bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interscanner and Intrascanner Comparison of Virtual Unenhanced Attenuation Values Derived From Twin Beam Dual-Energy and Dual-Source, Dual-Energy Computed Tomography
Authors: Obmann Markus M. , Kelsch Vanessa , Cosentino Aurelio , Hofmann Verena , Boll Daniel T. , Benz Matthias R. 
Published: August 2018

Objective
The aim of the current study was to evaluate the reliability and comparability of virtual unenhanced (VUE) attenuation values derived from scans of a single-source, dual-energy computed tomography using a split-filter (tbDECT) to a dual-source dual-energy CT (dsDECT).

Materials and Methods
In this retrospective study, comparisons for tbDECT and dsDECT were made within and between different dual-energy platforms. For the interscanner comparison, 126 patients were scanned with both scanners within a time interval of 224 ± 180 days; for the intrascanner comparison, another 90 patients were scanned twice with the same scanner within a time interval of 136 ± 140 days. Virtual unenhanced images were processed off of venous phase series. Attenuation values of 7 different tissues were recorded. Disagreement for VUE HU measurements greater than 10 HU between 2 scans was defined as inadequate.

Results
The interscanner analysis showed significant difference between tbDE and dsDE VUE CT values (P < 0.01) for 6 of 7 organs. Percentage of cases that had more than 10 HU difference between tbDE and dsDE for an individual patient ranged between 15% (left kidney) and 62% (spleen).
The intrascanner analysis showed no significant difference between repeat scans for both tbDECT and dsDECT (P > 0.05). However, intrascanner disagreements for the VUE HU measurements greater than 10 HU were recorded in 10% of patients scanned on the tbDECT and 0% of patients scanned on the dsDECT. The organs with the highest portion of greater than 10 HU errors were the liver and the aorta (both 20%).

Conclusions
Dual-energy techniques vary in reproducibility of VUE attenuation values. In the current study, tbDECT demonstrated higher variation in VUE HU measurements in comparison to a dsDECT. Virtual unenhanced HU measurements cannot be reliably compared on follow-up CT, if these 2 different dual-energy CT platforms are used.
Oxygen Perfusion (Persufflation) of Human Pancreata Enhances Insulin Secretion and Attenuates Islet Proinflammatory Signaling
Authors: Kelly Amy C. , Smith Kate E. , Purvis William G. , Min Catherine G. , Weber Craig S. , Cooksey Amanda M. , Hasilo Craig , Paraskevas Steven , Suszynski Thomas M. , Weegman Bradley P. , Anderson Miranda J. , Camacho Leticia E. , Harland Robert C. , Loudovaris Thomas , Jandova Jana , Molano Diana S. , Price Nicholas D. , Georgiev Ivan G. , Scott William E. , Manas Derek M.D. , Shaw James A.M. , O'Gorman Doug , Kin Tatsuya , McCarthy Fiona M. , Szot Gregory L. , Posselt Andrew M. , Stock Peter G. , Karatzas Theodore , Shapiro A.M. James , Lynch Ronald M. , Limesand Sean W. , Papas Klearchos K. 
Published: August 2018

Background
All human islets used in research and for the clinical treatment of diabetes are subject to ischemic damage during pancreas procurement, preservation, and islet isolation. A major factor influencing islet function is exposure of pancreata to cold ischemia during unavoidable windows of preservation by static cold storage (SCS). Improved preservation methods may prevent this functional deterioration. In the present study, we investigated whether pancreas preservation by gaseous oxygen perfusion (persufflation) better preserved islet function versus SCS.

Methods
Human pancreata were preserved by SCS or by persufflation in combination with SCS. Islets were subsequently isolated, and preparations in each group matched for SCS or total preservation time were compared using dynamic glucose-stimulated insulin secretion as a measure of β-cell function and RNA sequencing to elucidate transcriptomic changes.

Results
Persufflated pancreata had reduced SCS time, which resulted in islets with higher glucose-stimulated insulin secretion compared to islets from SCS only pancreata. RNA sequencing of islets from persufflated pancreata identified reduced inflammatory and greater metabolic gene expression, consistent with expectations of reducing cold ischemic exposure. Portions of these transcriptional responses were not associated with time spent in SCS and were attributable to pancreatic reoxygenation. Furthermore, persufflation extended the total preservation time by 50% without any detectable decline in islet function or viability.

