bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Physical Exercise and Cardiovascular Adaptation Monitoring in Pregnancy (PE-CAMP) Randomised Controlled Trial Protocol
Authors: Roldan-Reoyo O. , Mackintosh K A. , McNarry M A. , Jones S. , Emery S. , Uzun O. , Lewis M J. 
Published: April 2022

ABSTRACTBackgroundExercise can be beneficial to cardiovascular system function, but its influence during pregnancy is less well understood. Heterogeneity in research studies has led to a lack of consensus on whether physical exercise during pregnancy can elicit cardiovascular adaptations during a period in which the cardiovascular system is already being challenged. Furthermore, little research has been conducted regarding the influence of physical exercise on foetal heart rate (FHR). This paper presents the protocol for a randomised controlled trial which will evaluate the influence of supervised antenatal physical exercise on cardiovascular adaptations during and after pregnancy, as well as the FHR response to acute and chronic maternal exercise.MethodsThe PE-CAMP Study (Physical Exercise and Cardiovascular Adaptation Monitoring in Pregnancy) is a randomised controlled trial (RCT) in which pregnant women will be randomised into an intervention group (INT), which attended supervised physical exercise programme up to three days per week, or a comparison group (COMP) which followed standard health care. All participants were assessed at three time-points i) 18-22 weeks pregnant, time-point 1; ii) 33-37 weeks pregnant, time-point 2; and iii) 12-16 weeks postnatal, time-point 3. A standardised experimental protocol was used for data collection, including body composition assessment, upper-body flexibility and strength assessment, physical activity assessment via questionnaires and acceletometry, and haemodynamic and cardiovascular evaluation before, during and after an acute 10-minute exercise bout. Foetal heart rate will be assessed at the time-point 2 before, during and after acute exercise.DiscussionAlthough it is necessary and informative to continue investigating the effects of exercise on maternal cardiac and haemodynamic responses using specific laboratory-based tests, it is also critical to evaluate these influences during activities that are more achievable and realistic for pregnant women. The PE-CAMP study will provide data on the cardiac and haemodynamic responses to a typical acute bout of exercise, which could help inform future decisions and policies on maternal exercise prescription made by maternity healthcare providers and exercise professionals.Clinical Trials Registration NumberNCT03748888
Defining the age-dependent and tissue-specific circadian transcriptome in male mice
Authors: Wolff Christopher A. , Gutierrez-Monreal Miguel A. , Meng Lingsong , Zhang Xiping , Douma Lauren G. , Costello Hannah M. , Douglas Collin M. , Ebrahimi Elnaz , Alava Bryan R. , Morris Andrew R. , Endale Mehari M. , Crislip G. Ryan , Cheng Kit-yan , Schroder Elizabeth A. , Delisle Brian P. , Bryant Andrew J. , Gumz Michelle L. , Huo Zhiguang , Liu Andrew C. , Esser Karyn A. 
Published: April 2022

SUMMARYCellular circadian clocks direct a daily transcriptional program that supports homeostasis and resilience. Emerging evidence supports age-associated changes in circadian functions. To define age-dependent changes at the systems level, we profiled the circadian transcriptome in the hypothalamus, lung, heart, kidney, skeletal muscle, and adrenal gland in 3 age groups. We found age-dependent and tissue-specific clock output changes. Aging reduced the number of rhythmically expressed genes (REGs), indicative of weakened circadian control. Many genes gained rhythmicity in old tissues, reflecting an adaptive response. REGs were enriched for the hallmarks of aging, adding a new dimension to our understanding of aging. Differential gene expression analysis found that there were temporally distinct clusters of genes in tissue-specific manner. Increased daily gene expression variability is a common feature of aged tissues. This novel analysis extends the landscape of the understanding of aging and highlights the impact of aging on circadian clock function and temporal changes in gene expression.HIGHLIGHTS- Rhythmically expressed genes (REGs) in Young, but not Old mice, are enriched for the aging hallmarks across all tissues.- The numbers of REGs decline across all tissues with age implicating the circadian clock in altered homeostasis.- Age- and tissue-specific differentially expressed genes (DEGs) cluster at specific times of the day.- Increase in gene expression variability over a day is a common feature of aging tissues.
Chronic nicotine exposure alters sperm small RNA content in a C57BL/6J mouse model: Implications for multigenerational inheritance
Authors: Zeid Dana , Gould Thomas J. 
Published: April 2022

