bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intralesional Laser Treatment for Dermal Filler Complications
Authors: Schelke Leonie W. , Decates Tom S. , van der Lugt Claudia I. M. , Pelzer Levi , de Mey Gabrielle , Velthuis Peter J. 
Published: May 2018

Background:
For complications caused by filler treatments, in general, two treatment regimens are advised: systemic drugs and surgical removal of the material. Another possible treatment option would be removal of the material by intralesional laser treatment.

Methods:
Two hundred forty-two patients with complications caused by fillers were treated with intralesional laser treatment.

Results:
In the majority of patients, an improvement was achieved (92 percent), in 9 percent the complication was resolved, and in 3 percent it was not improved (unknown in the rest).

Conclusion:
Considering the large number of patients treated until now and the efficacy and good safety profile of this treatment, the authors plead that intralesional laser treatment may be considered as a treatment option before surgery.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Adipofascial Flaps With Acellular Dermal Matrix Compared With Myocutaneous Flap Reconstruction in Lumbar Myelomeningocele Defects
Authors: Pourtaheri Navid , Wang Derek , Calva Daniel , Chopra Karan , Kumar Anand R. 
Published: May 2018

Background:
Adipofascial flaps (AFF) with acellular dermal matrix (ADM) have the potential to reconstruct neural tube defects without sacrificing muscle that may be critical for long-term function. Comparative studies between myocutaneous flap (MF) reconstruction, the accepted standard reconstructive technique, and AFF/ADM remain under-reported. The aim of this study was to evaluate the safety and efficacy of myelomeningocele reconstruction using muscle sparing AFF/ADM versus MF.

Methods:
A retrospective comparison was conducted on consecutive myelomeningocele patients reconstructed with MF or AFF/ADM over an 84-month period. Data analyzed included: basic demographics, defect size, reconstructive technique, complications, and length of follow-up. A supplemental meta-analysis based on systematic review of literature was performed to compare alternative reconstructive options.

Results:
Twelve patients were identified who met inclusion criteria. Median age, weight, and defect size at reconstruction in the AFF/ADM group (n = 6) was 37.5 weeks, 3.25 kg, and 20.0 cm2, respectively, and in the MF group (n = 6) was 37 weeks, 3.6 kg, and 22.5 cm2 (P > 0.5). For the AFF/ADM versus MF groups, median follow-up was 33.8 versus 22.6 months, reoperation rate was 0% versus 17% (P = 1.0), and complex skin flap closure rate was 17% versus 100% (P = 0.015). No cerebrospinal fluid leaks or surgical site infections occurred in either group. Meta-analysis of the literature revealed no statistically significant difference in complications rates between muscle and nonmuscle flap reconstruction (P > 0.5); potential long-term sequelae of muscle flap harvest were not included.

Conclusions:
Muscle sparing AFF with ADM is a safe and effective surgical alternative to muscle flaps for lumbar myelomeningocele reconstruction.
Face Transplant: Status of Current Supporting Technology to Plan and Perform the Operation and Monitor the Graft in the Postoperative Period
Authors: Caterson Edward J. , McCarty Justin C. 
Published: May 2018

AbstractFace transplant has rapidly advanced since the first operation in 2005, and to date, 40 partial or full-face transplants have been performed. The safety and efficacy of this operation are aided at all phases by supporting technologies. These include advanced imaging techniques to plan the operation, devices to monitor the flap in the immediate perioperative period, and noninvasive imaging and serum markers to monitor for acute and chronic rejection. Some of the technologies, such as those used in the immediate perioperative period, have extensive evidence supporting their use, whereas those to detect acute or chronic rejection remain investigational. The technologies of today will continue to evolve and make the operation safer with improved outcomes; however, the most significant barrier for face transplant continues to be immunologic rejection.
The GalNAc-T Activation (GALA) Pathway: Drivers and Markers
Authors: Chia Joanne , Tay Felicia , Bard Frederic 
Published: May 2018

