bluuebunny/crossref_metadata_2025 huggingface dataset:
ATXN2L upregulated by epidermal growth factor promotes gastric cancer cell invasiveness and oxaliplatin resistance
Authors: Lin Li , Li Xiaoyin , Pan Changqie , Lin Wanying , Shao Ruoyang , Liu Yantan , Zhang Junhao , Luo Yuhao , Qian Kai , Shi Min , Bin Jianping , Liao Yulin , Liao Wangjun
Published: February 2019

For gastric cancer (GC) control, metastasis and chemoresistance are the major challenges, accompanied with various stresses. Ataxin-2-like (ATXN2L) was discovered as a novel regulator of stress granules, yet its function in cancers remained unknown. Hence, we wanted to explore the functions of ATXN2L to see whether it participates in stress-related cancer malignant activities. Clinical follow-up was performed to see the impact of ATXN2L on GC patient survival. As a result, ATXN2L expression was upregulated in GC tissue and indicated adverse prognosis for overall survival and recurrence. In GC cells, ATXN2L expression was knocked down and functional experiments were performed. ATXN2L promoted GC cell migration and invasion via epithelial to mesenchymal transition, yet no influence on proliferation was detected by ATXN2L interference. When adding the chemotherapeutic agent oxaliplatin to induce stress, silencing ATXN2L sensitized GC cells to oxaliplatin. Interestingly, oxaliplatin was found to in turn promote ATXN2L expression and stress granule assembly. Then, two acquired oxaliplatin-resistant strains were generated by long-term oxaliplatin induction. The oxaliplatin-resistant strains presented with elevated ATXN2L levels, while silencing ATXN2L in the strains reversed the oxaliplatin resistance by increasing reactive oxygen species production and apoptosis. These results suggested that ATXN2L was responsible for not only intrinsic but also acquired oxaliplatin chemoresistance. Finally, ATXN2L-related signaling was screened using bioinformatic methods, and epidermal growth factor (EGF) was verified to promote ATXN2L expression via PI3K/Akt signaling activation. Blocking EGFR/ATXN2L signaling reversed GC cell oxaliplatin resistance and inhibited migration. In conclusion, ATXN2L promotes cell invasiveness and oxaliplatin resistance and can be upregulated by EGF via PI3K/Akt signaling. ATXN2L may be an indicator and therapeutic target in GC, especially for oxaliplatin-based chemotherapy.
Observation of parity-time symmetry breaking transitions in a dissipative Floquet system of ultracold atoms
Authors: Li Jiaming , Harter Andrew K. , Liu Ji , de Melo Leonardo , Joglekar Yogesh N. , Luo Le
Published: February 2019

Open physical systems with balanced loss and gain, described by non-Hermitian parity-time $$\left( {{\cal P}{\cal T}} \right)$$

P
T

reflection symmetric Hamiltonians, exhibit a transition which could engender modes that exponentially decay or grow with time, and thus spontaneously breaks the $${\cal P}{\cal T}$$
P
T
-symmetry. Such $${\cal P}{\cal T}$$
P
T
-symmetry-breaking transitions have attracted many interests because of their extraordinary behaviors and functionalities absent in closed systems. Here we report on the observation of $${\cal P}{\cal T}$$
P
T
-symmetry-breaking transitions by engineering time-periodic dissipation and coupling, which are realized through state-dependent atom loss in an optical dipole trap of ultracold 6Li atoms. Comparing with a single transition appearing for static dissipation, the time-periodic counterpart undergoes $${\cal P}{\cal T}$$
P
T
-symmetry breaking and restoring transitions at vanishingly small dissipation strength in both single and multiphoton transition domains, revealing rich phase structures associated to a Floquet open system. The results enable ultracold atoms to be a versatile tool for studying $${\cal P}{\cal T}$$
P
T
-symmetric quantum systems.
Outcomes of controlled human malaria infection after BCG vaccination
Authors: Walk Jona , de Bree L. Charlotte J. , Graumans Wouter , Stoter Rianne , van Gemert Geert-Jan , van de Vegte-Bolmer Marga , Teelen Karina , Hermsen Cornelus C. , Arts Rob J. W. , Behet Marije C. , Keramati Farid , Moorlag Simone J. C. F. M. , Yang Annie S. P. , van Crevel Reinout , Aaby Peter , de Mast Quirijn , van der Ven André J. A. M. , Stabell Benn Christine , Netea Mihai G. , Sauerwein Robert W.
Published: February 2019

Recent evidence suggests that certain vaccines, including Bacillus-Calmette Guérin (BCG), can induce changes in the innate immune system with non-specific memory characteristics, termed ‘trained immunity’. Here we present the results of a randomised, controlled phase 1 clinical trial in 20 healthy male and female volunteers to evaluate the induction of immunity and protective efficacy of the anti-tuberculosis BCG vaccine against a controlled human malaria infection. After malaria challenge infection, BCG vaccinated volunteers present with earlier and more severe clinical adverse events, and have significantly earlier expression of NK cell activation markers and a trend towards earlier phenotypic monocyte activation. Furthermore, parasitemia in BCG vaccinated volunteers is inversely correlated with increased phenotypic NK cell and monocyte activation. The combined data demonstrate that BCG vaccination alters the clinical and immunological response to malaria, and form an impetus to further explore its potential in strategies for clinical malaria vaccine development.
Additively manufacturable micro-mechanical logic gates
Authors: Song Yuanping , Panas Robert M. , Chizari Samira , Shaw Lucas A. , Jackson Julie A. , Hopkins Jonathan B. , Pascall Andrew J.
Published: February 2019

