bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incomplete Facial Paralysis: The Use of the Ipsilateral Residual Facial Nerve as a Donor Nerve for Facial Reanimation
Authors: Gur Eyal , Zuker Ron M. , Zaretski Arik , Leshem David , Barnea Yoav , Arad Ehud , Yanko Ravit , Meilik Benjamin , Kedar Daniel J. , Fliss Ehud 
Published: April 2018

Background:
The reconstructive approach for incomplete facial paralysis is not yet determined. In this article, the authors present a new surgical approach for patients with incomplete facial paralysis in which residual, ineffective movement is detected preoperatively in the ipsilateral buccozygomatic territory of the paretic facial nerve.

Methods:
Sixteen patients with incomplete facial paralysis were found eligible for the procedure and underwent one-stage facial reanimation performed by the senior author (E.G.). Reanimation was performed using free gracilis muscle transfer with neural coaptation to an active facial nerve branch(es) responsible for the predetected buccozygomatic residual movement. Patients were reviewed in a systematic fashion using a combined still photographic and video scoring scale for symmetry at rest and at dynamic states.

Results:
Following surgery, improved symmetry was observed in the majority of observations of the mouth region at rest and while smiling and of the nasolabial fold region while smiling. There was no significant change in symmetry in the majority of observations of the eye region at rest and while smiling and the nasolabial fold region at rest. Video assessment of dynamic facial symmetry while smiling demonstrated improved symmetry in 91 percent of the observations (n = 191 observations). Comparison of mean scores for dynamic smile symmetry produced a statistically significant improvement of 1.68 points following surgery (p < 0.001).

Conclusion:
Based on this series, the authors recommend that use of the ipsilateral facial nerve buccozygomatic residual branch be considered as a donor nerve for facial reanimation using a free gracilis muscle transfer in patients with incomplete facial paralysis with residual preoperative movement in the midface.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Association Between Alexithymia and Risk of Incident Cardiovascular Diseases in the SUpplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) Cohort
Authors: Wiernik Emmanuel , Lemogne Cédric , Fezeu Léopold , Arnault Nathalie , Hercberg Serge , Kesse-Guyot Emmanuelle , Galan Pilar 
Published: April 2018

ABSTRACT

Objective
Although it has been suggested that alexythymia is associated with cardiovascular diseases, studies are scarce and a causal relationship is questionable. This study explored the prospective association between alexithymia and cardiovascular events in middle-aged participants without cardiovascular history at baseline.

Methods
The 26-item Toronto Alexithymia Scale (TAS-26) was completed by 5586 participants of the French SUpplémentation en VItamines et Minéraux AntioXydants cohort (41.4% of men, M [SD] age = 52.2 [6.3] years) in 1996–1997. Covariates measured at baseline included age, occupational status, depressive symptoms, smoking status, body mass index, hypertension, diabetes, hypercholesterolemia, and hypertriglyceridemia. The follow-up ran from January 1, 1998, to the date of the first cardiovascular event, the date of death or September 1, 2007, whichever occurred first. Cardiovascular events were validated by an independent expert committee. Hazard ratios and 95% confidence intervals were computed with Cox regressions.

Results
During an average of 8.9 years of follow-up, 171 first cardiovascular events were validated. After adjustment for age, sex, and occupational status, there was no association between baseline alexithymia and cardiovascular events at follow-up (hazard ratio [95% confidence interval] for 15 points of TAS-26 = 1.00 [0.81–1.23], p > .99). Adjusting for all covariates, using binary TAS-26 cut-offs or TAS-26 subscores yielded similar nonsignificant results.

Conclusions
In this large prospective study, alexithymia and cardiovascular events were not associated among a nonclinical population. This casts some doubt on whether alexithymia could be a meaningful target in the prevention of cardiovascular diseases.

