bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasminogen is a master regulator and a potential drug candidate for the healing of radiation wounds
Authors: Fallah Mahsa , Viklund Emil , Bäckman Assar , Brodén Jessica , Lundskog Bertil , Johansson Michael , Blomquist Michael , Wilczynska Malgorzata , Ny Tor
Published: March 2020

Around 95% of cancer patients undergoing radiotherapy experience cutaneous side effects, and some develop radiation wounds or fibrosis. Currently, there is no effective treatment for these indications. We show here that plasminogen administration enhanced the healing of radiation wounds via pleiotropic effects on gene expression. Using RNA sequencing, we found that plasminogen downregulated the expression of genes in the TLR, TNF, WNT, MAPK, and TGF-β signaling pathways, and enhanced the anti-inflammatory effect of arachidonic acid, leading to significantly decreased inflammation and improved remodeling of granulation tissue compared with placebo treatment. In addition, plasminogen induced metabolic changes, including decreased glycolysis. Importantly, many of the factors downregulated by plasminogen are pro-fibrotic. Therefore, in radiation wounds with excessive inflammation, plasminogen is able to enhance and redirect the healing process, such that it more closely resembles physiological healing with significantly reduced risk for developing fibrosis. This makes plasminogen an attractive drug candidate for the treatment of radiation wounds in cancer patients.
Observation of information flow in the anti-𝒫𝒯-symmetric system with nuclear spins
Authors: Wen Jingwei , Qin Guoqing , Zheng Chao , Wei Shijie , Kong Xiangyu , Xin Tao , Long Guilu
Published: March 2020

The recently theoretical and experimental researches on $${\mathcal{PT}}$$
PT
-symmetric system have attracted unprecedented attention because of the various interesting features and potential applications in extending canonical quantum mechanics. However, as the counterpart of $${\mathcal{PT}}$$
PT
-symmetry, there are few experimental researches on the anti-$${\mathcal{PT}}$$
PT
-symmetric quantum system because of the challenges in simulating anti-$${\mathcal{PT}}$$
PT
-symmetry in experiment. Here, we propose an algorithm for simulating the generalized anti-$${\mathcal{PT}}$$
PT
-symmetric system in the quantum circuit model. Utilizing the algorithm, we demonstrated the quantum simulation of anti-$${\mathcal{PT}}$$
PT
system experimentally, and an oscillation of information flow is observed in a nuclear magnetic resonance quantum simulator. The experiment showed that the information could recover from the environment completely when the anti-$${\mathcal{PT}}$$
PT
-symmetry is broken, whereas no information can be retrieved in the symmetry-unbroken phase. Our work opens the gate for the practical quantum simulation and experimental investigation of universal anti-$${\mathcal{PT}}$$
PT
-symmetric system in a quantum computer.
Immune predictors of oral poliovirus vaccine immunogenicity among infants in South India
Authors: Babji Sudhir , Manickavasagam Punithavathy , Chen Yin-Huai , Jeyavelu Nithya , Jose Nisha Vincy , Praharaj Ira , Syed Chanduni , Kaliappan Saravanakumar Puthupalayam , John Jacob , Giri Sidhartha , Venugopal Srinivasan , Kampmann Beate , Parker Edward P. K. , Iturriza-Gómara Miren , Kang Gagandeep , Grassly Nicholas C. , Uhlig Holm H.
Published: March 2020

Identification of the causes of poor oral vaccine immunogenicity in low-income countries might lead to more effective vaccines. We measured mucosal and systemic immune parameters at the time of vaccination with oral poliovirus vaccine (OPV) in 292 Indian infants aged 6–11 months, including plasma cytokines, leukocyte counts, fecal biomarkers of environmental enteropathy and peripheral blood T-cell phenotype, focused on gut-homing regulatory CD4+ populations. We did not find a distinct immune phenotype associated with OPV immunogenicity, although viral pathogens were more prevalent in stool at the time of immunization among infants who failed to seroconvert (63.9% vs. 45.6%,p = 0.002). Using a machine-learning approach, we could predict seroconversion a priori using immune parameters and infection status with a median 58% accuracy (cross-validation IQR: 50–69%) compared with 50% expected by chance. Better identification of immune predictors of OPV immunogenicity is likely to require sampling of mucosal tissue and improved oral poliovirus infection models.
Development of encoded Broccoli RNA aptamers for live cell imaging of alphavirus genomic and subgenomic RNAs
Authors: Nilaratanakul Voraphoj , Hauer Debra A. , Griffin Diane E.
Published: March 2020

Sindbis virus (SINV) can infect neurons and cause encephalomyelitis in mice. Nonstructural proteins are translated from genomic RNA and structural proteins from subgenomic RNA. While visualization of viral proteins in living cells is well developed, imaging of viral RNAs has been challenging. RNA aptamers that bind and activate conditional fluorophores provide a tool for RNA visualization. We incorporated cassettes of two F30-scaffolded dimers of the Broccoli aptamer into a SINV cDNA clone using sites in nsP3 (genomic RNA), the 3′UTR (genomic and subgenomic RNAs) and after a second subgenomic promoter resulting in 4–28 Broccoli copies. After addition of the cell-permeable 3,5-difluoro-4-hydroxybenzylidene imidazolinone (DFHBI-1T) conditional fluorophore and laser excitation, infected cells emitted green fluorescence that correlated with Broccoli copy numbers. All recombinant viruses replicated well in BHK and undifferentiated neural cells but viruses with 14 or more Broccoli copies were attenuated in differentiated neurons and mice. The signal survived fixation and allowed visualization of viral RNAs in differentiated neurons and mouse brain, as well as BHK cells. Subgenomic RNA was diffusely distributed in the cytoplasm with genomic RNA also in perinuclear vesicle-like structures near envelope glycoproteins or mitochondria. Broccoli aptamer-tagging provides a valuable tool for live cell imaging of viral RNA.
A novel endoscopic visible full-thickness cryoablation device on stomach
Authors: Zheng Wanwei , Liu Yao , Tseng Yujen , Zhang Jun , Li Wenshuai , Wang Bangting , Pan Yida , Zhu Jie , Luo Zhongguang , Luo Feifei , Liu Jie
Published: March 2020

