bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acclimation of bacterial cell state for high-throughput enzyme engineering using a DmpR-dependent transcriptional activation system
Authors: Kwon Kil Koang , Yeom Soo-Jin , Choi Su-Lim , Rha Eugene , Lee Hyewon , Kim Haseong , Lee Dae-Hee , Lee Seung-Goo 
Published: April 2020

AbstractGenetic circuit-based biosensors have emerged as an effective analytical tool in synthetic biology; these biosensors can be applied to high-throughput screening of new biocatalysts and metabolic pathways. Sigma 54 (σ54)-dependent transcription factor (TF) can be a valuable component of these biosensors owing to its intrinsic silent property compared to most of the housekeeping sigma 70 (σ70) TFs. Here, we show that these unique characteristics of σ54-dependent TFs can be used to control the host cell state to be more appropriate for high-throughput screening. The acclimation of cell state was achieved by using guanosine (penta)tetraphosphate ((p)ppGpp)-related genes (relA, spoT) and nutrient conditions, to link the σ54 TF-based reporter expression with the target enzyme activity. By controlling stringent programmed responses and optimizing assay conditions, catalytically improved tyrosine phenol lyase (TPL) enzymes were successfully obtained using a σ54-dependent DmpR as the TF component, demonstrating the practical feasibility of this biosensor. This combinatorial strategy of biosensors using σ factor-dependent TFs will allow for more effective high-throughput enzyme engineering with broad applicability.
Long-term voluntary running prevents the onset of symptomatic Friedreich’s ataxia in mice
Authors: Zhao Henan , Lewellen Bevan M. , Wilson Rebecca J. , Cui Di , Drake Joshua C. , Zhang Mei , Yan Zhen 
Published: April 2020

AbstractThe common clinical symptoms of Friedreich’s ataxia (FRDA) include ataxia, muscle weakness, type 2 diabetes and heart failure, which are caused by impaired mitochondrial function due to the loss of frataxin (FXN) expression. Endurance exercise is the most powerful intervention for promoting mitochondrial function; however, its impact on FRDA has not been studied. Here we found that mice with genetic knockout and knock-in of the Fxn gene (KIKO mice) developed exercise intolerance, glucose intolerance and moderate cardiac dysfunction at 6 months of age. These abnormalities were associated with impaired mitochondrial respiratory function concurrent with reduced iron regulatory protein 1 (Irp1) expression as well as increased oxidative stress, which were not due to loss of mitochondrial content and antioxidant enzyme expression. Importantly, long-term (4 months) voluntary running in KIKO mice starting at a young age (2 months) completely prevented the functional abnormalities along with restored Irp1 expression, improved mitochondrial function and reduced oxidative stress in skeletal muscle without restoring Fxn expression. We conclude that endurance exercise training prevents symptomatic onset of FRDA in mice associated with improved mitochondrial function and reduced oxidative stress. These preclinical findings may pave the way for clinical studies of the impact of endurance exercise in FRDA patients.
Digital Image Analysis of Heterogeneous Tuberculosis Pulmonary Pathology in Non-Clinical Animal Models using Deep Convolutional Neural Networks
Authors: Asay Bryce C. , Edwards Blake Blue , Andrews Jenna , Ramey Michelle E. , Richard Jameson D. , Podell Brendan K. , Gutiérrez Juan F. Muñoz , Frank Chad B. , Magunda Forgivemore , Robertson Gregory T. , Lyons Michael , Ben-Hur Asa , Lenaerts Anne J. 
Published: April 2020

