bluuebunny/crossref_metadata_2025 huggingface dataset:
Blurring out hydrogen: The dynamical structure of teflic acid
Authors: Herbers S. , Obenchain D. A. , Kraus P. , Wachsmuth D. , Grabow J.-U.
Published: May 2018

The microwave spectra of 10 teflic acid isotopologues were recorded in the frequency range of 3-25 GHz using supersonic jet-expansion Fourier transform microwave spectroscopy. Despite being asymmetric in its equilibrium structure, the delocalization of the hydrogen atom leads to a symmetric top vibrational ground state structure. In this work, we present the zero point structure obtained from the experimental rotational constants and an approach to determine the semi-experimental equilibrium structure aided by ab initio data. The Te–O bond length determined in the equilibrium structure is accurate to the picometer and can be used as a benchmark for computational methods treating relativistic effects.
Vapor-liquid equilibrium and equation of state of two-dimensional fluids from a discrete perturbation theory
Authors: Trejos Víctor M. , Santos Andrés , Gámez Francisco
Published: May 2018

The interest in the description of the properties of fluids of restricted dimensionality is growing for theoretical and practical reasons. In this work, we have firstly developed an analytical expression for the Helmholtz free energy of the two-dimensional square-well fluid in the Barker–Henderson framework. This equation of state is based on an approximate analytical radial distribution function for d-dimensional hard-sphere fluids (1 ≤ d ≤ 3) and is validated against existing and new simulation results. The so-obtained equation of state is implemented in a discrete perturbation theory able to account for general potential shapes. The prototypical Lennard-Jones and Yukawa fluids are tested in its two-dimensional version against available and new simulation data with semiquantitative agreement.
Interaction of wave with a body submerged below an ice sheet with multiple arbitrarily spaced cracks
Authors: Li Z. F. , Wu G. X. , Ji C. Y.
Published: May 2018

The problem of wave interaction with a body submerged below an ice sheet with multiple arbitrarily spaced cracks is considered, based on the linearized velocity potential theory together with the boundary element method. The ice sheet is modeled as a thin elastic plate with uniform properties, and zero bending moment and shear force conditions are enforced at the cracks. The Green function satisfying all the boundary conditions including those at cracks, apart from that on the body surface, is derived and is expressed in an explicit integral form. The boundary integral equation for the velocity potential is constructed with an unknown source distribution over the body surface only. The wave/crack interaction problem without the body is first solved directly without the need for source. The convergence and comparison studies are undertaken to show the accuracy and reliability of the solution procedure. Detailed numerical results through the hydrodynamic coefficients and wave exciting forces are provided for a body submerged below double cracks and an array of cracks. Some unique features are observed, and their mechanisms are analyzed.
Dotette: Programmable, high-precision, plug-and-play droplet pipetting
Authors: Fan Jinzhen , Men Yongfan , Hao Tseng Kuo , Ding Yi , Ding Yunfeng , Villarreal Fernando , Tan Cheemeng , Li Baoqing , Pan Tingrui
Published: May 2018

Manual micropipettes are the most heavily used liquid handling devices in biological and chemical laboratories; however, they suffer from low precision for volumes under 1 μl and inevitable human errors. For a manual device, the human errors introduced pose potential risks of failed experiments, inaccurate results, and financial costs. Meanwhile, low precision under 1 μl can cause severe quantification errors and high heterogeneity of outcomes, becoming a bottleneck of reaction miniaturization for quantitative research in biochemical labs. Here, we report Dotette, a programmable, plug-and-play microfluidic pipetting device based on nanoliter liquid printing. With automated control, protocols designed on computers can be directly downloaded into Dotette, enabling programmable operation processes. Utilizing continuous nanoliter droplet dispensing, the precision of the volume control has been successfully improved from traditional 20%–50% to less than 5% in the range of 100 nl to 1000 nl. Such a highly automated, plug-and-play add-on to existing pipetting devices not only improves precise quantification in low-volume liquid handling and reduces chemical consumptions but also facilitates and automates a variety of biochemical and biological operations.
Large electron capture-cross-section of the major nonradiative recombination centers in Mg-doped GaN epilayers grown on a GaN substrate
Authors: Chichibu S. F. , Shima K. , Kojima K. , Takashima S. , Edo M. , Ueno K. , Ishibashi S. , Uedono A.
Published: May 2018

Complementary time-resolved photoluminescence and positron annihilation measurements were carried out at room temperature on Mg-doped p-type GaN homoepitaxial films for identifying the origin and estimating the electron capture-cross-section (σn) of the major nonradiative recombination centers (NRCs). To eliminate any influence by threading dislocations, free-standing GaN substrates were used. In Mg-doped p-type GaN, defect complexes composed of a Ga-vacancy (VGa) and multiple N-vacancies (VNs), namely, VGa(VN)2 [or even VGa(VN)3], are identified as the major intrinsic NRCs. Different from the case of 4H-SiC, atomic structures of intrinsic NRCs in p-type and n-type GaN are different: VGaVN divacancies are the major NRCs in n-type GaN. The σn value approximately the middle of 10−13 cm2 is obtained for VGa(VN)n, which is larger than the hole capture-cross-section (σp = 7 × 10−14 cm2) of VGaVN in n-type GaN. Combined with larger thermal velocity of an electron, minority carrier lifetime in Mg-doped GaN becomes much shorter than that of n-type GaN.
Ultrafast photodissociation dynamics of 1,4-diiodobenzene
Authors: Stankus Brian , Zotev Nikola , Rogers David M. , Gao Yan , Odate Asami , Kirrander Adam , Weber Peter M.
Published: May 2018

