bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of Gonioscopy-assisted Transluminal Trabeculotomy in Vitrectomized Patients With Secondary Glaucoma After Silicone Oil Removal
Authors: Aktas Zeynep , Ucgul Ahmet Y. , Ozdek Sengul , Boluk Ceyda E.
Published: November 2020

Précis:

The present study demonstrates that surgical success rates of gonioscopy-assisted transluminal trabeculotomy (GATT) with a target intraocular pressure (IOP)≤21 mm Hg are 93.3% (for qualified success) and 26.7% (for complete success) in vitrectomized patients exhibiting secondary open-angle glaucoma (SOAG) after silicone oil (SO) removal, for an average follow-up of 37.5 months.

Purpose:

To report the long-term outcomes of GATT in vitrectomized patients exhibiting SOAG after SO removal.

Setting:

Retrospective case-series study.

Patient Population:

This retrospective case-series study enrolled vitrectomized patients who underwent uneventful GATT surgery between May 2014 and May 2019 at Gazi University Hospital for the treatment of medically uncontrolled SOAG after SO removal.

Main Outcome Measures:

At baseline and at each postoperative visit, a detailed ophthalmic examination consisting of slit-lamp biomicroscopy, indirect ophthalmoscopy, macular optical coherence tomography, and Goldmann applanation tonometry was performed in all patients. Baseline demographic and clinical characteristics, duration between pars plana vitrectomy and SO removal, duration between SO removal and onset of SOAG, follow-up time, need for antiglaucoma medication, visual acuity, and IOP measurements were noted. Surgical success was defined as an IOP≤21 and ≥6 mm Hg with (qualified success) and without (complete success) IOP-lowering medication.

Results:

A total of 15 patients had a history of pars plana vitrectomy with 1000 centistoke SO tamponade before the GATT surgery. GATT was performed in all patients with SOAG after SO removal. The mean age and follow-up of the patients were 53.6±11.8 years (range, 34 to 72 y) and 37.5±15.1 months (range, 12 to 61 mo), respectively. The average duration of SO tamponade in the vitreous cavity was 7.5±1.6 months (range, 5 to 10 mo). The average duration between the SO removal and the development of SOAG was 14.1±13.2 months (range, 2 to 46 mo). The mean IOP decreased from 31.0±4.1 mm Hg at baseline to 15.6±4.6 mm Hg at final visit. The mean final logMAR BCVA was 0.92±0.58 (range, 2 to 0.045). Qualified surgical success was achieved in 14 (93.3%) patients, whereas complete success was achieved in only 4 (26.7%) patients (P<0.001).

Conclusions:

GATT seems to be safe and successful procedure for controlling IOP in patients exhibiting SOAG after SO removal. However, most patients may require antiglaucoma medication during the follow-up, particularly within the first 2 postoperative years.
Creating an Environment to Support Transitioning New APRNs into Practice
Authors: DeGarmo Sean
Published: November 2020

Registered nurses (RNs) are leaving the bedside to become advanced practice registered nurses (APRNs). Failure to successfully transition APRNs into clinical practice represents a substantial financial burden to healthcare organizations. Organizations can use the standards of the Magnet Recognition Program® to help support, develop, and transition APRNs into their advanced practice role.
Comparing an All-RN Unit to a Mixed-Skill Unit at a Hospital
Authors: Dzikowicz Dillon J. , Schmitt Linda A. , Gastle Karen , Skermont Amanda , Carey Mary G.
Published: November 2020

OBJECTIVE

The aim of this study was to assess the differences in patient complications as well as patient and staff satisfaction between a mixed-skill unit and an all–registered nurse (RN) unit.

BACKGROUND

It is recognized that nursing care delivered by RNs results in better outcomes; however, more evidence is needed to support a change to an all-RN unit.

METHODS

A mixed unit with RNs and unlicensed assistive personnel was compared with an all-RN unit. Each unit had similar resources. Patient complications and patient and staff satisfaction were measured. Patient complications were reported in terms of 1,000 patient days over the study period to minimize noise fluctuations; t test and χ
2 compared means and frequencies, respectively.

RESULTS

The all-RN unit had a lower prevalence of patient complications. Patients reported better pain management, and nurse explanation, and reported higher satisfaction on the all-RN unit.

