bluuebunny/crossref_metadata_2025 huggingface dataset:
High temperature rise dominated cracking mechanisms in ultra-ductile and tough titanium alloy
Authors: Choisez L. , Ding L. , Marteleur M. , Idrissi H. , Pardoen T. , Jacques P. J.
Published: April 2020

Extensive use of titanium alloys is partly hindered by a lack of ductility, strain hardening, and fracture toughness. Recently, several β-metastable titanium alloys were designed to simultaneously activate both transformation-induced plasticity and twinning-induced plasticity effects, resulting in significant improvements to their strain hardening capacity and resistance to plastic localization. Here, we report an ultra-large fracture resistance in a Ti-12Mo alloy (wt.%), that results from a high resistance to damage nucleation, with an unexpected fracture phenomenology under quasi-static loading. Necking develops at a large uniform true strain of 0.3 while fracture initiates at a true fracture strain of 1.0 by intense through-thickness shear within a thin localized shear band. Transmission electron microscopy reveals that dynamic recrystallization occurs in this band, while local partial melting is observed on the fracture surface. Shear band temperatures of 1250–2450 °C are estimated by the fusible coating method. The reported high ductility combined to the unconventional fracture process opens alternative avenues toward Ti alloys toughening.
The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC
Authors: Verity Robert , Aydemir Ozkan , Brazeau Nicholas F. , Watson Oliver J. , Hathaway Nicholas J. , Mwandagalirwa Melchior Kashamuka , Marsh Patrick W. , Thwai Kyaw , Fulton Travis , Denton Madeline , Morgan Andrew P. , Parr Jonathan B. , Tumwebaze Patrick K. , Conrad Melissa , Rosenthal Philip J. , Ishengoma Deus S. , Ngondi Jeremiah , Gutman Julie , Mulenga Modest , Norris Douglas E. , Moss William J. , Mensah Benedicta A. , Myers-Hansen James L. , Ghansah Anita , Tshefu Antoinette K. , Ghani Azra C. , Meshnick Steven R. , Bailey Jeffrey A. , Juliano Jonathan J.
Published: April 2020

The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.
Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair
Authors: Wienert Beeke , Nguyen David N. , Guenther Alexis , Feng Sharon J. , Locke Melissa N. , Wyman Stacia K. , Shin Jiyung , Kazane Katelynn R. , Gregory Georgia L. , Carter Matthew A. M. , Wright Francis , Conklin Bruce R. , Marson Alex , Richardson Chris D. , Corn Jacob E.
Published: April 2020

Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification.
Endemism patterns are scale dependent
Authors: Daru Barnabas H. , Farooq Harith , Antonelli Alexandre , Faurby Søren
Published: April 2020

Areas of endemism are important in biogeography because they capture facets of biodiversity not represented elsewhere. However, the scales at which they are relevant to research and conservation are poorly analysed. Here, we calculate weighted endemism (WE) and phylogenetic endemism (PE) separately for all birds and amphibians across the globe. We show that scale dependence is widespread for both indices and manifests across grain sizes, spatial extents and taxonomic treatments. Variations in taxonomic opinions—whether species are treated by systematic ‘lumping’ or ‘splitting’—can profoundly affect the allocation of WE hotspots. Global patterns of PE can provide insights into complex evolutionary processes but this congruence is lost at the continental to country extents. These findings are explained by environmental heterogeneity at coarser grains, and to a far lesser extent at finer resolutions. Regardless of scale, we find widespread deficits of protection for endemism hotspots. Our study presents a framework for assessing areas for conservation that are robust to assumptions on taxonomy, spatial grain and extent.
Dysregulation of bile acids increases the risk for preterm birth in pregnant women
Authors: You Sangmin , Cui Ai-Min , Hashmi Syed F. , Zhang Xinmu , Nadolny Christina , Chen Yuan , Chen Qiwen , Bush Xin , Hurd Zachary , Ali Winifer , Qin Gang , Deng Ruitang
Published: April 2020

Preterm birth (PTB) is the leading cause of perinatal mortality and newborn complications. Bile acids are recognized as signaling molecules regulating a myriad of cellular and metabolic activities but have not been etiologically linked to PTB. In this study, a hospital-based cohort study with 36,755 pregnant women is conducted. We find that serum total bile acid levels directly correlate with the PTB rates regardless of the characteristics of the subjects and etiologies of liver disorders. Consistent with the findings from pregnant women, PTB is successfully reproduced in mice with liver injuries and dysregulated bile acids. More importantly, bile acids dose-dependently induce PTB with minimal hepatotoxicity. Furthermore, restoring bile acid homeostasis by farnesoid X receptor activation markedly reduces PTB and dramatically improves newborn survival rates. The findings thus establish an etiologic link between bile acids and PTB, and open an avenue for developing etiology-based therapies to prevent or delay PTB.
Single-cell transcriptional networks in differentiating preadipocytes suggest drivers associated with tissue heterogeneity
Authors: Ramirez Alfred K. , Dankel Simon N. , Rastegarpanah Bashir , Cai Weikang , Xue Ruidan , Crovella Mark , Tseng Yu-Hua , Kahn C. Ronald , Kasif Simon
Published: April 2020