The photodissociation dynamics of 1,4-diiodobenzene is investigated using ultrafast time-resolved photoelectron spectroscopy. Following excitation by laser pulses at 271 nm, the excited-state dynamics is probed by resonance-enhanced multiphoton ionization with 405 nm probe pulses. A progression of Rydberg states, which come into resonance sequentially, provide a fingerprint of the dissociation dynamics of the molecule. The initial excitation decays with a lifetime of 33 ± 4 fs, in good agreement with a previous study. The spectrum is interpreted by reference to ab initio calculations at the CASPT2(18,14) level, including spin-orbit coupling. We propose that both the 5B1 and 6B1 states are excited initially, and based on the calculations, we identify diabatic spin-orbit coupled states corresponding to the main dissociation pathways.
Developing a heat load index for lactating dairy cows
Authors: Lees J. C. , Lees A. M. , Gaughan J. B.
Published: May 2018

The temperature humidity index (THI) has been extensively used in the Australian dairy industry as an indicator of heat load conditions. However, there are limitations to the THI, where it does not account for solar radiation or wind speed. In addition, the THI has not been formulated in conjunction with physiological data. Thus, it is not apparent whether the THI provides the best prediction for impact of heat load on lactating dairy cattle. The aim of the present study was to develop a dairy heat load index (DHLI), based on the physiological responses of lactating dairy cows to environmental conditions. The study was undertaken at The University of Queensland, Gatton Campus, Australia, over three summers and two winters. Observations were conducted four times daily at 0800 hours, 1200 hours, 1400 hours and 1700 hours. Weather data were obtained every 10 min from an onsite, automated weather station. Panting score data were used to calculate a mean panting score of the herd. Developing the DHLI encompassed three different modelling techniques, including (1) linear regression, (2) broken stick regression and (3) non-linear logistic regression. Comparisons between the models indicated there was an increase in accuracy when using non-linear logistic regression (R2 = 0.542). The DHLI model developed was based on mean panting score, black globe temperature (°C) and relative humidity. By utilising the black globe temperature, the DHLI is able to incorporate the combined effects of ambient temperature, relative humidity, solar radiation and wind speed in a single unit measure. By combining climatic conditions and a physiological response, i.e. panting score, the DHLI model may become a more accurate prediction of heat load for lactating dairy cows. The DHLI produces a unit value between 0 and 100. When DHLI is 0, there would be no panting and, when DHLI is 100, all cows within the herd would be panting.
Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome
Authors: Depner Christopher M. , Melanson Edward L. , McHill Andrew W. , Wright Kenneth P.
Published: May 2018

Significance

Circadian misalignment (i.e., behavioral processes such as food intake or sleep occurring at inappropriate endogenous circadian times) commonly occurs during shift work and is associated with health problems. Identifying mechanisms underlying health problems associated with circadian misalignment will help develop precision medicine countermeasures. Thus, we investigated the impact of circadian misalignment on the human plasma proteome using a simulated nightshift protocol in healthy volunteers. We demonstrate that circadian and/or behavioral wake–sleep/food intake–fasting cycles regulate 24-h time-of-day patterns of the human plasma proteome. Further, we show that proteins altered during circadian misalignment are associated with biological pathways involved in immune function, metabolism, and cancer and with altered glucose and energy metabolism, identifying potential mechanisms contributing to metabolic dysregulation.
Biological species in the viral world
Authors: Bobay Louis-Marie , Ochman Howard
Published: May 2018

Significance

The biological species concept (BSC) has served as the basis for defining species for over 75 years. Members of a biological species are defined by their ability to exchange genetic material, and it was originally thought that asexual lineages were not amenable to species-level classification based on the BSC since clonal individuals are reproductively isolated from one another. In this study, we demonstrate that the rates and patterns of gene exchange in acellular organisms (viruses and bacteriophages) allow the assignment of true biological species, an essential step to organizing the tree of life. Our results show that a universal species definition, based on the BSC, can be used to define biological species in all major lifeforms.
Riboswitches for the alarmone ppGpp expand the collection of RNA-based signaling systems
Authors: Sherlock Madeline E. , Sudarsan Narasimhan , Breaker Ronald R.
Published: May 2018

Significance

Bacteria and other organisms make extensive use of signaling molecules that are derived from ribonucleotides or their derivatives. Previously, five riboswitch classes had been discovered that sense the four RNA-derived signaling molecules: c-di-GMP, c-di-AMP, c-AMP-GMP, and ZTP. We now report the discovery and biochemical validation of bacterial riboswitches for the widespread alarmone guanosine tetraphosphate (ppGpp), which signals metabolic and physiological adaptations to starvation. These findings expand the number of natural partnerships between riboswitches and ribonucleotide-like signaling molecules, and provide RNA-based sensors for detecting ppGpp production in cells.
Two
Ck1δ
transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock
Authors: Fustin Jean-Michel , Kojima Rika , Itoh Kakeru , Chang Hsin-Yi , Ye Shiqi , Zhuang Bowen , Oji Asami , Gibo Shingo , Narasimamurthy Rajesh , Virshup David , Kurosawa Gen , Doi Masao , Manabe Ichiro , Ishihama Yasushi , Ikawa Masahito , Okamura Hitoshi
Published: May 2018

