bluuebunny/crossref_metadata_2025 huggingface dataset:
Copanlisib promotes growth inhibition and apoptosis by modulating the AKT/FoxO3a/PUMA axis in colorectal cancer
Authors: Yan Ji , Yang Shida , Tian Hong , Zhang Yang , Zhao Hongmei
Published: November 2020

Colorectal cancer (CRC) is the type of cancer with the third highest incidence and is associated with high mortality and low 5-year survival rates. We observed that copanlisib, an inhibitor of PI3K (pan-class I phosphoinositide 3-kinase) that preferentially inhibits PI3Kδ and PI3Kα, impedes the growth of CRC cells by inducing apoptosis via PUMA. There was a marked increase in the expression of PUMA independent of p53 after treatment with copanlisib. The response of CRC cells to copanlisib could be predicted by PUMA expression. Copanlisib was found to induce PUMA expression through FoxO3a by directly binding to the PUMA promoter after inhibiting AKT signaling. PUMA deficiency mitigated the apoptosis induced by copanlisib. Caspase activation and mitochondrial dysfunction led to copanlisib resistance, as observed through a clonogenic assay, whereas enhanced expression of PUMA increased the copanlisib-induced susceptibility to apoptosis. Moreover, the antitumor effects of copanlisib were suppressed by a deficiency of PUMA in a xenograft model, and caspase activation and reduced apoptosis were also observed in vivo. Copanlisib-mediated chemosensitization seemed to involve the concurrent induction of PUMA expression via mechanisms that were both dependent and independent of p53. These observations indicate that apoptosis mediated by PUMA is crucial for the anticancer effects of copanlisib and that manipulation of PUMA may aid in enhancing anticancer activities.
Epigenetic conflict on a degenerating Y chromosome increases mutational burden in Drosophila males
Authors: Wei Kevin H.-C. , Gibilisco Lauren , Bachtrog Doris
Published: November 2020

Large portions of eukaryotic genomes consist of transposable elements (TEs), and the establishment of transcription-repressing heterochromatin during early development safeguards genome integrity in Drosophila. Repeat-rich Y chromosomes can act as reservoirs for TEs (‘toxic’ Y effect), and incomplete epigenomic defenses during early development can lead to deleterious TE mobilization. Here, we contrast the dynamics of early TE activation in two Drosophila species with vastly different Y chromosomes of different ages. Zygotic TE expression is elevated in male embryos relative to females in both species, mostly due to expression of Y-linked TEs. Interestingly, male-biased TE expression diminishes across development in D. pseudoobscura, but remains elevated in D. miranda, the species with the younger and larger Y chromosome. The repeat-rich Y of D. miranda still contains many actively transcribed genes, which compromise the formation of silencing heterochromatin. Elevated TE expression results in more de novo insertions of repeats in males compared to females. This lends support to the idea that the ‘toxic’ Y chromosome can create a mutational burden in males when genome-wide defense mechanisms are compromised, and suggests a previously unappreciated epigenetic conflict on evolving Y chromosomes between transcription of essential genes and silencing of selfish DNA.
Divergent architecture of the heterotrimeric NatC complex explains N-terminal acetylation of cognate substrates
Authors: Grunwald Stephan , Hopf Linus V. M. , Bock-Bierbaum Tobias , Lally Ciara C. M. , Spahn Christian M. T. , Daumke Oliver
Published: November 2020

The heterotrimeric NatC complex, comprising the catalytic Naa30 and the two auxiliary subunits Naa35 and Naa38, co-translationally acetylates the N-termini of numerous eukaryotic target proteins. Despite its unique subunit composition, its essential role for many aspects of cellular function and its suggested involvement in disease, structure and mechanism of NatC have remained unknown. Here, we present the crystal structure of the Saccharomyces cerevisiae NatC complex, which exhibits a strikingly different architecture compared to previously described N-terminal acetyltransferase (NAT) complexes. Cofactor and ligand-bound structures reveal how the first four amino acids of cognate substrates are recognized at the Naa30–Naa35 interface. A sequence-specific, ligand-induced conformational change in Naa30 enables efficient acetylation. Based on detailed structure–function studies, we suggest a catalytic mechanism and identify a ribosome-binding patch in an elongated tip region of NatC. Our study reveals how NAT machineries have divergently evolved to N-terminally acetylate specific subsets of target proteins.
Construction of a complete set of Neisseria meningitidis mutants and its use for the phenotypic profiling of this human pathogen
Authors: Muir Alastair , Gurung Ishwori , Cehovin Ana , Bazin Adelme , Vallenet David , Pelicic Vladimir
Published: November 2020

The bacterium Neisseria meningitidis causes life-threatening meningitis and sepsis. Here, we construct a complete collection of defined mutants in protein-coding genes of this organism, identifying all genes that are essential under laboratory conditions. The collection, named NeMeSys 2.0, consists of individual mutants in 1584 non-essential genes. We identify 391 essential genes, which are associated with basic functions such as expression and preservation of genome information, cell membrane structure and function, and metabolism. We use this collection to shed light on the functions of diverse genes, including a gene encoding a member of a previously unrecognised class of histidinol-phosphatases; a set of 20 genes required for type IV pili function; and several conditionally essential genes encoding antitoxins and/or immunity proteins. We expect that NeMeSys 2.0 will facilitate the phenotypic profiling of a major human bacterial pathogen.
LncRNA DILA1 inhibits Cyclin D1 degradation and contributes to tamoxifen resistance in breast cancer
Authors: Shi Qianfeng , Li Yudong , Li Shunying , Jin Liang , Lai Hongna , Wu Yanqing , Cai Zijie , Zhu Mengdi , Li Qian , Li Ying , Wang Jingru , Liu Yujie , Wu Zongqi , Song Erwei , Liu Qiang
Published: November 2020

