bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphogenetic mechanism of the acquisition of the dinosaur-type acetabulum
Authors: Egawa Shiro , Saito Daisuke , Abe Gembu , Tamura Koji
Published: October 2018

Understanding morphological evolution in dinosaurs from a mechanistic viewpoint requires the elucidation of the morphogenesis that gave rise to derived dinosaurian traits, such as the perforated acetabulum. In the current study, we used embryos of extant animals with ancestral- and dinosaur-type acetabula, namely, geckos and turtles (with unperforated acetabulum), and birds (with perforated acetabulum). We performed comparative and experimental analyses, focusing on inter-tissue interaction during embryogenesis, and found that the avian perforated acetabulum develops via a secondary loss of cartilaginous tissue in the acetabular region. This cartilage loss might be mediated by inter-tissue interaction with the hip interzone, a mesenchymal tissue that exists in the embryonic joint structure. Furthermore, the data indicate that avian pelvic anlagen is more susceptible to paracrine molecules, e.g. Wnt ligand, secreted by the hip interzone than ‘reptilian’ anlagen. We hypothesize that during the emergence of dinosaurs, the pelvic anlagen became susceptible to the Wnt ligand, which led to the loss of the cartilaginous tissue and to the perforation in the acetabular region. Thus, the current evolutionary-developmental biology study deepens our understanding of morphological evolution in dinosaurs and provides it with a novel perspective.
A facile energy-saving route of fabricating thermoelectric Sb
2
Te
3
-Te nanocomposites and nanosized Te
Authors: Liu En-Yu , Lin Fei-Hung , Yang Zong-Ren , Liu Chia-Jyi
Published: October 2018

A facile energy-saving route is developed for fabricating Sb
2
Te
3
-Te nanocomposites and nanosized Te powders. The fabrication route not only avoids using organic chemicals, but also keeps the energy consumption to a minimum. The fabrication procedure involves two steps. Energetic precursors of nanosized powders of Sb and Te are produced at room temperature followed by hot pressing at 400°C under 70 MPa for 1 h. The resulting Sb
2
Te
3
-Te nanocomposite exhibits enhanced power factor. The dimensionless figure of merit
zT
value of the Sb
2
Te
3
-Te nanocomposite is 0.29 at 475 K.
Scaling the phase-planes of social dilemma strengths shows game-class changes in the five rules governing the evolution of cooperation
Authors: Ito Hiromu , Tanimoto Jun
Published: October 2018

Game theory has been extensively applied to help explain how cooperative behaviour is promoted in human and animal societies. How do humans and animals establish reciprocity when confronting a social dilemma? In 2006, Nowak theoretically proved that numerous mechanisms and models for evolving cooperative behaviour reported over the last few decades can be distilled into five reciprocity mechanisms (rules). Additionally, universal scaling parameters were proposed to measure two different types of dilemmas, namely, the gamble-intending dilemma (GID) and risk-averting dilemma (RAD). In this work, by drawing a RAD–GID phase-plane diagram for pair-wise games, we prove that these five rules have four different dilemma resolution (relaxation) mechanisms. These diagrams also demonstrate whether and when game-class change (resolution of a dilemma) occurs, thus implying how defectors can be eliminated.
Microstructure, local electronic structure and optical behaviour of zinc ferrite thin films on glass substrate
Authors: Singh Jitendra Pal , Lee Byeong-Hyeon , Lim Weon Cheol , Shim Cheol-Hwee , Lee Jihye , Chae Keun Hwa
Published: October 2018

Zinc ferrite thin films were deposited using a radio-frequency-sputtering method on glass substrates. As-deposited films were annealed at 200°C for 1, 3 and 5 h, respectively. X-ray diffraction studies revealed the amorphous nature of as-grown and annealed films. Thickness of as-deposited film is 96 nm as determined from Rutherford backscattering spectroscopy which remains almost invariant with annealing. Transmission electron microscopic investigations envisaged a low degree of crystalline order in as-deposited and annealed films. Thicknesses estimated from these measurements were almost 62 nm. Roughness values of these films were almost 1–2 nm as determined from atomic force microscopy. X-ray reflectivity measurements further support the results obtained from TEM and AFM. Near-edge X-ray absorption fine structure measurements envisaged 3+ and 2+ valence states of Fe and Zn ions in these films. UV–Vis spectra of these films were characterized by a sharp absorption in the UV region. All films exhibited almost the same value of optical band gap within experimental error, which is close to 2.86 eV.
Quality characteristics of madeleine added with halla gold kiwifruit fermented by lactic acid bacteria
Authors: Ryu Ji-yeon , Park Hyun Jeong , Lee Su Lim , Koh So Yae , Lim Ji Hee , Kim Hyeon A , Somi Kim
Published: October 2018

Fermented halla gold kiwifruit (FHK) was prepared with Lactobacillus plantarum CK10, a bacterium derived from kimchi. We investigated the quality characteristics and antioxidative activity of madeleine added with FHK. The madeleine dough was prepared by mixing flour, sugar, baking powder, and then followed by adding salt, rum, different amount of the FHK (0, 1, and 3%) and butter. The total titratable acidity of madeleine increased significantly with the amounts of added FHK (p<0.05), while the pH value and total soluble solids showed the reverse trend. The color of madeleine became substantially redder with increasing amounts of FHK (p<0.05), and it appeared darker and less yellow at the same time. The total polyphenol contents of madeleines increased significantly with increasing amounts of FHK (p<0.05), but there was little difference in the total flavonoid content. When the antioxidant activities were measured in terms of 2,2-diphenyl-1-picrylhydrazyl (DPPH)-and 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid-diammonium salt (ABTS)-radical scavenging, both measured activities of madeleines increased dramatically with added FHK in a dose-dependent manner. Our results suggested that the acidity, color, polyphenol content, and antioxidant activities of madeleines can be improved by adding the fermented gold kiwifruit.
Free amino acids extracted from dried Gugija (Lycium chinensis) under different extraction conditions
Authors: Lee Gee-Dong
Published: October 2018