White adipose tissue plays an important role in physiological homeostasis and metabolic disease. Different fat depots have distinct metabolic and inflammatory profiles and are differentially associated with disease risk. It is unclear whether these differences are intrinsic to the pre-differentiated stage. Using single-cell RNA sequencing, a unique network methodology and a data integration technique, we predict metabolic phenotypes in differentiating cells. Single-cell RNA-seq profiles of human preadipocytes during adipogenesis in vitro identifies at least two distinct classes of subcutaneous white adipocytes. These differences in gene expression are separate from the process of browning and beiging. Using a systems biology approach, we identify a new network of zinc-finger proteins that are expressed in one class of preadipocytes and is potentially involved in regulating adipogenesis. Our findings gain a deeper understanding of both the heterogeneity of white adipocytes and their link to normal metabolism and disease.
A drug-inducible sex-separation technique for insects
Authors: Kandul Nikolay P. , Liu Junru , Hsu Alexander D. , Hay Bruce A. , Akbari Omar S.
Published: April 2020

Here, we describe a drug-inducible genetic system for insect sex-separation that demonstrates proof-of-principle for positive sex selection inD. melanogaster. The system exploits the toxicity of commonly used broad-spectrum antibiotics geneticin and puromycin to kill the non-rescued sex. Sex-specific rescue is achieved by inserting sex-specific introns into the coding sequences of antibiotic-resistance genes. When raised on geneticin-supplemented food, the sex-sorter line establishes 100% positive selection for female progeny, while the food supplemented with puromycin positively selects 100% male progeny. Since the described system exploits conserved sex-specific splicing mechanisms and reagents, it has the potential to be adaptable to other insect species of medical and agricultural importance.
Contributions of recycled wastewater to clean water and sanitation Sustainable Development Goals
Authors: Tortajada Cecilia
Published: April 2020

Water resources are essential for every development activity, not only in terms of available quantity but also in terms of quality. Population growth and urbanisation are increasing the number of users and uses of water, making water resources scarcer and more polluted. Changes in rainfall patterns threaten to worsen these effects in many areas. Water scarcity, due to physical lack or pollution, has become one of the most pressing issues globally, a matter of human, economic and environmental insecurity. Wastewater, whose value had not been appreciated until recently, is increasingly recognised as a potential ‘new’ source of clean water for potable and non-potable uses, resulting in social, environmental and economic benefits. This paper discusses the potential of recycled wastewater (also known as reused water) to become a significant source of safe water for drinking purposes and improved sanitation in support of the Sustainable Development Goals.
Effects of a Sudden Drop in Salinity on Scapharca subcrenata Antioxidant Defenses and Metabolism Determined Using LC-MS Non-targeted Metabolomics
Authors: Zhang Mo , Li Li , Liu Ying , Gao Xiaolong
Published: April 2020

In this experiment, the effects of a sudden drop in salinity on the antioxidant defense system and related gene expression of the ark shell Scapharca subcrenata were examined. The sudden drop in seawater salinity after a rainstorm was simulated, and subsequently differentially expressed metabolic markers were identified by LC-MS non-targeted metabolomics. When the salinity dropped to 14‰ (S14), the total anti-oxidant content, activity of Na+/K+-ATPase, superoxide dismutase (SOD), and catalase (CAT), content of malondialdehyde, and expression levels of Mn-SOD, CAT, and C-type lectin of S. subcrenata were significantly higher than in groups with salinity of 22‰ (S22) or 30‰ (S30) (P < 0.05). The activity of glutathione peroxidase (GPx), the content of reduced glutathione, and the expression levels of GPx were not significantly different between S14 and S22, but the values in each group were significantly higher than those in S30 (P < 0.05). Using the metabolomics technique, 361, 271, and 264 metabolites with significant differences were identified from S22 vs. S14, S30 vs. S14, and S30 vs. S22, respectively. The drop in salinity was accompanied by up-regulation of phosphatidylcholine (PC) (20:4 (5Z, 8Z, 11Z, 14Z)/P-18: 1 (11Z)), PC (16:0/22: 6 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)), phosphatidylethanolamine (PE) (18:4 (6Z, 9Z, 12Z, 15Z)/24:1 (15Z)), phosphatidylinositol (PI) (20:1 (11Z)/0:0), phalluside-1, C16 sphinganine, and LacCer (d18:0/14:0) and by significant down-regulation of PI-Cer (d18:1/14:0) and PE (14:0/16:1(9Z). The results of this study illustrate how these nine metabolites can be used as metabolic markers for the response of S. subcrenata to a sudden drop in salinity. They also provide the theoretical groundwork for selection of bottom areas with salinity that is optimal for release and proliferation of S. subcrenata, which is needed to restore the declining populations of this species.
Multiaxial Lenticular Stress-Strain Relationship of Native Myocardium is Preserved by Infarct-Induced Natural Heart Regeneration in Neonatal Mice
Authors: Wang Hanjay , Bennett-Kennett Ross , Paulsen Michael J. , Hironaka Camille E. , Thakore Akshara D. , Farry Justin M. , Eskandari Anahita , Lucian Haley J. , Shin Hye Sook , Wu Matthew A. , Imbrie-Moore Annabel M. , Steele Amanda N. , Stapleton Lyndsay M. , Zhu Yuanjia , Dauskardt Reinhold H. , Woo Y. Joseph
Published: April 2020

