bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Dehydrated Amniotic Membrane Skin Substitute in Facial Burns: Is There a Outcome Difference Between Adult and Pediatric Patients?
Authors: Puyana Salomon , Ruiz Samuel , Elkbuli Adel , Bernal Eileen , McKenney Mark , Lim Rizal , Askari Morad , Mir Haaris 
Published: November 2019

Introduction:
Facial burns have significant physical and psychological effects on patients, and minimizing morbidity continues to be a challenge for reconstructive surgeons. Advancements have allowed the development of various skin substitutes. Among these, human dehydrated amniotic skin substitutes represent novel technology, yet their outcome has not been sufficiently studied to guide practice. The objective of our study is to compare the safety of amniotic membrane skin substitutes in the treatment of adult and pediatric facial burns.

Methods:
The authors performed a retrospective review of our institutional burn registry, with 90 burn patients meeting the inclusion criteria. Demographic and outcome measures included age, percentage of total body surface area (TBSA), Injury Severity Score (ISS), and complications (eg, pigmentation, hypertrophic scar, infection, and delayed healing). Paired sample t test and Chi-squared test were used, with significance defined as P < 0.05.

Results:
Seventy-seven adults and 13 pediatric patients with facial burns who had received dehydrated amniotic membrane skin substitutes were included in the analysis. The mean age was 40.8 years for adults and 5.6 years for children. Mean TBSA was similar, with 9.6% (1−57%) in adults and 6.0% (2−14%) in children. The mean ISS did not significantly differ between groups (4.0 versus 2.2, P = ns). Pediatric patients with facial burns treated with amniotic membranes had a higher incidence of dyspigmentation relative to adult patients (46.2% versus 9.1%, P ≤ 0.05). Remaining morbidities were not significantly different between adult and pediatric patients. All patients, irrespective of group, healed by the second post-operative week.

Conclusion:
Dehydrated amniotic membrane skin substitutes are a safe alternative in the treatment of facial burns across all ages.
Nasal Septum Actinomycosis Mimicking Mucocele
Authors: Lee Dong Hoon , Yoon Tae Mi , Lee Joon Kyoo , Lim Sang Chul 
Published: November 2019

Abstract
Actinomycosis commonly occurs in the cervicofacial region, but rarely in the paranasal sinus. The authors report an unusual case of nasal septum actinomycosis that was mistaken for a mucocele. The patient was treated accordingly using antibiotic therapy after endoscopic sinus surgery was performed. It is noteworthy that actinomycosis of the nasal septum could appear as a mucocele without central calcification or bony destruction in imaging studies.
Update on posterior cortical atrophy
Authors: Holden Samantha K. , Bettcher Brianne M. , Pelak Victoria S. 
Published: November 2019

Purpose of review
Non-amnestic (or atypical) presentations of neurodegenerative dementias are underrecognized and underdiagnosed, including posterior cortical atrophy (PCA) syndrome, which is characterized by prominent visuospatial and visuoperceptual dysfunction at presentation. It is most commonly due to Alzheimer's disease pathology, while Lewy body disease, corticobasal degeneration, and prion disease are neuropathological entities that are less frequently associated with PCA. The diagnosis of PCA is often delayed, to the detriment of the patient, and awareness and understanding of PCA will improve detection, prognostication, and treatment.

Recent findings
The natural history of PCA appears to be distinct from typical Alzheimer's disease and significant heterogeneity exists within the PCA syndrome, with the underlying causes of this heterogeneity beginning to be explored. Functional and molecular imaging can assist in better understanding PCA, particularly assessment of network disruptions that contribute to clinical phenotypes. Cerebrospinal fluid biomarkers are useful to detect underlying pathology, but measures of retinal thickness are less promising. There are currently no adequate treatment options for PCA.