Cyclin D1 is one of the most important oncoproteins that drives cancer cell proliferation and associates with tamoxifen resistance in breast cancer. Here, we identify a lncRNA, DILA1, which interacts with Cyclin D1 and is overexpressed in tamoxifen-resistant breast cancer cells. Mechanistically, DILA1 inhibits the phosphorylation of Cyclin D1 at Thr286 by directly interacting with Thr286 and blocking its subsequent degradation, leading to overexpressed Cyclin D1 protein in breast cancer. Knocking down DILA1 decreases Cyclin D1 protein expression, inhibits cancer cell growth and restores tamoxifen sensitivity both in vitro and in vivo. High expression of DILA1 is associated with overexpressed Cyclin D1 protein and poor prognosis in breast cancer patients who received tamoxifen treatment. This study shows the previously unappreciated importance of post-translational dysregulation of Cyclin D1 contributing to tamoxifen resistance in breast cancer. Moreover, it reveals the novel mechanism of DILA1 in regulating Cyclin D1 protein stability and suggests DILA1 is a specific therapeutic target to downregulate Cyclin D1 protein and reverse tamoxifen resistance in treating breast cancer.
On-surface lithium donor reaction enables decarbonated lithium garnets and compatible interfaces within cathodes
Authors: Yang Ya-Nan , Li Ying-Xiang , Li Yi-Qiu , Zhang Tao
Published: November 2020

Lithium garnets have been widely studied as promising electrolytes that could enable the next-generation all-solid-state lithium batteries. However, upon exposure to atmospheric moisture and carbon dioxide, insulating lithium carbonate forms on the surface and deteriorates the interfaces within electrodes. Here, we report a scalable solid sintering method, defined by lithium donor reaction that allows for complete decarbonation of Li6.4La3Zr1.4Ta0.6O12 (LLZTO) and yields an active LiCoO2 layer for each garnet particle. The obtained LiCoO2 coated garnets composite is stable against air without any Li2CO3. Once working in a solid-state lithium battery, the LiCoO2-LLZTO@LiCoO2 composite cathode maintains 81% of the initial capacity after 180 cycles at 0.1 C. Eliminating CO2 evolution above 4.0 V is confirmed experimentally after transforming Li2CO3 into LiCoO2. These results indicate that Li2CO3 is no longer an obstacle, but a trigger of the intimate solid-solid interface. This strategy has been extended to develop a series of LLZTO@active layer materials.
Developing a pathway-independent and full-autonomous global resource allocation strategy to dynamically switching phenotypic states
Authors: Wu Junjun , Bao Meijiao , Duan Xuguo , Zhou Peng , Chen Caiwen , Gao Jiahua , Cheng Shiyao , Zhuang Qianqian , Zhao Zhijun
Published: November 2020

A grand challenge of biological chemical production is the competition between synthetic circuits and host genes for limited cellular resources. Quorum sensing (QS)-based dynamic pathway regulations provide a pathway-independent way to rebalance metabolic flux over the course of the fermentation. Most cases, however, these pathway-independent strategies only have capacity for a single QS circuit functional in one cell. Furthermore, current dynamic regulations mainly provide localized control of metabolic flux. Here, with the aid of engineering synthetic orthogonal quorum-related circuits and global mRNA decay, we report a pathway-independent dynamic resource allocation strategy, which allows us to independently controlling two different phenotypic states to globally redistribute cellular resources toward synthetic circuits. The strategy which could pathway-independently and globally self-regulate two desired cell phenotypes including growth and production phenotypes could totally eliminate the need for human supervision of the entire fermentation.
Next-generation sequencing analysis of circulating micro-RNA expression in response to parabolic flight as a spaceflight analogue
Authors: Jirak Peter , Wernly Bernhard , Lichtenauer Michael , Franz Marcus , Knost Thorben , Abusamrah Thaer , Kelm Malte , Bimpong-Buta Nana-Yaw , Jung Christian
Published: November 2020

Understanding physiologic reactions to weightlessness is an indispensable requirement for safe human space missions. This study aims to analyse changes in the expression of circulating miRNAs following exposure to gravitational changes. Eight healthy volunteers (age: 24.5 years, male: 4, female: 4) were included. Each subject underwent 31 short-term phases of weightlessness and hypergravity induced by parabolic flight as a spaceflight analogue. At baseline, 1 and 24 h after parabolic flight, venous blood was withdrawn. Analysis of circulating miRNAs in serum was conducted by means of next generation sequencing. In total, 213 miRNAs were robustly detected (TPM > 5) by small RNA sequencing in all 24 samples. Four miRNAs evidenced a significant change in expression after adjusting for multiple testing. Only miR-223-3p showed a consistent significant decrease 24 h after parabolic flight compared to baseline values and values at 1 h after parabolic flight. miR-941 and miR-24-3p showed a significant decrease 24 h after parabolic flight compared to 1 h after parabolic flight but not to baseline values. miR-486-5p showed a significant increase 24 h after parabolic flight compared to 1 h after parabolic flight but not to baseline values. A target network analysis identified genes of the p53 signaling pathway and the cell cycle highly enriched among the targets of the four microRNAs. Our findings suggest cellular adaption to gravitational changes at the post-transcriptional level. Based on our results, we suggest a change in cell cycle regulation as potential explanation for adaptational changes observed in space missions.
Deconfinement of Mott localized electrons into topological and spin–orbit-coupled Dirac fermions
Authors: Pizarro José M. , Adler Severino , Zantout Karim , Mertz Thomas , Barone Paolo , Valentí Roser , Sangiovanni Giorgio , Wehling Tim O.
Published: November 2020