Clinical Trial Registration
Clinicaltrials.gov (NCT00272428).
Mercury methylating microbial communities of boreal forest soils
Authors: Xu Jingying , Buck Moritz , Eklöf Karin , Osman Omneya , Schaefer Jeffra K. , Bishop Kevin , Björn Erik , Skyllberg Ulf , Bertilsson Stefan , Bravo Andrea G. 
Published: April 2018

AbstractThe formation of the potent neurotoxic methylmercury (MeHg) is a microbially mediated process that has raised much concern because MeHg poses threats to wildlife and human health. Since boreal forest soils can be a source of MeHg in aquatic networks, it is crucial to understand the biogeochemical processes involved in the formation of this pollutant. High-throughput sequencing of 16S rRNA and the mercury methyltransferase,hgcA, combined with geochemical characterisation of soils, were used to determine the microbial populations contributing to MeHg formation in forest soils across Sweden. ThehgcAsequences obtained were distributed among diverse clades, includingProteobacteria, Firmicutes, andMethanomicrobia,withDeltaproteobacteria, particularlyGeobacteraceae, dominating the libraries across all soils examined. Our results also suggest that MeHg formation is linked to the composition of also non-mercury methylating bacterial communities, likely providing growth substrate (e.g. acetate) for thehgcA-carrying microorganisms responsible for the actual methylation process. While previous research focused on mercury methylating microbial communities of wetlands, this study provides some first insights into the diversity of mercury methylating microorganisms in boreal forest soils.ImportanceDespite a global state of awareness that mercury, and methylmercury in particular, is a neurotoxin that millions of people continue to be exposed to, there are sizable gaps in our fundamental understanding of the processes and organisms involved in methylmercury formation. In the present study we shed light on the diversity of the microorganisms responsible for methylmercury formation in boreal forest soils. All the microorganisms identified have a relevant role on the processing of organic matter in soils. Moreover, our results show that the formation of methylation formation is not only linked to mercury methylating microorganisms but also to the presence of non-mercury methylating bacterial communities that contribute to methylmercury formation by the appropriate substrate to the microorganisms responsible for the actual methylation process. This study improves current knowledge on the diversity of organisms involved in methylmercury formation in soils.
Multilayer view of pathogenic SNVs in human interactome throughin-silicoedgetic profiling
Authors: Cui Hongzhu , Zhao Nan , Korkin Dmitry 
Published: April 2018

ABSTRACTNon-synonymous mutations linked to the complex diseases often have a global impact on a biological system, affecting large biomolecular networks and pathways. However, the magnitude of the mutation-driven effects on the macromolecular network is yet to be fully explored. In this work, we present an systematic multi-level characterization of human mutations associated with genetic disorders by determining their individual and combined interaction-rewiring, “edgetic”, effects on the human interactome. Ourin-silicoanalysis highlights the intrinsic differences and important similarities between the pathogenic single nucleotide variants (SNVs) and frameshift mutations. We show that pathogenic SNVs are more likely to cause gene pleiotropy than pathogenic frameshift mutations and are enriched on the protein interaction interfaces. Functional profiling of SNVs indicates widespread disruption of the protein-protein interactions and synergistic effects of SNVs. The coverage of our approach is several times greater than the recently published experimental study and has the minimal overlap with it, while the distributions of determined edgotypes between the two sets of profiled mutations are remarkably similar. Case studies reveal the central role of interaction-disrupting mutations in type 2 diabetes mellitus, and suggest the importance of studying mutations that abnormally strengthen the protein interactions in cancer. With the advancement of next-generation sequencing technology that drives precision medicine, there is an increasing demand in understanding the changes in molecular mechanisms caused by the patient-specific genetic variation. The current and futurein-silicoedgotyping tools present a cheap and fast solution to deal with the rapidly growing datasets of discovered mutations.
Pushing the limits of de novo genome assembly for complex prokaryotic genomes harboring very long, near identical repeats
Authors: Schmid Michael , Frei Daniel , Patrignani Andrea , Schlapbach Ralph , Frey Jürg E. , Remus-Emsermann Mitja N.P. , Ahrens Christian H. 
Published: April 2018