ABSTRACTMultigenerational inheritance is a non-genomic form of heritability characterized by altered phenotypes in the first generation born from the exposed parent. Multigenerational factors may account for inconsistencies and gaps in heritable nicotine addiction vulnerability. Our lab previously found that F1 offspring of male C57BL/6J mice chronically exposed to nicotine exhibited altered hippocampus functioning and related learning, nicotine-seeking, nicotine metabolism, and basal stress hormones. In an effort to identify germline mechanisms underlying these multigenerational phenotypes, the current study sequenced small RNA extracted from sperm of males chronically administered nicotine using our previously established exposure model. We identified 16 miRNAs whose expression in sperm was dysregulated by nicotine exposure. A literature review of previous research on these transcripts suggested an enrichment for regulation of psychological stress and learning. mRNAs predicted to be regulated by differentially expressed sperm small RNAs were further analyzed using biological enrichment analysis, which also supported enrichment of gene expression pathways involved in hippocampus-dependent learning. Our findings point to links between nicotine-exposed F0 sperm miRNA and altered F1 phenotypes in this multigenerational inheritance model. Specifically, differentially expressed F0 sperm miRNAs may regulate the previously observed changes in F1 learning and stress. These findings provide a valuable foundation for future functional validation of these hypotheses and characterization of mechanisms underlying male-line multigenerational inheritance.
Algorithmic design of 3D wireframe RNA polyhedra
Authors: Elonen Antti , Natarajan Ashwin K. , Kawamata Ibuki , Oesinghaus Lukas , Mohammed Abdulmelik , Seitsonen Jani , Suzuki Yuki , Simmel Friedrich C. , Kuzyk Anton , Orponen Pekka 
Published: April 2022

AbstractWe address the problem of de novo design and synthesis of nucleic acid nanostructures, a challenge that has been considered in the area of DNA nanotechnology since the 1980s and more recently in the area of RNA nanotechnology. Towards this goal, we introduce a general algorithmic design process and software pipeline for rendering 3D wireframe polyhedral nanostructures in single-stranded RNA. To initiate the pipeline, the user creates a model of the desired polyhedron using standard 3D graphic design software. As its output, the pipeline produces an RNA nucleotide sequence whose corresponding RNA primary structure can be transcribed from a DNA template and folded in the laboratory. As case examples, we design and characterize experimentally three 3D RNA nanostructures: a tetrahedron, a bipyramid and a prism. The design software is openly available, and also provides an export of the targeted 3D structure into the oxRNA molecular dynamics simulator for easy simulation and visualization.
Osteoclast-mediated resorption primes the skeleton for successful integration during axolotl limb regeneration
Authors: Riquelme-Guzmán Camilo , Tsai Stephanie L. , Paz Karen Carreon , Nguyen Congtin , Oriola David , Schuez Maritta , Brugués Jan , Currie Joshua D. , Sandoval-Guzmán Tatiana 
Published: April 2022