The interplay of electronic correlations, spin–orbit coupling and topology holds promise for the realization of exotic states of quantum matter. Models of strongly interacting electrons on honeycomb lattices have revealed rich phase diagrams featuring unconventional quantum states including chiral superconductivity and correlated quantum spin Hall insulators intertwining with complex magnetic order. Material realizations of these electronic states are, however, scarce or inexistent. In this work, we propose and show that stacking 1T-TaSe2 into bilayers can deconfine electrons from a deep Mott insulating state in the monolayer to a system of correlated Dirac fermions subject to sizable spin–orbit coupling in the bilayer. 1T-TaSe2 develops a Star-of-David charge density wave pattern in each layer. When the Star-of-David centers belonging to two adyacent layers are stacked in a honeycomb pattern, the system realizes a generalized Kane–Mele–Hubbard model in a regime where Dirac semimetallic states are subject to significant Mott–Hubbard interactions and spin–orbit coupling. At charge neutrality, the system is close to a quantum phase transition between a quantum spin Hall and an antiferromagnetic insulator. We identify a perpendicular electric field and the twisting angle as two knobs to control topology and spin–orbit coupling in the system. Their combination can drive it across hitherto unexplored grounds of correlated electron physics, including a quantum tricritical point and an exotic first-order topological phase transition.
Olive oil from the 79 A.D. Vesuvius eruption stored at the Naples National Archaeological Museum (Italy)
Authors: Sacchi Raffaele , Cutignano Adele , Picariello Gianluca , Paduano Antonello , Genovese Alessandro , Siano Francesco , Nuzzo Genoveffa , Caira Simonetta , Lubritto Carmine , Ricci Paola , D’Auria Alessia , Di Pasquale Gaetano , Motta Andrea , Addeo Francesco
Published: November 2020

Using a range of chromatographic, spectroscopic, and mass spectrometric analytical techniques, we characterized one of the “edible items” found at the Vesuvius archeological sites and guarded at the National Archaeological Museum of Naples (MANN) in Naples, Italy. We authenticated the specimen contained in a glass bottle (Mann-S1 sample) as originally olive oil and mapped the deep evolution throughout its 2000 years of storage. Triacylglycerols were completely hydrolyzed, while the resulting (hydroxy) fatty acids had partly condensed into rarely found estolides. A complex pattern of volatile compounds arose mainly from breakdown of oleic acid. With excellent approximation, radiocarbon dating placed the find at the time of the Plinian Mount Vesuvius eruption in 79 A.D., indicating that Mann-S1 is probably the oldest residue of olive oil in the world found in bulk amount (nearly 0.7 L).
Collective dynamics of dark web marketplaces
Authors: ElBahrawy Abeer , Alessandretti Laura , Rusnac Leonid , Goldsmith Daniel , Teytelboym Alexander , Baronchelli Andrea
Published: November 2020

Dark web marketplaces are websites that facilitate trade in illicit goods, mainly using Bitcoin. Since dark web marketplaces are unregulated, they do not offer any user protection, so police raids and scams regularly cause large losses to marketplace participants. However, the uncertainty has not prevented the proliferation of dark web marketplaces. Here, we investigate how the dark web marketplace ecosystem reorganises itself following marketplace closures. We analyse 24 separate episodes of unexpected marketplace closure by inspecting 133 million Bitcoin transactions among 38 million users. We focus on “migrating users” who move their trading activity to a different marketplace after a closure. We find that most migrating users continue their trading activity on a single coexisting marketplace, typically the one with the highest trading volume. User migration is swift and trading volumes of migrating users recover quickly. Thus, although individual marketplaces might appear fragile, coordinated user migration guarantees overall systemic resilience.
An empirical model to evaluate the effects of environmental humidity on the formation of wrinkled, creased and porous fibre morphology from electrospinning
Authors: Zhang Duo , Davoodi Pooya , Li Xia , Liu Ye , Wang Wenyu , Huang Yan Yan Shery
Published: November 2020

Controlling environmental humidity level and thus moisture interaction with an electrospinning solution jet has led to a fascinating range of polymer fibre morphological features; these include surface wrinkles, creases and surface/internal porosity at the individual fibre level. Here, by cross-correlating literature data of far-field electrospinning (FFES), together with our experimental data from near-field electrospinning (NFES), we propose a theoretical model, which can account, phenomenologically, for the onset of fibre microstructures formation from electrospinning solutions made of a hydrophobic polymer dissolved in a water-miscible or polar solvent. This empirical model provides a quantitative evaluation on how the evaporating solvent vapour could prevent or disrupt water vapor condensation onto the electrospinning jet; thus, on the condition where vapor condensation does occur, morphological features will form on the surface, or bulk of the fibre. A wide range of polymer systems, including polystyrene, poly(methyl methacrylate), poly-l-lactic acid, polycaprolactone were tested and validated. Our analysis points to the different operation regimes associated FFES versus NFES, when it comes to the system’s sensitivity towards environmental moisture. Our proposed model may further be used to guide the process in creating desirable fibre microstructure.
Resveratrol attenuates TLR-4 mediated inflammation and elicits therapeutic potential in models of sepsis
Authors: Wang Binbin , Bellot Gregory Lucien , Iskandar Kartini , Chong Tsung Wen , Goh Fera Yiqian , Tai June Jingyi , Schwarz Herbert , Wong Siew Cheng , Pervaiz Shazib
Published: November 2020