Early examples of computers were almost exclusively based on mechanical devices. Although electronic computers became dominant in the past 60 years, recent advancements in three-dimensional micro-additive manufacturing technology provide new fabrication techniques for complex microstructures which have rekindled research interest in mechanical computations. Here we propose a new digital mechanical computation approach based on additively-manufacturable micro-mechanical logic gates. The proposed mechanical logic gates (i.e., NOT, AND, OR, NAND, and NOR gates) utilize multi-stable micro-flexures that buckle to perform Boolean computations based purely on mechanical forces and displacements with no electronic components. A key benefit of the proposed approach is that such systems can be additively fabricated as embedded parts of microarchitected metamaterials that are capable of interacting mechanically with their surrounding environment while processing and storing digital data internally without requiring electric power.
Making silver a stronger n-dopant than cesium via in situ coordination reaction for organic electronics
Authors: Bin Zhengyang , Dong Guifang , Wei Pengcheng , Liu Ziyang , Zhang Dongdong , Su Rongchuan , Qiu Yong , Duan Lian
Published: February 2019

N-doping is an effective way to increase the electron conductivity of organic semiconductors and achieve ohmic cathode contacts in organic electronics. To avoid the use of difficult-to-handle highly reactive n-dopants, air-stable precursors are widely used nowadays, which could decompose to release reactive species in a subtractive way though always with unwanted and even harmful byproducts during processing. Here, we show that air-stable metals, such as copper, silver and gold, could release free electrons readily in the presence of chelating ligands, as the irreversible coordination reaction between metal ions and the ligands would push the equilibrium between metals and metal ions to the forward direction. By using a well-designed multi-functional electron transport material with a strong nucleophilic quality, 4,7-dimethoxy-1,10-phenanthroline (p-MeO-Phen), silver could function as an n-dopant stronger than cesium and could be used to fabricate organic light-emitting diodes with higher performance than the cesium-doped control device.
Full-color laser displays based on organic printed microlaser arrays
Authors: Zhao Jinyang , Yan Yongli , Gao Zhenhua , Du Yuxiang , Dong Haiyun , Yao Jiannian , Zhao Yong Sheng
Published: February 2019

Laser displays, which exploit characteristic advantages of lasers, represent a promising next-generation display technology based on the ultimate visual experience they provide. However, the inability to obtain pixelated laser arrays as self-emissive full-color panels hinders the application of laser displays in the flat-panel sector. Due to their excellent optoelectronic properties and processability, organic materials have great potential for the production of periodically patterned multi-color microlaser arrays. Here, we demonstrate for the first time full-color laser displays on precisely patterned organic red-green-blue (RGB) microlaser matrices through inkjet printing. Individual RGB laser pixels are realized by doping respective luminescent dyes into the ink materials, resulting in a wide achievable color gamut 45% larger than the standard RGB space. Using as-prepared microlaser arrays as full-color panels, we achieve dynamic laser displays for video playing through consecutive beam scanning. These results represent a major step towards full-color laser displays with outstanding color expression.
Tailoring vertical phase distribution of quasi-two-dimensional perovskite films via surface modification of hole-transporting layer
Authors: Liu Tiefeng , Jiang Youyu , Qin Minchao , Liu Junxue , Sun Lulu , Qin Fei , Hu Lin , Xiong Sixing , Jiang Xueshi , Jiang Fangyuan , Peng Ping , Jin Shengye , Lu Xinhui , Zhou Yinhua
Published: February 2019

Vertical phase distribution plays an important role in the quasi-two-dimensional perovskite solar cells. So far, the driving force and how to tailor the vertical distribution of layer numbers have been not discussed. In this work, we report that the vertical distribution of layer numbers in the quasi-two-dimensional perovskite films deposited on a hole-transporting layer is different from that on glass substrate. The vertical distribution could be explained by the sedimentation equilibrium because of the colloidal feature of the perovskite precursors. Acid addition will change the precursors from colloid to solution that therefore changes the vertical distribution. A self-assembly layer is used to modify the acidic surface property of the hole-transporting layer that induces the appearance of desired vertical distribution for charge transport. The quasi-two-dimensional perovskite cells with the surface modification display a higher open-circuit voltage and a higher efficiency comparing to reference quasi-two-dimensional cells.
Author Correction: Biofortification of field-grown cassava by engineering expression of an iron transporter and ferritin
Authors: Narayanan Narayanan , Beyene Getu , Chauhan Raj Deepika , Gaitán-Solís Eliana , Gehan Jackson , Butts Paula , Siritunga Dimuth , Okwuonu Ihuoma , Woll Arthur , Jiménez-Aguilar Dulce M. , Boy Erick , Grusak Michael A. , Anderson Paul , Taylor Nigel J.
Published: February 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Biological Characterization of Computationally Designed Analogs of peptide TVFTSWEEYLDWV (Pep2-8) with Increased PCSK9 Antagonistic Activity
Authors: Lammi Carmen , Sgrignani Jacopo , Arnoldi Anna , Grazioso Giovanni
Published: February 2019

The inhibition of the PCSK9/LDLR protein-protein interaction (PPI) is a promising strategy for developing new hypocholesterolemic agents. Recently, new antibodies have been approved for therapy, but the high cost and low patients’ compliance stimulate the development of alternatives. Starting from the structural information available for the complex between PCSK9 and TVFTSWEEYLDWV (Pep2-8) peptide inhibitor and using computational methods, in this work we identified two Pep2-8 analogs as potential inhibitors of the PCSK9/LDLR PPI. Their biological characterization confirmed the theoretical outcomes. Remarkably, the treatment of HepG2 cells with these peptides increased the LDLR protein level on the cellular membrane, with activities that were 100 and 50 times better than the one of Pep2-8 tested at a 50 μM concentration. Moreover, they were 50 and 5 times more active than Pep2-8 in improving the functional ability of HepG2 cells to uptake extracellular LDL.
Revealing the Hippocampal Connectome through Super-Resolution 1150-Direction Diffusion MRI
Authors: Maller Jerome J. , Welton Thomas , Middione Matthew , Callaghan Fraser M. , Rosenfeld Jeffrey V. , Grieve Stuart M.
Published: February 2019

