bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling of the muscle-specific dystroglycan interactome reveals the role of Hippo signaling in muscular dystrophy and age-dependent muscle atrophy
Authors: Yatsenko Andriy S. , Kucherenko Mariya M. , Xie Yuanbin , Aweida Dina , Urlaub Henning , Scheibe Renate J. , Cohen Shenhav , Shcherbata Halyna R. 
Published: January 2020

AbstractBackgroundDystroglycanopathies are a group of inherited disorders characterized by vast clinical and genetic heterogeneity and caused by abnormal functioning of the ECM receptor dystroglycan (Dg). Remarkably, among many cases of diagnosed dystroglycanopathies, only a small fraction can be linked directly to mutations in Dg or its regulatory enzymes, implying the involvement of other, not-yet-characterized, Dg-regulating factors. To advance disease diagnostics and develop new treatment strategies, new approaches to find dystroglycanopathy-related factors should be considered. The Dg complex is highly evolutionarily conserved; therefore, model genetic organisms provide excellent systems to address this challenge. In particular,Drosophilais amenable to experiments not feasible in any other system, allowing original insights about the functional interactors of the Dg complex.MethodsTo identify new players contributing to dystroglycanopathies, we usedDrosophilaas a genetic muscular dystrophy model. Using mass spectrometry, we searched for muscle-specific Dg interactors. Next, in silico analyses allowed us to determine their association with diseases and pathological conditions in humans. Using immunohistochemical, biochemical, and genetic interaction approaches followed by the detailed analysis of the muscle tissue architecture, we verified Dg interaction with some of the discovered factors. Analyses of mouse muscles and myocytes were used to test if interactions are conserved in vertebrates.ResultsThe muscle-specific Dg complexome revealed novel components that influence the efficiency of Dg function in the muscles. We identified the closest human homologs for Dg-interacting partners, determined their significant enrichment in disease-associations, and verified some of the newly identified Dg interactions. We found that Dg associates with two components of the mechanosignaling Hippo pathway: the WW domain-containing proteins Kibra and Yorkie. Importantly, this conserved interaction manages adult muscle size and integrity.ConclusionsThe results presented in this study provide a new list of muscle-specific Dg interactors, further analysis of which could aid not only in the diagnosis of muscular dystrophies, but also in the development of new therapeutics. To regulate muscle fitness during aging and disease, Dg associates with Kibra and Yorkie and acts as a transmembrane Hippo signaling receptor that transmits extracellular information to intracellular signaling cascades, regulating muscle gene expression.
A secretion biosensor for monitoring Sec-dependent protein export in Corynebacterium glutamicum
Authors: Jurischka Sarah , Bida Astrid , Dohmen-Olma Doris , Kleine Britta , Potzkei Janko , Binder Stephan , Schaumann Georg , Bakkes Patrick J. , Freudl Roland 
Published: January 2020

Abstract
Background
In recent years, the industrial workhorse Corynebacterium glutamicum has gained increasing interest as a host organism for the secretory production of heterologous proteins. Generally, the yield of a target protein in the culture supernatant depends on a multitude of interdependent biological and bioprocess parameters which have to be optimized. So far, the monitoring of such optimization processes depends on the availability of a direct assay for the respective target protein that can be handled also in high throughput approaches. Since simple assays, such as standard enzymatic activity assays, are not always at hand, the availability of a general protein secretion biosensor is highly desirable.

Results
High level secretion of proteins via the Sec protein export pathway leads to secretion stress, a phenomenon that is thought to be caused by the accumulation of incompletely or misfolded proteins at the membrane-cell envelope interface. We have analyzed the transcriptional responses of C. glutamicum to the secretory production of two different heterologous proteins and found that, in both cases, the expression of the gene encoding a homologue of the extracytosolic HtrA protease was highly upregulated. Based on this finding, a C. glutamicum Sec secretion biosensor strain was constructed in which the htrA gene on the chromosome was replaced by the eyfp gene. The fluorescence of the resulting reporter strain responded to the secretion of different heterologous proteins (cutinase from Fusarium solani pisi and alkaline phosphatase PhoA from Escherichia coli) in a dose-dependent manner. In addition, three differently efficient signal peptides for the secretory production of the cutinase could be differentiated by the biosensor signal. Furthermore, we have shown that an efficient signal peptide can be separated from a poor signal peptide by using the biosensor signal of the respective cells in fluorescence activated cell sorting experiments.