Significance

The most abundant modification in mRNA is the
N
6
-methylation of internal adenosines (m6A), but m6A’s physiological function is unknown for most mRNAs. Here we show that Casein Kinase 1 Delta mRNA (
Ck1δ
), coding for a critical kinase in the control of circadian rhythms, is regulated by m6A. When m6A is inhibited, the expression of two CK1δ isoforms, uncharacterized until now, increases due to enhanced translation. This increase in CK1δs leads to a slower clock because of increased phosphorylation of the clock protein PER2 at a key residue, leading to the stabilization of PER2 protein.
Trait overdispersion and the role of sociality in the assembly of social spider communities across the Americas
Authors: Fernandez-Fournier Philippe , Guevara Jennifer , Hoffman Catherine , Avilés Leticia
Published: May 2018

Significance

Ecological theory predicts that communities should contain species that exhibit little overlap in their use of resources, typically assuming differences in body size or morphology. Here we show that level of sociality—whether individuals live solitarily or in groups—can be a powerful dimension separating species in niche space. In 50+ communities of the spider genus
Anelosimus
across the Americas, we show that co-occurring species are more likely to differ in their level of sociality than expected by chance. We also show that differences in level of sociality lead to greater differences in resource use (size of the prey captured) than differences in body size, highlighting the importance of sociality in the assemblage of natural communities.
Xenoprotein engineering via synthetic libraries
Authors: Gates Zachary P. , Vinogradov Alexander A. , Quartararo Anthony J. , Bandyopadhyay Anupam , Choo Zi-Ning , Evans Ethan D. , Halloran Kathryn H. , Mijalis Alexander J. , Mong Surin K. , Simon Mark D. , Standley Eric A. , Styduhar Evan D. , Tasker Sarah Z. , Touti Faycal , Weber Jessica M. , Wilson Jessica L. , Jamison Timothy F. , Pentelute Bradley L.
Published: May 2018

Significance

Combinatorial protein libraries—prepared via molecular biology-based approaches—are invaluable tools for protein engineering. The inclusion of noncanonical amino acids in such libraries is of considerable interest. However, at present no approach competes with chemical synthesis in terms of the variety and number of noncanonical amino acids that can be simultaneously incorporated into a protein molecule. Here, we describe selection from synthetic libraries as a strategy for protein engineering. The approach enables identification of small (∼30 aa), functional protein variants comprising a virtually unlimited variety of noncanonical amino acids. Increasing the throughput of synthetic library screening, which was achieved through this effort, is anticipated to improve the utility of synthetic libraries for identifying polypeptide-based ligands with de novo function.
Continuous intrathecal orexin delivery inhibits cataplexy in a murine model of narcolepsy
Authors: Kaushik Mahesh K. , Aritake Kosuke , Imanishi Aya , Kanbayashi Takashi , Ichikawa Tadashi , Shimizu Tetsuo , Urade Yoshihiro , Yanagisawa Masashi
Published: May 2018

Significance

Narcolepsy is a chronic neurological disorder that severely affects the day-to-day life and general well-being of the affected individuals. Unfortunately, treatments available to date are symptomatic therapies with an array of adverse effects. Animal studies showed that orexin peptide can be a mechanistic therapy to treat narcolepsy. However, nonpermeability of orexin to brain–blood barrier limits its use in humans. Here we showed that orexin delivered via intrathecal route at the lumbar level significantly inhibited narcoleptic symptoms in mice without altering sleep/wake profile. Although the outcome of intrathecal treatment may be different in clinical studies, our data indicate the possibility that orexin can be delivered intrathecally in humans, using an implantable, refillable, and programmable miniature pump to treat narcolepsy.
Structure of xyloglucan xylosyltransferase 1 reveals simple steric rules that define biological patterns of xyloglucan polymers
Authors: Culbertson Alan T. , Ehrlich Jacqueline J. , Choe Jun-Yong , Honzatko Richard B. , Zabotina Olga A.
Published: May 2018

Significance

The recalcitrant nature of the plant cell wall presents a significant challenge in the industrial processing of biomass. Poor understanding of plant polysaccharide biosynthesis impedes efforts to engineer cell walls susceptible to efficient and unnatural pathways of degradation. Despite numerous genetic and in vitro studies of the xyloglucan xylosyltransferases (XXT1, XXT2, and XXT5), the specific roles of each in the xylosylation of the xyloglucan backbone is unclear. On the basis of steric constraints imposed by the active-site cleft of structures presented here, we propose a multienzyme complex capable of producing the xylosylation patterns of native xyloglucans. This model significantly extends our limited understanding of branched polysaccharide biosynthesis.
Encephalitis is mediated by ROP18 of
Toxoplasma gondii
, a severe pathogen in AIDS patients
Authors: An Ran , Tang Yuewen , Chen Lijian , Cai Haijian , Lai De-Hua , Liu Kang , Wan Lijuan , Gong Linli , Yu Li , Luo Qingli , Shen Jilong , Lun Zhao-Rong , Ayala Francisco J. , Du Jian
Published: May 2018