Sepsis is a potentially fatal condition triggered by systemic inflammatory response to infection. Due to the heightened immune reactivity and multi-organ pathology, treatment options are limited and several clinical trials have not produced the desired outcome, hence the interest in the discovery of novel therapeutic strategies. The polyphenol resveratrol (RSV) has shown promise against several pathological states, including acute and chronic inflammation. In this study, we evaluated its therapeutic potential in a murine model of sepsis and in patients undergoing transrectal ultrasound biopsy. RSV was able to inhibit lipopolysaccharide (LPS) stimulated inflammatory responses through blocking Phospholipase D (PLD) and its downstream signaling molecules SphK1, ERK1/2 and NF-κB. In addition, RSV treatment resulted in the downregulation of MyD88, an adaptor molecule in the TLR4 signaling pathway, and this effect at least in part, involved RSV-induced autophagy. Notably, RSV protected mice against polymicrobial septic shock induced upon cecal ligation and puncture, and inhibited pro-inflammatory cytokine production by human monocytes from transrectal ultrasound (TRUS) biopsy patients. Together, these findings demonstrate the immune regulatory activity of RSV and highlight its therapeutic potential in the management of sepsis.
Motion around triangular points in the restricted three-body problem with radiating heterogeneous primaries surrounded by a belt
Authors: Singh Jagadish , Haruna Sunusi
Published: November 2020

The present paper studies the locations and linear stability of the triangular equilibrium points when both primaries are radiating and considered as heterogeneous spheroid with three layers of different densities. Additionally, we include the effects of small perturbations in the Coriolis and centrifugal forces and potential from a belt (circumbinary disc). It is observed that the positions of the triangular equilibrium points are substantially affected by all parameters (except a perturbation in Coriolis force) involved in the system.The stabilty of motion is found only when $$0 < \mu < \mu_{c}$$

0
<
μ
<

μ
c

, where $$\mu_{c}$$

μ
c

is the critical mass value which depends on the combined effect of radiation pressures and heterogeneity of the primaries, small perturbations and the potential from a belt.It is also seen that the Coriolis force and the belt have stabilizing effect,while the centrifugal force, radiation and heterogeineity of the primaries have destabilizing behaviour.The net effect is that the size of the region of stability decreases when the value of these parameters increases where $$\mu$$
μ
is the mass ratio and $$k_{1} ,k_{2}$$

k
1

,

k
2

characterize heterogeneity of both primaries. A practical application of this model could be the study of motion of a dust grain near the heterogeneous and luminous binary stars surrounded by a belt.Finally, we carried out and discuss numerical experiments aiming at computing the positions of triangular points and critical masses of three binary systems: Archid, Xi Booties and Kruger 60.
Antifungal and anti-inflammatory potential of the endangered aromatic plant Thymus albicans
Authors: Roxo Mariana , Zuzarte Mónica , Gonçalves Maria José , Alves-Silva Jorge M. , Cavaleiro Carlos , Cruz Maria Teresa , Salgueiro Lígia
Published: November 2020

Thymus albicans is an endemic species of the Iberian Peninsula with a vulnerable conservation status. In an attempt to contribute to the valorization of this species, the present study brings new insights on the antifungal and anti-inflammatory mechanism of action of T. albicans essential oil. The antifungal activity of the oil and its major compounds was assessed for the first time against standard and clinically isolated strains of yeasts and filamentous fungi. The effect on the two major virulence factors of Candida albicans (germ tube formation and biofilm disruption) was considered in more detail. At 0.08 μL/mL, the oil inhibited C. albicans germ tube formation by more than 40% and decreased biofilm biomass at MIC values, thus pointing out its antivirulent potential. The anti-inflammatory activity of the essential oil was investigated on LPS-stimulated mouse macrophages (RAW 264.7) by evaluating the levels of several pro-inflammatory mediators, namely nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). T. albicans oil reduced the production of nitrites, a NO derived sub-product, at non-cytotoxic concentrations of 0.32 and 0.64 μL/mL, by 27 and 41%, respectively. In addition, the iNOS protein levels of essential oil pre-treated cells were reduced by 14%. Overall, the high essential oil yield of T. albicans as well as its bioactive effects at concentrations without cytotoxicity, encourage further studies on the potential pharmacological applications of this species. Furthermore, these results raise awareness for the need to preserve endangered species that may hold relevant medicinal value.
A variable structure pneumatic soft robot
Authors: Huang Wenkai , Xiao Junlong , Xu Zhipeng
Published: November 2020

In this paper, a variable structure pneumatic soft robot is proposed. Its structure is variable in that when it grasps irregular objects, it can adapt to different sizes by active expansion or contraction. Its expansion range is from diameter 200 to 300 mm, its four soft pneumatic actuators (SPAs) can be rotated independently to adapt to different shapes, and it has high flexibility. The active compliant grasping method enables it to capture at the best position, which can improve the success rate of capture and reduce damage to the object being grasped. The experiment proves the effectiveness of the variable structure mechanism, and the proposed soft robot has low cost and a simple manufacturing process, so the mechanism has great application prospects.
Computational methods for visualizing and measuring verapamil efficacy for cerebral vasospasm
Authors: Abumoussa Andrew , Flores Alex , Ho James , Niethammer Marc , Sasaki-Adams Deanna , Lee Yueh Z.
Published: November 2020