Conclusions
We have succeeded in the construction of a C. glutamicum biosensor strain that allows for the monitoring of Sec-dependent secretion of heterologous proteins in a dose-dependent manner, independent of a direct assay for the desired target protein.
Serum FFAs profile analysis of Normal weight and obesity individuals of Han and Uygur nationalities in China
Authors: Ma Yinghua , Qiu Tongtong , Zhu Jiaojiao , Wang Jingzhou , Li Xue , Deng Yuchun , Zhang Xueting , Feng Jiale , Chen Keru , Wang Cuizhe , Xie Jianxin , Zhang Jun 
Published: January 2020

AbstractBackgroundHan and Uygur are the two main nationalities living in Xinjiang, China. There are significant differences in the incidence of metabolic diseases for two nationalities, but the specific reasons are not clear. Obesity is an important risk factor for the development of metabolic syndrome, which may be closely related to the increase of serum free fatty acids (FFAs) content. This study aims to use metabolomics to compare the changes of serum FFAs profiles between normal weight (NW) and obese (OB) individuals of two nationalities, screening out the differential FFAs, predicting and evaluating their relationship with diseases.MethodsThirty-four kinds of FFAs in serum were detected by ultra-high-pressure liquid chromatography–mass spectrometry (UHPLC-MS) and distinctions in FFAs profiles were evaluated using a metabolomics method while Receiver operating characteristics (ROC) and logistic regression models were used to explore FFAs significant for diagnosing obesity and obesity-associated comorbidities.ResultsIn the Han nationality, ten kinds of FFAs (C7:0, C8:0, C9:0, C10:0, C11:0, C14:0, C18:2, C20:3, C20:4 and C22:6) showed significant differences between NW and OB individuals. These differential FFAs may be related to hypertension and gestational diabetes mellitus. In the Uygur nationality, C20:3 and C20:5 showed significant differences between NW and OB individuals. C9:0 and C19:0, which were screened out among the female subjects, showed a good ability to predict obesity status in Uygur females (AUC = 0.950).ConclusionIn both the Han and Uygur nationalities, the FFAs profiles of NW individuals differed from those of OB individuals. The significantly differential FFAs are closely related to obesity and may be important risk factors for obesity and related metabolic diseases.
Assessment of left ventricular diastolic function after Transcatheter aortic valve implantation in aortic stenosis patients by echocardiographic according to different guidelines
Authors: Guo Yao , Sun Minmin , Chen Haiyan , Kong Dehong , Shu Xianhong , Pan Cuizhen 
Published: January 2020

Abstract
Background
To evaluate the detailed dynamic change of left ventricular diastolic function (LVDF) by echocardiography in aortic stenosis (AS) patients receiving transcatheter aortic valve implantation (TAVI) and compare LVDF classification according to 2009 ASE/EAE and 2016 ASE/EACVI recommendations.

Methods
Thirty-five AS patients receiving TAVI underwent echocardiography the day before operation (PRE), on the third day (3D), in the first-month (1 M) and the six-month (6 M) after TAVI. LVDF was analyzed using 2D and doppler imaging to get parameters including E/A, E/e’, isovolumic relaxation time (IVRT), deceleration time, LA area, LA volume index (LAVI) and systolic tricuspid regurgitation velocity (TR). LVDF classification was evaluated four times for each patient according to 2009 and 2016 recommendations respectively and the results were compared.

Results
The decrease of IVRT and TR occurred immediately post surgery up to 1-month. Improvement of E/e’ occurred late from 3-day to 1-month. LA area and LAVI decreased continuously shortly after operation till 6-month. Forty-four percent (62/140) by 2009 recommendations were reclassified with different grades when using 2016 guidelines. Comparing PRE and 6 M, with 2009 guidelines, 19 patients improved 1 grade, 8 patients improved 2 grades; with 2016 guidelines, 9 patients improved 1 grade, 13 patients improved 2 grades, 1 patient improved 3 grades.