Neonatal mice exhibit natural heart regeneration after myocardial infarction (MI) on postnatal day 1 (P1), but this ability is lost by postnatal day 7 (P7). Cardiac biomechanics intricately affect long-term heart function, but whether regenerated cardiac muscle is biomechanically similar to native myocardium remains unknown. We hypothesized that neonatal heart regeneration preserves native left ventricular (LV) biomechanical properties after MI. C57BL/6J mice underwent sham surgery or left anterior descending coronary artery ligation at age P1 or P7. Echocardiography performed 4 weeks post-MI showed that P1 MI and sham mice (n = 22, each) had similar LV wall thickness, diameter, and ejection fraction (59.6% vs 60.7%, p = 0.6514). Compared to P7 shams (n = 20), P7 MI mice (n = 20) had significant LV wall thinning, chamber enlargement, and depressed ejection fraction (32.6% vs 61.8%, p < 0.0001). Afterward, the LV was explanted and pressurized ex vivo, and the multiaxial lenticular stress-strain relationship was tracked. While LV tissue modulus for P1 MI and sham mice were similar (341.9 kPa vs 363.4 kPa, p = 0.6140), the modulus for P7 MI mice was significantly greater than that for P7 shams (691.6 kPa vs 429.2 kPa, p = 0.0194). We conclude that, in neonatal mice, regenerated LV muscle has similar biomechanical properties as native LV myocardium.
A new non-invasive index for prognosis evaluation in patients with aortic stenosis
Authors: Sim Hui Wen , Ngiam Nicholas Jinghao , Zhong Liang , Tan Benjamin Yong-Qiang , Low Lyndon Y , Djohan Andie Hartanto , Boey Elaine , Kong William Kok Fai , Tan Ru San , Poh Kian Keong
Published: April 2020

The global left ventricular (LV) contractility index,dσ*/dtmaxmeasures the maximal rate of change in pressure-normalized LV wall stress. We aim to describe the trend ofdσ*/dtmaxin differing severity of aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF) and the association ofdσ*/dtmaxwith clinical outcomes in moderate AS and severe AS. We retrospectively studied a total of 1738 patients with AS (550 mild AS, 738 moderate AS, 450 severe AS) and preserved LVEF ≥ 50% diagnosed from 1stJanuary 2001 to 31stDecember 2015.dσ*/dtmaxworsened with increasing severity of AS despite preserved LVEF (mild AS: 3.69 ± 1.28 s−1, moderate AS: 3.17 ± 1.09 s−1, severe AS: 2.58 ± 0.83 s−1,p < 0.001). Lowdσ*/dtmax < 2.8 s−1was independently associated with a higher composite outcome of aortic valve replacement, congestive cardiac failure admissions and all-cause mortality (adjusted hazard ratio 1.48, 95% CI: 1.25–1.77,p < 0.001). In conclusion,dσ*/dtmaxdeclined with worsening AS despite preserved LVEF. Lowdσ*/dtmax < 2.8 s−1was independently associated with adverse clinical outcomes in moderate AS and severe AS with preserved LVEF.
Discovery of Ternary Silicon Titanium Nitride with Spinel-Type Structure
Authors: Bhat Shrikant , Lale Abhijeet , Bernard Samuel , Zhang Wei , Ishikawa Ryo , Haseen Shariq , Kroll Peter , Wiehl Leonore , Farla Robert , Katsura Tomoo , Ikuhara Yuichi , Riedel Ralf
Published: April 2020

Here we report on the discovery of a ternary silicon titanium nitride with the general composition (Si1−x,Tix)3N4with x = 0 < x < 1 and spinel-type crystal structure. The novel nitride is formed from an amorphous silicon titanium nitride (SiTiN) precursor under high-pressure/high-temperature conditions in a large volume high-pressure device. Under the conditions of 15–20 GPa and 1800–2000 °C, spinel-type γ-Si3N4and rock salt-type c-TiN are formed. In addition, crystals of the discovered nano-sized ternary phase (Si1−x,Tix)3N4embedded in γ-Si3N4are identified. The ternary compound is formed due to kinetically-controlled synthesis conditions and is analyzed to exhibit the spinel-type structure with ca. 8 atom% of Ti. The Ti atoms occur in both Ti3+and Ti4+oxidation states and are located on the Si sites. The ternary nano-crystals have to be described as (Si,Ti)3N4with N-vacancies resulting in the general composition (Si4+1−xTi4+x-δTi3+δ)3N4-δ.
Publisher Correction: Island Ancestors and New World Biogeography: A Case Study from the Scorpions (Buthidae: Centruroidinae)
Authors: Esposito Lauren A. , Prendini Lorenzo
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Genetic diversity and ecology of coronaviruses hosted by cave-dwelling bats in Gabon
Authors: Maganga Gael Darren , Pinto Anaïs , Mombo Illich Manfred , Madjitobaye Mankomra , Mbeang Beyeme Antoine Mitte , Boundenga Larson , Ar Gouilh Meriadeg , N’Dilimabaka Nadine , Drexler Jan Felix , Drosten Christian , Leroy Eric Maurice
Published: April 2020