The amounts of free amino acids extracted from dried Gugija (Lycium chinensis Mill) were monitored under different extraction conditions. The response methodology was applied using the ethanol concentration (X1 0-80%) and extraction time (X2 1-5 h) as operational parameters with regard to various free amino acids (glycine, serine, alanine, threonine, proline, valine, methionine, isoleucine, leucine, tyrosine, tryptophan, phenylalanine, asparagine, lysine, arginine, histidine, carnosine, ornithine, aspartic acid, glutamic acid, phosphoserine, hydroxyproline, γ-amino-n-butyric acid, taurine, phosphoethanolamine, citrulline, β-alanine, β-amino-isobutyric acid, hydroxylysine, sarcocine, and ethanolamine) and their sum. Under the optimum conditions, the free amino acid contents were asparagine 186.28, phosphoethanolamine 166.21, proline 46.51, alanine 43.35, aspartic acid 27.23, hydroxyproline 21.17, glutamic acid 16.53, taurine 16.24, arginine 14.66, serine 11.65, γ-amino-n-butyric acid 10.82, leucine 10.52, tryptophan 8.75, ethanolamine 8.49, and total free amino acid 629 mg/100 g. The coefficients of determination (R2) of the models for methionine, arginine, histidine, carnosine, ornithine, aspartic acid, phosphoserine and γ-amino-n-butyric acid were within 0.9052-0.9810 (p<0.01-0.05). For the total free amino acids, the R2 of the model was 0.8608 (p<0.1), the extraction yield ranged from 282 to 641 mg/100 g depending on the extraction conditions and was the highest when extracted for 5 h with 20% ethanol.
Comparison of volatile flavor compounds of Artemisia annua L. extracted by simultaneous steam distillation extraction and solid-phase micro extraction
Authors: Hong Young Shin , Son Ji Hyeon , Jeong Ji Young , Song Ok Yeon , Lee Jin Ha , Kim Kyoung Su
Published: October 2018

This study was conducted to compare the volatile flavor compounds of Artemisia annua L. after extraction by simultaneous steam distillation extraction (SDE) and solid-phase micro extraction (SPME) followed by gas chromatography-mass spectrometry (GC-MS) analysis. Via SDE and SPME processes, 79 (1,254.00 mg/kg) and 39 (488.74 mg/kg) compounds were identified respectively. The compounds extracted by SDE included 27 alcohols, 13 aldehydes, 22 hydrocarbons, 3 esters, 12 ketones, 1 oxide and 1 N-containing compound, on the other hand, using the SPME method, 7 alcohols, 5 aldehydes, 1 ester, 18 hydrocarbons, 7 ketones, and 1 oxide were extracted. The major volatile flavor compounds of Artemisia annua L. isolated by the two methods were caryophyllene oxide, β-caryophyllene, camphor, β-selinene, γ-muurolene, 1,8-cineol, (E)-pinocarveol and pinocarvone. The sesquiterpene named caryophyllene oxide was the most abundant volatile flavor compound with relative contents of 234.16 mg/kg and 195.44 mg/kg obtained by the SDE and SPME methods, respectively. Among the identified volatiles, sabinene, β-pinene, α-terpinene, γ-terpinene, yomogi alcohol, myrtenol, (Z)-nerolidol, p-cymen-8-ol and eugenol were detected by the SDE method only while (E)-anethole and α-cubebene were detected by the SPME method only. This study confirmed that the composition and contents of the volatile flavor compounds vary between different extraction methods. More volatile flavor compounds were identified using the SDE method than the SPME method.
Comparative analysis of elemental compositions of selected edible wild plants
Authors: Hong Young Shin , Kim Kyong Su
Published: October 2018

This study aimed to determine the elemental compositions of selected edible wild plant species, Hemerocallis fulva, Allium victorialis, Syneilesis palmata and Ligularia fischeri. The samples were dried, crushed, and subjected to microwave-assisted digestion. The macro and micro elements were analyzed by inductively coupled plasma-optical emission spectrometery (ICP-OES), and ICP-mass spectrometry (ICP-MS), respectively. The macro elements in the analyzed species decreased in the order K˃Ca˃P˃Mg˃S˃Fe˃Zn˃Na, and the micro elements followed the order Mn˃Ba˃Rb˃Cu˃Ni˃Ga˃Li˃Cr˃V˃Co˃Be˃Se. The percentage ratio of calcium content for potassium in the samples was 42.9% (A. victorialis) > 42.4% (S. palmata) > 33.8% (L. fischeri) > 25.3% (H. fulva). The calcium content was 13.7, 10.9, 6.4, and 2.9 times higher than the phosphorus content in S. palmata, L. fischeri, A. victorialis, and H. fulva, respectively (p<0.05). Manganese was the most predominant among the trace minerals, and it followed the order of A. victorialis > H. fulva > L. fischeri > S. palmata. In general, these wild plants are richer in calcium as compared to other common vegetables, and hence can be considered a good source for calcium that is lacking in Korean food products.
Antioxidant and biological activities of untreated and steam-treated Corni fructus extracts
Authors: Gu Yul Ri , Hong Joo-Heon
Published: October 2018