Cryoablation has been used for the treatment of various sorts of solid visceral tumors, but few are reported on gastric tumor via endoscope, in terms of accurate control of ablation site, freezing depth and effective temperature. Thus, we developed a novel device, which could perform accurate cryoablation on the stomach via endoscope. This study aimed to evaluate the efficacy and safety of the device on porcine stomach. Results showed that the novel device could provide direct view of the operation space, allowing accurate and safe ablation of the stomach. Three minutes cryoablation caused a transmural, 1 cm radius gastric lesion. On serosal side, the temperature dropped to −64.2 °C, −34.1 °C, 26.1 °C at the center, 1 cm and 2 cm from center, respectively. Histopathology revealed acute ruptured cells with damaged glands in mucosa, partial disruption in muscularis propria and serosal slight exudation. Three months later, scar formed with complete recovery of gastric structure. No active bleeding or perforation of stomach, nor injury or adhesion of adjacent organs was observed. This endoscopic cryoablation device allowed safe, full-thickness cryoablation with effective temperature, which may provide an alternative treatment for gastric tumor.
The Ionospheric view of the 2011 Tohoku-Oki earthquake seismic source: the first 60 seconds of the rupture
Authors: Bagiya Mala S. , Thomas Dhanya , Astafyeva Elvira , Bletery Quentin , Lognonné Philippe , Ramesh Durbha Sai
Published: March 2020

Using the specific satellite line of sight geometry and station location with respect to the source, Thomas et al. [Scientific Reports, https://doi.org/10.1038/s41598-018-30476-9] developed a method to infer the detection altitude of co-seismic ionospheric perturbations observed in Global Positioning System (GPS) – Total Electron Content (TEC) measurements during the Mw 7.4 March 9, 2011 Sanriku-Oki earthquake, a foreshock of the Mw 9.0, March 11, 2011 Tohoku-Oki earthquake. Therefore, in addition to the spatio-temporal evolution, the altitude information of the seismically induced ionospheric signatures can also be derived now using GPS-TEC technique. However, this method considered a point source, in terms of a small rupture area (~90 km) during the Tohoku foreshock, for the generation of seismo-acoustic waves in 3D space and time. In this article, we explore further efficacy of GPS-TEC technique during co-seismic ionospheric sounding for an extended seismic source varying simultaneously in space and time akin to the rupture of Mw 9.0 Tohoku-Oki mainshock and the limitations to be aware of in such context. With the successful execution of the method by Thomas et al. during the Tohoku-Oki mainshock, we not only estimate the detection altitude of GPS-TEC derived co-seismic ionospheric signatures but also delineate, for the first time, distinct ground seismic sources responsible for the generation of these perturbations, which evolved during the initial 60 seconds of the rupture. Simulated tsunami water excitation over the fault region, to envisage the evolution of crustal deformation in space and time along the rupture, formed the base for our model analysis. Further, the simulated water displacement assists our proposed novel approach to delineate the ground seismic sources entirely based on the ensuing ionospheric perturbations which were otherwise not well reproduced by the ground rupture process within this stipulated time. Despite providing the novel information on the segmentation of the Tohoku-Oki seismic source based on the co-seismic ionospheric response to the initial 60 seconds of the event, our model could not reproduce precise rupture kinematics over this period. This shortcoming is also credited to the specific GPS satellite-station viewing geometries.
Tau protein- induced sequestration of the eukaryotic ribosome: Implications in neurodegenerative disease
Authors: Banerjee Senjuti , Ferdosh Sehnaz , Ghosh Amar Nath , Barat Chandana
Published: March 2020

The human tau is a microtubule-associated intrinsically unstructured protein that forms intraneuronal cytotoxic deposits in neurodegenerative diseases, like tauopathies. Recent studies indicate that in Alzheimer’s disease, ribosomal dysfunction might be a crucial event in the disease pathology. Our earlier studies had demonstrated that amorphous protein aggregation in the presence of ribosome can lead to sequestration of the ribosomal components. The present study aims at determining the effect of incubation of the full-length tau protein (Ht40) and its microtubule binding 4-repeat domain (K18) on the eukaryotic ribosome. Our in vitro studies show that incubation of Ht40 and the K18 tau variants with isolated non-translating yeast ribosome can induce a loss of ribosome physical integrity resulting in formation of tau-rRNA-ribosomal protein aggregates. Incubation with the tau protein variants also led to a disappearance of the peak indicating the ribosome profile of the HeLa cell lysate and suppression of translation in the human in vitro translation system. The incubation of tau protein with the ribosomal RNA leads to the formation of tau-rRNA aggregates. The effect of K18 on the yeast ribosome can be mitigated in the presence of cellular polyanions like heparin and tRNA, thereby indicating the electrostatic nature of the aggregation process.
Comparative morphometric analysis of lungs of the semifossorial giant pouched rat (Cricetomys gambianus) and the subterranean Nigerian mole rat (Cryptomys foxi)
Authors: Maina John N. , Igbokwe Casmir O.
Published: March 2020