Conclusions
The conventional 2D echocardiography could effectively reflect variation process of LVDF in AS patients after TAVI. For LVDD classification, obvious differences resulted by the 2009 and updated recommendations were found, and more patients can be regarded as benefiting from TAVI by 2016.
recommendations.
Safety results of ixekizumab with 1822.2 patient-years of exposure: an integrated analysis of 3 clinical trials in adult patients with psoriatic arthritis
Authors: Combe Bernard , Rahman Proton , Kameda Hideto , Cañete Juan D. , Gallo Gaia , Agada Noah , Xu Wen , Genovese Mark C. 
Published: January 2020

Abstract
Background
The long-term safety was assessed in patients with psoriatic arthritis who were treated with ixekizumab in three clinical trials (SPIRIT-P1/-P2/-P3).

Methods
Integrated safety data from three trials (controlled and uncontrolled), including two pivotal phase 3, randomized, double-blind clinical trials: SPIRIT-P1 and SPIRIT-P2, were assessed. Safety data were integrated from the all ixekizumab exposure safety population (defined as all patients receiving ≥ 1 dose of ixekizumab). We report exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) at 1-year intervals up to 3 years for adverse events.

Results
Total exposure to IXE reached 1822.2 PY (1118 patients). The IRs/100 PY for the following treatment discontinuations were as follows: adverse events (5.3); serious infections (1.3); injection-site reactions (12.7); infections (34.2); and deaths (0.3). The IRs for treatment-emergent adverse events decreased or remained stable over time, the most common being upper respiratory tract infection, nasopharyngitis, and injection-site reactions. The IRs for serious adverse events and serious infections remained stable over time, whereas for injection-site reactions and general infections, IRs decreased with longer ixekizumab exposure. Opportunistic infections were limited to oral and esophageal candida and localized herpes zoster. No suicide or self-injury-related behaviors were reported. The IRs/100 PY for safety topics of special interest included inflammatory bowel disease (adjudicated; 0.1), depression (1.6), malignancies (0.7), and major adverse cardiovascular events (0.6).

Conclusions
The findings of this integrated safety analysis in patients with psoriatic arthritis are consistent with the known safety profile of ixekizumab. No unexpected safety signals were observed with ixekizumab treatment in patients with psoriatic arthritis.

Trial registration
SPIRIT-P1 (NCT01695239; Registered August 08, 2012), SPIRIT-P2 (NCT02349295; September 23, 2014), and SPIRIT-P3 (NCT02584855; August 04, 2015).
Hybridizing extended ant lion optimizer with sine cosine algorithm approach for abrupt motion tracking
Authors: Zhang Huanlong , Gao Zeng , Zhang Jie , Liu Junfeng , Nie Zhicheng , Zhang Jianwei 
Published: January 2020

AbstractIn view of the problem that the conventional tracker does not adapt to abrupt motion, we propose a tracking algorithm based on the hybrid extended ant lion optimizer with sine cosine algorithm (EALO-SCA) in this paper. Firstly, the multiple elites is used to replace the single elite in the standard ant lion optimizer (ALO). The extended ALO (EALO) can enhance the global exploration ability, which can handle abrupt motion. Secondly, considering that sine cosine algorithm (SCA) has strong local exploitation operator, a hybrid EALO-SCA tracker is proposed using the advantages of both EALO and SCA. The proposed approach can improve tracking accuracy and efficiency. Finally, extensive experimental results in both quantitative and qualitative measures prove that the proposed algorithm is very competitive compared to 7 state-of-the-art trackers, especially for abrupt motion tracking.
Asymptotical stability of Runge–Kutta methods for nonlinear impulsive differential equations
Authors: Zhang Gui-Lai 
Published: January 2020

AbstractIn this paper, asymptotical stability of the exact solutions of nonlinear impulsive ordinary differential equations is studied under Lipschitz conditions. Under these conditions, asymptotical stability of Runge–Kutta methods is studied by the theory of Padé approximation. And two simple examples are given to illustrate the conclusions.
3D supervirtual refraction interferometry
Authors: Lu Kai , Chávez-Pérez Sergio 
Published: January 2020

We have developed the theory and practice of 3D supervirtual interferometry (SVI) for enhancing the signal-to-noise ratio (S/N) of refraction arrivals in 3D data. Unlike 2D SVI, 3D SVI requires an extra integration along the inline direction to compute the stationary source-receiver pairs for enhanced stacking of the refraction events. The result is a significant increase in the S/N of first arrivals in the far-offset traces. We have evaluated 3D synthetic and field data examples to demonstrate the effectiveness of the proposed method. For the synthetic data tests, SVI has extended the source-receiver offset range of pickable traces from 11 to 15 km. In the field data example, SVI has extended the source-receiver offset of traces with pickable first-arrival traveltimes from 12 km to a maximum of 18 km, and the total number of reliable traveltime picks has increased by 12%, which contributes to a deeper velocity update in the traveltime tomogram.
Spatiotemporal regulation of GSK3β levels by miRNA-26a controls axon development in cortical neurons
Authors: Lucci Cristiano , Mesquita-Ribeiro Raquel , Rathbone Alex , Dajas-Bailador Federico 
Published: January 2020

