bluuebunny/crossref_metadata_2025 huggingface dataset:
A spectroscopic study of weak metallic emission lines in a B3 V star ι Herculis
Authors: Sadakane Kozo , Nishimura Masayoshi
Published: February 2019

We present a list of weak emission lines (WELs) observed in a sharp-lined B3 V star ι Her (HD 160762) using high-resolution (R = 65000) and high-S/N (∼1300) spectral data. The list covers a spectral region between 4900 Å and 10000 Å. We registered 207 WELs in this star and identified 190 lines including ten ions (nine elements). Emission lines of C ii, N i, Cr ii, Mn ii, and Ni ii have been identified among normal B-type stars for the first time. Seventeen emission lines remain unidentified. We compared our list with the published list of WELs for 3 Cen A (Wahlgren & Hubrig, 2004, A&A, 418, 1073) and found that the numbers of detected emission lines reflect differences in abundance between these two stars. We detected 13 C i emission lines in ι Her (normal in C), while only one C i emission line was found in 3 Cen A (deficient in C). Many emission lines of P ii and Cu ii have been detected in 3 Cen A (over-abundant in both P and Cu), while no emission line of these ions has been found in ι Her. Many emission lines of Fe ii are visible in the shorter-wavelength side of 6000 Å in ι Her, while these emission lines are missing in 3 Cen A. Close inspections of spectral data of 3 Cen A reveal that the apparently missing Fe ii lines appear as absorption lines in this star. Because these two stars have nearly the same atmospheric parameters (Teff and log g), a physical interpretation that is independent of these two parameters is needed to account for this observation.
The Crust–Mantle Transition of the Khantaishir Arc Ophiolite (Western Mongolia)
Authors: Gianola Omar , Schmidt Max W , Jagoutz Oliver , Rickli Jörg , Bruguier Olivier , Sambuu Oyungerel
Published: February 2019

The crust–mantle transition of the Khantaishir ophiolite in western Mongolia is well exposed. The mantle section shows an up to 4 km thick refractory harzburgitic mantle with local dunite channels and lenses. Towards its top, the mantle is increasingly replaced by discrete zones of pyroxenite, which form a kilometre-wide and hundreds of metres-thick horizon at the contact with the overlying crustal section. The plutonic crustal section is composed of gabbros, gabbronorites, tonalites and minor plagiogranites. The lower part of the crustal section is intercalated with pyroxenite lenses, forming a layered sequence, whereas the upper part is cut by volcanic dykes associated with the overlying basalt–andesitic volcanic section. Most of the ultramafic rocks and gabbronorites show a depletion in high field strength elements and positive anomalies for Sr and Pb, whereas gabbros, tonalites and plagiogranites are enriched in large ion lithophile elements and have slightly enriched rare earth element patterns. Non-modal fractional melting models indicate that the most depleted harzburgites of the ophiolite originated after 20–25% of melt extraction from the mantle. Leached minerals and whole-rocks from the crust–mantle transition of the Khantaishir ophiolite define a Sm–Nd isochron at 540 ± 12 Ma, which is interpreted as the formation age of the crust–mantle transition. Additionally, minerals and whole-rocks display a restricted εNd(t=540 Ma) composition (+3·5 to +7·0) and a large scatter in εSr(t=540 Ma) (–19·8 to +14·2). Clinopyroxenes in the crust–mantle transition rocks indicate that they were in equilibrium with a boninitic-like melt, consistent with the lavas observed in the volcanic section of the ophiolite. It is therefore inferred that the Khantaishir ophiolite represents a slice of an incipient oceanic island-arc formed in a suprasubduction environment.
Paraquat Exposure Increases Oxidative Stress Within the Dorsal Striatum of Male Mice With a Genetic Deficiency in One-carbon Metabolism
Authors: Jadavji Nafisa M , Murray Lauren K , Emmerson Joshua T , Rudyk Chris A , Hayley Shawn , Smith Patrice D
Published: February 2019

Paraquat is an herbicide that is commonly used worldwide. Exposure to paraquat results in Parkinson’s disease (PD)-like symptoms including dopaminergic cell loss. Nutrition has also been linked in the pathogenesis of PD, such as reduced levels of folic acid, a B-vitamin, and component of one-carbon metabolism. Within one-carbon metabolism, methylenetetrahydrofolate reductase (MTHFR) catalyzes the irreversible conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. A polymorphism in MTHFR (677 C&→T) has been reported in 5%–15% of North American and European human populations. The MTHFR polymorphism is also prevalent in PD patients. The goal of this study was to investigate the impact of paraquat-induced PD-like pathology in the context of reduced levels of MTHFR. Three-month-old male Mthfr+/− mice, which model the MTHFR polymorphism observed in humans, were administered intraperitoneal injections of paraquat (10 mg/kg) or saline 6 times over 3 weeks. At the end of paraquat treatment, motor and memory function were assessed followed by collection of brain tissue for biochemical analysis. Mthfr+/– mice treated with paraquat showed impaired motor function. There was increased microglial activation within the substantia nigra (SN) of Mthfr+/− mice treated with paraquat. Additionally, all Mthfr+/− mice that were treated with paraquat showed increased oxidative stress within the dorsal striatum, but not the SN. The present results show that paraquat exposure increases PD-like pathology in mice deficient in one-carbon metabolism.
Effect of Planting Date and Inoculum Density on Severity of Fusarium Wilt of Lettuce in California
Authors: Paugh Kelley R. , Gordon Thomas R.
Published: February 2019