Significance

As a neurotropic parasite,
Toxoplasma
predominantly interacts with neurons throughout CNS infection and causes severe damage to the brain. In patients with severe immune dysfunction, dormant encysted bradyzoites can reactivate into fast-replicating tachyzoites and may cause damage to the brain. We report that an endoplasmic reticulum (ER)-associated protein, RTN1-C, is a substrate of ROP18 kinase. ROP18 phosphorylation of RTN1-C triggers ER stress-mediated apoptosis. Phosphorylated RTN1-C enhances GRP78 acetylation via attenuating the activity of histone deacetylases and is associated with neural apoptosis. These results link
Toxoplasma
’s effector ROP18 to RTN1-C, the CNS predominantly expressed protein, as well as ER stress-induced apoptosis via GRP78 acetylation, which may provide new insight into the preferential invasion of the central nervous system by
Toxoplasma
.
Postsynaptic δ1 glutamate receptor assembles and maintains hippocampal synapses via Cbln2 and neurexin
Authors: Tao Wucheng , Díaz-Alonso Javier , Sheng Nengyin , Nicoll Roger A.
Published: May 2018

Significance

The delta glutamate receptors (GluD1 and GluD2) shared high homology with ionotropic glutamate receptors but, surprisingly, are not gated by glutamate, or any other known ligand. GluD2 is only expressed in cerebellar Purkinje cells, where it forms a scaffolding complex with Cbln1 and presynaptic neurexin 1β (+S4). Might other synapses in the brain use a similar mechanism? We have found that GluD1, a long-neglected receptor subtype, powerfully and specifically regulates synapses in the hippocampus. We show that Cbln2 interacts with GluD1 and presynaptic neurexin 1β (+S4). This tripartite complex plays critical roles in both synaptogenesis and maintenance. Finally, we provide evidence that our results likely apply to synapses throughout the forebrain where GluD1 is widely expressed.
Uncovering universal rules governing the selectivity of the archetypal DNA glycosylase TDG
Authors: Dodd Thomas , Yan Chunli , Kossmann Bradley R. , Martin Kurt , Ivanov Ivaylo
Published: May 2018

Significance

The most prominent epigenetic modification in mammalian genomes is cytosine methylation at position 5 on the pyrimidine ring. Thymine DNA glycosylase (TDG) plays a central role in the pathways for 5-methyl cytosine removal and thus influences gene silencing, stem cell differentiation, and alterations in normal development. Additionally, methylation abnormalities in DNA are often observed in diseases, specifically cancer. Here we examine the mechanisms by which TDG detects, extrudes, and excises modified bases in DNA. Using path-sampling methodologies, we compute minimum free energy paths for TDG base extrusion. The computed paths reveal a unique mechanism underpinning TDG selectivity for DNA lesions or modified bases, which involves DNA sculpting, global protein dynamics, conformational gating, and specific protein–nucleic acid interactions.
Systematic prediction of genes functionally linked to CRISPR-Cas systems by gene neighborhood analysis
Authors: Shmakov Sergey A. , Makarova Kira S. , Wolf Yuri I. , Severinov Konstantin V. , Koonin Eugene V.
Published: May 2018

Significance

The CRISPR-Cas systems that mediate adaptive immunity in bacteria and archaea encompass a small set of core
cas
genes that are essential in diverse systems belonging to the same subtype, type, or class. However, a much greater number of genes only sporadically co-occur with CRISPR-Cas, and for most of these, involvement in CRISPR-Cas functions has not been demonstrated. We developed a computational strategy that provides for systematic identification of CRISPR-linked proteins and prediction of their functional association with CRISPR-Cas systems, and employed it to identify 79 previously undetected, putative CRISPR-accessory proteins. A large fraction of these proteins are predicted to be membrane-associated, revealing a potentially unknown side of CRISPR biology.
Recombinant
Escherichia coli
as a biofactory for various single- and multi-element nanomaterials
Authors: Choi Yoojin , Park Tae Jung , Lee Doh C. , Lee Sang Yup
Published: May 2018

Significance

Nanomaterials (NMs) including metals, metal oxides, and quantum dots are increasingly used for developing various materials of industrial use. Conventional NM synthesis by chemical and physical methods requires rather harsh and environmentally hazardous conditions. Here we report biosynthesis of various NMs by employing a recombinant
Escherichia coli
strain co-expressing metallothionein and phytochelatin synthase. A Pourbaix diagram was employed to predict producibility and crystallinity of NMs. We were able to synthesize 60 different crystalline and amorphous NMs comprising a single-element or multi-elements, including those never biosynthesized or synthesized chemically before. The biosynthesized NMs were analyzed for their size, shape, composition, and other characteristics. The strategy reported here will be useful for producing under mild conditions various single- and multi-element NMs for industrial use.
Consistent and powerful non-Euclidean graph-based change-point test with applications to segmenting random interfered video data
Authors: Shi Xiaoping , Wu Yuehua , Rao Calyampudi Radhakrishna
Published: May 2018