Summary
Continued efforts to characterize PCA are needed, and greater awareness and understanding of atypical presentations of neurodegenerative dementias could serve to elucidate pathobiological mechanisms of underlying disease.
Mind the Outgroup: Influence of Taxon Sampling on Total-Evidence Dating of Pimpliform Parasitoid Wasps (Hymenoptera, Ichneumonidae)
Authors: Spasojevic Tamara , Broad Gavin R. , Sääksjärvi Ilari E. , Schwarz Martin , Ito Masato , Korenko Stanislav , Klopfstein Seraina 
Published: November 2019

ABSTRACTTaxon sampling is a central aspect of phylogenetic study design, but it has received limited attention in the context of molecular dating and especially in the framework of total-evidence dating, a widely used dating approach that directly integrates molecular and morphological information from extant and fossil taxa. We here assess the impact of different outgroup sampling schemes on age estimates in a total-evidence dating analysis under the uniform tree prior. Our study group are Pimpliformes, a highly diverse, rapidly radiating group of parasitoid wasps of the family Ichneumonidae. We cover 201 extant and 79 fossil taxa, including the oldest fossils of the family from the Early Cretaceous and the first unequivocal representatives of extant subfamilies from the mid Paleogene. Based on newly compiled molecular data from ten nuclear genes and a morphological matrix that includes 222 characters, we show that age estimates become both older and less precise with the inclusion of more distant and more poorly sampled outgroups. In addition, we discover an artefact that might be detrimental for total-evidence dating: “bare-branch attraction”, namely high attachment probabilities of, especially, older fossils to terminal branches for which morphological data are missing. After restricting outgroup sampling and adding morphological data for the previously attracting, bare branches, we recover a Middle and Early Jurassic origin for Pimpliformes and Ichneumonidae, respectively. This first age estimate for the group not only suggests an older origin than previously thought, but also that diversification of the crown group happened before the Cretaceous-Paleogene boundary. Our case study demonstrates that in order to obtain robust age estimates, total-evidence dating studies need to be based on a thorough and balanced sampling of both extant and fossil taxa, with the aim of minimizing evolutionary rate heterogeneity and missing morphological information.
Contextual flexibility inPseudomonas aeruginosacentral carbon metabolism during growth in single carbon sources
Authors: Dolan Stephen K. , Kohlstedt Michael , Trigg Stephen , Ramirez Pedro Vallejo , Wittmann Christoph , Kaminski Clemens F. , Welch Martin 
Published: November 2019

AbstractPseudomonas aeruginosais an opportunistic human pathogen, particularly noted for causing infections in the lungs of people with cystic fibrosis (CF). Previous studies have shown that the gene expression profile ofP. aeruginosaappears to converge towards a common metabolic program as the organism adapts to the CF airway environment. However, at a systems level, we still have only a limited understanding of how these transcriptional changes impact on metabolic flux. To address this, we analysed the transcriptome, proteome and fluxome ofP. aeruginosagrown on glycerol or acetate. These carbon sources were chosen because they are the primary breakdown products of airway surfactant, phosphatidylcholine, which is known to be a major carbon source forP. aeruginosain the CF airways. We show that the flux of carbon through central metabolism is radically different on each carbon source. For example, the newly-recognised EDEMP cycle plays an important role in supplying NADPH during growth on glycerol. By contrast, the EDEMP cycle is attenuated during growth on acetate, and instead, NADPH is primarily supplied by the isocitrate dehydrogenase(s)-catalyzed reaction. Perhaps more importantly, our proteomic and transcriptomic analyses reveal a global remodelling of gene expression during growth on the different carbon sources, with unanticipated impacts on aerobic denitrification, electron transport chain architecture, and the redox economy of the cell. Collectively, these data highlight the remarkable metabolic plasticity ofP. aeruginosa; a plasticity which allows the organism to seamlessly segue between different carbon sources, maximising the energetic yield from each.ImportancePseudomonas aeruginosais an opportunistic human pathogen, well-known for causing infections in the airways of people with cystic fibrosis. Although it is clear thatP. aeruginosais metabolically well-adapted to life in the CF lung, little is currently known about how the organism metabolises the nutrients available in the airways. In this work, we use a combination of gene expression and isotope tracer (“fluxomic”) analyses to find out exactly where the input carbon goes during growth on two CF-relevant carbon sources, acetate and glycerol (derived from the breakdown of lung surfactant). We find that carbon is routed (“fluxed”) through very different pathways during growth on these substrates, and that this is accompanied by an unexpected remodelling of the cell’s electron transfer pathways. Having access to this “blueprint” is important because the metabolism ofP. aeruginosais increasingly being recognised as a target for the development of much-needed antimicrobial agents.
Brainstem organoids from human pluripotent stem cells contain neural crest population
Authors: Eura Nobuyuki , Matsui Takeshi K. , Luginbühl Joachim , Matsubayashi Masaya , Nanaura Hitoki , Shiota Tomo , Kinugawa Kaoru , Iguchi Naohiko , Kiriyama Takao , Zheng Canbin , Kouno Tsukasa , Lan Yan Jun , Kongpracha Pornparn , Wiriyasermkul Pattama , Sakaguchi Yoshihiko M. , Nagata Riko , Komeda Tomoya , Morikawa Naritaka , Kitayoshi Fumika , Jong Miyong , Kobashigawa Shinko , Nakanishi Mari , Hasegawa Masatoshi , Saito Yasuhiko , Shiromizu Takashi , Nishimura Yuhei , Kasai Takahiko , Takeda Maiko , Kobayashi Hiroshi , Inagaki Yusuke , Tanaka Yasuhito , Makinodan Manabu , Kishimoto Toshifumi , Kuniyasu Hiroki , Nagamori Shushi , Muotri Alysson R. , Shin Jay W. , Sugie Kazuma , Mori Eiichiro 
Published: November 2019

