bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inclusion of a 3D-printed Hyperelastic bone mesh improves mechanical and osteogenic performance of a mineralized collagen scaffold
Authors: Dewey Marley J. , Nosatov Andrey V. , Subedi Kiran , Shah Ramille , Jakus Adam , Harley Brendan A.C. 
Published: June 2020

ABSTRACTRegenerative repair of craniomaxillofacial bone injuries is challenging due to both the large size and irregular shape of many defects. Mineralized collagen scaffolds have previously been shown to be a promising biomaterial implant to accelerate craniofacial bone regenerationin vivo. Here we describe inclusion of a 3D-printed polymer or ceramic-based mesh into a mineralized collagen scaffold to improve mechanical and biological activity. Mineralized collagen scaffolds were reinforced with 3D-printed Fluffy-PLG (ultraporous polylactide-co-glycolide co-polymer) or Hyperelastic Bone (90wt% calcium phosphate in PLG) meshes. We show degradation byproducts and acidic release from the printed structures have limited negative impact on the viability of mesenchymal stem cells. Further, inclusion of a mesh formed from Hyperelastic Bone generates a reinforced composite with significantly improved mechanical performance (elastic modulus, push-out strength). Composites formed from the mineralized collagen scaffold and either Hyperelastic Bone or Fluffy-PLG reinforcement both supported human bone-marrow derived mesenchymal stem cell osteogenesis and new bone formation. Strikingly, composites reinforced with Hyperelastic Bone mesh elicited significantly increased secretion of osteoprotegerin, a soluble glycoprotein and endogenous inhibitor of osteoclast activity. These results suggest that architectured meshes can be integrated into collagen scaffolds to boost mechanical performance and actively instruct cell processes that aid osteogenicity; specifically, secretion of a factor crucial to inhibiting osteoclast-mediated bone resorption. Future work will focus on further adapting the polymer mesh architecture to confer improved shape-fitting capacity as well as to investigate the role of polymer reinforcement on MSC-osteoclast interactions as a means to increase regenerative potential.
Axonal TAU sorting requires the C-terminus of TAU but is independent of ANKG and TRIM46 enrichment at the AIS
Authors: Bell M. , Bachmann S. , Klimek J. , Langerscheidt F. , Zempel H. 
Published: June 2020

AbstractSomatodendritic missorting of the axonal protein TAU is a hallmark of Alzheimer’s disease and related tauopathies. Cultured rodent primary neurons and iPSC-derived neurons are used for studying mechanisms of neuronal polarity, including TAU trafficking. However, these models are expensive, time-consuming and/or require the sacrification of animals. In this study, we evaluated four differentiation procedures to generate mature neuron cultures from human SH-SY5Y neuroblastoma cells, in comparison to mouse primary neurons, and tested their TAU sorting capacity. We show that SH-SY5Y-derived neurons, differentiated with sequential RA/BDNF treatment, are suitable for investigating axonal TAU sorting. These human neurons show pronounced neuronal polarity, axodendritic outgrowth, expression of the neuronal maturation markers TAU and MAP2, and, importantly, efficient axonal sorting of endogenous and transfected human wild type TAU, similar to primary neurons. We demonstrate that axonal TAU enrichment requires the presence of the C-terminal half, as a C-terminus-lacking construct (N-term-TAUHA) is not axonally enriched in both neuronal cell models. Moreover, SH-SY5Y-derived neurons do not show formation of a classical axon initial segment (AIS), indicated by the lack of Ankyrin G (ANKG) and tripartite motif-containing protein 46 (TRIM46) at the proximal axon, which suggests that successful axonal TAU sorting is independent of classical AIS formation. Taken together, our results suggest i) that SH-SY5Y-derived neurons are a valuable human neuronal cell model for studying TAU sorting, which is readily accessible at low cost and without animal need, and that ii) the mechanisms of axonal TAU targeting require the TAU C-terminal half but are independent of ANKG or TRIM46 enrichment at the proximal axon.
The mitochondrial genomes of 11 aquatic macroinvertebrate species from Cyprus
Authors: Macher Jan-Niklas , Drakou Katerina , Papatheodoulou Athina , van der Hoorn Berry , Vasquez Marlen 
Published: June 2020