Cerebral vasospasm is a dreaded sequelae of aneurysmal subarachnoid hemorrhage (aSAH), requiring timely intervention with therapeutic goals of improving brain perfusion. There are currently no standardized real-time, objective assessments of the interventional procedures performed to treat vasospasm. Here we describe real-time techniques to quantify cerebral perfusion during interventional cerebral angiography. We retrospectively analyzed 39 consecutive cases performed to treat clinical vasospasm and quantified the changes in perfusion metrics between pre- and post- verapamil administrations. With Digital Subtraction Angiography (DSA) perfusion analysis, we are able to identify hypoperfused territories and quantify the exact changes in cerebral perfusion for each individual case and vascular territory. We demonstrate that perfusion analysis for DSA can be performed in real time. This provides clinicians with a colorized map which directly visualizes hypoperfused tissue, combined with associated perfusion statistics. Quantitative thresholds and analysis based on DSA perfusion may assist with real-time dosage estimation and help predict response to treatment, however future prospective analysis is required for validation.
Network inference from population-level observation of epidemics
Authors: Di Lauro F. , Croix J.-C. , Dashti M. , Berthouze L. , Kiss I. Z.
Published: November 2020

Using the continuous-time susceptible-infected-susceptible (SIS) model on networks, we investigate the problem of inferring the class of the underlying network when epidemic data is only available at population-level (i.e., the number of infected individuals at a finite set of discrete times of a single realisation of the epidemic), the only information likely to be available in real world settings. To tackle this, epidemics on networks are approximated by a Birth-and-Death process which keeps track of the number of infected nodes at population level. The rates of this surrogate model encode both the structure of the underlying network and disease dynamics. We use extensive simulations over Regular, Erdős–Rényi and Barabási–Albert networks to build network class-specific priors for these rates. We then use Bayesian model selection to recover the most likely underlying network class, based only on a single realisation of the epidemic. We show that the proposed methodology yields good results on both synthetic and real-world networks.
Infection of dogs by Leishmania infantum elicits a general response of IgG subclasses
Authors: Olías-Molero A. I. , Moreno I. , Corral M. J. , Jiménez-Antón M. D. , Day M. J. , Domínguez M. , Alunda J. M.
Published: November 2020

Leishmania infantum is the etiological agent of zoonotic visceral leishmaniasis. In endemic areas, canine infections are considered the main source of infection for human populations. Therefore, any control of human leishmaniasis must include the control of canine infections. Chemotherapy of leishmaniasis is inadequate and canine immunoprophylaxis has important limitations. Reports on the response of infected dogs are abundant but no clear picture of immune events has emerged. To shed some light on these shortcomings the specific IgG subclass response was followed in 20 Beagle dogs experimentally infected with L. infantum using monoclonal antibodies (MAb) specific for canine IgG1, IgG2, IgG3 and IgG4, along with ELISA and flow cytometry. Results showed that parasitic infection elicits a general response of all IgG subclasses, with a predominant IgG1 response and without any evidence of IgG1/IgG2 dichotomy. These findings suggest that the inconsistent results reported previously could be related to the lack of specific reagents and not to the actual differences in the immune response of infected animals. Differential IgG subclass reactivity in ELISA and cytometry and the analysis of the reacting antigens could facilitate the diagnosis and prognosis of the disease and provide a useful tool for adequate therapeutics and vaccine development against leishmaniasis.
Prediction of amyloid β PET positivity using machine learning in patients with suspected cerebral amyloid angiopathy markers
Authors: Jung Young Hee , Lee Hyejoo , Kim Hee Jin , Na Duk L. , Han Hyun Jeong , Jang Hyemin , Seo Sang Won
Published: November 2020

Amyloid-β(Aβ) PET positivity in patients with suspected cerebral amyloid angiopathy (CAA) MRI markers is predictive of a worse cognitive trajectory, and it provides insights into the underlying vascular pathology (CAA vs. hypertensive angiopathy) to facilitate prognostic prediction and appropriate treatment decisions. In this study, we applied two interpretable machine learning algorithms, gradient boosting machine (GBM) and random forest (RF), to predict Aβ PET positivity in patients with CAA MRI markers. In the GBM algorithm, the number of lobar cerebral microbleeds (CMBs), deep CMBs, lacunes, CMBs in dentate nuclei, and age were ranked as the most influential to predict Aβ positivity. In the RF algorithm, the absence of diabetes was additionally chosen. Cut-off values of the above variables predictive of Aβ positivity were as follows: (1) the number of lobar CMBs > 16.4(GBM)/14.3(RF), (2) no deep CMBs(GBM/RF), (3) the number of lacunes > 7.4(GBM/RF), (4) age > 74.3(GBM)/64(RF), (5) no CMBs in dentate nucleus(GBM/RF). The classification performances based on the area under the receiver operating characteristic curve were 0.83 in GBM and 0.80 in RF. Our study demonstrates the utility of interpretable machine learning in the clinical setting by quantifying the relative importance and cutoff values of predictive variables for Aβ positivity in patients with suspected CAA markers.
Operando direct observation of spin-states and charge-trappings of blue light-emitting-diode materials in thin-film devices
Authors: Osawa Fumiya , Marumoto Kazuhiro
Published: November 2020