AbstractGenerating a complete, de novo genome assembly for prokaryotes is often considered a solved problem. However, we here show that Pseudomonas koreensis P19E3 harbors multiple, near identical repeat pairs up to 70 kilobase pairs in length. Beyond long repeats, the P19E3 assembly was further complicated by a shufflon region. Its complex genome could not be de novo assembled with long reads produced by Pacific Biosciences’ technology, but required very long reads from the Oxford Nanopore Technology. Another important factor for a full genomic resolution was the choice of assembly algorithm.Importantly, a repeat analysis indicated that very complex bacterial genomes represent a general phenomenon beyond Pseudomonas. Roughly 10% of 9331 complete bacterial and a handful of 293 complete archaeal genomes represented this dark matter for de novo genome assembly of prokaryotes. Several of these dark matter genome assemblies contained repeats far beyond the resolution of the sequencing technology employed and likely contain errors, other genomes were closed employing labor-intense steps like cosmid libraries, primer walking or optical mapping. Using very long sequencing reads in combination with assemblers capable of resolving long, near identical repeats will bring most prokaryotic genomes within reach of fast and complete de novo genome assembly.
Evidence for multifactorial processes underlying phenotypic variation in bat visual opsins
Authors: Sadier Alexa , Davies Kalina T. J. , Yohe Laurel R. , Yun Kun , Donat Paul , Hedrick Brandon P. , Dumont Elizabeth R. , Dávalos Liliana M. , Rossiter Stephen J. , Sears Karen E. 
Published: April 2018

AbstractStudies of opsin genes offer insights into the evolutionary history and molecular basis of vertebrate color vision, but most assume intact open reading frames equate to functional phenotypes. Despite known variation in opsin repertoires and associated visual phenotypes, the genetic basis of such patterns has not been examined at each step of the central dogma. By comparing sequences, gene expression, and protein localization across a hyperdiverse group of mammals, noctilionoid bats, we find evidence that independent losses of S-opsin arose through disruptions at different stages of protein synthesis, while maintenance relates to frugivory. Discordance between DNA, RNA, and protein reveals that the loss of short-wave sensitivity in some lineages resulted from transcriptional and post-transcriptional changes in addition to degradation of open reading frames. These mismatches imply that visual phenotypes cannot reliably be predicted from genotypes alone, and connect ecology to multiple mechanisms behind the loss of color in vertebrates.
Molecular mechanisms controlling the multistage post-translational processing of endogenous Nrf1α/TCF11 proteins to yield distinct proteoforms within the coupled positive and negative feedback circuits
Authors: Xiang Yuancai , Wang Meng , Hu Shaofan , Qiu Lu , Yang Fang , Zhang Zhengwen , Yu Siwang , Pi Jingbo , Zhang Yiguo 
Published: April 2018

ABSTRACTIn an attempt to terminate the chaotic state of the literature on Nrf1/TCF11 with various confused molecular masses, we herein establish a generally acceptable criterion required for identification of its endogenous full-length proteins and derivative isoforms expressed differentially in distinct experimental cell lines. Further work has been focused on the molecular mechanisms that dictate the successive multistate post-translational modifications (i.e. glycosylation by OST, deglycosylation by NGLY, and ubiquitination by Hrd1) of this CNC-bZIP protein and its proteolytic processing to yield multiple isoforms. Several lines of experimental evidence have demonstrated that the nascent Nrf1α/TCF11 polypeptide (non-glycosylated) is transiently translocated into the endoplasmic reticulum (ER), in which it becomes an inactive glycoprotein-A, and also folded in a proper topology within and around membranes. Thereafter, dynamic repositioning of the ER-resident domains in Nrf1 glycoprotein is driven by p97-fueled retrotranslocation into extra-ER compartments. Therein, glycoprotein of Nrf1 is allowed for digestion into a deglycoprotein-B and then its progressive proteolytic processing by cytosolic DDI-1/2 and proteasomes to yield distinct proteoforms (i.e. protein-C/D). The processing is accompanied by removal of a major N-terminal ~12.5-kDa polypeptide from Nrf1α. Interestingly, our present study has further unraveled that coupled positive and negative feedback circuits exist between Nrf1 and its cognate target genes, including those encoding its regulators p97, Hrd1, DDI-1 and proteasomes. These key players are differentially or even oppositely involved in diverse cellular signalling responses to distinct extents of ER-derived proteotoxic and oxidative stresses induced by different concentrations of proteasomal inhibitors.
Direct RNA Sequencing of the Complete Influenza A Virus Genome
Authors: Keller Matthew W. , Rambo-Martin Benjamin L. , Wilson Malania M. , Ridenour Callie A. , Shepard Samuel S. , Stark Thomas J. , Neuhaus Elizabeth B. , Dugan Vivien G. , Wentworth David E. , Barnes John R. 
Published: April 2018

