bluuebunny/crossref_metadata_2025 huggingface dataset:
External power amplification drives prey capture in a spider web
Authors: Han S. I. , Astley H. C. , Maksuta D. D. , Blackledge T. A.
Published: May 2019

Power amplification allows animals to produce movements that exceed the physiological limits of muscle power and speed, such as the mantis shrimp’s ultrafast predatory strike and the flea’s jump. However, all known examples of nonhuman, muscle-driven power amplification involve anatomical structures that store energy from a single cycle of muscular contraction. Here, we describe a nonhuman example of external power amplification using a constructed device: the web of the triangle-weaver spider,
Hyptiotes cavatus
, which uses energy stored in the silk threads to actively tangle prey from afar.
Hyptiotes
stretches its web by tightening a separate anchor line over multiple cycles of limb motion, and then releases its hold on the anchor line when insects strike the web. Both spider and web spring forward 2 to 3 cm with a peak acceleration of up to 772.85 m/s
2
so that up to four additional adhesive capture threads contact the prey while jerking caused by the spider’s sudden stop subsequently wraps silk around the prey from all directions. Using webs as external “tools” to store energy offers substantial mechanical advantages over internal tissue-based power amplification due to the ability of
Hyptiotes
to load the web over multiple cycles of muscular contraction and thus release more stored energy during prey capture than would be possible with muscle-driven anatomical elastic-energy systems. Elastic power amplification is an underappreciated component of silk’s function in webs and shows remarkable convergence to the fundamental mechanical advantages that led humans to engineer power-amplifying devices such as catapults and ballistae.
Hatchet ribozyme structure and implications for cleavage mechanism
Authors: Zheng Luqian , Falschlunger Christoph , Huang Kaiyi , Mairhofer Elisabeth , Yuan Shuguang , Wang Juncheng , Patel Dinshaw J. , Micura Ronald , Ren Aiming
Published: May 2019

Small self-cleaving ribozymes catalyze site-specific cleavage of their own phosphodiester backbone with implications for viral genome replication, pre-mRNA processing, and alternative splicing. We report on the 2.1-Å crystal structure of the hatchet ribozyme product, which adopts a compact pseudosymmetric dimeric scaffold, with each monomer stabilized by long-range interactions involving highly conserved nucleotides brought into close proximity of the scissile phosphate. Strikingly, the catalytic pocket contains a cavity capable of accommodating both the modeled scissile phosphate and its flanking 5′ nucleoside. The resulting modeled precatalytic conformation incorporates a splayed-apart alignment at the scissile phosphate, thereby providing structure-based insights into the in-line cleavage mechanism. We identify a guanine lining the catalytic pocket positioned to contribute to cleavage chemistry. The functional relevance of structure-based insights into hatchet ribozyme catalysis is strongly supported by cleavage assays monitoring the impact of selected nucleobase and atom-specific mutations on ribozyme activity.
Imaging-based pooled CRISPR screening reveals regulators of lncRNA localization
Authors: Wang Chong , Lu Tian , Emanuel George , Babcock Hazen P. , Zhuang Xiaowei
Published: May 2019

Significance

In this work, we developed an imaging-based pooled-library CRISPR screening approach that provides readouts of both phenotype and genotype of individual cells by high-resolution, high-content imaging. This approach promises to substantially expand the phenotype space accessible to pooled genetic screening by allowing the probing of complex cellular phenotypes, such as cell morphology and subcellular organization of different molecular species, as well as their dynamics. Applying this approach to screen for genetic factors involved in nuclear RNA localization, we identified both positive and negative regulators that control lncRNA localization to nuclear speckles.
GROWTH POLE RING protein forms a 200-nm-diameter ring structure essential for polar growth and rod shape in
Agrobacterium tumefaciens
Authors: Zupan J. R. , Grangeon R. , Robalino-Espinosa J. S. , Garnica N. , Zambryski P.
Published: May 2019

Significance

The extensively studied rod-shaped bacteria
Escherichia coli
,
Bacillus subtilis
, and
Caulobacter crescentus
grow by dispersed insertion of new cell wall material along the entire length of the cell. An alternative prokaryotic growth mode—polar growth—is used by some Actinomycetales and Proteobacteria. The latter phylum includes the family Rhizobiaceae, of which
Agrobacterium tumefaciens
is a prominent member. The factors responsible for polar growth are largely unknown. Here we describe GROWTH POLE RING (GPR) protein from
Agrobacterium
with a striking localization as a ring of six foci at the growth pole. GPR is potentially the polar growth organizer in
Agrobacterium
, as its absence leads to severe morphological defects, including loss of cylindrical cell shape, while its overproduction leads to ectopic growth poles.
Metameric
Authors: Tulkens Stéphan , Sandra Dominiek , Daelemans Walter
Published: May 2019

An oft-cited shortcoming of Interactive Activation as a
psychological model of word reading is that it lacks the ability to
simultaneously represent words of different lengths.