Little research on coronaviruses has been conducted on wild animals in Africa. Here, we screened a wide range of wild animals collected in six provinces and five caves of Gabon between 2009 and 2015. We collected a total of 1867 animal samples (cave-dwelling bats, rodents, non-human primates and other wild animals). We explored the diversity of CoVs and determined the factors driving the infection of CoVs in wild animals. Based on a nested reverse transcription-polymerase chain reaction, only bats, belonging to the Hipposideros gigas (4/156), Hipposideros cf. ruber (13/262) and Miniopterus inflatus (1/249) species, were found infected with CoVs. We identified alphacoronaviruses in H. gigas and H. cf. ruber and betacoronaviruses in H. gigas. All Alphacoronavirus sequences grouped with Human coronavirus 229E (HCoV-229E). Ecological analyses revealed that CoV infection was significantly found in July and October in H. gigas and in October and November in H. cf ruber. The prevalence in the Faucon cave was significantly higher. Our findings suggest that insectivorous bats harbor potentially zoonotic CoVs; highlight a probable seasonality of the infection in cave-dwelling bats from the North-East of Gabon and pointed to an association between the disturbance of the bats’ habitat by human activities and CoV infection.
Fully automated rapid quantification of Hepatitis C Virus RNA in human plasma and serum by integrated on-chip RT-qPCR and capillary electrophoresis
Authors: Chan Samuel D. H. , Toyoda Hidenori , Sanjeeviraman Jayashree , Souppe Aurelie , Iwamoto Mari , Wu Warren , Eto Daisuke , Tada Toshifumi , Kumada Takashi , Zhang Jian-Ping
Published: April 2020

The quantification of hepatitis C virus (HCV) is essential for the management of chronic hepatitis C therapy. We have developed a fully automated microfluidic RT-qPCR system for rapid quantitative detection of HCV RNA in human EDTA-plasma and serum, and the performance of the method was assessed. The platform for the assay, µTASWako g1 Fully Automated Genetic Analyzer, performs automated sample preparation and RNA extraction, followed by amplification and detection on an integrated RT-qPCR-CE (capillary electrophoresis (CE)) microfluidic chip. The total assay time from sample input to data output is less than 120 minutes. The HCV assay has a linear quantitative range of 15 to 107 IU/mL, with a limit of detection (LOD) of 10.65 IU/mL in EDTA-plasma and 12.43 IU/mL in serum. The assay has a reproducibility of SD ≤ 0.16 log10 IU/mL and an accuracy of ≤ 0.22 log10 IU/mL difference when compared to the assigned values. The main HCV genotypes 1 to 6 are detected with an accuracy of ± 0.3 log10 IU/mL. The assay is specific for HCV RNA and is free of interference from non-HCV pathogens, elevated levels of anti-viral and anti-bacterial drugs, and common endogenous interferents. In the linear quantitative range, the assay is highly correlated with the Roche cobas AmpliPrep/cobas TaqMan HCV Test, version 2.0 (r2 = 0.949). As the assay is highly sensitive, accurate and specific, and provides reliable quantification of HCV in plasma and serum, it can potentially be applicable for monitoring the therapy and management of HCV infection.
Intervention-induced changes in neural connectivity during motor preparation may affect cortical activity at motor execution
Authors: Wilkins Kevin B. , Dewald Julius P. A. , Yao Jun
Published: April 2020

Effective interventions have demonstrated the ability to improve motor function by reengaging ipsilesional resources, which appears to be critical and feasible for hand function recovery even in individuals with severe chronic stroke. However, previous studies focus on changes in brain activity related to motor execution. How changes in motor preparation may facilitate these changes at motor execution is still unclear. To address this question, 8 individuals with severe chronic hemiparetic stroke participated in a device-assisted intervention for seven weeks. We then quantified changes in both coupling between regions during motor preparation and changes in topographical cortical activity at motor execution for both hand opening in isolation and together with the shoulder using high-density EEG. We hypothesized that intervention-induced changes in cortico-cortico interactions during motor preparation would lead to changes in activity at motor execution specifically towards an increased reliance on the ipsilesional hemisphere. In agreement with this hypothesis, we found that, following the intervention, individuals displayed a reduction in coupling from ipsilesional M1 to contralesional M1 within gamma frequencies during motor preparation for hand opening. This was followed by a reduction in activity in the contralesional primary sensorimotor cortex during motor execution. Similarly, during lifting and opening, a shift to negative coupling within ipsilesional M1 from gamma to beta frequencies was accompanied by an increase in ipsilesional primary sensorimotor cortex activity following the intervention. Together, these results show that intervention-induced changes in coupling within or between motor regions during motor preparation may affect cortical activity at execution.
Determination of Residential Soil Gas Radon Risk Indices Over the Lithological Units of a Southwestern Nigeria University
Authors: Esan Deborah Tolulope , Sridhar Mynepalli Kameswara Chandra , Obed Rachel , Ajiboye Yinka , Afolabi Olusegun , Olubodun Babakayode , Oni Olatunde Michael
Published: April 2020

