bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensory regulated Wnt production from neurons helps make organ development robust to environmental changes in C. elegans
Authors: Modzelewska Katarzyna , Brown Louise , Culotti Joseph , Moghal Nadeem 
Published: June 2020

ABSTRACT
Long-term survival of an animal species depends on development being robust to environmental variations and climate changes. We used C. elegans to study how mechanisms that sense environmental changes trigger adaptive responses that ensure animals develop properly. In water, the nervous system induces an adaptive response that reinforces vulval development through an unknown backup signal for vulval induction. This response involves the heterotrimeric G-protein EGL-30//Gαq acting in motor neurons. It also requires body-wall muscle, which is excited by EGL-30-stimulated synaptic transmission, suggesting a behavioral function of neurons induces backup signal production from muscle. We now report that increased acetylcholine during liquid growth activates an EGL-30-Rho pathway, distinct from the synaptic transmission pathway, that increases Wnt production from motor neurons. We also provide evidence that this neuronal Wnt contributes to EGL-30-stimulated vulval development, with muscle producing a parallel developmental signal. As diverse sensory modalities stimulate motor neurons via acetylcholine, this mechanism enables broad sensory perception to enhance Wnt-dependent development. Thus, sensory perception improves animal fitness by activating distinct neuronal functions that trigger adaptive changes in both behavior and developmental processes.
PP2A­-B55γ counteracts Cdk1 and regulates proper spindle orientation through the cortical dynein adaptor NuMA
Authors: Keshri Riya , Rajeevan Ashwathi , Kotak Sachin 
Published: June 2020

ABSTRACT
Proper orientation of the mitotic spindle is critical for accurate development and morphogenesis. In human cells, spindle orientation is regulated by the evolutionarily conserved protein NuMA, which interacts with dynein and enriches it at the cell cortex. Pulling forces generated by cortical dynein orient the mitotic spindle. Cdk1-mediated phosphorylation of NuMA at threonine 2055 (T2055) negatively regulates its cortical localization. Thus, only NuMA not phosphorylated at T2055 localizes at the cell cortex. However, the identity and the mechanism of action of the phosphatase complex involved in T2055 dephosphorylation remains elusive. Here, we characterized the PPP2CA-B55γ (PPP2R2C)–PPP2R1B complex that counteracts Cdk1 to orchestrate cortical NuMA for proper spindle orientation. In vitro reconstitution experiments revealed that this complex is sufficient for T2055 dephosphorylation. Importantly, we identified polybasic residues in NuMA that are critical for T2055 dephosphorylation, and for maintaining appropriate cortical NuMA levels for accurate spindle elongation. Furthermore, we found that Cdk1-mediated phosphorylation and PP2A-B55γ-mediated dephosphorylation at T2055 are reversible events. Altogether, this study uncovers a novel mechanism by which Cdk1 and its counteracting PP2A-B55γ complex orchestrate spatiotemporal levels of cortical force generators for flawless mitosis.
Effects of a local auxiliary protein on the two-dimensional affinity of a TCR–peptide MHC interaction
Authors: Junghans Victoria , Chouliara Manto , Santos Ana Mafalda , Hatherley Deborah , Petersen Jan , Dam Tommy , Svensson Lena M. , Rossjohn Jamie , Davis Simon J. , Jönsson Peter 
Published: June 2020

ABSTRACT
The affinity of T-cell receptors (TCRs) for major histocompatibility complex molecules (MHCs) presenting cognate antigens likely determines whether T cells initiate immune responses, or not. There exist few measurements of two-dimensional (2D) TCR–MHC interactions, and the effect of auxiliary proteins on binding is unexplored. Here, Jurkat T-cells expressing the MHC molecule HLA-DQ8-glia-α1 and the ligand of an adhesion protein (rat CD2) were allowed to bind supported lipid bilayers (SLBs) presenting fluorescently labelled L3-12 TCR and rat CD2, allowing measurements of binding unconfounded by cell signaling effects or co-receptor binding. The 2D Kd for L3-12 TCR binding to HLA-DQ8-glia-α1, of 14±5 molecules/μm2 (mean±s.d.), was only marginally influenced by including CD2 up to ∼200 bound molecules/μm2 but higher CD2 densities reduced the affinity up to 1.9-fold. Cell–SLB contact size increased steadily with ligand density without affecting binding for contacts at up to ∼20% of total cell area, but beyond this lamellipodia appeared, giving an apparent increase in bound receptors of up to 50%. Our findings show how parameters other than the specific protein–protein interaction can influence binding behavior at cell–cell contacts.
Neuronal MT1-MMP mediates ECM clearance and Lrp4 cleavage for agrin deposition and signaling in presynaptic development
Authors: Oentaryo Marilyn Janice , Tse Anna Chung-Kwan , Lee Chi Wai 
Published: June 2020