We present an implementation of the Interactive Activation
model, which we call Metameric, that can simulate words of different lengths,
and show that there is nothing inherent to Interactive Activation which prevents
it from simultaneously representing multiple word lengths. We provide an
in-depth analysis of which specific factors need to be present, and show that
the inclusion of three specific adjustments, all of which have been published in
various models before, lead to an Interactive Activation model which is fully
capable of representing words of different lengths. Finally, we show that our
implementation is fully capable of representing all words between 2 and 11
letters in length from the English Lexicon Project (31, 416 words) in a single
model. Our implementation is completely open source, heavily optimized, and
includes both command line and graphical user interfaces, but is also agnostic
to specific input data or problems. It can therefore be used to simulate a
myriad of other models, e.g., models of spoken word recognition. The
implementation can be accessed at www.github.com/clips/metameric.
Colophons and Marginal Notes of the Avestan Manuscripts of the Pouladi’s Collection in Yazd
Authors: Gholami Saloumeh , Pouladi Mehraban
Published: May 2019

About 150 years ago, after Avestan researchers such as Jackson, Browne, and Westergaard had unsuccessfully attempted to discover new manuscripts in Iran, it was assumed that there were few or no Avestan manuscripts remaining in Iran. However, recent research and fieldwork in Iran have resulted in important findings disproving this assumption. Since 2011, more than eighty-five Avestan manuscripts have been discovered in Iran. One of these important discoveries has been Pouladi’s Collection, which was found in February 2016 in a Zoroastrian house in the Priests’ Quarter (Mahalle-ye Dastūrān) in Yazd. This article deals with the secondary life of Avestan manuscripts of Pouladi’s Collection, focusing on colophons and marginal notes.

The article makes available a collection of Middle Persian and New Persian colophons and marginal notes, all which have been excerpted, transcribed, and translated for the first time from the Avestan manuscripts of Pouladi’s Collection, copied mostly in the seventeenth and eighteenth centuries. Based on different types of colophons, this contribution establishes a classification of colophons and marginal notes of this collection with regard to formal, contextual, and functional characteristics.
MetaQUBIC: a computational pipeline for gene-level functional profiling of metagenome and metatranscriptome
Authors: Ma Anjun , Sun Minxuan , McDermaid Adam , Liu Bingqiang , Ma Qin
Published: May 2019

Motivation

Metagenomic and metatranscriptomic analyses can provide an abundance of information related to microbial communities. However, straightforward analysis of this data does not provide optimal results, with a required integration of data types being needed to thoroughly investigate these microbiomes and their environmental interactions.

Results

Here, we present MetaQUBIC, an integrated biclustering-based computational pipeline for gene module detection that integrates both metagenomic and metatranscriptomic data. Additionally, we used this pipeline to investigate 735 paired DNA and RNA human gut microbiome samples, resulting in a comprehensive hybrid gene expression matrix of 2.3 million cross-species genes in the 735 human fecal samples and 155 functional enriched gene modules. We believe both the MetaQUBIC pipeline and the generated comprehensive human gut hybrid expression matrix will facilitate further investigations into multiple levels of microbiome studies.

Availability and implementation

The package is freely available at https://github.com/OSU-BMBL/metaqubic.

Supplementary information

Supplementary data are available at Bioinformatics online.
deepDR: a network-based deep learning approach toin silicodrug repositioning
Authors: Zeng Xiangxiang , Zhu Siyi , Liu Xiangrong , Zhou Yadi , Nussinov Ruth , Cheng Feixiong
Published: May 2019

Motivation

Traditional drug discovery and development are often time-consuming and high risk. Repurposing/repositioning of approved drugs offers a relatively low-cost and high-efficiency approach toward rapid development of efficacious treatments. The emergence of large-scale, heterogeneous biological networks has offered unprecedented opportunities for developing in silico drug repositioning approaches. However, capturing highly non-linear, heterogeneous network structures by most existing approaches for drug repositioning has been challenging.

Results

In this study, we developed a network-based deep-learning approach, termed deepDR, for in silico drug repurposing by integrating 10 networks: one drug–disease, one drug-side-effect, one drug–target and seven drug–drug networks. Specifically, deepDR learns high-level features of drugs from the heterogeneous networks by a multi-modal deep autoencoder. Then the learned low-dimensional representation of drugs together with clinically reported drug–disease pairs are encoded and decoded collectively via a variational autoencoder to infer candidates for approved drugs for which they were not originally approved. We found that deepDR revealed high performance [the area under receiver operating characteristic curve (AUROC) = 0.908], outperforming conventional network-based or machine learning-based approaches. Importantly, deepDR-predicted drug–disease associations were validated by the ClinicalTrials.gov database (AUROC = 0.826) and we showcased several novel deepDR-predicted approved drugs for Alzheimer’s disease (e.g. risperidone and aripiprazole) and Parkinson’s disease (e.g. methylphenidate and pergolide).

Availability and implementation

Source code and data can be downloaded from https://github.com/ChengF-Lab/deepDR

Supplementary information

Supplementary data are available online at Bioinformatics.
Behavioural avoidance of sperm ageing depends on genetic similarity of mates in a monogamous seabird
Authors: Pineaux Maxime , Blanchard Pierrick , Danchin Étienne , Hatch Scott A , Helfenstein Fabrice , Mulard Hervé , White Joël , Leclaire Sarah , Wagner Richard H
Published: May 2019

Inbreeding, i.e. the mating of genetically related individuals, can lead to reduced fitness and is considered to be a major selective force of mate choice. Although inbreeding avoidance has been found in numerous taxa, individuals may face constraints when pairing, leading to mating with suboptimal partners. In such circumstances, individuals that are able to avoid factors exacerbating detrimental effects of inbreeding should be favoured. Using the socially and genetically monogamous black-legged kittiwake (Rissa tridactyla), we explored whether the detrimental effects of inbreeding are exacerbated by sperm ageing (i.e. the post-meiotic senescence of sperm cells, mainly occurring within the female tracts after copulation), and whether they can be mitigated by behavioural tactics. First, by experimentally manipulating the age of the fertilizing sperm, we found that hatching failure due to sperm ageing increased with higher genetic similarity between mates. We then investigated whether more genetically similar pairs exhibited mating behaviours that prevent fertilization by old sperm. The more genetically similar mates were, the less likely they were to copulate early in the reproductive season and the more females performed post-copulatory sperm ejections. By flexibly adapting their behaviour in response to within-pair genetic similarity, kittiwakes may avoid exacerbation of inbreeding costs due to sperm ageing.
Follicle-stimulating hormone and luteinizing hormone increase Ca2+ in the granulosa cells of mouse ovarian follicles†
Authors: Egbert Jeremy R , Fahey Paul G , Reimer Jacob , Owen Corie M , Evsikov Alexei V , Nikolaev Viacheslav O , Griesbeck Oliver , Ray Russell S , Tolias Andreas S , Jaffe Laurinda A
Published: May 2019

