bluuebunny/crossref_metadata_2025 huggingface dataset:
Eastern Mediterranean Deep Water Formation During Sapropel S1: A Reconstruction Using Geochemical Records Along a Bathymetric Transect in the Adriatic Outflow Region
Authors: Filippidi A. , De Lange G. J.
Published: March 2019

Eastern Mediterranean thermohaline circulation is directly influenced by middle‐ and low‐latitude climate systems. The dramatic paleoclimate changes during the last African Humid Period (~10–6 ka BP) were captured in Mediterranean sediments as the distinctly organic‐rich unit sapropel S1. Here, deepwater formation variability during S1 deposition is reconstructed. We use geochemical records of three cores along a bathymetric transect (775‐, 1,359‐, and 1,908‐m water depths), at the transition between the Adriatic DW‐ formation area and the Eastern Mediterranean. In all three cores, sedimentation rates are distinctly higher during S1, corresponding with enhanced runoff emanating from the Adriatic hinterland. Hence, major runoff did not only come from southern but also from northern borderlands in this period. During sapropel formation, enhanced levels of primary productivity occurred in the surface waters and oxygen‐depleted conditions in the bottom waters for all sites. Conditions for sediment and bottom‐water below ~1.4 km water depth were sulfidic throughout S1, but for intermediate depth (775 m) were anoxic only during the first part (S1a). Bottom‐water oxygenation interrupted S1 formation at water depths down to ~1.4 km, during two brief episodes, at 8.2 and 7.4 cal. ka BP. From the 7.4 cal. ka BP ventilation onward, the transition to more oxygenated bottom‐water conditions was more progressive for the intermediate water depth site (775 m) than for the deeper sites. Conditions remained fully oxic for all water depths following the S1‐MarkerBed ventilation event. Possibly, the onset of continuously oxic conditions started slightly earlier at intermediate depth (775 m; 6.6 ± 0.3 cal. ka BP) than at greater depths (1,359 m, 1,908 m; 6.0 ± 0.3 cal. ka BP).
Cellular energy stress induces AMPK-mediated regulation of glioblastoma cell proliferation by PIKE-A phosphorylation
Authors: Zhang Shuai , Sheng Hao , Zhang Xiaoya , Qi Qi , Chan Chi Bun , Li Leilei , Shan Changliang , Ye Keqiang
Published: March 2019

Phosphoinositide 3-kinase enhancer-activating Akt (PIKE-A), which associates with and potentiates Akt activity, is a pro-oncogenic factor that play vital role in cancer cell survival and growth. However, PIKE-A physiological functions under energy/nutrient deficiency are poorly understood. The AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that is a principal regulator of energy homeostasis and has a critical role in metabolic disorders and cancers. In this present study, we show that cellular energy stress induces PIKE-A phosphorylation mediated by AMPK activation, thereby preventing its carcinogenic action. Moreover, AMPK directly phosphorylates PIKE-A Ser-351 and Ser-377, which become accessible for the interaction with 14-3-3β, and in turn stimulates nuclear translocation of PIKE-A. Nuclear PIKE-A associates with CDK4 and then disrupts CDK4-cyclinD1 complex and inhibits the Rb pathway, resulting in cancer cell cycle arrest. Our data uncover a molecular mechanism and functional significance of PIKE-A phosphorylation response to cellular energy status mediated by AMPK.
Cryo-thermal therapy induces macrophage polarization for durable anti-tumor immunity
Authors: He Kun , Jia Shengguo , Lou Yue , Liu Ping , Xu Lisa X.
Published: March 2019

Many cancer therapies are being developed for the induction of durable anti-tumor immunity, especially for malignant tumors. The activation of antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), can bridge innate and adaptive immune responses against tumors. However, APCs have an immunosuppressive phenotype and reversing it for effective tumor-specific antigen presenting is critical in developing new cancer treatment strategies. We previously developed a novel cryo-thermal therapy to treat malignant melanoma in a mouse model; long-term survival and durable anti-tumor immunity were achieved, but the mechanism involved was unclear. This study revealed cryo-thermal therapy-induced macrophage polarization to the M1 phenotype and modulated the phenotypic and functional maturation of DCs with high expression of co-stimulatory molecules, increased pro-inflammatory cytokine production, and downregulated immuno-inhibitory molecule expression. Further, we observed CD4+T-cell differentiation into Th1 and cytotoxic T-cell sub-lineages and generation of cytotoxic CD8+T cells, in which M1 macrophage polarization had a direct, important role. The results indicated that cryo-thermal-induced macrophage polarization to the M1 phenotype was essential to mediate durable anti-tumor immunity, leading to long-term survival. Thus, cryo-thermal therapy is a promising strategy to reshape host immunosuppression, trigger persistent memory immunity for tumor eradication, and inhibit metastasis in the long term.
Scale-free networks are rare
Authors: Broido Anna D. , Clauset Aaron
Published: March 2019

Real-world networks are often claimed to be scale free, meaning that the fraction of nodes with degree k follows a power law k−α, a pattern with broad implications for the structure and dynamics of complex systems. However, the universality of scale-free networks remains controversial. Here, we organize different definitions of scale-free networks and construct a severe test of their empirical prevalence using state-of-the-art statistical tools applied to nearly 1000 social, biological, technological, transportation, and information networks. Across these networks, we find robust evidence that strongly scale-free structure is empirically rare, while for most networks, log-normal distributions fit the data as well or better than power laws. Furthermore, social networks are at best weakly scale free, while a handful of technological and biological networks appear strongly scale free. These findings highlight the structural diversity of real-world networks and the need for new theoretical explanations of these non-scale-free patterns.
Essential and non-overlapping IL-2Rα-dependent processes for thymic development and peripheral homeostasis of regulatory T cells
Authors: Toomer Kevin H. , Lui Jen Bon , Altman Norman H. , Ban Yuguang , Chen Xi , Malek Thomas R.
Published: March 2019