AbstractAquatic macroinvertebrates are often identified based on morphology, but molecular approaches like DNA barcoding, metabarcoding and metagenomics are increasingly used for species identification. These approaches require the availability of DNA references deposited in public databases. Here we report the mitochondrial genomes of 11 aquatic macroinvertebrates species from Cyprus, a European Union island country in the Mediterranean. Only three of the molecularly identified species could be assigned to a species name, highlighting the need for taxonomic work that leads to the formal description and naming of species, and the need for further genetic work to fill the current gaps in reference databases containing aquatic macroinvertebrates.Graphical Abstract
MAP Kinase OsMEK2 and OsMPK1 Signaling for Ferroptotic Cell Death in Rice-Magnaporthe oryzaeInteractions
Authors: Dangol Sarmina , Singh Raksha , Nguyen Khoa Nam , Chen Yafei , Wang Juan , Lee Hyeon Gu , Hwang Byung Kook , Jwa Nam-Soo 
Published: June 2020

ABSTRACTMitogen-activated protein kinase (MAPK) signaling is required for plant cell death responses to invading microbial pathogens. Ferric ions and reactive oxygen species (ROS) accumulate in rice (Oryza sativa) tissues undergoing cell death duringMagnaporthe oryzaeinfection. Here, we report that rice MAP kinase (OsMEK2 and OsMPK1) signaling cascades are involved in iron- and ROS-dependent ferroptotic cell death responses of rice toM. oryzaeinfection. OsMEK2 interacted with OsMPK1 in the cytoplasm, and OsMPK1 moved from the cytoplasm into the nucleus to bind to the OsWRKY90 transcription factor.OsMEK2expression may trigger OsMPK1-OsWRKY90 signaling pathways in the nucleus. AvirulentM. oryzaeinfection inΔOsmek2mutant rice did not trigger iron and ROS accumulation and lipid peroxidation, and also downregulatedOsMPK1,OsWRKY90,OsRbohB, andOsPR-1bexpression. However,OsMEK2overexpression induced ROS-and iron-dependent cell death in rice duringM. oryzaeinfection. The downstream MAP kinase (OsMPK1) overexpression induced ROS- and iron-dependent ferroptotic cell death in the compatible rice-M.oryzaeinteraction. These data suggest that the OsMEK2-OsMPK1-OsWRKY90 signaling cascade is involved in the ferroptotic cell death in rice. The small-molecule inducer erastin triggered iron- and lipid ROS-dependent, butOsMEK2-independent, ferroptotic cell death inΔOsmek2mutant plants duringM. oryzaeinfection. Disease-related cell death was lipid ROS-dependent and iron-independent in theΔOsmek2mutant plants. These combined results suggest thatOsMEK2andOsMPK1expression positively regulates iron- and ROS-dependent ferroptotic cell death via OsMEK2-OsMPK1-OsWRKY90signaling pathways, and blast disease (susceptibility)-related cell death was ROS-dependent but iron-independent in rice-M. oryzaeinteractions.
Novel microRNA multivariate biomarkers of response to immunotherapy against HPV E6 oncogene
Authors: Fleeman Rebecca M. , Deiter Gina , Lambert Kristen , Proctor Elizabeth A. , Phaëton Rébécca 
Published: June 2020

AbstractCervical cancer is caused by the persistent infection high-risk types of human papillomavirus (HPV) in over 99.9% of cases. To favor malignant transformation, HPV E6 and E7 oncogenes disrupt both p53 and retinoblastoma (Rb) respectively and control microRNA (miR) networks. We have previously demonstrated the therapeutic potential of anti-HPV E6 monoclonal antibodies (mAbs) in experimental models of human cervical cancer; yet the underlying mechanism remains unclear. Here, we sought to determine if anti-HPV E6 mAbs modulate the miR signatures of HPV E6 oncogenes. To this end, we performed qRT-PCR to measure the expression of thirty-four miRs and found that univariate analysis is not able to identify novel interactions characteristic of complex biological systems. Thus, we utilized partial least squares discriminant analysis (PLSDA) to identify signatures of co-varying miRs specific to mAb treatment. These miR signatures predictively discriminate between anti-HPV E6 mAb response and control mAb treatment, which may provide mechanistic insight into the action of anti-HPV E6 mAbs.
RecombinantHelicobacter pyloriCagA protein induces endoplasmic reticulum stress and autophagy in human cells
Authors: Nami Babak , Azzawri Ali , Ucar Vasfiye B , Acar Hasan 
Published: June 2020