ABSTRACTFor the first time, a complete genome of an RNA virus has been sequenced in its original form. Previously, RNA was sequenced by the chemical degradation of radiolabelled RNA, a difficult method that produced only short sequences. Instead, RNA has usually been sequenced indirectly by copying it into cDNA, which is often amplified to dsDNA by PCR and subsequently analyzed using a variety of DNA sequencing methods. We designed an adapter to short highly conserved termini of the influenza virus genome to target the (-) sense RNA into a protein nanopore on the Oxford Nanopore MinION sequencing platform. Utilizing this method and total RNA extracted from the allantoic fluid of infected chicken eggs, we demonstrate successful sequencing of the complete influenza virus genome with 100% nucleotide coverage, 99% consensus identity, and 99% of reads mapped to influenza. By utilizing the same methodology we can redesign the adapter in order to expand the targets to include viral mRNA and (+) sense cRNA, which are essential to the viral life cycle. This has the potential to identify and quantify splice variants and base modifications, which are not practically measurable with current methods.
Visual reconstruction from 2-photon calcium imaging suggests linear readout properties of neurons in mouse primary visual cortex
Authors: Garasto Stef , Bharath Anil A. , Schultz Simon R. 
Published: April 2018

AbstractDeciphering the neural code, that is interpreting the responses of sensory neurons from the perspective of a downstream population, is an important step towards understanding how the brain processes sensory stimulation. While previous work has focused on classification algorithms to identify the most likely stimulus label in a predefined set of categories, fewer studies have approached a full stimulus reconstruction task. Outstanding questions revolve around the type of algorithm that is most suited to decoding (i.e. full reconstruction, in the context of this study), especially in the presence of strong encoding non-linearities, and the possible role of pairwise correlations. We present, here, the first pixel-by-pixel reconstruction of a complex natural stimulus from 2-photon calcium imaging responses of mouse primary visual cortex (V1). We decoded the activity of approximately 100 neurons from layer 2/3 using an optimal linear estimator and an artificial neural network. We also investigated how much accuracy is lost in this decoding operation when ignoring pairwise neural correlations. We found that a simple linear estimator is sufficient to extract relevant stimulus features from the neural responses, and that it was not significantly outperformed by a non-linear decoding algorithm. The importance of pairwise correlations for reconstruction accuracy was also limited. The results of this study suggest that, conditional on the spatial and temporal limits of the recording technique, V1 neurons display linear readout properties, with low information content in the joint distribution of their activity.
Precise detection of S phase onset reveals decoupled G1/S transition events
Authors: Grant Gavin D. , Kedziora Katarzyna M. , Limas Juanita C. , Purvis Jeremy E. , Cook Jeanette Gowen 
Published: April 2018

AbstractThe eukaryotic cell division cycle is the process by which cells duplicate their genomes and proliferate. Transitions between sequential cell cycle phases are tightly orchestrated to ensure precise and efficient cell cycle progression. Interrogating molecular events at these transitions is important for understanding normal and pathological cell proliferation and mechanisms that ensure genome stability. A popular fluorescent reporter system known as “FUCCI” has been widely adopted for identifying cell cycle phases. Using time-lapse fluorescence microscopy, we quantitatively analyzed the dynamics of the FUCCI reporters relative to the transitions into and out of S phase. Although the original reporters reflect the E3 ubiquitin ligase activities for which they were designed, SCFSkp2 and APCCdh1, their dynamics are significantly and variably offset from actual S phase boundaries. To precisely mark these transitions, we generated and thoroughly validated a new reporter containing a PCNA-interacting protein degron whose oscillations are directly coupled to the process of DNA replication itself. We combined this reporter with the geminin-based APCCdh1 reporter to create “PIP-FUCCI.” PIP degron reporter dynamics closely correlate with S phase transitions irrespective of reporter expression levels. Using PIP-FUCCI, we made the unexpected observation that the apparent timing of APCCdh1 inactivation frequently varies relative to the onset of S phase. We demonstrate that APCCdh1 inactivation is not a strict pre-requisite for S phase entry, though delayed APCCdh1 inactivation correlates with longer S phase. Our results illustrate the benefits of precise delineation of cell cycle phase boundaries for uncovering the sequences of molecular events at critical cell cycle transitions.
Translation elongation and mRNA stability are coupled through the ribosomal A-site
Authors: Hanson Gavin , Alhusaini Najwa , Morris Nathan , Sweet Thomas , Coller Jeff 
Published: April 2018