CONCLUSIONS

An all-RN unit provided superior outcomes compared with a mixed-skill unit without additional costs.
Application of Transcranial Color-coded Duplex Sonography in the Diagnosis and Management of Straight Sinus Thrombosis With Dural Arteriovenous Fistulae
Authors: Zhu Xueli , Gong Xiping , Zhang Bin , Zhou Shengjun , Wang Fumin , He Wen
Published: November 2020

Introduction:

Transcranial color-coded duplex sonography (TCCS) with and without ultrasound contrast agent has been used to diagnose cerebral venous thrombosis, however, no experience in the diagnosis of patients with cerebral venous thrombosis and with dural arteriovenous fistula (dAVF) by contrast-enhanced TCCS has been reported yet.

Case Report:

The authors reported a 49-year-old male patient with straight sinus (StS) thrombosis and dAVF. Plain TCCS and contrast-enhanced TCCS demonstrated the direct presentation of the selected feeder and drainage veins of the dAVFs, arterialized venous flow waveform, and an enlarged optic nerve sheath diameter, indicating an increased intracranial pressure, and a filling defect in the StS even after administration of an ultrasound contrast agent. After intravascular thrombolysis and blockage of 2 feeders of the dAVF, TCCS still showed retrograde flow direction in the left basal vein and significantly elevated flow velocity in the StS, reflecting a high venous pressure caused by a high volume of arteriovenous shunt and severe stenosis in the StS. The patient’s clinical manifestation did not substantially improve until 3 stents were implanted in the StS, and TCCS unveiled that the stents were well filled with flow signal, and the flow velocity in the StS dramatically decreased.

Conclusions:

TCCS could provide reliable data about the feeder and drainage veins of dAVF in our case. The extent of an increase in venous flow velocity may be closely associated with clinical manifestations, which may influence therapy. Moreover, TCCS possesses a unique advantage in terms of evaluating the patency of the stents compared with other neuroimaging techniques.
Hirayama Disease Presenting as 4-Limb Paresthesia
Authors: Fereidan-Esfahani Mahboobeh , Tobin William Oliver
Published: November 2020

Introduction:

Hirayama disease is a rare clinical entity that presents typically as a unilateral, slowly progressive arms weakness, mostly occurring in young men.

Case Report:

We report a case of Hirayama disease in a 20-year-old man presenting with a 4-year history of progressive paresthesia starting in his left arm, progressing to the right arm 1 year later. Four months before the presentation, he experienced bilateral foot paresthesias. Examination revealed weakness of the abductor digiti minimi, hallux extension weakness, and postural tremor bilaterally. He had hypersensitivity to pinprick in both hands with ulnar and median distribution. Sensory examination in the legs was normal. He had a postural tremor in both hands, which worsened on neck flexion. Spinal fluid analysis, including oligoclonal band testing, was normal. Electromyography demonstrated bilateral chronic C7 and C8 radiculopathies. Laboratory tests were normal. Flexion-extension magnetic resonance imaging demonstrated laxity of the dura and ligamentum flavum, with compression of cervical cord, maximal at C5-C6 in neck flexion.

Conclusions:

Laxity of the posterior dura during neck flexion has been postulated to lead to asymmetric lower cervical cord atrophy. Involvement of all 4 limbs is rare, and the condition can be mistaken for progressive multiple sclerosis.
Predicting the Need For Vasopressors in the Intensive Care Unit Using an Attention Based Deep Learning Model
Authors: Kwak Gloria Hyunjung , Ling Lowell , Hui Pan
Published: November 2020

Background:

Previous models on prediction of shock mostly focused on septic shock and often required laboratory results in their models. The purpose of this study was to use deep learning approaches to predict vasopressor requirement for critically ill patients within 24 h of intensive care unit (ICU) admission using only vital signs.

Methods:

We used data from the Medical Information Mart for Intensive Care III database and the eICU Collaborative Research Database to develop a vasopressor prediction model. We performed systematic data preprocessing using matching of cohorts, oversampling, and imputation to control for bias, class imbalance, and missing data. Bidirectional long short-term memory (Bi-LSTM), a multivariate time series model, was used to predict the need for vasopressor therapy using serial physiological data collected 21 h prior to prediction time.