Radiation dose from natural sources is mainly from exposure to radon in the environment. Radon has its origin from uranium-bearing bedrocks and overburden. In the present study, assessment of the level of radon over the three lithological units upon which the residential areas of ObafemiAwolowo University Campus, Ile-Ife (OAU) was situated was carried out. Soil gas radon concentration measurement was carried out at a constant depth of 0.80 m across the three lithologies (granite gneiss, grey gneiss and mica schist) using a RAD7 electronic radon detector. A total of 138 in-situ soil gas radon measurements were carried out. Obtained experimental data were analysed and summarised using descriptive and inferential statistics with statistical significance set at p < 0.05. A radon potential map was also developed using existing permeability data of the soils in the area. Soil radon concentration varied across the different lithologies ranging from 0.04 kBq/m3 – 190 kBq/m3 with a mean value of 14 kBq/m3. The mean value of Rn-222 concentration obtained in the three lithologies are 3.5 ± 5.9, 11.5 ± 25.8 and 28.4 ± 37.4 kBq/m3 for granite gneiss, grey gneiss and mica schist respectively. There is a statistically significant difference (p < 0.001) in the mean concentration of radon-222 measured on the three lithologies. The granite gneiss and grey gneiss lithologies have been designated into low radon index, while mica schist lithology has been designated as medium radon index. 34% of the sampled areas exhibit high radon risk based on Swedish risk criteria, thereby warranting protective actions.
Author Correction: Robot-assisted Nipple-sparing Mastectomy with Immediate Breast Reconstruction: An Initial Experience
Authors: Park Hyung Seok , Lee Jeea , Lee Dong Won , Song Seung Yong , Lew Dae Hyun , Il Kim Seung , Cho Young Up
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Increased stiffness of the tumor microenvironment in colon cancer stimulates cancer associated fibroblast-mediated prometastatic activin A signaling
Authors: Bauer Jessica , Emon Md Abul Bashar , Staudacher Jonas J. , Thomas Alexandra L. , Zessner-Spitzenberg Jasmin , Mancinelli Georgina , Krett Nancy , Saif M. Taher , Jung Barbara
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Rab27a plays a dual role in metastatic propensity of pancreatic cancer
Authors: Kren Nancy , Michaud Daniel , Bagchi Sukriti , Greene Kevin , Pylayeva-Gupta Yuliya
Published: April 2020

Pancreatic cancer is an aggressive malignancy, often diagnosed at metastatic stages. Several studies have implicated systemic factors, such as extracellular vesicle release and myeloid cell expansion, in the establishment of pre-metastatic niches in cancer. The Rab27a GTPase is overexpressed in advanced cancers, can regulate vesicle trafficking, and has been previously linked to non-cell autonomous control of tumor growth and metastasis, however, the role of Rab27a itself in the metastatic propensity of pancreatic cancer is not well understood. Here, we have established a model to study how Rab27a directs formation of the pre-metastatic niche. Loss of Rab27a in pancreatic cancer cells did not decrease tumor growth in vivo, but resulted in altered systemic myeloid cell expansion, both in the primary tumors and at the distant organ sites. In metastasis assays, loss of Rab27a expression in tumor cells injected into circulation compromised efficient outgrowth of metastatic lesions. However, Rab27a knockdown cells had an unexpected advantage at initial steps of metastatic seeding, suggesting that Rab27a may alter cell-autonomous invasive properties of the tumor cells. Gene expression analysis of gene expression revealed that downregulation of Rab27a increased expression of genes involved in epithelial-to-mesenchymal transition pathways, consistent with our findings that primary tumors arising from Rab27a knockdown cells were more invasive. Overall, these data reveal that Rab27a can play divergent roles in regulating pro-metastatic propensity of pancreatic cancer cells: by generating pro-metastatic environment at the distant organ sites, and by suppressing invasive properties of the cancer cells.
Generation of orbital angular momentum modes via holographic leaky-wave metasurfaces
Authors: Oraizi Homayoon , Emamian Hedieh
Published: April 2020

Recently, electromagnetic (EM) waves carrying orbital angular momentum (OAM) has received considerable attention in increasingly many different realms, such as communication systems, super-resolution imaging, optical communications and quantum state manipulation. In this paper, two different kinds of two dimensional (2-D) holographic leaky-wave metasurfaces with a single OAM mode at a single frequency (18 GHz) are introduced through designs and experiments. The classic leaky-wave and a microwave holography theorem are combined to construct the holographic leaky-wave metasurfaces. The leaky wave metasurfaces-based holographic concept are implemented with isotropic artificial surface impedances and made of hexagonal metallic patches. By varying the size of the metallic patches, the effective impedances may be realized. The monopole launchers are utilized for the excitation of TM surface mode, whereby their wave functions can be approximated by the Hankel function of the second kind. The objective waves represented by the desired beams carrying different orbital angular momentum modes. Electromagnetic full-wave simulations and experimental measurements have been performed to substantiate the proposed method.
Bats distress vocalizations carry fast amplitude modulations that could represent an acoustic correlate of roughness
Authors: Hechavarría Julio C. , Jerome Beetz M. , García-Rosales Francisco , Kössl Manfred
Published: April 2020

Communication sounds are ubiquitous in the animal kingdom, where they play a role in advertising physiological states and/or socio-contextual scenarios. Human screams, for example, are typically uttered in fearful contexts and they have a distinctive feature termed as “roughness”, which depicts amplitude fluctuations at rates from 30–150 Hz. In this article, we report that the occurrence of fast acoustic periodicities in harsh sounding vocalizations is not unique to humans. A roughness-like structure is also present in vocalizations emitted by bats (species Carollia perspicillata) in distressful contexts. We report that 47.7% of distress calls produced by bats carry amplitude fluctuations at rates ~1.7 kHz (>10 times faster than temporal modulations found in human screams). In bats, rough-like vocalizations entrain brain potentials and are more effective in accelerating the bats’ heart rate than slow amplitude modulated sounds. Our results are consistent with a putative role of fast amplitude modulations (roughness in humans) for grabbing the listeners attention in situations in which the emitter is in distressful, potentially dangerous, contexts.
Quantitative 129Xe MRI detects early impairment of gas-exchange in a rat model of pulmonary hypertension
Authors: Virgincar Rohan S. , Nouls John C. , Wang Ziyi , Degan Simone , Qi Yi , Xiong Xinyu , Rajagopal Sudarshan , Driehuys Bastiaan
Published: April 2020