AbstractThe enzymes GALNTs add GalNAc sugar to Ser and Thr residues, forming the Tn glycan. GALNTs are activated by trafficking from Golgi to ER, a process driven by the Src kinase and negatively regulated by ERK8. This GALNTs activation (aka GALA) pathway induces high Tn levels and is a key driver of liver tumor growth. Recently, Tabak and colleagues have contested our previous data that EGF stimulation can induce GALNTs relocation. Here, we show that relocation induced by EGF is actually detectable in the images acquired by Tabak et al. Furthermore, we show that expression of EGFR enhances relocation and appears required to drive relocation induced by ERK8 depletion. We also propose that quantification of O-glycosylation of the ER resident protein PDIA4 provides an alternative measure of GALA. In sum, we demonstrate that non-reproducibility was due to experimental errors, that EGFR is indeed a driver of GALA and propose additional markers to facilitate the study of this pathway.
Streptococcal dTDP-L-rhamnose biosynthesis enzymes: functional characterization and lead compound identification
Authors: van der Beek Samantha L. , Zorzoli Azul , Çanak Ebru , Chapman Robert N. , Meyer Benjamin H. , Boons Geert-Jan , Dorfmueller Helge C. , van Sorge Nina M. 
Published: May 2018

SummaryBiosynthesis of the nucleotide sugar precursor dTDP-L-rhamnose is critical for the viability and virulence of many human pathogenic bacteria, includingStreptococcus pyogenes(Group AStreptococcus; GAS) andStreptococcus mutans. Those pathogens require dTDP-L-rhamnose for the production of structurally similar rhamnose polysaccharides in their cell wall. Via heterologous expression inS. mutans, we confirm that GAS RmlB and RmlC are critical for dTDP-L-rhamnose biosynthesis through their action as dTDP-glucose-4,6-dehydratase and dTDP-4-keto-6-deoxyglucose-3,5-epimerase enzymes, respectively. Complementation with GAS RmlB and RmlC containing specific point mutations corroborated the conservation of previous identified catalytic residues in these enzymes. Bio-layer interferometry was used to identify and confirm inhibitory lead compounds that bind to GAS dTDP-rhamnose biosynthesis enzymes RmlB, RmlC and GacA. One of the identified compounds, Ri03, inhibited growth of GAS as well as several other rhamnose-dependent streptococcal pathogens with an MIC50of 120-410 μM. We therefore conclude that inhibition of dTDP-L-rhamnose biosynthesis such as Ri03 affect streptococcal viability and can serve as a lead compound for the development of a new class of antibiotics that targets dTDP-rhamnose biosynthesis in pathogenic bacteria.
IL-17RA-signaling modulates CD8+ T cell survival and exhaustion duringTrypanosoma cruziinfection
Authors: Boari Jimena Tosello , Furlan Cintia L. Araujo , Vernengo Facundo Fiocca , Rodriguez Constanza , Ramello María C. , Vesely María C. Amezcua , Serrán Melisa Gorosito , Nuñez Nicolás G. , Richer Wilfrid , Piaggio Eliane , Montes Carolina L. , Gruppi Adriana , Rodríguez Eva V. Acosta 
Published: May 2018

AbstractThe IL-17 family contributes to host defense against many intracellular pathogens by mechanisms not fully understood. CD8+ T lymphocytes are key elements against intracellular microbes and their survival and appropriate response is orchestrated by several cytokines. Here, we demonstrated that IL-17RA-signaling cytokines sustain pathogen-specific CD8+ T cell immunity. Absence of IL-17RA and IL-17A/F duringTrypanosoma cruziinfection resulted in increased tissue parasitism and reduced frequency of parasite-specific CD8+ T cells. Impaired IL-17RA-signalingin vivoincreased apoptosis of parasite-specific CD8+ T cells while recombinant IL-17in vitrodown-regulated the pro-apoptotic protein BAD and promoted activated CD8+ T cell survival. Phenotypic, functional and trancriptomic profiling showed thatT. cruzi-specific CD8+ T cells arising in IL-17RA-deficient mice presented features of cell dysfunction. PD-L1 blockade partially restored the magnitude of CD8+ T cell responses and parasite control in these mice. Adoptive transfer experiments established that IL-17RA-signaling is intrinsically required for the proper maintenance of functional effector CD8+ T cells. Altogether, our results identify IL-17RA and IL-17A as critical factors for sustaining CD8+ T cell immunity toT. cruzi.
Identification of cryptic stator subunits from an apicomplexan ATP synthase
Authors: Huet Diego , Rajendran Esther , Dooren Giel G. Van , Lourido Sebastian 
Published: May 2018

