bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genes with evidence of positive selection as potentially related to coloniality and the evolution of morphological features among the lophophorates and entoprocts
Authors: Santagata Scott 
Published: July 2020

AbstractEvolutionary mechanisms that underlie the origins of coloniality among organisms are diverse. Some animal colonies may be comprised strictly of clonal individuals formed from asexual budding or comprised of a chimera of clonal and sexually produced individuals that fuse secondarily. This investigation focuses on select members of the lophophorates and entoprocts whose evolutionary relationships remain enigmatic even in the age of genomics. Using transcriptomic data sets, two coloniality‐based hypotheses are tested in a phylogenetic context to find candidate genes showing evidence of positive selection and potentially convergent molecular signatures among solitary species and taxa‐forming colonies from aggregate groups or clonal budding. Approximately 22% of the 387 orthogroups tested showed evidence of positive selection in at least one of the three branch‐site tests (CODEML, BUSTED, and aBSREL). Only 12 genes could be reliably associated with a developmental function related to traits linked with coloniality, neuroanatomy, or ciliary fields. Genes testing for both positive selection and convergent molecular characters include orthologues of Radial spoke head, Elongation translation initiation factors, SEC13, and Immediate early response gene5. Maximum likelihood analyses included here resulted in tree topologies typical of other phylogenetic investigations based on wider genomic information. Further genomic and experimental evidence will be needed to resolve whether a solitary ancestor with multiciliated cells that formed aggregate groups gave rise to colonial forms in bryozoans (and perhaps the entoprocts) or that the morphological differences exhibited by phoronids and brachiopods represent trait modifications from a colonial ancestor.
Frizzled3 expression and colony development in hydractiniid hydrozoans
Authors: Sanders Steven M. , Travert Matthew K. , Cartwright Paulyn 
Published: July 2020

AbstractHydractiniid hydrozoan colonies are comprised of individual polyps connected by tube‐like stolons or a sheet‐like mat. Mat and stolons function to integrate the colony through continuous epithelia and shared gastrovascular cavity. Although mechanisms of hydrozoan polyp development have been well studied, little is known about the signaling processes governing the patterning of colonies. Here we investigate the Wnt receptor family Frizzled. Phylogenetic analysis reveals that hydrozoans possess four Frizzled orthologs. We find that one of these genes, Frizzled3, shows a spatially restricted expression pattern in colony‐specific tissue in two hydractiniid hydrozoans, Hydractinia symbiolongicarpus and Podocoryna carnea, in a manner that corresponds to their distinct colony forms (stolonal mat in Hydractinia and free stolons in Podocoryna). Interestingly, Frizzled3 was lost in the genome of Hydra, which is a solitary polyp and thus lacks colony‐specific tissue. Current evidence suggests that the Wnt signaling pathway plays a key role in the evolution of colony diversity and colony loss in Hydrozoa.
Cellular dynamics of double fertilization and early embryogenesis in flowering plants
Authors: Shin Ji Min , Yuan Ling , Ohme‐Takagi Masaru , Kawashima Tomokazu 
Published: July 2020

AbstractFlowering plants (angiosperms) perform a unique double fertilization in which two sperm cells fuse with two female gamete cells in the embryo sac to develop a seed. Furthermore, during land plant evolution, the mode of sexual reproduction has been modified dramatically from motile sperm in the early‐diverging land plants, such as mosses and ferns as well as some gymnosperms (Ginkgo and cycads) to nonmotile sperm that are delivered to female gametes by the pollen tube in flowering plants. Recent studies have revealed the cellular dynamics and molecular mechanisms for the complex series of double fertilization processes and elucidated differences and similarities between animals and plants. Here, together with a brief comparison with animals, we review the current understanding of flowering plant zygote dynamics, covering from gamete nuclear migration, karyogamy, and polyspermy block, to zygotic genome activation as well as asymmetrical division of the zygote. Further analyses of the detailed molecular and cellular mechanisms of flowering plant fertilization should shed light on the evolution of the unique sexual reproduction of flowering plants.
Delays in repeat HIV viral load testing for those with elevated viral loads: a national perspective from South Africa
Authors: Fox Matthew P , Brennan Alana T , Nattey Cornelius , MacLeod William B , Harlow Alyssa , Mlisana Koleka , Maskew Mhairi , Carmona Sergio , Bor Jacob 
Published: July 2020