ABSTRACTEarly events during axolotl limb regeneration include an immune response and the formation of a wound epithelium. These events are linked to a clearance of damaged tissue prior to blastema formation and regeneration of the missing structures. Here, we report the resorption of calcified skeletal tissue as an active, cell-driven and highly regulated event. This process, carried out by osteoclasts, is essential for a successful integration of the newly formed skeleton. Indeed, the extent of resorption is directly correlated with the integration efficiency. Moreover, we identified the wound epithelium as a major regulator of skeletal resorption, likely creating a zone of influence in which signals involved in recruitment/differentiation of osteoclasts are released. Finally, we reported a correlation between resorption and blastema formation, particularly, a coordination of resorption with cartilage condensation. In sum, our results identify resorption as a major event upon amputation, playing a critical role in the overall process of skeletal regeneration.
The molecular architecture of cell cycle arrest
Authors: Stallaert Wayne , Taylor Sovanny R. , Kedziora Katarzyna M. , Johnson Martha S. , Taylor Colin D. , Sobon Holly K. , Young Catherine L. , Limas Juanita C. , Holloway Jonah Varblow , Cook Jeanette Gowen , Purvis Jeremy E. 
Published: April 2022

AbstractThe cellular decision governing the transition between proliferative and arrested states is crucial to the development and function of every tissue. While the molecular mechanisms that regulate the proliferative cell cycle are well established, we know comparatively little about what happens to cells as they diverge into cell cycle arrest. We performed hyperplexed imaging of 49 cell cycle effectors to obtain a map of the molecular architecture that governs cell cycle exit and progression into reversible (“quiescent”) and irreversible (“senescent”) arrest states. Using this map, we found multiple points of divergence from the proliferative cell cycle; identified stress-specific states of arrest; and resolved the molecular mechanisms governing these fate decisions, which we validated by single-cell, time-lapse imaging. Notably, we found that cells can exit into senescence from either G1 or G2; however, both subpopulations converge onto a single senescent state with a G1-like molecular signature. Cells can escape from this “irreversible” arrest state through the upregulation of G1 cyclins. This comprehensive map provides a first glimpse of the overall organization of cell proliferation and arrest.
Regulated use of alternative Transcription Start Sites controls the production of cytosolic or mitochondrial forms of branched-chain aminotransferase in Kluyveromyces marxianus
Authors: Coral-Medina Angela , Fenton Darren A. , Varela Javier , Camarasa Carole , Baranov Pavel V. , Morrissey John P. 
Published: April 2022

ABSTRACTFollowing a whole genome duplication (WGD) event approximately 100 million years ago, the yeast lineage from which the model Saccharomyces cerevisiae derives maintained two copies of genes where it was necessary to synthesise proteoforms with different sub-cellular localisation. In contrast, yeasts that did not undergo the WGD event have a single gene that must encode both proteoforms. We adopted an integrated in silico and experimental approach to study how this is achieved with BAT1, a gene that encodes mitochondrial and cytosolic forms of a branched chain aminotransferase (BCAT) in pre-WGD yeast such as Kluyveromyces marxianus. We determined that condition-specific regulation of alternative transcription sites gives rise to mRNA isoforms that differ at the 5’end and that, when decoded, generate a mitochondrial or cytosolic proteoform. Furthermore, targeted mutants lacking specific transcription factors were generated to establish how this differentiation was regulated. As in S. cerevisiae, Gcn4 and Leu3 activated expression of the mRNA encoding the mitochondrial proteoform under conditions when branched chain amino acid synthesis was required. Unlike S. cerevisiae, however, K. marxianus lacked tight regulation of the mRNA encoding the cytosolic proteoform supporting the hypothesis that maintaining paralogous genes in post-WGD yeasts facilitated development of more sophisticated expression control mechanisms.
Molecular mechanism of Afadin substrate recruitment to the receptor phosphatase PTPRK via its pseudophosphatase domain
Authors: Hay Iain M. , Mulholland Katie E. , Graham Stephen C. , Sharpe Hayley J. , Deane Janet E. 
Published: April 2022