The aim of this study was to investigate functional food material for the antioxidant and biological activities of untreated and steam-treated Corni fructus extracts in extraction solvents (through hot-water extraction, 50% ethanol extraction, and 50% methanol extraction). The yield of UCH (hot-water extract of untreated Corni fructus) was 47.45% and it was higher than those of extracts (13.20-27.18%) obtained by the other extraction methods. The total phenolic and flavonoid contents were 12.23 g/100 g (SCE, 50% ethanol extract of steam-treated Corni fructus) and 5.08 g/100 g (SCE), respectively, and the total sugar content was 71.32 g/100 g (SCH, hot-water extract of steam-treated Corni fructus). The main organic acid components of the extracts were oxalic acid, citric acid, malic acid, formic acid, and gallic acid. The DPPH and ABTS radical scavenging activities of SCE at 1,000 μg/mL were 72.37% and 43.15%, respectively. The ferric-reducing antioxidant power of SCE at 1,000 μg/mL was 689.49 μM. The extracts were investigated for their function in L-132, RAW 264.7, HeLa, and MCF-7 cell lines. The SCE performed better than the other extracts in terms of its protective effects against oxidative stress in L-132 cells and increased the production of NO. Further the SCE showed antitumor activities against HeLa and MCF-7 cancer cells. Therefore, the SCE extracts is a good functional food material for the prevention of woman disease. Therefore, in our study, the SCE extracts is good functional food material for the prevention of oxidant, immunological, and tumor related disease.
An analytical method for quantifying diazinon, chlorfenapyr, and lufenuron in Napa cabbage using QuEChERS and HPLC-UV
Authors: Gotah Ahmed , Garcia Coralia V. , Lee Sam-Pin , Whang Key
Published: October 2018

A QuEChERS method was developed for the analysis of diazinon, chlorfenapyr, and lufenuron in Napa cabbage. These pesticides represent three different chemical classes and are commonly used in cabbage production in Korea. The objective of the proposed method is a fast, inexpensive, and easy extraction of pesticides, followed by rapid analysis. The proposed method involves a microscale extraction using acetonitrile and dispersive solid phase extraction (SPE), allowing for time and materials savings. The pesticides were separated and quantified using reversed-phase HPLC-UV at 220 nm. The calibration curves showed good linearity (R2>0.97), and the limits of detection and quantification were ≤0.05 and 1 mg/kg, respectively. Intraday and interday recoveries were in the range 97-116% and 101-112% with RSD% ≤9% for concentrations between 0.5-5 mg/kg. Abnormal recoveries and a substantial matrix effect were initially observed for lufenuron, signaling that optimization of lufenuron recovery requires a slight modification of the method. The proposed method was tested on cabbage samples sold at local markets, which showed no detectable residues of the target pesticides. The proposed method could thus be used for monitoring these pesticides in cabbage and similar vegetables.
Efficient conversion of conjugated linoleic acid c9,t11 by Lactobacillus fermentation from vegetable oil to generate fermented milk with high CLA content
Authors: Yang Hee-Sun , Lee Sang-Cheon , Huh Chang-Ki
Published: October 2018

The purpose of this study was to develop a functional and valuable dairy product with high conjugated linoleic acid (CLA) content through a fermentation method utilizing vegetable oil and probiotic lactic acid bacteria. Bifidobacterium breve KCTC 3419 was selected as a standard strain for high efficiency conversion of the CLA c9,t11. This standard strain was mixed in a definite ratio of 4:3:3 with Lactobacillus sakei LJ011 isolated from kimchi and the commercially available YF-L812 culture to generate a high-efficiency CLA conversion starter stock for use in fermented milk production. CLA conversion by safflower seed oil fermentation by the starter stock yielded the highest CLA containing fermented milk. The pH level, titratable acidity, and number of lactic acid bacteria in the fermented milk were altered to suitable levels during the fermented milk production process. The CLA content of CLA-fermented milk was maintained at 0.1% of the total CLA content during the storage period of 2 weeks.
Development of fermented pumpkin porridge as a meal replacement
Authors: Park Jung Suk , Na Hwan Sik
Published: October 2018

This study was performed to investigate the effects on addition rate of dried pumpkin leaf and seed to pumpkin porridge, as well as to examine the quality characteristics of fermented pumpkin porridge. For enzyme activities amylase and protease from fermented pumpkin porridge were examined. Fermented pumpkin porridge was prepared with different amount of pumpkin leaf and seed powder in the ratio of 0.25, 0.5, or 1.0% according to the quantity of porridge. With an increase in the quantity of fermented pumpkin leaf and seed powder added, the carbohydrate and crude protein contents of pumpkin porridge increased, whereas the crude lipid contents decreased. The total sugar contents in the control sample (without fermented pumpkin powder) was higher (26.23±2.15%) than that of the others (18.31-19.05%). Major free sugars in the samples were sucrose, glucose and fructose. The total free sugar contents in the control samples was higher (36.54±1.41%) than that in the other samples containing fermented pumpkin porridge powders. The Hunter’s L, a, and b value decreased as the contents of fermented pumpkin leaf and seed powder increased. Our results reveal that, adding fermented pumpkin leaf and seed powder could improve the quality of pumpkin porridge and addition of 1% powder is optimal.
Effects of mixed culture of Bacillus subtilis and Lactobacillus acidophilus on Cheonggukjang quality
Authors: Jang Eun Ho , Nam Donghun , Na Ha Gyoon , Jang Ki-Hyo
Published: October 2018

