bluuebunny/crossref_metadata_2025 huggingface dataset:
Short- and Long-term Risks of Highly Active Antiretroviral Treatment with Incident Opportunistic Infections among People Living with HIV/AIDS
Authors: Yen Yung-Feng , Chen Marcelo , Jen I.-An , Chuang Pei-Hung , Lee Chun-Yuan , Lin Su-I. , Chen Yi-Ming Arthur
Published: March 2019

Highly active antiretroviral therapy (HAART) causes a rapid increase of CD4 + T cells counts during the first 3–6 months of treatment and may enhance the development of opportunistic infections (OIs). However, the short- and long-term effects of HAART exposure on the development of incident OIs has not been extensively studied. This nationwide longitudinal study followed up a total of 26,258 people living with HIV/AIDS (PLWHA) to ascertain the short- and long-term effects of HAART on incident OIs. During 150,196 person-years of follow-up, 6,413 (24.4%) PLWHA had new onset of OIs. After adjusting for demographics, comorbidities, and AIDS status, PLWHA who received HAART were more likely to develop OIs than those who did not receive HAART. Considering the short- and long-term effects of HAART on the development of OIs, HAART was found to be a risk factor for developing OIs during the first 90 days of treatment, but a protective factor against OIs after 180 days of HAART use. The risk for the development of active OIs significantly decreased as the duration of HAART increased (P < 0.001). Our study suggests that HAART is a risk factor for developing OIs in the short term, but is a protective factor in the long term.
Relationship between Daily and In-laboratory Gait Speed among Healthy Community-dwelling Older Adults
Authors: Takayanagi Naoto , Sudo Motoki , Yamashiro Yukari , Lee Sangyoon , Kobayashi Yoshiyuki , Niki Yoshifumi , Shimada Hiroyuki
Published: March 2019

Gait speed in laboratory settings (in-laboratory gait speed) is one of the important indicators associated with the decline in functional abilities in older adulthood. Recently, it has become possible to measure gait speed during daily living (daily gait speed) using accelerometers. However, the relationship between these two gait speed parameters is unclear. This study aimed to compare in-laboratory gait speed, measured by a sheet-type pressure sensor, and daily gait speed, measured by an accelerometer, in healthy community-dwelling older adults. Participants were aged ≥60 years, residing in Takahama city, Aichi, Japan. To calculate daily gait speed, participants were instructed to wear a tri-axial accelerometer on their waist. A total of 1965 participants were included in the final analysis. The results showed a weak association (r = 0.333, p < 0.001) between the two gait speed parameters. Furthermore, average daily gait speed was significantly lower than average in-laboratory gait speed. However, both gait speed parameters declined significantly with age. These results suggest that, in addition to in-laboratory gait speed, daily gait speed may be a helpful parameter for predicting decline in functional abilities.
Metabolomic study of saxitoxin analogues and biosynthetic intermediates in dinoflagellates using 15N-labelled sodium nitrate as a nitrogen source
Authors: Cho Yuko , Tsuchiya Shigeki , Omura Takuo , Koike Kazuhiko , Oikawa Hiroshi , Konoki Keiichi , Oshima Yasukatsu , Yotsu-Yamashita Mari
Published: March 2019

A stable-isotope-labelling method using 15N-labelled sodium nitrate as a nitrogen source was developed for the toxic dinoflagellate Alexandrium catenella. The labelled saxitoxin analogues (STXs), their precursor, and the biosynthetic intermediates were analyzed by column-switching high-resolution hydrophilic interaction liquid chromatography with mass spectrometry. The low contents on Day 0, high 15N incorporation % of Int-C’2 and Int-E’ suggested that their turn-over rates are high and that the sizes of the pool of these compounds are smaller than those of the other intermediates. The experimentally determined isotopomer distributions showed that arginine, Int-C’2, 11-hydroxy-Int-C’2, Int-E’, GTX5, GTX4, C1, and C2, each existed as a combination of three populations that consisted of the non-labelled molecules and the labelled isotopomers representing molecules newly synthesized by incorporation of 15N assimilated from the medium with two different incorporation rates. The order of 15N incorporation % values of the labelled populations predicted by this model largely agreed with the proposed biosynthetic route. The stable-isotope-labelling method will be useful for understanding the complex mechanism of nitrogen flux in STX-producing dinoflagellates.
A universal constant for dark matter-baryon interplay
Authors: Chan Man Ho
Published: March 2019

Recent studies point out that there exists some rough scaling relations for dark matter and some tight connections between dark matter and baryons. However, most of the relations and tight connections can only be found in galaxies, but not in galaxy clusters. In this article, we consider a new expression that can characterize the properties of dark matter-baryon interplay for both galactic and galaxy cluster scales. By using the archival observational data of galaxies and galaxy clusters, we show that the value$${\boldsymbol{K}}{\boldsymbol{=}}{\bar{{\boldsymbol{n}}}}_{{\boldsymbol{D}}}{\bar{{\boldsymbol{n}}}}_{{\boldsymbol{B}}}{{\boldsymbol{r}}}_{{\boldsymbol{o}}}{\boldsymbol{V}}{\boldsymbol{/}}{{\boldsymbol{v}}}^{{\bf{4}}}$$K=n¯Dn¯BroV/v4is almost a constant and scale independent within the optical radiusro, where$${\bar{{\boldsymbol{n}}}}_{{\boldsymbol{D}}}$$n¯Dis the average dark matter number density,$${\bar{{\boldsymbol{n}}}}_{{\boldsymbol{B}}}$$n¯Bis the average baryon number density,vis the characteristic velocity andVis the interacting volume. This would be the first universal relation between dark matter and baryons on both galactic and galaxy cluster scales. We anticipate this result to be a starting point to explain the small-scale problem and the scaling relations for dark matter in galaxies. The constantKdiscovered may reveal some underlying global interaction between dark matter and baryons.
Seasonal and diel acoustic presence of North Atlantic minke whales in the North Sea
Authors: Risch Denise , Wilson Samuel C. , Hoogerwerf Mathilde , van Geel Nienke C. F. , Edwards Ewan W. J. , Brookes Kate L.
Published: March 2019

