bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Astrin-SKAP Complex Reduces Friction at the Kinetochore-Microtubule Interface
Authors: Rosas-Salvans Miquel , Sutanto Renaldo , Suresh Pooja , Dumont Sophie 
Published: November 2021

ABSTRACTThe kinetochore links chromosomes to spindle microtubules to drive chromosome segregation at cell division. While we know nearly all mammalian kinetochore proteins, how these give rise to the strong yet dynamic microtubule attachments required for function remains poorly understood. Here, we focus on the Astrin-SKAP complex, which localizes to bioriented kinetochores and is essential for chromosome segregation, but whose mechanical role is unclear. Live imaging reveals that SKAP depletion dampens movement and decreases coordination of metaphase sister kinetochores, and increases tension between them. Using laser ablation to isolate kinetochores bound to polymerizing vs depolymerizing microtubules, we show that without SKAP kinetochores move slower on both polymerizing and depolymerizing microtubules, and that more force is needed to rescue microtubules to polymerize. Thus, in contrast to previously described kinetochore proteins that increase grip on microtubules under force, Astrin-SKAP reduces grip, increasing attachment dynamics and force responsiveness and reducing friction. Together, our findings suggest a model where the Astrin-SKAP complex effectively “lubricates” correct, bioriented attachments to help preserve them.
Oxidative Modification of LHC II Associated with Photosystem II and PS I-LHC I-LHC II Membranes
Authors: Kale Ravindra S. , Seep Jacob , Sallans Larry , Frankel Laurie K. , Bricker Terry M. 
Published: November 2021

AbstractUnder aerobic conditions the production of Reactive Oxygen Species (ROS) by electron transport chains is unavoidable, and occurs in both autotrophic and heterotrophic organisms. In photosynthetic organisms both Photosystem II (PS II) and Photosystem I (PS I), in addition to the cytochrome b6/f complex, are demonstrated sources of ROS. All of these membrane protein complexes exhibit oxidative damage when isolated from field-grown plant material. An additional possible source of ROS in PS I and PS II is the distal, chlorophyll-containing light-harvesting array LHC II, which is present in both photosystems. These serve as possible sources of 1O2 produced by the interaction of 3O2 with 3chl* produced by intersystem crossing. We have hypothesized that amino acid residues close to the sites of ROS generation will be more susceptible to oxidative modification than distant residues. In this study, we have identified oxidized amino acid residues in a subset of the spinach LHC II proteins (Lhcb1 and Lhcb2) that were associated with either PS II membranes (i.e. BBYs) or PS I-LHC I-LHC II membranes, both of which were isolated from field-grown spinach. We identified oxidatively modified residues by high-resolution tandem mass spectrometry. Interestingly, two different patterns of oxidative modification were evident for the Lhcb1 and Lhcb2 proteins from these different sources. In the LHC II associated with PS II membranes, oxidized residues were identified to be located on the stromal surface of Lhcb1 and, to a much lesser extent, Lhcb2. Relatively few oxidized residues were identified as buried in the hydrophobic core of these proteins. The LHC II associated with PS I-LHC I-LHC II membranes, however, exhibited fewer surface-oxidized residues but, rather a large number of oxidative modifications buried in the hydrophobic core regions of both Lhcb1 and Lhcb2, adjacent to the chlorophyll prosthetic groups. These results appear to indicate that ROS, specifically 1O2, can modify the Lhcb proteins associated with both photosystems and that the LHC II associated with PS II membranes represent a different population from the LHC II associated with PS I-LHC I-LHC II membranes.
Asking the Wrong Questions About American Science Education: Insights from a Longitudinal Study of High School Biotechnology Lab Instruction
Authors: Micklos Dave , Barone Lindsay 
Published: November 2021