In this study, the quality characteristics of Cheonggukjang prepared with the mixed culture of Bacillus subtilis and Lactobacillus acidophilus were investigated. One of the most common characteristics of Cheonggukjang is the formation of viscous substance, which is the mixture of a fructose polymer and poly-gamma-glutamic acid. After the first Cheonggukjang fermentation, sucrose (0, 2.5, and 7.5 %) and a Lactobacillus acidophilus strain, containing the enzyme responsible for the production of exopolysaccharide, were supplemented, and then the second fermentation was carried out at 40℃ for 48 h. Changes in soluble solid contents, extension of viscous substance, pH, reducing sugar, amino-type and ammonia-type nitrogen content, enzyme activities, including α-amylase and protease, and isoflavone content were evaluated. The presence of sucrose in the starting fermentation materials decreased pH, aglycone-formed isoflavone, amino-type nitrogen, and protease activity, however, increased extension of viscous substance. Growth of acid-producing microbes, including L. acidophilus KCTC 3925, was stimulated by sucrose. In conclusion, the present study indicated that the mixed culture of B. subtilis and L. acidophilus changes the quality characteristics of Cheonggukjang, increasing formation of viscous substance.
Absorption characteristics of black elephant garlic powder containing maltodextrin
Authors: Park Jong-Jin , Park Dae-Hee , Lee Jae-Jun , Lee Sung-Yeon , Olawuyi Ibukunoluwa Fola , Lee Won-Young
Published: October 2018

In this study, we investigated the characteristics of black elephant garlic powder with maltodextrin. The quality parameters were analyzed such as water absorption, color value, solubility, average particle size and aqueous stability. The mixture ratios (black elephant garlic extract:maltodextrin) were 4:6, 5:5, 6:4, and 7:3. After homogenizing, the mixtures were lyophilized to produce garlic powders. The powders showed high solubility (90.87-96.93%). The lightness (L) decreased with increasing extract amount, whereas the redness (a) and yellowness (b) values increased. The average particle size decreased with increasing maltodextrin content except the 7:3 mixture ratio. The aqueous stability of the powders after 8 h ranged between 0.54 and 0.64. The absorption characteristics were measured under different relative humidities (11-84%) and temperatures (25 and 35℃) to calculate the mono-layer moisture content, the Guggenheim-Anderson-Boer (GAB) and Brunauer-Emmett-Teller (BET) equations were applied. Overall, the mixture of 4:6 presented a low equilibrium moisture content and low mono-layer moisture content regardless of the temperature. Caurie, Halsey, Kuhn, Oswin and Mizrahi models were applied to evaluate the suitability of the isotherm curve. Among them, the Halsey and Kuhn models both showed good fit because they presented high R2 values (0.934-0.992 and 0.955-0.990, respectively) and low deviations (4.829-9.436% and 5.043-9.989%, respectively).
Anti-amnestic effect of Spirulina platensis in high-fat diet-induced obese mice
Authors: Park Seon Kyeong , Han Hye Ju , Kim Jong Min , Kang Jin Yong , Park Su Bin , Yoo Seol Ki , Jeong Jae Hong , Kwon Jong Hee , Heo Ho Jin
Published: October 2018

The aim of this study was to examine the ameliorating effect of Spirulina platensis (SP) on cognitive dysfunction in high-fat-diet (HFD) mice. Glucose tolerance was evaluated using the intraperitoneal glucose tolerance test (IPGTT). The results showed that the area under the curve (AUC) decreased 20% in the SP group compared to that in the HFD group. The ameliorating effect on HFD-induced learning and memory impairment was investigated using Y-maze and Morris water maze tests. The administration of SP effectively restored learning and memory function compared to that in the HFD group. Using blood serum analysis, liver and kidney function and lipid metabolism-related biomarkers were measured. Generally, administration of SP effectively restored lipid-metabolism by increasing HDLC (HTR) and decreasing LDLC. The antioxidant effects in tissues were also investigated by measuring the superoxide dismutase (SOD) content, oxidized glutathione (GSH)/total GSH ratio, and malondialdehyde (MDA) content, and the administration of SP effectively improved the antioxidant system in the brain and liver tissues. The improvement of cognitive function was confirmed by the inhibitory effect of acetylcholinesterase (AChE) as a biomarker of the cholinergic system, which plays an important role in neurotransmission, and the SP group showed significant inhibition of AChE. Based on these results, SP could be used to improve brain function by ameliorating the HFD condition.
HSF2BP Negatively Regulates Homologous Recombination in DNA Interstrand Crosslink Repair in Human Cells by Direct Interaction With BRCA2
Authors: Brandsma Inger , Sato Koichi , van Rossum-Fikkert Sari E. , Reuter Marcel , Odijk Hanny , Verkaik Nicole , van den Tempel Nathalie , Oostra Anneke B. , Dekkers Dick H. W. , Bezstarosti Karel , Demmers Jeroen A. A. , Lebbink Joyce , Wyman Claire , Dorsman Josephine C. , van Gent Dik C. , Knipscheer Puck , Kanaar Roland , Zelensky Alex N.
Published: October 2018