Results:

Using data from 10,941 critically ill patients from 209 ICUs, our model achieved an initial area under the curve of 0.96 (95% CI 0.96–0.96) to predict the need for vasopressor therapy in 2 h within the first day of ICU admission. After matching to control class imbalance, the Bi-LSTM model had area under the curve of 0.83 (95% CI 0.82–0.83). Heart rate, respiratory rate, and mean arterial pressure contributed most to the model.

Conclusions:

We used Bi-LSTM to develop a model to predict the need for vasopressor for critically ill patients for the first 24 h of ICU admission. With attention mechanism, respiratory rate, mean arterial pressure, and heart rate were identified as key sequential determinants of vasopressor requirements.
Spider webs inspiring soft robotics
Authors: Vollrath Fritz , Krink Thiemo
Published: November 2020

In soft robotics, bio-inspiration ranges from hard- to software. Orb web spiders provide excellent examples for both. Adapted sensors on their legs may use morphological computing to fine-tune feedback loops that supervise the handling and accurate placement of silk threads. The spider's webs embody the decision rules of a complex behaviour that relies on navigation and piloting laid down in silk by behaviour charting inherited rules. Analytical studies of real spiders allow the modelling of path-finding construction rules optimized in evolutionary algorithms. We propose that deconstructing spiders and unravelling webs may lead to adaptable robots able to invent and construct complex novel structures using relatively simple rules of thumb.
Honeybee lifespan: the critical role of pre-foraging stage
Authors: Prado Alberto , Requier Fabrice , Crauser Didier , Le Conte Yves , Bretagnolle Vincent , Alaux Cédric
Published: November 2020

Assessing the various anthropogenic pressures imposed on honeybees requires characterizing the patterns and drivers of natural mortality. Using automated lifelong individual monitoring devices, we monitored worker bees in different geographical, seasonal and colony contexts creating a broad range of hive conditions. We measured their life-history traits and notably assessed whether lifespan is influenced by pre-foraging flight experience. Our results show that the age at the first flight and onset of foraging are critical factors that determine, to a large extent, lifespan. Most importantly, our results indicate that a large proportion (40%) of the bees die during pre-foraging stage, and for those surviving, the elapsed time and flight experience between the first flight and the onset of foraging is of paramount importance to maximize the number of days spent foraging. Once in the foraging stage, individuals experience a constant mortality risk of 9% and 36% per hour of foraging and per foraging day, respectively. In conclusion, the pre-foraging stage during which bees perform orientation flights is a critical driver of bee lifespan. We believe these data on the natural mortality risks in honeybee workers will help assess the impact of anthropogenic pressures on bees.
Targeting diamondback moths in greenhouses by attracting specific native parasitoids with herbivory-induced plant volatiles
Authors: Uefune Masayoshi , Abe Junichiro , Shiojiri Kaori , Urano Satoru , Nagasaka Koukichi , Takabayashi Junji
Published: November 2020

We investigated the recruitment of specific parasitoids using a specific blend of synthetic herbivory-induced plant volatiles (HIPVs) as a novel method of pest control in greenhouses. In the Miyama rural area in Kyoto, Japan, diamondback moth (DBM) (
Plutella xylostella
, Lepidoptera: Plutellidae) larvae are an important pest of cruciferous crops in greenhouses, and
Cotesia vestalis
(Hymenoptera: Braconidae), a larval parasitoid of DBM, is found in the surrounding areas. Dispensers of HIPVs that attracted
C. vestalis
and honey feeders were set inside greenhouses (treated greenhouses). The monthly incidence of DBMs in the treated greenhouses was significantly lower than that in the untreated greenhouses over a 2-year period. The monthly incidences of
C. vestalis
and DBMs were not significantly different in the untreated greenhouses, whereas monthly
C. vestalis
incidence was significantly higher than monthly DBM incidence in the treated greenhouses. Poisson regression analyses showed that, in both years, a significantly higher number of
C. vestalis
was recorded in the treated greenhouses than in the untreated greenhouses when the number of DBM adults increased. We concluded that DBMs were suppressed more effectively by
C. vestalis
in the treated greenhouses than in the untreated greenhouses.
Integrated phylogenomic and fossil evidence of stick and leaf insects (Phasmatodea) reveal a Permian–Triassic co-origination with insectivores
Authors: Tihelka Erik , Cai Chenyang , Giacomelli Mattia , Pisani Davide , Donoghue Philip C. J.
Published: November 2020