Conclusions
These data demonstrate that pancreas preservation by persufflation rather than SCS before islet isolation reduces inflammatory responses and promotes metabolic pathways in human islets, which results in improved β cell function.
Multifocal motor neuropathy
Authors: Beadon Katie , Guimarães-Costa Raquel , Léger Jean-Marc 
Published: August 2018

Purpose of review
Multifocal motor neuropathy (MMN) has specific clinical and electrophysiologic features but can be difficult to diagnose if cases are not typical. Intravenous immunoglobulin (IVIg) remains the core initial and long-term treatment. In this review, recent advances in the diagnosis, monitoring and treatment of MMN are discussed.

Recent findings
The pathology of MMN likely depends on immune-mediated attack of the nodes of Ranvier and paranodal regions leading to conduction block. Antiganglioside antibodies are present in over 50% of patients. The sensitivity of antibody detection can be improved by testing for GM1/galactocerebroside (GM1/GalC) complexes. Complement activation plays a key role in the pathophysiology of MMN. Subcutaneous immunoglobulins are an efficacious alternative to IVIg for maintenance therapy in MMN. Complement inhibitor eculizumab may be a potential future treatment, but further studies are necessary.

Summary
The European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) guidelines for the diagnosis of MMN are currently widely used but probably need revision. Nerve ultrasound and plexus/nerve MRI can be helpful in diagnostic dilemmas. Monitoring of disease and response to treatment may improve using disease-specific evaluation scales such as MMN-Rasch-built overall disability scale. Further research into the pathophysiology of MMN is necessary to direct future treatment strategies.
Choosing the right label for single-molecule tracking in live bacteria: Side-by-side comparison of photoactivatable fluorescent protein and Halo tag dyes
Authors: Banaz Nehir , Mäkelä Jarno , Uphoff Stephan 
Published: August 2018

AbstractVisualizing and quantifying molecular motion and interactions inside living cells provides crucial insight into the mechanisms underlying cell function. This has been achieved by super-resolution localization microscopy and single-molecule tracking in conjunction with photoactivatable fluorescent proteins. An alternative labelling approach relies on genetically-encoded protein tags with cell-permeable fluorescent ligands which are brighter and less prone to photobleaching than fluorescent proteins but require a laborious labelling process. Either labelling method is associated with significant advantages and disadvantages that should be taken into consideration depending on the microscopy experiment planned. Here, we describe an optimised procedure for labelling Halo-tagged proteins in liveEscherichia colicells. We provide a side-by-side comparison of Halo tag with different fluorescent ligands against the popular photoactivatable fluorescent protein PAmCherry. Using test proteins with different intracellular dynamics, we evaluated fluorescence intensity, background, photostability, and single-molecule localization and tracking results. Capitalising on the brightness and extended spectral range of fluorescent Halo ligands, we also demonstrate high-speed and dual-colour single-molecule tracking.
HIF-2α drives an intrinsic vulnerability to ferroptosis in clear cell renal cell carcinoma
Authors: Zou Yilong , Palte Michael J. , Deik Amy A. , Li Haoxin , Eaton John K. , Wang Wenyu , Tseng Yuen-Yi , Deasy Rebecca , Alimova Maria , Dančík Vlado , Leshchiner Elizaveta S. , Viswanathan Vasanthi S. , Signoretti Sabina , Choueiri Toni K. , Boehm Jesse S. , Wagner Bridget K. , Doench John , Clish Clary B. , Clemons Paul A. , Schreiber Stuart L. 
Published: August 2018