Significance

A webcam collects tons of short video clips for home security, fire inspection, and animal’s behavior study, etc. For efficiency, effectiveness, and economy of the variety of purposes of the use of the video data, we need to remove informationless data. To solve this problem, we propose two non-Euclidean graph-based change-point tests: SHP* and MST*. The proposed test SHP* is not only distribution-free but also, consistent. As shown in the real data example of a bee’s flower visitation, it has successfully detected both landing and departure times of a bee from the video data with random interference.
Characterization of gossypol biosynthetic pathway
Authors: Tian Xiu , Ruan Ju-Xin , Huang Jin-Quan , Yang Chang-Qing , Fang Xin , Chen Zhi-Wen , Hong Hui , Wang Ling-Jian , Mao Ying-Bo , Lu Shan , Zhang Tian-Zhen , Chen Xiao-Ya
Published: May 2018

Significance

Cotton is an important crop, and terpenoids form the largest group of natural products. Gossypol and related sesquiterpene aldehydes in cotton function as phytoalexins against pathogens and pests but pose human health concerns, as cotton oil is still widely used as vegetable oil. We report the isolation and identification of four enzymes and the recharacterization of one previously reported P450. We are now close to the completion of the gossypol pathway, an important progress in agricultural and plant sciences, and the data are beneficial to improving food safety. Among the six compounds (intermediates) isolated following gene silencing, one affected plant disease resistance significantly. Thus, these “hidden natural products” harbor interesting biological activities worthy of exploration.
Thickness effect on electrical properties of copper oxide thin films
Authors: Kamli Kenza , Hadef Zakaria , Chouial Baghdadi , Hadjoudja Bouzid
Published: May 2018

Copper oxide (CuO) thin films were deposited by spray pyrolysis technique on glass substrates heated to 300°C. The effect of films thickness on the electrical characteristics (resistivity, free carrier concentration and Hall mobility of carriers) and morphological properties of CuO have been investigated. The obtained results indicate that the thickness increasing (longer periods of deposition time) have permitted the improvement of electrical characteristics of our films (decrease of the resistivity, increase of the free carriers concentration and the carriers Hall mobility). Scanning electron microscopy images of the samples prove that the films morphology change according to the film thickness and also show more homogeneity of CuO thin film grown at higher thicknesses.
Students’ Reparticularization of Chinese Language and Culture at the University of Rwanda Confucius Institute
Authors: Stambach Amy , Wamalwa Kevin
Published: May 2018

This article examines the reparticularization of Chinese language and culture in a teaching-learning context at the University of Rwanda. It critiques models of dissemination that suggest direct inscription of semiotic value onto local contexts of use. Ethnographically, the article demonstrates that students’ uptake of what their teachers deem real or authentic is in fact a metapragmatic reconstrual of teachers’ lexemic tokens “real” and “original” that teachers enact in their teaching activities. Students’ reconstrual incrementally alters teachers’ sign values and links their users to one other. Students’ reparticularized sign values, in turn, link their users to distinct activity routines beyond learning Chinese and kung fu in the classroom. The article argues that language and kung fu classes for students are one phase segment of larger sets of activities students undertake to become competitive in a challenging job market.
Tunable Band Gap in Piezoelectric Composite Rod Based on the Inter-Coupling Effect*
Authors: Fang Ze-Qun , Hou Zhi-Lin
Published: May 2018

The longitudinal wave propagating in one-dimensional periodic piezoelectric composite rod with inter-coupling between different piezoelectric segments is investigated. The analytical formulae for such a structure are shown and the dispersion relation is calculated. The results show that, by introducing the inter-coupling between the different piezoelectric segments, which is accomplished by serially connecting every n piezoelectric segment into supercells, some tunable Bragg band gaps can accordingly be opened in the low frequency region. The investigation could provide a new guideline for the tunable phononic crystal under passive control.
Apple, Acaricide Evaluation, 1986
Authors: Beers E. H. , Baird R. J. , Eisner E. A.
Published: May 2018

This test was conducted in a commercial orchard containing mixed ages of trees with under-tree irrigation. The block had a history of reduced effectiveness of control with Plictran. A randomized complete block design was used, with 4 single-tree replicates per treatment. Materials were applied on 6 Jun as a dilute spray to the point of drip with a handgun sprayer operating at 400-500 psi. Per acre rates were based on 400 gal/acre. Mites were sampled weekly. Twenty-five leaves were collected from each tree (100 per treatment), brushed with a mite brushing machine, and mites of each species counted.
Institutional review of glial tumors treated with chemotherapy: the first description of PCV-related pseudoprogression
Authors: Sharma Ankur M , Willcock Michael , Bucher Oliver , Amaratunga Thelina , Khan M Nazir , Loewen Shaun K , Quon Harvey , Essig Marco , Pitz Marshall
Published: May 2018

Background

Pseudoprogression refers to areas of enhancement on MRI postadjuvant chemoradiation that arise as a result of treatment-related effects. Pseudoprogression has been well described with temozolomide-based chemoradiation but has not been studied in the setting of procarbazine, lomustine, and vincristine (PCV) chemotherapy. We reviewed patients treated with PCV to investigate the occurrence of pseudoprogression.