AbstractIntroductionIn South Africa, HIV patients with an elevated viral load (VL) should receive repeat VL testing after adherence counselling. We set out to use a national HIV Cohort to describe time to repeat viral load testing across South Africa and identify predictors of time to repeat testing.MethodsWe conducted a cohort study of prospectively collected laboratory data. HIV treatment guidelines have changed over time in South Africa, but call for repeat VL testing within six months if 400 to 1000 copies/mL and two to three months if >1000 copies/mL. We included patients with suppressed viral loads (indicating they are on ART) and a first elevated VL (>400 copies/mL) between April 2004 and December 2014. Follow‐up began at first elevated VL and continued until repeat testing, loss to follow‐up or December 2016. We calculated adjusted hazard ratios (aHR) using Cox proportional hazard models.ResultsOf 371,648 patients with a VL > 400, 83.9% (311,790) had a repeat VL, in a median (IQR) of 7.0 (4.1 to 12.2) months. Of those with a first viral load 400 to 1000 copies/mL, 56.4% had a repeat VL within guideline recommended six months (defined as up to nine months), whereas among those >1000 copies/mL only 47.7% had a repeat viral load within guideline recommended two to three months (defined as up to six months). We found a small increase in repeat testing associated with higher VL value (aHR 1.11; 95% CI: 1.10 to 1.12 comparing >1000 vs 400 to 1000 copies/mL) and very low CD4 counts at first elevated VL (aHR 1.16; 95% CI: 1.13 to 1.19 comparing CD4 < 50 vs <500 cells/mm3). We also found strong variation in time to repeat VL testing by province.ConclusionsMedian time to repeat viral load testing for those with an elevated viral load was longer than guidelines recommend. Future work should identify whether delays are due to patient or provider factors.
p67phox-derived self-assembled peptides prevent Nox2 NADPH oxidase activation by an auto-inhibitory mechanism
Authors: Bechor Edna , Zahavi Anat , Berdichevsky Yevgeny , Pick Edgar 
Published: July 2020

Abstract
Activation of the Nox2-dependent NADPH oxidase is the result of a conformational change in Nox2 induced by interaction with the cytosolic component p67phox. In preliminary work we identified a cluster of overlapping 15-mer synthetic peptides, corresponding to p67phox residues 259-279, which inhibited oxidase activity in an in vitro, cell-free assay, but the results did not point to a competitive mechanism. We recently identified an auto-inhibitory intramolecular bond in p67phox, one extremity of which was located within the 259-279 sequence, and we hypothesized that inhibition by exogenous peptides might mimic intrinsic auto-inhibition. In this study, we found that: (i) progressive N- and C-terminal truncation of inhibitory p67phox peptides, corresponding to residues 259-273 and 265-279, revealed that inhibitory ability correlated with the presence of residues 265NIVFVL270, exposed at either the N- or C-termini of the peptides; (ii) inhibition of oxidase activity was associated exclusively with self-assembled peptides, which pelleted upon centrifugation at 12,000 ×g; (iii) self-assembled p67phox peptides inhibited oxidase activity by specific binding of p67phox and the ensuing depletion of this component, essential for interaction with Nox2; and (iv) peptides subjected to scrambling or reversing the order of residues in NIVFVL retained the propensity for self-assembly, oxidase inhibitory ability, and specific binding of p67phox, indicating that the dominant parameter was the hydrophobic character of five of the six residues. This appears to be the first description of inhibition of oxidase activity by self-assembled peptides derived from an oxidase component, acting by an auto-inhibitory mechanism.
Modulation of neutrophil extracellular traps release by Klebsiella pneumoniae
Authors: Birnberg-Weiss Federico , Castillo Luis A , Pittaluga Jose R , Martire-Greco Daiana , Gómez Sonia A , Landoni Verónica I , Fernández Gabriela C 
Published: July 2020