IL-2R signaling is essential for regulatory T cell (Treg) function. However, the precise contribution of IL-2 during Treg thymic development, peripheral homeostasis and lineage stability remains unclear. Here we show that IL-2R signaling is required by thymic Tregs at an early step for expansion and survival, and a later step for functional maturation. Using inducible, conditional deletion of CD25 in peripheral Tregs, we also find that IL-2R signaling is indispensable for Treg homeostasis, whereas Treg lineage stability is largely IL-2-independent. CD25 knockout peripheral Tregs have increased apoptosis, oxidative stress, signs of mitochondrial dysfunction, and reduced transcription of key enzymes of lipid and cholesterol biosynthetic pathways. A divergent IL-2R transcriptional signature is noted for thymic Tregs versus peripheral Tregs. These data indicate that IL-2R signaling in the thymus and the periphery leads to distinctive effects on Treg function, while peripheral Treg survival depends on a non-conventional mechanism of metabolic regulation.
Evidence of nematic order and nodal superconducting gap along [110] direction in RbFe2As2
Authors: Liu Xi , Tao Ran , Ren Mingqiang , Chen Wei , Yao Qi , Wolf Thomas , Yan Yajun , Zhang Tong , Feng Donglai
Published: March 2019

Unconventional superconductivity often intertwines with various forms of order, such as the nematic order which breaks the rotational symmetry of the lattice. Here we report a scanning tunneling microscopy study on RbFe2As2, a heavily hole-doped Fe-based superconductor (FeSC). We observe significant symmetry breaking in its electronic structure and magnetic vortex which differentiates the (π, π) and (π, -π) directions of the unfolded Brillouin zone. It is thus a novel nematic state, distinct from the nematicity of undoped/lightly-doped FeSCs which breaks the (π, 0)/(0, π) equivalence. Moreover, we observe a clear V-shaped superconducting gap. The gap is suppressed on surface Rb vacancies and step edges, and the suppression is particularly strong at the [110]-oriented edges. This is possibly due to a $${{d}}_{{{x}}^2 - {{y}}^2}$$

d

x

2

-

y

2

like pairing component with nodes along the [110] directions. Our results thus highlight the intimate connection between nematicity and superconducting pairing in iron-based superconductors.
High-resolution structure determination of sub-100 kDa complexes using conventional cryo-EM
Authors: Herzik Mark A. , Wu Mengyu , Lander Gabriel C.
Published: March 2019

Determining high-resolution structures of biological macromolecules amassing less than 100 kilodaltons (kDa) has been a longstanding goal of the cryo-electron microscopy (cryo-EM) community. While the Volta phase plate has enabled visualization of specimens in this size range, this instrumentation is not yet fully automated and can present technical challenges. Here, we show that conventional defocus-based cryo-EM methodologies can be used to determine high-resolution structures of specimens amassing less than 100 kDa using a transmission electron microscope operating at 200 keV coupled with a direct electron detector. Our ~2.7 Å structure of alcohol dehydrogenase (82 kDa) proves that bound ligands can be resolved with high fidelity to enable investigation of drug-target interactions. Our ~2.8 Å and ~3.2 Å structures of methemoglobin demonstrate that distinct conformational states can be identified within a dataset for proteins as small as 64 kDa. Furthermore, we provide the sub-nanometer cryo-EM structure of a sub-50 kDa protein.
Genome maps across 26 human populations reveal population-specific patterns of structural variation
Authors: Levy-Sakin Michal , Pastor Steven , Mostovoy Yulia , Li Le , Leung Alden K. Y. , McCaffrey Jennifer , Young Eleanor , Lam Ernest T. , Hastie Alex R. , Wong Karen H. Y. , Chung Claire Y. L. , Ma Walfred , Sibert Justin , Rajagopalan Ramakrishnan , Jin Nana , Chow Eugene Y. C. , Chu Catherine , Poon Annie , Lin Chin , Naguib Ahmed , Wang Wei-Ping , Cao Han , Chan Ting-Fung , Yip Kevin Y. , Xiao Ming , Kwok Pui-Yan
Published: March 2019

Large structural variants (SVs) in the human genome are difficult to detect and study by conventional sequencing technologies. With long-range genome analysis platforms, such as optical mapping, one can identify large SVs (>2 kb) across the genome in one experiment. Analyzing optical genome maps of 154 individuals from the 26 populations sequenced in the 1000 Genomes Project, we find that phylogenetic population patterns of large SVs are similar to those of single nucleotide variations in 86% of the human genome, while ~2% of the genome has high structural complexity. We are able to characterize SVs in many intractable regions of the genome, including segmental duplications and subtelomeric, pericentromeric, and acrocentric areas. In addition, we discover ~60 Mb of non-redundant genome content missing in the reference genome sequence assembly. Our results highlight the need for a comprehensive set of alternate haplotypes from different populations to represent SV patterns in the genome.
Variable outcomes of human heart attack recapitulated in genetically diverse mice
Authors: Salimova Ekaterina , Nowak Kristen J. , Estrada Ana C. , Furtado Milena B. , McNamara Elyshia , Nguyen Quang , Balmer Lois , Preuss Christoph , Holmes Jeffrey W. , Ramialison Mirana , Morahan Grant , Rosenthal Nadia A.
Published: March 2019