Lungs of the rodent species, the African giant pouched rat (Cricetomys gambianus) and the Nigerian mole rat (Cryptomys foxi) were investigated. Significant morphometric differences exist between the two species. The volume of the lung per unit body mass was 2.7 times larger; the respiratory surface area 3.4 times greater; the volume of the pulmonary capillary blood 2 times more; the harmonic mean thickness of the blood-gas (tissue) barrier (τht) ~29% thinner and; the total pulmonary morphometric diffusing capacity (DLo2) for O22.3 times more inC. foxi.C. gambianusoccupies open burrows that are ventilated with air whileC. foxilives in closed burrows. The less morphometrically specialized lungs ofC. gambianusmay be attributed to its much larger body mass (~6 times more) and possibly lower metabolic rate and its semifossorial life whereas the ‘superior’ lungs ofC. foximay largely be ascribed to the subterranean hypoxic and hypercapnic environment it occupies. Compared to other rodents species that have been investigated hitherto, the τht was mostly smaller in the lungs of the subterranean species andC. foxihas the highest mass-specific DLo2. The fossorial- and the subterranean rodents have acquired various pulmonary structural specializations that relate to habitats occupied.
Delayed two steps PRP injection strategy for the improvement of fat graft survival with superior angiogenesis
Authors: Li Yuan , Mou Shan , Xiao Peng , Li Guining , Li Jialun , Tong Jing , Wang Jiecong , Yang Jie , Sun Jiaming , Wang Zhenxing
Published: March 2020

Platelet-rich plasma (PRP) has been widely used to improve the fat retention rate in autologous fat transplantation since it possesses a good angiogenesis capability in vivo. However, due to the short half-life of growth factors released from PRP and its uneven distribution in injected fat tissue, the strategy of PRP in fat transplantation needs further improvement. Since the capillaries started to grow into fat grafts in 1 week and vascular growth peaks in the second week after transplantation, we hypothesized that delayed two-steps PRP injection into the interior of grafts, accompanied with the extent of neovascularization might theoretically promote microvessel growth inside transplanted adipose tissue. 24 nude mice were divided into three groups: Blank group (0.35 mL fat mixed with 0.15 mL saline, N = 8), Single step group (0.35 mL fat mixed with 0.15 mLPRP, N = 8), and Two steps group (0.35 mL fat (day 0) + 0.075 mL PRP (day 7) + 0.075 mL PRP (day 14), N = 8). At 6 and 14 weeks post-transplantation, grafts were dissected, weighted, and assessed for histology, angiogenesis, fat regeneration and inflammation level. The weight and volume of the fat samples revealed no statistical difference among the three groups at 6 weeks after fat transplantation. The weight and volume of the Two steps group fat samples showed significantly higher compared to that in Blank and Single step groups at 14 weeks after fat transplantation (weight: 137.25 ± 5.60 mg versus 87.5 ± 3.90 mg,106.75 ± 2.94 mg, respectively; volume: 0.13 ± 0.01 mL versus 0.08 ± 0.01 mL, 0.09 ± 0.01 mL, respectively). Histological assessments indicated that delayed two-steps PRP injection strategy helps to improve adipose tissue content and reduce the composition of fibrous connective tissue at 14 weeks after fat transplantation. At 6 weeks and 14 weeks after transplantation, CD31 immunofluorescence indicated that delayed two-steps PRP injection strategy helps to improve angiogenesis and significantly higher compared to that in Blank and Single step groups (6 weeks: 28.75 ± 4.54 versus 10.50 ± 2.06, 21.75 ± 1.85; 14 weeks: 21.75 ± 2.86 versus 9.87 ± 2.08, 11.75 ± 1.47, respectively). Preadipocyte count indicated delayed two-steps PRP injection strategy might promote fat regeneration and significantly higher compared to that in Blank and Single step groups at 14 weeks (129.75 ± 6.57 versus 13.50 ± 3.50, 17.12 ± 6.23, respectively). In this study, we demonstrated that the novel delayed two-steps PRP injection strategy remarkably enhanced the long-term fat retention rate and improved the neovascularization extent in the interior of the fat graft. Platelet-rich plasma, Delayed two-steps injection, Angiogenesis, Fat transplantation
Late weaning and maternal closeness, associated with advanced motor and visual maturation, reinforce autonomy in healthy, 2-year-old children
Authors: Villar José , Ochieng Roseline , Staines-Urias Eleonora , Fernandes Michelle , Ratcliff Marc , Purwar Manorama , Barros Fernando , Horta Bernardo , Cheikh Ismail Leila , Albernaz Elaine , Kunnawar Naina , Temple Sophie , Giuliani Francesca , Sandells Tamsin , Carvalho Maria , Ohuma Eric , Jaffer Yasmin , Alison Noble J. , Gravett Michael , Pang Ruyan , Lambert Ann , Bertino Enrico , Di Nicola Paola , Papageorghiou Aris , Stein Alan , Bhutta Zulfiqar , Kennedy Stephen
Published: March 2020

We studied neurodevelopmental outcomes and behaviours in healthy 2-year old children (N = 1306) from Brazil, India, Italy, Kenya and the UK participating in the INTERGROWTH-21stProject. There was a positive independent relationship of duration of exclusive breastfeeding (EBF) and age at weaning with gross motor development, vision and autonomic physical activities, most evident if children were exclusively breastfed for ≥7 months or weaned at ≥7 months. There was no association with cognition, language or behaviour. Children exclusively breastfed from birth to <5 months or weaned at >6 months had, in a dose-effect pattern, adjusting for confounding factors, higher scores for “emotional reactivity”. The positive effect of EBF and age at weaning on gross motor, running and climbing scores was strongest among children with the highest scores in maternal closeness proxy indicators. EBF, late weaning and maternal closeness, associated with advanced motor and vision maturation, independently influence autonomous behaviours in healthy children.
Comparative temporal metabolomics studies to investigate interspecies variation in three Ocimum species
Authors: Rastogi Shubhra , Shah Saumya , Kumar Ritesh , Kumar Ajay , Shasany Ajit Kumar
Published: March 2020