Hyperpolarized 129Xe magnetic resonance imaging (MRI) is capable of regional mapping of pulmonary gas-exchange and has found application in a wide range of pulmonary disorders in humans and animal model analogs. This study is the first application of 129Xe MRI to the monocrotaline rat model of pulmonary hypertension. Such models of preclinical pulmonary hypertension, a disease of the pulmonary vasculature that results in right heart failure and death, are usually assessed with invasive procedures such as right heart catheterization and histopathology. The work here adapted from protocols from clinical 129Xe MRI to enable preclinical imaging of rat models of pulmonary hypertension on a Bruker 7 T scanner. 129Xe spectroscopy and gas-exchange imaging showed reduced 129Xe uptake by red blood cells early in the progression of the disease, and at a later time point was accompanied by increased uptake by barrier tissues, edema, and ventilation defects—all of which are salient characteristics of the monocrotaline model. Imaging results were validated by H&E histology, which showed evidence of remodeling of arterioles. This proof-of-concept study has demonstrated that hyperpolarized 129Xe MRI has strong potential to be used to non-invasively monitor the progression of pulmonary hypertension in preclinical models and potentially to also assess response to therapy.
Neurons promote encephalitogenic CD4+ lymphocyte infiltration in experimental autoimmune encephalomyelitis
Authors: Nakazato Yuki , Fujita Yuki , Nakazato Masamitsu , Yamashita Toshihide
Published: April 2020

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by neuroinflammation, leading to demyelination and axonal degeneration. Neuronal excitotoxity mediated by Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) results in neuronal damage in experimental autoimmune encephalitis (EAE), an animal model of MS. Here, we define a critical role of excitatory neurons in the pathogenesis of CD4+lymphocyte accumulation in EAE. We silenced the activity of excitatory neurons in a mouse model of targeted EAE using inhibitory designer receptors exclusively activated by designer drugs (DREADD) under a CaMKIIα promoter. Neuronal silencing mitigated clinical disease scores in EAE, reduced the expression ofc-fos, Tnfα,Ccl2, andCcr2mRNAs in targeted EAE lesions, and prevented the migration of CD4+lymphocytes towards neurons.Ccl2shRNA treatment of targeted EAE suppressed the migration of CD4+lymphocytes and alleviated the motor deficits of EAE. Our findings indicate that neuronal activation in EAE promotes the migration of CCR2+CD4+lymphocytes and that neuronal silencing with an inhibitory DREADD alleviates clinical and molecular markers of disease. Neuronal CCL2 is thought to be involved in promoting lymphocytes migration.
Genetic basis for virulence differences of various Cryptosporidium parvum carcinogenic isolates
Authors: Audebert Christophe , Bonardi Franck , Caboche Ségolène , Guyot Karine , Touzet Hélène , Merlin Sophie , Gantois Nausicaa , Creusy Colette , Meloni Dionigia , Mouray Anthony , Viscogliosi Eric , Certad Gabriela , Benamrouz-Vanneste Sadia , Chabé Magali
Published: April 2020

Cryptosporidium parvum is known to cause life-threatening diarrhea in immunocompromised hosts and was also reported to be capable of inducing digestive adenocarcinoma in a rodent model. Interestingly, three carcinogenic isolates of C. parvum, called DID, TUM1 and CHR, obtained from fecal samples of naturally infected animals or humans, showed higher virulence than the commercially available C. parvum IOWA isolate in our animal model in terms of clinical manifestations, mortality rate and time of onset of neoplastic lesions. In order to discover the potential genetic basis of the differential virulence observed between C. parvum isolates and to contribute to the understanding of Cryptosporidium virulence, entire genomes of the isolates DID, TUM1 and CHR were sequenced then compared to the C. parvum IOWA reference genome. 125 common SNVs corresponding to 90 CDSs were found in the C. parvum genome that could explain this differential virulence. In particular variants in several membrane and secreted proteins were identified. Besides the genes already known to be involved in parasite virulence, this study identified potential new virulence factors whose functional characterization can be achieved through CRISPR/Cas9 technology applied to this parasite.
The Animal Lectin Galectin-8 Promotes Cytokine Expression and Metastatic Tumor Growth in Mice
Authors: Shatz-Azoulay Hadas , Vinik Yaron , Isaac Roi , Kohler Ulrike , Lev Sima , Zick Yehiel
Published: April 2020

Secreted animal lectins of the galectin family are key players in cancer growth and metastasis. Here we show that galectin-8 (gal-8) induces the expression and secretion of cytokines and chemokines such as SDF-1 and MCP-1 in a number of cell types. This involves gal-8 binding to a uPAR/LRP1/integrin complex that activates JNK and the NFkB pathway. Cytokine and chemokine secretion, induced by gal-8, promotes migration of cancer cells toward cells treated with this lectin. Indeed, immune-competent gal-8 knockout (KO) mice express systemic lower levels of cytokines and chemokines while the opposite is true for gal-8 transgenic animals. Accordingly, gal-8 KO mice experience reduced tumor size and smaller and fewer metastatic lesions when injected with cancer cells. These results suggest the existence of a ‘vicious cycle’ whereby gal-8 secreted by the tumor microenvironment, promotes secretion of chemoattractants at the metastatic niche that promote further recruitment of tumor cells to that site. This study further implicate gal-8 in control of cancer progression and metastasis through its effects on the production of immunoregulatory cytokines.
Generation of two successive attosecond pulses in separate spectral domains
Authors: Kovács Katalin , Tosa Valer
Published: April 2020