ABSTRACTThe mitochondrial ATP synthase is a macromolecular motor that uses the proton gradient to generate ATP. Proper ATP synthase function requires a stator linking the catalytic and rotary portions of the complex. However, sequence-based searches fail to identify genes encoding stator subunits in apicomplexan parasites like Toxoplasma gondii or the related organisms that cause malaria. Here, we identify 11 previously unknown subunits from the Toxoplasma ATP synthase, which lack homologs outside the phylum. Hidden Markov modeling suggests that two of them—ICAP2 and ICAP18—share distant homology with mammalian stator subunits. Our analysis shows that both proteins form part of the ATP synthase complex. Depletion of ICAP2 leads to aberrant mitochondrial morphology, decreased oxygen consumption, and disassembly of the complex, consistent with its role as an essential component of the Toxoplasma ATP synthase. Our findings highlight divergent features of the central metabolic machinery in apicomplexans, which may reveal new therapeutic opportunities.
Regulation of the error-prone DNA polymerase polκ by oncogenic signaling and its contribution to drug resistance
Authors: Temprine Kelsey , Langdon Erin M , Mehta Krisha , Clapp Averill , White Richard M 
Published: May 2018

AbstractMutations in the proofreading domains of the replicative DNA polymerases polδ and polε are associated with elevated mutation rates in cancer, but the roles of other DNA polymerases in tumorigenesis remain poorly understood. One such polymerase is polκ, an enzyme that plays a key role in translesion synthesis. polκ contributes to cell survival in the face of DNA damage but can be highly mutagenic due to lack of a proofreading domain. Here we demonstrate that cancer cells under stress from oncogene inhibition upregulate polκ and shift its localization from the cytoplasm to the nucleus. This effect can be phenocopied by mTOR inhibition or glucose deprivation, analogous to stress-induced mutagenesis inE. coliwhereby cell stress and nutrient deprivation can upregulate and activate DinB/pol IV (the bacterial orthologue of polκ). We find that cancer cells normally sequester polκ in the cytoplasm via exportin-1, likely to prevent excess mutagenesis from the error-prone nature of this polymerase. Subverting the normal nuclear-cytoplasmic shuttling by forced overexpression of nuclear polκ increases resistance of melanoma cells to the BRAFV600Einhibitor vemurafenib. This data suggests a mechanism by which cancer cells regulate the expression and localization of the error-prone polymerase polκ, abrogation of which can contribute to drug resistance.One Sentence Summary:Cancer cells under stress from oncogene or mTOR inhibition dysregulate the error-prone DNA polymerase polκ, which contributes to drug resistance in melanoma cells.
PathogenicDDX3Xmutations impair RNA metabolism and neurogenesis during fetal cortical development
Authors: Lennox Ashley L. , Jiang Ruiji , Suit Lindsey , Fregeau Brieana , Sheehan Charles J. , Aldinger Kimberly A. , Moey Ching , Lobach Iryna , Mirzaa Ghayda , Afenjar Alexandra , Babovic-Vuksanovic Dusica , Bézieau Stéphane , Blackburn Patrick R. , Bunt Jens , Burglen Lydie , Charles Perrine , Chung Brian H.Y. , Cogné Benjamin , DeBrosse Suzanne , Di Donato Nataliya , Faivre Laurence , Héron Delphine , Innes A. Micheil , Isidor Bertrand , Johnson-Kerner Bethany L. , Keren Boris , Kimball Amy , Klee Eric W. , Kuentz Paul , Küry Sébastien , Martin-Coignard Dominique , Mignot Cyril , Miyake Noriko , Nava Caroline , Nizon Mathilde , Rodriguez Diana , Blok Lot Snijders , Thauvin-Robinet Christel , Thevenon Julien , Vincent Marie , Ziegler Alban , Dobyns William , Richards Linda J. , Barkovich A. James , Floor Stephen N. , Silver Debra L. , Sherr Elliott H. 
Published: May 2018