Abstract
One of the main bactericidal mechanisms of polymorphonuclear neutrophils (PMN) is the release of neutrophil extracellular traps (NETs), which capture and destroy pathogens. Klebsiella pneumoniae (Kpn) producer of carbapenemase (KPC) and belonging to the sequence type 258 (ST258), is a hyper epidemic clone that causes a large number of infections worldwide associated with high persistence and mortality. It is necessary to investigate the interaction of Kpn KPC with the immune system to improve prevention and treatment of infections mediated by this bacterium. Based on the hypothesis that Kpn is able to subvert PMN-mediated death, the aim was to assess whether Kpn KPC ST258 could modulate the bactericidal response of PMN, focusing on NETs formation, compared to another opportunistic pathogen, as Escherichia coli (Eco). The results showed that the release of NETs was absent when PMN were challenged with Kpn KPC, while Eco was a strong inducer of NETosis. Moreover, Kpn KPC was able to inhibit NETosis induced by Eco. The inhibition of Kpn KPC-mediated NETs formation still occurred in spite of exogenous addition of hydrogen peroxide (H2O2), did not involve bacterial-released soluble factors or cell wall components, and was dependent on bacterial viability. Moreover, when degranulation was investigated, we found that Kpn KPC affected only the mobilization of primary granules, which harbor the proteins with more potent bactericidal properties and those related to NETosis. In conclusion, Kpn KPC ST258 effectively managed to evade the PMN response by inhibiting the release of NETs, and primary granule mobilization.
Neuronal gamma oscillations and activity‐dependent potassium transients remain regular after depletion of microglia in postnatal cortex tissue
Authors: Lewen Andrea , Ta Thuy‐Truc , Cesetti Tiziana , Hollnagel Jan‐Oliver , Papageorgiou Ismini E. , Chausse Bruno , Kann Oliver 
Published: July 2020

AbstractMicroglial cells (resident macrophages) feature rapid activation in CNS disease and can acquire multiple phenotypes exerting neuroprotection or neurotoxicity. The functional impact of surveying (“resting”) microglia on neural excitability and neurotransmission in physiology is widely unknown, however. We addressed this issue in male rat hippocampal slice cultures (in situ) by pharmacological microglial ablation within days and by characterizing neuronal gamma‐band oscillations (30–70 Hz) that are highly sensitive to neuromodulators and disturbances in ion and energy regulation. Gamma oscillations support action potential timing and synaptic plasticity, associate with higher brain functions like perception and memory, and require precise communication between excitatory pyramidal cells and inhibitory (GABAergic) interneurons. The slice cultures featured well‐preserved hippocampal cytoarchitecture and parvalbumin‐positive interneuron networks, microglia with ramified morphology, and low basal levels of IL‐6, TNF‐α, and nitric oxide (NO). Stimulation of slice cultures with the pro‐inflammatory cytokine IFN‐γ or bacterial LPS serving as positive controls for microglial reactivity induced MHC‐II expression and increased cytokine and NO release. Chronic exposure of slice cultures to liposome‐encapsulated clodronate reduced the microglial cell population by about 96%, whereas neuronal structures, astrocyte GFAP expression, and basal levels of cytokines and NO were unchanged. Notably, the properties of gamma oscillations reflecting frequency, number and synchronization of synapse activity were regular after microglial depletion. Also, electrical stimulus‐induced transients of the extracellular potassium concentration ([K+]o) reflecting cellular K+ efflux, clearance and buffering were unchanged. This suggests that nonreactive microglia are dispensable for neuronal homeostasis and neuromodulation underlying network signaling and rhythm generation in cortical tissue.
The clinical implication of new‐onset in‐hospital atrial fibrillation in patients with acute decompensated heart failure
Authors: Kamioka Masashi , Yoshihisa Akiomi , Nodera Minoru , Misaka Tomofumi , Yokokawa Tetsuro , Kaneshiro Takashi , Nakazato Kazuhiko , Ishida Takafumi , Takeishi Yasuchika 
Published: July 2020

AbstractBackgroundTo investigate the clinical implication of the temporal difference in atrial fibrillation (AF)‐onset in acute decompensated heart failure (ADHF) and its impact on post‐discharge prognosis.Methods336 new‐onset ADHF patients without any history of AF before admission were enrolled (201 males, 63 ± 16 year‐old) and classified into two groups based on their history of AF: the Control group (No AF was detected during hospitalization, n = 278), and the In‐hos‐AF group (AF occurred during hospitalization, n = 58). Post discharge prognosis including rehospitalization due to worsening HF, cardiac death, all‐cause death and cerebrovascular event were compared.ResultsKaplan‐Meier analysis demonstrated that the incidence of rehospitalization due to HF, cardiac death, all‐cause death and cerebrovascular event in the In‐hos‐AF group was not significantly different from that in the Control group (P > 0.05 respectively). However, when AF recurred in the In‐hos‐AF group patients (n = 24, 41%) after discharge, the incidence of rehospitalization due to HF and cardiac deaths were higher than those without AF recurrence (P = 0.018 and P = 0.027 respectively). Cox proportional analysis revealed that AF developing after discharge was proven to be an independent risk factor for rehospitalization due to HF (HR 1.845, P = 0.043), cardiac death (HR 3.562, P = 0.013) and all‐cause deaths (HR 2.138, P = 0.020).ConclusionClinical outcomes of new‐onset in‐hospital AF patients were as good as those without AF history until AF recurrence. However, AF recurrence led to worse prognosis. Therefore, treatment for new‐onset in‐hospital AF in ADHF patients might be postponed until AF recurrence.
Long‐term outcomes of anterior cruciate ligament reconstruction surgery: 2020 OREF clinical research award paper
Authors: Fleming Braden C. , Fadale Paul D. , Hulstyn Michael J. , Shalvoy Robert M. , Tung Glenn A. , Badger Gary J. 
Published: July 2020