Seven lettuce cultivars were transplanted into a field infested with Fusarium oxysporum f. sp. lactucae (causal agent of Fusarium wilt of lettuce) in August and September of 2014, 2015, and 2016. For moderately susceptible cultivars, 1- or 2-week differences in planting date had a significant effect on severity of Fusarium wilt. In growth chamber experiments, cultivars of moderate susceptibility were maintained in a growth chamber under cool conditions (23/18°C), and a subset of plants was transferred to a warm chamber (33/23°C) for 1 week, at weekly intervals after transplanting. Plants exposed to high temperatures at 2 and 3 weeks after transplanting (WAT) had more severe symptoms of Fusarium wilt than those exposed at 4 WAT. In October 2015, April 2016, August 2016, and August 2017, moderately susceptible cultivars were planted into field soil with an inoculum density gradient. Moderately susceptible cultivars were little affected by Fusarium wilt where inoculum densities of F. oxysporum f. sp. lactucae were <125 per gram of soil, even in warm planting windows. Adjusting planting dates to avoid high temperatures during a critical stage of growth and maintaining low inoculum density in soil can contribute to management of Fusarium wilt in moderately susceptible lettuce cultivars.
The Simple Pediatric Activity Ultrasound Score (SPAUSS) for the Accurate Detection of Pediatric Inflammatory Bowel Disease
Authors: Kellar Amelia , Wilson Stephanie , Kaplan Gilaad , DeBruyn Jennifer , Tanyingoh Divine , Novak Kerri L.
Published: February 2019

Objective:

The aim of the study was to identify the most significant ultrasound (US) parameters that predict inflammatory activity and develop a simple US activity score.

Methods:

Patients were identified through retrospective evaluation of an established database of children with inflammatory bowel disease (IBD). Patients with endoscopy and US within 60 days were included (N = 75). US parameters evaluated included: bowel wall thickness (BWT), mesenteric inflammatory fat, lymphadenopathy, and hyperemia. The weighted kappa statistic was calculated to assess agreement between sonographic and endoscopically identified disease location. Using a proportional odds model and ordinal logistic regression, statistically significant (P < 0.05) parameters were used to generate a score. Variables were weighted to classify individuals into severity classes. Receiver operating characteristic curves were plotted to demonstrate the score's discriminative and predictive capacity.

Results:

There was substantial agreement between US and endoscopy for all disease locations (weighted kappa = 0.85) and substantial agreement for ileocolonic disease (weighted kappa = 0.96). Two sonographic parameters were identified as contributing significantly to disease activity: BWT and mesenteric inflammatory fat (P < 0.05). A predictive score was developed incorporating BWT, hyperemia and inflammatory fat, and receiver operating characteristic curve curves demonstrated good predictive capacity to distinguish between the absence of disease (normal) and active disease with an area under the curve of 82.1%.

Conclusions:

The most important sonographic parameters for predicting disease activity were BWT and mesenteric inflammatory fat. When combined with hyperemia into a simple score, there was accurate detection of inflammatory activity in children with inflammatory bowel disease. This score may facilitate noninvasive, bedside detection of inflammation, and standardize the use of US in children.
Energy-dependent transport at dural lymphatic vessels is necessary for Aβ brain clearance in Alzheimer’s disease
Authors: Romanova Liudmila , Phillips Heidi , Calip Gregory S. , Hauser Kyle , Peterson Daniel A. , Lazarov Orly , Predescu Daniel , Predescu Sanda , Schneider Julie , Kordower Jeff , Hansen Eric , Lam Cornelius H. , Janson Christopher G.
Published: February 2019

Viewed as an imbalance between production and clearance of toxic Aβ peptides, Alzheimer’s disease is a candidate for therapies to augment brain waste removal. Prior work has shown that Aβ accumulates in meninges with aging as a byproduct of normal brain activity, in parallel with build-up of Aβ oligomers in neurons, blood vessels, and interstitial fluid. Using the TgF344-AD rat model of Alzheimer’s disease, we now report that dural lymphatic vessels specifically accumulate neurotoxic pyroglutamate amyloid beta (pE3-Aβ) with aging. Notably, accelerated amyloidosis is observed in meninges after ligation of cervical lymphatics, together with significantly increased pE3-Aβ and Aβ42 deposition in upstream brain regions implicated in Alzheimer’s disease. Blockade of lymphatic clearance is not sufficiently compensated by other efflux pathways, suggesting a necessary role of Aβ clearance at the level of lymphatics. We further report that dural lymphatic cells actively clear Aβ via energy-dependent mechanisms, and lymphatic Aβ transport is significantly impaired both in normal aging and in Alzheimer’s disease. Dural lymphatic cells isolated from the TgF344-AD rat show ultrastructural abnormalities in mitochondria and abnormal cytoplasmic inclusions, with a distinct transcriptional profile implicating failure of energy-dependent transport. Finally, using human meninges treated with FocusDeep tissue clearing, we demonstrate using whole mount panoramic imaging that dural lymphatic vessels comprise a structurally diverse intracranial vascular network that accumulates pE3-Aβ with aging, similar to the rat model. We conclude that intracranial meningeal and extracranial cervical lymphatic vessels are targets for Alzheimer’s disease therapies focused on improving amyloid clearance.