In mammalian ovarian follicles, follicle stimulating hormone (FSH) and luteinizing hormone (LH) signal primarily through the G-protein Gs to elevate cAMP, but both of these hormones can also elevate Ca2+ under some conditions. Here, we investigate FSH- and LH-induced Ca2+ signaling in intact follicles of mice expressing genetically encoded Ca2+ sensors, Twitch-2B and GCaMP6s. At a physiological concentration (1 nM), FSH elevates Ca2+ within the granulosa cells of preantral and antral follicles. The Ca2+ rise begins several minutes after FSH application, peaks at ∼10 min, remains above baseline for another ∼10 min, and depends on extracellular Ca2+. However, suppression of the FSH-induced Ca2+ increase by reducing extracellular Ca2+ does not inhibit FSH-induced phosphorylation of MAP kinase, estradiol production, or the acquisition of LH responsiveness. Like FSH, LH also increases Ca2+, when applied to preovulatory follicles. At a physiological concentration (10 nM), LH elicits Ca2+ oscillations in a subset of cells in the outer mural granulosa layer. These oscillations continue for at least 6 h and depend on the activity of Gq family G-proteins. Suppression of the oscillations by Gq inhibition does not inhibit meiotic resumption, but does delay the time to 50% ovulation by about 3 h. In summary, both FSH and LH increase Ca2+ in the granulosa cells of intact follicles, but the functions of these Ca2+ rises are only starting to be identified.
Core–periphery segregation in evolving prisoner’s dilemma networks
Authors: Sohn Yunkyu , Choi Jung-Kyoo , Ahn T K
Published: May 2019

Dense cooperative networks are an essential element of social capital for prosperous societies. These networks enable individuals to overcome collective action dilemmas by enhancing trust. In many biological and social settings, network structures evolve endogenously as agents exit relationships and build new ones. However, the interplay between game strategy and interaction structure by which evolutionary dynamics leads to self-organization of dense cooperative networks has not been understood. Our prisoner’s dilemma experiments with exit and partner choice options show that core–periphery segregation of cooperators and defectors drives the emergence of cooperation. Cooperators’ Quit-for-Tat and defectors’ Roving strategy lead to a highly asymmetric core and periphery structure. Densely connected to each other at the core, cooperators successfully isolate defectors at the periphery and earn larger payoffs.
Transcriptional dynamics of pluripotent stem cell-derived endothelial cell differentiation revealed by single-cell RNA sequencing
Authors: McCracken Ian R , Taylor Richard S , Kok Fatma O , de la Cuesta Fernando , Dobie Ross , Henderson Beth E P , Mountford Joanne C , Caudrillier Axelle , Henderson Neil C , Ponting Chris P , Baker Andrew H
Published: May 2019

Aims

Pluripotent stem cell-derived endothelial cell products possess therapeutic potential in ischaemic vascular disease. However, the factors that drive endothelial differentiation from pluripotency and cellular specification are largely unknown. The aims of this study were to use single-cell RNA sequencing (scRNA-seq) to map the transcriptional landscape and cellular dynamics of directed differentiation of human embryonic stem cell-derived endothelial cells (hESC-EC) and to compare these cells to mature endothelial cells from diverse vascular beds.

Methods and results

A highly efficient directed 8-day differentiation protocol was used to generate a hESC-derived endothelial cell product (hESC-ECP), in which 66% of cells co-expressed CD31 and CD144. We observed largely homogeneous hESC and mesodermal populations at Days 0 and 4, respectively, followed by a rapid emergence of distinct endothelial and mesenchymal populations. Pseudotime trajectory identified transcriptional signatures of endothelial commitment and maturation during the differentiation process. Concordance in transcriptional signatures was verified by scRNA-seq analysis using both a second hESC line RC11, and an alternative hESC-EC differentiation protocol. In total, 105 727 cells were subjected to scRNA-seq analysis. Global transcriptional comparison revealed a transcriptional architecture of hESC-EC that differs from freshly isolated and cultured human endothelial cells and from organ-specific endothelial cells.

Conclusion

A transcriptional bifurcation into endothelial and mesenchymal lineages was identified, as well as novel transcriptional signatures underpinning commitment and maturation. The transcriptional architecture of hESC-ECP was distinct from mature and foetal human EC.
Micra pacemaker implant after cardiac implantable electronic device extraction: feasibility and long-term outcomes
Authors: Zucchelli Giulio , Barletta Valentina , Della Tommasina Veronica , Viani Stefano , Parollo Matteo , Mazzocchetti Lorenzo , Cellamaro Tea , Paperini Luca , Di Cori Andrea , De Lucia Raffaele , Segreti Luca , Soldati Ezio , Bongiorni Maria Grazia
Published: May 2019

Aims

We aimed at investigating the feasibility and outcome of Micra implant in patients who have previously undergone transvenous lead extraction (TLE), in comparison to naïve patients implanted with the same device.