AbstractHelicobacter pylori(Hp) CagA protein has a key role in the development of gastric cancer by the intruding in many intracellular processes of host human cell. Endoplasmic reticulum (ER) stress is an essential process for cellular homeostasis that modulates survival and death and is linked to several complex diseases including cancer. CagA protein is found in the serum ofHp-positive individuals and also in the supernatant ofHpculture. Limited studies report that recombinant CagA can alter gene expression and signaling pathways and induce the death of human cells. In this study, we investigated the effect of exogenous recombinant CagA protein treatment on ER stress and autophagy of human cell. AGS, MKN45, and HEK293 cells were treated with 1 µg/ml of recombinant CagA protein and then ER stress was studied by quantitative-PCR of spliced XBP-1 mRNA, immunofluorescence staining of ATF6 protein nuclear localization and real-time quantitative-PCR and/or western blot expression of GRP78, GRP94, ATF4 and CHOP genes. Autophagy was studied by western blot assessment of the conversion of LC3-I to LC3-II and LC3 aggregation. Cell proliferation and death were investigated by MTT assay and trypan blue staining respectively. As result, treatment with recombinant CagA enhanced XBP-1mRNA splicing, nuclear localization of ATF6, and the expression of ER stress signaling target genes in the cells. Recombinant CagA also induced LC3 protein conversion and aggregation in the cells. Reduced cell proliferation and increased cell death were determined in the cells treated with recombinant CagA. These results show that exogenous recombinant CagA protein causes cell death by inducing ER stress and autophagy in human cells. We conclude that CagA protein exogenously localizes in/on human cells and induces ER stress via disturbing protein machinery leading the human cell to death, however, the mechanism of CagA-host cell interaction is to be investigated.
Pseudomonas aeruginosauses c-di-GMP phosphodiesterases RmcA and MorA to regulate biofilm maintenance
Authors: Katharios S.L. , Whitfield G.B. , Howell P.L. , O’Toole G.A. 
Published: June 2020

AbstractWhile the early stages of biofilm formation have been well characterized, less is known about the requirements forPseudomonas aeruginosato maintain a mature biofilm. We utilized aP. aeruginosa-phage interaction to find thatrmcAandmorA, two genes which encode for c-di-GMP-degrading phosphodiesterase (PDEs) enzymes, are important for the regulation of biofilm maintenance. Deletion of these genes initially results in an elevated biofilm phenotype characterized by increased production of c-di-GMP, Pel polysaccharide and biofilm biomass. In contrast to the wild-type strain, these mutants were unable to maintain the biofilm when exposed to carbon-limited conditions. The susceptibility to nutrient limitation, and subsequent loss of biofilm viability of these mutants, was phenotypically reproduced with a stringent response mutant (ΔrelAΔspoT), indicating that the ΔrmcAand ΔmorAmutants may be unable to appropriately respond to nutrient limitation. Genetic and biochemical data indicate that RmcA and MorA physically interact with the Pel biosynthesis machinery, supporting a model whereby unregulated Pel biosynthesis contributes to the death of the ΔrmcAand ΔmorAmutant strains in an established biofilm when nutrient-limited. These findings provide evidence that c-di-GMP-mediated regulation is required for mature biofilms ofP. aeruginosato effectively respond to changing availability of nutrients. Furthermore, the PDEs involved in biofilm maintenance are distinct from those required for establishing a biofilm, thus indicating that a wide variety of c-di-GMP metabolizing enzymes in organisms likeP. aeruginosalikely allows for discrete control over the formation, maintenance or dispersion of biofilms.ImportanceRecent advances in our understanding of c-di-GMP signaling have provided key insights into the regulation of biofilms. Despite an improved understanding of how they initially form, the processes that facilitate the long-term maintenance of these multicellular communities remain opaque. We found thatP. aeruginosarequires two phosphodiesterases, RmcA and MorA, to maintain a mature biofilm and thatP. aeruginosabiofilms lacking these PDEs succumb to nutrient limitation and die. The biofilm maintenance deficiency observed in ΔrmcAand ΔmorAmutants was also found in the stringent response defective ΔrelAΔspoTstrain, suggesting that a regulatory intersection between c-di-GMP signaling, EPS biosynthesis and the nutrient limitation response is important for persistent surface growth. We uncover components of an important regulatory system needed forP. aeruginosato persist in nutrient-poor conditions, and provide some of the first evidence that maintaining a mature biofilm is an active process.
ASSESSING THE RELATIONSHIP BETWEEN MONOALLELIC PARK2 MUTATIONS AND PARKINSON’S RISK
Authors: Lubbe Steven J , Bustos Bernabe , Hu Jing , Krainc Dimitri , Joseph Theresita , Hehir Jason , Tan Manuela , Zhang Weijia , Escott-Price Valentina , Williams Nigel M , Blauwendraat Cornelis , Singleton Andrew B , Morris Huw R ,   for International Parkinson’s Disease Genomics Consortium (IPDGC)
Published: June 2020