Despite frequent records from other parts of the North Atlantic, minke whales have never been acoustically recorded in the North Sea. This study investigated the detectability of pulse trains previously associated with this species in other regions, in acoustic data from ten sites along the east coast of Scotland. Since preliminary results confirmed pulse train presence, subsequently, an automated detector was applied to these data to record the seasonal and diel presence of minke whale pulse trains. Minke whales were detected from May to November, with most detections occurring in June, July and October. No acoustic detections were made in December, January or in the month of April, whilst no data were available for February and March. This pattern of acoustic presence supports available visual data and suggested an absence of minke whales from the study area during winter. Minke whale acoustic presence showed a statistically significant diel pattern, with a detection peak during night time. This study established the acoustic detectability of minke whales in the North Sea and highlights the potential of using passive acoustic monitoring to study the seasonal presence and spatial distribution of minke whales in the North Sea and wider Northeast Atlantic.
Impact of Polymerase Fidelity on Background Error Rates in Next-Generation Sequencing with Unique Molecular Identifiers/Barcodes
Authors: Filges Stefan , Yamada Emiko , Ståhlberg Anders , Godfrey Tony E.
Published: March 2019

Liquid biopsy and detection of tumor-associated mutations in cell-free circulating DNA often requires the ability to identify single nucleotide variants at allele frequencies below 0.1%. Standard sequencing protocols cannot achieve this level of sensitivity due to background noise from DNA damage and polymerase induced errors. Addition of unique molecular identifiers allows identification and removal of errors responsible for this background noise. Theoretically, high fidelity enzymes will also reduce error rates in barcoded NGS but this has not been thoroughly explored. We evaluated the impact of polymerase fidelity on the magnitude of error reduction at different steps of barcoded NGS library construction. We find that barcoding itself displays largest impact on error reduction, even with low fidelity polymerases. Use of high fidelity polymerases in the barcoding step of library construction further suppresses error in barcoded NGS, and allows detection of variant alleles below 0.1% allele frequency. However, the improvement in error correction is modest and is not directly proportional to polymerase fidelity. Depending on the specific application, other polymerase characteristics such as multiplexing capacity, PCR efficiency, buffer requirements and ability to amplify targets with high GC content may outweigh the relatively small additional decrease in error afforded by ultra-high fidelity polymerases.
Screening for HPV infection in exfoliated cervical cells of women from different ethnic groups in Yili, Xinjiang, China
Authors: Pan Zhenzhen , Song Yuning , Zhe Xiangyi , Wang Weibin , Zhu Junling , Zheng Weinan , Li Hongtao , Li Dongmei , Cao Dongdong , Pan Zemin , Shao Renfu
Published: March 2019

We investigated the infection status and genotype distribution of human papillomavirus (HPV) in women of different ages and various ethnic groups in the Yili region, Xinjiang, China. We checked the HPV genotypes of 3,445 samples of exfoliated cervical cells using the PCR–reverse dot blot method. The total infection rate of HPV was 25.60% (882/3,445). The ethnic stratification showed that the infection rates were 22.87% (196/857) in Uygur, 21.55% (122/566) in Kazak, and 27.89% (564/2,022) in Han individuals. The most prevalent high-risk genotypes were HPV16, HPV52, and HPV53 in Uygur and Kazak and HPV16, HPV52, and HPV58 in Han ethnic groups. The age stratification showed that the infection rates in Han, Uygur, and Kazak women were up to 40.9% (61/149) in those aged 26–30 years, 41.5% (22/53) in those over 61 years old, and 30.2% (29/96) in those 46–50 years old, respectively. Therefore, HPV infection and HPV genotype distribution varied among the different age groups of the three ethnic groups.
Improvement of telescope resolution using a diffractive phase modulater
Authors: Wen Yuxiang , Wang Kunpeng , Kuang Dengfeng
Published: March 2019

Metasurface, fluorescent microscopy and scanning near-field optical microscopy can improve the resolution of microscopes remarkably, while the resolution of the telescope remains unimproved constrained by its giant objective lenses and distant targets. Here we put forward a way to raise the resolution of telescopes simply by adding a binary optical thin surface around its focal plane. Simulation results show that the surface can raise the image quality in the Cassegrain and Kepler telescope. By nano-lathe, we fabricated a designed binary surface and experiment it in the Kepler telescope. The results are consistent with those of simulation results. More details of the calibrated target are resolvable on the image plane after applying the binary optical surface. It proves that the binary optic surface can make contribute to the resolution of the telescope, thus is beneficial in astronomy, military surveillance field.
Decoding the contents and strength of imagery before volitional engagement
Authors: Koenig-Robert Roger , Pearson Joel
Published: March 2019