Clinical variation in patient responses to myocardial infarction (MI) has been difficult to model in laboratory animals. To assess the genetic basis of variation in outcomes after heart attack, we characterized responses to acute MI in the Collaborative Cross (CC), a multi-parental panel of genetically diverse mouse strains. Striking differences in post-MI functional, morphological, and myocardial scar features were detected across 32 CC founder and recombinant inbred strains. Transcriptomic analyses revealed a plausible link between increased intrinsic cardiac oxidative phosphorylation levels and MI-induced heart failure. The emergence of significant quantitative trait loci for several post-MI traits indicates that utilizing CC strains is a valid approach for gene network discovery in cardiovascular disease, enabling more accurate clinical risk assessment and prediction.
Inter-chromosomal coupling between vision and pigmentation genes during genomic divergence
Authors: Hench Kosmas , Vargas Marta , Höppner Marc P. , McMillan W. Owen , Puebla Oscar
Published: March 2019

Recombination between loci underlying mate choice and ecological traits is a major evolutionary force acting against speciation with gene flow. The evolution of linkage disequilibrium between such loci is therefore a fundamental step in the origin of species. Here, we show that this process can take place in the absence of physical linkage in hamlets—a group of closely related reef fishes from the wider Caribbean that differ essentially in colour pattern and are reproductively isolated through strong visually-based assortative mating. Using full-genome analysis, we identify four narrow genomic intervals that are consistently differentiated among sympatric species in a backdrop of extremely low genomic divergence. These four intervals include genes involved in pigmentation (sox10), axial patterning (hoxc13a), photoreceptor development (casz1) and visual sensitivity (SWSandLWSopsins) that develop islands of long-distance and inter-chromosomal linkage disequilibrium as species diverge. The relatively simple genomic architecture of species differences facilitates the evolution of linkage disequilibrium in the presence of gene flow.
Assessing metastatic potential of breast cancer cells based on EGFR dynamics
Authors: Liu Yen-Liang , Chou Chao-Kai , Kim Mirae , Vasisht Rohan , Kuo Yu-An , Ang Phyllis , Liu Cong , Perillo Evan P. , Chen Yu-An , Blocher Katherine , Horng Hannah , Chen Yuan-I , Nguyen Duc Trung , Yankeelov Thomas E. , Hung Mien-Chie , Dunn Andrew K. , Yeh Hsin-Chih
Published: March 2019

Derailed transmembrane receptor trafficking could be a hallmark of tumorigenesis and increased tumor invasiveness, but receptor dynamics have not been used to differentiate metastatic cancer cells from less invasive ones. Using single-particle tracking techniques, we  developed a phenotyping asssay named Transmembrane Receptor Dynamics (TReD), studied the dynamics of epidermal growth factor receptor (EGFR) in seven breast epithelial cell lines and developed a phenotyping assay named Transmembrane Receptor Dynamics (TReD). Here we show a clear evidence that increased EGFR diffusivity and enlarged EGFR confinement size in the plasma membrane (PM) are correlated with the enhanced metastatic potential in these cell lines. By comparing the TReD results with the gene expression profiles, we found a clear negative correlation between the EGFR diffusivities and the breast cancer luminal differentiation scores (r = −0.75). Upon the induction of epithelial-mesenchymal transition (EMT), EGFR diffusivity significantly increased for the non-tumorigenic MCF10A (99%) and the non-invasive MCF7 (56%) cells, but not for the highly metastatic MDA-MB-231 cell. We believe that the reorganization of actin filaments during EMT modified the PM structures, causing the receptor dynamics to change. TReD can thus serve as a new biophysical marker to probe the metastatic potential of cancer cells and even to monitor the transition of metastasis.
Early-Life Exposure to the Chinese Famine Is Associated with Higher Methylation Level in the INSR Gene in Later Adulthood
Authors: Wang Zhenghe , Song Jieyun , Li Yanhui , Dong Bin , Zou Zhiyong , Ma Jun
Published: March 2019

We examined the association between the China famine exposure in early life and DNA methylation of INSR (hg18, chr19:7110130-7110574) and CPT1A (hg18, chr11: 68286513-68286952) related to growth and metabolism in 235 subjects selected from two provinces in China. The subjects were categorized into prenatal famine-exposed group and non-exposed group based on their birthdates. DNA methylation at the INSR gene locus was assayed from peripheral white blood cells using the Sequenom’s MassARRAY system. Two dependent samples t-test was used to compare the difference between the exposed group and non-exposed group. DNA methylation level of INSR was higher among individuals who exposed to the China famine in the fetus than that of non-exposed group (d = 3.3%, P = 0.006). A significant interaction between famine exposure and province was observed for INSR (Pinteraction < 0.001). DNA methylation level of INSR was positively associated with triglyceride (β = 0.011, P = 0.021), and negatively associated with high-density lipoprotein cholesterol (β = −0.039, P = 0.021). Moreover, exposed group had higher meat consumption than non-exposed group in severe exposure area. Prenatal exposure to the China famine plus later life eating habits might regulate epigenome.
The Reaction of Dimerization by Itself Reduces the Noise Intensity of the Protein Monomer
Authors: Liu Feng-You , Lo Shih-Chiang , Shu Che-Chi
Published: March 2019