ABSTRACTBiallelic PARK2 (Parkin) mutations cause autosomal recessive Parkinson’s (PD); however, the role of monoallelic PARK2 mutations as a risk factor for PD remains unclear. We investigated the role of single heterozygous PARK2 mutations in three large independent case-control cohorts totalling 10,858 PD cases and 8,328 controls. Overall, after exclusion of biallelic carriers, single PARK2 mutations were more common in PD than controls conferring a >1.5-fold increase in risk of PD (P=0.035), with meta-analysis (19,574 PD cases and 468,488 controls) confirming increased risk (OR=1.65, P=3.69E-07). Carriers were shown to have significantly younger ages at onset compared to non-carriers (NeuroX: 56.4 vs. 61.4 years; Exome: 38.5 vs. 43.1 years). Stratifying by mutation type, we provide preliminary evidence for a more pathogenic risk profile for single PARK2 copy number variant (CNV) carriers compared to single nucleotide variant carriers. Studies that did not assess biallelic PARK2 mutations or consist of predominantly early-onset cases may be biasing these estimates, and removal of these resulted in a loss of association (OR=1.23, P=0.614; n=4). Importantly, when we looked for additional CNVs in 30% of PD cases with apparent monoallellic PARK2 mutations we found that 44% had biallelic mutations suggesting that previous estimates may be influenced by cryptic biallelic mutation status. While this study supports the association of single PARK2 mutations with PD, it highlights confounding effects therefore caution is needed when interpreting current risk estimates. Together, we demonstrate that comprehensive assessment of biallelic mutation status is essential when elucidating PD risk associated with monoallelic PARK2 mutations.
Predicting the disease outcome in COVID-19 positive patients through Machine Learning: a retrospective cohort study with Brazilian data
Authors: de Souza Fernanda Sumika Hojo , Hojo-Souza Natália Satchiko , dos Santos Edimilson Batista , da Silva Cristiano Maciel , Guidoni Daniel Ludovico 
Published: June 2020

AbstractThe first officially registered case of COVID-19 in Brazil was on February 26, 2020. Since then, the situation has worsened with more than 672, 000 confirmed cases and at least 36, 000 reported deaths at the time of this writing. Accurate diagnosis of patients with COVID-19 is extremely important to offer adequate treatment, and avoid overloading the healthcare system. Characteristics of patients such as age, comorbidities and varied clinical symptoms can help in classifying the level of infection severity, predict the disease outcome and the need for hospitalization. Here, we present a study to predict a poor prognosis in positive COVID-19 patients and possible outcomes using machine learning. The study dataset comprises information of 13, 690 patients concerning closed cases due to cure or death. Our experimental results show the disease outcome can be predicted with a ROC AUC of 0.92, Sensitivity of 0.88 and Specificity of 0.82 for the best prediction model. This is a preliminary retrospective study which can be improved with the inclusion of further data. Conclusion: Machine learning techniques fed with demographic and clinical data along with comorbidities of the patients can assist in the prognostic prediction and physician decision-making, allowing a faster response and contributing to the non-overload of healthcare systems.
Safe Non-opioid and Non-barbiturate containing Acute Medication Combinations in Headache: An Exhaustive Approach Based on DrugBank Database
Authors: Kaytser Victor , Zhang Pengfei 
Published: June 2020

Structured AbstractBackgroundRational polypharmacy in abortive medications use is often inevitable for patients with refractory headaches.ObjectiveWe seek to enumerate an exhaustive list of headaches abortive medications that are without drug-drug interactions.MethodsWe updated a list of acute medications based on the widely used Jefferson Headache Manual with novel abortive medications including ubrogepant, lasmiditan, and rimegepant. Opioids and barbiturate containing products are excluded. We then conducted an exhaustive search of all pair-wise interactions for this list of medication via DrugBank API. Using this interaction list, we filtered all possible two, three, and four drug combinations of abortive medications. The resultant list of medication was then reapplied to DrugBank to verify the lack of known drug-drug interaction.ResultsThere are 192 medication combinations that do not contain any drug-drug interactions. Most common elements in these combinations are ubrogepant, prochlorperazine, followed by tizanidine. There are 67 three-drug combinations that do not contain interaction. Only 2 of the four-drug combinations do not yield some form of drug-drug interactions.ConclusionThis list of headaches abortive medications without drug-drug interactions is a useful tool for clinicians seeking to more effectively manage refractory headaches.
Health concern affects egg consumption among older adults in Tamale Metropolis, Northern Ghana
Authors: Garti Humphrey , Wemakor Anthony , Akwalpua Emmanuella , Saeed Nawaf 
Published: June 2020