We demonstrate that two different single attosecond pulses (SAP) can be obtained from naturally separated spectral domains formed during high-order harmonic generation and propagation in a gas medium. We propose a feasible experimental configuration in which one can obtain an SAP in a lower energy domain (<300 eV), or another SAP in a higher energy domain (>300 eV). Without filtering, a double attosecond pulse emission with fixed temporal separation is obtained. The gap between the two spectral domains is close to the onset of the water window.
Analyzing the advantages of subcutaneous over transcutaneous electrical stimulation for activating brainwaves
Authors: Kang Wonok , Lee Jiho , Kim Yu Ri , Chung Woo Ram , Na Duk L. , Shon Young-Min , Park Sung-Min
Published: April 2020

Transcranial electrical stimulation (TES) is a widely accepted neuromodulation modality for treating brain disorders. However, its clinical efficacy is fundamentally limited due to the current shunting effect of the scalp and safety issues. A newer electrical stimulation technique called subcutaneous electrical stimulation (SES) promises to overcome the limitations of TES by applying currents directly at the site of the disorder through the skull. While SES seems promising, the electrophysiological effect of SES compared to TES is still unknown, thus limiting its broader application. Here we comprehensively analyze the SES and TES to demonstrate the effectiveness and advantages of SES. Beagles were bilaterally implanted with subdural strips for intracranial electroencephalography and electric field recording. For the intracerebral electric field prediction, we designed a 3D electromagnetic simulation framework and simulated TES and SES. In the beagle model, SES induces three to four-fold larger cerebral electric fields compared to TES, and significant changes in power ratio of brainwaves were observed only in SES. Our prediction framework suggests that the field penetration of SES would be several-fold larger than TES in human brains. These results demonstrate that the SES would significantly enhance the neuromodulatory effects compared to conventional TES and overcome the TES limitations.
Nerve conduction during acute blood-flow restriction with and without low-intensity exercise Nerve conduction and blood-flow restriction
Authors: Mendonca Goncalo V. , Mouro Miguel , Vila-Chã Carolina , Pezarat-Correia Pedro
Published: April 2020

Despite being apparently safe for most individuals, the impact of low intensity (LI) blood-flow restricted (BFR) exercise on nerve function and integrity is still obscure. We explored whether BFR (with and without exercise) alters the properties of nerve conduction measured at the level of the restricted limb. Thirteen healthy, young men (22.0 ± 1.7 years) were included in this study. Arterial occlusion pressure was taken at rest. Soleus M- and H-recruitment curves were constructed for all participants. H-wave latencies and amplitudes were obtained in three testing conditions (non-BFR vs. 60 vs. 80% BFR) at four different time points: [#1] non-restricted baseline, [#2] time control either with or without BFR, [#3] non-restricted pre-exercise, [#4] LI exercise either with or without BFR. Nerve conduction was estimated using the difference between the latency of H and M wave. BFR did not affect H-wave amplitude, either with or without exercise. The changes in the difference between H- and M-wave latency of over time were similar between all conditions (condition-by-time interaction: F = 0.7, p = 0.47). In conclusion, our data indicate that performing LI exercise with BFR, set at 60 or 80% BFR, does not exert a negative impact on sciatic-tibial nerve function. Thus, from a neurological standpoint, we provide preliminary evidence that LI BFR exercise may be regarded as a safe mode of resistance training in healthy young men.
The effect of threshold level on bone segmentation of cranial base structures from CT and CBCT images
Authors: Friedli Luca , Kloukos Dimitrios , Kanavakis Georgios , Halazonetis Demetrios , Gkantidis Nikolaos
Published: April 2020

The use of a single grey intensity threshold is one of the most straightforward and widely used methods to segment cranial base surface models from a 3D radiographic volume. In this study we used thirty Cone Beam Computer Tomography (CBCT) scans from three different machines and ten CT scans of growing individuals to test the effect of thresholding on the subsequently produced anterior cranial base surface models. From each scan, six surface models were generated using a range of voxel intensity thresholds. The models were then superimposed on a manually selected reference surface model, using an iterative closest point algorithm. Multivariate tests showed significant effects of the machine type, threshold value, and superimposition on the spatial position and the form of the created models. For both, CT and CBCT machines, the distance between the models, as well as the variation within each threshold category, was consistently increasing with the magnitude of difference between thresholds. The present findings highlight the importance of accurate anterior cranial base segmentation for reliable assessment of craniofacial morphology through surface superimposition or similar methods that utilize this anatomical structure as reference.
Enhanced orbital adipogenesis in a mouse model of T-cell-mediated autoimmunity, zymosan A-treated SKG mice: Implications for Graves’ ophthalmopathy
Authors: Park Sera , Park Dae-Young , Kim Jaeryung , Woo Kyung In , Kim Yoon-Duck , Han Jisang , Chung Tae-Young , Cha Hoon-Suk , Lim Dong Hui
Published: April 2020

