risk.Article summaryStrengths and limitations of the studyTo the best of our knowledge, this is the most recent systematic review on the topic of using multiple mammogram images to define risk of breast cancer.This review was performed strictly following systematic review guidelines including a medical librarian with expertise in searching, multiple independent reviewers involved in study selection and data extraction, and reporting following PRISMA 2020 guidelines.Due to heterogeneity of methods for assessment and classification (categorical and continuous) of mammographic features including breast density and time to breast cancer, we did not perform risk of bias or conduct a meta-analysis.Few studies looked at repeated measures of non-density features.
Selective clonal persistence of human retroviruses in vivo: radial chromatin organization, integration site and host transcription
Authors: Melamed Anat , Fitzgerald Tomas W , Wang Yuchuan , Ma Jian , Birney Ewan , Bangham Charles R M 
Published: November 2021

AbstractThe human retroviruses HTLV-1 and HIV-1 persist in vivo, despite the host immune response and antiretroviral therapy, as a reservoir of latently infected T-cell clones. It is poorly understood what determines which clones survive in the reservoir and which are lost. We compared >160,000 HTLV-1 integration sites from T-cells isolated ex vivo from naturally-infected subjects with >230,000 integration sites from in vitro infection, to identify the genomic features that determine selective clonal survival. Three factors explained >40% of the observed variance in clone survival of HTLV-1 in vivo: the radial intranuclear position of the provirus, its absolute genomic distance from the centromere, and the intensity of host genome transcription flanking the provirus. The radial intranuclear position of the provirus and its distance from the centromere also explained ~7% of clonal persistence of HIV-1 in vivo. Selection for transcriptionally repressive nuclear compartments favours clonal persistence of human retroviruses in vivo.
8 Å structure of the nuclear ring of the Xenopus laevis nuclear pore complex solved by cryo-EM and AI
Authors: Ren He , Tai Linhua , Zhu Yun , Huang Xiaojun , Sun Fei , Zhang Chuanmao 
Published: November 2021

ABSTRACTThe nuclear pore complex (NPC), one of the largest protein complexes in eukaryotes, serves as a physical gate to regulate nucleocytoplasmic transport. Here, we determined the 8 Å resolution cryo-electron microscopic (cryo-EM) structure of the nuclear ring (NR) from the Xenopus laevis NPC, with local resolutions reaching 4.9 Å. With the aid of AlphaFold2, we managed to build a pseudoatomic model of the NR, including the Y complexes and flanking components. In this most comprehensive and accurate model to date, the almost complete Y complex structure exhibits much tighter interaction in the hub region. Each NR asymmetric subunit contains two copies of Y complexes, one copy of Nup205 that connects the Y complexes to the neighbouring complex, one copy of ELYS that stabilizes the long arm region of the inner Y complex, and one copy of newly identified Nup93 that forms a bridge across the stems of Y complexes. These in-depth structural features represent a great advance in understanding the assembly of NPCs.
Discovery of Potent Inhibitors of α-Synuclein Aggregation Using Structure-Based Iterative Learning
Authors: Horne Robert I. , Andrzejewska Ewa , Alam Parvez , Brotzakis Z. Faidon , Srivastava Ankit , Aubert Alice , Nowinska Magdalena , Gregory Rebecca C. , Staats Roxine , Possenti Andrea , Chia Sean , Sormanni Pietro , Ghetti Bernardino , Caughey Byron , Knowles Tuomas P. J. , Vendruscolo Michele 
Published: November 2021

AbstractMachine learning methods hold the promise to reduce the costs and the failure rates of conventional drug discovery pipelines. This issue is especially pressing for neurodegenerative diseases, where the development of disease-modifying drugs has been particularly challenging. To address this problem, we describe here a machine learning approach to identify small molecule inhibitors of α-synuclein aggregation, a process implicated in Parkinson’s disease and other synucleinopathies. Because the proliferation of α-synuclein aggregates takes place through autocatalytic secondary nucleation, we aim to identify compounds that bind the catalytic sites on the surface of the aggregates. To achieve this goal, we use structure-based machine learning in an iterative manner to first identify and then progressively optimize secondary nucleation inhibitors. Our results demonstrate that this approach leads to the facile identification of compounds two orders of magnitude more potent than previously reported ones.
The C. elegans TspanC8 tetraspanin TSP-14 exhibits isoform-specific localization and function
Authors: Liu Zhiyu , Shi Herong , Liu Jun 
Published: November 2021