AbstractACL injuries place the knee at risk for post‐traumatic osteoarthritis (PTOA) despite surgical anterior cruciate ligament (ACL) reconstruction. One parameter thought to affect PTOA risk is the initial graft tension. This randomized controlled trial (RCT) was designed to compare outcomes between two graft tensioning protocols that bracket the range commonly used. At 7 years postsurgery, we determined that most outcomes between the two tension groups were not significantly different, that they were inferior to an uninjured matched control group, and that PTOA was progressing in both groups relative to controls. The trial database was also leveraged to gain insight into mechanisms of PTOA following ACL injury. We determined that the inflammatory response at the time of injury undermines one of the joint's lubricating mechanisms. We learned that patients continue to protect their surgical knee 5 years postinjury compared to controls during a jump‐pivot activity. We also established that presurgical knee function and mental health were correlated with symptomatic PTOA at 7 years, that there were specific anatomical factors associated with poor outcomes, and that there were no changes in outcomes due to tunnel widening in patients receiving hamstring tendon autografts. We also validated a magnetic resonance imaging technique to noninvasively assess graft strength. In conclusion, the RCT determined that initial graft tensioning does not have a major influence on 7‐year outcomes. Therefore, surgeons can reconstruct the ACL using a graft tensioning protocol that is within the window of the two graft tensioning techniques evaluated in this RCT.
Prediction of local fixed charge density loss in cartilage following ACL injury and reconstruction: A computational proof‐of‐concept study with MRI follow‐up
Authors: Orozco Gustavo A. , Bolcos Paul , Mohammadi Ali , Tanaka Matthew S. , Yang Mingrui , Link Thomas M. , Ma Benjamin , Li Xiaojuan , Tanska Petri , Korhonen Rami K. 
Published: July 2020

AbstractThe purpose of this proof‐of‐concept study was to develop three‐dimensional patient‐specific mechanobiological knee joint models to simulate alterations in the fixed charged density (FCD) around cartilage lesions during the stance phase of the walking gait. Two patients with anterior cruciate ligament (ACL) reconstructed knees were imaged at 1 and 3 years after surgery. The magnetic resonance imaging (MRI) data were used for segmenting the knee geometries, including the cartilage lesions. Based on these geometries, finite element (FE) models were developed. The gait of the patients was obtained using a motion capture system. Musculoskeletal modeling was utilized to calculate knee joint contact and lower extremity muscle forces for the FE models. Finally, a cartilage adaptation algorithm was implemented in both FE models. In the algorithm, it was assumed that excessive maximum shear and deviatoric strains (calculated as the combination of principal strains), and fluid velocity, are responsible for the FCD loss. Changes in the longitudinal T1ρ and T2 relaxation times were postulated to be related to changes in the cartilage composition and were compared with the numerical predictions. In patient 1 model, both the excessive fluid velocity and strain caused the FCD loss primarily near the cartilage lesion. T1ρ and T2 relaxation times increased during the follow‐up in the same location. In contrast, in patient 2 model, only the excessive fluid velocity led to a slight FCD loss near the lesion, where MRI parameters did not show evidence of alterations. Significance: This novel proof‐of‐concept study suggests mechanisms through which a local FCD loss might occur near cartilage lesions. In order to obtain statistical evidence for these findings, the method should be investigated with a larger cohort of subjects.
Hydrogels with Cell Adhesion Peptide‐Decorated Channel Walls for Cell Guidance
Authors: Wang Shuang , Sarwat Mariah , Wang Peng , Surrao Denver C. , Harkin Damien G. , St John James A. , Bolle Eleonore C. L. , Forget Aurelien , Dalton Paul D. , Dargaville Tim R. 
Published: July 2020