Methods and results

Eighty-three patients (65 males, 78.31%; 77.27 ± 9.96 years) underwent Micra implant at our centre. The entire cohort was divided between ‘post-extraction’ (Group 1) and naïve patients (Group 2). In 23 of 83 patients (20 males, 86.96%; 73.83 ± 10.29 years), Micra was implanted after TLE. Indication to TLE was an infection in 15 patients (65.21%), leads malfunction in four (17.39%), superior vena cava syndrome in three (13.05%), and severe tricuspid regurgitation in one case (4.35%). The implant procedure was successful in all patients and no device-related events occurred at follow-up (median: 18 months; interquartile range: 1–24). No differences were observed between groups in fluoroscopy time (13.88 ± 10.98 min vs. 13.15 ± 6.64 min, P = 0.45), single device delivery (Group 1 vs. Group 2: 69.56% vs. 55%, P = 0.22), electrical performance at implant and at 12-month follow-up (Group 1 vs. Group 2: pacing threshold 0.48 ± 0.05 V/0.24 ms vs. 0.56 ± 0.25 V/0.24 ms, P = 0.70; impedance 640 ± 148.83 Ohm vs. 583.43 ± 99.7 Ohm, P = 0.27; and R wave amplitude 10.33 ± 2.88 mV vs. 12.62 ± 5.31 mV, P = 0.40). A non-apical site of implant was achievable in the majority of cases (72.3%) without differences among groups (78.26% vs. 70%; P = 0.42).

Conclusion

Micra implant is an effective and safe procedure in patients still requiring a ventricular pacing after TLE, with similar electrical performance and outcome compared with naïve patients at long-term follow-up.
Multidecadal dynamics of the Arctic copepod Limnocalanus macrurus in relation to environmental variability in the Baltic Sea
Authors: Einberg Heli , Klais Riina , Rubene Gunta , Kornilovs Georgs , Putnis Ivars , Ojaveer Henn
Published: May 2019

The Arctic Limnocalanus macrurus is a prominent representative of large copepods which performs several essential functions in freshwater and marine ecosystems. Being a cold stenotherm species, its distribution is primarily confined to deeper water layers. Based on the long-term observations from one of the largest spatially confined natural populations of this species in the Baltic Sea, we detected profound long-term variability of L. macrurus during 1958–2016: high abundances before the 1980s, then nearly disappearance in the 1990s and recovery in the 2000s. The main environmental parameters explaining the interannual variability of L. macrurus in spring were herring spawning stock biomass in preceding year, winter severity, and bottom water temperature in preceding summer. The effect of winter severity and water temperature was also non-linear. The sliding window correlation analysis pointed to a non-stationary relationship between the abundance of L. macrurus and the key variables. Given the observed pronounced seasonality in the population structure of L. macrurus (young stages dominated in the beginning of the year and only adults were left in the population in summer and autumn) we identified the dynamics of key environmental variables to understand this species under different ecosystem configurations and different combinations of drivers of change.
The accelerating rotation of the magnetic He-weak star HD 142990
Authors: Shultz M , Rivinius Th , Das B , Wade G A , Chandra P
Published: May 2019

HD 142990 (V 913 Sco; B5 V) is a He-weak star with a strong surface magnetic field and a short rotation period (Prot ∼ 1 d). Whilst it is clearly a rapid rotator, recent determinations of Prot are in formal disagreement. In this paper, we collect magnetic and photometric data with a combined 40-yr baseline in order to re-evaluate Prot and examine its stability. Both period analysis of individual data sets and O − C analysis of the photometric data demonstrate that Prot has decreased over the past 30 yr, violating expectations from magnetospheric braking models, but consistent with behaviour reported for 2 other hot, rapidly rotating magnetic stars, CU Vir and HD 37776. The available magnetic and photometric time series for HD 142990 can be coherently phased assuming a spin-up rate $\dot{P}$ of approximately −0.6 s yr−1, although there is some indication that $\dot{P}$ may have slowed in recent years, possibly indicating an irregular or cyclic rotational evolution.
The Local Group on FIRE: dwarf galaxy populations across a suite of hydrodynamic simulations
Authors: Garrison-Kimmel Shea , Hopkins Philip F , Wetzel Andrew , Bullock James S , Boylan-Kolchin Michael , Kereš Dušan , Faucher-Giguère Claude-André , El-Badry Kareem , Lamberts Astrid , Quataert Eliot , Sanderson Robyn
Published: May 2019

We present a new set of high-resolution hydrodynamic cosmological zoom-in simulations that apply the Feedback In Realistic Environments physics to both Local Group (LG)-like and isolated Milky Way (MW)-like volumes (10 host systems in total with a baryonic particle mass ${\simeq } 3500\!-\!7000\,{\rm M}_\odot$). We study the stellar mass functions, circular velocity or mass profiles, and velocity dispersions of the dwarf galaxy populations. The simulations reproduce the stellar mass function and central densities of MW satellite dwarfs for $M_\ast \ge 10^{5.5}\,{\rm M}_\odot$ and predict the existence of ∼3 unidentified galaxies with $M_\ast \sim 10^5\,{\rm M}_\odot$ within 300 kpc of the MW. Overall, we find no evidence for the classical missing satellites or too-big-to-fail (TBTF) problems for satellite galaxies in our sample. Among the satellites, TBTF is resolved primarily by subhalo disruption and overall mass-loss; central density profiles of subhaloes are of secondary importance. For non-satellite galaxies, our LG-like simulations predict as many as ∼10 as-of-yet unseen galaxies at distances $0.3\!-\!1\, \mathrm{Mpc}$ from both hosts, with $M_\ast \simeq 10^{5-6}\,{\rm M}_\odot$ (in haloes with Vmax ∼ 20 km s−1), albeit with large halo-to-halo variance. None of our simulations produces a compact, baryon-dominated, high-density dwarf elliptical-type galaxy (with Vcirc ≳ 35 km s−1 at $r\lt 1\,$ kpc), of which six may appear in the LG (but none in the MW). It may therefore remain a challenge to reproduce the full diversity of the dwarf population, including both the highest and lowest density systems.
Top Questions in the Diagnosis and Treatment of Pulmonary M. abscessus Disease
Authors: Nathavitharana Ruvandhi R , Strnad Luke , Lederer Philip A , Shah Maunank , Hurtado Rocio M
Published: May 2019