SUMMARYThe discussion of American science education is often framed by the questions: Why do American precollege students do poorly on international science assessments and what we are doing wrong? Rather we need to ask: Why do so many international students come to US universities for science, what are we doing right in science, and how do we stay ahead in science education? Poor scores on international assessments belie the fact that the U.S. has the best science education system in the world. Our study of 6,200 high school teachers in 1998 and 2018 documented striking success in retooling classrooms for labbased instruction in biotechnology and provided a pre-COVID-19 snapshot of what is right with American biology education. However, it also highlights the need revitalize our precollege teaching resource with a renewed National Science Foundation commitment to in-service training.
A framework for multiplex imaging optimization and reproducible analysis
Authors: Eng Jennifer , Bucher Elmar , Hu Zhi , Zheng Ting , Gibbs Summer L. , Chin Koei , Gray Joe W. 
Published: November 2021

AbstractMultiplex imaging technologies are increasingly used for single-cell phenotyping and spatial characterization of tissues; however, transparent methods are needed for comparing the performance of platforms, protocols and analytical pipelines. We developed a python software, mplexable, for reproducible image processing and utilize Jupyter notebooks to share our optimization of signal removal, antibody specificity, background correction and batch normalization of the multiplex imaging with a focus on cyclic immunofluorescence (CyCIF). Our work both improves the CyCIF methodology and provides a framework for multiplexed image analytics that can be easily shared and reproduced.
A Binary Matrix Method to Enumerate, Hierarchically Order and Structurally Classify Peptide Aggregation
Authors: Tagad Amol , Singh Reman Kumar , Patwari G. Naresh 
Published: November 2021

ABSTRACTProtein aggregation is a common and complex phenomenon in biological processes, yet a robust analysis of this aggregation process remains elusive. The commonly used methods such as center-of-mass to center-of-mass (COM–COM) distance, the radius of gyration (Rg), hydrogen bonding (HB) and solvent accessible surface area (SASA) do not quantify the aggregation accurately. Herein, a new and robust method that uses an aggregation matrix (AM) approach to investigate peptide aggregation in a MD simulation trajectory is presented. A nxn two-dimensional aggregation matrix (AM) is created by using the inter-peptide Cα–Cα cut-off distances which are binarily encoded (0 or 1). These aggregation matrices are analyzed to enumerate, hierarchically order and structurally classify the aggregates. Comparison of the present AM method suggests that it is superior to the HB method since it can incorporate non-specific interactions and Rg, COM–COM methods since the cut-off distance is independent of the length of the peptide. More importantly, the present method can structurally classify the peptide aggregates, which the conventional Rg, COM– COM and HB methods fail. The unique selling point of this method is its ability to structurally classify peptide aggregates using two-dimensional matrices.Abstract Figure
Regional opportunities for Siberian tundra conservation in the next 1000 years
Authors: Kruse Stefan , Herzschuh Ulrike 
Published: November 2021

AbstractThe biodiversity of tundra areas in northern high latitudes is threatened by invasion of forests under global warming. However, poorly understood nonlinear responses of the treeline ecotone mean the timing and extent of tundra losses are unclear but policymakers need such information to optimize conservation efforts. Our individual based model LAVESI, developed for the Siberian tundra-taiga ecotone, can help improve our understanding. Consequently, we simulated treeline migration trajectories until the end of the millennium, causing a loss of tundra area when advancing north. Our simulations reveal that the treeline follows climate warming with a severe, century-long time lag, which is overcompensated by infilling of stands in the long run even when temperatures cool again. Our simulations reveal that only under ambitious mitigation strategies (RCP 2.6) will ~30% of original tundra areas remain in the north but separated into two disjunct refugia.
Dexamethasone induces senescence of lung epithelial cells and augments TGF-β1-mediated production of the fibrosis mediator serpin E1 (plasminogen activator inhibitor-1)
Authors: Longhorne Francesca. L. , Wilkinson Holly N. , Hardman Matthew J. , Hart Simon P. 
Published: November 2021

AbstractBackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive, incurable scarring disease of the lungs with a prognosis worse than most cancers. Pathologically, IPF is characterised by upregulation of the pro-fibrotic cytokine transforming growth factor-β1 (TGF-β1), activation of fibroblasts, and deposition of collagen in the alveolar interstitium. Recent evidence has highlighted the role of senescent type 2 alveolar epithelial cells in the pathogenesis of IPF. In a clinical trial, a treatment regimen containing a corticosteroid drug accelerated pulmonary fibrosis leading to more hospitalizations and deaths, particularly in patients with telomere shortening which drives cellular senescence.AimTo investigate the potential pro-fibrotic actions of corticosteroids on lung epithelial cellsin vitro, including effects on cellular senescence and interactions with TGF-β1.MethodsThe synthetic glucocorticoid dexamethasone (DEX) was incubated with A549 and BEAS-2B human lung epithelial cells in the presence or absence of TGF-β1. Cellular senescence was assessed by morphology, senescence-associated beta-galactosidase (SA β-Gal) expression, and qPCR for transcription of senescence-associated molecular markers. Conditioned media were screened for growth factors and cytokines and cultured with human lung fibroblasts. An IPF lung tissue RNA array dataset was re-analysed with a focus on senescence markers.ResultsDEX induced senescence in lung epithelial cells associated with increased p21 (CDKN1A) expression independently of p16 (CDKN2A) or p53 (TP53). DEX amplified upregulation of the pro-fibrotic mediator serpin E1/plasminogen activator inhibitor-1 (PAI-1) in the presence of TGF-β1. The senescence-associated secretory phenotype from lung epithelial cells treated with DEX plus TGF-β1-treated contained increased concentrations of GM-CSF and IL-6 and when incubated with primary human lung fibroblasts there were trends to increased senescence and production of fibrosis markers. Upregulation of senescence markers was demonstrated by analysis of an IPF transcriptomic dataset.DiscussionDEX induces senescence in lung epithelial cell linesin vitroand interacts with TGF-β1 to amplify production of the pro-fibrotic mediator serpin E1 (PAI-1). This may be a mechanism by which corticosteroids promote pulmonary fibrosis in susceptible individuals. Serpin E1/PAI-1 is a potential druggable target in pulmonary fibrosis.
Design of novel specific primers for helicobacter detection with diagnostic utility evaluation of different 16srRNA genus-specific primers: A comparative study
Authors: Abdelmalek Shaymaa , Shokry Karim , Hamed Wafy , Abdelnalser Mohammed , Aboubakr Ashraf , Elenin Sameh Abou , Ali Mohamed , Mostafa Mohamed , Abou-Okada Mahmoud 
Published: November 2021

AbstractMolecular diagnosis of helicobacters by PCR is simpler, more accurate, and feasible compared to other diagnostic methods. Validity and accuracy are highly dependent on the PCR primer design, diffusion time, and mutation rate of helicobacters. This study aimed to design 16srRNA -specific primers for Helicobacter spp. and H. pylori. Application of comparative statistical analysis of the diagnostic utility of the most available 16srRNA genus-specific primers. The new primers were designed using bioinformatics tools (MAFFT MSA and Gblocks command line). A comparative study was applied on nine genus-specific 16srRNA primers in comparison to the ConsH using Insilco and laboratory evaluation. The results demonstrated that the best specificity and sensitivity of the primers designed for this study compared to other primers. The comparative study revealed that the heminested outer/inner primers were the worst. Although H276,16srRNA(a), HeliS/Heli-nest, and Hcom had acceptable diagnostic utility, false positive and false negative results were obtained. Specificity testing on clinical samples indicated a surprising result; that H. pylori was not the sole enemy that we were looking for, but the NPH should be considered as a real risk prognostic for gastric diseases, consequently, a specific diagnosis and treatment should be developed. This study concluded that our designed primers were the most specific and sensitive in comparison with other primers. in addition, Insilco evaluation is not accurate enough for primer assessment and that the laboratory evaluation is mandatory.
General factors of white matter microstructure from DTI and NODDI in the developing brain
Authors: Vaher Kadi , Galdi Paola , Cabez Manuel Blesa , Sullivan Gemma , Stoye David Q , Quigley Alan J , Thrippleton Michael J , Bogaert Debby , Bastin Mark E , Cox Simon R , Boardman James P 
Published: November 2021