ABSTRACT
Agrin is a crucial factor that induces postsynaptic differentiation at neuromuscular junctions (NMJs), but how secreted agrin is locally deposited in the context of extracellular matrix (ECM) environment and its function in presynaptic differentiation remain largely unclear. Here, we report that the proteolytic activity of neuronal membrane-type 1 matrix metalloproteinase (MT1-MMP; also known as MMP14) facilitates agrin deposition and signaling during presynaptic development at NMJs. Firstly, agrin deposition along axons exhibits a time-dependent increase in cultured neurons that requires MMP-mediated focal ECM degradation. Next, local agrin stimulation induces the clustering of mitochondria and synaptic vesicles, two well-known presynaptic markers, and regulates vesicular trafficking and surface insertion of MT1-MMP. MMP inhibitor or MT1-MMP knockdown suppresses agrin-induced presynaptic differentiation, which can be rescued by treatment with the ectodomain of low-density lipoprotein receptor-related protein 4 (Lrp4). Finally, neuronal MT1-MMP knockdown inhibits agrin deposition and nerve-induced acetylcholine receptor clustering in nerve-muscle co-cultures and affects synaptic structures at Xenopus NMJs in vivo. Collectively, our results demonstrate a previously unappreciated role of agrin, as well as dual functions of neuronal MT1-MMP proteolytic activity in orchestrating agrin deposition and signaling, in presynaptic development.
Chromokinesin KIF4A teams up with stathmin 1 to regulate abscission in a SUMO-dependent manner
Authors: Cuijpers Sabine A. G. , Willemstein Edwin , Ruppert Jan G. , van Elsland Daphne M. , Earnshaw William C. , Vertegaal Alfred C. O. 
Published: June 2020

ABSTRACT
Cell division ends when two daughter cells physically separate via abscission, the cleavage of the intercellular bridge. It is not clear how the anti-parallel microtubule bundles bridging daughter cells are severed. Here, we present a novel abscission mechanism. We identified chromokinesin KIF4A, which is adjacent to the midbody during cytokinesis, as being required for efficient abscission. KIF4A is regulated by post-translational modifications. We evaluated modification of KIF4A by the ubiquitin-like protein SUMO. We mapped lysine 460 in KIF4A as the SUMO acceptor site and employed CRISPR-Cas9-mediated genome editing to block SUMO conjugation of endogenous KIF4A. Failure to SUMOylate this site in KIF4A delayed cytokinesis. SUMOylation of KIF4A enhanced the affinity for the microtubule destabilizer stathmin 1 (STMN1). We here present a new level of abscission regulation through the dynamic interactions between KIF4A and STMN1 as controlled by SUMO modification of KIF4A.
Walking with added mass magnifies salient features of human foot energetics
Authors: Papachatzis Nikolaos , Malcolm Philippe , Nelson Carl A. , Takahashi Kota Z. 
Published: June 2020

ABSTRACT
The human foot serves numerous functional roles during walking, including shock absorption and energy return. Here, we investigated walking with added mass to determine how the foot would alter its mechanical work production in response to a greater force demand. Twenty-one healthy young adults walked with varying levels of added body mass: 0%, +15% and +30% (relative to their body mass). We quantified mechanical work performed by the foot using a unified deformable segment analysis and a multi-segment foot model. We found that walking with added mass tended to magnify certain features of the foot's functions. Magnitudes of both positive and negative mechanical work, during stance in the foot, increased when walking with added mass. Yet, the foot preserved similar amounts of net negative work, indicating that the foot dissipates energy overall. Furthermore, walking with added mass increased the foot's negative work during early stance phase, highlighting the foot's role as a shock-absorber. During mid to late stance, the foot produced greater positive work when walking with added mass, which coincided with greater work from the structures spanning the midtarsal joint (i.e. arch). While this study captured the overall behavior of the foot when walking with varying force demands, future studies are needed to further determine the relative contribution of active muscles and elastic tissues to the foot's overall energy.
Improving estimates of diving lung volume in air-breathing marine vertebrates
Authors: Fahlman Andreas , Sato Katsufumi , Miller Patrick 
Published: June 2020