Stick and leaf insects (Phasmatodea) are a distinctive insect order whose members are characterized by mimicking various plant tissues such as twigs, foliage and bark. Unfortunately, the phylogenetic relationships among phasmatodean subfamilies and the timescale of their evolution remain uncertain. Recent molecular clock analyses have suggested a Cretaceous–Palaeogene origin of crown Phasmatodea and a subsequent Cenozoic radiation, contrasting with fossil evidence. Here, we analysed transcriptomic data from a broad diversity of phasmatodeans and, combined with the assembly of a new suite of fossil calibrations, we elucidate the evolutionary history of stick and leaf insects. Our results differ from recent studies in the position of the leaf insects (Phylliinae), which are recovered as sister to a clade comprising Clitumninae, Lancerocercata, Lonchodinae, Necrosciinae andXenophasmina. We recover a Permian to Triassic origin of crown Phasmatodea coinciding with the radiation of early insectivorous parareptiles, amphibians and synapsids. Aschiphasmatinae and Neophasmatodea diverged in the Jurassic–Early Cretaceous. A second spur in origination occurred in the Late Cretaceous, coinciding with the Cretaceous Terrestrial Revolution, and was probably driven by visual predators such as stem birds (Enantiornithes) and the radiation of angiosperms.
Fruit flies can learn non-elemental olfactory discriminations
Authors: Durrieu Matthias , Wystrach Antoine , Arrufat Patrick , Giurfa Martin , Isabel Guillaume
Published: November 2020

Associative learning allows animals to establish links between stimuli based on their concomitance. In the case of Pavlovian conditioning, a single stimulus A (the conditional stimulus, CS) is reinforced unambiguously with an unconditional stimulus (US) eliciting an innate response. This conditioning constitutes an ‘elemental’ association to elicit a learnt response from A
+
without US presentation after learning. However, associative learning may involve a ‘complex’ CS composed of several components. In that case, the compound may predict a different outcome than the components taken separately, leading to ambiguity and requiring the animal to perform so-called non-elemental discrimination. Here, we focus on such a non-elemental task, the negative patterning (NP) problem, and provide the first evidence of NP solving in
Drosophila
. We show that
Drosophila
learn to discriminate a simple component (A or B) associated with electric shocks (+) from an odour mixture composed either partly (called ‘feature-negative discrimination’ A
+
versus AB
−
) or entirely (called ‘NP’ A
+
B
+
versus AB
−
) of the shock-associated components. Furthermore, we show that conditioning repetition results in a transition from an elemental to a configural representation of the mixture required to solve the NP task, highlighting the cognitive flexibility of
Drosophila
.
Genotype and sex-based host variation in behaviour and susceptibility drives population disease dynamics
Authors: White Lauren A. , Siva-Jothy Jonathon A. , Craft Meggan E. , Vale Pedro F.
Published: November 2020

Host heterogeneity in pathogen transmission is widespread and presents a major hurdle to predicting and minimizing disease outbreaks. UsingDrosophila melanogasterinfected withDrosophilaC virus as a model system, we integrated experimental measurements of social aggregation, virus shedding, and disease-induced mortality from different genetic lines and sexes into a disease modelling framework. The experimentally measured host heterogeneity produced substantial differences in simulated disease outbreaks, providing evidence for genetic and sex-specific effects on disease dynamics at a population level. While this was true for homogeneous populations of single sex/genetic line, the genetic background or sex of the index case did not alter outbreak dynamics in simulated, heterogeneous populations. Finally, to explore the relative effects of social aggregation, viral shedding and mortality, we compared simulations where we allowed these traits to vary, as measured experimentally, to simulations where we constrained variation in these traits to the population mean. In this context, variation in infectiousness, followed by social aggregation, was the most influential component of transmission. Overall, we show that host heterogeneity in three host traits dramatically affects population-level transmission, but the relative impact of this variation depends on both the susceptible population diversity and the distribution of population-level variation.
Amphipithecine primates are stem anthropoids: cranial and postcranial evidence
Authors: Jaeger J.-J. , Sein C. , Gebo D. L. , Chaimanee Y. , Nyein M. T. , Oo T. Z. , Aung M. M. , Suraprasit K. , Rugbumrung M. , Lazzari V. , Soe A. N. , Chavasseau O.
Published: November 2020