Mycobacterium abscessus disease is particularly challenging to treat, given the intrinsic drug resistance of this species and the limited data on which recommendations are based, resulting in a greater reliance on expert opinion. We address several commonly encountered questions and management considerations regarding pulmonary Mycobacterium abscessus disease, including the role of subspecies identification, diagnostic criteria for determining disease, interpretation of drug susceptibility test results, approach to therapy including the need for parenteral antibiotics and the role for new and repurposed drugs, and the use of adjunctive strategies such as airway clearance and surgical resection.
Vintage-Specific Driving Restrictions
Authors: Barahona Nano , Gallego Francisco A , Montero Juan-Pablo
Published: May 2019

Local air pollution has led authorities in many cities around the world to impose limits on car use by means of driving restrictions or license-plate bans. By placing uniform restrictions on all cars, many of these programs have created incentives for drivers to buy additional, more polluting cars. We study vintage-specific restrictions, which place heavy limits on older, polluting vehicles and no limits on newer, cleaner ones. We use a novel model of the car market and results from Santiago’s 1992 program, the earliest program to use vintage-specific restrictions, to show that such restrictions should be designed to work exclusively through the extensive margin (type of car driven), never through the intensive margin (number of miles driven). If so, vintage restrictions can yield important welfare gains by moving the fleet composition toward cleaner cars, comparing well to alternative instruments such as scrappage subsidies and pollution-based registration fees.
RAPID MACULAR CAPILLARY LOSS IN PATIENTS WITH UNCONTROLLED TYPE 1 DIABETES
Authors: Lavia Carlo , Feldman-Billard Sylvie , Erginay Ali , Guérin Olivia , Virgili Gianni , Gaudric Alain , Tadayoni Ramin , Dupas Bénédicte
Published: May 2019

Purpose:

To analyze the evolution of macular vessel density (VD) over 1 year, during early worsening of diabetic retinopathy, in patients with uncontrolled Type 1 diabetes (T1D).

Methods:

Retrospective study of 12 eyes of 9 patients with T1D with early worsening of diabetic retinopathy imaged with optical coherence tomography angiography. The following data were collected at the time of pan retinal photocoagulation initiation and after 6 and 12 months: vessel density within three retinal plexuses—superficial vascular plexus, intermediate capillary plexus, and deep capillary plexus; foveal avascular zone area, acircularity index, and flow density (FD)-300; central macular thickness; and HbA1c levels.

Results:

A history of rapid reduction in blood glucose was found in seven of nine cases. Vessel density was significantly decreased at 12 months in all plexuses: from 44.68 ± 4.75 to 40.23 ± 7.13 in the superficial vascular plexus (P = 0.008), from 42.72 ± 4.86 to 37.12 ± 8.64 in the intermediate capillary plexus (P = 0.03), and from 22.68 ± 3.93 to 19.66 ± 4.92 in the deep capillary plexus (P = 0.004). Intermediate capillary plexus and deep capillary plexus changes were strongly correlated (r = 0.86, P < 0.001) and were significant as early as 6 months. The mean foveal avascular zone area increased (P = 0.05) and the FD-300 decreased (P = 0.03). No significant change in acircularity index, central macular thickness, and visual acuity were observed over time.

Conclusion:

Early worsening of diabetic retinopathy induces a rapid macular capillary dropout mainly affecting the intermediate capillary plexus and deep capillary plexus.
Pediatric disaster preparedness: identifying challenges and opportunities for emergency department planning
Authors: Gilchrist Nancy , Simpson Joelle N.
Published: May 2019

Purpose of review

To review the current literature on best practices for pediatric disaster preparedness in an emergency department (ED).

Recent findings

Children have unique anatomical, physiologic, immunologic, and psychosocial needs that impact their vulnerability to and resilience in a disaster, yet they have been historically underrepresented in disaster planning at local and national levels. Lessons learned from recent disaster events, disaster research, and disaster experts provide guidance on pediatric disaster preparedness for ED.

All EDs should include children in their disaster plans and exercises. ED staff should be knowledgeable about their role in institutional disaster operations and familiar with standard disaster management principles.
Risk Factors of Multidrug Resistant Pathogens Induced Infection in Severe Acute Pancreatitis
Authors: Li Xina , Li Le , Liu Lu , Hu Yingying , Zhao Shuang , Sun Jialiang , Wang Gang , Hai Xin
Published: May 2019

Purpose:

A retrospective study was first performed to assess the multidrug resistant (MDR) pathogen in severe acute pancreatitis (SAP) patients who were treated using the step-up approach. We aim to assess the risk factors between MDR pathogen and potential covariates in SAP patients.

Methods:

The clinical data of 51 SAP patients who were treated from June, 2013 to December, 2016 were retrospectively collected. A total of 23 patients in the MDR group and 28 patients in the non-MDR group were reviewed. The risk factors for MDR pathogen-induced infections in SAP patients were analyzed.