Ocimum is one of the most revered medicinally useful plants which have various species. Each of the species is distinct in terms of metabolite composition as well as the medicinal property. Some basil types are used more often as an aromatic and flavoring ingredient. It would be informative to know relatedness among the species which though belong to the same genera while exclusively different in terms of metabolic composition and the operating pathways. In the present investigation the similar effort has been made in order to differentiate three commonly occurring Ocimum species having the high medicinal value, these are Ocimum sanctum, O. gratissimum and O. kilimandscharicum. The parameters for the comparative analysis of these three Ocimum species comprised of temporal changes in number leaf trichomes, essential oil composition, phenylpropanoid pathway genes expression and the activity of important enzymes. O. gratissimum was found to be richest in phenylpropanoid accumulation as well as their gene expression when compared to O. sanctum while O. kilimandscharicum was found to be accumulating terpenoid. In order to get an overview of this qualitative and quantitative regulation of terpenes and phenylpropenes, the expression pattern of some important transcription factors involved in secondary metabolism were also studied.
Maternal obesity and severe pre-eclampsia among immigrant women: a mediation analysis
Authors: Siddiqui Ayesha , Deneux-Tharaux Catherine , Luton Dominique , Schmitz Thomas , Mandelbrot Laurent , Estellat Candice , Howell Elizabeth A. , Khoshnood Babak , Bertille Nathalie , Azria Elie
Published: March 2020

We investigated the extent to which pre-pregnancy obesity mediates the association between maternal place of birth and severe pre-eclampsia in the PreCARE cohort of pregnant women in Paris (n = 9,579). Adjusted path analysis logistic regression models were used to assess the role of pre-pregnancy obesity as a mediator in the association between maternal place of birth and the development of severe pre-eclampsia. We calculated 1. adjusted odds ratios and 95% confidence intervals for the total exposure-outcome association and for the direct and indirect/obesity-mediated components 2. the indirect/obesity-mediated effect. Ninety-five (0.99%) women developed severe pre-eclampsia, 47.6% were non-European immigrants, 16.3% were born in Sub-Saharan Africa, and 12.6% were obese (BMI > = 30 kg/m2). Women experiencing severe pre-eclampsia were more likely to be from Sub-Saharan Africa (p = 0.023) and be obese (p = 0.048). Mothers from Sub-Saharan Africa had an increased risk of severe pre-eclampsia compared to European-born mothers (aOR 2.53, 95% CI 1.39–4.58) and the obesity-mediated indirect effect was 18% of the total risk (aOR 1.18, 95%CI 1.03–1.35). In conclusion, Sub-Saharan African immigrant women have a two-fold higher risk of developing severe pre-eclampsia as compared to European-born women, one-fifth of which is mediated by pre-pregnancy obesity. Our results quantify the potential benefit of decreasing obesity among at-risk women.
Usefulness of diffusion tensor imaging findings as biomarkers for amyotrophic lateral sclerosis
Authors: Baek Seol-Hee , Park Jinseok , Kim Yoo Hwan , Seok Hung Youl , Oh Ki-Wook , Kim Hee-Jin , Kwon Ye-Ji , Sim Youngbo , Tae Woo-Suk , Kim Seung Hyun , Kim Byung-Jo
Published: March 2020

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. However, no reliable biomarkers have been identified to represent the clinical status. This study aimed to investigate whether diffusion tensor imaging (DTI) findings are useful imaging biomarkers to indicate the clinical status of ALS patients. Ninety-six probable or definite ALS cases and 47 age- and sex-matched, normal controls were enrolled. Demographic and clinical data were collected at the time of DTI. DTI data were acquired using a 3-Tesla magnetic resonance imaging scanner and analysed by voxel-wise statistical analyses for fractional anisotropy, axial diffusivity, radial diffusivity, mean diffusivity, and mode of anisotropy. Compared with the healthy control group, the ALS group had significant differences in DTI scalars in the diffuse tracts of the brain, which was predominant in the corticospinal tract at the brainstem and cerebellar peduncle area. Furthermore, the DTI values correlated with the ALS functional rating scale-revised (ALSFRS-R) scores and the delta ALSFRS-R score representing the rate of disease progression. The subgroup analysis revealed a more severe and widespread brain degeneration was observed in rapidly progressive ALS. Therefore, our results suggest that DTI findings are useful as imaging biomarkers for evaluating the clinical severity and rate of disease progression in ALS.
Cofilin dysregulation alters actin turnover in frataxin-deficient neurons
Authors: Muñoz-Lasso Diana C. , Mollá Belén , Calap-Quintana Pablo , García-Giménez José Luis , Pallardo Federico V. , Palau Francesc , Gonzalez-Cabo Pilar
Published: March 2020