Since their discovery in 1927, the phylogenetic status of the Myanmar amphipithecines has been highly debated. These fossil primates are recognized either as anthropoids or as adapiform strepsirrhines. This uncertainty was largely the consequence of a limited fossil record consisting mostly of jaw fragments but lacking the critical cranial elements that might resolve this debate. We report here cranial remains associated with an ulna from a single individual pertaining to the amphipithecine
Ganlea megacanina
. In addition to anthropoid-like dentognathic characters,
Ganlea
displays several ulna and skull features that testify to its anthropoid affinities (e.g. short subvertically oriented lacrimal duct, lacrimal foramen and bone inside the orbit, maxillary contribution to the lower orbital rim, fused metopic suture). By contrast to crown anthropoids, however,
Ganlea
lacks postorbital closure, confirming that postorbital closure appeared later than many anthropoid dentognathic characters and evolved convergently in extant tarsiers and anthropoids. Thus, amphipithecines must now be recognized as stem anthropoids offering a unique window on the early evolution of cranial and skeletal features in anthropoids, and reinforcing the hypothesis of an origin and early diversification of anthropoids in Asia.
Solving post-prandial reduction in performance by adaptive regurgitation in a freshwater fish
Authors: Zhao Jian , Wen Yanci , Zhu Songming , Ye Jinyun , Zhu Junjie , Ye Zhangying , Jordan Alex
Published: November 2020

Foraging animals must balance benefits of food acquisition with costs induced by a post-prandial reduction in performance. Eating to satiation can lead to a reduction in locomotor and escape performance, which increases risk should a threat subsequently arises, but limiting feeding behaviour may be maladaptive if food intake is unnecessarily reduced in the prediction of threats that do not arise. The efficacy of the trade-off between continued and interrupted feeding therefore relies on information about the future risk, which is imperfect. Here, we find that black carp (Mylopharyngodon piceus) can balance this trade-off using ana posterioristrategy; by eating to satiation but regurgitating already ingested food when a threat arises. While degrees of satiation (DS) equal to or greater than 60% reduce elements of escape performance (turning angle, angular velocity, distance moved, linear velocity), at 40% DS or lower, performance in these tasks approaches levels comparable to that at 0% satiation. After experiencing a chasing event, we find that fish are able to regurgitate already ingested food, thereby changing the amount of food in their gastrointestinal tract to consistent levels that maintain high escape performance. Remarkably, regurgitation results in degrees of satiation between 40 and 60% DS, regardless of whether they had previously fed to 40, 60 or 100% DS. Using this response, fish are able to maximize food intake, but regurgitate extra food to maintain escape performance when they encounter a threat. This novel strategy may be effective for continual grazers and species with imperfect information about the level of threat in their environment.
Bumblebees moving up: shifts in elevation ranges in the Pyrenees over 115 years
Authors: Marshall Leon , Perdijk Floor , Dendoncker Nicolas , Kunin William , Roberts Stuart , Biesmeijer Jacobus C.
Published: November 2020

In a warming climate, species are expected to shift their geographical ranges to higher elevations and latitudes, and if interacting species shift at different rates, networks may be disrupted. To quantify the effects of ongoing climate change, repeating historical biodiversity surveys is necessary. In this study, we compare the distribution of a plant–pollinator community between two surveys 115 years apart (1889 and 2005–06), reporting distribution patterns and changes observed for bumblebee species and bumblebee-visited plants in the Gavarnie-Gèdre commune in the Pyrenees, located in southwest Europe at the French–Spanish border. The region has warmed significantly over this period, alongside shifts in agricultural land use and forest. The composition of the bumblebee community shows relative stability, but we observed clear shifts to higher elevations for bumblebees (averaging 129 m) and plants (229 m) and provide preliminary evidence that some bumblebee species shift with the plants they visit. We also observe that some species have been able to occupy the same climate range in both periods by shifting elevation range. The results suggest the need for long-term monitoring to determine the role and impact of the different drivers of global change, especially in montane habitats where the impacts of climate changes are anticipated to be more extreme.
Micromonospora fluminis sp. nov., isolated from mountain river sediment
Authors: Camacho Pozo Miladis Isabel , Wieme Anneleen D. , Rodríguez Pérez Suyén , Llauradó Maury Gabriel , Peeters Charlotte , Snauwaert Cindy , Lescaylle Veranes Yaneisy , Peña Zamora Leonor , Schumann Peter , Vandamme Peter A.
Published: November 2020