The tumor suppressor BRCA2 is essential for homologous recombination, replication fork stability and DNA interstrand crosslink (ICL) repair in vertebrates. We show that a functionally uncharacterized protein, HSF2BP, is involved in a novel, direct and highly evolutionarily conserved interaction with BRCA2. Although HSF2BP was previously described as testis-specific, we find it is expressed in mouse ES cells, in human cancer cell lines, and in tumor samples. Elevated levels of HSF2BP sensitize human cells to ICL-inducing agents (mitomycin C and cisplatin) and PARP inhibitors, resulting in a phenotype characteristic of cells from Fanconi anemia (FA) patients. We biochemically recapitulate the suppression of ICL repair and establish that excess HSF2BP specifically compromises homologous recombination by preventing BRCA2 and RAD51 loading at the ICL. As increased ectopic expression of HSF2BP occurs naturally, we suggest that it can be considered as a causative agent in FA and a source of cancer-promoting genomic instability.
The genome-wide, multi-layered architecture of chromosome pairing in earlyDrosophilaembryos
Authors: Erceg Jelena , Abed Jumana AlHaj , Goloborodko Anton , Lajoie Bryan R. , Fudenberg Geoffrey , Abdennur Nezar , Imakaev Maxim , McCole Ruth B. , Nguyen Son C. , Saylor Wren , Joyce Eric F. , Senaratne T. Niroshini , Hannan Mohammed A. , Nir Guy , Dekker Job , Mirny Leonid A. , Wu Chao-ting
Published: October 2018

Genome organization involvescisandtranschromosomal interactions, both implicated in gene regulation, development, and disease. Here, we focused ontransinteractions inDrosophila, where homologous chromosomes are paired in somatic cells from embryogenesis through adulthood. We first addressed the long-standing question of whether pairing extends genome-wide and, to this end, developed a haplotype-resolved Hi-C approach that uses a new strategy to minimize homolog misassignment and thus robustly distinguishtrans-homolog fromciscontacts. This approach revealed striking genome-wide pairing inDrosophilaembryos. Moreover, we discovered pairing to be surprisingly structured, withtrans-homolog domains and interaction peaks, many coinciding with the positions of analogouscisfeatures. We also found a significant correlation between pairing and the chromatin accessibility mediated by the pioneer factor Zelda. Our findings reveal a complex, highly structured organization underlying homolog pairing, first discovered more than a century ago.

One Sentence Summary

A robust approach for haplotype-resolved Hi-C reveals highly-structured homolog pairing in early stageDrosophilaembryos.
Highly structured homolog pairing reflects functional organization of theDrosophilagenome
Authors: Abed Jumana AlHaj , Erceg Jelena , Goloborodko Anton , Nguyen Son C. , McCole Ruth B. , Saylor Wren , Fudenberg Geoffrey , Lajoie Bryan R. , Dekker Job , Mirny Leonid A. , Wu Ting (C.-ting)
Published: October 2018

Trans-homolog interactions encompass potent regulatory functions, which have been studied extensively inDrosophila,where homologs are paired in somatic cells and pairing-dependent gene regulation, or transvection, is well-documented. Nevertheless, the structure of pairing and whether its functional impact is genome-wide have eluded analysis. Accordingly, we generated a diploid cell line from divergent parents and applied haplotype-resolved Hi-C, discovering that homologs pair relatively precisely genome-wide in addition to establishingtrans-homolog domains and compartments. We also elucidated the structure of pairing with unprecedented detail, documenting significant variation across the genome. In particular, we characterized two forms: tight pairing, consisting of contiguous small domains, and loose pairing, consisting of single larger domains. Strikingly, active genomic regions (A-type compartments, active chromatin, expressed genes) correlated with tight pairing, suggesting that pairing has a functional role genome-wide. Finally, using RNAi and haplotype-resolved Hi-C, we show that disruption of pairing-promoting factors results in global changes in pairing.

One Sentence Summary

Haplotype-resolved Hi-C reveals structures of homolog pairing and global implications for gene activity in hybrid PnM cells.
Immune profiling of cord blood after prolonged rupture of membranes
Authors: Tsaliki Evdokia , Turner Carolin T , Venturini Cristina , Kam Christy , Strang Angela , Bailey Sarah , Rodgers Alison , Levine Adam P , Chain Benjamin M , Simpson Nandi , Riley Eleanor M. , Field Nigel , Brocklehurst Peter , Noursadeghi Mahdad
Published: October 2018

We hypothesised that foetal immune responses to an infectious challenge may be detected by genome-wide transcriptional profiling of cord blood. In order to test this hypothesis, we sought to identify transcriptomic changes in post-natal cord blood samples following prolonged pre-labour rupture of membranes (PROM) as a surrogate for increased risk of infection. By comparison to controls we found increased levels of blood transcripts in a subset of prolonged PROM cases, significantly enriched for innate immune system signalling pathways. These changes were idiosyncratic, suggesting qualitative and quantitative variation in foetal immune responses which may reflect differences in exposure and/or in host genetics. Our data support the view that PROM represents an infection risk to the foetus. In addition, we propose that cord blood transcriptional profiling offers exciting opportunities to identify immune correlates of clinical outcome following potential in utero exposures to infection. These may be used to elucidate the mechanisms of immunological protection and pathology in the foetus and identify biomarkers to stratify the risk of adverse outcomes.
Quantitative reconstruction of time-varying 3D cell forces with traction force optical coherence microscopy
Authors: Mulligan Jeffrey A. , Feng Xinzeng , Adie Steven G.
Published: October 2018

Cellular traction forces (CTFs) play an integral role in both physiological processes and disease, and are a topic of interest in mechanobiology. Traction force microscopy (TFM) is a family of methods used to quantify CTFs in a variety of settings. State-of-the-art 3D TFM methods typically rely on confocal fluorescence microscopy, which can impose limitations on acquisition speed, volumetric coverage, and temporal sampling or coverage. In this report, we present the first quantitative implementation of a new TFM technique: traction force optical coherence microscopy (TF-OCM). TF-OCM leverages the capabilities of optical coherence microscopy and computational adaptive optics (CAO) to enable the quantitative reconstruction of 3D CTFs in scattering media with minute-scale temporal resolution. We applied TF-OCM to quantify CTFs exerted by isolated NIH-3T3 fibroblasts embedded in Matrigel, with five-minute temporal sampling, using images which spanned a 500×500×500 μm3 field-of-view. Due to the reliance of TF-OCM on computational imaging methods, we have provided extensive discussion of the underlying equations, assumptions, and failure modes of these methods. TF-OCM has the potential to advance studies of biomechanical behavior in scattering media, and may be especially well-suited to the study of cell collectives such as spheroids, a prevalent model in mechanobiology research.
EEG signal diversity during propofol sedation: an increase in sedated but responsive, a decrease in sedated and unresponsive subjects
Authors: Bola Michał , Orłowski Paweł , Płomecka Martyna , Marchewka Artur
Published: October 2018