Results:

Hyperlipidemia was the leading cause of SAP in our study. The mean duration of hospital stay was significantly longer in the patients with MDR pathogen infections (P=0.0135). The hospitalization expenses of MDR group were much higher than those in non-MDR group. The mortality of MDR group (56.5%) was higher than that in non-MDR group (28.6%) (P=0.0436). Gram-negative isolates (63.8%) were commonly detected in SAP patients. Acinetobacter baumannii was the most common MDR pathogens. Systemic disease (P 
= 0.0136), initial use of carbapenem (P 
= 0.0438), and open necrosectomy (P 
= 0.0002) were the potential risk factors for MDR pathogen-induced infections in SAP. Furthermore, the logistic regression analysis revealed that open necrosectomy was the independent variable for MDR infections (OR: 15.6, 95% CI: 2.951–82.469, P 
= 0.0012).

Conclusions:

MDR pathogen-induced infections were common in SAP patients and Acinetobacter baumannii was the main pathogen. Meanwhile, open necrosectomy was the independent risk factor for the infection of MDR pathogen.
Direct Oral Feeding Following Minimally Invasive Esophagectomy (NUTRIENT II trial)
Authors: Berkelmans Gijs H. K. , Fransen Laura F. C. , Dolmans-Zwartjes Annemarie C. P. , Kouwenhoven Ewout A. , van Det Marc J. , Nilsson Magnus , Nieuwenhuijzen Grard A. P. , Luyer Misha D. P.
Published: May 2019

Objective:

Patients undergoing an esophagectomy are often kept nil-by-mouth postoperatively out of fear for increasing anastomotic leakage and pulmonary complications. This study investigates the effect of direct start of oral feeding following minimally invasive esophagectomy (MIE) compared with standard of care.

Background:

Elements of enhanced recovery after surgery (ERAS) protocols have been successfully introduced in patients undergoing an esophagectomy. However, start of oral intake, which is an essential part of the ERAS protocols, remains a matter of debate.

Methods:

Patients in this multicenter, international randomized controlled trial were randomized to directly start oral feeding (intervention) after a MIE with intrathoracic anastomosis or to receive nil-by-mouth and tube feeding for 5 days postoperative (control group). Primary outcome was time to functional recovery. Secondary outcome parameters included anastomotic leakage, pneumonia rate, and other surgical complications scored by predefined definitions.

Results:

Baseline characteristics were similar in the intervention (n = 65) and control (n = 67) group. Functional recovery was 7 days for patients receiving direct oral feeding compared with 8 days in the control group (P = 0.436). Anastomotic leakage rate did not differ in the intervention (18.5%) and control group (16.4%, P = 0.757). Pneumonia rates were comparable between the intervention (24.6%) and control group (34.3%, P = 0.221). Other morbidity rates were similar, except for chyle leakage, which was more prevalent in the standard of care group (P = 0.032).

Conclusion:

Direct oral feeding after an esophagectomy does not affect functional recovery and did not increase incidence or severity of postoperative complications.
Presynaptic GABAergic receptors modulate inhibitory synaptic feedback in the avian cochlear nucleus angularis
Authors: Eisenbach Stefanie L. , Soueidan Sara E. , MacLeod Katrina M.
Published: May 2019

Inhibition plays multiple critical roles in the neural processing of sound. In the avian auditory brain stem, the cochlear nuclei receive their principal inhibitory feedback from the superior olivary nucleus (SON) in lieu of local inhibitory circuitry. In the timing pathway, GABAergic inhibitory feedback underlies gain control to enhance sound localization. In the cochlear nucleus angularis (NA), which processes intensity information, how the inhibitory feedback is integrated is not well understood. Using whole cell patch-clamp recordings in chick brain stem slices, we investigated the effects of GABA release on the inhibitory (presumed SON) and excitatory (8th nerve) synaptic inputs onto NA neurons. Pharmacological activation of the metabotropic GABAB receptors with baclofen profoundly suppressed both evoked excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs). Baclofen similarly reduced the frequency of spontaneous IPSCs and EPSCs, but had no significant effect on the current kinetics or amplitudes, indicating a presynaptic locus of modulation. Trains of IPSCs showed substantial transient and sustained short-term synaptic facilitation. Baclofen application reduced the initial IPSC amplitude, but enhanced the relative facilitation over the train via changes in release probability. Comparable levels of GABAB receptor mediated blockade also shifted short-term synaptic plasticity of EPSCs toward less depression. Evoked (but not spontaneous) release of GABA was sufficient to suppress basal release at inhibitory synapses in slices. Overall, the modulation of excitatory and inhibitory inputs of NA neurons via GABAB receptor activation appears to parallel that in the timing pathway.

New and Noteworthy

Avian cochlear nucleus angularis (NA) neurons are responsible for encoding sound intensity and provide level information for gain control feedback via the superior olivary nucleus. This GABAergic inhibitory feedback was itself modulated in NA via presynaptic, metabotropic GABAB receptor mediated suppression. Excitatory transmission was modulated by the same receptors, suggesting parallel homosynaptic and heterosynaptic mechanisms in both cochlear nuclei.
Efficient pan-cancer whole-slide image classification and outlier detection using convolutional neural networks
Authors: Bilaloglu Seda , Wu Joyce , Fierro Eduardo , Sanchez Raul Delgado , Ocampo Paolo Santiago , Razavian Narges , Coudray Nicolas , Tsirigos Aristotelis
Published: May 2019