Spin-states and charge-trappings in blue organic light-emitting diodes (OLEDs) are important issues for developing high-device-performance application such as full-color displays and white illumination. However, they have not yet been completely clarified because of the lack of a study from a microscopic viewpoint. Here, we report operando electron spin resonance (ESR) spectroscopy to investigate the spin-states and charge-trappings in organic semiconductor materials used for blue OLEDs such as a blue light-emitting material 1-bis(2-naphthyl)anthracene (ADN) using metal–insulator–semiconductor (MIS) diodes, hole or electron only devices, and blue OLEDs from the microscopic viewpoint. We have clarified spin-states of electrically accumulated holes and electrons and their charge-trappings in the MIS diodes at the molecular level by directly observing their electrically-induced ESR signals; the spin-states are well reproduced by density functional theory. In contrast to a green light-emitting material, the ADN radical anions largely accumulate in the film, which will cause the large degradation of the molecule and devices. The result will give deeper understanding of blue OLEDs and be useful for developing high-performance and durable devices.
Design of an ELC resonator-based reusable RF microfluidic sensor for blood glucose estimation
Authors: Govind Greeshmaja , Akhtar M. Jaleel
Published: November 2020

Design of a reusable microfluidic sensor for blood glucose estimation at microwave frequencies is presented. The sensing unit primarily comprises a complementary electric LC (CELC) resonator, which is made reusable by filling the test sample in a glass capillary before mounting it inside a groove cut in the central arm of the resonator. The use of glass capillary in the present situation to contain the blood sample actually eliminates the possibility of any direct contact of the sensor with the test sample, and hence wards off any coincidental contamination of the sensor. Usage of the capillary provides additional benefits as only microliters of the sample are required, besides offering sterile measuring environment since these capillaries are disposable. The capillary made of borosilicate glass is highly biocompatible and exhibits exceptionally high chemical resistance in corrosive environments. Apart from reusability, the novelty of the proposed sensor also lies in its enhanced sensitivity which is quite an essential factor when it comes to the measurement of glucose concentration in the human physiological range. The applicability of the proposed scheme for glucose sensing is demonstrated by performing RF measurements of aqueous glucose solutions and goat blood samples using the fabricated sensor.
Expression of a novel brain specific isoform of C3G is regulated during development
Authors: Sriram Divya , Chintala Ramulu , Parthasaradhi B. V. V. , Nayak Sanjeev Chavan , Mariappan Indumathi , Radha Vegesna
Published: November 2020

Mice lacking C3G (RapGEF1), a ubiquitously expressed protein essential for neuronal differentiation, show multiple defects in brain development. Function of C3G in neurogenesis is poorly defined. Here, we identify brain specific expression of a novel C3G isoform in mice and humans. This isoform has an insert in the Crk-binding region, generating a polypeptide of 175 kDa, unlike the previously known 140 kDa form expressed in all other tissues. In the adult mouse brain, C3G expression is seen in neurons, but was not detectable in GFAP-positive cells. C3G levels were high in the CA3 region of hippocampus and in mitral cells of olfactory bulb. Neural progenitor cells positive for Doublecortin and Nestin, show expression of C3G. During development, C3G is expressed in precursor cells prior to their differentiation into mature neurons or astrocytes. The 175 kDa as well as 140 kDa forms are seen in embryonic mouse brain, while only the 175 kDa variant is seen in post-natal brain. Human cerebral organoids generated from induced pluripotent stem cells predominantly expressed the 140 kDa polypeptides, and the 175 kDa isoform appeared upon maturation. This study describes developmental regulation and neuronal expression of a brain specific isoform of C3G, a molecule essential for normal development of the mammalian brain.
A Bayesian Belief Network model to link sanitary inspection data to drinking water quality in a medium resource setting in rural Indonesia
Authors: Daniel D. , Iswarani Widya Prihesti , Pande Saket , Rietveld Luuk
Published: November 2020

Assessing water quality and identifying the potential source of contamination, by Sanitary inspections (SI), are essential to improve household drinking water quality. However, no study link the water quality at a point of use (POU), household level or point of collection (POC), and associated SI data in a medium resource setting using a Bayesian Belief Network (BBN) model. We collected water samples and applied an adapted SI at 328 POU and 265 related POC from a rural area in East Sumba, Indonesia. Fecal contamination was detected in 24.4 and 17.7% of 1 ml POC and POU samples, respectively. The BBN model showed that the effect of holistic—combined interventions to improve the water quality were larger compared to individual intervention. The water quality at the POU was strongly related to the water quality at the POC and the effect of household water treatment to improve the water quality was more prominent in the context of better sanitation and hygiene conditions. In addition, it was concluded that the inclusion of extra “external” variable (fullness level of water at storage), besides the standard SI variables, could improve the model’s performance in predicting the water quality at POU. Finally, the BBN approach proved to be able to illustrate the interdependencies between variables and to simulate the effect of the individual and combination of variables on the water quality.
Toxoplasma gondii and multiple sclerosis: a population-based case–control study
Authors: Nicoletti Alessandra , Cicero Calogero Edoardo , Giuliano Loretta , Todaro Valeria , Lo Fermo Salvatore , Chisari Clara , D’Amico Emanuele , Paradisi Vincenza , Mantella Antonia , Bartoloni Alessandro , Sofia Vito , Patti Francesco , Zappia Mario
Published: November 2020