During a bioprospection of bacteria with antimicrobial activity, the actinomycete strain A38Twas isolated from a sediment sample of the Carpintero river located in the Gran Piedra Mountains, Santiago de Cuba province (Cuba). This strain was identified as a member of the genusMicromonosporaby means of a polyphasic taxonomy study. Strain A38Twas an aerobic Gram-positive filamentous bacterium that produced single spores in a well-developed vegetative mycelium. An aerial mycelium was absent. The cell wall containedmeso-diaminopimelic acid and the whole-cell sugars were glucose, mannose, ribose and xylose. The major cellular fatty acids were isoC15:0, 10 methyl C17:0, anteiso-C17:0and iso-C17:0. The predominant menaquinones were MK-10(H4) and MK-10(H6). Phylogenetic analysis of 16S rRNA gene sequences revealed that this strain was closely related toMicromonospora tulbaghiaeDSM 45142T(99.5 %),Micromonospora citreaDSM 43903T(99.4 %),Micromonospora marinaDSM 45555T(99.4 %),Micromonospora maritimaDSM 45782T(99.3 %),Micromonospora sediminicolaDSM 45794T(99.3 %),Micromonospora aurantiacaDSM 43813T(99.2 %) andMicromonospora chaiyaphumensisDSM 45246T(99.2 %). The results of OrthoANIu analysis showed the highest similarity toMicromonospora chalceaDSM 43026T(96.4 %). However, the 16S rRNA andgyrBgene sequence-based phylogeny and phenotypic characteristics provided support to distinguish strain A38Tas a novel species. On the basis of the results presented here, we propose to classify strain A38T(=LMG 30467T=CECT 30034T) as the type strain of the novel speciesMicromonospora fluminissp. nov.
Lentilactobacillus kribbianus sp. nov., isolated from the small intestine of a mini pig
Authors: Bai Lu , Paek Jayoung , Shin Yeseul , Park Ho-Yong , Chang Young Hyo
Published: November 2020

A Gram-stain-positive, facultative anaerobic, rod-shaped bacteria isolated from the small intestine of a mini pig was designated as strain YH-lac9T. 16S rRNA gene sequence analysis revealed that the strain belongs to the genus

Lentilactobacillus

and is closely related to

Lentilactobacillus senioris

JCM 17472T,

Lentilactobacillus rapi

JCM 15042T and

Lentilactobacillus diolivorans

JCM 13927T, with 97.6, 96.2 and 95.7 % sequence similarity, respectively. Analysis of housekeeping gene sequences (pheS and recA) revealed that the strain formed a sub-cluster with

L. senioris

, supporting the results of 16S rRNA gene sequences analysis. The average nucleotide identity value for YH-lac9T and the most closely related strain is 74.1 %. The main fatty acids are C18 : 1ω9c, summed feature 7, C16 : 0 and summed feature 8. The G+C content of the genomic DNA is 37.8 mol%. In view of its chemotaxonomic, phenotypic and phylogenetic properties, YH-lac9T (=KCTC 25005=JCM 33997) represents a novel taxon. The name Lentilactobacillus kribbianus sp. nov. is proposed.
Optimized use of Oxford Nanopore flowcells for hybrid assemblies
Authors: Lipworth Samuel , Pickford Hayleah , Sanderson Nicholas , Chau Kevin K. , Kavanagh James , Barker Leanne , Vaughan Alison , Swann Jeremy , Andersson Monique , Jeffery Katie , Morgan Marcus , Peto Timothy E. A. , Crook Derrick W. , Stoesser Nicole , Walker A. Sarah
Published: November 2020