Is it possible to predict the freely chosen content of voluntary imagery from prior neural signals? Here we show that the content and strength of future voluntary imagery can be decoded from activity patterns in visual and frontal areas well before participants engage in voluntary imagery. Participants freely chose which of two images to imagine. Using functional magnetic resonance (fMRI) and multi-voxel pattern analysis, we decoded imagery content as far as 11 seconds before the voluntary decision, in visual, frontal and subcortical areas. Decoding in visual areas in addition to perception-imagery generalization suggested that predictive patterns correspond to visual representations. Importantly, activity patterns in the primary visual cortex (V1) from before the decision, predicted future imagery vividness. Our results suggest that the contents and strength of mental imagery are influenced by sensory-like neural representations that emerge spontaneously before volition.
Sex-specific spatial and temporal gene expressions of Pheromone biosynthesis activating neuropeptide (PBAN) and binding proteins (PBP/OBP) in Spoladea recurvalis
Authors: Senthilkumar Rajendran , Srinivasan Ramasamy
Published: March 2019

Spoladea recurvalis is one of the most destructive insect pests of amaranth, a leafy vegetable in both Asia and Africa. The present study characterized the pheromone biosynthesis-activating neuropeptide (DH-PBAN) and pheromone/odorant binding proteins in S. recurvalis. The open reading frame of 600 base pairs encodes a 200-amino acid protein possessing five neuropeptide motifs (DH, PBAN, α-, β-, and γ- subesophageal ganglion neuropeptides) and shares a characteristic conserved C-terminal pentapeptide fragment FXPRL. The full-length genome of Spre-DH-PBAN was 4,295 bp in length and comprised of six exons interspersed by five introns. Sequence homology and phylogenetic analysis of Spre-DH-PBAN have high similarity to its homologs in Crambidae of Lepidopteran order. We quantitatively measured the relative expression level (qRT_PCR) of Spre-DH-PBAN gene, the binding proteins such as odorant binding proteins (OBPs) and pheromone binding protein (PBPs) at different developmental stages. The results confirmed their role in recognition and chemoreception of sex pheromone components, and they were distinct, tissue- and sex-specific. This is the first report on the molecular analysis of PBAN gene and binding proteins, which can improve the understanding of molecular mechanisms of growth, development, and reproductive behavior of S. recurvalis, and may become effective targets for controlling this insect.
Increased risk of benign paroxysmal positional vertigo in osteoporosis: a nationwide population-based cohort study
Authors: Byun Hayoung , Chung Jae Ho , Lee Seung Hwan , Park Chul Won , Kim Eun Mi , Kim Inah
Published: March 2019

Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral vertigo, which results from dislodged vestibular otoliths. Because the otoliths are mainly composed of calcium carbonate, it has been suggested that BPPV may be associated with osteoporosis. We aimed to assess the incidence and recurrence of BPPV in osteoporosis patients using a nationwide population-based cohort study with matched control. We used the database of the National Health Insurance Service of Korea, a universal system covering all 50 million Koreans. Osteoporosis was defined as patients who underwent bone mineral density tests and visited a clinic three or more times between Jan 2004 and Dec 2006. A control cohort consisted of non-osteoporotic subjects socio-demographically matched in a ratio of 1:1. The incidence and recurrence of BPPV between Jan 2007 and Dec 2016 were evaluated. A total of 177,797 osteoporosis patients and the same number of matched controls were identified. The incidence rates (IR) of BPPV in the osteoporosis patients and controls were 31.58 and 18.09 per 1000 persons, respectively (ratio of IR, IRR = 1.75, 95% CI 1.67–1.83). The IRs of recurrent BPPV were 187.3/1000 in the osteoporosis, 163.5/1000 in the controls (IRR = 1.15, 95% CI 1.02–1.28). In multivariate analysis, osteoporosis, female gender (adjusted HR = 1.76), age <65 (adjusted HR = 0.8), living in a metropolis, earning more than the lowest income and hypertension were significantly associated with increased risk of BPPV development. For recurrence, osteoporosis was the only meaningful risk factor (adjusted HR = 1.12). In conclusion, the risks of BPPV development and recurrence are higher in osteoporosis. Physicians might consider informing osteoporosis patients of the risk of developing BPPV and related falls.
Diagnostic value of digital clock drawing test in comparison with CERAD neuropsychological battery total score for discrimination of patients in the early course of Alzheimer’s disease from healthy individuals
Authors: Müller Stephan , Herde Laura , Preische Oliver , Zeller Anja , Heymann Petra , Robens Sibylle , Elbing Ulrich , Laske Christoph
Published: March 2019

The early detection of cognitive impairment or dementia is in the focus of current research as the amount of cognitively impaired individuals will rise intensely in the next decades due to aging population worldwide. Currently available diagnostic tools to detect mild cognitive impairment (MCI) or dementia are time-consuming, invasive or expensive and not suitable for wide application as required by the high number of people at risk. Thus, a fast, simple and sensitive test is urgently needed to enable an accurate detection of people with cognitive dysfunction and dementia in the earlier stages to initiate specific diagnostic and therapeutic interventions. We examined digital Clock Drawing Test (dCDT) kinematics for their clinical utility in differentiating patients with amnestic MCI (aMCI) or mild Alzheimer’s dementia (mAD) from healthy controls (HCs) and compared it with the diagnostic value of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery total score. Data of 381 participants (138 patients with aMCI, 106 patients with mAD and 137 HCs) was analyzed in the present study. All participants performed the clock drawing test (CDT) on a tablet computer and underwent the CERAD test battery and depression screening. CERAD total scores were calculated by subtest summation, excluding MMSE scores. All tablet variables (i.e. time in air, time on surface, total time, velocity, pressure, pressure/velocity relation, strokes per minute, time not painting, pen-up stroke length, pen-up/pen-down relation, and CDT score) during dCDT performance were entered in a forward stepwise logistic regression model to assess, which parameters best discriminated between aMCI or mAD and HC. Receiver operating characteristics (ROC) curves were constructed to visualize the specificity in relation to the sensitivity of dCDT variables against CERAD total scores in categorizing the diagnostic groups. dCDT variables provided a slightly better diagnostic accuracy of 81.5% for discrimination of aMCI from HCs than using CERAD total score (accuracy 77.5%). In aMCI patients with normal CDT scores, both dCDT (accuracy 78.0%) and CERAD total scores (accuracy 76.0%) were equally accurate in discriminating against HCs. Finally, in differentiating patients with mAD from healthy individuals, accuracy of both dCDT (93.0%) and CERAD total scores (92.3%) was excellent. Our findings suggest that dCDT is a suitable screening tool to identify early cognitive dysfunction. Its performance is comparable with the time-consuming established psychometric measure (CERAD test battery).
Excess water storage induced by viscous strain localization during high-pressure shear experiment
Authors: Précigout Jacques , Stünitz Holger , Villeneuve Johan
Published: March 2019