Transitions between wakefulness and anesthesia are accompanied by profound changes in brain functioning. A key challenge is thus to disentangle neuronal mechanisms specific to loss and recovery of consciousness, from more general effects that are not directly related to the capacity for conscious experience. Measures of neuronal diversity have been recently proposed to constitute a robust correlate of the global states of consciousness. In the present study we investigated whether EEG signal diversity is indeed related to behavioral responsiveness during propofol sedation, or rather to the general drug-related effects. To this end, we reanalyzed data collected from 20 subjects sedated with propofol. Based on the responsiveness to auditory stimuli all subjects were subdivided into two subgroups - responsive (n = 13), who remains awake throughout the experiment, and drowsy (n = 7), who becomes unresponsive during moderate sedation. Resting state EEG recorded during wakefulness and sedation was characterized by the Mean Information Gain (MIG) and Fluctuation complexity (FC) - information-theory measures estimating signal diversity or complexity, respectively. The main finding is that the drowsy group exhibited a decrease in diversity during sedation but, unexpectedly, the responsive group exhibited a robust increase in diversity (ANOVA group x state interaction: F(3) = 7.81, p < 0.001; BF10 > 197). However, signal complexity neither differentiated the subgroups, nor decreased reliably during sedation (t-test wake vs. moderate sedation: t(19) = 2.57, p = 0.092; BF10 = 3.08). Further, we show that a change in signal diversity is negatively correlated with a delta power change (r = −0.62, p = 0.002), and positively correlated with a beta power change (r = 0.84, p < 0.001). Finally, we show that MIG behaves in a qualitatively similar manner to Lempel-Ziv – another diversity measures used in several recent studies. Overall, we revealed that propofol sedation is initially related to an increase in EEG signal diversity, and that only upon loss of responsiveness EEG diversity decreases. The qualitatively different pattern of changes in the responsive and drowsy groups makes EEG diversity a robust indirect index of responsiveness and, presumably, consciousness.
Genetic networks underlying natural variation in basal and induced activity levels inDrosophila melanogaster
Authors: Watanabe Louis P. , Gordon Cameron , Momeni Mina Y. , Riddle Nicole C.
Published: October 2018

Exercise is recommended by health professionals across the globe as part of a healthy lifestyle to prevent and/or treat the consequences of obesity. While overall, the health benefits of exercise and an active lifestyle are well understood, very little is known about how genetics impacts an individual’s inclination for and response to exercise. To address this knowledge gap, we investigated the genetic architecture underlying natural variation in activity levels in the model systemDrosophila melanogaster. Activity levels were assayed in the Drosophila Genetics Reference Panel 2 fly strains at baseline and in response to a gentle exercise treatment using the Rotational Exercise Quantification System. We found significant, sex-dependent variation in both activity measures and identified over 100 genes that contribute to basal and induced exercise activity levels. This gene set was enriched for genes with functions in the central nervous system and in neuromuscular junctions and included several candidate genes with known activity phenotypes such as flightlessness or uncoordinated movement. Interestingly, there were also several chromatin proteins among the candidate genes, two of which were validated and shown to impact activity levels. Thus, the study described here reveals the complex genetic architecture controlling basal and exercise-induced activity levels inD. melanogasterand provides a resource for exercise biologists.
Association study of long-term kidney transplant rejection using whole-exome sequencing
Authors: Gioia Louis , Kurian Sunil , Mondala Tony S. , Bassaganyas Laia , Kwok Pui-Yan , Salomon Daniel R. , Su Andrew I.
Published: October 2018

Long-term renal allograft rejection is the most common outcome in kidney transplantation. Continuing the crusade to extend allograft function after the first year post-transplantation, we attempted to associate genetic factors that might contribute to long-term allograft outcomes by sequencing the exomes of patients diagnosed with chronic allograft nephropathy/interstitial fibrosis and tubular atrophy. A variety of association analyses were employed, but these analyses failed to identify statistically significant associations. The study was underpowered to detect the association of rare genomic variants with small effect sizes. However, it confirmed previous reports of the absence of large effects from common variants. We have made both the study data and analysis workflow available for public use, and we hope that these resources will help to power future meta-analyses that may detect smaller effects.
Rhizosphere microbes influence host circadian clock function
Authors: Hubbard Charley J. , McMinn Robby , Weinig Cynthia
Published: October 2018