ABSTRACT
Both the establishment of neuronal polarity and axonal growth are crucial steps in the development of the nervous system. The local translation of mRNAs in the axon provides precise regulation of protein expression, and is now known to participate in axon development, pathfinding and synaptic formation and function. We have investigated the role of miR-26a in early stage mouse primary cortical neuron development. We show that micro-RNA-26a-5p (miR-26a) is highly expressed in neuronal cultures, and regulates both neuronal polarity and axon growth. Using compartmentalised microfluidic neuronal cultures, we identified a local role for miR-26a in the axon, where the repression of local synthesis of GSK3β controls axon development and growth. Removal of this repression in the axon triggers local translation of GSK3β protein and subsequent transport to the soma, where it can impact axonal growth. These results demonstrate how the axonal miR-26a can regulate local protein translation in the axon to facilitate retrograde communication to the soma and amplify neuronal responses, in a mechanism that influences axon development.
The ciliary phosphatidylinositol phosphatase Inpp5e plays positive and negative regulatory roles in Shh signaling
Authors: Constable Sandii , Long Alyssa B. , Floyd Katharine A. , Schurmans Stéphane , Caspary Tamara 
Published: January 2020

ABSTRACT
Sonic hedgehog (Shh) signal transduction specifies ventral cell fates in the neural tube and is mediated by the Gli transcription factors that play both activator (GliA) and repressor (GliR) roles. Cilia are essential for Shh signal transduction and the ciliary phosphatidylinositol phosphatase Inpp5e is linked to Shh regulation. In the course of a forward genetic screen for recessive mouse mutants, we identified a functional null allele of inositol polyphosphate-5-phosphatase E (Inpp5e), ridge top (rdg), with expanded ventral neural cell fates at E10.5. By E12.5, Inpp5erdg/rdg embryos displayed normal neural patterning and this correction over time required Gli3, the predominant repressor in neural patterning. Inpp5erdg function largely depended on the presence of cilia and on smoothened, the obligate transducer of Shh signaling, indicating that Inpp5e functions within the cilium to regulate the pathway. These data indicate that Inpp5e plays a more complicated role in Shh signaling than previously appreciated. We propose that Inpp5e attenuates Shh signaling in the neural tube through regulation of the relative timing of GliA and GliR production, which is important in understanding how the duration of Shh signaling regulates neural tube patterning.
In vivo interactions between myosin XI, vesicles and filamentous actin are fast and transient in Physcomitrella patens
Authors: Bibeau Jeffrey P. , Furt Fabienne , Mousavi S. Iman , Kingsley James L. , Levine Max F. , Tüzel Erkan , Vidali Luis 
Published: January 2020

ABSTRACT
The actin cytoskeleton and active membrane trafficking machinery are essential for polarized cell growth. To understand the interactions between myosin XI, vesicles and actin filaments in vivo, we performed fluorescence recovery after photobleaching and showed that the dynamics of myosin XIa at the tip of the spreading earthmoss Physcomitrella patens caulonemal cells are actin-dependent and that 50% of myosin XI is bound to vesicles. To obtain single-particle information, we used variable-angle epifluorescence microscopy in protoplasts to demonstrate that protein myosin XIa and VAMP72-labeled vesicles localize in time and space over periods lasting only a few seconds. By tracking data with Hidden Markov modeling, we showed that myosin XIa and VAMP72-labeled vesicles exhibit short runs of actin-dependent directed transport. We also found that the interaction of myosin XI with vesicles is short-lived. Together, this vesicle-bound fraction, fast off-rate and short average distance traveled seem be crucial for the dynamic oscillations observed at the tip, and might be vital for regulation and recycling of the exocytosis machinery, while simultaneously promoting vesicle focusing and vesicle secretion at the tip, necessary for cell wall expansion.
Myo1e modulates the recruitment of activated B cells to inguinal lymph nodes
Authors: Girón-Pérez Daniel A. , Vadillo Eduardo , Schnoor Michael , Santos-Argumedo Leopoldo 
Published: January 2020