ABSTRACTThe air volume in the respiratory system of marine tetrapods provides a store of O2 to fuel aerobic metabolism during dives; however, it can also be a liability, as the associated N2 can increase the risk of decompression sickness. In order to more fully understand the physiological limitations of different air-breathing marine vertebrates, it is therefore important to be able to accurately estimate the air volume in the respiratory system during diving. One method that has been used to do so is to calculate the air volume from glide phases – periods of movement during which no thrust is produced by the animal – which many species conduct during ascent periods, when gases are expanding owing to decreasing hydrostatic pressure. This method assumes that there is conservation of mass in the respiratory system, with volume changes only driven by pressure. In this Commentary, we use previously published data to argue that both the respiratory quotient and differences in tissue and blood gas solubility potentially alter the mass balance in the respiratory system throughout a dive. Therefore, near the end of a dive, the measured volume of gas at a given pressure may be 12–50% less than from the start of the dive; the actual difference will depend on the length of the dive, the cardiac output, the pulmonary shunt and the metabolic rate. Novel methods and improved understanding of diving physiology will be required to verify the size of the effects described here and to more accurately estimate the volume of gas inhaled at the start of a dive.
Pulmonary artery enlargement on routine staging 18F-fluodeoxyglucose positron emission tomography/CT for lung and oesophageal cancer
Authors: Ji-Xu Antonio , Yang Yunfei , Bradley Kevin M 
Published: June 2020

Objective:
Pulmonary hypertension (PH) is an underdiagnosed condition associated with poor survival and increased post-operative mortality in lung cancer. CT-based parameters of pulmonary artery enlargement are strong predictors of PH. We used these parameters to investigate pulmonary artery enlargement in lung and oesophageal cancer.

Methods:
Consecutive patients with lung cancer (n = 100) or oesophageal cancer (n = 100) undergoing staging 18F-fluodeoxyglucose PET/CT were retrospectively identified. The transverse diameter of the main pulmonary artery (mPA) and ascending aorta, and the pulmonary artery-to-ascending aorta (PA:A) ratio were obtained. Abnormal values were defined following the Framingham Heart Study cohort.

Results:
Lung cancer patients had a significantly increased mPA diameter compared to the oesophageal cancer patients (males: 27.29 ± 0.39 vs. 25.88 ± 0.24 mm, females: 26.10 ± 0.28 vs. 24.45 ± 0.18 mm). Similarly, a significantly increased proportion of these patients had an abnormal mPA diameter (males: 35.1% vs 12.5%, females: 32.6% vs 10.7%). Lung cancer patients also had a significantly higher PA:A ratio (males: 0.83 ± 0.01 vs. 0.79 ± 0.008, females: 0.85 ± 0.01 vs. 0.79 ± 0.009), with a larger proportion having an abnormal PA:A ratio (males: 24.6% vs 11.1%, females: 27.9% vs 14.3%).

Conclusion:
Simple measurements of mPA diameter and PA:A ratio reveal that lung cancer patients exhibit increased rates of pulmonary artery enlargement compared to oesophageal cancer patients.

Advances in knowledge:
This study demonstrates there is an increased prevalence of pulmonary enlargement in lung cancer, easily detected on routine staging scans, holding implications for further work-up and risk stratification.
Open Access of COVID-19-related publications in the first quarter of 2020: a preliminary study based in PubMed
Authors: Arrizabalaga Olatz , Otaegui David , Vergara Itziar , Arrizabalaga Julio , Méndez Eva 
Published: June 2020

