bluuebunny/crossref_metadata_2025_split huggingface dataset:
OpenSense: An open-source toolbox for Inertial-Measurement-Unit-based measurement of lower extremity kinematics over long durations
Authors: Al Borno Mazen , O’Day Johanna , Ibarra Vanessa , Dunne James , Seth Ajay , Habib Ayman , Ong Carmichael , Hicks Jennifer , Uhlrich Scott , Delp Scott 
Published: July 2021

AbstractBackgroundThe ability to measure joint kinematics in natural environments over long durations using inertial measurement units (IMUs) could enable at-home monitoring and personalized treatment of neurological and musculoskeletal disorders. However, drift, or the accumulation of error over time, inhibits the accurate measurement of movement over long durations. We sought to develop an open-source workflow to estimate lower extremity joint kinematics from IMU data that was accurate, and capable of assessing and mitigating drift.MethodsWe computed IMU-based estimates of kinematics using sensor fusion and an inverse kinematics approach with a constrained biomechanical model. We measured kinematics for 11 subjects as they performed two 10-minute trials: walking and a repeated sequence of varied lower-extremity movements. To validate the approach, we compared the joint angles computed with IMU orientations to the joint angles computed from optical motion capture using root mean square (RMS) difference and Pearson correlations, and estimated drift using a linear regression on each subject’s RMS differences over time.ResultsIMU-based kinematic estimates agreed with optical motion capture; median RMS differences over all subjects and all minutes were between 3-6 degrees for all joint angles except hip rotation and correlation coefficients were moderate to strong (r = 0.60 to 0.87). We observed minimal drift in the RMS differences over ten minutes; the average slopes of the linear fits to these data were near zero (−0.14 to 0.17 deg/min).ConclusionsOur workflow produced joint kinematics consistent with those estimated by optical motion capture, and could mitigate kinematic drift even in the trials of continuous walking without rest, obviating the need for explicit sensor recalibration (e.g. sitting or standing still for a few seconds or zero-velocity updates) used in current drift-mitigation approaches. This could enable long-duration measurements, bringing the field one step closer to estimating kinematics in natural environments.
Optimized nickase- and nuclease-based prime editing in human and mouse cells
Authors: Adikusuma Fatwa , Lushington Caleb , Arudkumar Jayshen , Godahewa Gelshan I. , Chey Yu C.J. , Gierus Luke , Piltz Sandra , Reti Daniel , Wilson Laurence OW. , Bauer Denis C. , Thomas Paul Q. 
Published: July 2021

ABSTRACTPrecise genomic modification using prime editing (PE) holds enormous potential for research and clinical applications. Currently, the delivery of PE components to mammalian cell lines requires multiple plasmid vectors. To overcome this limitation, we generated all-in-one prime editing (PEA1) constructs that carry all the components required for PE, along with a selection marker. We tested these constructs (with selection) in HEK293T, K562, HeLa and mouse embryonic stem (ES) cells. We discovered that PE efficiency in HEK293T cells was much higher than previously observed, reaching up to 95% (mean 67%). The efficiency in K562 and HeLa cells, however, remained low. To improve PE efficiency in K562 and HeLa, we generated a nuclease prime editor and tested this system in these cell lines as well as mouse ES cells. PE-nuclease greatly increased prime editing initiation, however, installation of the intended edits was often accompanied by extra insertions derived from the repair template. Finally, we show that zygotic injection of the nuclease prime editor can generate correct modifications in mouse fetuses with up to 100% efficiency. In summary, PE-nuclease and the PEA1 plasmids provide new tools to generate intended edits with high efficiency.
Associations between Acoustic Features of Maternal Speech and Infants’ Emotion Regulation following a Social Stressor
Authors: Kolacz Jacek , daSilva Elizabeth B. , Lewis Gregory F. , Bertenthal Bennett I. , Porges Stephen W. 
Published: July 2021