SUMMARYKidney cancers are characterized by extensive metabolic reprogramming and resistance to a broad range of anti-cancer therapies. By interrogating the Cancer Therapeutics Response Portal compound sensitivity dataset, we show that cells of clear-cell renal cell carcinoma (ccRCC) possess a lineage-specific vulnerability to ferroptosis that can be exploited by inhibiting glutathione peroxidase 4 (GPX4). Using genome-wide CRISPR screening and lipidomic profiling, we reveal that this vulnerability is driven by the HIF-2α–HILPDA pathway by inducing a polyunsaturated fatty acyl (PUFA)-lipid-enriched cell state that is dependent on GPX4 for survival and susceptible to ferroptosis. This cell state is developmentally primed by the HNF-1β–1-Acylglycerol-3-Phosphate O-Acyltransferase 3 (AGPAT3) axis in the renal lineage. In addition to PUFA metabolism, ferroptosis is facilitated by a phospholipid flippase TMEM30A involved in membrane topology. Our study uncovers an oncogenesis-associated vulnerability, delineates the underlying mechanisms and suggests targeting GPX4 to induce ferroptosis as a therapeutic opportunity in ccRCC.HIGHLIGHTSccRCC cells exhibit strong susceptibility to GPX4 inhibition-induced ferroptosisThe GPX4-dependent and ferroptosis-susceptible state in ccRCC is associated with PUFA-lipid abundanceThe HIF-2α–HILPDA axis promotes the selective deposition of PUFA-lipids and ferroptosis susceptibilityAGPAT3 selectively synthesizes PUFA-phospholipids and primes renal cells for ferroptosis
Theta oscillations show impaired interference detection in the elderly during selective memory retrieval
Authors: Ferreira Catarina S. , Jesús Maraver Maria , Hanslmayr Simon , Teresa Bajo 
Published: August 2018

ABSTRACTSeemingly effortless tasks, such as recognizing faces and retrieving names, become significantly harder as people get older. These age-related difficulties may be partially due to the concurrent activation of related competitors. However, it remains unclear whether older adults struggle with detecting an early interference signal or with suppressing irrelevant competitors once competition is detected. To investigate this question, we used the retrieval practice paradigm, shown to elicit interference, while recording electrophysiological activity in young and older adults. In two experiments, young participants showed the typical Retrieval Induced Forgetting (RIF) effect whereas the elderly did not. Neurally, young adults were more capable to detect interference than the older, as evidenced by an increase in mid-frontal theta power (~4-8Hz). This efficient interference detection allowed young adults to recruit inhibitory mechanisms that overcome competition, as traced by a theta power reduction across retrieval cycles. No such reduction was found for the elderly, indicating that the lack of an early interference detection signal renders older adults unable to recruit memory selection mechanisms, eliminating RIF.AUTHORS NOTEThis research was supported by the doctoral research grants AP2009-2215 to C.S.F and BES-2013-066842 to M.J.M.; by grants PSI2012-33625; PSI2015-65502-C2-1-P from the Spanish Ministry of Economy and Competiveness, and by the Economic Council of the Andalusian Government P08-HUM-03600-Feder and P12-CTS-2369-Feder to T.B.Declaration of interestThe authors have no conflicts of interest to disclose
A specialized MreB-dependent complex mediates the formation of stalk-specific peptidoglycan in Caulobacter crescentus
Authors: Billini Maria , Biboy Jacob , Kühn Juliane , Vollmer Waldemar , Thanbichler Martin 
Published: August 2018

AbstractMany bacteria have complex cell shapes, but the mechanisms producing their distinctive morphologies are still poorly understood.Caulobacter crescentus, for instance, exhibits a stalk-like extension that carries an adhesive holdfast mediating surface attachment. This structure forms through zonal peptidoglycan biosynthesis at the old cell pole and elongates extensively under phosphate-limiting conditions. We analyzed the composition of cell body and stalk peptidoglycan and identified significant differences in the nature and proportion of peptide crosslinks, indicating that the stalk represents a distinct subcellular domain with specific mechanical properties. To identify factors that participate in stalk formation, we systematically inactivated and localized predicted components of the cell wall biosynthetic machinery ofC. crescentus. Our results show that the biosynthesis of stalk peptidoglycan involves a dedicated peptidoglycan biosynthetic complex that combines specific components of the divisome and elongasome, suggesting that the repurposing of pre-existing machinery provides a straightforward means to evolve new morphological traits.
Structure-activity relationship of flavin analogs that target the FMN riboswitch
Authors: Vicens Quentin , Mondragón Estefanía , Reyes Francis E. , Coish Philip , Berman Paul Aristoff Judd , Kaur Harpreet , Kells Kevin W. , Wickens Phil , Wilson Jeffery , Gadwood Robert C. , Schostarez Heinrich J. , Suto Robert K. , Blount Kenneth F. , Batey Robert T. 
Published: August 2018