AbstractPreterm birth is closely associated with diffuse white matter dysmaturation inferred from diffusion MRI and neurocognitive impairment in childhood. Diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) are distinct dMRI modalities, yet metrics derived from these two methods share variance across tracts. This raises the hypothesis that dimensionality reduction approaches may provide efficient whole-brain estimates of white matter microstructure that capture (dys)maturational processes. To investigate the optimal model for accurate classification of generalised white matter dysmaturation in preterm infants we assessed variation in DTI and NODDI metrics across 16 major white matter tracts using principal component analysis and structural equation modelling, in 79 term and 141 preterm infants at term equivalent age. We used logistic regression models to evaluate performances of single-metric and multimodality general factor frameworks for efficient classification of preterm infants based on variation in white matter microstructure. Single-metric general factors from DTI and NODDI capture substantial shared variance (41.8-72.5%) across 16 white matter tracts, and two multimodality factors captured 93.9% of variance shared between DTI and NODDI metrics themselves. General factors associate with preterm birth and a single model that includes all seven DTI and NODDI metrics provides the most accurate prediction of microstructural variations associated with preterm birth. This suggests that despite global covariance of dMRI metrics in neonates, each metric represents information about specific (and additive) aspects of the underlying microstructure that differ in preterm compared to term subjects.HighlightsWe measured variation of 7 DTI and NODDI metrics across 16 major tractsGeneral factors for DTI and NODDI capture substantial shared variance across tractsGeneral factors also capture substantial shared variance between DTI and NODDISingle-metric and multimodality factors associate with gestational age at birthThe best preterm prediction model contains all 7 single-metric g-factors
Kv3 channels contribute to the excitability of sub-populations of spinal cord neurons in lamina VII
Authors: Mullen Pierce , Pilati Nadia , Large Charles H. , Deuchars Jim , Deuchars Susan 
Published: November 2021

AbstractAutonomic parasympathetic preganglionic neurons (PGN) drive contraction of the bladder during micturition but remain quiescent during bladder filling. This quiescence is postulated to be due to recurrent inhibition of PGN by fast-firing adjoining interneurons. Here, we defined four distinct neuronal types within lamina VII of the lumbosacral spinal cord, where PGN are situated, by combining whole cell patch clamp recordings with k-means clustering of a range of electrophysiological parameters. Additional morphological analysis separated these neuronal classes into parasympathetic preganglionic populations (PGN) and a fast firing interneuronal population. Kv3 channels are voltage-gated potassium channels (Kv) that allow fast and precise firing of neurons. We found that blockade of Kv3 channels by tetraethylammonium (TEA) reduced neuronal firing frequency and isolated high-voltage-activated Kv currents in the fast-firing population but had no effect in PGN populations. Furthermore, Kv3 blockade potentiated the local and descending inhibitory inputs to PGN indicating that Kv3-expressing inhibitory neurons are synaptically connected to PGN. Taken together, our data reveal that Kv3 channels are crucial for fast and regulated neuronal output of a defined population that may be involved in intrinsic spinal bladder circuits that underpin recurrent inhibition of PGN.Significance statementNeural circuits in the spinal cord and pons mediate the micturition reflex. The spinal cord drives bladder contraction during micturition through the activation of parasympathetic preganglionic neurons in lamina VII of the lumbosacral spinal cord. Despite the significant contribution of these neurons to a crucial physiological reflex, neurons in this region have been under-characterised. This study therefore elucidated and thoroughly characterised distinct neuronal populations in this lamina; we propose that these populations included a fast firing interneuron and subtypes of parasympathetic preganglionic neurons. Further investigation revealed the critical importance of Kv3 channels in the fast firing ability of the interneurons, as well as in synaptic release onto parasympathetic preganglionic neurons.
Priority conservation areas and a global population estimate for the Critically Endangered Philippine Eagle derived from modelled range metrics using remote sensing habitat characteristics
Authors: Sutton Luke J. , Ibañez Jayson C. , Salvador Dennis I. , Taraya Rowell L. , Opiso Guiller S. , Senarillos Tristan Luap P. , McClure Christopher J.W. 
Published: November 2021