Visual analysis of solid tissue mounted on glass slides is currently the primary method used by pathologists for determining the stage, type and subtypes of cancer. Although whole slide images are usually large (10s to 100s thousands pixels wide), an exhaustive though time-consuming assessment is necessary to reduce the risk of misdiagnosis. In an effort to address the many diagnostic challenges faced by trained experts, recent research has been focused on developing automatic prediction systems for this multi-class classification problem. Typically, complex convolutional neural network (CNN) architectures, such as Google’s Inception, are used to tackle this problem. Here, we introduce a greatly simplified CNN architecture, PathCNN, which allows for more efficient use of computational resources and better classification performance. Using this improved architecture, we trained simultaneously on whole-slide images from multiple tumor sites and corresponding non-neoplastic tissue. Dimensionality reduction analysis of the weights of the last layer of the network capture groups of images that faithfully represent the different types of cancer, highlighting at the same time differences in staining and capturing outliers, artifacts and misclassification errors. Our code is available online at:https://github.com/sedab/PathCNN.
Metabolic Architecture of the Deep Ocean Microbiome
Authors: Acinas Silvia G. , Sánchez Pablo , Salazar Guillem , Cornejo-Castillo Francisco M. , Sebastián Marta , Logares Ramiro , Sunagawa Shinichi , Hingamp Pascal , Ogata Hiroyuki , Lima-Mendez Gipsi , Roux Simon , González José M. , Arrieta Jesús M. , Alam Intikhab S. , Kamau Allan , Bowler Chris , Raes Jeroen , Pesant Stéphane , Bork Peer , Agustí Susana , Gojobori Takashi , Bajic Vladimir , Vaqué Dolors , Sullivan Matthew B. , Pedrós-Alió Carlos , Massana Ramon , Duarte Carlos M. , Gasol Josep M.
Published: May 2019

The deep sea, the largest compartment of the ocean, is an essential component of the Earth system, but the functional exploration of its microbial communities lags far behind that of other marine realms. Here we analyze 58 bathypelagic microbial metagenomes from the Atlantic, Indian, and Pacific Oceans in an unprecedented sampling effort from the Malaspina Global Expedition, to resolve the metabolic architecture of the deep ocean microbiome. The Malaspina Deep-Sea Gene Collection, 71% of which consists of novel genes, reveals a strong dichotomy between the functional traits of free-living and particle-attached microorganisms, and shows relatively patchy composition challenging the paradigm of a uniform dark ocean ecosystem. Metagenome Assembled Genomes uncovered 11 potential new phyla, establishing references for deep ocean microbial taxa, and revealed mixotrophy to be a widespread trophic strategy in the deep ocean. These results expand our understanding of the functional diversity, metabolic versatility, and carbon cycling in the largest ecosystem on Earth.

One Sentence Summary

A whole community genomic survey of the deep microbiome sheds light on the microbial and functional diversity of the dark ocean.
Background free tracking of single RNA in living cells using catalytically inactive CasE
Authors: Gao Feng , Sun Yue , Jiang Feng , Bai Xiaoyue , Han Chunyu
Published: May 2019

RNAs have important and diverse functions. Visualizing an isolated RNA in living cells provide us essential information of its roles. By now, there are two kinds of live RNA imaging systems invented, one is the MS2 system and the other is the Cas13a system. In this study, we show that when fused with split-Fp, CasE can be engineered into a live RNA tracking tool.
Enhanced and Unified Anatomical Labeling for a Common Mouse Brain Atlas
Authors: Chon Uree , Vanselow Daniel J. , Cheng Keith C. , Kim Yongsoo
Published: May 2019

Anatomical atlases in standard coordinates are necessary for the interpretation and integration of research findings in a common spatial context. However, the two most-used mouse brain atlases, the Franklin and Paxinos (FP) and the common coordinate framework (CCF) from the Allen Institute for Brain Science, have accumulated inconsistencies in anatomical delineations and nomenclature, creating confusion among neuroscientists. To overcome these issues, we adopted the FP labels into the CCF to merge two labels in the single atlas framework. We used cell type specific transgenic mice and an MRI atlas to adjust and further segment our labels. Moreover, new segmentations were added to the dorsal striatum using cortico-striatal connectivity data. Lastly, we have digitized our anatomical labels based on the Allen ontology, created a web-interface for visualization, and provided tools for comprehensive comparisons between the Allen and FP labels. Our open-source labels signify a key step towards a unified mouse brain atlas.
Quantifying Three-dimensional Chromatin Organization Utilizing Scanning Transmission Electron Microscopy: ChromSTEM
Authors: Li Yue , Roth Eric , Agrawal Vasundhara , Eshein Adam , Fredrick Jane , Almassalha Luay , Shim Anne , Bleher Reiner , Dravid Vinayak P. , Backman Vadim
Published: May 2019

Chromatin organization over a wide range of length scales plays a critical role in the regulation of gene expression and deciphering these processes requires high-resolution, three-dimensional, quantitative imaging of chromatin structure in vitro. Herein we introduce ChromSTEM, a method which utilizes high angle annular dark field imaging and tomography in scanning transmission electron microscopy in combination with DNA-specific staining for electron microscopy. We utilized ChromSTEM to quantify chromatin structure in cultured cells and tissue biopsies through local DNA distribution and the scaling behavior of chromatin polymer. We observed that chromatin is densely packed with an average volume concentration of over 30% with heterochromatin having a two-fold higher density compared to euchromatin. Chromatin was arranged into spatially well-defined nanoscale packing domains with fractal internal structure and genomic size between 100 and 400 kb, comparable to that of topologically associated domains. The packing domains varied in DNA concentration and fractal dimension and had one of the distinct states of chromatin packing with differential ratio of DNA content to the chromatin volume concentration. Finally, we observed a significant intercellular heterogeneity of chromatin organization even within a genetically uniform cell population, which demonstrates the imperative for high-throughput characterization of chromatin structure at the single cell level.
Dynamics of the Cortico-Cerebellar Loop Fine-Tune Dexterous Movement
Authors: Guo Jian-Zhong , Sauerbrei Britton , Cohen Jeremy D. , Mischiati Matteo , Graves Austin , Pisanello Ferruccio , Branson Kristin , Hantman Adam W.
Published: May 2019