Because of the small particle number of intracellular species participating in genetic circuits, stochastic fluctuations are inevitable. This intracellular noise is detrimental to precise regulation. To maintain the proper function of a cell, some natural motifs attenuate the noise at the protein level. In many biological systems, the protein monomer is used as a regulator, but the protein dimer also exists. In the present study, we demonstrated that the dimerization reaction reduces the noise intensity of the protein monomer. Compared with two common noise-buffering motifs, the incoherent feedforward loop (FFL) and negative feedback control, the coefficient of variation (COV) in the case of dimerization was 25% less. Furthermore, we examined a system with direct interaction between proteins and other ligands. Both the incoherent FFL and negative feedback control failed to buffer the noise, but the dimerization was effective. Remarkably, the formation of only one protein dimer was sufficient to cause a 7.5% reduction in the COV.
Genetic polymorphism and phylogenetic differentiation of the Huaxia Platinum System in three Chinese minority ethnicities
Authors: Liu Jing , Wang Zheng , He Guanglin , Wang Mengge , Hou Yiping
Published: March 2019

Short tandem repeats (STRs) with features of high polymorphism and abundant evolution information play a significant role in genetic applications such as human forensics, anthropology and population genetics. The Huaxia Platinum System was specifically exploited to allow coamplification of all markers in the expanded Combined DNA Index System and the Chinese National Database. Herein, in continuation of our previous studies, 493 unrelated individuals were firstly genotyped to investigate the efficacy of this novel system in three minority ethnicities of China (Hui, Tibetan and Uygur). Additionally, genetic relationships among our three investigated populations and other previously published populations were analyzed using pairwise genetic distances, multidimensional scaling (MDS), principal component analysis (PCA), cladogram and STRUCTURE. The combined match probabilities (CMP) for the Hui, Tibetan and Uygur groups were 1.6894 × 10−27, 6.1666 × 10−27 and 5.0655 × 10−27, respectively, and the combined powers of exclusion (CPE) were 0.999999999646627, 0.999999999304935 and 0.999999999433994. Population comparison analysis manifested that the Hui and Tibetan populations had genetic affinities with the Han, Yi and Korean populations, while the Uygur group had a close relationship with the Kazakh population. The aforementioned results suggested that the Huaxia Platinum System is a polymorphic and effective tool that is appropriate for personal identification and population genetics.
Differences in monocyte: lymphocyte ratio and Tuberculosis disease progression in genetically distinct populations of macaques
Authors: Sibley Laura , Gooch Karen , Wareham Alice , Gray Susan , Chancellor Andrew , Dowall Stuart , Bate Simon , Marriott Anthony , Dennis Mike , White Andrew D. , Marsh Philip D. , Fletcher Helen , Sharpe Sally
Published: March 2019

Monocyte:lymphocyte ratio (M:L) has been identified as a risk factor in development of TB disease in children and those undergoing treatment for HIV in co-infected individuals. Retrospective analysis was performed using M:L data collected from TB modelling studies performed in Rhesus macaques of Indian genotype (RM), cynomolgus macaque of Chinese genotype (CCM) and cynomolgus macaque of Mauritian genotype (MCM), which found that the more susceptible populations (RM and MCM) had higher M:L ratios than the least susceptible population (CCM). Following Mycobacterium tuberculosis exposure, significant increases in M:L ratio were observed in susceptible RM and MCM within 12 weeks of TB infection, whereas M:L in CCM remained stable, suggesting that changes in M:L ratio may also act as a biomarker of TB disease progression. The frequency of PPD-specific interferon gamma (IFNγ) secreting cells (SFU) were compared, with the more susceptible macaque populations showing an association between M:L and IFNγ SFU frequency. Investigation of the genes associated with monocyte-derived antigen presenting cells revealed differences between RM and CCM, highlighting differences in their monocyte populations, as well as overall M:L ratio. Differences in M:L ratio between macaque populations could be used to explore immunological mechanisms in susceptible populations that would complement human population studies.
New molecular insights on the response of the green alga Tetraselmis suecica to nitrogen starvation
Authors: Lauritano Chiara , De Luca Daniele , Amoroso Mariano , Benfatto Salvatore , Maestri Simone , Racioppi Claudia , Esposito Francesco , Ianora Adrianna
Published: March 2019

Microalgae are currently considered one of the most promising resources for biofuel production, aquaculture feedstock and new pharmaceuticals. Among them, green algae of the genusTetraselmisare extensively studied for their lipid accumulation in nutrient-starvation conditions. In this paper, we present the full-transcriptome ofTetraselmis suecicaand differential expression analysis between nitrogen-starved and -repleted conditions (at stationary phase) focusing not only on lipid metabolism but giving new insights on nutrient starvation responses. Transcripts involved in signal transduction pathways, stress and antioxidant responses and solute transport were strongly up-regulated whenT.suecicawas cultured under nitrogen starvation. On the contrary, transcripts involved in amino acid synthesis, degradation of sugars, secondary metabolite synthesis, as well as photosynthetic activity were down-regulated under the same conditions. Among differentially expressed transcripts, a polyketide synthase and three lipoxygenases (involved in the synthesis of secondary metabolites with antipredator, anticancer and anti-infective activities) were identified, suggesting the potential synthesis of bioactive compounds by this microalga. In addition, the transcript for a putative nitrilase, enzyme used in nitrile bioremediation, is here reported for the first time forT. suecica. These findings give new insights onT. suecicaresponses to nutrient starvation and on possible biotechnological applications for green algae.
Entrainment of superoxide rhythm by menadione in HCT116 colon cancer cells
Authors: Kizhuveetil Uma , Palukuri Meghana V. , Sharma Priyanshu , Karunagaran Devarajan , Rengaswamy Raghunathan , Suraishkumar G. K.
Published: March 2019