Hybrid assemblies are highly valuable for studies of

Enterobacteriaceae

due to their ability to fully resolve the structure of mobile genetic elements, such as plasmids, which are involved in the carriage of clinically important genes (e.g. those involved in antimicrobial resistance/virulence). The widespread application of this technique is currently primarily limited by cost. Recent data have suggested that non-inferior, and even superior, hybrid assemblies can be produced using a fraction of the total output from a multiplexed nanopore [Oxford Nanopore Technologies (ONT)] flowcell run. In this study we sought to determine the optimal minimal running time for flowcells when acquiring reads for hybrid assembly. We then evaluated whether the ONT wash kit might allow users to exploit shorter running times by sequencing multiple libraries per flowcell. After 24 h of sequencing, most chromosomes and plasmids had circularized and there was no benefit associated with longer running times. Quality was similar at 12 h, suggesting that shorter running times are likely to be acceptable for certain applications (e.g. plasmid genomics). The ONT wash kit was highly effective in removing DNA between libraries. Contamination between libraries did not appear to affect subsequent hybrid assemblies, even when the same barcodes were used successively on a single flowcell. Utilizing shorter run times in combination with between-library nuclease washes allows at least 36

Enterobacteriaceae

isolates to be sequenced per flowcell, significantly reducing the per-isolate sequencing cost. Ultimately this will facilitate large-scale studies utilizing hybrid assembly, advancing our understanding of the genomics of key human pathogens.
ProteoMill: Efficient network-based functional analysis portal for proteomics data
Authors: Rydén M , Englund M , Ali N
Published: November 2020

Functional analysis has become a common approach to incorporate biological knowledge into the analysis of omics data, and to explore molecular events that govern a disease state. It is though only one step in a wider analytical pipeline that typically requires use of multiple individual analysis software. There is currently a need for a well-integrated omics analysis tool that performs all the steps. The ProteoMill portal is developed as an R Shiny application and integrates all necessary steps from data-upload, converting identifiers, to quality control, differential expression and network-based functional analysis into a single fast, interactive easy to use workflow. Further, it maintains annotation data sources up to date, overcoming a common problem with use of outdated information, and seamlessly integrates multiple R-packages for an improved user-experience. The functionality provided in this software can benefit researchers by facilitating the exploratory analysis of proteomics data.

ProteoMill is available for free athttps://proteomill.com.
SlSWEET15 exports sucrose from phloem and seed coat in tomato to supply carbon for fruit and seed development
Authors: Ko Han-Yu , Ho Li-Hsuan , Neuhaus H. Ekkehard , Guo Woei-Jiun
Published: November 2020

Tomato, an important fruit crop worldwide, requires efficient sugar allocation for fruit development. However, molecular mechanisms for sugar import to fruits remain poorly understood. Expression of SWEET (Sugars Will Eventually be Exported Transporters) proteins is closely linked with hexose ratio in tomato fruits and may be involved in sugar allocation. Here, using quantitative PCR, we discovered thatSlSWEET15was highly expressed in developing fruits compared to vegetative organs. Based onin situhybridization and GUS fusion analyses,SlSWEET15 proteins accumulated in vascular tissues and seed coats, major sites of sucrose unloading in fruits. LocalizingSlSWEET15-GFP to the plasma membrane supported its putative role in apoplasmic sucrose unloading. The sucrose transport activity ofSlSWEET15 was confirmed by complementary growth assays in a yeast mutant. Elimination of theSlSWEET15 function by CRISPR/cas9 gene editing significantly decreased average sizes and weights of fruits, with severe defects in seed filling and embryo development. Together, we confirmed the role ofSlSWEET15 in mediating sucrose efflux from the releasing phloem to the fruit apoplasm and subsequent import into parenchyma cells during fruit development. Furthermore,SlSWEET15-mediated sucrose efflux was also required for sucrose unloading from the seed coat to the developing embryo.