One Sentence Summary

Lymphatic vessels remove Aβ from the brain via energy-dependent active transport mechanisms, and blockage of extracranial lymphatic drainage is sufficient to cause significant acceleration of intracranial Alzheimer’s Aβ pathology in both meninges and brain.
Aerobic bacteria as Escherichia coli can survive in ESwabTM medium after a 3 month-freezing at −80°C but not after multiple thawing
Authors: Saliba Rindala , Zahar Jean Ralph , Carbonnelle Etienne , Lescat Mathilde
Published: February 2019

Pretesting of procedures for specimen conservation should be part of preliminary studies for trials especially when quantification of bacteria must be performed in a second time. Quantitative epidemiological studies of multidrug resistant organisms sampled from rectal swabs could be then particularly favored. The aim of this preliminary study, was to evaluate the performance of the flocked swab with liquefied Amies transport medium ESwab™, for the survival evaluation of aerobic bacteria, from rectal swab sampling according to the number of freezing at −80°C and thawing cycles and the time of freezing. We first observed that quantification was not reliable after F/T cycles whereas a unique freezing could be performed especially when studying E. coli isolates. The second experiment allowed us to observe that this stability could be obtained until 3 month-freezing. Our study represents a preliminary study, confirming the utility of ESwab™ in microbiological diagnostics and research studies, not only for molecular bacterial tests, but also, for the maintenance of bacterial viability in clinical specimens.
A New Experimental Model Of Muscle Pain In Humans Based On Short-Wave Diathermy
Authors: Mista Christian A. , Laugero Silvio , Adur Javier , Andersen Ole K. , Biurrun Manresa Jose
Published: February 2019

Experimental models of pain in humans are crucial for understanding pain mechanisms. The most often used muscle pain models involve the injection of algesic substances, such as hypertonic saline solution or nerve growth factor, or exercise-induced delayed onset muscle soreness (DOMS). However, these models are either invasive or take substantial time to develop, and the elicited level of pain/soreness is difficult to control. To overcome these shortcomings, we propose to elicit muscle pain by a localized application of short-wave diathermy (SWD). In this crossover study, SWD was administered to eighteen healthy volunteers to the wrist extensor muscle group, with a constant stimulation intensity and up to 4 minutes. We measured pressure pain threshold (PPT) and pinprick sensitivity (PPS) and performed a psychophysical evaluation of muscle soreness at baseline and at 0, 30 and 60 minutes. SWD evoked localized muscle pain/soreness in the wrist extensor muscle group and a decrease of PPT in the treated arm compared with the control arm that lasted for at least 60 minutes, reflecting ongoing hyperalgesia after SWD application. PPS was not significantly altered 30 to 60 min following SWD, suggesting a minimal contribution from skin tissue to sustained hyperalgesia.
UK phenomics platform for developing and validating EHR phenotypes: CALIBER
Authors: Denaxas Spiros , Gonzalez-Izquierdo Arturo , Direk Kenan , Fitzpatrick Natalie , Banerjee Amitava , Dobson Richard , Fatemifar Ghazaleh , Kuan Valerie , Lumbers Tom , Pasea Laura , Patel Riyaz , Hingorani Aroon , Sudlow Cathie , Hemingway Harry
Published: February 2019

Objective

Electronic health records are a rich source of information on human diseases, but the information is variably structured, fragmented, curated using different coding systems and collected for purposes other than medical research. We describe an approach for developing, validating and sharing reproducible phenotypes from national structured Electronic Health Records (EHR) in the UK with applications for translational research.

Materials and Methods

We implemented a rule-based phenotyping framework, with up to six approaches of validation. We applied our framework to a sample of 15 million individuals in a national EHR data source (population based primary care, all ages) linked to hospitalization and death records in England. Data comprised continuous measurements such as blood pressure, medication information and coded diagnoses, symptoms, procedures and referrals, recorded using five controlled clinical terminologies: a) Read (primary care, subset of SNOMED-CT), b) ICD-9, ICD-10 (secondary care diagnoses and cause of mortality), c) OPCS-4 (hospital surgical procedures) and d) Gemscript Drug Codes.

Results

The open-access CALIBER Portal (https://www.caliberresearch.org/portal) demonstrates phenotyping algorithms for 50 diseases, syndromes, biomarkers and lifestyle risk factors and provides up to six validation layers. These phenotyping algorithms have been used by 40 national/international research groups in 60 peer-reviewed publications.

Conclusion

Herein, we describe the UK EHR phenomics approach, CALIBER, with initial evidence of validity and use, as an important step towards international use of UK EHR data for health research.
The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease
Authors: Oñate Maritza , Catenaccio Alejandra , Salvadores Natalia , Saquel Cristian , Martinez Alexis , Moreno-Gonzalez Ines , Gamez Nazaret , Soto Paulina , Soto Claudio , Hetz Claudio , Court Felipe A.
Published: February 2019