SummaryThe brainstem controls heartbeat, blood pressure and respiration, which are life-sustaining functions, therefore, disorders of the brainstem can be lethal. Brain organoids derived from human pluripotent stem cells recapitulate the course of human brain development and are expected to be useful for medical research on central nervous system disorders. However, existing organoid models have limitations, hampering the elucidation of diseases affecting specific components of the brain. Here, we developed a method to generate human brainstem organoids (hBSOs), containing neural crest stem cells as well as midbrain/hindbrain progenitors, noradrenergic and cholinergic neurons, and dopaminergic neurons, demonstrated by specific electrophysiological signatures. Single-cell RNA sequence analysis, together with proteomics and electrophysiology, revealed that the cellular population in these organoids was similar to that of the human brainstem and neural crest, which raises the possibility of making use of hBSOs in grafting for transplantation, efficient drug screenings and modeling the neural crest diseases.
Subcellular mRNA localization regulates ribosome biogenesis in migrating cells
Authors: Dermit Maria , Dodel Martin , Lee Flora C. Y. , Azman Muhammad S. , Schwenzer Hagen , Jones J. Louise , Blagden Sarah P. , Ule Jernej , Mardakheh Faraz K. 
Published: November 2019

AbstractTranslation of Ribosomal Protein-coding mRNAs (RP-mRNAs) constitutes a key step in ribosome biogenesis, but the mechanisms which modulate RP-mRNAs translation in coordination with other cellular processes are poorly defined. Here we show that the subcellular localization of RP-mRNAs acts as a key regulator of their translation during cell migration. As cells migrate into their surroundings, RP-mRNAs localize to actin-rich protrusions at the front the cells. This localization is mediated by La-related protein 6 (LARP6), an RNA binding protein that is enriched in protrusions. Protrusions act as hotspots of translation for RP-mRNAs, resulting in enhancement of ribosome biogenesis and overall protein synthesis, which is required for sustained migration. In human breast carcinomas, Epithelial to Mesenchymal Transition (EMT) upregulates LARP6 expression to enhance ribosome biogenesis and support invasive growth. Our findings reveal LARP6 mediated mRNA localization as a key regulator of ribosome biogenesis during cell migration, and demonstrate a role for this process in cancer progression downstream of EMT.
A 2-Compartment Bone Tumor Model for Testing the Efficacy of Cancer Drugs
Authors: Komez Aylin , Buyuksungur Arda , Antmen Ezgi , Swieszkowski Wojciech , Hasirci Nesrin , Hasirci Vasif 
Published: November 2019