AbstractEfforts to develop effective and safe drugs for treatment of tuberculosis require preclinical evaluation in animal models. Alongside efficacy testing of novel therapies, effects on pulmonary pathology and disease progression are monitored by using histopathology images from these infected animals. To compare the severity of disease across treatment cohorts, pathologists have historically assigned a semi-quantitative histopathology score that may be subjective in terms of their training, experience, and personal bias. Manual histopathology therefore has limitations regarding reproducibility between studies and pathologists, potentially masking successful treatments. This report describes a pathologist-assistive software tool that reduces these user limitations, while providing a rapid, quantitative scoring system for digital histopathology image analysis. The software, called ‘Lesion Image Recognition and Analysis’ (LIRA), employs convolutional neural networks to classify seven different pathology features, including three different lesion types from pulmonary tissues of the C3HeB/FeJ tuberculosis mouse model. LIRA was developed to improve the efficiency of histopathology analysis for mouse tuberculosis infection models, this approach has also broader applications to other disease models and tissues. The full source code and documentation is available from https://Github.com/TB-imaging/LIRA.
Ospemifene displays broad-spectrum synergistic interactions with itraconazole through potent interference with fungal efflux activities
Authors: Eldesouky Hassan E. , Salama Ehab A. , Hazbun Tony R. , Mayhoub Abdelrahman S. , Seleem Mohamed N. 
Published: April 2020

AbstractAzole antifungals are vital therapeutic options for treating invasive mycotic infections. However, the emergence of azole-resistant isolates combined with limited therapeutic options presents a growing challenge in medical mycology. To address this issue, we utilized microdilution checkerboard assays to evaluate nine stilbene compounds for their ability to interact synergistically with azole drugs, particularly against azole-resistant fungal isolates. Ospemifene displayed the most potent azole chemosensitizing activity, and its combination with itraconazole displayed broad-spectrum synergistic interactions against Candida albicans, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus (ΣFICI = 0.05–0.50). Additionally, in a Caenorhabditis elegans infection model, the ospemifene-itraconazole combination significantly reduced fungal CFU burdens in infected nematodes by ~75–96%. Nile Red efflux assays and RT-qPCR analysis suggest ospemifene interferes directly with fungal efflux systems, thus permitting entry of azole drugs into fungal cells. This study identifies ospemifene as a novel antifungal adjuvant that augments the antifungal activity of itraconazole against a broad range of fungal pathogens.
Polyfunctional HIV-1 specific response by CD8+ T lymphocytes expressing high levels of CD300a
Authors: Vitallé Joana , Terrén Iñigo , Gamboa-Urquijo Leire , Orrantia Ane , Tarancón-Díez Laura , Genebat Miguel , Leal Manuel , Ruiz-Mateos Ezequiel , Borrego Francisco , Zenarruzabeitia Olatz 
Published: April 2020

AbstractCD300a receptor is found on different CD8+ T cell subsets and its expression has been associated to a more cytotoxic molecular signature. CD300a has an important role in some viral infections and its expression levels are known to be modulated by human immunodeficiency virus (HIV)−1 infection on several cell types. The main objective of this work was to investigate CD300a expression and its regulation during HIV-1 specific CD8+ T cell responses. CD300a receptor expression was analysed by multiparametric flow cytometry on CD8+ T lymphocytes from HIV negative donors, naive HIV-1+ individuals and HIV-1+ subjects under suppressive combined antiretroviral therapy (cART). HIV-1 specific CD8+ T cell response was studied by stimulating cells with HIV-1 derived peptides or with a Gag HIV-1 peptide. Our results showed that HIV-1 specific CD8+ T cells expressing higher levels of CD300a were more polyfunctional showing an increased degranulation and cytokine production. Moreover, we observed an up-regulation of CD300a expression after Gag HIV-1 peptide stimulation. Finally, our results demonstrated an inverse correlation between CD300a expression on CD8+ T lymphocytes and HIV disease progression markers. In conclusion, CD300a expression is associated to a better and more polyfunctional HIV-1 specific CD8+ T cell response.
A novel mechanical chest compressor with rapid deployment in all population cardiopulmonary resuscitation
Authors: Sung Chih-Wei , Wang Hung-Chih , Shieh Jiann-Shing , Jaw Fu-Shan 
Published: April 2020