Abnormalities in actin cytoskeleton have been linked to Friedreich’s ataxia (FRDA), an inherited peripheral neuropathy characterised by an early loss of neurons in dorsal root ganglia (DRG) among other clinical symptoms. Despite all efforts to date, we still do not fully understand the molecular events that contribute to the lack of sensory neurons in FRDA. We studied the adult neuronal growth cone (GC) at the cellular and molecular level to decipher the connection between frataxin and actin cytoskeleton in DRG neurons of the well-characterised YG8R Friedreich’s ataxia mouse model. Immunofluorescence studies in primary cultures of DRG from YG8R mice showed neurons with fewer and smaller GCs than controls, associated with an inhibition of neurite growth. In frataxin-deficient neurons, we also observed an increase in the filamentous (F)-actin/monomeric (G)-actin ratio (F/G-actin ratio) in axons and GCs linked to dysregulation of two crucial modulators of filamentous actin turnover, cofilin-1 and the actin-related protein (ARP) 2/3 complex. We show how the activation of cofilin is due to the increase in chronophin (CIN), a cofilin-activating phosphatase. Thus cofilin emerges, for the first time, as a link between frataxin deficiency and actin cytoskeleton alterations.
Locating neural transfer effects of n-back training on the central executive: a longitudinal fMRI study
Authors: Miró-Padilla Anna , Bueichekú Elisenda , Ávila César
Published: March 2020

The large number of behavioral studies testing whether working memory training improves performance on an untrained task have yielded inconclusive results. Moreover, some studies have investigated the possible neural changes during the performance of untrained tasks after training. Here, we studied the transfer from n-back training to the Paced Auditory Serial Addition Test (PASAT), two different tasks that use the central executive system to maintain verbal stimuli. Participants completed fMRI sessions at baseline, immediately after one week of training, and at the five-week follow-up. Although behavioral transfer effects were not obtained, training was associated with decreased activation in the anterior dorsolateral prefrontal cortex (DLPFC; BA 9/46) while performing the PASAT that remained stable five weeks later. Consistent with our hypothesis, the changes in the anterior DLFPC largely overlapped with the n-back task fMRI activations. In conclusion, working memory training improves efficiency in brain areas involved in the trained task that may affect untrained tasks, specifically in brain areas responsible for the same cognitive processes.
Size-Tailored Physicochemical Properties of Monodisperse Polystyrene Nanoparticles and the Nanocomposites Made Thereof
Authors: Homaeigohar Shahin , Kabir Rakibul , Elbahri Mady
Published: March 2020

The latex monodisperse polystyrene (PS) colloids are important for different advanced applications (e.g. in coating, biotechnology etc.). However, the size dependency of their structural properties that impacts the characteristics of the nanocomposites composed thereof is largely unknown. Here, monodisperse PS nanoparticles (MPNPs) are synthesized via emulsion polymerization in five sizes (50, 150, 300, 350, and 450 nm). The size of the PS MPNPs is tailored by controlling the reaction time, temperature, and amount of surfactant and initiator. The correlation between the particle size and structural properties of the PS MPNPs is established by different thermomechanical and optical characterizations. The smaller particles (50 and 150 nm) show a lower glass transition (Tg) and thermal decomposition temperature and a lower Raman peak intensity. Yet, they trigger a higher IR absorption, thanks to a larger surface area. When incorporated in a polyvinyl alcohol (PVA) matrix, the smaller particles impart the resulting nanocomposite a higher tensile strength, and elastic and storage moduli. Whereas, they decline the elongation and loss factor. The very few examples of the MPNPs incorporated polymeric nanocomposites have been unstudied from this perspective. Thus, these tangible knowledge can profit scalable production of this kind of nanocomposite materials for different applications in a cost/energy efficient manner.
Specificity of synapse formation in Aplysia: paracrine and autocrine signaling regulates bidirectional molecular interactions between sensory and non-target motor neurons
Authors: Alexandrescu Anamaria , Carew Thomas James
Published: March 2020

The formation of appropriate neural connections during development is critical for the proper wiring and functioning of the brain. Although considerable research suggests that the specificity of synapse formation is supported by complex intercellular signaling between potential presynaptic and postsynaptic partners, the extracellular factors and the intracellular signal transduction pathways engaged in this process remain largely unknown. Using the sensory-motor neural circuit that contributes to learning in defensive withdrawal reflexes in Aplysia californica, we investigated the molecular processes governing the interactions between sensory neurons and both target and non-target motor neurons during synapse formation in culture. We found that evolutionarily-conserved intercellular and intracellular signaling mechanisms critical for learning-related plasticity are also engaged during synaptogenesis in this in vitro model system. Our results reveal a surprising bidirectional regulation of molecular signaling between sensory neurons and non-target motor neurons. This regulation is mediated by signaling via both paracrine and autocrine diffusible factors that induce differential effects on transcription and on protein expression/activation in sensory neurons and in target and non-target motor neurons. Collectively, our data reveal novel molecular mechanisms that could underlie the repression of inappropriate synapse formation, and suggest mechanistic similarities between developmental and learning-related plasticity.
Single-shot all-optical switching of magnetization in Tb/Co multilayer-based electrodes
Authors: Avilés-Félix L. , Olivier A. , Li G. , Davies C. S. , Álvaro-Gómez L. , Rubio-Roy M. , Auffret S. , Kirilyuk A. , Kimel A. V. , Rasing Th. , Buda-Prejbeanu L. D. , Sousa R. C. , Dieny B. , Prejbeanu I. L.
Published: March 2020