Strain localization in viscously deformed rocks commonly results in fine-grained shear zones where massive fluid circulation is regularly observed. Recently attributed to strain-induced pumping, this phenomenon may have major implications for the distribution of ores deposits and rock rheology. However, although grain size reduction and/or creep cavitation have been proposed as important processes, the source mechanism of fluid concentration remains unresolved, particularly at high pressure. Here we use secondary ion mass spectrometry to document the H2O content of fine-grained olivine across an experimental shear zone, which developed with grain size reduction during a H2O-saturated shear experiment at 1.2 GPa and 900 °C. Through data interpolation, the olivine matrix reveals high fluid concentrations where shear strain is localized. These concentrations far exceed the predicted amount of H2O that grain boundaries can contain, excluding grain size reduction as a unique source of water storage. Instead, we show that H2O increases per unit of grain boundary across the shear zone, suggesting that cavitation and “healing” processes compete with each other to produce a larger pore volume with increasing strain rate. This provides an alternative process for fluids to be collected where strain rate is the highest in deep shear zones.
A microfluidic platform towards automated multiplexed in situ sequencing
Authors: Maïno N. , Hauling T. , Cappi G. , Madaboosi N. , Dupouy D. G. , Nilsson M.
Published: March 2019

Advancements in multiplexed in situ RNA profiling techniques have given unprecedented insight into spatial organization of tissues by enabling single-molecule quantification and sub-micron localization of dozens to thousands of RNA species simultaneously in cells and entire tissue sections. However, the lack of automation of the associated complex experimental procedures represents a potential hurdle towards their routine use in laboratories. Here, we demonstrate an approach towards automated generation and sequencing of barcoded mRNA amplicons in situ, directly in fixed cells. This is achieved through adaptation of a microfluidic tool compatible with standard microscope slides and cover glasses. The adapted tool combines a programmable reagent delivery system with temperature controller and flow cell to perform established in situ sequencing protocols, comprising hybridization and ligation of gene-specific padlock probes, rolling circle amplification of the probes yielding barcoded amplicons and identification of amplicons through barcode sequencing. By adapting assay parameters (e.g. enzyme concentration and temperature), we achieve a near-identical performance in identifying mouse beta-actin transcripts, in comparison with the conventional manual protocol. The technically adapted assay features i) higher detection efficiency, ii) shorter protocol time, iii) lower consumption of oligonucleotide reagents but slightly more enzyme. Such an automated microfluidic tissue processor for in situ sequencing studies would greatly enhance its research potentials especially for cancer diagnostics, thus paving way to rapid and effective therapies.
Towards a dynamic list of Amazonian tree species
Authors: ter Steege Hans , Mota de Oliveira Sylvia , Pitman Nigel C. A. , Sabatier Daniel , Antonelli Alexandre , Guevara Andino Juan E. , Aymard Gerardo A. , Salomão Rafael P.
Published: March 2019

To provide an empirical foundation for estimates of the Amazonian tree diversity, we recently published a checklist of 11,675 tree species recorded to date in the region (ter Steege H, et al. (2016) The discovery of the Amazonian tree flora with an updated checklist of all known tree taxa. Scientific Reports 6:29549). From this total of plant records compiled from public databases and literature, widely used in studies on the Amazonian plant diversity, only 6,727 tree species belong to the first taxonomically-vetted checklist published for the region (Cardoso D, et al. (2017) Amazon plant diversity revealed by a taxonomically verified species list. PNAS 114:10695-10700). The striking difference in these two numbers spurred us to evaluate both lists, in order to release an improved Amazonian tree list; to discuss species inclusion criteria; and to highlight the ecological importance of verifying the occurrence of “non-Amazonian” trees in the region through the localization and identification of specimens. A number of species in the 2016 checklist that are not trees, non-native, synonyms, or misspellings were removed and corresponded to about 23% of the names. Species not included in the taxonomically-vetted checklist but verified by taxonomists to occur in Amazonia as trees were retained. Further, the inclusion of recently recorded/new species (after 2016), and recent taxonomic changes added up to an updated checklist including 10,071 species recorded for the Amazon region and shows the dynamic nature of establishing an authoritative checklist of Amazonian tree species. Completing and improving this list is a long-term, high-value commitment that will require a collaborative approach involving ecologists, taxonomists, and practitioners.
Nucleation and Formation of a Primary Clot in Insect Blood
Authors: Aprelev Pavel , Bruce Terri F. , Beard Charles E. , Adler Peter H. , Kornev Konstantin G.
Published: March 2019