AbstractCardiopulmonary resuscitation (CPR) resuscitates patients suffering from cardiac arrest. Mechanical chest compression CPR highlights the need for high CPR quality to facilitate survival and neurological recovery. However, current CPR devices cannot be used on pregnant women or infants. These devices’ long re-setup times interrupt CPR and can cause cerebral ischemia. This study designed a novel device with a crank-sliding mechanism. The polar coordinate system (r, θ, z) shortened the setup time and enabled adjustment without moving the patient. We compared our device with commercial products (e.g., LUCAS-2) by quantifying the compression pressure. Control groups for manual CPR of trained physicians and untrained citizens were recruited. We used Resusci Anne products as models. Our results indicated that our design exhibited performance similar to that of LUCAS-2 in adults (557.8 vs. 623.6 mmHg, p = 0.217) and met the current CPR standard guidelines. Notably, our device is applicable to pregnant women [565 vs. 564.5 (adults) mmHg, p = 0.987] and infants [570.8 vs. 564.5 (adults) mmHg, p = 0.801] without lowering the compression quality. The overall compression quality and stability of mechanical chest compression CPR were favorable to those of manual CPR. Our device provides an innovative prototype for the next generation of CPR facilities.
Reduced microbial diversity induces larger volatile organic compound emissions from soils
Authors: Abis Letizia , Loubet Benjamin , Ciuraru Raluca , Lafouge Florence , Houot Sabine , Nowak Virginie , Tripied Julie , Dequiedt Samuel , Maron Pierre Alain , Sadet-Bourgeteau Sophie 
Published: April 2020

AbstractMicroorganisms in soil are known to be a source and a sink of volatile organic compounds (VOCs). The role of the microbial VOCs on soil ecosystem regulation has been increasingly demonstrated in the recent years. Nevertheless, little is known about the influence of the microbial soil community structure and diversity on VOC emissions. This novel study analyzed the effect of reduced microbial diversity in soil on VOC emissions. We found that reduced levels of microbial diversity in soil increased VOC emissions from soils, while the number of different VOCs emitted decreased. Furthermore, we found that Proteobacteria, Bacteroidetes and fungi phyla were positively correlated to VOC emissions, and other prokaryotic phyla were either negatively correlated or very slightly positively correlated to VOCs emissions. Our interpretation is that Proteobacteria, Bacteroidetes and fungi were VOC producers while the other prokaryotic phyla were consumers. Finally, we discussed the possible role of VOCs as mediators of microbial interactions in soil.
Fine mapping and candidate gene analysis of the white flower gene Brwf in Chinese cabbage (Brassica rapa L.)
Authors: Zhang Ning , Chen Lin , Ma Shuai , Wang Ruofan , He Qiong , Tian Min , Zhang Lugang 
Published: April 2020

AbstractFlower color can be applied to landscaping and identification of the purity of seeds in hybrid production. However, the molecular basis of white flower trait remains largely unknown inBrassica rapa. In this study, an F2population was constructed from the cross between 15S1040 (white flower) and 92S105 (yellow flower) for fine mapping of white flower genes inB.rapa. Genetic analysis indicated that white flower trait is controlled by two recessive loci,Brwf1andBrwf2. Using InDel and SNP markers,Brwf1was mapped to a 49.6-kb region on chromosome A01 containing 9 annotated genes, and among them,Bra013602encodes a plastid-lipid associated protein (PAP);Brwf2was located in a 59.3-kb interval on chromosome A09 harboring 12 annotated genes, in whichBra031539was annotated as acarotenoid isomerasegene (CRTISO). The amino acid sequences of BrPAP and BrCRTISO were compared between two yellow-flowered and three white-flowered lines and critical amino acid mutations of BrPAP and BrCRTISO were identified between yellow-flowered and white-flowered lines. Therefore,Bra013602andBra031539were predicted as potential candidates for white flower trait. Our results provide a foundation for further identification ofBrwfand increase understanding of the molecular mechanisms underlying white flower formation in Chinese cabbage.
A comparative study of extracellular vesicle-associated and cell-free DNA and RNA for HPV detection in oropharyngeal squamous cell carcinoma
Authors: Nguyen Bella , Meehan Katie , Pereira Michelle R. , Mirzai Bob , Lim Si Hong , Leslie Connull , Clark Michael , Sader Chady , Friedland Peter , Lindsay Andrew , Tang Colin , Millward Michael , Gray Elin S. , Lim Annette M. 
Published: April 2020