ABSTRACTBackgroundEggs are nutrient dense and rich source of quality protein and their consumption could significantly reduce incidence of chronic and infectious diseases especially in the elderly. This study determined egg consumption and factors that influence consumption among the elderly in Tamale metropolis.MethodsAnalytical cross-sectional study was conducted among 387 older adults 60 years and above. Data on egg consumption, nutritional knowledge and awareness of health implications of egg intake were collected using structured questionnaire. Relationships between egg consumption, nutritional knowledge and awareness of health effects of egg consumption were determined in bivariate and multivariate analysis.ResultsRespondents without awareness that egg intake increases risk of diseases were 10 times more likely to eat eggs compared to those who had awareness [Adjusted Odds Ratio 10.24; 95% Confidence Interval (CI) 4.20 – 25.00; p= 0.001]. Respondents with awareness that egg consumption was bad for health were less likely to consume eggs compared to those who thought egg intake was good for health [AOR 0.02; 95 % CI, 0.01 – 0.05, p < 0.001].ConclusionEgg consumption was low among the study population and was affected by health concerns: awareness that egg consumption was not good for health and exposes them to the risk of certain diseases
FMRP activates the translation of large autism/intellectual disability proteins and stimulates N-end rule E3 ligase Poe/UBR4 production within puromycin-sensitive RNP particles
Authors: Greenblatt Ethan J. , Spradling Allan C. 
Published: June 2020

ABSTRACTMutations in Fmr1, encoding the RNA binding protein FMRP, are leading causes of intellectual disability, autism, and female infertility, but FMRP’s mechanism of action is controversial. In contrast to its previously postulated function as a translation repressor acting by stalling elongation, we recently found that FMRP activates translation initiation of large proteins in Drosophila oocytes up to ∼2-fold. We report here that FMRP’s function as a translational activator is conserved in the mammalian brain. Reanalysis of mouse cortex ribosome profiling data shows that translation of large proteins in Fmr1 mutants is down-regulated 2.0-1.2-fold; ribosome stalling appears not to influence FMRP target protein translation in either cortex or oocyte tissue. Consistent with an activator function, most FMRP targets are associated with clinical syndromes when reduced, but not when over-expressed. Fmr1-dependent translation of one target, the N-end rule E3 ligase Poe/UBR4, occurs in microscopically visible ribonucleoprotein particles. These “Poe particles” require FMRP for their formation, are distinct from P bodies, and depend on actively elongating ribosomes, as indicated by their dissolution following a brief puromycin treatment. N-end rule-mediated proteolysis via Poe/UBR4 restrains cell growth and limits MAPK signaling in nervous tissue. Thus, loss of FMRP reduces production of an important growth repressor.
RPA complexes inCaenorhabditis elegansmeiosis; unique roles in replication, meiotic recombination and apoptosis
Authors: Hefel Adam , Cronin Nicholas , Harrel Kailey , Patel Pooja , Spies Maria , Smolikove Sarit 
Published: June 2020

AbstractReplication Protein A (RPA) is critical complex that acts in replication and promotes homologous recombination by allowing recombinase recruitment to processed DSB ends. Most organisms possess three RPA subunits (RPA1, RPA2, RPA3) that form a trimeric complex critical for viability. TheCaenorhabditis elegansgenome encodes for RPA-1, RPA-2 and an RPA-2 paralog RPA-4. In our analysis, we determine that RPA-2 is critical for germline replication, and normal repair of meiotic DSBs. Interestingly, RPA-1 but not RPA-2 is essential for replication, contradictory to what is seen in other organisms, that require both subunits. In the germline, both RPA-1/2 and RPA-1/4 complexes form, but RPA-1/4 is less abundant and its formation is repressed by RPA-2. While RPA-4 does not participate in replication or recombination, we find that RPA-4 inhibit RAD-51 filament formation and promotes apoptosis on a subset of damaged nuclei. Altogether these findings point to sub-functionalization and antagonistic roles of RPA complexes inC. elegans.