AbstractTetraspanin proteins are a unique family of highly conserved four-pass transmembrane proteins in metazoans. While much is known about their biochemical properties, the in vivo functions and distribution patterns of different tetraspanin proteins are less understood. Previous studies have shown that two paralogous tetraspanins that belong to the TspanC8 subfamily, TSP-12 and TSP-14, function redundantly to promote both Notch signaling and bone morphogenetic protein (BMP) signaling in C. elegans. TSP-14 has two isoforms, TSP-14A and TSP-14B, where TSP-14B has an additional 24 amino acids at its N-terminus compared to TSP-14A. By generating isoform specific knock-ins and knock-outs using CRISPR, we found that TSP-14A and TSP-14B share distinct as well as overlapping expression patterns and functions. While TSP-14A functions redundantly with TSP-12 to regulate body size and embryonic and vulva development, TSP-14B primarily functions redundantly with TSP-12 to regulate postembryonic mesoderm development. Importantly, TSP-14A and TSP-14B exhibit distinct subcellular localization patterns. TSP-14A is localized apically and on early and late endosomes. TSP-14B is localized to the basolateral cell membrane. We further identified a di-leucine motif within the N-terminal 24 amino acids of TSP-14B that serves as a basolateral membrane targeting sequence, and showed that the basolateral membrane localization of TSP-14B is important for its function. Our work highlights the diverse and intricate functions of TspanC8 tetraspanins in C. elegans, and demonstrates the importance of dissecting the functions of these important proteins in an intact living organism.Author summaryTetraspanin proteins are a unique family of highly conserved four-pass transmembrane proteins in higher eukaryotes. Abnormal expression of certain tetraspanins is associated with various types of diseases, including cancer. Understanding the functions of different tetraspanin proteins in vivo is crucial in deciphering the link between tetraspanins and their associated disease states. We have previously identified two tetraspanins, TSP-12 and TSP-14, that share redundant functions in regulating multiple aspects of C. elegans development. Here we show that TSP-14 has two protein isoforms. Using CRISPR knock-in and knock-out technology, we have found that the two isoforms share unique, as well as overlapping expression patterns and functions. Furthermore, they exhibit distinct subcellular localization patterns. Our work highlights the diverse and intricate functions of tetraspanin proteins in a living multicellular organism, and demonstrates that protein isoforms are another mechanism C. elegans uses to increase the diversity and versatility of its proteome.
First evidence of in vitro cytotoxic effects of marine microlitter on Merluccius merluccius and Mullus barbatus, two Mediterranean commercial fish species
Authors: Miccoli A , Mancini E , Saraceni PR , Della Ventura G , Scapigliati G , Picchietti S 
Published: November 2021

AbstractMarine litter is composed mainly of plastics and is recognized as a serious threats to marine ecosystems. Ecotoxicological approaches have started elucidating the potential severity of microplastics (MPs) in controlled laboratory studies with pristine materials but no information exist on marine environmental microlitter as a whole. Here, we characterized the litter in the coastal Northern Tyrrhenian sea and in the stomach of two fish species of socio-economic importance, and exposed primary cell cultures of mucosal and lymphoid organs to marine microlitter for evaluating possible cytotoxic effects. An average of 0.30 ± 0.02 microlitter items m-3 was found in water samples. μFT-IR analysis revealed that plastic particles, namely HDPE, polyamide and polypropylene were present in 100% and 83.3% of Merluccius merluccius and Mullus barbatus analyzed, which overall ingested 14.67 ± 4.10 and 5.50 ± 1.97 items/individual, respectively. Moreover, microlitter was confirmed as a vector of microorganisms. Lastly, the apical end-point of viability was found to be significantly reduced in splenic cells exposed in vitro to two microlitter conditions. Considering the role of the spleen in the mounting of adaptive immune responses, our results warrant more in-depth investigations for clarifying the actual susceptibility of these two species to anthropogenic microlitter.Highlights0.30 ± 0.02 microlitter items m-3 were found at the surface of coastal Northern Tyrrhenian sea14.67 ± 4.10 and 5.50 ± 1.97 items/individual were retrieved from the stomach of hakes and mulletsThe ingested microlitter contained plastic itemsMicrolitter was validated as a carrier of bacteria, fungi and flagellatesSplenic cells exposed to two microlitter conditions for 72 hours suffered cytotoxicity
Establishment of well-differentiated camelid airway cultures to study Middle East respiratory syndrome coronavirus
Authors: Gultom Mitra , Kratzel Annika , Portmann Jasmine , Stalder Hanspeter , Bätzner Astrid Chanfon , Gantenbein Hans , Gurtner Corinne , Ebert Nadine , Posthaus Horst , Zanolari Patrik , Pfaender Stephanie , Thiel Volker , Dijkman Ronald 
Published: November 2021