Background: The COVID-19 outbreak has made funders, researchers and publishers agree to have research publications, as well as other research outputs, such as data, become openly available. In this extraordinary research context of the SARS CoV-2 pandemic, publishers are announcing that their coronavirus-related articles will be made immediately accessible in appropriate open repositories, like PubMed Central, agreeing upon funders’ and researchers’ instigation. Methods: This work uses Unpaywall, OpenRefine and PubMed to analyse the level of openness of articles about COVID-19, published during the first quarter of 2020. It also analyses Open Access (OA) articles published about previous coronavirus (SARS CoV-1 and MERS CoV) as a means of comparison. Results: A total of 5,611 COVID-19-related articles were analysed from PubMed. This is a much higher amount for a period of 4 months compared to those found for SARS CoV-1 and MERS during the first year of their first outbreaks (335 and 116 articles, respectively). Regarding the levels of openness, 88.8% of the SARS CoV-2 papers are freely available; similar rates were found for the other coronaviruses. Deeper analysis showed that (i) 67.4% of articles belong to an undefined Bronze category; (ii) 76.4% of all OA papers don’t carry any license, followed by 10.4% which display restricted licensing. These patterns were found to be repeated in the three most frequent publishers: Elsevier, Springer and Wiley. Conclusions: Our results suggest that, although scientific production is much higher than during previous epidemics and is open, there is a caveat to this opening, characterized by the absence of fundamental elements and values ​​on which Open Science is based, such as licensing.
Managing Changes in Organizational Budgeting Model of Russian Bank in Conditions of Implementation of Agile Approaches in It Projects
Authors: Dudukin Timofey 
Published: June 2020

The research project described in this article is intended to identify the requirements for the target organizational budgeting model of a company implementing agile approach in managing IT projects and to develop recommendations concerning these requirements. To collect data relevant for the research an interview and a questionnaire were conducted among the key participants of processes of managing project portfolio, and also some materials from meetings inside the company were used. The most significant results of this project ready to be applied in other companies are:
•• the activity-based costs allocation model, which allows to improve the project planning quality and to increase the benefits estimation objectiveness;
•• the open access integrated IS model providing the transparency of project portfolio budgeting process and possibilities for cascading the metrics of strategic goals achievement set in Balanced Scorecards and increments delivered by agile-teams.
Bias–Variance Trade-Off and Shrinkage of Weights in Forecast Combination
Authors: Blanc Sebastian M. , Setzer Thomas 
Published: June 2020

Combining forecasts is an established approach for improving forecast accuracy. So-called optimal weights (OWs) estimate combination weights by minimizing errors on past forecasts. Yet the most successful and common approach ignores all training data and assigns equal weights (EWs) to forecasts. We analyze this phenomenon by relating forecast combination to statistical learning theory, which decomposes forecast errors into three components: bias, variance, and irreducible error. In this framework, EWs minimize the variance component (errors resulting from estimation uncertainty) but ignore the bias component (errors from under-sensitivity to training data). OWs, in contrast, minimize the bias and ignore the variance component. Reducing one component in general increases the other. To address this trade-off between bias and variance, we first derive the expected squared error of a combination using weights between EWs and OWs (technically, OWs shrunk toward EWs) and decompose it into the three error components. We then use the components to derive the shrinkage factor between EWs and OWs that minimizes the expected error. We evaluate the approach on forecasts from the Federal Reserve Bank of Philadelphia’s Survey of Professional Forecasters. For these forecasts, we first show that assumptions regarding the error distribution that are commonly used in theoretical analyses are likely to be violated in practice. We then demonstrate that our approach improves over EWs and OWs if the assumptions are met, for instance, as the result of using a standardization procedure for the training data. This paper was accepted by Han Bleichrodt, decision analysis.
The effect of tourniquet uses on total blood loss, early function, and pain after primary total knee arthroplasty
Authors: Zhao Hai-Yan , Yeersheng Releken , Kang Xue-Wen , Xia Ya-Yi , Kang Peng-De , Wang Wen-Ji 
Published: June 2020