The hippocampus is a key component of emotional and memory circuits and is broadly connected throughout the brain. We tracked the whole-brain connections of white matter fibres from the hippocampus using ultra-high angular resolution diffusion MRI in both a single 1150-direction dataset and a large normal cohort (n = 94; 391-directions). Using a connectomic approach, we identified six dominant pathways in terms of strength, length and anatomy, and characterised them by their age and gender variation. The strongest individual connection was to the ipsilateral thalamus. There was a strong age dependence of hippocampal connectivity to medial occipital regions. Overall, our results concur with preclinical and ex-vivo data, confirming that meaningful in vivo characterisation of hippocampal connections is possible in an individual. Our findings extend the collective knowledge of hippocampal anatomy, highlighting the importance of the spinal-limbic pathway and the striking lack of hippocampal connectivity with motor and sensory cortices.
Three-Dimensional Textile Platform for Electrochemical Devices and its Application to Dye-Sensitized Solar Cells
Authors: Yun Min Ju , Sim Yeon Hyang , Cha Seung I. , Seo Seon Hee , Lee Dong Yoon
Published: February 2019

The demand for easy-to-use portable electric devices that are combined with essential items in everyday life, such as apparel, has increased. Hence, significant research has been conducted into the development of wearable technology by fabrication of electronic devices with a textile structure based on fiber or fabric. However, the challenge to develop a fabrication method for wearable devices based on weaving or sewing technology still remains. In this study, we have proposed and fabricated a 3-D textile with two electrodes and one spacer in a single sheet of fabric, utilizing a commercial weaving machine. The two electrodes fulfil the role of electron transfer and the spacer between the electrodes circulates electrons and prevents electrical shorting. Hence, the 3-D textile could be applied to a wide range of electrochemical devices. In addition, it is possible to control the textile structure, size and quantity and change the electrode or spacer materials by replacing the thread. We applied the 3-D textile to dye-sensitized solar cells (DSSCs) which has distinctive advantages such as low manufacturing cost, esthetic appearance for interior or exterior application and high power output under relatively weak light illuminations. The 3-D textile DSSCs were fabricated through a continuous process, from manufacturing to encapsulation, using a non-volatile electrolyte and demonstrated a specific power of 1.7% (1 sun, 1.5 A.M.). The 3-D textile DSSCs were electrically connected in parallel and series by twisting, stainless steel wires, which were used as the weft, and a light-emitting diode lamp was turned on using 3-D textile DSSCs connected in series. This study represents the first stage in the development and application of wearable textile devices.
CXCR4 signaling regulates metastatic onset by controlling neutrophil motility and response to malignant cells
Authors: Tulotta C. , Stefanescu C. , Chen Q. , Torraca V. , Meijer A. H. , Snaar-Jagalska B. E.
Published: February 2019

Developing tumors interact with the surrounding microenvironment. Myeloid cells exert both anti- and pro-tumor functions and chemokines are known to drive immune cell migration towards cancer cells. It is documented that CXCR4 signaling supports tumor metastasis formation in tissues where CXCL12, its cognate ligand, is abundant. On the other hand, the role of the neutrophilic CXCR4 signaling in driving cancer invasion and metastasis formation is poorly understood. Here, we use the zebrafish xenotransplantation model to study the role of CXCR4 signaling in driving the interaction between invasive human tumor cells and host neutrophils, supporting early metastasis formation. We found that zebrafish cxcr4 (cxcr4b) is highly expressed in neutrophils and experimental micrometastases fail to form in mutant larvae lacking a functional Cxcr4b. We demonstrated that Cxcr4b controls neutrophil number and motility and showed that Cxcr4b transcriptomic signature relates to motility and adhesion regulation in neutrophils in tumor-naïve larvae. Finally, Cxcr4b deficient neutrophils failed to interact with cancer cells initiating early metastatic events. In conclusion, we propose that CXCR4 signaling supports the interaction between tumor cells and host neutrophils in developing tumor metastases. Therefore, targeting CXCR4 on tumor cells and neutrophils could serve as a double bladed razor to limit cancer progression.
Mapping Natural Dyes in Archeological Textiles by Imaging Mass Spectrometry
Authors: Kramell Annemarie Elisabeth , García-Altares María , Pötsch Maria , Kluge Ralph , Rother Annekatrin , Hause Gerd , Hertweck Christian , Csuk René
Published: February 2019

Organic dyes of animal and plant origin have often been used by our ancestors to create textiles with polychromic ornamental patterns, and dyestuff analyses reveal how ancient cultures used these natural colorants. Mass spectrometry can characterize ancient colorants from these textiles, but its combination with separation techniques such as liquid chromatography requires the destruction of the pattern to extract organic dyes from the fabrics. In this study we applied mass spectrometry imaging (MS imaging) on colorful patterned textiles to show the spatial distribution of indigo-type and anthraquinone-type dyes. We evaluated different sample preparation techniques for matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)-MS imaging, e.g. the production of imprints in TLC (thin layer chromatography) aluminum sheets and the embedding of the material in Technovit7100 to produce thin sections. Our protocol enabled the detection of indigo-type dyes directly on a historic textile of more than 2,000 years old embedded in Technovit7100. This is the first-time application of MALDI-TOF-MS imaging to map different organic dyestuffs on archeological remains.
Oncosuppressor-Mutated Cells as a Liquid Biopsy Test for Cancer-Screening
Authors: Abdouh Mohamed , Gao Zu-Hua , Arena Vincenzo , Arena Manuel , Burnier Miguel N. , Arena Goffredo Orazio
Published: February 2019