Reactive oxygen species (ROS) are primary effectors of cytotoxicity induced by many anti-cancer drugs. Rhythms in the pseudo-steady-state (PSS) levels of particular intracellular ROS in cancer cells and their relevance to drug effectiveness are unknown thus far. We report that the PSS levels of intracellular superoxide (SOX), an important ROS, exhibit an inherent rhythm in HCT116 colon cancer cells, which is entrained (reset) by the SOX inducer, menadione (MD). This reset was dependent on the expression of p53, and it doubled the sensitivity of the cells to MD. The period of oscillation was found to have a linear correlation with MD concentration, given by the equation, T, in h = 23.52 − 1.05 [MD concentration in µM]. Further, we developed a mathematical model to better understand the molecular mechanisms involved in rhythm reset. Biologically meaningful parameters were obtained through parameter estimation techniques; the model can predict experimental profiles of SOX, establish qualitative relations between interacting species in the system and serves as an important tool to understand the profiles of various species. The model was also able to successfully predict the rhythm reset in MD treated hepatoma cell line, HepG2.
Species-specific alterations in Anopheles mosquito olfactory responses caused by Plasmodium infection
Authors: Stanczyk N. M. , Brugman V. A. , Austin V. , Sanchez-Roman Teran F. , Gezan S. A. , Emery M. , Visser T. M. , Dessens J. T. , Stevens W. , Smallegange R. C. , Takken W. , Hurd H. , Caulfield John , Birkett M. , Pickett J. , Logan J. G.
Published: March 2019

Mosquitoes infected with malaria parasites have demonstrated altered behaviour that may increase the probability of parasite transmission. Here, we examine the responses of the olfactory system in Plasmodium falciparum infected Anopheles gambiae, Plasmodium berghei infected Anopheles stephensi, and P. berghei infected An. gambiae. Infected and uninfected mosquitoes showed differential responses to compounds in human odour using electroantennography coupled with gas chromatography (GC-EAG), with 16 peaks triggering responses only in malaria-infected mosquitoes (at oocyst, sporozoite or both stages). A selection of key compounds were examined with EAG, and responses showed differences in the detection thresholds of infected and uninfected mosquitoes to compounds including lactic acid, tetradecanoic acid and benzothiazole, suggesting that the changes in sensitivity may be the reason for differential attraction and biting at the oocyst and sporozoite stages. Importantly, the different cross-species comparisons showed varying sensitivities to compounds, with P. falciparum infected An. gambiae differing from P. berghei infected An. stephensi, and P. berghei infected An. gambiae more similar to the P. berghei infected An. stephensi. These differences in sensitivity may reflect long-standing evolutionary relationships between specific Plasmodium and Anopheles species combinations. This highlights the importance of examining different species interactions in depth to fully understand the impact of malaria infection on mosquito olfactory behaviour.
Examining the relationship between body mass index and adverse cardio-metabolic profiles among Australian Indigenous and non-Indigenous young adults
Authors: Sevoyan Arusyak , Davison Belinda , Rumbold Alice , Moore Vivienne , Singh Gurmeet
Published: March 2019

Australian Indigenous young people have a 10-fold excess of deaths from ischaemic heart disease compared with non-Indigenous Australians, yet the reasons behind this remain understudied. This paper aims to describe cardio-metabolic profiles among Australian Indigenous (n = 459) and non-Indigenous (n = 117) young adults (21–27 years). The association between body size and an adverse cardio-metabolic profile (≥3 abnormal cardio-metabolic markers) is assessed by gender and urban/rural residence, employing regression analyses. The prevalence of obesity was highest among urban Indigenous participants, both males and females (22% and 23%, respectively). Overall, BMI showed a significant positive association with an adverse cardio-metabolic profile. Moreover, adverse cardio-metabolic profile was present in a substantial proportion of Indigenous participants even in overweight and normal BMI categories. Among females, this could reflect elevated waist circumference, which was present in half of those of normal weight. Remote Indigenous females had the highest predicted probability of having an adverse cardio-metabolic profile across all BMI categories (13% for underweight, 54% for normal BMI, 93% for overweight, and 99% for obese). Our findings highlight the associations between obesity and adverse cardio-metabolic profiles among Indigenous and non-Indigenous youth. Culturally-relevant strategies that address lifestyle risks, including access to healthy food, are urgently needed in this age group.
Novel Hg2+-Selective Signaling Probe Based on Resorufin Thionocarbonate and its μPAD Application
Authors: Choi Myung Gil , Park So Young , Park Ka Young , Chang Suk-Kyu
Published: March 2019

In this study, a novel resorufin thionocarbonate-based Hg2+-selective signaling probe (RT) for microfluidic paper-based analytical device (μPAD) applications is reported. The designed probe, RT, was readily synthesized by the one-step reaction of resorufin with phenyl thionochloroformate. The RT probe displayed a prominent color change from yellow to pink and a marked turn-on fluorescence signaling behavior exclusively toward the Hg2+ ion. The signaling of RT was due to Hg2+-induced hydrolysis of the phenyl thionocarbonate moiety to form the parent resorufin dye, which restored its spectroscopic properties. In addition, RT exhibited the Hg2+-selective signaling behavior without interference by coexisting environmentally relevant metal ions. The detection limit for Hg2+ in simulated wastewater samples was estimated to be 5.8 × 10−8 M. In particular, an RT-equipped μPAD prepared using a wax printing technique enabled simple and convenient determination of Hg2+ ions in simulated wastewater samples, with a detection limit of 5.9 × 10−6 M.
Zero-reflection acoustic metamaterial with a negative refractive index
Authors: Park Choon Mahn , Lee Sang Hun
Published: March 2019