Blood clotting at wound sites is critical for preventing blood loss and invasion by microorganisms in multicellular animals, especially small insects vulnerable to dehydration. The mechanistic reaction of the clot is the first step in providing scaffolding for the formation of new epithelial and cuticular tissue. The clot, therefore, requires special materials properties. We have developed and used nano-rheological magnetic rotational spectroscopy with nanorods to quantitatively study nucleation of cell aggregates that occurs within fractions of a second. Using larvae of Manduca sexta, we discovered that clot nucleation is a two-step process whereby cell aggregation is the time-limiting step followed by rigidification of the aggregate. Clot nucleation and transformation of viscous blood into a visco-elastic aggregate happens in a few minutes, which is hundreds of times faster than wound plugging and scab formation. This discovery sets a time scale for insect clotting phenomena, establishing a materials metric for the kinetics of biochemical reaction cascades. Combined with biochemical and biomolecular studies, these discoveries can help design fast-working thickeners for vertebrate blood, including human blood, based on clotting principles of insect blood.
The genetic vulnerability to cisplatin ototoxicity: a systematic review
Authors: Tserga Evangelia , Nandwani Tara , Edvall Niklas K. , Bulla Jan , Patel Poulam , Canlon Barbara , Cederroth Christopher R. , Baguley David M.
Published: March 2019

Ototoxicity is one of the major side-effects of platinum-based chemotherapy, in particular cisplatin (cis-diammine dichloroplatinum II). To our knowledge, no systematic review has previously provided a quantitative summary estimate of the impact of genetics upon the risk of developing hearing loss. We searched Embase, Medline, ASSIA, Pubmed, Scopus, and Web of Science, for studies documenting the genetic risk of ototoxicity in patients with cancer treated with cisplatin. Titles/abstracts and full texts were reviewed for inclusion. Meta-analytic estimates of risk (Odds Ratio) from the pooled data were calculated for studies that have been repeated twice or more. The search identified 3891 papers, of which 30 were included. The majority were retrospective (44%), ranging from n = 39 to n = 317, some including only patients younger than 25 years of age (33%), and some on both genders (80%). The most common cancers involved were osteosarcoma (53%), neuroblastoma (37%), prostate (17%) and reproductive (10%). Most studies performed genotyping, though only 5 studies performed genome-wide association studies. Nineteen single-nucleotide polymorphisms (SNPs) from 15 genes were repeated more than twice. Meta-analysis of group data indicated that rs1872328 on ACYP2, which plays a role in calcium homeostasis, increases the risk of ototoxicity by 4.61 (95% CI: 3.04–7.02; N = 696, p < 0.0001) as well as LRP2 rs4668123 shows a cumulated Odds Ratio of 3.53 (95% CI: 1.48–8.45; N = 118, p = 0.0059), which could not be evidenced in individual studies. Despite the evidence of heterogeneity across studies, these meta-analytic results from 30 studies are consistent with a view of a genetic predisposition to platinum-based chemotherapy mediated ototoxicity. These new findings are informative and encourage the genetic screening of cancer patients in order to identify patients with greater vulnerability of developing hearing loss, a condition having a potentially large impact on quality of life. More studies are needed, with larger sample size, in order to identify additional markers of ototoxic risk associated with platinum-based chemotherapy and investigate polygenic risks, where multiple markers may exacerbate the side-effects.
Active propagation of dendritic electrical signals in C. elegans
Authors: Shindou Tomomi , Ochi-Shindou Mayumi , Murayama Takashi , Saita Ei-ichiro , Momohara Yuto , Wickens Jeffery R. , Maruyama Ichiro N.
Published: March 2019

Active propagation of electrical signals in C. elegans neurons requires ion channels capable of regenerating membrane potentials. Here we report regenerative depolarization of a major gustatory sensory neuron, ASEL. Whole-cell patch-clamp recordings in vivo showed supralinear depolarization of ASEL upon current injection. Furthermore, stimulation of animal’s nose with NaCl evoked all-or-none membrane depolarization in ASEL. Mutant analysis showed that EGL-19, the α1 subunit of L-type voltage-gated Ca2+ channels, is essential for regenerative depolarization of ASEL. ASEL-specific knock-down of EGL-19 by RNAi demonstrated that EGL-19 functions in C. elegans chemotaxis along an NaCl gradient. These results demonstrate that a natural substance induces regenerative all-or-none electrical signals in dendrites, and that these signals are essential for activation of sensory neurons for chemotaxis. As in other vertebrate and invertebrate nervous systems, active information processing in dendrites occurs in C. elegans, and is necessary for adaptive behavior.
Simulation of blast lung injury induced by shock waves of five distances based on finite element modeling of a three-dimensional rat
Authors: Yang Chang , Dong-hai Zhang , Ling-ying Liu , Yong-hui Yu , Yang Wu , Li-wei Zang , Rui-guo Han , Jia-ke Chai
Published: March 2019