AbstractMessenger RNA (mRNA) degradation plays a critical role in regulating transcript levels in eukaryotic cells. Previous work by us and others has shown that codon identity exerts a powerful influence on mRNA stability. InSaccharomyces cerevisiae, studies using a handful of reporter mRNAs show that optimal codons increase translation elongation rate, which in turn increase mRNA stability. However, a direct link between elongation rate and mRNA stability has not been established across the entire yeast transcriptome. In addition, there is evidence from work in higher eukaryotes that amino acid identity influences mRNA stability, raising the question as to whether the impact of translation elongation on mRNA decay is at the level of tRNA decoding, amino acid incorporation, or some combination of each. To address these questions, we performed ribosome profiling of wildtype yeast. In good agreement with other studies, our data showed faster codon-specific elongation over optimal codons and faster transcript-level elongation correlating with transcript optimality. At both the codon-level and transcript-level, faster elongation correlated with increased mRNA stability. These findings were reinforced by showing increased translation efficiency and kinetics for a panel of 11HIS3reporter mRNAs of increasing codon optimality. While we did observe that elongation measured by ribosome profiling is composed of both amino acid identity and synonymous codon effects, further analyses of these data establish that A-site tRNA decoding rather than other steps of translation elongation is driving mRNA decay in yeast.
RNAs as proximity labeling media for identifying nuclear speckle positions relative to the genome
Authors: Chen Weizhong , Yan Zhangming , Li Simin , Huang Norman , Huang Xuerui , Zhang Jin , Zhong Sheng 
Published: April 2018

AbstractNuclear speckles are interchromatin structures enriched in RNA splicing factors. Determining their relative positions with respect to the folded nuclear genome could provide critical information on co-and post-transcriptional regulation of gene expression. However, it remains challenging to identify which parts of the nuclear genome are in proximity to nuclear speckles, due to physical separation between nuclear speckle cores and chromatin. We hypothesized that noncoding RNAs including small nuclear RNAs, 7SK and Malat1, which accumulate at the periphery of nuclear speckles (nsaRNA,nuclearspeckleassociated RNA), may extend to sufficient proximity to the nuclear genome. Leveraging a transcriptome-genome interaction assay (MARGI), we identified nsaRNA-interacting genomic sequences, which exhibited clustering patterns (nsaPeaks) in the genome, suggesting existence of relatively stable interaction sites for nsaRNAs in nuclear genome. Posttranscriptional pre-mRNAs, which are known to be clustered to nuclear speckles, exhibited proximity to nsaPeaks but rarely to other genomic regions. Furthermore, CDK9 proteins that localize to the vicinity of nuclear speckles produced ChIP-seq peaks that overlapped with nsaPeaks. Our combined DNA FISH and immunofluorescence analysis in 182 single cells revealed a 3-fold increase in odds for nuclear speckles to localize near an nsaPeak than its neighboring genomic sequence. These data suggest a model that nsaRNAs locate in sufficient proximity to nuclear genome and leave identifiable genomic footprints, thus revealing the parts of genome proximal to nuclear speckles.
Insights into centriole biogenesis and evolution revealed by cryoTomography of doublet and triplet centrioles
Authors: Greenan G. , Keszthelyi B. , Vale R. D. , Agard D. A. 
Published: April 2018

AbstractCentrioles are cylindrical assemblies comprised of 9 singlet, doublet, or triplet microtubules, essential for the formation of motile and sensory cilia. While the structure of the cilium is being defined at increasing resolution, centriolar structure remains poorly understood. Here, we used electron cryo-tomography to determine the structure of mammalian (triplet) andDrosophila(doublet) centrioles at 25 Å resolution. Mammalian centrioles have two distinct domains: a 200 nm proximal core region connected by A-C linkers, and a distal domain where the C-tubule is incomplete and a pair of novel linkages stabilize the assembly producing a geometry more closely resembling the ciliary axoneme.Drosophilacentrioles more closely resemble the mammalian core, but with their doublets linked through A tubules. The commonality of core region length, and the abrupt transition in mammalian centrioles, suggests a conserved length-setting mechanism. The unexpected linker diversity suggests how unique centriolar architectures arise in different tissues and organisms.