We reported on the ability of immortalized or oncosuppressor-mutated cells (OMCs) to uptake circulating cancer-factors and give tumors when transplanted into mice. This led to the first biological based liquid biopsy test, which we called MATER-D platform. In the present study, we showed for the first time that a different type of OMCs (PTEN-deficient human epithelial MCF10A cells) turn malignant when exposed to cancer patient’s sera, confirming the concept that different cells with diverse oncosuppressor mutations can uptake cancer factors and be used in biological based liquid biopsy tests. Our observations were confirmed in a large variety of solid and haematological malignancies. This test was able to detect dysplasia and carcinomas in situ lesions in different organs and circulating factors in cancer patients years after the removal of their lesions. To our knowledge, this ability is unique and not shared by other liquid biopsy platforms. Immunohistochemistry analysis of the xenotransplants revealed identical patterns of differentiation regardless of the cancer type, showing that differentiation through horizontal transfer might be dependent on the nature of the target cells rather than the type of cancer factors. These data strengthen the notion that OMC-based liquid biopsy tests might be promising platforms for cancer screening.
Explaining the unique nature of individual gait patterns with deep learning
Authors: Horst Fabian , Lapuschkin Sebastian , Samek Wojciech , Müller Klaus-Robert , Schöllhorn Wolfgang I.
Published: February 2019

Machine learning (ML) techniques such as (deep) artificial neural networks (DNN) are solving very successfully a plethora of tasks and provide new predictive models for complex physical, chemical, biological and social systems. However, in most cases this comes with the disadvantage of acting as a black box, rarely providing information about what made them arrive at a particular prediction. This black box aspect of ML techniques can be problematic especially in medical diagnoses, so far hampering a clinical acceptance. The present paper studies the uniqueness of individual gait patterns in clinical biomechanics using DNNs. By attributing portions of the model predictions back to the input variables (ground reaction forces and full-body joint angles), the Layer-Wise Relevance Propagation (LRP) technique reliably demonstrates which variables at what time windows of the gait cycle are most relevant for the characterisation of gait patterns from a certain individual. By measuring the time-resolved contribution of each input variable to the prediction of ML techniques such as DNNs, our method describes the first general framework that enables to understand and interpret non-linear ML methods in (biomechanical) gait analysis and thereby supplies a powerful tool for analysis, diagnosis and treatment of human gait.
TRIB1 and TRPS1 variants, G × G and G × E interactions on serum lipid levels, the risk of coronary heart disease and ischemic stroke
Authors: Zhang Qing-Hui , Yin Rui-Xing , Chen Wu-Xian , Cao Xiao-Li , Wu Jin-Zhen
Published: February 2019

This study aimed to assess the association of the tribbles pseudokinase 1 (TRIB1) and transcriptional repressor GATA binding 1 (TRPS1) single nucleotide polymorphisms (SNPs) and the gene-gene (G × G) and gene-environment (G × E) interactions with serum lipid levels, the risk of coronary heart disease (CHD) and ischemic stroke (IS) in the Guangxi Han population. Genotyping of the rs2954029, rs2980880, rs10808546, rs231150, rs2737229 and rs10505248 SNPs was performed in 625 controls and 1146 unrelated patients (CHD, 593 and IS, 553). The genotypic and allelic frequencies of some SNPs were different between controls and patients (CHD, rs2954029 and rs231150; IS, rs2954029 and rs2980880; P < 0.05-0.01). Two SNPs were associated with increased risk of CHD (rs2954029 and rs231150) and IS (rs2954029) in different genetic models. Several SNPs in controls were associated with total cholesterol (rs2954029, rs2980880 and rs2737229), triglyceride (rs2954029 and rs10808546), low-density lipoprotein cholesterol (rs2954029), high-density lipoprotein cholesterol (rs2980880 and rs231150) and apolipoprotein A1 (rs2737229) levels. The rs2954029TA/AA-age (>60 year) interaction increased the risk of CHD, whereas the rs10808546CT/TT-drinking interaction decreased the risk of IS. The rs2954029A-rs2980880C-rs10808546C haplotype was associated with increased risk of CHD and IS. The rs2954029A-rs2980880T-rs10808546C haplotype was associated with increased risk of CHD. The rs2954029-rs231150 interactions had an increased risk of both CHD and IS. These results suggest that several TRIB1 and TRPS1 SNPs were associated with dyslipidemia and increased risk of CHD and IS in our study population. The G × G and G × E interactions on serum lipid levels, and the risk of CHD and IS were also observed.
Hydrophilic Quantum Dots Functionalized with Gd(III)-DO3A Monoamide Chelates as Bright and Effective T1-weighted Bimodal Nanoprobes
Authors: Pereira Maria I. A. , Pereira Goreti , Monteiro Camila A. P. , Geraldes Carlos F. G. C. , Cabral Filho Paulo E. , Cesar Carlos L. , de Thomaz André A. , Santos Beate S. , Pereira Giovannia A. L. , Fontes Adriana
Published: February 2019