The circadian clock is an important determinant of individual fitness that is entrained by local conditions. In addition to known abiotic inputs that entrain the circadian clock, individual pathogenic soil bacteria affect the circadian period of plant hosts. Yet, in nature, plants interact with diverse microbial communities including hundreds to thousands of microbial taxa, and the effect of these communities on clock function remains unclear. In Arabidopsis thaliana, we used diverse rhizosphere inoculates and both wild-type and clock mutant genotypes to test the effect of complex rhizosphere microbial communities on the host circadian clock. Host plants with an intact rhizosphere microbiome expressed a circadian period that was closer to 24 hrs in duration and significantly shorter (by 60 minutes on average) relative to plants grown with a disrupted microbiome. Wild-type host genotypes differed significantly in clock sensitivity to microbiome treatments, where the effect was most pronounced in the Landsberg erecta genotype and least in the Columbia genotype. Rhizosphere microbes collected from a host genotype with a short-period phenotype (toc1-21) and used as inoculate significantly shortened the long-period phenotype of the ztl-1 clock mutant genotype. The results indicate that complex rhizosphere microbial communities significantly affect host clock function.
Crystal structure of m4-1BB/4-1BBL complex reveals an unusual dimeric ligand that undergoes structural changes upon receptor binding
Authors: Bitra Aruna , Doukov Tzanko , Destito Giuseppe , Croft Michael , Zajonc Dirk M.
Published: October 2018

The interaction between the 4-1BB and its ligand 4-1BBL provides co-stimulatory signals for T cell activation and proliferation, but differences in the mouse and human molecules might result in differential engagement of this pathway. Here, we report the crystal structure of mouse 4-1BBL and of the mouse 4-1BB/4-1BBL complex, together provide insights into the molecular recognition of the cognate receptor by m4-1BBL. In contrast to all human or mouse TNF ligands that form non-covalent mostly trimeric assemblies, the m4-1BBL structure formed a novel disulfide linked dimeric assembly. The structure showed that certain differences in the amino acid composition along the intramolecular interface, together with two specific residues (Cys 246 and Ser 256) that are exclusively present in m4-1BBL, are responsible for unique dimerization. Unexpectedly, upon binding to m4-1BB, m4-1BBL undergoes structural changes within each protomer, in addition the individual m4-1BBL protomers rotate with respect to each other, leading to a different dimerization interface with more inter-subunit interactions. In the m4-1BB/4-1BBL complex, each receptor monomer binds exclusively to a single ligand subunit with contributions of cysteine-rich domain (CRD) 1, CRD2 and CRD3. Furthermore, structure-guided mutagenesis of the binding interface revealed that novel binding interactions with the GH loop, rather than the DE loop, are energetically critical and define the species based receptor selectivity for m4-1BBL. A comparison with the human 4-1BB/4-1BBL complex highlighted several differences between the ligand and receptor binding interfaces and provide an explanation for the absence of inter species cross-reactivity between human and mouse 4-1BB and 4-1BBL molecules.
Value-based Decision Making Takes Place in the Action Domain in the Prefrontal Cortex
Authors: Lin Zhongqiao , Nie Chechang , Zhang Yuanfeng , Chen Yang , Yang Tianming
Published: October 2018

Value-based decision making is a process in which humans or animals maximize their gain by selecting appropriate options and performing the corresponding actions to acquire them. Whether the evaluation process of the options in the brain can be independent from their action contingency has been hotly debated. To address the question, we trained rhesus monkeys to make decisions by integrating evidence and studied whether the integration occurred in the stimulus or the action domain in the brain. After the monkeys learned the task, we recorded both from the orbitofrontal (OFC) and dorsolateral prefrontal (DLPFC) cortices. We found that the OFC neurons encoded the value associated with the single piece of evidence in the stimulus domain. Importantly, the representations of the value in the OFC was transient and the information was not integrated across time for decisions. The integration of evidence was observed only in the DLPFC and only in the action domain. We further used a neural network model to show how the stimulus-to-action transition of value information may be computed in the DLPFC. Our results indicated that the decision making in the brain is computed in the action domain without an intermediate stimulus-based decision stage.
Nanopore formation in the cuticle of an insect olfactory sensillum
Authors: Ando Toshiya , Sekine Sayaka , Inagaki Sachi , Misaki Kazuyo , Badel Laurent , Moriya Hiroyuki , Sami Mustafa M. , Itakura Yuki , Chihara Takahiro , Kazama Hokto , Yonemura Shigenobu , Hayashi Shigeo
Published: October 2018

Nanometer-level patterned surface structures form the basis of biological functions including superhydrophobicity, structural coloration, and light absorption [1-3]. In insects, the cuticle overlying the olfactory sensilla has multiple small (50–200-nm diameter) pores [4-8], which are supposed to function as a filter that admits odorant molecules, while preventing the entry of larger airborne particles and limiting water loss. However, the cellular processes underlying the patterning of extracellular matrices into functional nano-structures remain unknown. Here we show that cuticular nanopores inDrosophilaolfactory sensilla originate from a curved ultrathin film that is formed in the outermost envelope layer of the cuticle, and secreted from specialized protrusions in the plasma membrane of the hair forming (trichogen) cell. The envelope curvature coincides with plasma membrane undulations associated with endocytic structures. Thegore-tex/Osiris23gene encodes an endosomal protein that is essential for envelope curvature, nanopore formation, and odor receptivity, and is expressed specifically in developing olfactory trichogen cells. The 24-memberOsirisgene family is expressed in cuticle-secreting cells, and is found only in insect genomes. These results reveal an essential requirement for nanopores for odor reception and identifyOsirisgenes as a platform for investigating the evolution of surface nano-fabrication in insects.
Epigenetic drift during long-term culture of cells in vitro
Authors: Franzen Julia , Georgomanolis Theodoros , Selich Anton , Kuo Chao-Chung , Stöger Reinhard , Brant Lilija , Mulabdić Melita Sara , Fernandez-Rebollo Eduardo , Grezella Clara , Ostrowska Alina , Begemann Matthias , Nikolić Miloš , Rath Björn , Ho Anthony D. , Rothe Michael , Schambach Axel , Papantonis Argyris , Wagner Wolfgang
Published: October 2018