Aims The aim of this study was to examine whether tourniquet use can improve perioperative blood loss, early function recovery, and pain after primary total knee arthroplasty (TKA) in the setting of multiple-dose intravenous tranexamic acid. Methods This was a prospective, randomized clinical trial including 180 patients undergoing TKA with multiple doses of intravenous tranexamic acid. One group was treated with a tourniquet during the entire procedure, the second group received a tourniquet during cementing, and the third group did not receive a tourniquet. All patients received the same protocol of intravenous tranexamic acid (20 mg/kg) before skin incision, and three and six hours later (10 mg/kg). The primary outcome measure was perioperative blood loss. Secondary outcome measures were creatine kinase (CK), CRP, interleukin-6 (IL-6), visual analogue scale (VAS) pain score, limb swelling ratio, quadriceps strength, straight leg raising, range of motion (ROM), American Knee Society Score (KSS), and adverse events. Results The mean total blood loss was lowest in the no-tourniquet group at 867.32 ml (SD 201.11), increased in the limited-tourniquet group at 1024.35 ml (SD 176.35), and was highest in the tourniquet group at 1,213.00 ml (SD 211.48). The hidden blood loss was lowest in the no-tourniquet group (both p < 0.001). There was less mean intraoperative blood loss in the tourniquet group (77.48 ml (SD 24.82)) than in the limited-tourniquet group (137.04 ml (SD 26.96)) and the no-tourniquet group (212.99 ml (SD 56.35); both p < 0.001). Patients in the tourniquet group showed significantly higher levels of muscle damage and inflammation biomarkers such as CK, CRP, and IL-6 than the other two groups (p < 0.05). Outcomes for VAS pain scores, limb swelling ratio, quadriceps strength, straight leg raising, ROM, and KSS were significantly better in the no-tourniquet group at three weeks postoperatively (p < 0.05), but there were no significant differences at three months. No significant differences were observed among the three groups with respect to transfusion rate, thrombotic events, or the length of hospital stay. Conclusion Patients who underwent TKA with multiple doses of intravenous tranexamic acid but without a tourniquet presented lower total blood loss and hidden blood loss, and they showed less postoperative inflammation reaction, less muscle damage, lower VAS pain score, and better early knee function. Our results argue for not using a tourniquet during TKA. Cite this article: Bone Joint Res 2020;9(6):322–332.
Synovial chondromatosis of the temporomandibular joint: a case report
Authors: Barraclough O , Wilson G , Power A 
Published: June 2020

Synovial chondromatosis is a rare benign condition. It most commonly affects the large joints. Presentation in the temporomandibular joint is rare. Our case was an incidental radiological finding and not diagnosed immediately, highlighting the ease with which conditions such as this can be missed, particularly in asymptomatic patients. Only 45% of patients with synovial chondromatosis show radiographic changes. Findings as significant as ours are unusual. An increased professional awareness of the radiological signs of synovial chondromatosis would be beneficial to improve diagnosis and prognosis for patients.
Beam tracking algorithm for marine applications using visible light communication
Authors: Feng Renhai , Chang Yanyan , Mao Xurui 
Published: June 2020

Visible light communication (VLC) offers a unique advantage of electromagnetic interference immunity and wide bandwidth. It has gradually become the main candidate in marine communication with great potential. As a green communication link, VLC requires reliable beam tracking as a prerequisite. Therefore, based on the received signal strength of a single-input–multiple-output system in the VLC scenario, this paper first proposes a geometrical algorithm for transmitter localization. On this basis, a linear iterative algorithm using Taylor expansion, implicit function theorem, and time-domain expansion is presented to realize online beam tracking. Under the marine VLC system, an iterative denoising algorithm based on the hidden Markov model and principal component analysis is proposed for denoising. Simulation results show that the proposed algorithms have predominance in high tracking accuracy (within 10 cm) and desirable real-time performance.
Nanophotonic tantala waveguides for supercontinuum generation pumped at 1560  nm
Authors: Lamee Kieran F. , Carlson David R. , Newman Zachary L. , Yu Su-Peng , Papp Scott B. 
Published: June 2020

We experimentally demonstrate efficient and broadband supercontinuum generation in nonlinear tantala (

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a

2

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) waveguides using a 1560 nm femtosecond seed laser. With incident pulse energies as low as 100 pJ, we create spectra spanning up to 1.6 octaves across the visible and infrared. Fabricated devices feature propagation losses as low as 10 dB/m, and they can be dispersion engineered through lithographic patterning for specific applications. We show a waveguide design suitable for low-power self-referencing of a fiber frequency comb that produces dispersive-wave radiation directly at the second-harmonic wavelength of the seed laser. A fiber-connectorized, hermetically sealed module with 2 dB per facet insertion loss and watt-level average-power handling is also described. Highly efficient and fully packaged tantala waveguides may open new possibilities for the integration of nonlinear nanophotonics into systems for precision timing, quantum science, biological imaging, and remote sensing.