Ever since the first observation of all-optical switching of magnetization in the ferrimagnetic alloy GdFeCo using femtosecond laser pulses, there has been significant interest in exploiting this process for data-recording applications. In particular, the ultrafast speed of the magnetic reversal can enable the writing speeds associated with magnetic memory devices to be potentially pushed towards THz frequencies. This work reports the development of perpendicular magnetic tunnel junctions incorporating a stack of Tb/Co nanolayers whose magnetization can be all-optically controlled via helicity-independent single-shot switching. Toggling of the magnetization of the Tb/Co electrode was achieved using either 60 femtosecond-long or 5 picosecond-long laser pulses, with incident fluences down to 3.5 mJ/cm2, for Co-rich compositions of the stack either in isolation or coupled to a CoFeB-electrode/MgO-barrier tunnel-junction stack. Successful switching of the CoFeB-[Tb/Co] electrodes was obtained even after annealing at 250 °C. After integration of the [Tb/Co]-based electrodes within perpendicular magnetic tunnel junctions yielded a maximum tunneling magnetoresistance signal of 41% and RxA value of 150 Ωμm2 with current-in-plane measurements and ratios between 28% and 38% in nanopatterned pillars. These results represent a breakthrough for the development of perpendicular magnetic tunnel junctions controllable using single laser pulses, and offer a technologically-viable path towards the realization of hybrid spintronic-photonic systems featuring THz switching speeds.
Right Atrial Deformation Using Cardiovascular Magnetic Resonance Myocardial Feature Tracking Compared with Two-Dimensional Speckle Tracking Echocardiography in Healthy Volunteers
Authors: Truong Vien T. , Palmer Cassady , Young Michael , Wolking Sarah , Ngo Tam N. M. , Sheets Brandy , Hausfeld Chelsey , Ornella Allison , Taylor Michael D. , Zareba Karolina M. , Raman Subha V. , Mazur Wojciech
Published: March 2020

Speckle tracking echocardiography (STE), and more recently, cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) provides insight into all phases of atrial function. The aim of our study was to compare all phases of RA strain using CMR-FT and STE and also assess the relationship between RA and LA strain. A total of 61 healthy volunteers with mean age of 45 ± 13 years had adequate tracking for analysis on CMR-FT and 2D-STE. Females had larger RA reservoir strain (39 ± 15% vs. 32 ± 13%, p = 0.046) and conduit strain (26 ± 12% vs. 20 ± 9%, p = 0.03) when compared to males, but was not the case with booster strain (14 ± 7% vs. 12 ± 6%, p = 0.45). In comparison with STE derived strain, the RA reservoir and conduit strain were not significantly different between CMR-FT and the three echocardiography gating methods (p > 0.05 for all). Noticeably, there were no significant differences in strain and strain rate between RA and LA function using CMR-FT (p > 0.05 for all). RA strain and strain rate using CMR-FT had fair and good intra- and inter-observer reproducibility and had superior reproducibility compared to STE derived strain.
Differential impact of the ERBB receptors EGFR and ERBB2 on the initiation of precursor lesions of pancreatic ductal adenocarcinoma
Authors: Meyers Nora , Gérard Claude , Lemaigre Frédéric P. , Jacquemin Patrick
Published: March 2020

Earlier diagnosis of pancreatic ductal adenocarcinoma (PDAC) requires better understanding of the mechanisms driving tumorigenesis. In this context, depletion of Epidermal Growth Factor Receptor (EGFR) is known to impair development of PDAC-initiating lesions called acinar-to-ductal metaplasia (ADM) and Pancreatic Intraepithelial Neoplasia (PanIN). In contrast, the role of v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2), the preferred dimerization partner of EGFR, remains poorly understood. Here, using a mouse model with inactivation of Erbb2 in pancreatic acinar cells, we found that Erbb2 is dispensable for inflammation- and KRasG12D-induced development of ADM and PanIN. A mathematical model of EGFR/ERBB2-KRAS signaling, which was calibrated on mouse and human data, supported the observed roles of EGFR and ERBB2. However, this model also predicted that overexpression of ERBB2 stimulates ERBB/KRAS signaling; this prediction was validated experimentally. We conclude that EGFR and ERBB2 differentially impact ERBB signaling during PDAC tumorigenesis, and that the oncogenic potential of ERBB2 is only manifested when it is overexpressed. Therefore, the level of ERBB2, not only its mere presence, needs to be considered when designing therapies targeting ERBB signaling.
Comparison of the short-term outcomes of using DST and PPH staplers in the treatment of grade III and IV hemorrhoids
Authors: Wang Tzu-Hsuan , Kiu Kee-Thai , Yen Min-Hsuan , Chang Tung-Cheng
Published: March 2020

Stapled hemorrhoidopexy has a few advantages such as less postoperative pain and faster recovery compared with conventional hemorrhoidectomy. There are two major devices used for stapled hemorrhoidopexy, PPH stapler (Ethicon EndoSurgery) and DST stapler (Covidien). This study was conducted to investigate the postoperative outcomes among patients with grade III and IV hemorrhoids who underwent hemorrhoidopexy with either of these two devices. A total of 242 consecutive patients underwent stapled hemorrhoidopexy with either PPH stapler (110 patients) or DST stapler (132 patients) at a single center in 2017. We performed a retrospective case–control study to compare the short-term postoperative outcomes and the complications between these two groups. After matching the cases in terms of age, gender, and the grade of hemorrhoids, there were 100 patients in each group (PPH versus DST). There were no significant differences in the postoperative visual analog scale (VAS) score and analgesic usage. Among complications, the incidence of anorectal stricture was significantly higher in the DST group (p = 0.02). Evaluation of the mucosal specimen showed that the total surface area, the muscle/mucosa ratio and the surface area of the muscle were also significantly higher in the DST group (p = 0.03). Further analysis of the DST group demonstrated that patients with anorectal stricture after surgery are younger than patients without anorectal stricture, and higher muscle/mucosa ratio (p = 0.03) and a higher surface area of the muscle (p = 0.03) also measured in the surgical specimen. The two devices provide similar outcomes of postoperative recovery. Patients who underwent DST stapled hemorrhoidopexy had a higher incidence rate of stricture, larger area of muscle excision, and higher muscle/mucosa ratio in the surgical specimen. Further investigation is warranted for a better understanding of the correlation between muscle excision and anorectal stricture.
Solvent extraction and gas chromatography–mass spectrometric determination of probable carcinogen 1,4-dioxane in cosmetic products
Authors: Alsohaimi Ibrahim Hotan , Khan Mohammad Rizwan , Ali Hazim Mohammed , Azam Mohammad , Alammari Ahmed Moid
Published: March 2020