AbstractProtein tyrosine phosphatase receptor-type kappa (PTPRK) is a transmembrane receptor that links extracellular homophilic interactions to intracellular catalytic activity. Previously we showed that PTPRK promotes cell-cell adhesion by selectively dephosphorylating several cell junction regulators including the protein Afadin (Fearnley et al., 2019). Here we demonstrate that Afadin is recruited for dephosphorylation by directly binding to the PTPRK D2 pseudophosphatase domain. We mapped this interaction to a putative coiled coil (CC) domain in Afadin that is separated by more than 100 amino acids from the substrate pTyr residue. We identify the residues that define PTP specificity, explaining how Afadin is selectively dephosphorylated by PTPRK yet not by the closely-related receptor tyrosine phosphatase PTPRM. Our work demonstrates that PTP substrate specificity can be determined by protein-protein interactions distal to the active site. This explains how PTPRK and other PTPs achieve substrate specificity despite a lack of specific sequence context at the substrate pTyr. Furthermore, by demonstrating that these interactions are phosphorylation-independent and mediated via binding to a non-catalytic domain, we highlight how receptor PTPs could function as intracellular scaffolds in addition to catalyzing protein dephosphorylation.
Robust cone-mediated signaling persists late into rod photoreceptor degeneration
Authors: Scalabrino Miranda L. , Thapa Mishek , Chew Lindsey A. , Zhang Esther , Xu Jason , Sampath A.P. , Chen Jeannie , Field Greg D. 
Published: April 2022

AbstractRod photoreceptor degeneration causes deterioration in the morphology and physiology of cone photoreceptors along with changes in retinal circuits. These changes could diminish visual signaling at cone-mediated light levels, thereby limiting the efficacy of treatments such as gene therapy for rescuing normal, cone-mediated vision. However, the impact of progressive rod death on cone-mediated signaling remains unclear. A mouse model of rod degeneration was used to investigate the fidelity of retinal ganglion cell (RGC) signaling throughout disease progression. Despite clear deterioration of cone morphology with rod death, cone-mediated signaling among RGCs remained surprisingly robust: spatiotemporal receptive fields changed little and the mutual information between stimuli and spiking responses was relatively constant. This relative stability held until nearly all rods had died and cones had completely lost well-formed outer segments. Interestingly, RGC information rates were higher and more stable for natural movies than checkerboard noise as degeneration progressed. The main change in RGC responses with photoreceptor degeneration was a decrease in response gain. These results suggest that gene therapies for rod degenerative diseases are likely to successfully prolong cone-mediated vision even if there are changes to cone morphology and density.
Hyperactive somatostatin interneurons near amyloid plaque and cell-type-specific firing deficits in a mouse model of Alzheimer’s disease
Authors: Algamal Moustafa , Russ Alyssa N. , Miller Morgan R. , Hou Steven S. , Maci Megi , Munting Leon P. , Zhao Qiuchen , Gerashchenko Dmitry , Bacskai Brian J. , Kastanenka Ksenia V. 
Published: April 2022

AbstractAlzheimer’s disease (AD) is characterized by synaptic loss and neuronal network dysfunction. These network deficits are mediated by early alterations in neuronal firing rates that coincide with amyloid plaque accumulation. Mounting evidence supports that inhibitory networks are impaired in AD, but the mechanisms driving these inhibitory deficits are poorly understood. Here we use in vivo multiphoton calcium imaging to determine the relationship between amyloid accumulation and the spontaneous activity of excitatory neurons and inhibitory interneurons in an APP/PS1 mouse model of Alzheimer’s disease. We show that somatostatin-expressing (SOM) interneurons are hyperactive, while parvalbumin-expressing interneurons are hypoactive in APP/PS1 mice. Only SOM interneuron hyperactivity correlated with proximity to amyloid plaque. These inhibitory deficits were accompanied by decreased excitatory neurons activity and decreased pairwise activity correlations in APP/PS1 mice. Our study identifies cell-specific interneuronal firing deficits driven by amyloid pathology in APP/PS1 mice and provides new insights for targeting inhibitory circuits in Alzheimer’s disease.
Phenotyping technology for assessing protein content in seaweed by field spectroscopy and a machine learning algorithm
Authors: Shalev Niva Tadmor , Ghermandi Andrea , Tchernov Dan , Shemesh Eli , Israel Alvaro , Brook Anna 
Published: April 2022