AbstractPurpose: This study compares the detection sensitivity of two separate liquid biopsy sources, cell-free (cf) DNA/RNA and extracellular vesicle (EV)-associated DNA/RNA (EV-DNA/RNA), to identify circulating Human Papilloma Virus (HPV) DNA/RNA in plasma obtained from patients with oropharyngeal squamous cell carcinoma (OPCSCC). We also report on the longitudinal changes observed in HPV-DNA levels in response to treatment. Experimental design: A prospective study was conducted that included 22 patients with locally advanced disease and six patients with metastatic OPCSCC. Twenty-three patients had HPV-related OPCSCC defined by p16 immunohistochemistry. Levels of circulating HPV-DNA and HPV-RNA from plasma-derived cf-DNA/RNA and EV-DNA/RNA were quantified using digital droplet PCR. Results: Circulating HPV-DNA was detected with higher sensitivity in cf-DNA compared to EV-DNA at 91% vs. 42% (p = <0.001). Similarly, circulating tumoral HPV-RNA was detected at a higher sensitivity in cf-RNA compared to EV-RNA, at 83% vs. 50% (p = 0.0019). In the locally advanced cohort, 100% (n = 16) of HPV-OPCSCC patients demonstrated a reduction in circulating HPV-DNA levels in cf-DNA following curative treatment, with 81% of patients demonstrating complete clearance to undetectable levels. However, in metastatic HPV-OPCSCC patients (n = 4), HPV-DNA levels did not correlate with treatment response. Conclusion: Our study demonstrates that although HPV-DNA/RNA can be detected in EV associated DNA/RNA, cf-DNA/RNA is the more sensitive liquid biopsy medium. As circulating HPV-DNA levels were found to only correlate with treatment response in the locally advanced but not metastatic setting in our small cohort of patients, the use of HPV-DNA as a dynamic biomarker to monitor treatment response requires further evaluation.
Phosphorylation of vaccinia-related kinase 1 at threonine 386 transduces glucose stress signal in human liver cells
Authors: Yokobori Kosuke , Miyauchi Yuu , Williams Jason G. , Negishi Masahiko 
Published: April 2020

Abstract
Vaccinia-related kinase 1 (VRK1) is a chromatin-associated Ser-Thr kinase that regulates numerous downstream factors including DNA repair as well as stress factors c-Jun and p53. Both c-Jun and p53 are phosphorylated at Ser63 and Thr18, respectively, in response to low glucose (40 mg/dl of medium) but not high glucose (140 mg/dl of medium) in human hepatoma-derived Huh-7 cells. Here, we have determined the molecular mechanism by which VRK1 phosphorylates these residues in response to glucose in Huh-7 cells. Human VRK1 auto-phosphorylates Ser376 and Thr386 in in vitro kinase assays. In Huh-7 cells, this auto-phosphorylation activity is regulated by glucose signaling; Thr386 is auto-phosphorylated only in low glucose medium, while Ser376 is not phosphorylated in either medium. A correlation of this low glucose response phosphorylation of Thr386 with the phosphorylation of c-Jun and p53 suggests that VRK1 phosphorylated at Thr386 catalyzes this phosphorylation. In fact, VRK1 knockdown by siRNA decreases and over-expression of VRK1 T386D increases phosphorylated c-Jun and p53 in Huh-7 cells. Phosphorylation by VRK1 of c-Jun but not p53 is regulated by cadherin Plakophilin-2 (PKP2). The PKP2 is purified from whole extracts of Huh-7 cells cultured in low glucose medium and is characterized to bind a C-terminal peptide of the VRK1 molecules to regulate its substrate specificity toward c-Jun. siRNA knockdowns show that PKP2 transduces low glucose signaling to VRK1 only to phosphorylate c-Jun, establishing the low glucose-PKP2-VRK1-c-Jun pathway as a glucose stress signaling pathway.
Angular differential kernel phases
Authors: Laugier Romain , Martinache Frantz , Cvetojevic Nick , Mary David , Ceau Alban , N’Diaye Mamadou , Kammerer Jens , Lozi Julien , Guyon Olivier , Lopez Coline 
Published: April 2020