Magnetic resonance imaging (MRI) is a powerful non-invasive diagnostic tool that enables distinguishing healthy from pathological tissues, with high anatomical detail. Nevertheless, MRI is quite limited in the investigation of molecular/cellular biochemical events, which can be reached by fluorescence-based techniques. Thus, we developed bimodal nanosystems consisting in hydrophilic quantum dots (QDs) directly conjugated to Gd(III)-DO3A monoamide chelates, a Gd(III)-DOTA derivative, allowing for the combination of the advantages of both MRI and fluorescence-based tools. These nanoparticulate systems can also improve MRI contrast, by increasing the local concentration of paramagnetic chelates. Transmetallation assays, optical characterization, and relaxometric analyses, showed that the developed bimodal nanoprobes have great chemical stability, bright fluorescence, and high relaxivities. Moreover, fluorescence correlation spectroscopy (FCS) analysis allowed us to distinguish nanosystems containing different amounts of chelates/QD. Also, inductively coupled plasma optical emission spectrometry (ICP – OES) indicated a conjugation yield higher than 75%. Our nanosystems showed effective longitudinal relaxivities per QD and per paramagnetic ion, at least 5 times [per Gd(III)] and 100 times (per QD) higher than the r1 for Gd(III)-DOTA chelates, suitable for T1-weighted imaging. Additionally, the bimodal nanoparticles presented negligible cytotoxicity, and efficiently labeled HeLa cells as shown by fluorescence. Thus, the developed nanosystems show potential as strategic probes for fluorescence analyses and MRI, being useful for investigating a variety of biological processes.
A diet-change modulates the previously established bacterial gut community in juvenile brown trout (Salmo trutta)
Authors: Michl Stéphanie C. , Beyer Matt , Ratten Jenni-Marie , Hasler Mario , LaRoche Julie , Schulz Carsten
Published: February 2019

The aim of the present study was to investigate the impact of dietary plant proteins on the gut microbiome of first feeding brown trout (Salmo trutta) reproduced from wild stocks and to evaluate whether the initial microbiome of brown trout fry can be permanently manipulated by the first feeding diet. Therefore, brown trout fry was fed diets based on either 0%, 50% or 90% plant-derived proteins from first feeding onwards and via 16S rRNA gene sequencing a strong dietary influence on the bacterial gut community on phylum and order level was detected. Proteobacteria and Fusobacteria were significantly enhanced when fishmeal was integrated into the experimental diet, whereas plant-derived proteins significantly promoted Firmicutes and Bacteroidetes. In order to evaluate whether the first feeding diet had a permanent effect on the initially established microbial gut community of juvenile brown trout, a cross-over diet-change was applied 61 days post first feeding. 48 days after the diet-change, the gut microbiome of all dietary groups was significantly different from the one initially established after first feeding. Moreover, the first feeding diet had no statistically significant influence on the gut microbiome after the diet-change, demonstrating no permanent effect on the gut microbiome formation.
Aerosol emission and superemission during human speech increase with voice loudness
Authors: Asadi Sima , Wexler Anthony S. , Cappa Christopher D. , Barreda Santiago , Bouvier Nicole M. , Ristenpart William D.
Published: February 2019

Mechanistic hypotheses about airborne infectious disease transmission have traditionally emphasized the role of coughing and sneezing, which are dramatic expiratory events that yield both easily visible droplets and large quantities of particles too small to see by eye. Nonetheless, it has long been known that normal speech also yields large quantities of particles that are too small to see by eye, but are large enough to carry a variety of communicable respiratory pathogens. Here we show that the rate of particle emission during normal human speech is positively correlated with the loudness (amplitude) of vocalization, ranging from approximately 1 to 50 particles per second (0.06 to 3 particles per cm3) for low to high amplitudes, regardless of the language spoken (English, Spanish, Mandarin, or Arabic). Furthermore, a small fraction of individuals behaves as “speech superemitters,” consistently releasing an order of magnitude more particles than their peers. Our data demonstrate that the phenomenon of speech superemission cannot be fully explained either by the phonic structures or the amplitude of the speech. These results suggest that other unknown physiological factors, varying dramatically among individuals, could affect the probability of respiratory infectious disease transmission, and also help explain the existence of superspreaders who are disproportionately responsible for outbreaks of airborne infectious disease.
Mosaic dental morphology in a terminal Pleistocene hominin from Dushan Cave in southern China
Authors: Liao Wei , Xing Song , Li Dawei , Martinón-Torres María , Wu Xiujie , Soligo Christophe , Bermúdez de Castro José María , Wang Wei , Liu Wu
Published: February 2019

Recent studies reveal high degrees of morphological diversity in Late Pleistocene humans from East Asia. This variability was interpreted as complex demographic patterns with several migrations and possible survival of archaic groups. However, lack of well-described, reliably classified and accurately dated sites has seriously limited understanding of human evolution in terminal Pleistocene. Here we report a 15,000 years-oldH. sapiens(Dushan 1) in South China with unusual mosaic features, such as large dental dimensions, cingulum-like structures at the dentine level in the posterior dentition and expression of a “crown buccal vertical groove complex”, all of which are uncommon in modern humans and more typically found in Middle Pleistocene archaic humans. They could represent the late survival of one of the earliest modern humans to settle in an isolated region of southern China and, hence, the retention of primitive-like traits. They could also represent a particularity of this group and, hence, reflect a high degree of regional variation. Alternatively, these features may be the result of introgression from some late-surviving archaic population in the region. Our study demonstrates the extreme variability of terminal Pleistocene populations in China and the possibility of a complex demographic story in the region.
The neurobiology of placebo effects in sports: EEG frontal alpha asymmetry increases in response to a placebo ergogenic aid
Authors: Broelz Ellen K. , Enck Paul , Niess Andreas M. , Schneeweiss Patrick , Wolf Sebastian , Weimer Katja
Published: February 2019