According to the hygiene hypothesis, parasites could have a protective role in the development of Multiple Sclerosis (MS). Our aim was to assess the association between presence of anti-Toxoplasma gondii antibodies and MS. MS patients were randomly selected from a population-based incident cohort of MS patients in the city of Catania. Age and sex-matched controls were randomly selected from the general population. Clinical and sociodemographic variables were recorded with a structured questionnaire and a blood sample was taken for serological analysis. Specific T. gondii IgG have been detected with a commercial kit. Adjusted Odds Ratios (ORs) were estimated using unconditional logistic regression. 129 MS subjects (66.7% women with a mean age 44.7 ± 11.0 years) and 287 controls (67.3% women with a mean age 48.1 ± 15.6 years) have been enrolled in the study. Anti-T. gondii antibodies were found in 38 cases (29.5%) and 130 controls (45.4%) giving an adjusted OR of 0.56 (95%CI 0.34–0.93). History of mononucleosis and high educational level were significantly associated with MS (adjOR 2.22 and 1.70 respectively) while an inverse association was found between high educational level and T. gondii seropositivity (adjOR 0.42). Our results further support the protective role of parasitic infections in MS.
Twist2 is NFkB-responsive when p120-catenin is inactivated and EGFR is overexpressed in esophageal keratinocytes
Authors: Lehman Heather L. , Kidacki Michal , Stairs Douglas B.
Published: November 2020

Esophageal squamous cell carcinoma (ESCC) is among the most aggressive and fatal cancer types. ESCC classically progresses rapidly and frequently causes mortality in four out of five patients within two years of diagnosis. Yet, little is known about the mechanisms that make ESCC so aggressive. In a previous study we demonstrated that p120-catenin (p120ctn) and EGFR, two genes associated with poor prognosis in ESCC, work together to cause invasion. Specifically, inactivation of p120ctn combined with overexpression of EGFR induces a signaling cascade that leads to hyperactivation of NFkB and a resultant aggressive cell type. The purpose of this present study was to identify targets that are responsive to NFkB when p120ctn and EGFR are modified. Using human esophageal keratinocytes, we have identified Twist2 as an NFkB-responsive gene. Interestingly, we found that when NFkB is hyperactivated in cells with EGFR overexpression and p120ctn inactivation, Twist2 is significantly upregulated. Inhibition of NFkB activity results in nearly complete loss of Twist2 expression, suggesting that this potential EMT-inducing gene, is a responsive target of NFkB. There exists a paucity of research on Twist2 in any cancer type; as such, these findings are important in ESCC as well as in other cancer types.
Use of machine learning to classify adult ADHD and other conditions based on the Conners’ Adult ADHD Rating Scales
Authors: Christiansen Hanna , Chavanon Mira-Lynn , Hirsch Oliver , Schmidt Martin H. , Meyer Christian , Müller Astrid , Rumpf Hans-Juergen , Grigorev Ilya , Hoffmann Alexander
Published: November 2020

A reliable diagnosis of adult Attention Deficit/Hyperactivity Disorder (ADHD) is challenging as many of the symptoms of ADHD resemble symptoms of other disorders. ADHD is associated with gambling disorder and obesity, showing overlaps of about 20% with each diagnosis. It is important for clinical practice to differentiate between conditions displaying similar symptoms via established diagnostic instruments. Applying the LightGBM algorithm in machine learning, we were able to differentiate subjects with ADHD, obesity, problematic gambling, and a control group using all 26 items of the Conners’ Adult ADHD Rating Scales (CAARS-S: S) with a global accuracy of .80; precision (positive predictive value) ranged between .78 (gambling) and .92 (obesity), recall (sensitivity) between .58 for obesity and .87 for ADHD. Models with the best 5 and best 10 items resulted in less satisfactory fits. The CAARS-S seems to be a promising instrument to be applied in clinical practice also for multiclassifying disorders displaying symptoms resembling ADHD.
Real-time detection of somatic hybrid cells during electrofusion of carrot protoplasts with stably labelled mitochondria
Authors: Gieniec Miron , Siwek Julianna , Oleszkiewicz Tomasz , Maćkowska Katarzyna , Klimek-Chodacka Magdalena , Grzebelus Ewa , Baranski Rafal
Published: November 2020

Somatic hybridisation in the carrot, as in other plant species, enables the development of novel plants with unique characteristics. This process can be induced by the application of electric current to isolated protoplasts, but such electrofusion requires an effective hybrid cell identification method. This paper describes the non-toxic fluorescent protein (FP) tagging of protoplasts which allows discrimination of fusion components and identification of hybrids in real-time during electrofusion. One of four FPs: cyan (eCFP), green (sGFP), yellow (eYFP) or the mCherry variant of red FP (RFP), with a fused mitochondrial targeting sequence, was introduced to carrot cell lines of three varieties usingAgrobacterium-mediated transformation. After selection, a set of carrot callus lines with either GFP, YFP or RFP-labelled mitochondria that showed stable fluorescence served as protoplast sources. Various combinations of direct current (DC) parameters on protoplast integrity and their ability to form hybrid cells were assessed during electrofusion. The protoplast response and hybrid cell formation depended on DC voltage and pulse time, and varied among protoplast sources. Heterofusants (GFP + RFP or YFP + RFP) were identified by detection of a dual-colour fluorescence. This approach enabled, for the first time, a comprehensive assessment of the carrot protoplast response to the applied electric field conditions as well as identification of the DC parameters suitable for hybrid formation, and an estimation of the electrofusion success rate by performing real-time observations of protoplast fluorescence.
Boosting carrier mobility and stability in indium–zinc–tin oxide thin-film transistors through controlled crystallization
Authors: On Nuri , Kim Bo Kyoung , Kim Yerin , Kim Eun Hyun , Lim Jun Hyung , Hosono Hideo , Kim Junghwan , Yang Hoichang , Jeong Jae Kyeong
Published: November 2020