Parkinson’s disease (PD) is the second most common neurodegenerative condition, characterized by motor impairment due to the progressive degeneration of dopaminergic neurons in the substantia nigra and depletion of dopamine release in the striatum. Accumulating evidence suggest that degeneration of axons is an early event in the disease, involving destruction programs that are independent of the survival of the cell soma. Necroptosis, a programmed cell death process, is emerging as a mediator of neuronal loss in models of neurodegenerative diseases. Here, we demonstrate activation of necroptosis in postmortem brain tissue from PD patients and in a toxin-based mouse model of the disease. Inhibition of key components of the necroptotic pathway resulted in a significant delay of 6-hydroxydopamine dependent axonal degeneration of dopaminergic and cortical neurons in vitro. Genetic ablation of necroptosis mediators MLKL and RIPK3, as well as pharmacological inhibition of RIPK1 in vivo, decreased dopaminergic neuron degeneration, improving motor performance. Together, these findings suggest that axonal degeneration in PD is mediated by the necroptosis machinery, a process here referred to as necroaxoptosis, a druggable pathway to target dopaminergic neuronal loss.
Automated acquisition of knowledge beyond pathologists
Authors: Yamamoto Yoichiro , Tsuzuki Toyonori , Akatsuka Jun , Ueki Masao , Morikawa Hiromu , Numata Yasushi , Takahara Taishi , Tsuyuki Takuji , Shimizu Akira , Maeda Ichiro , Tsuchiya Shinichi , Kanno Hiroyuki , Kondo Yukihiro , Fukumoto Manabu , Tamiya Gen , Ueda Naonori , Kimura Go
Published: February 2019

Deep learning algorithms have been successfully used in medical image classification and cancer detection. In the next stage, the technology of acquiring explainable knowledge from medical images is highly desired. Herein, fully automated acquisition of explainable features from annotation-free histopathological images is achieved via revealing statistical distortions in datasets by introducing the way of pathologists’ examination into a set of deep neural networks. As validation, we compared the prediction accuracy of prostate cancer recurrence using our algorithm-generated features with that of diagnosis by an expert pathologist using established criteria on 13,188 whole-mount pathology images. Our method found not only the findings established by humans but also features that have not been recognized so far, and showed higher accuracy than human in prognostic prediction. This study provides a new field to the deep learning approach as a novel tool for discovering uncharted knowledge, leading to effective treatments and drug discovery.
cyAbrB transcriptional regulators as safety devices to inhibit heterocyst differentiation in Anabaena
Authors: Higo Akiyoshi , Nishiyama Eri , Nakamura Kota , Hihara Yukako , Ehira Shigeki
Published: February 2019

Cyanobacteria are monophyletic organisms that perform oxygenic photosynthesis. While they exhibit great diversity, they have a common set of genes. However, the essentiality of them for viability has hampered the elucidation of their functions. One example of the genes is cyabrB1 encoding a transcriptional regulator. In the present study, we investigated the function of cyabrB1 in heterocyst-forming cyanobacterium Anabaena sp. PCC 7120 through CRISPR interference, a method we recently utilized for the photosynthetic production of a useful chemical in the strain. Conditional knockdown of cyabrB1 in the presence of nitrate resulted in formation of heterocysts. Two genes, hetP and hepA, which are required for heterocyst formation, were up-regulated by cyabrB1 knockdown in the presence of combined nitrogen sources. The genes are known to be induced by HetR, a master regulator of heterocyst formation. hetR was not induced by cyabrB1 knockdown. hetP and hepA were repressed by direct binding of cyAbrB1 to their promoter regions in a HetR-independent manner. In addition, the over-expression of cyabrB1 abolished heterocyst formation upon nitrogen depletion. Also, knockout of cyabrB2, a paralogue gene of cyabrB1, in addition to cyabrB1 knockdown, enhanced heterocyst formation in the presence of nitrate, suggesting functional redundancy of cyAbrB proteins. We propose that a balance between amounts of HetR and cyAbrB1 is a key factor influencing heterocyst differentiation during nitrogen step-down. cyAbrB proteins are essential safety devices inhibiting heterocyst differentiation.

Importance

Spore formation in Bacillus subtilis and Streptomyces represents non-terminal differentiation and has been extensively studied as models of prokaryotic cell differentiation. In the two organisms, many cells differentiate simultaneously, and the differentiation is governed by a network in which one regulator stands at the top. Differentiation of heterocysts in Anabaena sp. PCC 7120 has also been extensively studied. The differentiation is unique because it is terminal and only 5-10% vegetative cells differentiate into heterocysts. In the present study, we identified cyAbrB1 as a repressor of two genes that are essential for heterocyst formation, hetP and hepA, independent of HetR, which is a master activator for heterocyst differentiation. The finding is reasonable for unique cell differentiation of Anabaena because cyAbrB1 could suppress heterocyst differentiation tightly in vegetative cells, while only cells in which HetR is over-expressed could differentiate into heterocysts.
An Event-Related Potential Study of Onset Primacy in Visual Change Detection
Authors: Van Pelt Jennifer , Lowe Benjamin G. , Robinson Jonathan E. , Donaldson Maria J. , Johnston Patrick , Yamamoto Naohide
Published: February 2019

Onset primacy is a behavioural phenomenon whereby humans identify the appearance of an object (onset) with greater efficiency than other kinds of visual change, such as the disappearance of an object (offset). The default mode hypothesis explains this phenomenon by postulating that the attentional system is optimised for onset detection in its initial state. The present study extended this hypothesis by combining a change detection task and measurement of the P300 event-related potential, which was thought to index the amount of processing resources available to detecting onsets and offsets. In an experiment, while brain activity was monitored by electroencephalography, participants indicated the locations of onsets and offsets under the condition in which they occurred equally often in the same locations across trials. Although there was no reason to prioritise detecting one type of change over the other, onsets were detected more quickly and they evoked a larger P300 than offsets. These results suggest that processing resources are preferentially allocated to onset detection. This biased allocation may be a basis on which the attentional system defaults to the ‘onset detection’ mode.
GDNF receptor agonist supports dopamine neurons in vitro and protects their function in animal model of Parkinson’s
Authors: Mahato Arun Kumar , Renko Juho-Matti , Kopra Jaakko , Visnapuu Tanel , Korhonen Ilari , Pulkkinen Nita , Bespalov Maxim , Ronken Eric , Piepponen T. Petteri , Voutilainen Merja , Tuominen Raimo K. , Karelson Mati , Sidorova Yulia A. , Saarma Mart
Published: February 2019