AbstractMany range-restricted taxa are currently experiencing population declines yet lack fundamental information regarding distribution and population size. Establishing baseline estimates for both these key biological parameters is however critical for directing conservation planning for at-risk range-restricted species. The International Union for the Conservation of Nature (IUCN) Red List uses three range metrics that define species distributions and inform extinction risk assessments: extent of occurrence (EOO), area of occupancy (AOO) and area of habitat (AOH). However, calculating all three metrics using standard IUCN approaches relies on a geographically representative sample of locations, which for rare species is often spatially biased. Here, we apply model-based interpolation using Species Distribution Models (SDMs), correlating occurrences with remote-sensing covariates, to calculate IUCN range metrics, protected area coverage and a global population estimate for the Critically Endangered Philippine Eagle (Pithecophaga jefferyi). Our final range wide continuous SDM had high predictive accuracy (Continuous Boyce Index = 0.927) and when converted to a binary model estimated an AOH = 23,185 km2, a maximum EOO = 605,759 km2, a minimum EOO = 272,272 km2, with an AOO = 53,867 km2. Based on inferred habitat from the AOH metric, we estimate a global population of 318 breeding pairs (range: 258-362 pairs), or 636 mature individuals, across the Philippine Eagle global range. Protected areas covered 34 % of AOH, 15 % less than the target representation, with the continuous model identifying key habitat as priority conservation areas. We demonstrate that even when occurrences are geographically biased, robust habitat models can be built that enable quantification of baseline IUCN range metrics, protected area coverage, and a population size estimate. In the absence of adequate location data for many rare and threatened taxa, our method is a promising spatial modelling tool with widespread applications, in particular for island endemics facing high extinction risk.
The Endosomal Sorting Complex, ESCRT, has diverse roles in blood progenitor maintenance, lineage choice and immune response
Authors: Ray Arindam , Rai Yashashwinee , Inamdar Maneesha S 
Published: November 2021

AbstractMost hematological malignancies are associated with reduced expression of one or more components of the Endosomal Sorting Complex Required for Transport (ESCRT). However, the roles of ESCRT in stem cell and progenitor maintenance are not resolved. The difficulty in parsing signaling pathway roles in relation to their canonical cargo sorting function poses a challenge. TheDrosophilahematopoietic organ, the larval lymph gland, provides a path to dissect the roles of cellular trafficking pathways such as ESCRT in blood development and maintenance.Drosophilahas 13 core ESCRT components. Knockdown of individual ESCRTs showed that only Vps28 and Vp36 were required in all lymph gland progenitors. Using the well-conserved ESCRT-II complex (Vps22, Vps25 and Vps36) as an example of the range of phenotypes seen upon ESCRT depletion, we show that ESCRTs have cell autonomous as well as non-autonomous roles in progenitor maintenance and differentiation. ESCRT depletion also sensitized posterior lymph gland progenitors to respond to immunogenic cues such as wasp infestation. We also identify key heterotypic roles for ESCRT in position-dependent control of Notch activation to suppress crystal cell differentiation. Our study shows that the cargo sorting machinery can determine progenitor identity and capacity to adapt to the dynamic environments that blood cells are exposed to. These mechanisms for control of cell fate may tailor developmental diversity in multiple contexts.
Distractibility and impulsivity neural states are distinct from attention states and modulate the implementation of attention
Authors: Amengual JL , Di Bello F , Ben Hadj Hassen S , Hamed Suliann Ben 
Published: November 2021

AbstractIn the context of visual attention, it has been classically assumed that missing the response to a target or erroneously selecting a distractor occurs as a consequence of the (miss)allocation of attention in space. In the present paper, we challenge this view and provide evidence that, in addition to encoding spatial attention, prefrontal neurons also encode a distractibility-to-impulsivity state. Using supervised dimensionality reduction techniques, we identify two partially overlapped neuronal subpopulations associated either with attention or overt behaviour. The degree of overlap accounts for the behavioural gain associated with the good allocation of attention. We further describe the neural variability accounting for distractibility-to-impulsivity behaviour by a two dimensional state associated with optimality in task and responsiveness. Overall, we thus show that behavioural performance arises from the integration of task-specific neuronal processes and pre-existing neuronal states describing task-independent behavioural states, shedding new light on attention disorders such as ADHD.