AbstractA method is reported for making hollow channels within hydrogels decorated with cell‐adhesion peptides exclusively at the channel surface. Sacrificial fibers of different diameters are used to introduce channels within poly(ethylene glycol) hydrogels crosslinked with maleimide‐thiol chemistry, which are backfilled with a cysteine‐containing peptide solution which is conjugated to the lumen with good spatial efficiency. This allows for peptide patterning in only the areas of the hydrogel where they are needed when used as cell‐guides, reducing the amount of required peptide 20‐fold when compared to bulk functionalization. The power of this approach is highlighted by successfully using these patterned hydrogels without active perfusion to guide fibroblasts and olfactory ensheathing cells—the latter having unique potential in neural repair therapies.
Porous microneedles on a paper for screening test of prediabetes
Authors: Lee Hakjae , Bonfante Gwenaël , Sasaki Yui , Takama Nobuyuki , Minami Tsuyoshi , Kim Beomjoon 
Published: July 2020

AbstractPorous microneedles are expected to have a variety of potential for applications in diagnostics owing to their ability to penetrate human skin painlessly and extract bio‐fluid by capillary action. In this paper, a ‘Porous Microneedle on a Paper substrate’ (PMP) is proposed as a novel platform for direct integration of sensors. A microneedle array with height of approximately 840 μm was prepared on a paper. The fabrication process consists of salt leaching and heat press moulding. In this method, the salt particles are utilized as porogen materials. Mixture of the biodegradable polymer and the salt was shaped into microneedles by moulding. Furthermore, the polymer penetrated the paper matrix owing to heating during the pressing process. Subsequently, the salt particles are removed to develop the porous structure. Various ratios of salt to polymer were investigated to adjust the porosity of microneedles as well as their sample absorption property. A paper‐based glucose sensor was integrated into the platform to demonstrate the absorption property of the microneedles, and showed successful sample extraction and glucose concentration analysis from agarose gel‐based skin mimic. The developed platform has the potential to integrate various paper‐based bio‐sensors to painless, disposal and fast screening and diagnostic test for patient, as well as those with prediabetes.
Modern approaches in gene therapy of motor neuron diseases
Authors: Zakharova Maria 
Published: July 2020

AbstractMotor neuron disorders are a group of neurodegenerative diseases characterized by muscle weakness, loss of ambulation, respiratory insufficiency, leading to an early death. Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis are the most common and fatal motor neuron diseases. The last 3 years became very successful for novel gene therapy approaches in SMA in infants. Two innovative drugs—nusinersen (Spinraza) and onasemnogene abeparvovec (Zolgensma) have been approved by health authorities. The numerous molecular and genetic overlaps between different neurodegenerative diseases are of great importance in the development of innovative therapeutic strategies, including viral vector therapy and RNA modulating approaches.
Spectrum of gene mutations identified by targeted next‐generation sequencing in Chinese leukemia patients
Authors: Yao Hongxia , Wu Congming , Chen Yueqing , Guo Li , Chen Wenting , Pan Yanping , Fu Xiangjun , Wang Guyun , Ding Yipeng 
Published: July 2020

AbstractBackgroundDespite targeted sequencing have identified several mutations for leukemia, there is still a limit of mutation screening for Chinese leukemia. Here, we used targeted next‐generation sequencing for testing the mutation patterns of Chinese leukemia patients.MethodsWe performed targeted sequencing of 504 tumor‐related genes in 109 leukemia samples to identify single‐nucleotide variants (SNVs) and insertions and deletions (INDELs). Pathogenic variants were assessed based on the American College of Medical Genetics and Genomics (ACMG) guidelines. The functional impact of pathogenic genes was explored through gene ontology (GO), pathway analysis, and protein–protein interaction network in silico.ResultsWe identified a total of 4,655 SNVs and 614 INDELs in 419 genes, in which PDE4DIP, NOTCH2, FANCA, BCR, and ROS1 emerged as the highly mutated genes. Of note, we were the first to demonstrate an association of PDE4DIP mutation and leukemia. Based on ACMG guidelines, 39 pathogenic and likely pathogenic mutations in 27 genes were found. GO annotation showed that the biological process including gland development, leukocyte differentiation, respiratory system development, myeloid leukocyte differentiation, mesenchymal to epithelial transition, and so on were involved.ConclusionOur study provided a map of gene mutations in Chinese patients with leukemia and gave insights into the molecular pathogenesis of leukemia.