Motor symptoms of Parkinson’s disease (PD) are caused by degeneration and progressive loss of nigrostriatal dopamine neurons. Currently no cure for this disease is available. Existing drugs alleviate PD symptoms, but fail to halt neurodegeneration. Glial cell line-derived neurotrophic factor (GDNF) is able to protect and repair dopamine neuronsin vitroand in animal models of PD, but its clinical use is complicated by pharmacokinetic properties. In the present study we demonstrate the ability of a small molecule agonist of GDNF receptor RET to support the survival of cultured dopamine neurons only when they express GDNF receptors. In addition, BT13 activates intracellular signaling cascadesin vivo, stimulates release of dopamine and protect the function of dopaminergic neurons in a 6-hydroxydopamine (6-OHDA) rat model of PD. In contrast to GDNF, BT13 is able to penetrate through the blood-brain-barrier. Thus, BT13 serves as an excellent tool compound for the development of novel disease-modifying treatments against PD.
Transcriptional kinetics of X-chromosome upregulation
Authors: Larsson Anton J. M. , Coucoravas Christos , Sandberg Rickard , Reinius Björn
Published: February 2019

Ohno’s hypothesis postulates that X-chromosome upregulation rectifies X-dose imbalance relative to autosomal genes, present in two active copies per cell. Here we dissected X-upregulation into kinetics of transcription, inferred from allele-specific single-cell RNA-sequencing (scRNAseq) data from somatic mouse cells. We confirmed increased X-chromosome expression, and remarkably found that the X-chromosome achieved upregulation by elevated burst frequencies. This provides mechanistic insights into X-chromosome upregulation.
Sensorimotor adaptation compensates for distortions of 3D shape information
Authors: Cesanek Evan , Taylor Jordan A. , Domini Fulvio
Published: February 2019

Visual perception often fails to recover the veridical 3D shape of objects in the environment due to ambiguity and variability in the available depth cues. However, we rely heavily on 3D shape estimates when planning movements, for example reaching to pick up an object from a slanted surface. Given the wide variety of distortions that can affect 3D perception, how do our actions remain accurate across different environments? One hypothesis is that the visuomotor system performs selective filtering of 3D information to minimize distortions. Indeed, some studies have found that actions appear to preferentially target stereo information when it is put in conflict with texture information. However, since these studies analyze averages over multiple trials, this apparent preference could be produced by sensorimotor adaptation. In Experiment 1, we create a set of cue-conflict stimuli where one available depth cue is affected by a constant bias. Sensory feedback rapidly aligns the motor output with physical reality in just a few trials, which can make it seem as if action planning selectively relies on the reinforced cue—yet no change in the relative influences of the cues is necessary to eliminate the constant errors. In contrast, when one depth cue becomes less correlated with physical reality, variable movement errors will occur, causing canonical adaptation to fail as the opposite error corrections cancel out. As a result, canonical adaptation cannot explain the preference for stereo found in studies with variable errors. However, Experiment 2 shows that persistent errors can produce a novel form of adaptation that gradually reduces the relative influence of an unreliable depth cue. These findings show that grasp control processes are continuously modified based on sensory feedback to compensate for both biases and noise in 3D visual processing, rather than having a hardwired preference for one type of depth information.
Production, purification, and kinetics of the poly-β-hydroxybutyrate depolymerase fromMicrobacterium paraoxydansRZS6: A novel biopolymer-degrading organism isolated from a dumping yard
Authors: Sayyed RZ , Wani SJ , Alyousef Abdullah A. , Alqasim Abdulaziz , Syed Asad
Published: February 2019

Poly-β-hydroxybutyrate (PHB) depolymerase can decompose biodegradable polymers and therefore has great commercial significance in the bioplastic sector. However, few reports have described PHB depolymerases based on isolates obtained from plastic-contaminated sites that reflect the potential of the source organism. In this study, we evaluatedMicrobacterium paraoxydansRZS6 as a producer of extracellular PHB depolymerase isolated from a plastic-contaminated site in the municipal area of Shahada, Maharashtra, India, for the first time. The isolate was identified using the polyphasic approach, i.e., 16S rRNA gene sequencing, gas chromatographic analysis of fatty acid methyl esters, and BIOLOG identification, and was found to hydrolyze PHB on minimal salt medium containing PHB as the only source of carbon. Both isolates produced PHB depolymerase at 30°C within 2 days and at 45°C within 4 days. The enzyme was purified most efficiently using an octyl-sepharose CL-4B column, with the highest purification yield of 6.675 U/mg/mL. The enzyme required Ce2+and Mg2+ions but was inhibited by Fe2+ions and mercaptoethanol. Moreover, enzyme kinetic analysis revealed that the enzyme was a metalloenzyme requiring Mg2+ions, with optimum enzyme activity at 45°C (thermophilic) and under neutrophilic conditions (optimum pH = 7). The presence of Fe2+ions (1 mM) and mercaptoethanol (1000 ppm) completely inhibited the enzyme activity. The molecular weight of the enzyme (40 kDa), as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, closely resembled that of PHB depolymerase fromAureobacterium saperdae. Scale-up from the shake-flask level to a laboratory-scale bioreactor further enhanced the enzyme yield. Our findings highlighted the applicability ofM. paraoxydansas a producer of extracellular PHB depolymerase isolated from a plastic-contaminated site in the municipal area of Shahada, Maharashtra, India.
Spatial and temporal profiling of receptor membrane insertion controls commissural axon responses to midline repellents
Authors: Pignata Aurora , Ducuing Hugo , Boubakar Leila , Gardette Thibault , Kindbeiter Karine , Bozon Muriel , Tauszig-Delamasure Servane , Falk Julien , Thoumine Olivier , Castellani Valérie
Published: February 2019