The performance enhancing (ergogenic) placebo effect is elicited by an inert treatment and caused by positive affective appraisal of effort perception. Frontal alpha asymmetry (FAA) is a neurobiological correlate of positive affect. This study investigates, whether receiving an ergogenic placebo increases FAA and whether scores on the behavioral inhibition and activation system (BIS/BAS) scales affect this increase in FAA. Nineteen competitive male cyclists (37.26 ± 9.82 years) performed two maximum effort time trials. The first served as baseline for the second intervention time trial, where athletes received a placebo ergogenic aid or no treatment. We recorded FAA using EEG throughout all time trials and assessed BIS/BAS by questionnaire. There was a significant difference in change from baseline to intervention time trial in FAA during cycling in response to the placebo ergogenic aid compared to the control group. BIS, the BAS subscale Drive and the BAS-BIS difference score significantly co-varied with the change in FAA from baseline to intervention time trial in response to the placebo ergogenic aid. Administering a placebo ergogenic aid significantly influenced FAA during maximum effort cycling. Those athletes with a more pronounced goal seeking persistence and an overall dominance of the BAS over the BIS showed a significantly greater increase in FAA in response to a placebo ergogenic aid. A more pronounced BIS, however, seems to antagonize the increase in FAA associated with the ergogenic placebo response.
Nitrogen availability alters flavonoid accumulation in Cyclocarya paliurus via the effects on the internal carbon/nitrogen balance
Authors: Deng Bo , Li Yuanyuan , Xu Dandan , Ye Qingqing , Liu Guihua
Published: February 2019

Cyclocarya paliurus has traditionally been used in medicines and nutraceutical foods. The aims of this study were to determine whether flavonoid accumulation in C. paliurus is dependent on nitrogen (N) availability and to investigate the internal C (carbon)/N balance under controlled conditions. One-year-old seedlings were grown under five increasing available N level treatments (N1–5) and were harvested throughout the 15-d experimental period. The greatest total chlorophyll amount and photosynthetic rate were achieved during the intermediate N treatments (N3 and N4). The greatest starch level was detected in N3. The total C level was relatively stable, but the total N and free amino acid levels increased, which resulted in a decreased C:N ratio. The flavonoid contents in roots and stalks decreased, while leaves showed a different pattern (peaking in N3). The flavonoid level was closely correlated with flavanone-3-hydroxylase activity, which displayed a similar variation pattern, and their levels were significantly positively correlated with those of total C and starch. Thus, the partitioning of C among primary and secondary metabolisms could be responsible for flavonoid biosynthesis and provide the basis for maintaining high yields, which increases the nutritional values of crops and medicinal plants.
Extreme sensitivity in Snowball Earth formation to mountains on PaleoProterozoic supercontinents
Authors: Walsh Amber , Ball Thomas , Schultz David M.
Published: February 2019

During the PaleoProterozoic 2.45 to 2.2 billion years ago, several glaciations may have produced Snowball Earths. These glacial cycles occurred during large environmental change when atmospheric oxygen was increasing, a supercontinent was assembled from numerous landmasses, and collisions between these landmasses formed mountain ranges. Despite uncertainties in the composition of the atmosphere and reconstruction of the landmasses, paleoclimate model simulations can test the sensitivity of the climate to producing a Snowball Earth. Here we present a series of simulations that vary the atmospheric methane concentration and latitudes of west–east-oriented mountain ranges on an idealised supercontinent. For a given methane concentration, the latitudes of mountains control whether a Snowball Earth forms or not. Significantly, mountains in middle latitudes inhibited Snowball Earth formation, and mountains in low latitudes promoted Snowball Earth formation, with the supercontinent with mountains at ±30° being most conducive to forming a Snowball Earth because of reduced albedo at low latitudes. We propose that the extreme sensitivity of a Snowball Earth to reconstructions of the paleogeography and paleoatmospheric composition may explain the observed glaciations, demonstrating the importance of high-quality reconstructions to improved understanding of this early period in Earth’s history.
Members of the endocannabinoid system are distinctly regulated in inflammatory bowel disease and colorectal cancer
Authors: Grill Magdalena , Högenauer Christoph , Blesl Andreas , Haybaeck Johannes , Golob-Schwarzl Nicole , Ferreirós Nerea , Thomas Dominique , Gurke Robert , Trötzmüller Martin , Köfeler Harald C. , Gallé Birgit , Schicho Rudolf
Published: February 2019

Preclinical studies have demonstrated that the endocannabinoid system (ECS) plays an important role in the protection against intestinal inflammation and colorectal cancer (CRC); however, human data are scarce. We determined members of the ECS and related components of the ‘endocannabinoidome’ in patients with inflammatory bowel disease (IBD) and CRC, and compared them to control subjects. Anandamide (AEA) and oleoylethanolamide (OEA) were increased in plasma of ulcerative colitis (UC) and Crohn’s disease (CD) patients while 2-arachidonoylglycerol (2-AG) was elevated in patients with CD, but not UC. 2-AG, but not AEA, PEA and OEA, was elevated in CRC patients. Lysophosphatidylinositol (LPI) 18:0 showed higher levels in patients with IBD than in control subjects whereas LPI 20:4 was elevated in both CRC and IBD. Gene expression in intestinal mucosal biopsies revealed different profiles in CD and UC. CD, but not UC patients, showed increased gene expression for the 2-AG synthesizing enzyme diacylglycerol lipase alpha. Transcripts of CNR1 and GPR119 were predominantly decreased in CD. Our data show altered plasma levels of endocannabinoids and endocannabinoid-like lipids in IBD and CRC and distinct transcript profiles in UC and CD. We also report alterations for less known components in intestinal inflammation, such as GPR119, OEA and LPI.
Green light irradiation during sex differentiation induces female-to-male sex reversal in the medaka Oryzias latipes
Authors: Hayasaka Oki , Takeuchi Yutaka , Shiozaki Kazuhiro , Anraku Kazuhiko , Kotani Tomonari
Published: February 2019