AbstractIn 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in Saudi Arabia and was mostly associated with severe respiratory illness in humans. Dromedary camels are the zoonotic reservoir for MERS-CoV. To investigate the biology of MERS-CoV in camelids, we developed a well-differentiated airway epithelial cell (AEC) culture model for Llama glama and Camelus bactrianus. Histological characterization revealed progressive epithelial cellular differentiation with well-resemblance to autologous ex vivo tissues. We demonstrate that MERS-CoV displays a divergent cell tropism and replication kinetics profile in both AEC models. Furthermore, we observed that in the camelid AEC models MERS-CoV replication can be inhibited by both type I and III interferons (IFNs). In conclusion, we successfully established camelid AEC cultures that recapitulate the in vivo airway epithelium and reflect MERS-CoV infection in vivo. In combination with human AEC cultures, this system allows detailed characterization of the molecular basis of MERS-CoV cross-species transmission in respiratory epithelium.
Heritability of hippocampal functional and microstructural organisation
Authors: Bayrak Şeyma , Vos de Wael Reinder , Schaare H. Lina , Hettwer Meike D. , Caldairou Benoit , Bernasconi Andrea , Bernasconi Neda , Bernhardt Boris C. , Valk Sofie L. 
Published: November 2021

AbstractThe hippocampus is a uniquely infolded allocortical structure in the medial temporal lobe that consists of the microstructurally and functionally distinct subregions: subiculum, cornu ammonis, and dentate gyrus. The hippocampus is a remarkably plastic region that is implicated in learning and memory. At the same time it has been shown that hippocampal subregion volumes are heritable, and that genetic expression varies along a posterior to anterior axis. Here, we studied how a heritable, stable, hippocampal organisation may support its flexible function in healthy adults. Leveraging the twin set-up of the Human Connectome Project with multimodal neuroimaging, we observed that the functional connectivity between hippocampus and cortex was heritable and that microstructure of the hippocampus genetically correlated with cortical microstructure. Moreover, both functional and microstructural organisation could be consistently captured by anterior-to-posterior and medial-to-lateral axes across individuals. However, heritability of functional, relative to microstructural, organisation was found reduced, suggesting individual variation in functional organisation of subfields is under low genetic control. Last, we demonstrate that structure and function couple along its genetic axes, suggesting an interplay of stability and plasticity within the hippocampus. Our study provides new insights on the heritability of the hippocampal formation and illustrates how genetic axes may scaffold hippocampal structure and function.
Disentangling the effects of jasmonate and tissue loss on the sex allocation of an annual plant
Authors: Villamil Nora , Sommervogel Benoit , Pannell John R. 
Published: November 2021

AbstractSelection through pollinators plays a major role in the evolution of reproductive traits. However, herbivory can also induce changes in plant sexual expression and sexual systems, potentially influencing conditions governing transitions between sexual systems. Previous work has shown that herbivory has a strong effect on sex allocation in the wind-pollinated annual plantMercurialis annua, likely mediated by resource loss. It is also known that many plants respond to herbivory by inducing signalling, and endogenous responses to it, via the plant hormone jasmonate. Here, we attempt to uncouple the effects of herbivory on sex allocation inM. annuathrough resource limitation (tissue loss) versus plant responses to jasmonate hormone signalling. We used a two-factorial experiment with four treatment combinations: control, herbivory (25% chronic tissue loss), jasmonate, and combined herbivory and jasmonate. We estimated the effects of tissue loss and defence-inducing hormones on reproductive allocation, male reproductive effort, and sex allocation. Tissue loss caused plants to reduce their male reproductive effort, resulting in changes in combined sex allocation. However, application of jasmonate after herbivory reversed its effect on male investment. Our results show that herbivory has consequences on plant sex expression and sex allocation, and that defence-related hormones such as jasmonate can buffer the impacts. We discuss the physiological mechanisms that might underpin the effects of herbivory on sex allocation, and their potential implications for the evolution of plant sexual systems.
A small molecule stabilises the disordered native state of the Alzheimer’s Aβ peptide
Authors: Löhr Thomas , Kohlhoff Kai , Heller Gabriella T. , Camilloni Carlo , Vendruscolo Michele 
Published: November 2021