Accurate perception of guidance cues is crucial for axonal pathfinding. During their initial navigation in the spinal cord, commissural axons are kept insensitive to midline repellents. Through yet unclear mechanisms acting during midline crossing in the floor plate, they switch on responsiveness to various repulsive signals, that establish a permanent midline barrier and propel the axons for exit. Whether these gains of response are coupled to occur in synchrony or rather are independently activated through signaling-specific programs is fully unknown. We set-up a paradigm for live imaging and super resolution analysis of guidance receptor dynamics during commissural growth cone navigation in chick and mouse embryos. We uncovered a remarkable program of delivery and allocation of receptors at the growth cone surface, generating receptor-specific spatial and temporal profiles. This reveals a mechanism whereby commissural growth cones can discriminate coincident repulsive signals that they functionalize at different time points of their navigation.
Plant-microbe specificity varies as a function of elevation
Authors: Cobian Gerald M. , Egan Cameron , Amend Anthony S.
Published: February 2019

Specialized associations between interacting species are a fundamental determinant of the diversity and distribution of both partners. How specialization of guilds of organisms varies along environmental gradients underpins popular theories of biogeography and macroecology, whereas the degree of specialization of a species is typically considered fixed. However, the extent to which environmental context impacts specialization dynamics is seldom examined empirically. In this study, we examine how specialization within a bipartite network consisting of three co-occurring plant species and their foliar fungal endophyte symbionts changes along a 1 000-meter elevation gradient where host species were held constant. The gradient, along the slope of Mauna Loa shield volcano, represents the entire elevational range of two of the three plants. Network and plant specialization values displayed a parabolic relationship with elevation, and were highest at middle elevations, whereas bipartite associations were least specific at low and high elevations. Shannon’s diversity of fungal endophytes negatively correlated with specificity, and was highest at the ends of the transects. Although plant host was a strong determinant of fungal community composition within sites, fungal species turnover was high among sites and plant host predicted a weak, though significant proportion of compositional variance. There was no evidence of spatial or elevational patterning in fungal community compositon. Our work demonstrates that specificity can be a plastic trait which is influenced by the environment and centrality of the host within its natural range.
Endophilin-A controls recruitment, priming and fusion of neurosecretory vesicles
Authors: Gowrisankaran Sindhuja , Steubler Vicky , Houy Sébastien , Peña del Castillo Johanna G. , Gelker Monika , Kroll Jana , Pinheiro Paulo S. , Halbsgut Nils , Raimundo Nuno , Sørensen Jakob B. , Milosevic Ira
Published: February 2019

Endophilins-A are conserved endocytic adaptors with membrane curvature-sensing and - inducing properties. We show here that, independently of their role in endocytosis, endophilin-A1 and endophilin-A2 regulate exocytosis of neurosecretory vesicles. The number of neurosecretory vesicles was not altered in chromaffin cells without endophilin, yet fast capacitance and amperometry measurements revealed reduced exocytosis, smaller vesicle pools and changed fusion kinetics. Both endophilin-A1 (brain-enriched) and A2 (ubiquitous) rescued exocytic defects, but endophilin-A2 was more efficient. Distribution of neurosecretory vesicles was altered in the plasma membrane proximity, but levels and distributions of main exocytic and endocytic factors were unchanged, and slow compensatory endocytosis was not robustly affected. Endophilin’s role in exocytosis is mediated through its SH3-domain and, at least in part, interaction with intersectin, a coordinator of exocytic and endocytic traffic. Altogether, we report that endophilins-A, key endocytic proteins linked to neurodegeneration, directly regulate exocytosis by controlling vesicle recruitment, priming and fusion.