Waves are reflected to varying degrees at the boundary between two different media. A reduction of this reflection is important for many materials, including acoustic metamaterials. Here, we theoretically develop a balanced acoustic metamaterial that exhibits zero reflection between the metamaterial and air over its entire refractive index range, regardless of the sign of the refractive index. The metamaterial is realized using unit cell structures containing membranes and open tubes, and the material performance is verified experimentally, demonstrating sound reflectance of less than 10% in the frequency region that satisfies the homogeneous medium condition. The zero-reflection characteristic of the acoustic balanced metamaterial can improve the performance of new acoustic devices such as the invisibility cloak and super-lens and can also contribute to basic research of acoustic metamaterials.
Using Machine Learning to Predict Sensorineural Hearing Loss Based on Perilymph Micro RNA Expression Profile
Authors: Shew Matthew , New Jacob , Wichova Helena , Koestler Devin C. , Staecker Hinrich
Published: March 2019

Hearing loss (HL) is the most common neurodegenerative disease worldwide. Despite its prevalence, clinical testing does not yield a cell or molecular based identification of the underlying etiology of hearing loss making development of pharmacological or molecular treatments challenging. A key to improving the diagnosis of inner ear disorders is the development of reliable biomarkers for different inner ear diseases. Analysis of microRNAs (miRNA) in tissue and body fluid samples has gained significant momentum as a diagnostic tool for a wide variety of diseases. In previous work, we have shown that miRNA profiling in inner ear perilymph is feasible and may demonstrate distinctive miRNA expression profiles unique to different diseases. A first step in developing miRNAs as biomarkers for inner ear disease is linking patterns of miRNA expression in perilymph to clinically available metrics. Using machine learning (ML), we demonstrate we can build disease specific algorithms that predict the presence of sensorineural hearing loss using only miRNA expression profiles. This methodology not only affords the opportunity to understand what is occurring on a molecular level, but may offer an approach to diagnosing patients with active inner ear disease.
Application of a robotic THz imaging system for sub-surface analysis of ancient human remains
Authors: Stübling Eva-Maria , Rehn Arno , Siebrecht Tabea , Bauckhage Yannick , Öhrström Lena , Eppenberger Patrick , Balzer Jan C. , Rühli Frank , Koch Martin
Published: March 2019

We used a robotic-based THz imaging system to investigate the sub-surface structure of an artificially mummified ancient Egyptian human left hand. The results obtained are compared to the results of a conventional CT and a micro-CT scan. Using such a robotic THz system promises new insights into the sub-surface structure of human remains. The depth resolution of the THz images exceeds the resolution of a conventional CT scan and is comparable with a micro-CT scan. The advantage of THz measurements over micro-CT scans is the fact that even comparatively large samples, like complete bodies, can be scanned. These would not fit into a conventional micro-CT scanner.
Optical diffraction phenomena around the edges of photodetectors: A simplified method for metrological applications
Authors: Santhanakrishnan T. , Rajesh R. , Awasthi Ram Lochan , Sreehari C. V.
Published: March 2019

An optical method for simultaneous generation and detection of diffraction of light around the edges of photodetectors is reported in this paper along with its application for vibration sensing. The method makes use of an innovative illumination of light beam in which the laser light is made to incident at the interface between the active and opaque regions of a photodetector. Diffraction and induced interference occur together at the sensing area of the photodetector. The same photodetector responds to the dynamic intensity variations corresponding to the diffraction induced interference pattern and concurrently generates a dynamic electrical output. Comparing to the established diffraction techniques employing edges, the proposed method is simple to implement and extends the measurement applications. The experimental results obtained here verify the efficacy of the proposed method indicating its suitability for a novel class of sensors to be employed in practical circumstances.
The mechanism of eutectic modification by trace impurities
Authors: Moniri Saman , Xiao Xianghui , Shahani Ashwin J.
Published: March 2019

In the quest toward rational design of materials, establishing direct links between the attributes of microscopic building blocks and the macroscopic performance limits of the bulk structures they comprise is essential. Building blocks of concern to the field of crystallization are the impurities, foreign ingredients that are either deliberately added to or naturally present in the growth medium. While the role of impurities has been studied extensively in various materials systems, the inherent complexity of eutectic crystallization in the presence of trace, often metallic impurities (‘eutectic modification’) remains poorly understood. In particular, the origins behind the drastic microstructural changes observed upon modification are elusive. Herein, we employ an integrated imaging approach to shed light on the influence of trace metal impurities during the growth of an irregular (faceted–non-faceted) eutectic. Our dynamic and 3D synchrotron-based X-ray imaging results reveal the markedly different microstructural and, for the first time, topological properties of the eutectic constituents that arise upon modification, not fully predicted by the existing theories. Together withex situcrystallographic characterization of the fully-solidified specimen, our multi-modal study provides a unified picture of eutectic modification: The impurities selectively alter the stacking sequence of the faceted phase, thereby inhibiting its steady-state growth. Consequently, the non-faceted phase advances deeper into the melt, eventually engulfing the faceted phase in its wake. We present a quantitative topological framework to rationalize these experimental observations.
A large-scale metabolomics study to harness chemical diversity and explore biochemical mechanisms in ryegrass
Authors: Subbaraj Arvind K. , Huege Jan , Fraser Karl , Cao Mingshu , Rasmussen Susanne , Faville Marty , Harrison Scott J. , Jones Chris S.
Published: March 2019