In the present work, a method based on solvent extraction and gas chromatography–mass spectrometry (GC-MS) has been validated for the determination of 1,4-dioxane in cosmetics. Various solvents including ethyl acetate, hexane, methanol, dichloromethane and acetone have been used for the extraction of 1,4-dioxane, among them the ethyl acetate was found to be the most efficient extracting solvent. This method has offered excellent quality parameters for instance linearity (R2 > 0.9991), limit of detection (LOD, 0.00065-0.00091 µg/mL), limit of quantification (LOQ, 0.00217–0.00304 µg/mL) and, precision intra-day (1.65–2.60%, n = 5) and inter-day (0.16–0.32%, n = 5) in terms of relative standard deviation (RSD%). A total of thirty-nine cosmetic samples of different brands and origin have been studied. Among them, the 1,4-dioxane was found in twenty-three samples (FB1-FB7, MC1-MC4, MC6-MC8, HS3, HS5, BL1-BL3, BL5 and PLD1-PLD3) at the levels between 0.15 µg/mL and 9.92 µg/mL, whereas in sixteen samples (MC5, HS1, HS2, SG1-SG5, BL4 and HP1- HP6) was found to be not detected. The recovery values were achieved between 93% and 99% in both low and high level of spiked samples. In comparison to the traditional analytical techniques, the proposed method was found to be very sensitive and cost-effective for the routine analysis of 1,4-dioxane at low concentration in cosmetics.
Organotypic culture as a research and preclinical model to study uterine leiomyomas
Authors: Salas Ana , López Judith , Reyes Ricardo , Évora Carmen , de Oca Francisco Montes , Báez Delia , Delgado Araceli , Almeida Teresa A.
Published: March 2020

Organotypic cultures of tissue slices have been successfully established in lung, prostate, colon, gastric and breast cancer among other malignancies, but until now anex vivomodel based on tissue slices has not been established for uterine leiomyoma. In the present study, we describe a method for culturing tumour slides onto an alginate scaffold. Morphological integrity of tissue slices was maintained for up to 7 days of culture, with cells expressing desmin, estrogen and progesterone receptors. Driver mutations were present in theex vivoslices at all-time points analyzed. Cultivated tumour slices responded to ovarian hormones stimulation upregulating the expression of genes involved in leiomyoma pathogenesis. This tissue model preserves extracellular matrix, cellular diversity and genetic background simulating more in-vivo-likesituations. As a novelty, this platform allows encapsulation of microspheres containing drugs that can be tested on theex vivotumour slices. After optimizing drug release rates, microspheres would then be directly tested in animal models through local injection.
Microbial community profiling of ammonia and nitrite oxidizing bacterial enrichments from brackishwater ecosystems for mitigating nitrogen species
Authors: Baskaran Viswanathan , Patil Prasanna K. , Antony M. Leo , Avunje Satheesha , Nagaraju Vinay T. , Ghate Sudeep D. , Nathamuni Suganya , Dineshkumar N. , Alavandi Shankar V. , Vijayan Kizhakedath K.
Published: March 2020

Nitrogen species such as ammonia and nitrite are considered as major stressors in modern aquaculture practices. We developed enrichments of ammonia oxidising bacteria (AOB) and nitrite oxidising bacteria (NOB) for effective mitigation of nitrogenous wastes in the shrimp culture operations. The objective of this study was to understand the microbial community composition of AOB and NOB enrichments using the V3-V4 region of the 16S rDNA gene by Illumina MiSeq sequencing. The analysis revealed 2948 and 1069 OTUs at 97% similarity index and Shannon alpha diversity index of 7.64 and 4.85 for AOB and NOB enrichments, respectively. Comparative analysis showed that a total of 887 OTUs were common among AOB and NOB enrichments. The AOB and NOB enrichment were dominated by Eubacteria at 96% and 99.7% respectively. Proteobacterial phylum constituted 31.46% (AOB) and 39.75% (NOB) and dominated by α-Proteobacteria (20%) in AOB and γ-Proteobacteria (16%) in NOB. Among the species in AOB enrichment (2,948) two sequences were assigned to ammonia oxidising bacterial group belonging to Nitrosomonas, and Nitrosococcus genera and two belonged to archaeon group comprising Nitrosopumilus and Candidatus Nitrososphaeraea genera. The NOB enrichment was predominated by Nitrospiraceae and Thermodesulfovibrionaceae. Further, the data revealed the presence of heterotrophic bacteria contributing to the process of nitrification and form microcosm with the AOB and NOB. PICRUSt analysis predicted the presence of 24 different nitrogen cycling genes involved in nitrification, denitrification, ammonia and nitrogen transporter family, nitrate reduction and ammonia assimilation. The study confirms the presence of many lesser known nitrifying bacteria along with well characterised nitrifiers.
Human health risk assessment of elevated and variable iron and manganese intake with arsenic-safe groundwater in Jashore, Bangladesh
Authors: Ghosh Gopal Chandra , Khan Md. Jahed Hassan , Chakraborty Tapos Kumar , Zaman Samina , Kabir A. H. M. Enamul , Tanaka Hiroaki
Published: March 2020