AbstractDe novogermline mutations in the RNA helicaseDDX3Xaccount for 1-3% of unexplained intellectual disability (ID) cases in females, and are associated with autism, brain malformations, and epilepsy. Yet, the developmental and molecular mechanisms by whichDDX3Xmutations impair brain function are unknown. Here we use human and mouse genetics, and cell biological and biochemical approaches to elucidate mechanisms by which pathogenicDDX3Xvariants disrupt brain development. We report the largest clinical cohort to date withDDX3Xmutations (n=78), demonstrating a striking correlation between recurrent dominant missense mutations, polymicrogyria, and the most severe clinical outcomes. We show thatDdx3xcontrols cortical development by regulating neuronal generation and migration. SevereDDX3Xmissense mutations profoundly disrupt RNA helicase activity and induce ectopic RNA-protein granules and aberrant translation in neural progenitors and neurons. Together, our study demonstrates novel mechanisms underlyingDDX3Xsyndrome, and highlights roles for RNA-protein aggregates in the pathogenesis of neurodevelopmental disease.
Microbial Reduction of Metal-Organic Frameworks Enables Synergistic Chromium Removal
Authors: Springthorpe Sarah K. , Dundas Christopher M. , Keitz Benjamin K. 
Published: May 2018

AbstractMicrobe-material redox interactions underpin many emerging technologies, including bioelectrochemical cells and bioremediation. However, commonly utilized material substrates, such as metal oxides, suffer from a lack of tunability and can be challenging to characterize. In contrast, metal-organic frameworks, a class of porous materials, exhibit well-defined structures, high crystallinity, large surface areas, and extensive chemical tunability. Here, we report that metal-organic frameworks can support the growth of the electroactive bacterium Shewanella oneidensis. Specifically, we demonstrate that Fe(III)-containing frameworks, MIL-100 and Fe-BTC, can be reduced by the bacterium via its extracellular electron transfer pathways and that reduction rate/extent is tied to framework structure, surface area, and particle morphology. In a practical application, we show that cultures containing S. oneidensis and reduced frameworks can remediate lethal concentrations of Cr(VI), and that pollutant removal exceeds the performance of either component in isolation or bioreduced iron oxides. Repeated cycles of Cr(VI) dosing had little effect on bacterial viability or Cr(VI) adsorption capacity, demonstrating that the framework confers protection to the bacteria and that no regenerative step is needed for continued bioremediation. In sum, our results show that metal-organic frameworks can serve as microbial respiratory substrates and suggest that they may offer a promising alternative to metal oxides in applications seeking to combine the advantages of bacterial metabolism and synthetic materials.
PRX9andPRX40are extensin peroxidases essential for maintaining tapetum and microspore cell wall integrity duringArabidopsisanther development
Authors: Jacobowitz Joseph R. , Weng Jing-Ke 
Published: May 2018

AbstractPollen and microspore development is an essential step in the life cycle of all land plants that generate male gametes. Within flowering plants, pollen development occurs inside of the anther. Here, we report the identification of two class III peroxidase-encoding genes,PRX9andPRX40, that are genetically redundant and essential for proper anther and pollen development inArabidopsis thaliana.Arabidopsisdouble mutants devoid of functionalPRX9andPRX40are male-sterile. The mutant anthers display swollen, hypertrophic tapetal cells and pollen grains, suggesting disrupted cell wall integrity. These phenotypes ultimately lead to nearly 100%-penetrant pollen degeneration upon anther maturation. Using immunochemical and biochemical approaches, we show thatPRX9andPRX40are likely extensin peroxidases that contribute to the establishment of tapetal cell wall integrity during anther development. This work identifiesPRX9andPRX40as the first extensin peroxidases to be described inArabidopsisand highlights the importance of extensin cross-linking during plant development.
Global transcriptional analysis ofGeobacter sulfurreducensunder palladium reducing conditions reveals new key cytochromes involved
Authors: Hernández-Eligio Alberto , Pat-Espadas Aurora M. , Vega-Alvarado Leticia , Huerta-Amparán Manuel , Cervantes Francisco J. , Juárez Katy 
Published: May 2018