AbstractCaregiver voices may provide cues to mobilize or calm infants. This study examined whether maternal prosody predicted changes in infants’ biobehavioral state during the Still Face, a stressor in which the mother withdraws and reinstates social engagement. Ninety-four dyads participated in the study (infant age 4-8 months). Infants’ heart rate and respiratory sinus arrhythmia (measuring cardiac vagal tone) were derived from an electrocardiogram (ECG). Infants’ behavioral distress was measured by negative vocalizations, facial expressions, and gaze aversion. Mothers’ vocalizations were measured with spectral analysis and spectro-temporal modulation using a two-dimensional fast Fourier transformation of the audio spectrogram. High values on the maternal prosody composite were associated with decreases in infants’ heart rate (β=-.26, 95% CI: [-.46, -.05]) and behavioral distress (β=-.20, 95% CI: [-.38, -.02]), and increases in cardiac vagal tone in infants whose vagal tone was low during the stressor (1 SD below mean β=.39, 95% CI: [.06, .73]). High infant heart rate predicted increases in the maternal prosody composite (β=.18, 95% CI: [.03, .33]). These results suggest specific vocal acoustic features of speech that are relevant for regulating infants’ biobehavioral state and demonstrate mother-infant bi-directional dynamics.
Functional constraints on insect immune system components govern their evolutionary trajectories
Authors: Ruzzante Livio , Feron Romain , Reijnders Maarten J.M.F. , Thiébaut Antonin , Waterhouse Robert M. 
Published: July 2021

AbstractThe role of constraints in shaping evolutionary outcomes is often investigated in the contexts of developmental biology and population genetics, in terms of the capacity to generate new variants as well as how selection either limits or promotes consequent phenotypic change. Comparative genomics also recognises the role of constraints, in terms of shaping the evolution of gene and genome architectures, sequence evolutionary rates, and gene gains and losses, as well as on molecular phenotypes. Characterising patterns of genomic change where putative functions and interactions of system components are relatively well-described offers opportunities to explore whether genes with similar or analogous roles exhibit similar evolutionary trajectories, possibly governed by common constraints. Using insect innate immunity as our study system, we hypothesise that quantitative characterisation of gene evolutionary histories can define distinct dynamics associated with different functional roles. We develop metrics that quantify gene evolutionary histories, employ these to characterise evolutionary features of immune gene repertoires, and explore relationships between gene family evolutionary profiles and their roles in immunity to understand how different constraints may relate to distinct dynamics. We identified three main axes of evolutionary trajectories characterised by gene duplication and synteny, maintenance/stability and sequence conservation, and loss and sequence divergence, highlighting similar and contrasting patterns across these axes amongst subsets of immune genes. Our results indicate that where and how genes participate in immune responses limit the range of possible evolutionary scenarios they exhibit. Comparative genomics approaches therefore offer opportunities to characterise how functional constraints on different components of biological systems govern their evolutionary trajectories.
Neutrophil and natural killer cell imbalances prevent muscle stem cell mediated regeneration following murine volumetric muscle loss
Authors: Larouche Jacqueline A. , Kurpiers Sarah J. , Yang Benjamin A. , Davis Carol , Fraczek Paula M. , Hall Matthew , Brooks Susan V. , Shea Lonnie D. , Aguilar Carlos A. 
Published: July 2021

ABSTRACTVolumetric muscle loss (VML) overwhelms the innate regenerative capacity of mammalian skeletal muscle (SkM), leading to numerous disabilities and reduced quality of life. Immune cells are critical responders to muscle injury and guide tissue resident stem cell and progenitor mediated myogenic repair. However, how immune cell infiltration and inter-cellular communication networks with muscle stem cells are altered following VML and drive pathological outcomes remains underexplored. Herein, we contrast the cellular and molecular mechanisms of VML injuries that result in fibrotic degeneration or regeneration of SkM. Following degenerative VML injuries, we observe heightened infiltration of natural killer (NK) cells as well as persistence of neutrophils beyond two weeks post injury. Functional validation of NK cells revealed an antagonistic role on neutrophil accumulation in part via inducing apoptosis and CCR1 mediated chemotaxis. The persistent infiltration of neutrophils in degenerative VML injuries was found to contribute to impairments in muscle stem cell regenerative function, which was also attenuated by transforming growth factor beta 1 (TGFβ1). BlockingTGFβsignaling reduced neutrophil accumulation and fibrosis, as well as improved muscle specific force. Collectively, these results enhance our understanding of immune cell-stem cell crosstalk that drives regenerative dysfunction and provide further insight into possible avenues for fibrotic therapy exploration.SINGLE SENTENCE SUMMARYComparison of muscle injuries resulting in regeneration or fibrosis reveals inter-cellular communication between neutrophils and natural killer cells impacts muscle stem cell mediated repair.
A validation standard for Area of Habitat maps for terrestrial birds and mammals
Authors: Dahal Prabhat R. , Lumbierres Maria , Butchart Stuart H. M. , Donald Paul F. , Rondinini Carlo 
Published: July 2021