AbstractWe produced a three dimensional (3D) bone tumor model (BTM) to study the interactions between healthy and tumor cells in a tumor tissue microenvironment, migration of the tumor cells and the efficacy of an anticancer drug, Doxorubicin, for personalized medicine applications. The model consisted of two compartments: (a) a healthy bone tissue mimic, poly(lactic acid-co-glycolic acid) (PLGA)/beta-tricalcium phosphate (β-TCP) sponge that was seeded with human fetal osteoblastic cells (hFOB) and human umbilical vein endothelial cells (HUVECs), and (b) a tumor mimic, a lyophilized collagen sponge that was seeded with human osteosarcoma cells (Saos-2). The tumor component was introduced to a central cavity created in the healthy bone mimic and together they constituted the total 3D model (3D-BTM). The scaffolds were characterized by determining their mechanical properties, studying their topography and stability with compression tests, microCT, SEM, confocal microscopy and gravimetry. Porosities of the sponges were determined from µCT data as 96.7% and 86% for PLGA/TCP and collagen sponges, respectively. The average diameters of the pores were measured by using ImageJ (NIH, USA) as 199±52 µm for PLGA/TCP and 50-150 μm for collagen scaffolds. Young’ modulus of the PLGA/TCP and collagen sponges were determined as 4.76MPa and 140kPa, respectively. Cells seeded on the two sponges were studied independently and together on the BTM. Cell proliferation, morphology, calcium phosphate forming capacity and ALP production were studied on both healthy bone and tumor mimics. All types of cells showed cellular extensions and spread on and in the scaffolds indicating good cell-material interactions. Angiogenic developments in BTM were studied along with migration of cells between the components with immunocytochemistry, SEM, microCT, qRT-PCR and agarose gel electrophoresis. Confocal microscopy showed that a direct contact was established between the cells present in different parts of the BTM; and the HUVEC cells within the healthy bone mimic were observed to migrate into the tumor mimic. This was confirmed by the increase in the levels of angiogenic factors VEGF, bFGF, and IL-8 in the tumor component. The IC50 of Doxorubicin on Saos-2 cells was determined as 0.1876 µg.mL−1. Doxorubicin was administered to the BTM at 2.7 µg.mL−1 concentration and after allowing one day for interaction, the cell number was determined with Alamar Blue cell viability test as 7-fold lesser compared to 24 h earlier. Apoptosis of the osteosarcoma cells was measured by caspase-3 enzyme activity assay. These results demonstrate the suitability of the 3D BTM model for use in the investigation of activities and migrations of cells in a tumor tissue. These will be very useful in studying metastatic capabilities of cells in addition to personalized drug treatments.
Comparison of in vitro and in planta toxicity of Vip3A for lepidopteran herbivores
Authors: Khan Muhammad Hassaan , Jander Georg , Mukhtar Zahid , Arshad Muhammad , Sarwar Muhammad , Asad Shaheen 
Published: November 2019

AbstractAgricultural pest infestation is as old as domestication of food crops and contributes a major share to the cost of crop production. Transgenic production of Vip3A, an insecticidal protein from Bacillus thuringiensis, effectively controls lepidopteran pests. A synthetic vip3A gene was evaluated its efficacy against Spodoptera litura (cotton leafworm), Spodoptera exigua (beet armyworm), Spodoptera frugiperda (fall armyworm), Helicoverpa armigera (cotton bollworm), Helicoverpa zea (corn earworm), Heliothis virescens (tobacco budworm), and Manduca sexta (tobacco hornworm). In artificial diet assays, the Vip3A concentration causing 50% mortality was H. zea > H. virescens > S. exigua > H. armigera > M. sexta > S. frugiperda > S. litura. In contrast, on vip3A transgenic tobacco the order of resistance (time until 50% lethality) was M. sexta > H. virescens > S. litura > H. zea > H. armigera > S. exigua > S. frugiperda. There was no significant correlation between the artificial diet and transgenic tobacco effects. Notably, the two insect species that are best-adapted for growth on tobacco, M. sexta and H. virescens, showed the greatest tolerance of vip3A-transgenic tobacco. This may indicate synergistic effects of Vip3A and endogenous plant defense mechanisms, e.g. nicotine, to which M. sexta and H. virescens would have greater resistance. Together, our results show that artificial diet assays are a poor predictor of Vip3A efficacy in transgenic plants, lepidopteran species vary in their sensitivity to Vip3A in diet-dependent manner, and that host plant adaptation of the targeted herbivores should be considered when designing transgenic plants for pest control.
Dynamic neurotransmitter specific transcription factor expression profiles duringDrosophiladevelopment
Authors: Estacio-Gómez Alicia , Hassan Amira , Walmsley Emma , Le Lily Wong , Southall Tony D. 
Published: November 2019