AbstractDetermining seaweed protein concentration and the associated phenotype is critical for food industries that require precise tools to moderate concentration fluctuations and attenuate risks. Algal protein extraction and profiling have been widely investigated, but content determination involves a costly, time-consuming, and high-energy, laboratory-based fractionation technique. The present study examines the potential of field spectroscopy technology as a precise, high-throughput, non-destructive tool for on-site detection of red seaweed protein concentration. By using information from a large dataset of 144 Gracilaria sp. specimens, studied in a land-based cultivation set-up, under six treatment regimes during two cultivation seasons, and an artificial neural network, machine learning algorithm and diffuse visible–near infrared reflectance spectroscopy, predicted protein concentrations in the algae were obtained. The prediction results were highly accurate (R2 = 0.95; RMSE = 0.84), exhibiting a high correlation with the analytically determined values. External validation of the model derived from a separate trial, exhibited even better results (R2 = 0.99; RMSE = 0.45). This model, trained to convert phenotypic spectral measurements and pigment intensity into accurate protein content predictions, can be adapted to include diversified algae species and usages.HighlightNon-destructive determination of protein content in the edible red seaweed Gracilaria sp. by in-situ, VIS-NIR spectroscopy and a machine learning algorithm.
Neuropsychological assessments for dementia research in the COVID-19 era: comparing remote and face-to-face testing
Authors: Requena-Komuro Maï-Carmen , Jiang Jessica , Dobson Lucianne , Benhamou Elia , Russell Lucy , Bond Rebecca L , Brotherhood Emilie V , Greaves Caroline , Barker Suzie , Rohrer Jonathan D , Crutch Sebastian J , Warren Jason D , Hardy Chris JD 
Published: April 2022

AbstractObjectivesWe explored whether adapting traditional neuropsychological tests for online administration against the backdrop of COVID-19 was feasible for people with diverse forms of dementia and healthy older controls. We compared face-to-face and remote settings to ascertain whether remote administration affected performance.DesignWe used a longitudinal design for healthy older controls who completed face-to-face neuropsychological assessments between three and four years before taking part remotely. For patients, we used a cross-sectional design, contrasting a prospective remote cohort with a retrospective face-to-face cohort matched in age, education, and disease duration.SettingRemote assessments were performed using video-conferencing and online testing platforms, with participants using a personal computer or tablet and situated in a quiet room in their own home. Face-to-face assessments were carried out in dedicated testing rooms in our research centre.ParticipantsThe remote cohort comprised ten healthy older controls (also seen face-to-face 3-4 years previously) and 25 patients (n=8 Alzheimer’s disease (AD); n=3 behavioural variant frontotemporal dementia (bvFTD); n=4 semantic dementia (SD); n=5 progressive nonfluent aphasia (PNFA); n=5 logopenic aphasia (LPA)). The face-to-face patient cohort comprised 64 patients (n=25 AD; n=12 bvFTD; n=9 SD; n=12 PNFA; n=6 LPA).Primary and secondary outcome measuresThe outcome measures comprised the strength of evidence under a Bayesian analytic framework for differences in performances between face-to-face and remote testing environments on a general neuropsychological (primary outcomes) and neurolingustic battery (secondary outcomes).ResultsThere was evidence to suggest comparable performance across testing environments for all participant groups, for a range of neuropsychological tasks across both batteries.ConclusionsOur findings suggest that remote delivery of neuropsychological tests for dementia research is feasible.Strengths and limitations of this studyMethodological strengths of this study includeDiverse patient cohorts representing rare dementias with specific communication difficultiesSampling of diverse and relevant neuropsychological domainsUse of Bayesian statistics to quantify the strength of evidence for the putative null hypothesis (no effect between remote and face-to-face testing)Limitations includeRelatively small cohort sizesLack of direct head-to-head comparisons of test environment in the same patients