AbstractArea of Habitat (AOH) is a deductive model which maps the distribution of suitable habitat at suitable altitudes for a species inside its broad geographical range. AOH maps have been validated using presence-only data for small subsets of species for different taxonomic groups, but no standard validation method exists when absence data are not available. We develop a novel two-step validation protocol for AOH which includes first a model-based evaluation of model prevalence (i.e, the proportion of suitable habitat within a species’ range), and second a validation using species point localities (presence-only) data. We applied the protocol to AOH maps of terrestrial birds and mammals. In the first step we built logistic regression models to predict expected model prevalence (the proportion of the range retained as AOH) as a function of each species’ elevation range, mid-point of elevation range, number of habitats, realm and, for birds, seasonality. AOH maps with large difference between observed and predicted model prevalence were identified as outliers and used to identify a number of sources of systematic error which were then corrected when possible. For the corrected AOH, only 1.7% of AOH maps for birds and 2.3% of AOH maps for mammals were flagged as outliers in terms of the difference between their observed and predicted model prevalence. In the second step we calculated point prevalence, the proportion of point localities of a species falling in pixels coded as suitable in the AOH map. We used 48,336,141 point localities for 4889 bird species and 107,061 point localities for 420 mammals. Where point prevalence exceeded model prevalence, the AOH was a better reflection of species’ distribution than random. We also found that 4689 out of 4889 (95.9%) AOH maps for birds, and 399 out of 420 (95.0%) AOH maps for mammals were better than random. Possible reasons for the poor performance of a small proportion of AOH maps are discussed.
Light and electron microscopy continuum-resolution imaging of 3D cell cultures
Authors: D’Imprima Edoardo , Garcia Montero Marta , Gawrzak Sylwia , Ronchi Paolo , Zagoriy Ievgeniia , Schwab Yannick , Jechlinger Martin , Mahamid Julia 
Published: July 2021

Summary3D cell cultures, in particular organoids, are emerging models to investigate healthy or diseased tissues. Understanding the complex cellular sociology in organoids requires integration of imaging modalities across spatial and temporal scales. We present a multi-scale imaging approach that traverses millimeter-scale live-cell light microscopy to nano-scale volume electron microscopy by performing 3D cell cultures in a single carrier amenable to all imaging steps. This allows to follow organoids growth, probe their morphology with fluorescent markers, identify areas of interest and analyze their 3D ultrastructure. We demonstrate this workflow on mouse and human 3D cultures, and use automated image segmentation to annotate and quantitatively analyze subcellular structures in patient-derived colorectal cancer organoids. Our analyses reveal local organization of diffraction-limited cell junctions in compact and polarized epithelia. The continuum resolution imaging pipeline is thus suited to foster basic and translational organoid research by simultaneously exploiting the advantages of light and electron microscopy.HighlightsEstablishment of 3D cell cultures in sample carriers directly amenable to high-pressure freezing (HPF)3D cell cultures in HPF carriers allow drug treatment and live-cell imagingMulti-scale imaging of 3D cultures from live-cell light microscopy to volume electron microscopyEstablishments of HPF conditions for mouse and patient-derived organoidsDeep-learning automatic segmentation of ultrastructural detail and quantitative data-mining reveal different subcellular organization associated with epithelium polarity
Mitochondrial dysfunction triggers secretion of the immunosuppressive factor α-fetoprotein
Authors: Jett Kimberly A. , Baker Zakery N. , Hossain Amzad , Boulet Aren , Cobine Paul A. , Ghosh Sagnika , Ng Philip , Yilmaz Orhan , Barreto Kris , DeCoteau John , Mochoruk Karen , Ioannou George N. , Savard Christopher , Yuan Sai , Lowden Christopher , Kim Byung-Eun , Cheng Hai-Ying Mary , Battersby Brendan J. , Gohil Vishal M. , Leary Scot C. 
Published: July 2021