Abstract Figure

Recruitment, priming and fusion of secretory vesicles is controlled by endophilin

Lack of endophilins alters the distribution of secretory vesicles near the PM

Endophilin’s role in exocytosis is mediated through its SH3-domain

Endophilin regulates intersectin localization by keeping it away from the PM
Dissection of the cellular function of the ZBED6 transcription factor in mouse myoblast cells using gene editing, RNAseq and proteomics
Authors: Younis Shady , Naboulsi Rakan , Wang Xuan , Cao Xiaofang , Larsson Mårten , Sargsyan Ernest , Bergsten Peter , Welsh Nils , Andersson Leif
Published: February 2019

The transcription factor ZBED6 acts as a repressor ofIgf2and affects directly or indirectly the transcriptional regulation of thousands of genes. Here, we use gene editing in mouse C2C12 myoblasts and show that ZBED6 regulatesIgf2exclusively through its binding site 5′-GGCTCG-3′ in intron 1 ofIgf2. Deletion of this motif (Igf2ΔGGCT) or complete ablation ofZbed6leads to ~20-fold up-regulation of IGF2 protein. Quantitative proteomics revealed an activation of Ras signaling pathway in bothZbed6-/-andIgf2ΔGGCTmyoblasts, and a significant enrichment of mitochondrial membrane proteins among proteins showing altered expression inZbed6-/-myoblasts. BothZbed6-/-andIgf2ΔGGCTmyoblasts showed a faster growth rate and developed myotube hypertrophy. These cells exhibited an increased O2consumption rate, due to IGF2 up-regulation. Transcriptome analysis revealed ~30% overlap between differentially expressed genes inZbed6-/-andIgf2ΔGGCTmyotubes, with an enrichment of up-regulated genes involved in muscle development. In contrast, ZBED6-overexpression in myoblasts led to cell apoptosis, cell cycle arrest, reduced mitochondrial activities and ceased myoblast differentiation. The similarities in growth and differentiation phenotypes observed inZbed6-/-andIgf2ΔGGCTmyoblasts demonstrates that ZBED6 affects mitochondrial activity and myogenesis largely through its regulation of IGF2 expression. This study suggests that the interaction between ZBED6-Igf2may be a therapeutic target for human diseases where anabolism is impaired.
Leptin and adiponectin dynamics at patients with rectal neoplasm - gender differences
Authors: Florescu Alexandru , Branisteanu Dumitru , Bilha Stefana , Scripcariu Dragos , Florescu Ioana , Scripcariu Viorel , Dimofte Gabriel , Grigoras Ioana
Published: February 2019

Background.

Numerous studies associate adipokines with colorectal malignancy, but few data deal with patients suffering exclusively of rectal carcinoma (RC). Aims. We evaluated leptin and adiponectin levels in RC patients compared to healthy population and their dynamics after surgery. Material and methods. Serum leptin and adiponectin were evaluated before surgery in 59 RC consecutive patients (38 males and 21 females), and in age and weight matched healthy controls. Measurements were repeated at 24, 72 hours and 7 days after surgery. Results. Adipokine levels were higher in women. Controls had higher leptin (32.±4.34 vs 9.51±1.73 ng/ml in women and 11±2.66 vs 2.54±0.39 ng/ml in men, p=0.00048 and 0.0032) and lower adiponectin (9±0.64 vs 11.85±1.02 µg/ml in women and 7.39±0.51 vs 8.5±0.62 µg/ml in men, p=0.017 and 0.019) than RC patients. Surgery caused an increase of leptin from 5.11±0.8 to 18.7±2.42 ng/ml, p=6.85 × 108, and a decrease of adiponectin from 9.71±0.58 to 7.87±0.47 µg/ml, p=1.4 × 1010 for all RC patients and returned thereafter to the initial range at 7 days. Adipokines were correlated with body weight (BW). The significance of correlation persisted after surgery only in males, but disappeared in females. Adipokines were not modified by tumor position, presurgical chemoradiotherapy or surgical technique. Women with RC experiencing weight loss had higher adiponectin than women without weight modifications (p<0.05 at all time points). Conclusions. Adipokine levels of patients with RC differ from the healthy population, possibly reflecting an adaptation to disease. Adipokine modifications after surgery may be related to acute surgical stress. Whether leptin and adiponectin directly interact is not clear. Women have higher adipokine levels, more so after significant weight loss, but the strength of their correlation with BW decreases after surgery. These data suggest gender differences in the adipokine profile of RC patients which may find clinical applications.
A Community-based assessment of quality of health care received and client satisfaction in Lagos, Nigeria
Authors: Akinyinka Modupe Rebekah , Oluwole Esther Oluwakemi , Odusanya Olumuyiwa Omotola
Published: February 2019

Background

Quality of health care and client satisfaction are key elements in improving the performance of health systems. A community-based assessment was conducted to determine the level of client satisfaction and the perception of the quality of services received by citizens of Lagos State.

Methodology

A descriptive cross-sectional study using both quantitative and qualitative methods, was conducted in four local government areas of Lagos state selected by multi-stage sampling techniques. The survey instruments included an interviewer- administered, pre-tested questionnaire and a 10-itemed focus group discussion guide. The survey obtained information about quality of the facilities and services. The outcome variables were client satisfaction and service quality.

Results

Two thousand respondents were recruited with a mean age of 37.6±10.21 years. Almost all respondents (98%) rated the health facilities to be clean, 96% felt they received effective treatment from their providers. Six out of ten respondents rated the waiting time to be short and 60% felt that most drugs were available. Eight-five percent opined that the quality of care received was good and 95% were satisfied with the services received. There was a significant correlation between quality of care and client satisfaction (r=0.145, p=0.001). Service factors such as perceived effectiveness of treatment received, confidence in health providers and use of higher level of health care were predictive of client satisfaction and good service quality.