Methods

Adults diagnosed with World Health Organization grade II or III gliomas between 2010 and 2015 and treated with PCV or temozolomide were identified. Patient, tumor, treatment, and MRI data were retrospectively collected and analyzed. Pseudoprogression was defined as new enhancement seen on MRI within 6 months of completion of adjuvant radiotherapy or concurrent chemoradiation, which improved or remained stable on subsequent scans without therapeutic intervention. If MRI showed areas of new enhancement outside the 6-month post-treatment window, which resolved or remained stable without treatment, or in patients who did not receive adjuvant treatment, it was referred to as “atypical pseudoprogression.”

Results

Fifty-seven patients were identified. Nine (16%) patients were identified as having pseudoprogression on MRI. Two (4%) of these patients were treated with PCV and 7 (12%) were treated with temozolomide. Seventeen (30%) patients had atypical pseudoprogression: 8 (14%) treated with temozolomide, 8 (14%) treated with PCV, and 1 (2%) treated with both types of chemotherapy.

Conclusions

We describe the first 2 cases of PCV-related pseudoprogression and 17 cases of atypical pseudoprogression. As the re-emergence of adjuvant PCV occurs in clinical practice, the occurrence of classical and atypical pseudoprogression could have a significant impact on clinical decision making.
Macrovascular Decompression of Facial Nerve With Anteromedial Transposition of a Dolichoectatic Vertebral Artery: 3-Dimensional Operative Video
Authors: Tabani Halima , Yousef Sonia , Burkhardt Jan-Karl , Gandhi Sirin , Benet Arnau , Lawton Michael T
Published: May 2018

Most cranial nerve compression syndromes (ie, trigeminal neuralgia and hemifacial spasm) are caused by small arteries impinging on a nerve and are relieved by microvascular decompression. Rarely, cranial nerve compression syndromes can be caused by large artery impingement and can be relieved by macrovascular decompression. When present, this compression often occurs in association with degenerative atherosclerosis in the vertebral arteries (VA) and basilar artery. Conservative treatment is recommended for mild forms, but surgical transposition of the VA away from the root entry zone (REZ) can be considered. This video demonstrates macrovascular decompression of a dolichoectatic VA in a 74-yr-old female with refractory left hemifacial spasm. After obtaining IRB approval, patient consent was sought for the procedure. With the patient in three-quarter-prone position, a far-lateral craniotomy was performed. The dentate ligament was cut to free the VA, and the suprahypoglossal portion of the vagoaccessory triangle was widened. VA compressed the REZ of the facial nerve, but was mobilized anteromedially off the REZ. A muslin sling was wrapped around the VA and its tail brought down to the clival dura, which was punctured with a 19-gauge needle and enlarged with a dissector. The sling was pulled anteromedially to this puncture site and secured to the dura with an aneurysm clip, relieving the REZ of all compression. The patient tolerated the procedure with mild, transient hoarseness and her hemifacial spasm resolved completely. This case demonstrates the macrovascular decompression technique with anteromedial transposition of the vertebrobasilar artery, which can also be used for trigeminal neuralgia.
Neuroendocrine Regulation of Air Pollution Health Effects: Emerging Insights
Authors: Snow Samantha J , Henriquez Andres R , Costa Daniel L , Kodavanti Urmila P
Published: May 2018

Air pollutant exposures are linked to cardiopulmonary diseases, diabetes, metabolic syndrome, neurobehavioral conditions, and reproductive abnormalities. Significant effort is invested in understanding how pollutants encountered by the lung might induce effects in distant organs. The role of circulating mediators has been predicted; however, their origin and identity have not been confirmed. New evidence has emerged which implicates the role of neuroendocrine sympathetic-adrenal-medullary (SAM) and hypothalamic-pituitary-adrenal (HPA) stress axes in mediating a wide array of systemic and pulmonary effects. Our recent studies using ozone exposure as a prototypical air pollutant demonstrate that increases in circulating adrenal-derived stress hormones (epinephrine and cortisol/corticosterone) contribute to lung injury/inflammation and metabolic effects in the liver, pancreas, adipose, and muscle tissues. When stress hormones are depleted by adrenalectomy in rats, most ozone effects including lung injury/inflammation are diminished. Animals treated with antagonists for adrenergic and glucocorticoid receptors show inhibition of the pulmonary and systemic effects of ozone, whereas treatment with agonists restore and exacerbate the ozone-induced injury/inflammation phenotype, implying the role of neuroendocrine activation. The neuroendocrine system is critical for normal homeostasis and allostatic activation; however, chronic exposure to stressors may lead to increases in allostatic load. The emerging mechanisms by which circulating mediators are released and are responsible for producing multiorgan effects of air pollutants insists upon a paradigm shift in the field of air pollution and health. Moreover, since these neuroendocrine responses are linked to both chemical and nonchemical stressors, the interactive influence of air pollutants, lifestyle, and environmental factors requires further study.
Systemic Acquired Resistance and Salicylic Acid: Past, Present, and Future
Authors: Klessig Daniel F. , Choi Hyong Woo , Dempsey D’Maris Amick
Published: May 2018

This article is part of the Distinguished Review Article Series in Conceptual and Methodological Breakthroughs in Molecular Plant-Microbe Interactions.