Inflammation and remodelling of orbital tissue associated with enhanced adipogenesis commonly occur in Graves’ ophthalmopathy (GO), however, the underlying mechanisms that link immune cells and adipocytes in orbital inflammation are not well-known. The primary aim of this study was to elucidate how a genetically determined shift in the T-cell repertoire toward self-reactive T-cells could drive orbital adipogenesis. To induce the T-cell-mediated autoimmune response, SKG mice were intraperitoneally injected with zymosan A once at 8 weeks of age. After three months, orbital magnetic resonance imaging (MRI), histopathologic studies, and in vitro analyses were performed to evaluate inflammation and adipogenesis. The eyes of the zymosan A-treated SKG mice displayed proptosis and blepharitis. A detailed analysis of orbital adipose tissue showed enhanced orbital adipogenesis and cellular infiltration compared to controls. In addition, increased secretion of adipokines and other cytokines in the periorbital tissue was observed, together with elevated serum concentration of inflammatory cytokines. Orbital adipogenesis was enhanced in zymosan A-treated SKG mice, a novel mouse model for GO-like inflammatory adipose phenotypes most likely induced by T-cell mediated autoimmune responses. This mouse model gives us the opportunity to examine the underlying molecular mechanisms of enhanced adipogenesis in GO, ultimately providing a potential therapeutic target alternative to conventional GO treatment.
Transcriptional Upregulation of NLRC5 by Radiation Drives STING- and Interferon-Independent MHC-I Expression on Cancer Cells and T Cell Cytotoxicity
Authors: Zebertavage Lauren K. , Alice Alejandro , Crittenden Marka R. , Gough Michael J.
Published: April 2020

Radiation therapy has been shown to enhance the efficacy of various T cell-targeted immunotherapies that improve antigen-specific T cell expansion, T regulatory cell depletion, or effector T cell function. Additionally, radiation therapy has been proposed as a means to recruit T cells to the treatment site and modulate cancer cells as effector T cell targets. The significance of these features remains unclear. We set out to determine, in checkpoint inhibitor resistant models, which components of radiation are primarily responsible for overcoming this resistance. In order to model the vaccination effect of radiation, we used aListeria monocytogenesbased vaccine to generate a large population of tumor antigen specific T cells but found that the presence of cells with cytotoxic capacity was unable to replicate the efficacy of radiation with combination checkpoint blockade. Instead, we demonstrated that a major role of radiation was to increase the susceptibility of surviving cancer cells to CD8+ T cell-mediated control through enhanced MHC-I expression. We observed a novel mechanism of genetic induction of MHC-I in cancer cells through upregulation of the MHC-I transactivator NLRC5. These data support the critical role of local modulation of tumors by radiation to improve tumor control with combination immunotherapy.
Three-electrode galvanic microcells as a new antimicrobial tool
Authors: Spisak Wojciech , Chlebicki Andrzej , Kaszczyszyn Mariusz , Szar Mateusz , Kozak Jarosław , Olma Arletta
Published: April 2020

This study presents the first research related to fungal and bacterial growth within electromagnetic fields generated by three-electrode galvanic cells, with PDA growth medium as an electrolyte. We used galvanic microcells constructed with copper, bismuth and zinc metal bars. The configuration of these electrodes was a fundamental agent in the creation of a maximum inhibition zone and in bismuth ion movement. Fungal strains, such as Aspergillus tubingensis and Rhodotorula mucilaginosa, and the bacterium Micrococcus luteus were used as model organisms.
A comparison of the electrical characteristics, liquid composition, and toxicant emissions of JUUL USA and JUUL UK e-cigarettes
Authors: Talih Soha , Salman Rola , El-Hage Rachel , Karam Ebrahim , Salam Sally , Karaoghlanian Nareg , El-Hellani Ahmad , Saliba Najat , Shihadeh Alan
Published: April 2020

In 2018, JUUL entered the UK market, where EU regulations limit liquid nicotine concentration to 20 mg/mL, approximately one-third the level of JUUL products sold in the USA. We hypothesized that JUUL’s UK product was engineered to deliver greater electrical power and boost liquid vaporization such that the net nicotine delivery rate was similar to the US version. We compared electrical characteristics, liquid composition, and aerosol emissions of JUUL devices procured in the USA and the UK. Study outcomes included electrical power, total and freebase nicotine, propylene glycol/vegetable glycerin ratio, carbonyls, and reactive oxygen species. Liquids and aerosols were analyzed by GCMS, HPLC, and fluorescence. Compared to the US version, JUUL UK had approximately one-third the liquid nicotine concentration in the liquid (5.4 vs. 1.6 wt.%) and aerosol (4.7 and 1.3 wt.%). Other than nicotine concentration and yield, we found no differences in any other study outcome, including electrical power. Currently, JUUL UK emits nicotine at a far lower rate than the US product, offering an opportunity to study how this factor impacts user behavior, JUUL uptake, and other population-level outcomes across the two markets.
The origin of anticorrelation for photon bunching on a beam splitter
Authors: Ham Byoung S.
Published: April 2020

The Copenhagen interpretation, in which the core concepts are Heisenberg’s uncertainty principle and nonlocal EPR correlation, has been long discussed. Second-order anticorrelation in a beam splitter represents the origin of these phenomena and cannot be achieved classically. Here, the anticorrelation of nonclassicality in a beam splitter is interpreted using the concept of coherence. Unlike the common understanding of photons having a particle nature, anticorrelation is rooted in the wave nature of coherence optics, described by coherence optics, wherein quantum superposition between two input fields plays a key role. This interpretation may pose fundamental questions about the nature of nonclassicality and pave a road to coherence-based quantum information.