AbstractThe stabilisation of native states of proteins is a powerful drug discovery strategy. It is still unclear, however, whether this approach can be applied to intrinsically disordered proteins. Here we report a small molecule that stabilises the native state of the Aβ42 peptide, an intrinsically disordered protein fragment associated with Alzheimer’s disease. We show that this stabilisation takes place by a dynamic binding mechanism, in which both the small molecule and the Aβ42 peptide remain disordered. This disordered binding mechanism involves enthalpically favourable local π-stacking interactions coupled with entropically advantageous global effects. These results indicate that small molecules can stabilise disordered proteins in their native states through transient non-specific interactions that provide enthalpic gain while simultaneously increasing the conformational entropy of the proteins.
Biological integrity enhances the qualitative effectiveness of conditional mice-oak mutualisms
Authors: Morán-López Teresa , Sánchez-Dávila Jesús , Torre Ignasi , Navarro-Castilla Alvaro , Barja Isabel , Díaz Mario 
Published: November 2021

AbstractScatter-hoarding decisions by rodents are key for the long-term maintenance of scattered tree populations. Decisions are determined by seed value, competition and predation risk, so that they can be influenced by the integrity of the biological system composed by trees, rodents, ungulate competitors, and rodent predators. We manipulate and model the oak-mice interaction in a Spanish dehesa, an anthropogenic savanna system suffering chronic tree regeneration failure, and quantify the joint effect of intrinsic and extrinsic factors on acorn dispersal effectiveness. First, we conducted a large-scale cafeteria field experiment, where we modified ungulate presence and predation risk, and followed mouse scatter-hoarding decisions under contrasting levels of moonlight and acorn availability. Then, we estimated the net effects of competition and risk by means of transition probability models that simulated mouse scatter-hoarding decisions according to the environmental context. Our results show that suboptimal conditions for mice balance the interaction towards the mutualism as they force mice to forage less efficiently. Under stressful conditions (predation risks and presence of ungulates), lack of antipredatory cover around dehesa trees limited transportation of acorns, but also precluded mice activities outside tree canopies. As a result, post-dispersal predation rates were reduced and large acorns had a higher probability to survive. Our work shows that inter-specific interactions preventing efficient foraging by scatter-hoarders benefitted seed dispersal. Therefore, the maintenance of the full set of producers, consumers, dispersers and predators in ecosystems is key for promoting seed dispersal effectiveness in conditional mutualisms.
Efficient multi-gene expression in cell-free droplet microreactors
Authors: Restrepo Sierra Ana Maria , Arold Stefan T. , Grünberg Raik 
Published: November 2021

AbstractCell-free transcription and translation systems promise to accelerate and simplify the engineering of proteins, biological circuits and metabolic pathways. Their encapsulation on microfluidic platforms can generate millions of cell-free reactions in picoliter volume droplets. However, current methods struggle to create DNA diversity between droplets while also reaching sufficient protein expression levels. In particular, efficient multi-gene expression has remained elusive. We here demonstrate that co-encapsulation of DNA-coated beads with a defined cell-free system allows high protein expression while also supporting genetic diversity between individual droplets. We optimize DNA loading on commercially available microbeads through direct binding as well as through the sequential coupling of up to three genes via a solid-phase Golden Gate assembly or BxB1 integrase-based recombineering. Encapsulation with an off-the-shelf microfluidics device allows for single or multiple protein expression from a single DNA-coated bead per 14 pL droplet. We envision that this approach will help to scale up and parallelize the rapid prototyping of more complex biological systems.
Newly recruited intraepithelial Ly6A+CCR9+CD4+T cells protect against enteric viral infection
Authors: Parsa Roham , London Mariya , Rezende de Castro Tiago Bruno , Reis Bernardo , des Amorie Julian Buissant , Smith Jason G. , Mucida Daniel 
Published: November 2021

SummaryThe intestinal epithelium comprises the body’s largest surface exposed to viruses. However, a role for intraepithelial T lymphocytes in resistance against viral infections remain elusive. By fate-mapping T cells recruited to the murine intestinal epithelium, we observed accumulation of CD4+T cells after infection with murine norovirus (MNV) or mouse adenovirus type-2 (AdV), but not after reovirus infection. Intraepithelial CD4+T cells recruited after MNV or AdV infection co-express Ly6A and CCR9, and exhibit T helper 1 and cytotoxic profiles. Although these cells display a diverse TCR repertoire, they conferred protection against AdV and MNV bothin vivoand in an organoid co-culture model in an IFN-γ-dependent manner. Ablation of the T cell receptor (TCR) or the transcription factor ThPOK in CD4+T cells prior to infection prevented viral control, while TCR ablation during infection did not impact viral clearance. These results uncover a protective role for intraepithelial Ly6A+CCR9+CD4+T cells against enteric viruses.