Skillful control of movement requires coordination between brain areas that are reciprocally connected through polysynaptic pathways, forming closed loops. A prominent loop in mammals runs between cerebral cortex and cerebellum, which individually contribute to skilled arm control. But how and why do these regions interact? Here, we studied the mouse cortico-cerebellar loop by optogenetically perturbing the pontine nuclei (PN), which receive direct cortical inputs and project only to cerebellum. PN stimulation during rest propagated into cerebellar cortex, but the effect of stimulation was transformed downstream into a wide range of patterns in the deep cerebellar nuclei (DCN) and reduced to transient excitation in motor cortex. PN stimulation in a cued reaching task altered arm kinematics and impaired performance. Cerebellar and cortical dynamics during movement were not dominated by PN stimulation, but altered in line with behavioral changes. These results suggest that the cortico-cerebellar loop fine-tunes motor commands during skilled reaching.
Multimodal X-ray imaging of grain-level properties and performance in a polycrystalline solar cell
Authors: Ulvestad A. , Hruszkewycz S. O. , Holt M. V. , Hill M. O. , Calvo-Almazán I. , Maddali S. , Huang X. , Yan H. , Nazaretski E. , Chu Y. S. , Lauhon L. J. , Rodkey N. , Bertoni M. I. , Stuckelberger M. E.
Published: May 2019

The factors limiting the performance of alternative polycrystalline solar cells as compared with their single-crystal counterparts are not fully understood, but are thought to originate from structural and chemical heterogeneities at various length scales. Here, it is demonstrated that multimodal focused nanobeam X-ray microscopy can be used to reveal multiple aspects of the problem in a single measurement by mapping chemical makeup, lattice structure and charge collection efficiency simultaneously in a working solar cell. This approach was applied to micrometre-sized individual grains in a Cu(In,Ga)Se2 polycrystalline film packaged in a working device. It was found that, near grain boundaries, collection efficiency is increased, and that in these regions the lattice parameter of the material is expanded. These observations are discussed in terms of possible physical models and future experiments.
Hemisynthesis, crystal structure and inhibitory effect of sesquiterpenic thiosemicarbazones and thiazolidin-4-ones on the corrosion behaviour of stainless steel in 1 M H2SO4 solution
Authors: Bimoussa Abdoullah , Koumya Yassine , Abouelfida Abdesselam , Ait Itto Moulay Youssef , Benyaich Abdelaziz , Mentre Olivier , Ketatni El Mostafa , Auhmani Aziz , Auhmani Abdelwahed
Published: May 2019

Treatment of thiosemicarbazones prepared from sesquiterpenes with ethyl 2-bromoacetate in the presence of sodium acetate afforded the corresponding thiazolidin-4-ones. The structures of all the newly synthesized compounds were established by considering spectral and single-crystal X-ray diffraction data. The title compound, ethyl 2-((Z)-2-{(Z)-[(1aR,5aR,9aS)-1,1-dichloro-1a,5,5,7-tetramethyl-1a,2,3,4,5,5a,8,9-octahydro-1H-benzo[a]cyclopropa[b][7]annulen-8-ylidene]hydrazono}-4-oxothiazolidin-3-yl)acetate, C23H31Cl2N3O3S, 5, crystallizes in the orthorhombic noncentrosymmetric space group P212121 with Z = 4. Within the molecule in the crystal structure, the cyclohexene ring has an envelope conformation and the cycloheptane ring, to which it is fused, has a boat conformation. In the crystal, molecules are linked by C—H...Cl hydrogen bonds forming chains propagating along the b-axis direction. The absolute configuration of the molecule in the crystal could be fully confirmed from anomalous dispersion effects [Flack parameter = −0.04 (2)]. Thiosemicarbazones 1 and 2 are efficient inhibitors for steel corrosion in 1 M H2SO4 solution, with a maximum efficiency of 92.28% at 10−3 M. Furthermore, thiosemicarbazone compounds were found to be more efficient than thiazolidin-4-one derivatives. In addition, cyclic voltammetry was used to characterize the tested molecules, as well to estimate the experimental value of the energy band gap.
Ethylammonium hydrogen oxalate–oxalic acid (2/1)
Authors: Toure Assane , Diop Cheikh Abdoul Khadir , Diop Libasse , Plasseraud Laurent , Cattey Hélène
Published: May 2019

The reaction between ethylamine and oxalic acid in water in a 1:1 molar ratio afforded the title salt, C2H8N+·C2HO4
−·0.5C2H2O4. The hydrogen oxalate anions interact through hydrogen bonding and are organized into a chains propagating along the c-axis direction. The chains are connected to the neighbouring cations and oxalic acid molecules by N—H...O and O—H...O hydrogen bonds and N...O dipole–dipole contacts, leading to a supramolecular three-dimensional network.
2,3-Dichloro-3′,4′-dihydroxybiphenyl
Authors: Dhakal Ram , Parkin Sean , Lehmler Hans-Joachim
Published: May 2019

The title compound [systematic name: 4-(2,3-Dichlorophenyl)benzene-1,2-diol], C12H8Cl2O2, is a putative dihydroxylated metabolite of 2,3-dichlorobiphenyl (PCB 5). The title structure displays intramolecular O—H...O hydrogen bonding, and the π–π stacking distance between inversion-related chlorinated benzene rings of the title compound is 3.371 (3) Å. The dihedral angle between two benzene rings is 59.39 (8)°.