Groundwater through hand-operated tubewell (a type of water well) tapping is the main source of drinking water in Bangladesh. This study investigated iron and manganese concentration in groundwater across Jashore district–one of the worst arsenic contaminated area in Bangladesh. One working tubewell that had been tested previously for arsenic and marked safe (green) was selected from each unions of the district. Results revealed that approximately 73% and 87% of groundwater samples exceeded the limits for iron and manganese in Bangladesh drinking water, respectively. Additionally, spatial distribution of iron and manganese indicate that only 5% of the total surface area of groundwater is covered by safe level of iron and manganese. Human health risk due to ingestion of iron and manganese through drinking water was evaluated using hazard quotients (HQ) for adults and children. The result of the health risk assessment revealed that the non-carcinogenic health risks due to ingestion of iron (HQ up to 1.446 for adults and 0.590 for children) and manganese (HQ up to 2.459 for adults and 1.004 for children) contaminated groundwater are much higher among adults than children. On the basis of occurrences, spatial distribution and health risk assessment results, the area can be categorized as a high-risk zone for iron and manganese-related problems and needs special attention in order to protect public health of local residents.
The sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid is a glucose-dependent potentiator of insulin secretion
Authors: Minami Akira , Fujita Yuka , Shimba Sumika , Shiratori Mako , Kaneko Yukiko K. , Sawatani Toshiaki , Otsubo Tadamune , Ikeda Kiyoshi , Kanazawa Hiroaki , Mikami Yasuyo , Sekita Risa , Kurebayashi Yuuki , Takahashi Tadanobu , Miyagi Taeko , Ishikawa Tomohisa , Suzuki Takashi
Published: March 2020

Sialidase cleaves sialic acid residues from a sialoglycoconjugate: oligosaccharides, glycolipids and glycoproteins that contain sialic acid. Histochemical imaging of the mouse pancreas using a benzothiazolylphenol-based sialic acid derivative (BTP3-Neu5Ac), a highly sensitive histochemical imaging probe used to assess sialidase activity, showed that pancreatic islets have intense sialidase activity. The sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA) remarkably enhances glutamate release from hippocampal neurons. Since there are many similar processes between synaptic vesicle exocytosis and secretory granule exocytosis, we investigated the effect of DANA on insulin release from β-cells. Insulin release was induced in INS-1D cells by treatment with 8.3 mM glucose, and the release was enhanced by treatment with DANA. In a mouse intraperitoneal glucose tolerance test, the increase in serum insulin levels was enhanced by intravenous injection with DANA. However, under fasting conditions, insulin release was not enhanced by treatment with DANA. Calcium oscillations induced by 8.3 mM glucose treatment of INS-1D cells were not affected by DANA. Blood insulin levels in sialidase isozyme Neu3-deficient mice were significantly higher than those in WT mice under ad libitum feeding conditions, but the levels were not different under fasting conditions. These results indicate that DANA is a glucose-dependent potentiator of insulin secretion. The sialidase inhibitor may be useful for anti-diabetic treatment with a low risk of hypoglycemia.
Author Correction: Next Generation Sequencing of Pooled Samples: Guideline for Variants’ Filtering
Authors: Anand Santosh , Mangano Eleonora , Barizzone Nadia , Bordoni Roberta , Sorosina Melissa , Clarelli Ferdinando , Corrado Lucia , Martinelli Boneschi Filippo , D’Alfonso Sandra , De Bellis Gianluca
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Dynamical reorganization of the pluripotency transcription factors Oct4 and Sox2 during early differentiation of embryonic stem cells
Authors: Verneri Paula , Vazquez Echegaray Camila , Oses Camila , Stortz Martin , Guberman Alejandra , Levi Valeria
Published: March 2020

Pluripotency maintenance requires transcription factors (TFs) that induce genes necessary to preserve the undifferentiated state and repress others involved in differentiation. Recent observations support that the heterogeneous distribution of TFs in the nucleus impacts on gene expression. Thus, it is essential to explore how TFs dynamically organize to fully understand their role in transcription regulation. Here, we examine the distribution of pluripotency TFs Oct4 and Sox2 in the nucleus of embryonic stem (ES) cells and inquire whether their organization changes during early differentiation stages preceding their downregulation. Using ES cells expressing Oct4-YPet or Sox2-YPet, we show that Oct4 and Sox2 partition between nucleoplasm and a few chromatin-dense foci which restructure after inducing differentiation by 2i/LIF withdrawal. Fluorescence correlation spectroscopy showed distinct changes in Oct4 and Sox2 dynamics after differentiation induction. Specifically, we detected an impairment of Oct4-chromatin interactions whereas Sox2 only showed slight variations in its short-lived, and probably more unspecific, interactions with chromatin. Our results reveal that differentiation cues trigger early changes of Oct4 and Sox2 nuclear distributions that also include modifications in TF-chromatin interactions. This dynamical reorganization precedes Oct4 and Sox2 downregulation and may contribute to modulate their function at early differentiation stages.
Author Correction: New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections
Authors: McPhillie Martin , Zhou Ying , El Bissati Kamal , Dubey Jitender , Lorenzi Hernan , Capper Michael , Lukens Amanda K. , Hickman Mark , Muench Stephen , Verma Shiv Kumar , Weber Christopher R. , Wheeler Kelsey , Gordon James , Sanders Justin , Moulton Hong , Wang Kai , Kim Taek-Kyun , He Yuqing , Santos Tatiana , Woods Stuart , Lee Patty , Donkin David , Kim Eric , Fraczek Laura , Lykins Joseph , Esaa Farida , Alibana-Clouser Fatima , Dovgin Sarah , Weiss Louis , Brasseur Gael , Wirth Dyann , Kent Michael , Hood Leroy , Meunieur Brigitte , Roberts Craig W. , Hasnain S. Samar , Antonyuk Svetlana V. , Fishwick Colin , McLeod Rima
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.