Context. To reach its optimal performance, Fizeau interferometry requires that we work to resolve instrumental biases through calibration. One common technique used in high contrast imaging is angular differential imaging, which calibrates the point spread function and flux leakage using a rotation in the focal plane.
Aims. Our aim is to experimentally demonstrate and validate the efficacy of an angular differential kernel-phase approach, a new method for self-calibrating interferometric observables that operates similarly to angular differential imaging, while retaining their statistical properties.
Methods. We used linear algebra to construct new observables that evolve outside of the subspace spanned by static biases. On-sky observations of a binary star with the SCExAO instrument at the Subaru telescope were used to demonstrate the practicality of this technique. We used a classical approach on the same data to compare the effectiveness of this method.
Results. The proposed method shows smaller and more Gaussian residuals compared to classical calibration methods, while retaining compatibility with the statistical tools available. We also provide a measurement of the stability of the SCExAO instrument that is relevant to the application of the technique.
Conclusions. Angular differential kernel phases provide a reliable method for calibrating biased observables. Although the sensitivity at small separations is reduced for small field rotations, the calibration is effectively improved and the number of subjective choices is reduced.
Clinical Characteristics, Management, and Treatment Outcomes of
Primary Hypophysitis: A Monocentric Cohort
Authors: Oguz Seda Hanife , Soylemezoglu Figen , Sendur Suleyman Nahit , Mut Melike , Oguz Kader Karli , Dagdelen Selcuk , Erbas Tomris 
Published: April 2020

AbstractPrimary hypophysitis (PH) is a rare autoimmune inflammatory disease of the
pituitary gland. The aim of the study was to evaluate clinical
characteristics, disease management, and outcomes of cases with PH. Medical
records of PH patients admitted to Hacettepe University Hospital between
1999 and 2017 were analyzed retrospectively. Paraffin-embedded pathology
blocks were obtained for both re-examination and IgG4 immunostaining. Twenty
PH patients (15 females, 5 males) were evaluated. Mean age at diagnosis was
41.5±13.4 years. Some form of hormonal disorder was present in
63.2% of cases, hypogonadism (66.6%) being the most common.
Panhypopituitarism was present in 36.8%. All patients had pituitary
gland enlargement on magnetic resonance imaging; stalk thickening and loss
of neurohypophyseal bright spot were present in 17.6 and 23.5%,
respectively. Lymphocytic hypophysitis was the most common histopathological
subtype (50%). Among pathology specimens available for IgG and IgG4
immunostaining (n=10), none fulfilled the criteria for IgG4-related
hypophysitis. Four patients were given glucocorticoid treatment in diverse
protocols; as initial therapy in 3. Sixteen cases underwent surgery, 7 of
whom due to neuro-ophthalmologic involvement. Only 1 patient was observed
without any intervention. Reduction of pituitary enlargement was seen in all
surgical and glucocorticoid treated cases. None of the surgical patients
showed hormonal improvement while one case in glucocorticoid group improved.
PH should be considered in the differential diagnosis of sellar masses
causing hormonal deficiencies. MRI findings are usually helpful, but not yet
sufficient for definitive diagnosis of PH. Treatment usually improves
symptoms and reduces sellar masses while hormonal recovery is less
common.
Individualisierte multimodale Therapie retroperitonealer Weichteilsarkome
Authors: Ghadimi Markus 
Published: April 2020