ABSTRACTThe flavin mononucleotide (FMN) riboswitch is an emerging target for the development of novel RNA-targeting antibiotics. We previously discovered an FMN derivative —5FDQD— that protects mice against diarrhea-causingClostridium difficilebacteria. Here, we present the structure-based drug design strategy that led to the discovery of this fluoro-phenyl derivative with antibacterial properties. This approach involved the following stages: (1) structural analysis of all available free and bound FMN riboswitch structures; (2) design, synthesis and purification of derivatives; (3)in vitrotesting for productive binding using two chemical probing methods; (4)in vitrotranscription termination assays; (5) resolution of the crystal structures of the FMN riboswitch in complex with the most mature candidates. In the process, we delineated principles for productive binding to this riboswitch, thereby demonstrating the effectiveness of a coordinated structure-guided approach to designing drugs against RNA.GRAPHICAL ABSTRACTExploring the chemical structure landscape of FMN riboswitch binders.
Discovery of allele-specific protein-RNA interactions in human transcriptomes
Authors: Bahrami-Samani Emad , Xing Yi 
Published: August 2018

AbstractGene expression is tightly regulated at the post-transcriptional level through splicing, transport, translation, and decay. RNA-binding proteins (RBPs) play key roles in post-transcriptional gene regulation, and genetic variants that alter RBP-RNA interactions can affect gene products and functions. We developed a computational method ASPRIN (Allele-Specific Protein-RNA Interaction), that uses a joint analysis of CLIP-seq (cross-linking and immunoprecipitation followed by high-throughput sequencing) and RNA-seq data to identify genetic variants that alter RBP-RNA interactions by directly observing the allelic preference of RBP from CLIP-seq experiments as compared to RNA-seq. We used ASPRIN to systematically analyze CLIP-seq and RNA-seq data for 166 RBPs in two ENCODE (Encyclopedia of DNA Elements) cell lines. ASPRIN identified genetic variants that alter RBP-RNA interactions by modifying RBP binding motifs within RNA. Moreover, through an integrative ASPRIN analysis with population-scale RNA-seq data, we showed that ASPRIN can help reveal potential causal variants that affect alternative splicing via allele-specific protein-RNA interactions.
AlleleHMM: a data-driven method to identify allele-specific differences in distributed functional genomic marks
Authors: Chou Shao-Pei , Danko Charles G. 
Published: August 2018

AbstractHow DNA sequence variation influences gene expression remains poorly understood. Diploid organisms have two homologous copies of their DNA sequence in the same nucleus, providing a rich source of information about how genetic variation affects a wealth of biochemical processes. However, few computational methods have been developed to discover allele-specific differences in functional genomic data. Existing methods either treat each SNP independently, limiting statistical power, or combine SNPs across gene annotations, preventing the discovery of allele specific differences in unexpected genomic regions. Here we introduce AlleleHMM, a new computational method to identify blocks of neighboring SNPs that share similar allele-specific differences in mark abundance. AlleleHMM uses a hidden Markov model to divide the genome among three hidden states based on allele frequencies in genomic data: a symmetric state (state ‘S’) which shows no difference between alleles, and regions with a higher signal on the maternal (state M) or paternal (state P) allele. AlleleHMM substantially outperformed naive methods using both simulated and real genomic data, particularly when input data had realistic levels of overdispersion. Using PRO-seq data, AlleleHMM identified thousands of allele specific blocks of transcription in both coding and non-coding genomic regions. AlleleHMM is a powerful tool for discovering allele-specific regions in functional genomic datasets.
RNAmountAlign: efficient software for local, global, semiglobal pairwise and multiple RNA sequence/structure alignment
Authors: Bayegan Amir H , Clote Peter 
Published: August 2018

AbstractAlignment of structural RNAs is an important problem with a wide range of applications. Since function is often determined by molecular structure, RNA alignment programs should take into account both sequence and base-pairing information for structural homology identification. A number of successful alignment programs are heuristic versions of Sankoff’s optimal algorithm. Most of them require O(n4) run time. This paper describes C++ software, RNAmountAlign, for RNA sequence/structure alignment that runs in O(n3) time and O(n2) space; moreover, our software returns a p-value (transformable to expect value E) based on Karlin-Altschul statistics for local alignment, as well as parameter fitting for local and global alignment. Using incremental mountain height, a representation of structural information computable in cubic time, RNAmountAlign implements quadratic time pairwise local, global and global/semiglobal (query search) alignment using a weighted combination of sequence and structural similarity. RNAmountAlign is capable of performing progressive multiple alignment as well. Benchmarking of RNAmountAlign against LocARNA, LARA, FOLDALIGN, DYNALIGN and STRAL shows that RNAmountAlign has reasonably good accuracy and much faster run time supporting all alignment types.AvailabilityRNAmountAlign is publicly available at http://bioinformatics.bc.edu/clotelab/RNAmountAlign.
Development of whole-porcine monoclonal antibodies with potent neutralization activity against classical swine fever virus (CSFV) from single B cells
Authors: Dong Haisi , Lv Dongmei , Su Ang , Ma Lerong , Dong Jianwei , Guo Nannan , Ren Linzhu , Jiao Huping , Pang Daxin , Ouyang Hongsheng 
Published: August 2018