Salicylic acid (SA) is a critical plant hormone that regulates numerous aspects of plant growth and development as well as the activation of defenses against biotic and abiotic stress. Here, we present a historical overview of the progress that has been made to date in elucidating the role of SA in signaling plant immune responses. The ability of plants to develop acquired immunity after pathogen infection was first proposed in 1933. However, most of our knowledge about plant immune signaling was generated over the last three decades, following the discovery that SA is an endogenous defense signal. During this timeframe, researchers have identified i) two pathways through which SA can be synthesized, ii) numerous proteins that regulate SA synthesis and metabolism, and iii) some of the signaling components that function downstream of SA, including a large number of SA targets or receptors. In addition, it has become increasingly evident that SA does not signal immune responses by itself but, rather, as part of an intricate network that involves many other plant hormones. Future efforts to develop a comprehensive understanding of SA-mediated immune signaling will therefore need to close knowledge gaps that exist within the SA pathway itself as well as clarify how crosstalk among the different hormone signaling pathways leads to an immune response that is both robust and optimized for maximal efficacy, depending on the identity of the attacking pathogen.
The Effect of Cold Stress on Damping-Off of Soybean Caused by Pythium sylvaticum
Authors: Serrano M. , Robertson A. E.
Published: May 2018

To improve our understanding of the timing of cold stress and its effect on Pythium damping-off, we performed a factorial experiment with two cold stress temperatures (4 and 10°C); exposure to 96 h of cold stress at 0, 1, 2, 4, 6, and 8 days after planting; and inoculation with Pythium sylvaticum-infested millet or control. Increased susceptibility to damping-off resulting in reduced emergence was found in inoculated plants when the cold stress period began 2 or 4 days after planting. In the noninoculated controls, no effect of cold stress on emergence was observed. Slower seedling growth was observed during the cold stress period and in inoculated plants after exposure to cold stress. Seed exudation, mycelial growth, and sporangia germination of P. sylvaticum was evaluated at 4, 10, and 18°C. The greatest seed exudation was observed at 4°C. Low temperatures delayed mycelial growth of P. sylvaticum, although the pathogen was still able to grow at 4°C. Sporangia incubated for 3 h at 18°C in the presence of seed exudates had higher germination in comparison with sporangia incubated at 10 or 4°C. Moreover, more sporangia germinated in response to seed exudates that were previously collected from seed imbibed for 24 h at low temperatures (4°C). These results suggest that cold stress 2 to 4 days after planting increases soybean susceptibility to damping-off, presumably because of increased seed exudation and delayed seedling growth.
Designer human tissue: coming to a lab near you
Authors: Hay David C. , O'Farrelly Cliona
Published: May 2018

Human pluripotent stem cells (PSCs) offer a scalable alternative to primary and transformed human tissue. PSCs include human embryonic stem cells, derived from the inner cell mass of blastocysts unsuitable for human implantation; and induced PSCs, generated by the reprogramming of somatic cells. Both cell types display the ability to self-renew and retain pluripotency, promising an unlimited supply of human somatic cells for biomedical application. A distinct advantage of using PSCs is the ability to select for genetic background, promising personalized modelling of human biology ‘in a dish’ or immune-matched cell-based therapies for the clinic. This special issue will guide the reader through stem cell self-renewal, pluripotency and differentiation. The first articles focus on improving cell fidelity, understanding the innate immune system and the importance of materials chemistry, biofabrication and bioengineering. These are followed by articles that focus on industrial application, commercialization and label-free assessment of tissue formation. The special issue concludes with an article discussing human liver cell-based therapies past, present and future.

This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
Pluripotent stem cells: induction and self-renewal
Authors: Abu-Dawud R. , Graffmann N. , Ferber S. , Wruck W. , Adjaye J.
Published: May 2018

Pluripotent stem cells (PSCs) lie at the heart of modern regenerative medicine due to their properties of unlimited self-renewalin vitroand their ability to differentiate into cell types representative of the three embryonic germ layers—mesoderm, ectoderm and endoderm. The derivation of induced PSCs bypasses ethical concerns associated with the use of human embryonic stem cells and also enables personalized cell-based therapies. To exploit their regenerative potential, it is essential to have a firm understanding of the molecular processes associated with their induction from somatic cells. This understanding serves two purposes: first, to enable efficient, reliable and cost-effective production of excellent quality induced PSCs and, second, to enable the derivation of safe, good manufacturing practice-grade transplantable donor cells. Here, we review the reprogramming process of somatic cells into induced PSCs and associated mechanisms with emphasis on self-renewal, epigenetic control, mitochondrial bioenergetics, sub-states of pluripotency, naive ground state, naive and primed. A meta-analysis identified genes expressed exclusively in the inner cell mass and in the naive but not in the primed pluripotent state. We propose these as additional biomarkers defining naive PSCs.