Blast lung injury (BLI) caused by both military and civilian explosions has become the main cause of death for blast injury patients. By building three-dimensional (3D) models of rat explosion regions, we simulated the surface pressure of the skin and lung. The pressure distributions were performed at 5 distances from the detonation center to the center of the rat. When the distances were 40 cm, 50 cm, 60 cm, 70 cm and 80 cm, the maximum pressure of the body surface were 634.77kPa, 362.46kPa, 248.11kPa, 182.13kPa and 109.29kPa and the surfaces lung pressure ranges were 928–2916 Pa, 733–2254 Pa, 488–1236 Pa, 357–1189 Pa and 314–992 Pa. After setting 6 virtual points placed on the surface of each lung lobe model, simulated pressure measurement and corresponding pathological autopsies were then conducted to validate the accuracy of the modeling. For the both sides of the lung, when the distance were 40 cm, 50 cm and 60 cm, the Pearson’s values showed strong correlations. When the distances were 70 cm and 80 cm, the Pearson’s values showed weak linear correlations. This computational simulation provided dynamic anatomy as well as functional and biomechanical information.
Application of Locked Nucleic Acid Oligonucleotides for siRNA Preclinical Bioanalytics
Authors: Thayer Mai B. , Lade Julie M. , Doherty David , Xie Fang , Basiri Babak , Barnaby Omar S. , Bala Noor S. , Rock Brooke M.
Published: March 2019

Despite the exquisite potential of siRNA as a therapeutic, the mechanism(s) responsible for the robust indirect exposure-response relationships have not been fully elucidated. To understand the siRNA properties linked to potent activity, requires the disposition of siRNA to be characterized. A technical challenge in the characterization is the detection and quantitation of siRNA from biological samples. Described herein, a Locked Nucleic Acid (LNA) Hybridization-Ligation ECL ELISA was designed for ultra-sensitive quantification of both sense and antisense strands of siRNA independent of structural modifica-tions. This assay was applied to measure siRNA in serum and tissue homogenate in preclinical species. We observed rapid clearance of siRNA from the systemic circulation which contrasted the prolonged accumulation within the tissue. The assay was also able to distinguish and quantify free siRNA from RNA-induced silencing complex (RISC) and Argonaute 2 (Ago2) associated with therapeutic siRNA. We utilized an orthogonal method, LC-MS, to investigate 3′ exonuclease activity toward the antisense strand metabolism. Taken together, we have demonstrated that the LNA Hybridization-Ligation ECL ELISA is arobust analytical method with direct application to measuring the exposure of siRNA therapeutics seamlessly across biological matrices.
Platelet lysate outperforms FCS and human serum for co-culture of primary human macrophages and hMSCs
Authors: Tylek Tina , Schilling Tatjana , Schlegelmilch Katrin , Ries Maximilian , Rudert Maximilian , Jakob Franz , Groll Jürgen
Published: March 2019

In vitro co-cultures of different primary human cell types are pivotal for the testing and evaluation of biomaterials under conditions that are closer to the human in vivo situation. Especially co-cultures of macrophages and mesenchymal stem cells (MSCs) are of interest, as they are both present and involved in tissue regeneration and inflammatory reactions and play crucial roles in the immediate inflammatory reactions and the onset of regenerative processes, thus reflecting the decisive early phase of biomaterial contact with the host. A co-culture system of these cell types might thus allow for the assessment of the biocompatibility of biomaterials. The establishment of such a co-culture is challenging due to the different in vitro cell culture conditions. For human macrophages, medium is usually supplemented with human serum (hS), whereas hMSC culture is mostly performed using fetal calf serum (FCS), and these conditions are disadvantageous for the respective other cell type. We demonstrate that human platelet lysate (hPL) can replace hS in macrophage cultivation and appears to be the best option for co-cultivation of human macrophages with hMSCs. In contrast to FCS and hS, hPL maintained the phenotype of both cell types, comparable to that of their respective standard culture serum, as well as the percentage of each cell population. Moreover, the expression profile and phagocytosis activity of macrophages was similar to hS.
B-cell depletion induces a shift in self antigen specific B-cell repertoire and cytokine pattern in patients with bullous pemphigoid
Authors: Berkani Nicolas , Joly Pascal , Golinski Marie-Laure , Colliou Natacha , Lim Annick , Larbi Anis , Riou Gaetan , Caillot Frederique , Bernard Philippe , Bedane Christophe , Delaporte Emmanuel , Chaby Guillaume , Dompmartin Anne , Hertl Michael , Calbo Sebastien , Musette Philippe
Published: March 2019

Bullous Pemphigoid is the most common auto-immune bullous skin disease. It is characterized by the production of auto-antibodies directed against 2 proteins of the hemi-desmosome (BP180 and BP230). We assessed the efficacy and mechanisms of action of rituximab, an anti-CD20 monoclonal antibody, in 17 patients with severe and relapsing type of bullous pemphigoid. The phenotype, cytokine gene expression, and rearrangement of BP180-specific B-cell receptor genes were performed over 2 years following treatment. At the end of the study, 5 patients had died, 3 had withdrawn from the study, and 9 patients were in complete remission. The one- and two-year relapse rates were 44.1% (95% Confidence Interval (CI): 21.0–76.0%) and 66.5%, (95% CI: 38.4–91.4%), respectively. Phenotypic analyses confirmed dramatic B-cell depletion, which lasted for 9 to 12 months. The ELISA values of serum anti-BP180 antibodies and the frequency of BP180-specific circulating B cells decreased dramatically following treatment, which paralleled the improvement of skin lesions. During B-cell reconstitution, a polyclonal IgM repertoire appeared and a shift in the rearrangement of the B-cell receptor genes of BP180-specific circulating B cells was observed. Concurrently, we observed a decrease of IL-15, IL-6 and TNFα expressing BP180-specific B cells, and the emergence of IL-10 and IL-1RA-expressing BP180-specific IgM+ B cells in patients in complete remission off therapy, suggesting the functional plasticity of BP180-specific auto-immune B cells after rituximab treatment.
Near-zero metamaterial inspired UHF antenna for nanosatellite communication system
Authors: Alam Touhidul , Islam Mohammad Tariqul , Cho Mengu
Published: March 2019