This study investigated whether irradiation of a specific light wavelength could affect the sex differentiation of fish. We first found that the photoreceptor genes responsible for receiving red, green, and ultraviolet light were expressed in the eyes of medaka during the sex differentiation period. Second, we revealed that testes developed in 15.9% of genotypic females reared under green light irradiation. These female-to-male sex-reversed fish (i.e. neo-males) showed male-specific secondary sexual characteristics and produced motile sperm. Finally, progeny tests using the sperm of neo-males (XX) and eggs of normal females (XX) revealed that all F1 offspring were female, indicating for the first time in animals that irradiation with light of a specific wavelength can trigger sex reversal.
Measurement of Regional 2D Gas Transport Efficiency in Rabbit Lung Using Hyperpolarized 129Xe MRI
Authors: Ruppert Kai , Xin Yi , Hamedani Hooman , Amzajerdian Faraz , Loza Luis , Achekzai Tahmina , Duncan Ian F. , Profka Harrilla , Siddiqui Sarmad , Pourfathi Mehrdad , Sertic Federico , Cereda Maurizio F. , Kadlecek Stephen , Rizi Rahim R.
Published: February 2019

While hyperpolarized xenon-129 (HXe) MRI offers a wide array of tools for assessing functional aspects of the lung, existing techniques provide only limited quantitative information about the impact of an observed pathology on overall lung function. By selectively destroying the alveolar HXe gas phase magnetization in a volume of interest and monitoring the subsequent decrease in the signal from xenon dissolved in the blood inside the left ventricle of the heart, it is possible to directly measure the contribution of that saturated lung volume to the gas transport capacity of the entire lung. In mechanically ventilated rabbits, we found that both xenon gas transport and transport efficiency exhibited a gravitation-induced anterior-to-posterior gradient that disappeared or reversed direction, respectively, when the animal was turned from supine to prone position. Further, posterior ventilation defects secondary to acute lung injury could be re-inflated by applying positive end expiratory pressure, although at the expense of decreased gas transport efficiency in the anterior volumes. These findings suggest that our technique might prove highly valuable for evaluating lung transplants and lung resections, and could improve our understanding of optimal mechanical ventilator settings in acute lung injury.
Water-accelerated π-Stacking Reaction in Benzene Cluster Cation
Authors: Tachikawa Hiroto , Iura Ryoshu , Kawabata Hiroshi
Published: February 2019

Single molecule electron devices (SMEDs) have been widely studied through both experiments and theoretical calculations because they exhibit certain specific properties that general macromolecules do not possess. In actual SMED systems, a residual water molecule strongly affects the electronic properties of the SMED, even if only one water molecule is present. However, information about the effect of H2O molecules on the electronic properties of SMEDs is quite limited. In the present study, the effect of H2O on the ON-OFF switching property of benzene-based molecular devices was investigated by means of a direct ab initio molecular dynamics (AIMD) method. T- and H-shaped benzene dimers and trimers were examined as molecular devices. The present calculations showed that a H2O molecule accelerates the π-stacking formation in benzene molecular electronic systems. The times of stacking formation in a benzene dimer cation (n = 2) were calculated to be 460 fs (H2O) and 947 fs (no-H2O), while those in a trimer cation (n = 3) were 551 fs (H2O) and 1019 fs (no-H2O) as an average of the reaction time. This tendency was not dependent on the levels of theory used. Thus, H2O produced positive effects in benzene-based molecular electronics. The mechanism of π-stacking was discussed based on the theoretical results.
Magnetic-Field-Induced Suppression of Jahn-Teller Phonon Bands in (La0.6Pr0.4)0.7Ca0.3MnO3: the Mechanism of Colossal Magnetoresistance shown by Raman Spectroscopy
Authors: Merten S. , Shapoval O. , Damaschke B. , Samwer K. , Moshnyaga V.
Published: February 2019

A long-standing issue in the physics of the colossal magnetoresistance is the role of electron-phonon coupling, which manifests itself as Jahn-Teller polarons. The origin and architecture of polarons makes it possible to study their behavior by Raman spectroscopy, which allows to analyze the polaronic behavior in an applied magnetic field. We performed magnetic-field-dependent Raman spectroscopy on thin films of (La0.6Pr0.4)0.7Ca0.3MnO3 in a range of H = 0–50 kOe and compared the obtained Raman spectra with the magnetic field behavior of the electrical resistivity. In the vicinity of the Curie temperature, TC = 197 K, the intensity of the Jahn-Teller stretching mode at 614 cm−1 and of the bending mode at 443 cm−1 was found to be suppressed and enhanced, respectively. This observed behavior has a remarkable similarity with the field and temperature dependence of the colossal magnetoresistance in (La0.6Pr0.4)0.7Ca0.3MnO3. Our work provides direct evidence that the reduction of the amount of Jahn-Teller polarons at the phase transition is the main mechanism underlying the colossal magnetoresistance.
The impact of proliferation-migration tradeoffs on phenotypic evolution in cancer
Authors: Gallaher Jill A. , Brown Joel S. , Anderson Alexander R. A.
Published: February 2019