We investigated the effect of film thickness (geometrical confinement) on the structural evolution of sputtered indium-zinc-tin oxide (IZTO) films as high mobility n-channel semiconducting layers during post-treatment at different annealing temperatures ranging from 350 to 700 °C. Different thicknesses result in IZTO films containing versatile phases, such as amorphous, low-, and high-crystalline structures even after annealing at 700 °C. A 19-nm-thick IZTO film clearly showed a phase transformation from initially amorphous to polycrystalline bixbyite structures, while the ultra-thin film (5 nm) still maintained an amorphous phase. Transistors including amorphous and low crystalline IZTO films fabricated at 350 and 700 °C show reasonable carrier mobility (µFE) and on/off current ratio (ION/OFF) values of 22.4–35.9 cm2 V−1 s−1 and 1.0–4.0 × 108, respectively. However, their device instabilities against positive/negative gate bias stresses (PBS/NBS) are unacceptable, originating from unsaturated bonding and disordered sites in the metal oxide films. In contrast, the 19-nm-thick annealed IZTO films included highly-crystalline, 2D spherulitic crystallites and fewer grain boundaries. These films show the highest µFE value of 39.2 cm2 V−1 s−1 in the transistor as well as an excellent ION/OFF value of 9.7 × 108. Simultaneously, the PBS/NBS stability of the resulting transistor is significantly improved under the same stress condition. This promising superior performance is attributed to the crystallization-induced lattice ordering, as determined by highly-crystalline structures and the associated formation of discrete donor levels (~ 0.31 eV) below the conduction band edge.
Medication use and obesity in Brazil: results from the National Health Survey
Authors: Rimes-Dias Karina Abibi , Canella Daniela Silva
Published: November 2020

Noncommunicable diseases (NCDs) associated with obesity generally require drug treatment. The use of medications in individuals with obesity has not been extensively investigated. The objective of this study was to analyze the relation between obesity and medication use. Data from the Brazilian National Health Survey 2013 was used, including 59,402 individuals. Weight and height measures were used to calculate body mass index (BMI) and categorized individuals according to BMI classification (exposure). The number of medications used for treating nine obesity-related NCDs was the outcome variable. Multinomial regression analyses were performed. The risk of use of medications to treat at least one NCD increased progressively with rising BMI, where this risk was even higher for treating two or more diseases. The risk of having to treat two or more NCDs with medications was approximately 70% greater among individuals with overweight (adjusted RR = 1.66; 95%CI 1.46–1.89), 170% greater in those with class I obesity (adjusted RR = 2.68; 95%CI 2.29–3.12), 340% greater for class II obesity (adjusted RR = 4.44; 95%CI 3.54–5.56) and 450% greater among individuals with class III obesity (adjusted RR = 5.53; 95%CI 3.81–8.02), compared with normal-weight subjects. Obesity was directly associated with drug utilization and the number of medications used to treat obesity-related NCDs.
Whole genome integrity and enhanced developmental potential in ram freeze-dried spermatozoa at mild sub-zero temperature
Authors: Palazzese Luca , Anzalone Debora Agata , Turri Federica , Faieta Marco , Donnadio Anna , Pizzi Flavia , Pittia Paola , Matsukawa Kazutsugu , Loi Pasqualino
Published: November 2020

Freeze-dried spermatozoa typically shows a reduction in fertility primarily due to the DNA damage resulting from the sublimation process. In order to minimize the physical/mechanical damage resulting from lyophilization, here we focused on the freezing phase, comparing two cooling protocols: (i) rapid-freezing, where ram sperm sample is directly plunged into liquid nitrogen (LN-group), as currently done; (ii) slow-freezing, where the sample is progressively cooled to − 50 °C (SF-group). The spermatozoa dried in both conditions were analysed to assess residual water content by Thermal Gravimetric Analysis (TGA) and DNA integrity using Sperm Chromatin Structure Assay (SCSA). TGA revealed more than 90% of water subtraction in both groups. A minor DNA damage, Double-Strand Break (DSB) in particular, characterized by a lower degree of abnormal chromatin structure (Alpha-T), was detected in the SF-group, comparing to the LN-one. In accordance with the structural and DNA integrity data, spermatozoa from SF-group had the best embryonic development rates, comparing to LN-group: cleaved embryos [42/100 (42%) versus 19/75 (25.3%), P < 0.05, SL and LN respectively] and blastocyst formation [7/100 (7%) versus 2/75 (2.7%), P < 0.05, SF and LN respectively]. This data represents a significant technological advancement for the development of lyophilization as a valuable and cheaper alternative to deep-freezing in LN for ram semen.
Publisher Correction: Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes
Authors: De Talhouet Solene , Peron Julien , Vuilleumier Aurelie , Friedlaender Alex , Viassolo Valeria , Ayme Aurélie , Bodmer Alexandre , Treilleux Isabelle , Lang Noemie , Tille Jean-Christophe , Chappuis Pierre O. , Buisson Adrien , Giraud Sophie , Lasset Christine , Bonadona Valerie , Trédan Olivier , Labidi-Galy S. Intidhar
Published: November 2020

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