This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
Three-dimensional cell culture: from evolution to revolution
Authors: Alhaque Sharmin , Themis Michael , Rashidi Hassan
Published: May 2018

Recent advances in the isolation of tissue-resident adult stem cells and the identification of inductive factors that efficiently direct differentiation of human pluripotent stem cells along specific lineages have facilitated the development of high-fidelity modelling of several tissuesin vitro. Many of the novel approaches have employed self-organizing three-dimensional (3D) culturing of organoids, which offer several advantages over conventional two-dimensional platforms. Organoid technologies hold great promise for modelling diseases and predicting the outcome of drug responsesin vitro. Here, we outline the historical background and some of the recent advances in the field of three-dimensional organoids. We also highlight some of the current limitations of these systems and discuss potential avenues to further benefit biological research using three-dimensional modelling technologies.

This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
Intestinal organoids for modelling intestinal development and disease
Authors: Fair Kathryn L. , Colquhoun Jennifer , Hannan Nicholas R. F.
Published: May 2018

Gastrointestinal diseases are becoming increasingly prevalent in developed countries. Immortalized cells and animal models have delivered important but limited insight into the mechanisms that initiate and propagate these diseases. Human-specific models of intestinal development and disease are desperately needed that can recapitulate structure and function of the gutin vitro. Advances in pluripotent stem cells and primary tissue culture techniques have made it possible to culture intestinal epithelial cells in three dimensions that self-assemble to form ‘intestinal organoids'. These organoids allow for new, human-specific models that can be used to gain insight into gastrointestinal disease and potentially deliver new therapies to treat them. Here we review currentin vitromodels of intestinal development and disease, considering where improvements could be made and potential future applications in the fields of developmental modelling, drug/toxicity testing and therapeutic uses.

This article is part of the theme issue ‘Designer human tissue: coming to a lab near you'.
Innate immunity in stem cell-derived hepatocytes
Authors: Fischer Lena , Hay David C. , O'Farrelly Cliona
Published: May 2018

Stem cell-derived hepatocyte-like cells (HLCs) offer great opportunities for studies of host–pathogen interactions and tissue regeneration, as well as hepatotoxicity. To reliably predict the outcome of infection or to enhance graft survival, a finely tuned innate immune system is essential. Hepatocytes have long been considered solely metabolic and their critical innate immune potential is only recently gaining attention. Viral infection studies show that pathogen detection by cytosolic receptors leads to interferon (IFN) induction in primary hepatocytes and HLCs. IFN expression in HLCs is characterized by strong expression of type III IFN and low expression of type I IFN which is also a characteristic of primary hepatocytes. The response to IFN differs in HLCs with lower interferon-stimulated gene (ISG)-expression levels than in primary hepatocytes. Tumour necrosis factor-alpha (TNF-α) signalling is less studied in HLCs, but appears to be functional. Expression of toll-like receptors (TLR) 2–5, 7 and 9 has been reported in primary hepatocytes but has been poorly studied in HLCs. In summary, although they retain some immature features, HLCs are in many ways superior to hepatoma cell lines for cell-based modelling. In this review, we will provide an overview of innate immune signalling in HLCs and how this compares with primary hepatocytes.

This article is part of the themed issue ‘Designer human tissue: coming to a lab near you’.
New substrates for stem cell control
Authors: Schmidt Sara , Lilienkampf Annamaria , Bradley Mark
Published: May 2018

The capacity to culture stem cells in a controllable, robust and scalable manner is necessary in order to develop successful strategies for the generation of cellular and tissue platforms for drug screening, toxicity testing, tissue engineering and regenerative medicine. Creating substrates that support the expansion, maintenance or directional differentiation of stem cells would greatly aid these efforts. Optimally, the substrates used should be chemically defined and synthetically scalable, allowing growth under defined, serum-free culture conditions. To achieve this, the chemical and physical attributes of the substrates should mimic the natural tissue environment and allow control of their biological properties. Herein, recent advances in the development of materials to study/manipulate stem cells, both
in vitro
and
in vivo,
are described with a focus on the novelty of the substrates’ properties, and on application of substrates to direct stem cells.

This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
Three-dimensional bioprinting of stem-cell derived tissues for human regenerative medicine
Authors: Skeldon Gregor , Lucendo-Villarin Baltasar , Shu Wenmiao
Published: May 2018

Stem cell technology in regenerative medicine has the potential to provide an unlimited supply of cells for drug testing, medical transplantation and academic research. In order to engineer a realistic tissue model using stem cells as an alternative to human tissue, it is essential to create artificial stem cell microenvironment or niches. Three-dimensional (3D) bioprinting is a promising tissue engineering field that offers new opportunities to precisely place stem cells within their niches layer-by-layer. This review covers bioprinting technologies, the current development of ‘bio-inks’ and how bioprinting has already been applied to stem-cell culture, as well as their applications for human regenerative medicine. The key considerations for bioink properties such as stiffness, stability and biodegradation, biocompatibility and printability are highlighted. Bioprinting of both adult and pluriopotent stem cells for various types of artificial tissues from liver to brain has been reviewed. 3D bioprinting of stem-cell derived tissues for human regenerative medicine is an exciting emerging area that represents opportunities for new research, industries and products as well as future challenges in clinical translation.

This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.