ABSTRACT
The inclusion of lymphocytes in high endothelial venules and their migration to the lymph nodes are critical steps in the immune response. Cell migration is regulated by the actin cytoskeleton and myosins. Myo1e is a long-tailed class I myosin and is highly expressed in B cells, which have not been studied in the context of cell migration. By using intravital microscopy in an in vivo model and performing in vitro experiments, we studied the relevance of Myo1e for the adhesion and inclusion of activated B cells in high endothelial venules. We observed reduced expression of integrins and F-actin in the membrane protrusions of B lymphocytes, which might be explained by deficiencies in vesicular trafficking. Interestingly, the lack of Myo1e reduced the phosphorylation of focal adhesion kinase (FAK; also known as PTK2), AKT (also known as AKT1) and RAC-1, disturbing the FAK–PI3K–RAC-1 signaling pathway. Taken together, our results indicate a critical role of Myo1e in the mechanism of B-cell adhesion and migration.
Genetic engineering of Hoxb8-immortalized hematopoietic progenitors – a potent tool to study macrophage tissue migration
Authors: Accarias Solene , Sanchez Thibaut , Labrousse Arnaud , Ben-Neji Myriam , Boyance Aurélien , Poincloux Renaud , Maridonneau-Parini Isabelle , Le Cabec Véronique 
Published: January 2020

ABSTRACT
Tumor-associated macrophages (TAMs) are detrimental in most cancers. Controlling their recruitment is thus potentially therapeutic. We previously found that TAMs perform protease-dependent mesenchymal migration in cancer, while macrophages perform amoeboid migration in other tissues. Inhibition of mesenchymal migration correlates with decreased TAM infiltration and tumor growth, providing rationale for a new cancer immunotherapy specifically targeting TAM motility. To identify new effectors of mesenchymal migration, we produced ER-Hoxb8-immortalized hematopoietic progenitors (cells with estrogen receptor-regulated Hoxb8 expression), which show unlimited proliferative ability in the presence of estrogen. The functionality of macrophages differentiated from ER-Hoxb8 progenitors was compared to bone marrow-derived macrophages (BMDMs). They polarized into M1- and M2-orientated macrophages, generated reactive oxygen species (ROS), ingested particles, formed podosomes, degraded the extracellular matrix, adopted amoeboid and mesenchymal migration in 3D, and infiltrated tumor explants ex vivo using mesenchymal migration. We also used the CRISPR/Cas9 system to disrupt gene expression of a known effector of mesenchymal migration, WASP (also known as WAS), to provide a proof of concept. We observed impaired podosome formation and mesenchymal migration capacity, thus recapitulating the phenotype of BMDM isolated from Wasp-knockout mice. Thus, we validate the use of ER-Hoxb8-immortalized macrophages as a potent tool to investigate macrophage functionalities.
The cell polarity proteins Boi1 and Boi2 direct an actin nucleation complex to sites of exocytosis in Saccharomyces cerevisiae
Authors: Glomb Oliver , Wu Yehui , Rieger Lucia , Rüthnick Diana , Mulaw Medhanie A. , Johnsson Nils 
Published: January 2020

ABSTRACT
Owing to the local enrichment of factors that influence its dynamics and organization, the actin cytoskeleton displays different shapes and functions within the same cell. In yeast cells, post-Golgi vesicles ride on long actin cables to the bud tip. The proteins Boi1 and Boi2 (Boi1/2) participate in tethering and docking these vesicles to the plasma membrane. Here, we show in Saccharomyces cerevisiae that Boi1/2 also recruit nucleation and elongation factors to form actin filaments at sites of exocytosis. Disrupting the connection between Boi1/2 and the nucleation factor Bud6 impairs filament formation, reduces the directed movement of the vesicles to the tip and shortens the vesicles’ tethering time at the cortex. Transplanting Boi1 from the bud tip to the peroxisomal membrane partially redirects the actin cytoskeleton and the vesicular flow towards the peroxisome, and creates an alternative, rudimentary vesicle-docking zone. We conclude that Boi1/2, through interactions with Bud6 and Bni1, induce the formation of a cortical actin structure that receives and aligns incoming vesicles before fusion with the membrane.