AbstractSignaling circuits crucial to systemic physiology are widespread, yet uncovering their molecular underpinnings remains a barrier to understanding the etiology of many metabolic disorders. Here, we identify a copper-linked signaling circuit activated by disruption of mitochondrial function in the murine liver or heart that results in atrophy of the spleen and thymus and causes a peripheral white blood cell deficiency. We demonstrate that the leukopenia is caused by α-fetoprotein, which requires copper and the cell surface receptor CCR5 to promote white blood cell death. We further show that α-fetoprotein expression is upregulated in several cell types upon inhibition of oxidative phosphorylation, including a muscle cell model of Barth syndrome. Collectively, our data argue that α-fetoprotein secreted by bioenergetically stressed tissue suppresses the immune system, an effect which may explain the recurrent infections that are observed in a subset of mitochondrial diseases or in other disorders with mitochondrial involvement.
The number of cytokinesis nodes in mitotic fission yeast scales with cell size
Authors: Sayyad Wasim A. , Pollard Thomas D. 
Published: July 2021

AbstractCytokinesis nodes are assemblies of stoichiometric ratios of proteins associated with the plasma membrane, which serve as precursors for the contractile ring during cytokinesis by fission yeast. The total number of nodes is uncertain, because of the limitations of the methods used previously. Here we used the ∼140 nm resolution of Airyscan confocal microscopy to resolve a large population of small, unitary cytokinesis nodes in 3D reconstructions of whole fission yeast cells. Wild-type fission yeast cells make about 200 unitary cytokinesis nodes early in mitosis. Most, but not all of these nodes condense into a contractile ring. The number of cytokinesis nodes scales with cell size in four strains tested, although wide rga4Δ mutant cells form somewhat fewer cytokinesis nodes than expected from the overall trend. The surface density of Pom1 kinase on the plasma membrane around the equators of cells is similar with a wide range of node numbers, so Pom1 does not control cytokinesis node number. However, varying protein concentrations with the nmt1 promoter showed that the numbers of nodes increase above a baseline of about 200 with the total cellular concentration of either kinase Pom1 or Cdr2.
Socioeconomic determinants of primary school children dropout: a case study of Pakistan
Authors: Ali Kazim , Yaseen Muhammad Rizwan , Makhdum Muhammad Sohail Amjad , Quddoos Abdul , Sardar Azeem 
Published: July 2021

PurposeThe main purpose of this study is to identify the socioeconomic determinants of dropout from primary schools and to give policy suggestions to address the issue.Design/methodology/approachA total of 600 dropout and enrolled respondents were selected from 60 government primary schools of district Chiniot. School heads and parents of dropout children were taken as samples. The results were obtained by employing the Probit regression model.FindingsNumbers of family members, age of the family head, exchange marriage and poverty status have positive relationship with dropout from primary schools. The findings revealed a higher rate of dropout among girls, which is a major cause of concern.Practical implicationsEducation is regarded as a basic human right and a valuable human capital. It is included in Millennium Development Goals to achieve universal primary education and in Sustainable Development Goals as quality education. Underdeveloped countries are facing the problems of high dropout and lack of quality education, especially in Pakistan. These problems need to be addressed to keep pace with developed nations and to meet development goals.Originality/valueIt is recommended that government should create employment opportunities, family planning programs, legislature measures on exchange marriage and child labor. The involvement in co-curricular activities in learning and usage of audio-visual aids in the teaching process can improve the enrollment in the primary schools.
Growth inhibition of phytopathogenic spiroplasmas by membrane‐interactive antimicrobial peptides Novispirin T7 and Caerin 1.1
Authors: Wei Wei , Davis Robert E. , Mowery Joseph D. , Zhao Yan 
Published: July 2021