Perennial ryegrass (Lolium perenne) is integral to temperate pastoral agriculture, which contributes most of the milk and meat production worldwide. Chemical profiles and diversity of ryegrass offer several opportunities to harness specific traits and elucidate underlying biological mechanisms for forage improvement. We conducted a large-scale metabolomics study of perennial ryegrass comprising 715 genotypes, representing 118 populations from 21 countries. Liquid/gas chromatography–mass spectrometry based targeted and non-targeted techniques were used to analyse fructan oligosaccharides, lipids, fatty acid methyl esters, polar and semi-polar compounds. Fructan diversity across all genotypes was evaluated, high- and low-sugar groups identified, and fructan accumulation mechanisms explored. Metabolites differentiating the two groups were characterised, modules and pathways they represent deduced, and finally, visualisation and interpretation provided in a biological context. We also demonstrate a workflow for large-scale metabolomics studies from raw data through to statistical and pathway analysis. Raw files and metadata are available at the MetaboLights database.
Genome-wide interaction and pathway-based identification of key regulators in multiple myeloma
Authors: Chattopadhyay Subhayan , Thomsen Hauke , Yadav Pankaj , da Silva Filho Miguel Inacio , Weinhold Niels , Nöthen Markus M. , Hoffman Per , Bertsch Uta , Huhn Stefanie , Morgan Gareth J. , Goldschmidt Hartmut , Houlston Richard , Hemminki Kari , Försti Asta
Published: March 2019

Inherited genetic susceptibility to multiple myeloma has been investigated in a number of studies. Although 23 individual risk loci have been identified, much of the genetic heritability remains unknown. Here we carried out genome-wide interaction analyses on two European cohorts accounting for 3,999 cases and 7,266 controls and characterized genetic susceptibility to multiple myeloma with subsequent meta-analysis that discovered 16 unique interacting loci. These risk loci along with previously known variants explain 17% of the heritability in liability scale. The genes associated with the interacting loci were found to be enriched in transforming growth factor beta signaling and circadian rhythm regulation pathways suggesting immunoglobulin trait modulation, TH17 cell differentiation and bone morphogenesis as mechanistic links between the predisposition markers and intrinsic multiple myeloma biology. Further tissue/cell-type enrichment analysis associated the discovered genes with hemic-immune system tissue types and immune-related cell types indicating overall involvement in immune response.
Heterologous calcium-dependent inactivation of Orai1 by neighboring TRPV1 channels modulates cell migration and wound healing
Authors: Bastián-Eugenio Carlos Ernesto , Bohórquez-Hernández Arlette , Pacheco Jonathan , Sampieri Alicia , Asanov Alexander , Ocelotl-Oviedo Jose Pablo , Guerrero Adán , Darszon Alberto , Vaca Luis
Published: March 2019

Store-operated calcium entry (SOCE) is an essential calcium influx mechanism in animal cells. One of the most important auto regulatory control systems involves calcium-dependent inactivation (CDI) of the Orai channel, which prevents excessive calcium influx. In the present study we analyze the role of two channels in the induction of CDI on Orai1. Here we show that calcium entering through freely diffusing TRPV1 channels induce strong CDI on Orai1 while calcium entering through P2X4 channel does not. TRPV1 can induce CDI on Orai1 because both channels were found in close proximity in the cell membrane. This was not observed with P2X4 channels. To our knowledge, this is the first study demonstrating that calcium arising from different channels may contribute to the modulation of Orai1 through CDI in freely diffusing single channels of living cells. Our results highlight the role of TRPV1-mediated CDI on Orai1 in cell migration and wound healing.
Noncovalent Interactions in Biocatalysis – A Theoretical Perspective
Authors: Velmurugan Gunasekaran , Solomon Rajadurai Vijay , Senthilnathan Dhurairajan , Venuvanalingam Ponnambalam
Published: March 2019

Noncovalent interactions (NCIs) are Nature's choice for maintaining biological structure and carrying out many biological functions. These delicate forces become stronger and more specific when acting together. They were detected very early as short contacts in crystals or in gas-phase complexes but their systematic understanding is recent. Theoretical methods have greatly aided in understanding their nature and variety and this eventually led to their use in developing chemical, material, biological and technological applications. Recent developments in computer hardware and software have enabled scientists to probe the movements at the atomic level in the active site of complex biological systems and understand the biological processes. This chapter is devoted to explaining the role of NCIs in biocatalysis from a computational perspective. It first introduces the popular theoretical methods used to characterize NCIs and then explains the role of the three main NCIs, namely hydrogen bonding, halogen bonding and hydrophobic interactions, in biocatalysis through six case studies from the literature. The chapter ends with a summary and future directions of this topic.
Quantifying the pH shift induced by selective anodic electrochemical reactions in the ion concentration polarization phenomenon
Authors: Kim Wonseok , Oh Jeewhan , Kwon Soonhyun , Kim Kihong , Kim Sung Jae
Published: March 2019

We demonstrated how preconcentration and purification efficiencies developed by ICP (Ion Concentration Polarization) were governed by electrochemical reactions using two types of electrode configurations; large exposed electrode area (LEEA) and small exposed electrode area (SEEA).
A new route for fabricating polymer optical microcavities
Authors: Zhang Zhang , Yao Ni , Pan Jing , Zhang Lei , Fang Wei , Tong Limin
Published: March 2019

SU-8 microcavities with an ultra-smooth surface and high Q factors are demonstrated by using a simple and low cost self-assembly method.
Investigation on the role of interfacial water on the tribology between graphite and metals
Authors: Lim Yeonsoo , Park Haiwoong , Caron Arnaud
Published: March 2019

We investigated the role of interfacial water on the atomic-scale tribology of graphite by contact atomic force microscopy.
Crab shell-derived honeycomb-like graphitized hierarchically porous carbons for satisfactory rate performance of all-solid-state supercapacitors
Authors: Shi Weiwei , Chang Binbin , Yin Hang , Zhang Shouren , Yang Baocheng , Dong Xiaoping
Published: March 2019