AbstractClassical swine fever (CSF) is a highly contagious swine disease found worldwide that has caused devastating economic losses. However, there are few efficacious mAbs against the CSF virus (CSFV) that can be used for treatment because most mAbs against CSFV are derived from mouse hybridoma cells and these murine mAbs have disadvantages of inefficient effector functions elicitations and high immunogenicity in vivo. Accordingly, we characterized whole-porcine anti-CSFV neutralizing mAbs (NAbs) isolated directly from single B cells sorted from a CSFV-vaccinated pig using the fluoresceinated conserved linear neutralizing epitope of the CSFV E2 protein and fluorophore conjugated goat anti-pig IgG. Immunoglobulin (Ig) genes were isolated via nested PCR, and two porcine mAbs termed HK24 and HK44 were produced. We determined that these mAbs can bind to E2 protein and recognize sites within this major antigenic epitope. In addition, we found that mAbs HK24 and HK44 exhibit potent neutralizing activity against CSFV, and they can protect PK-15 cells from infections in vitro with potent IC50 values of 9.3 μg/ml and 0.62 μg/ml, respectively. Notably, we demonstrated that these two mAbs can be used as novel reagents for detecting virus infection. These data suggest that our results not only provide a method for efficiently obtaining mAbs against CSFV but also offer promising mAb candidates for development of antibody-based diagnostic and antiviral agents.ImportanceNeutralizing monoclonal antibodies (NAbs) can prevent and may slow the spread of virus infection. The discovery of NAbs that recognize classical swine fever virus (CSFV) necessitates new technologies because the NAbs produced by immunization and hybridoma technology could not be transferred to in vivo research. Multiple full-length human therapeutic antibodies have been produced via single-cell polymerase chain reactions but whole-porcine NAbs for CSFV have not been generated. In this study, two whole-porcine mAbs, named HK24 and HK44, were isolated from epitope-specific single B cells. We demonstrate that these two mAbs have potent neutralizing activity against CSFV and can protect cells against viral infection. Therefore, they may facilitate the development of vaccines or antiviral drugs that offer the advantages of stability and low immunogenicity.
The C-terminal tail of the bacterial translocation ATPase SecA modulates its activity
Authors: Jamshad Mohammed , Knowles Timothy J. , White Scott A. , Ward Douglas G. , Mohammed Fiyaz , Rahman Kazi , Hughes Gareth W. , Kramer Günter , Bukau Bernd , Huber Damon 
Published: August 2018

AbstractIn bacteria, the translocation of a subset of proteins across the cytoplasmic membrane by the Sec machinery requires SecA. Although SecA can recognise nascent polypeptides, the mechanism of cotranslational substrate protein recognition is not known. Here, we investigated the role of the C-terminal tail (CTT) of SecA, which consists of a flexible linker (FLD) and a small metal-binding domain (MBD), in its interaction with nascent polypeptides. Phylogenetic analysis and ribosome binding experiments indicated that the MBD interacts with 70S ribosomes. Disruption of the entire CTT or the MBD alone had opposing effects on ribosome binding, substrate-protein binding, ATPase activity and in vivo function. Autophotocrosslinking, mass spectrometry, x-ray crystallography and small-angle x-ray scattering experiments provided insight into the CTT-mediated conformational changes in SecA. Finally, photocrosslinking experiments indicated that binding of SecA to substrate protein affected its interaction with the ribosome. Taken together, our results suggest a mechanism for substrate protein recognition.Impact StatementSecA is an evolutionarily conserved ATPase that is required for the translocation of a subset of proteins across the cytoplasmic membrane in bacteria. We investigated how SecA recognises its substrate proteins at the ribosome as they are still being synthesised (i.e. cotranslationally).