Epsilon-and-mu-near-zero (EMNZ) metamaterial structure inspired UHF antenna for nanosatellite has been proposed in this paper. The antenna consists of 3 × 2-unit cell array on the ground plane and a meander line radiating patch. Coaxial probe feeding technique has been obtained to excite the antenna. The meander line enables the antenna to resonate at lower UHF band and the metamaterial array is used to make the resonant frequency stable by reducing the coupling effect with metallic nanosatellite structure. The metamaterial structure exhibits EMNZ characteristics from 385 MHz to 488.5 MHz, which facilitates stable resonant frequency and higher antenna efficiency when embedded with nanosatellite structure. The proposed EMNZ inspired antenna has achieved measured impedance bandwidth (S11 < −10 dB) of 14.92 MHz (391 MHz–405.92 MHz). The perceptible novelty of this paper is the development of EMNZ metamaterial that significantly improves the UHF antenna’s operating frequency stability as well as efficiency for low earth orbit nanosatellite communications.
Cytohesin-3 is required for full insulin receptor signaling and controls body weight via lipid excretion
Authors: Jux Bettina , Gosejacob Dominic , Tolksdorf Felix , Mandel Christa , Rieck Michael , Namislo Angrit , Pfeifer Alexander , Kolanus Waldemar
Published: March 2019

Insulin plays a central role in regulating metabolic homeostasis and guanine-nucleotide exchange factors of the cytohesin family have been suggested to be involved in insulin signal transduction. The Drosophila homolog of cytohesin-3, steppke, has been shown to be essential for insulin signaling during larval development. However, genetic evidence for the functional importance of cytohesin-3 in mammals is missing. We therefore analyzed the consequences of genetic cytohesin-3-deficiency on insulin signaling and function in young and aged mice, using normal chow or high-fat diet (HFD). Insulin-receptor dependent signaling events are significantly reduced in liver and adipose tissue of young cytohesin-3-deficient mice after insulin-injection, although blood glucose levels and other metabolic parameters remain normal in these animals. Interestingly, however, cytohesin-3-deficient mice showed a reduced age- and HFD-induced weight gain with a significant reduction of body fat compared to wild-type littermates. Furthermore, cytohesin-3-deficient mice on HFD displayed no alterations in energy expenditure, but had an increased lipid excretion instead, as well as a reduced expression of genes essential for bile acid synthesis. Our findings show for the first time that an intact cyth3 locus is required for full insulin signaling in mammals and might constitute a novel therapeutic target for weight reduction.
KBTBD11, a novel BTB-Kelch protein, is a negative regulator of osteoclastogenesis through controlling Cullin3-mediated ubiquitination of NFATc1
Authors: Narahara Shun , Sakai Eiko , Kadowaki Tomoko , Yamaguchi Yu , Narahara Haruna , Okamoto Kuniaki , Asahina Izumi , Tsukuba Takayuki
Published: March 2019

Kelch repeat and BTB domain-containing protein 11 (KBTBD11) is a member of the KBTBD subfamily of proteins that possess a BTB domain and Kelch repeats. Despite the presence of the Kbtbd11 gene in mammalian genomes, there are few reports about KBTBD11 at present. In this study, we identified the novel protein KBTBD11 as a negative regulator of osteoclast differentiation. We found that expression of KBTBD11 increased during osteoclastogenesis. Small-interfering-RNA-mediated knockdown of KBTBD11 enhanced osteoclast formation, and markedly increased the expression of several osteoclast marker genes compared with control cells. Conversely, KBTBD11 overexpression impaired osteoclast differentiation, and decreased the expression of osteoclast marker genes. Among six major signaling pathways regulating osteoclast differentiation, KBTBD11 predominantly influenced the nuclear factor of activated T cell cytoplasmic-1 (NFATc1) pathway. Mechanistically, KBTBD11 was found to interact with an E3 ubiquitin ligase, Cullin3. Further experiments involving immunoprecipitation and treatment with MG132, a proteasome inhibitor, showed that the KBTBD11–Cullin3 promotes ubiquitination and degradation of NFATc1 by the proteasome. Considering that NFATc1 is an essential factor for osteoclast differentiation, the KBTBD11 and Cullin3 probably regulate the levels of NFATc1 through the ubiquitin-proteasome degradation system. Thus, KBTBD11 negatively modulates osteoclast differentiation by controlling Cullin3-mediated ubiquitination of NFATc1.
A Mediterranean mesophotic coral reef built by non-symbiotic scleractinians
Authors: Corriero Giuseppe , Pierri Cataldo , Mercurio Maria , Nonnis Marzano Carlotta , Onen Tarantini Senem , Gravina Maria Flavia , Lisco Stefania , Moretti Massimo , De Giosa Francesco , Valenzano Eliana , Giangrande Adriana , Mastrodonato Maria , Longo Caterina , Cardone Frine
Published: March 2019