Valuable 3D honeycomb-like graphitized hierarchically porous carbons are synthesized from crab shell bio-waste for high rate capability of all-solid-state supercapacitors.
Controlled generation of spiky microparticles by ionic cross-linking within an aqueous two-phase system
Authors: Abbasi Niki , Navi Maryam , Nunes Janine K. , Tsai Scott S. H.
Published: March 2019

We describe a unique approach for controlled generation of spiky microparticles, based on ionic cross-linking within an aqueous two-phase system.
Employing structurally similar acceptors as crystalline modulators to construct high efficiency ternary organic solar cells
Authors: Jiang Huanxiang , Li Xiaoming , Liang Zezhou , Huang Gongyue , Chen Weichao , Zheng Nan , Yang Renqiang
Published: March 2019

Structurally similar acceptors could function as crystalline modulators to fine-tune the morphology for constructing efficient ternary organic solar cells.
Molecular tectonics: homochiral 1D and 2D cadmium based coordination networks
Authors: Larpent Patrick , Jouaiti Abdelaziz , Kyritsakas Nathalie , Hosseini Mir Wais
Published: March 2019

By combining enantiomerically pure tectons with Cd(NO3)2, a series of six new homochiral luminescent coordination networks are formed. The dimensionality and crystal packing of the latter are modulated by both the nature of the chiral side chains and the crystallization solvents.
The potential application of black and blue phosphorene as cathode materials in rechargeable aluminum batteries: a first-principles study
Authors: Xiao Xiang , Wang Mingyong , Tu Jiguo , Jiao Shuqiang
Published: March 2019

Developing a suitable cathode material for rechargeable aluminum-ion batteries (AIBs) is currently recognized as a key challenge in pushing AIBs from lab-level to industrial application.
The impact of lignin sulfonation on its reactivity with laccase and laccase/HBT
Authors: Hilgers Roelant , Twentyman-Jones Megan , van Dam Annemieke , Gruppen Harry , Zuilhof Han , Kabel Mirjam A. , Vincken Jean-Paul
Published: March 2019

This study shows and explains how sulfonation of lignin influences its reactivity with laccase and LMS (with mediator HBT), and what consequences this has for the overall outcome of laccase and LMS treatments.
Metal ion exchange in Prussian blue analogues: Cu(ii)-exchanged Zn–Co PBAs as highly selective catalysts for A3 coupling
Authors: Marquez Carlos , Cirujano Francisco G. , Smolders Simon , Van Goethem Cédric , Vankelecom Ivo , De Vos Dirk , De Baerdemaeker Trees
Published: March 2019

The occurrence of metal ion exchange in Zn3[Co(CN)6]2 and Cu3[Co(CN)6]2 Prussian blue analogues (Zn–Co and Cu–Co PBAs) was demonstrated for the first time.
RE2[B2(SO4)6] (RE= Y, La–Nd, Sm, Eu, Tb–Lu): a silicate-analogous host structure with weak coordination behaviour
Authors: Netzsch Philip , Hämmer Matthias , Gross Peter , Bariss Harijs , Block Theresa , Heletta Lukas , Pöttgen Rainer , Bruns Jörn , Huppertz Hubert , Höppe Henning A.
Published: March 2019

The very first thorough investigation of the rare earth borosulfatesRE2[B2(SO4)6] withRE= Y, La–Nd, Sm, Eu and Tb–Lu focusses on synthetic aspects and especially optical properties.
Horizons Community Board Collection – Nanobiomedicine
Authors: Dixit Chandra Kumar , Proctor Christopher M.
Published: March 2019

A themed collection on nanobiomedicine, guest edited by Nanoscale Horizons Community Board Member Chandra Kumar Dixit and Materials Horizons Community Board Member Christopher M. Proctor.
Recyclable magnetic covalent organic framework for the extraction of marine biotoxins
Authors: Romero Vanesa , Fernandes Soraia P. S. , Rodriguez-Lorenzo Laura , Kolen'ko Yury V. , Espiña Begoña , Salonen Laura M.
Published: March 2019

Facile synthesis of a recyclable magnetic covalent organic framework for the extraction of lipophilic marine biotoxins.
Transport of microtubules according to the number and spacing of kinesin motors on gold nano-pillars
Authors: Kaneko Taikopaul , Ando Suguru , Furuta Ken'ya , Oiwa Kazuhiro , Shintaku Hirofumi , Kotera Hidetoshi , Yokokawa Ryuji
Published: March 2019

Nano-patterning of kinesin molecules to control the number and arrangement of motors that transport a single microtubule filament is developed.
Synthesis of macrocyclic peptidomimetics via the Ugi-click-strategy
Authors: Zakharova Elena A. , Shmatova Olga I. , Kutovaya Irina V. , Khrustalev Victor N. , Nenajdenko Valentine G.
Published: March 2019

The Ugi-click-strategy was employed for the synthesis of 12–28 membered 1,2,3-triazole derived macrocyclic peptidomimetics.
Studies of PET nonwovens modified by novel antimicrobials configured with bothN-halamine and dual quaternary ammonium with different alkyl chain length
Authors: Chien Hsiu-Wen , Chen Ying-Yuan , Chen Yen-Lun , Cheng Chi-Hui , Lin Jui-Che
Published: March 2019

This work describes the synthesis of novel antimicrobial agents consisting ofN-halamine and dual quaternary ammonium with different alkyl chain lengths and their antimicrobial applications for PET nonwovens.