Conclusion

Most clients were satisfied with health services and felt that service quality was good.
(E)-1-(2-Hydroxy-6-methoxyphenyl)-3-(2,3,4-trimethoxyphenyl)prop-2-en-1-one
Authors: Lee Ji Hye , Koh Dongsoo
Published: February 2019

In the title molecule, C19H20O6, the dihedral angle formed by the benzene rings is 36.71 (2)°. The hydroxy group is involved in a weak intramolecular O—H...O hydrogen bond. In the crystal, two weak C—H...O hydrogen bonds link the molecules into chains along [001].
Sudden elevation of plasma D‐dimer levels induced by the combination therapy of dabrafenib and trametinib: Report of two cases
Authors: Akino Saki , Ohashi Hiroyuki , Okano Tatsuro , Takeuchi Sora , Kawakami Tamihiro , Soma Yoshinao , Kadono Takafumi
Published: February 2019

The combination therapy of dabrafenib and trametinib revolutionized the treatment for BRAF V600‐mutated melanoma. Various adverse events have been reported for this treatment, most notably fever. Herein, we report two cases of novel an adverse event, namely sudden and significant elevation of plasma D‐dimer level induced by this therapy. In the first case, the remarkable elevation of plasma D‐dimer level up to 87.4 mg/dL was noted on day 11, and in the second case, the plasma D‐dimer level reached 125.5 mg/dL on day 25. In both cases, D‐dimer levels gradually decreased after the cessation of this therapy. Although the exact cause is not clear, we assume two possible hypotheses: the first is that the combination therapy may induce disseminated intravascular coagulation, and the second is that the therapy induced pathological condition of secondary thrombotic microangiopathies. Our cases suggest that this thrombotic adverse event should not be overlooked, and coagulation parameters need to be monitored during the course of this treatment.
Human‐habitat associations in the native distributions of alien bird species
Authors: Cardador Laura , Blackburn Tim M.
Published: February 2019

The role of human tolerance is increasingly being proposed as a key driver of invasion success by alien species. Human‐habitat associations may facilitate both transport – making a species more available for introduction – and establishment – by creating environmental matching between human‐altered habitats at the sites of origin and introduction. Nevertheless, the assumption that alien species exhibit associations with human habitats in their native ranges has been largely overlooked.

We conduct the first global assessment of the relative importance of human‐habitat associations in shaping the native distributions of species introduced world‐wide, in relation to other key important drivers, that is climate and land‐use. For this, we applied deviance partitioning analysis and species distribution models (SDM) to 776 introduced alien bird species from five continents.

While an independent effect of climate, and a joint effect of climate and non‐urban land uses, appear as major factors governing alien species distribution in their native ranges, significant independent contributions of anthropogenic variables were found for most species. The effect of anthropogenic variables was mostly positive, or concave with highest responses at intermediate values. Notably, human‐habitat associations in the native distributions of alien birds were significantly higher than expected, relative to a pool of available species from the same bird families (N = 3,565). Thus, introduced alien birds are a non‐random sample with respect to their association with human‐altered habitats. However, an increase in introduction rates of species showing no response, or a negative response, to human influence has occurred over recent decades.

Synthesis and applications. To prevent invasions, understanding which species are most likely to become successful aliens outside their native range is essential. Our results support the hypothesis that association with humans may be an important driver of alien bird species distribution in their native ranges, and thus increase the likelihood that these species will end up being introduced and established elsewhere. To provide policymakers with robust predictions of invasion risk, we recommend including human‐habitat associations in invasion risk assessments, and accounting for them in species distribution models.
Richness of plant communities plays a larger role than climate in determining responses of species richness to climate change
Authors: Wang Qi , Zhang Zhenhua , Du Rui , Wang Shiping , Duan Jichuang , Iler Amy Marie , Piao Shilong , Luo Caiyun , Jiang Lili , Lv Wangwang , Zhang Lirong , Meng Fandong , Suonan Ji , Li Yaoming , Li Bowen , Liu Peipei , Dorji Tsechoe , Wang Zhezhen , Li Yinnian , Du Mingyuan , Zhou Huakun , Zhao Xinquan , Wang Yanfen
Published: February 2019

Experimental warming in situ suggests that warming could lead to a loss of biodiversity. However, species that remain in situ and experience climate change will interact with species tracking climate change, which could also affect patterns of biodiversity. The relative contribution of species gains and losses to net changes in species richness is still unclear.

We use transplanted plant communities to test the hypothesis that both the change in climate and ecological communities tracking climate change will influence how species richness responds to climate change. Three intact alpine plant communities were reciprocally transplanted to create scenarios in which species experienced warmer and wetter conditions (transferred to lower elevations) and cooler and drier conditions (transferred to higher elevations) over 10 years on the Tibetan Plateau. Communities transplanted into the same elevation as controls represent species tracking climate change.

Transferring to lower elevations generally caused a net increase in richness and a higher rate of gains relative to the control plots; the magnitude of this effect depended on the specific elevation. Transferring to higher elevations lead to either net increases or decreases in richness and gains, depending on elevation. Species gains predicted much more variation in changes in species richness (50%) than did species loss (9%).

Species richness at the receptor site and the donor site were both important predictors of variation in species richness, and the abiotic environment did not explain additional variation. Changes in cover of dominant plant species in response to transfers did not predict changes in species richness, species gain or species loss. Our results suggest that species gains from species tracking climate change at the receptor sites, rather than species loss from the donor sites, predicted changes in species richness.

Synthesis. Warming experiments with physical barriers to dispersal may overestimate the negative effect of warming on plant diversity by not accounting for species gains. Our study highlights the importance of biotic factors in addition to the abiotic environment, when considering how climate change will affect plant diversity.