AbstractSpiroplasma kunkelii and Spiroplasma citri, both helical‐shaped cell wall‐less bacteria, are the causative agents of corn stunt disease and citrus stubborn disease, respectively. Plants exhibiting natural resistance to these phytopathogenic spiroplasmas are currently lacking. Engineering artificial plant resistance using antimicrobial peptides (AMPs) has been conceived as a new approach to control the agronomically important spiroplasmal diseases. In preparation for such task, the present study focused on screening of AMPs that have potentials to curb the growth of S. kunkelii and S. citri. Four AMPs, including Novispirin T7, Caerin 1.1, Tricholongin and Dhvar4, were selected for in vitro growth inhibition test. A liquid assay method was developed for quick qualitative and quantitative evaluations of the AMPs. Our results demonstrated that Novispirin T7 and Caerin 1.1 were able to inhibit the growth of both phytopathogenic spiroplasmas with the efficacy comparable to that of tetracycline. Cell deformations were observed in spiroplasma cultures treated with these two peptides, indicating interactions of the AMPs with the spiroplasma cell membranes. The minimum inhibitory concentrations (MICs) of the AMPs against S. kunkelii and S. citri were determined.
Knowledge, views and expectations for cancer polygenic risk testing in clinical practice: A cross‐sectional survey of health professionals
Authors: Smit Amelia K. , Sharman Ashleigh R. , Espinoza David , Wallingford Courtney , Young Mary‐Anne , Dunlop Kate , Tiller Jane , Newson Ainsley J. , Meiser Bettina , Cust Anne E. , Yanes Tatiane 
Published: July 2021

AbstractPolygenic risk scores (PRS) are becoming increasingly available in clinical practice to evaluate cancer risk. However, little is known about health professionals' knowledge, attitudes, and expectations of PRS. An online questionnaire was distributed by relevant health professional organisations predominately in Australia, Canada and the US to evaluate health professionals' knowledge, views and expectations of PRS. Eligible participants were health professionals who provide cancer risk assessments. Results from the questionnaire were analysed descriptively and content analysis was undertaken of free‐text responses. In total, 105 health professionals completed the questionnaire (genetic counsellors 84%; oncologists 6%; clinical geneticists 4%; other 7%). Although responses differed between countries, most participants (61%) had discussed PRS with patients, 20% had ordered a test and 14% had returned test results to a patient. Confidence and knowledge around interpreting PRS were low. Although 69% reported that polygenic testing will certainly or likely influence patient care in the future, most felt unprepared for this. If scaled up to the population, 49% expect that general practitioners would have a primary role in the provision of PRS, supported by genetic health professionals. These findings will inform the development of resources to support health professionals offering polygenic testing, currently and in the future.
Fish reproductive activity reveals temporal variations predominating spatial heterogeneity in maintaining high functional diversity of a Neotropical reservoir
Authors: Gogola Tatiane Mary , Piana Pitágoras Augusto , da Silva Pedro Rogério Leandro , Topan Dhyego Amilton , Sanches Paulo Vanderlei 
Published: July 2021

AbstractThe reproductive activity of the fish assemblage in a large Neotropical reservoir was evaluated by surveying the occurrence of ichthyoplankton in response to spatial and temporal variation in environmental factors. Fish reproduction was investigated by capturing larvae along representative spatial gradients in the main body (longitudinal) and arms (lateral) of the reservoir. After identification, the captured larvae were classified into different groups according to the functional traits of their parental stock. Sampling occurred monthly at night from October to March over five reproductive periods between 2009 and 2016, using conical‐cylindrical plankton nets with flowmeter. Water samples were taken simultaneously allowing the measurement of environmental factors related to reproductive activity. The relationship between the environmental factors and the functional traits was assessed using RLQ and fourth‐corner analyses. An evaluation of 51,995 larvae revealed there was greater larval abundance in the lacustrine and transition zones of both longitudinal and lateral gradients. Occurrences often correlated with temporal instead of spatial gradients. Higher rainfall correlated with abundances of detritivorous and migratory species. Higher water levels correlated with higher abundances of non‐native species, species without parental care, with external fecundation, and partial spawning. Dry periods, with lower water and higher dissolved oxygen, correlated with higher abundances of insectivores and sedentary species. Although the presence of a dam‐free stretch of river upstream of the reservoir had a positive influence on fish larvae in the fluvial zone, the results did not show differentiation along either gradient. Thus, the composition of the functional groups of fish species that reproduce in the Itaipu Reservoir appears to be predominantly influenced by the temporal variation in environmental factors rather than the formation of spatial gradients.