Culture expansion of primary cells evokes highly reproducible DNA methylation (DNAm) changes at specific sites in the genome. These changes might be due to an directly regulated epigenetic process, or to gradual deregulation of the epigenetic state, which is often referred to as “epigenetic drift”. We have identified CG dinucleotides (CpGs) that become continuously hyper- or hypomethylated in the course of culture expansion of mesenchymal stem cells (MSCs) and other cell types. During reprogramming into induced pluripotent stem cells (iPSCs) particularly the culture-associated hypomethylation is reversed simultaneously with age-associated and pluripotency-associated DNAm changes. Bisulfite barcoded amplicon sequencing (BBA-seq) demonstrated that upon passaging the DNAm patterns of neighboring CpGs become more complex without evidence of continuous pattern development and without association to oligoclonal subpolulations of MSCs at later passages. Circularized chromatin conformation capture (4C) revealed reproducible changes in nuclear organization between early and late passages, while there was no preferential interaction with other genomic regions that also harbor culture-associated DNAm changes. Chromatin immunoprecipitation of CTCF did not show significant differences during long-term culture of MSCs, however culture-associated hypermethylation was enriched at CTCF binding sites and hypomethylated CpGs were devoid of CTCF. Taken together, our results indicate that DNAm changes during culture-expansion resembles epigenetic drift, which seems to occur in relation to chromatin conformation.
A global survey of arsenic related genes in soil microbiomes
Authors: Dunivin Taylor K , Yeh Susanna Y , Shade Ashley
Published: October 2018

Environmental resistomes include transferable microbial genes. One important resistome component is resistance to arsenic, a ubiquitous and toxic metalloid that can have negative and chronic consequences for human and animal health. The distribution of arsenic resistance and metabolism genes in the environment is not well understood. However, microbial communities and their resistomes mediate key transformations of arsenic that are expected to impact both biogeochemistry and local toxicity. We examined the phylogenetic diversity, genomic location (chromosome or plasmid), and biogeography of arsenic resistance and metabolism genes in 922 soil genomes and 38 metagenomes. To do so, we developed a bioinformatic toolkit that includes BLAST databases, hidden Markov models and resources for gene-targeted assembly of nine arsenic resistance and metabolism genes: acr3, aioA, arsB, arsC (grx), arsC (trx), arsD, arsM, arrA, and arxA. Though arsenic related genes were common, they were not universally detected, contradicting the common conjecture that all organisms have them. From major clades of arsenic related genes, we inferred their potential for horizontal and vertical transfer. Different types and proportions of genes were detected across soils, suggesting microbial community composition will, in part, determine local arsenic toxicity and biogeochemistry. While arsenic related genes were globally distributed, particular sequence variants were highly endemic (e.g., acr3), suggesting dispersal limitation. The gene encoding arsenic methylase arsM was unexpectedly abundant in soil metagenomes (median 48%), suggesting that it plays a prominent role in global arsenic biogeochemistry. Our analysis advances understanding of arsenic resistance, metabolism, and biogeochemistry, and our approach provides a roadmap for the ecological investigation of environmental resistomes.
Joint single cell DNA-Seq and RNA-Seq of cancer reveals subclonal signatures of genomic instability and gene expression
Authors: Andor Noemi , Lau Billy T. , Catalanotti Claudia , Kumar Vijay , Sathe Anuja , Belhocine Kamila , Wheeler Tobias D. , Price Andrew D. , Song Maengseok , Džakula Željko , Sorenson Jon , Stafford David , Bent Zachary , DeMare Laura , Hepler Lance , Jett Susana , Lin Bill Kengli , Maheshwari Shamoni , Makarewicz Anthony J. , Rahimi Mohammad , Sawhney Sanjam S. , Sauzade Martin , Shuga Joe , Sullivan-Bibee Katrina , Weinstein Adam , Yang Wei , Yin Yifeng , Kubit Matthew , Chen Jiamin , Grimes Susan M. , Suarez Carlos Jose , Poultsides George A. , Schnall-Levin Michael , Bharadwaj Rajiv , Ji Hanlee P.
Published: October 2018

Sequencing the genomes of individual cancer cells provides the highest resolution of intratumoral heterogeneity. To enable high throughput single cell DNA-Seq across thousands of individual cells per sample, we developed a droplet-based, automated partitioning technology for whole genome sequencing. We applied this approach on a set of gastric cancer cell lines and a primary gastric tumor. In parallel, we conducted a separate single cell RNA-Seq analysis on these same cancers and used copy number to compare results. This joint study, covering thousands of single cell genomes and transcriptomes, revealed extensive cellular diversity based on distinct copy number changes, numerous subclonal populations and in the case of the primary tumor, subclonal gene expression signatures. We found genomic evidence of positive selection – where the percentage of replicating cells per clone is higher than expected – indicating ongoing tumor evolution. Our study demonstrates that joining single cell genomic DNA and transcriptomic features provides novel insights into cancer heterogeneity and biology.

SIGNIFICANCE

We conducted a massively parallel DNA sequencing analysis on a set of gastric cancer cell lines and a primary gastric tumor in combination with a joint single cell RNA-Seq analysis. This joint study, covering thousands of single cell genomes and transcriptomes, revealed extensive cellular diversity based on distinct copy number changes, numerous subclonal populations and in the case of the primary tumor, subclonal gene expression signatures. We found genomic evidence of positive selection where the percentage of replicating cells per clone is higher than expected indicating ongoing tumor evolution. Our study demonstrates that combining single cell genomic DNA and transcriptomic features provides novel insights into cancer heterogeneity and biology.