ZusammenfassungRetroperitoneale Weichteilsarkome stellen eine histo- und molekularpathologisch differenzierte Gruppe mesenchymaler Malignome dar. Es treten in erster Linie Liposarkome und Leiomyosarkome auf – wesentlich seltener solitär-fibröse Tumoren, maligne periphere Nervenscheidentumoren und unklassifizierte pleomorphe Sarkome. In Abhängigkeit vom histopathologischen Subtyp ist ihr biologisches Verhalten hochvariabel, sodass ein differenziertes therapeutisches Vorgehen sinnvoll erscheint. Multimodale Therapiekonzepte verfügen bisher über nur geringe studiengeprüfte Evidenz, sollten aber in Abhängigkeit von Tumortopografie, Histopathologie und patientenspezifischen Faktoren geprüft werden. Die operative Strategie unterlag in den letzten 10 Jahren einer regen Kontroverse. Im Zentrum der Diskussion stand die Frage, ob eine radikale kompartimentelle Resektion unter Mitresektion klinisch-radiologisch nicht infiltrierter retroperitonealer Organe zu einem verbesserten onkologischen Langzeitergebnis beiträgt und somit zu empfehlen sei. Die Datenlage scheint diese Frage zu beantworten – ein differenziertes Vorgehen ist dennoch geboten. Entitäten mit niedrigem Lokalrezidivrisiko oder aggressivem, früh metastasierendem Verhalten sollten demnach eher organerhaltend, Tumoren mit hohem Lokalrezidivrisiko eher systematisch kompartimentell reseziert werden. Bei häufig und früh im Krankheitsverlauf metastasierenden Subentitäten sollte in der metastasenfreien Ersterkrankungssituation kritisch abgewogen werden, ob eine radikale kompartimentelle Resektion sinnvoll ist.
Benefits of CT Scanning for the Management of Knee Arthritis and Arthroplasty
Authors: Sodhi Nipun , Jacofsky David J. , Chee Alexander , Mont Michael A. 
Published: April 2020

AbstractThis review investigated the potential value of computed tomography (CT) scans for the evaluation and management of knee arthritis and arthroplasty. Specifically, we evaluated the following: (1) assessment of arthritis within knee compartments, (2) patellofemoral joint assessment, (3) implant sizing prediction, (4) component alignment, (5) soft-tissue protection, and (6) potential concerns with radiation exposure. To compare if CT or X-ray imaging is more accurate and clinically relevant, a search was performed using Boolean search operators and terms: “CT,” “radiograph,” “joint alignment,” “knee,” and “arthroplasty,” which yielded 661 results. Studies were evaluated based on (1) assessment of arthritis within knee compartments, (2) patellofemoral joint assessment, (3) implant sizing prediction, (4) component alignment, (5) soft-tissue protection, and (6) potential concerns with radiation exposure. Correlative and comparative analyses of imaging modalities to pre-, intra-, and postoperative clinical and patient-related factors were performed for the 63 included studies. CT scans were found to better detect medial and lateral arthritic changes, bony deformities, subchondral cysts, and cartilage losses. CT scans were shown to 99% accurately predict prosthetic sizes preoperatively. CT scans can also help better visualize surrounding anatomy, such as the posterior cruciate ligament, and have therefore been linked to better soft tissue protection during total knee arthroplasty. Although radiation is a potential concern, newer imaging protocols have comparable exposure to plain radiographs. Compared with plain radiographs, CT scans were found to be more accurate and provide more clinically relevant data. Therefore, the authors recommend the use of CT for the evaluation of certain patients with arthritis and for preoperative planning for knee arthroplasty.