This is the first description of a Mediterranean mesophotic coral reef. The bioconstruction extended for 2.5 km along the Italian Adriatic coast in the bathymetric range −30/−55 m. It appeared as a framework of coral blocks mostly built by two scleractinians, Phyllangia americana mouchezii (Lacaze-Duthiers, 1897) and Polycyathus muellerae (Abel, 1959), which were able to edify a secondary substrate with high structural complexity. Scleractinian corallites were cemented by calcified polychaete tubes and organized into an interlocking meshwork that provided the reef stiffness. Aggregates of several individuals of the bivalve Neopycnodonte cochlear (Poli, 1795) contributed to the compactness of the structure. The species composition of the benthic community showed a marked similarity with those described for Mediterranean coralligenous communities and it appeared to be dominated by invertebrates, while calcareous algae, which are usually considered the main coralligenous reef-builders, were poorly represented. Overall, the studied reef can be considered a unique environment, to be included in the wide and diversified category of Mediterranean bioconstructions. The main reef-building scleractinians lacked algal symbionts, suggesting that heterotrophy had a major role in the metabolic processes that supported the production of calcium carbonate. The large amount of available suspended organic matter in the area could be the main nutritional source for these species, as already suggested in the literature referred to Mediterranean cold-water corals.
DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass
Authors: Gordon Scott M. , Neufeld Edward B. , Yang Zhihong , Pryor Milton , Freeman Lita A. , Fan Xiao , Kullo Iftikhar J. , Biesecker Leslie G. , Remaley Alan T.
Published: March 2019

Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated Dennd5b−/− mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of Dennd5b results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In humans, two independent exome sequencing studies reveal that a common DENND5B variant, p.(R52K), is correlated with body mass index. These studies establish an important role for DENND5B in post-Golgi chylomicron secretion and a subsequent influence on body composition and peripheral lipoprotein metabolism.
ALDH1A1 regulates postsynaptic μ–opioid receptor expression in dorsal striatal projection neurons and mitigates dyskinesia through transsynaptic retinoic acid signaling
Authors: Pan Jing , Yu Jia , Sun Lixin , Xie Chengsong , Chang Lisa , Wu Junbing , Hawes Sarah , Saez–Atienzar Sara , Zheng Wang , Kung Justin , Ding Jinhui , Le Weidong , Chen Shengdi , Cai Huaibin
Published: March 2019

Aldehyde dehydrogenase 1A1 (ALDH1A1), a retinoic acid (RA) synthase, is selectively expressed by the nigrostriatal dopaminergic (nDA) neurons that preferentially degenerate in Parkinson’s disease (PD). ALDH1A1–positive axons mainly project to the dorsal striatum. However, whether ALDH1A1 and its products regulate the activity of postsynaptic striatal neurons is unclear. Here we show that μ–type opioid receptor (MOR1) levels were severely decreased in the dorsal striatum of postnatal and adult Aldh1a1 knockout mice, whereas dietary supplement of RA restores its expression. Furthermore, RA treatment also upregulates striatal MOR1 levels and signaling and alleviates L-DOPA–induced dyskinetic movements in pituitary homeobox 3 (Pitx3)–deficient mice that lack of ALDH1A1–expressing nDA neurons. Therefore, our findings demonstrate that ALDH1A1–synthesized RA is required for postsynaptic MOR1 expression in the postnatal and adult dorsal striatum, supporting potential therapeutic benefits of RA supplementation in moderating L-DOPA–induced dyskinesia.
Complex dielectric transformation of UV-vis diffuse reflectance spectra for estimating optical band-gap energies and materials classification
Authors: George Prince , Chowdhury Pradip
Published: March 2019

In this work, a complex dielectric transformation of UV-vis diffuse reflectance spectra is proposed to estimate the optical band-gap energies of an array of materials classified as semi-conductors, conductors and insulators and the results are compared with the more common Kubelka–Munk (K–M) transformation.
The hidden story in BaNiO3to BaNiO2transformation: adaptive structural series and NiO exsolution
Authors: Arévalo-López Angel M. , Huvé Marielle , Simon Pardis , Mentré Olivier
Published: March 2019

Crystal-to-crystal transformation from BaNiO3to BaNiO2is reported.
Synthesis of high melting point TiN mesocrystal powders by a metastable state strategy
Authors: Xiang Maoqiao , Song Miao , Zhu Qingshan , Yang Yafeng , Li Shaofu , Hu Chaoquan , Lv Pengpeng , Pan Feng , Ge Yu
Published: March 2019

Synthesis of high melting point non-oxide ceramic powders with mesocrystal structure is an important and challenging task.
Enhanced soot oxidation activity over CuO/CeO2 mesoporous nanosheets
Authors: Yang Shuaifeng , Wang Jinguo , Chai Wei , Zhu Jian , Men Yong
Published: March 2019

CuO/CeO2 mesoporous nanosheets exhibited superior soot oxidation activity owing to the synergistic effects.
The mechanistic duality of (thio)urea organocatalysts for ring-opening polymerization
Authors: Dharmaratne Nayanthara U. , Pothupitiya Jinal U. , Kiesewetter Matthew K.
Published: March 2019

Dual mechanisms for H-bond mediated ring-opening polymerization allow for precise control, high activity and new applications.
Side chain engineering on dithieno[3,2-b:2,3-d]pyrrol fused electron acceptors for efficient organic solar cells
Authors: Feng Haohao , Song Xin , Zhang Ming , Yu Jiangsheng , Zhang Zhuohan , Geng Renyong , Yang Linqiang , Liu Feng , Baran Derya , Tang Weihua
Published: March 2019

Two novel dithieno[3,2-b:2,3-d]pyrrol fused electron acceptors (FREAs) with branched alkyl side-chains have been developed.
New insights into spectral histopathology: infrared-based scoring of tumour aggressiveness of squamous cell lung carcinomas
Authors: Gaydou Vincent , Polette Myriam , Gobinet Cyril , Kileztky Claire , Angiboust Jean-François , Birembaut Philippe , Vuiblet Vincent , Piot Olivier
Published: March 2019

Spectral histopathology, based on infrared interrogation of tissue sections, proved a promising tool for helping pathologists in characterizing histological structures in a quantitative and automatic manner.