AbstractThe remarkable diversity of neurons in the nervous system is generated during development, when properties such as cell morphology, receptor profiles and neurotransmitter identities are specified. In order to gain a greater understanding of neurotransmitter specification we profiled the transcription state of cholinergic, GABAergic and glutamatergic neuronsin vivoat three developmental time points. We identified 86 differentially expressed transcription factors that are uniquely enriched, or uniquely depleted, in a specific neurotransmitter type. Some transcription factors show a similar profile across development, others only show enrichment or depletion at specific developmental stages. Profiling of Acj6 (cholinergic enriched) and Ets65A (cholinergic depleted) binding sitesin vivoreveals that they both directly bind theChATlocus, in addition to a wide spectrum of other key neuronal differentiation genes. We also show that cholinergic enriched transcription factors are expressed in mostly non-overlapping populations in the adult brain, implying the absence of combinatorial regulation of neurotransmitter fate in this context. Furthermore, our data underlines that, similar toC. elegans, there are no simple transcription factor codes for neurotransmitter type specification.
Mitochondrial clearance of Ca2+controls insulin secretion
Authors: Vishnu N , Hamilton A , Bagge A , Wernersson A , Cowan E , Barnard H , Sancak Y , Kamer K.J. , Spégel P , Fex M , Tengholm A , Mootha V.K. , Nicholls DG , Mulder H 
Published: November 2019

SUMMARYTransport of Ca2+from the cytosol to the mitochondrial matrix of insulin-secreting pancreatic β-cells facilitates nutrient-mediated insulin secretion. However, the underlying mechanism is unclear. The establishment of the molecular identity of the mitochondrial Ca2+uniporter (MCU) and associated proteins has allowed mitochondrial Ca2+transport to be modified in intact cells. We examined the consequences of deficiency of the accessory protein, MICU2, in rat and human insulin-secreting cell lines as well as in mouse islets. Glucose-induced mitochondrial Ca2+elevation and inner membrane hyperpolarization were reduced, together with cytosolic ATP/ADP-ratios and insulin secretion. Insulin secretion inMicu2knock out mice was attenuatedin vitroas well asin vivo. While KCl-evoked sub-plasmalemmal Ca2+increases were more pronounced, the global cytosolic Ca2+response was, surprisingly, diminished inMICU2-deficient cells. These findings were supported by selective inhibition of mitochondrial Ca2+uptake by mitochondrial depolarization. It is concluded that mitochondrial Ca2+transport plays an additional and hitherto unrecognized role in stimulated β-cells by regulating net Ca2+entry across the plasma membrane. This is likely accounted for by clearing of sub-plasmalemmal Ca2+levels by mitochondria located near the plasma membrane.
Peptidoglycan sensing prevents quiescence and promotes quorum-independent growth of uropathogenicEscherichia coli
Authors: DiBiasio Eric C. , Ranson Hilary J. , Johnson James R. , Rowley David C. , Cohen Paul S. , Camberg Jodi L. 
Published: November 2019

AbstractThe layer of peptidoglycan surrounding bacteria provides structural integrity for the bacterial cell wall. Many organisms, including human cells and diverse bacteria, detect peptidoglycan fragments that are released as bacteria grow. UropathogenicEscherichia coli(UPEC) strains are the leading cause of human urinary tract infections (UTIs) and many patients experience recurrent infection after successful antibiotic treatment. The source of recurrent infections may be persistent bacterial reservoirsin vivothat are in a quiescent state and, thus, are not susceptible to antibiotics. Here, we show that multiple UPEC strains require a quorum to proliferatein vitrowith glucose as the sole carbon source; at low density, the bacteria remain viable but enter a quiescent, non-proliferative state. Of all clinical UPEC isolates tested to date, 35% (51/145) enter this quiescent state, including archetypal strains CFT073 (from classic endemic lineage ST73) and JJ1886 (from recently emerged, multidrug-resistant pandemic lineage ST131). We further show that quorum-dependent UPEC quiescence is prevented and reversed by small molecules, called proliferants, that stimulate growth, such as L-lysine, L-methionine, and peptidoglycan (PG) stem peptides, including an isolated PG pentapeptide fromStaphylococcus aureus.Together, our results indicate that (i) uptake of L-lysine and (ii) PG peptide sensing by UPEC modulate the quorum-regulated decision to proliferate and further demonstrate that PG fragments are important for intra- and interspecies signaling in pathogenicE. coli.