Tumors are not static masses of cells but dynamic ecosystems where cancer cells experience constant turnover and evolve fitness-enhancing phenotypes. Selection for different phenotypes may vary with (1) the tumor niche (edge or core), (2) cell turnover rates, (3) the nature of the tradeoff between traits, and (4) whether deaths occur in response to demographic or environmental stochasticity. Using a spatially-explicit agent-based model, we observe how two traits (proliferation rate and migration speed) evolve under different tradeoff conditions with different turnover rates. Migration rate is favored over proliferation at the tumor’s edge and vice-versa for the interior. Increasing cell turnover rates slightly slows tumor growth but accelerates the rate of evolution for both proliferation and migration. The absence of a tradeoff favors ever higher values for proliferation and migration, while a convex tradeoff tends to favor proliferation, often promoting the coexistence of a generalist and specialist phenotype. A concave tradeoff favors migration at low death rates, but switches to proliferation at higher death rates. Mortality via demographic stochasticity favors proliferation, and environmental stochasticity favors migration. While all of these diverse factors contribute to the ecology, heterogeneity, and evolution of a tumor, their effects may be predictable and empirically accessible.
Natural ligand-nonmimetic inhibitors of the lipid-transfer protein CERT
Authors: Nakao Naoki , Ueno Masaharu , Sakai Shota , Egawa Daichi , Hanzawa Hiroyuki , Kawasaki Shohei , Kumagai Keigo , Suzuki Makoto , Kobayashi Shu , Hanada Kentaro
Published: February 2019

Lipid transfer proteins mediate inter-organelle transport of membrane lipids at organelle contact sites in cells, playing fundamental roles in the lipidome and membrane biogenesis in eukaryotes. We previously developed a ceramide-mimetic compound as a potent inhibitor of the ceramide transport protein CERT. Here we develop CERT inhibitors with structures unrelated to ceramide. To this aim, we identify a seed compound with no ceramide-like structure but with the capability of forming a hydrogen-bonding network in the ceramide-binding START domain, by virtual screening of ~3 × 106 compounds. We also establish a surface plasmon resonance-based system to directly determine the affinity of compounds for the START domain. Then, we subject the seed compound to a series of in silico docking simulations, efficient chemical synthesis, affinity analysis, protein-ligand co-crystallography, and various in vivo assays. This strategy allows us to obtain ceramide-unrelated compounds that potently inhibited the function of CERT in human cultured cells.
Halogen and chalcogen-bonding interactions in sulphur-rich π-electron acceptors
Authors: Le Gal Yann , Colas Adrien , Barrière Frédéric , Dorcet Vincent , Roisnel Thierry , Lorcy Dominique
Published: February 2019

Sulphur and iodine heteroatoms on the acceptor skeleton induce chalcogen⋯chalcogen and halogen-bonding interactions.
A Zn(ii) metal–organic framework with dinuclear [Zn2(N-oxide)2] secondary building units
Authors: Ochi Rika , Noro Shin-ichiro , Kubo Kazuya , Nakamura Takayoshi
Published: February 2019

A three-dimensional metal–organic framework with unprecedented [Zn2(N-oxide)2] secondary building units was synthesized using 3,5-pyridinedicarboxylic acid N-oxide.
Two metal–organic zeolites for highly sensitive and selective sensing of Tb3+
Authors: Li Meiling , Ren Guojian , Wang Fuxiang , Li Zhimeng , Yang Weiting , Gu Dongxu , Wang Yinghui , Zhu Guangshan , Pan Qinhe
Published: February 2019

Two metal–organic zeolites can sensitize the luminescence of the Tb3+ ion by energy transfer between the host frameworks and the guest Tb3+ ion, thus serving as Tb3+ ion sensors.
Influence of poly(lactide) stereocomplexes as nucleating agents on the crystallization behavior of poly(lactide)s
Authors: Ji Nuo , Hu Guang , Li Jianbo , Ren Jie
Published: February 2019

The influence of the addition of linear and four-arm poly(lactide) stereocomplexes on the crystallization behavior of poly(l-lactide) and poly(d-lactide) from the molten state was investigated.
Suppressing the formation of NOx and N2O in CO2/N2 dielectric barrier discharge plasma by adding CH4: scavenger chemistry at work
Authors: Snoeckx Ramses , Van Wesenbeeck Karen , Lenaerts Silvia , Cha Min Suk , Bogaerts Annemie
Published: February 2019

Significantly suppressing the in situ NOx formation during plasma based conversion of low-cost impure CO2 feeds, by adding chemical scavengers.
Laser-induced breakdown spectroscopy for the quantitative measurement of lithium concentration profiles in structured and unstructured electrodes
Authors: Smyrek Peter , Bergfeldt Thomas , Seifert Hans Jürgen , Pfleging Wilhelm
Published: February 2019

An advanced battery concept providing new diffusion pathways along the contour of electrode microstructures proved by 3D lithium elemental mapping.
Solid-state polymer electrolytes stabilized by task-specific salt additives
Authors: Zhao Qing , Chen Pengyu , Li Shuke , Liu Xiaotun , Archer Lynden A.
Published: February 2019

The interphases of the anode and cathode are stabilized by designing solid-state polymer electrolytes with salt additives.
Spiro-tBuBED: a new derivative of a spirobifluorene-based hole-transporting material for efficient perovskite solar cells
Authors: Lin Po-Han , Lee Kun-Mu , Ting Chang-Chieh , Liu Ching-Yuan
Published: February 2019

Perovskite solar cells using a new spirobifluorene core-based oligoaryl as the hole-transport layer display 18.6% efficiency without any device oxidation process.