AbstractGeobacter sulfurreducensis capable of reducing Pd(II) to Pd(0) using acetate as electron donor; however, the biochemical and genetic mechanisms involved in this process have not been described. In this work, we carried out transcriptome profiling analysis to identify the genes involved in Pd(II) reduction in this bacterium. Our results showed that 252 genes were upregulated while 141 were downregulated during Pd(II) reduction. Among the upregulated genes, 12 were related to energy metabolism and electron transport; 50 were classified as involved in protein synthesis; 42 were associated with regulatory functions and transcription, and 47 have no homologs with known function. RT-qPCR data confirmed upregulation of genes encoding PilA, the structural protein for the electrically conductive pili, as well asc-type cytochromes GSU1062, GSU2513, GSU2808, GSU2934, GSU3107, OmcH, OmcM, PpcA, PpcD under Pd(II)-reducing conditions. ΔpilAand ΔpilRmutant strains showed 20% and 40% decrease in the Pd(II)-reducing capacity, respectively, compared to the wild type strain, indicating the central role of the pili in this process. RT-qPCR data collected during Pd(II) reduction also confirmed downregulation of theomcB, omcC, omcZ,andomcSgenes, which have been shown to be involved in Fe(III) reduction and electrodes. Based on these results, we propose mechanisms involved in Pd(II) reduction byG. sulfurreducens.ImportanceGeobacter sulfurreducensis a versatile microorganism, known for its ability to reduce a wide range of environmentally relevant metals. It has been reported that this bacterium synthesizes palladium nanoparticles successfully. Yet, the biochemical and genetic mechanisms involved in this process had not been described previously. By using a transcriptome profile analysis to identify genes implicated in this process and genetic and physiological data, we propose a model for the biological reduction of Pd(II) byG. sulfurreducens. Moreover, the study also revealed the microbial reduction of Pd(II) coupled to growth, which shows not only unexpected ideas about its complex metabolism, but some key cytochromes involved in this pathway, which have not been previously associated with other metal reducing process for this bacterium. In brief the present work contributes to a better understanding of the biochemical and genetic mechanisms involved in Pd(II) reduction and put forward novel insights aboutG. sulfurreducensmetabolism.
Recalibration of path integration in hippocampal place cells
Authors: Jayakumar Ravikrishnan P. , Madhav Manu S. , Savelli Francesco , Blair Hugh T. , Cowan Noah J. , Knierim James J. 
Published: May 2018

SummaryHippocampal place cells are spatially tuned neurons that serve as elements of a “cognitive map” in the mammalian brain1. To detect the animal’s location, place cells are thought to rely upon two interacting mechanisms: sensing the animal’s position relative to familiar landmarks2,3and measuring the distance and direction that the animal has travelled from previously occupied locations4–7. The latter mechanism, known aspath integration, requires a finely tuned gain factor that relates the animal’s self-movement to the updating of position on the internal cognitive map, with external landmarks necessary to correct positional error that eventually accumulates8,9. Path-integration-based models of hippocampal place cells and entorhinal grid cells treat the path integration gain as a constant9–14, but behavioral evidence in humans suggests that the gain is modifiable15. Here we show physiological evidence from hippocampal place cells that the path integration gain is indeed a highly plastic variable that can be altered by persistent conflict between self-motion cues and feedback from external landmarks. In a novel, augmented reality system, visual landmarks were moved in proportion to the animal’s movement on a circular track, creating continuous conflict with path integration. Sustained exposure to this cue conflict resulted in predictable and prolonged recalibration of the path integration gain, as estimated from the place cells after the landmarks were extinguished. We propose that this rapid plasticity keeps the positional update in register with the animal’s movement in the external world over behavioral timescales (mean 50 laps over 35 minutes). These results also demonstrate that visual landmarks not only provide a signal to correct cumulative error in the path integration system, as has been previously shown4,8,16–19, but also rapidly fine-tune the integration computation itself.
Recruitment of occipital cortex by arithmetic processing follows computational bias in early blind
Authors: Crollen Virginie , Lazzouni Latifa , Bellemare Antoine , Rezk Mohamed , Lepore Franco , Noël Marie-Pascale , Seron Xavier , Collignon Olivier 
Published: May 2018

AbstractArithmetic reasoning activates the occipital cortex of early blind people (EB). This activation of visual areas may reflect functional flexibility or the intrinsic computational role of specific occipital regions. We contrasted these competing hypotheses by characterizing the brain activity of EB and sighted participants while performing subtraction, multiplication and a control verbal task. In both groups, subtraction selectively activated a bilateral dorsal network commonly activated during spatial processing. Multiplication triggered more activity in temporal regions thought to participate in memory retrieval. No between-group difference was observed for the multiplication task whereas subtraction induced enhanced activity in the right dorsal occipital cortex of the blind individuals only. As this area overlaps and exhibits increased functional connectivity with regions showing selective tuning to auditory spatial processing, our results suggest that the recruitment of occipital regions during high-level cognition in the blind actually relates to the intrinsic computational role of the reorganized regions.