One-sentence Summary

SlSWEET15, a specific sucrose uniporter in tomato, mediates apoplasmic sucrose unloading from releasing phloem cells and seed coat for carbon supply during fruit expansion and seed filling.
Pushing Raman spectroscopy over the edge: purported signatures of organic molecules in fossils are instrumental artefacts
Authors: Alleon Julien , Montagnac Gilles , Reynard Bruno , Brulé Thibault , Thoury Mathieu , Gueriau Pierre
Published: November 2020

Claims for the widespread preservation of fossilized biomolecules in many fossil animals have recently been reported in six studies, based on Raman microspectroscopy. Here, we show that the putative Raman signatures of organic compounds in these fossils are actually instrumental artefacts resulting from intense background luminescence. Raman spectroscopy relies upon the detection of photons scattered inelastically by matter as a result of its interaction with a laser beam. For many natural materials, this interaction also generates a luminescence signal that is often orders of magnitude more intense than the light produced by Raman scattering. Such luminescence, coupled with the transmission properties of the spectrometer, induced quasi-periodic ripples in the measured spectra that have been incorrectly interpreted as Raman signatures of organic molecules. Although several analytical strategies have been developed to overcome this common issue, Raman microspectroscopy as used in the studies questioned here cannot be used to identify fossil biomolecules.
Evaluating and Improving SSU rRNA PCR Primer Coverage for Bacteria, Archaea, and Eukaryotes Using Metagenomes from Global Ocean Surveys
Authors: McNichol Jesse , Berube Paul M. , Biller Steven J. , Fuhrman Jed A.
Published: November 2020

Small subunit ribosomal RNA (SSU rRNA) amplicon sequencing can quantitatively and comprehensively profile natural microbiomes, representing a critically important tool for studying diverse global ecosystems. However, results will only be accurate if PCR primers perfectly match the rRNA of all organisms present. To evaluate how well marine microorganisms across all 3 domains are detected by this method, we compared commonly-used primers with > 300 million rRNA gene sequences retrieved from globally-distributed marine metagenomes. The best-performing primers when comparing to 16S rRNA of Bacteria and Archaea were 515Y/926R and 515Y/806RB, which perfectly matched over 96% of all sequences. Considering Cyanobacteria and Chloroplast 16S rRNA, 515Y/926R had the highest coverage (99%), making this set ideal for quantifying marine primary producers. For eukaryotic 18S rRNA sequences, 515Y/926R also performed best (88%), followed by V4R/V4RB (18S rRNA-specific; 82%) – demonstrating that the 515Y/926R combination performs best overall for all 3 domains. Using Atlantic and Pacific Ocean samples, we demonstrate high correspondence between 515Y/926R amplicon abundances (generated for this study) and metagenomic 16S rRNA (median R2=0.98, n=272), indicating amplicons can produce equally accurate community composition data versus shotgun metagenomics. Our analysis also revealed that expected performance of all primer sets could be improved with minor modifications, pointing toward a nearly-completely universal primer set that could accurately quantify biogeochemically-important taxa in ecosystems ranging from the deep-sea to the surface. In addition, our reproducible bioinformatic workflow can guide microbiome researchers studying different ecosystems or human health to similarly improve existing primers and generate more accurate quantitative amplicon data.

Significance Statement

PCR amplification and sequencing of marker genes is a low-cost technique for monitoring prokaryotic and eukaryotic microbial communities across space and time, but will only work optimally if environmental organisms match PCR primer sequences exactly. In this study, we evaluated how well primers match globally-distributed short-read oceanic metagenomes. Our results demonstrate primer sets vary widely in performance, and that at least for marine systems, rRNA amplicon data from some primers lack significant biases compared to metagenomes. We also show that it is possible to create a nearly universal primer set for diverse saline environments by defining a specific mixture of a few dozen oligonucleotides and present a software pipeline that can guide rational design of primers for any environment with available meta’omic data.
Mapping the genetic architecture of human traits to cell types in the kidney identifies mechanisms of disease and potential treatments
Authors: Sheng Xin , Ma Ziyuan , Wu Junnan , Liu Hongbo , Qiu Chengxiang , Miao Zhen , Seasock Matthew J. , Palmer Matthew , Shin Myung K. , Duffin Kevin L. , Pullen Steven S. , Edwards Todd L. , Hellwege Jacklyn N. , Hung Adriana M. , Li Mingyao , Voight Benjamin , Coffman Thomas , Brown Christopher D. , Susztak Katalin
Published: November 2020

The functional interpretation of GWAS remains challenging due to cell-type dependent influences of genetic variants.

Here, we generated comprehensive maps of expression quantitative trait loci (eQTL) for 659 microdissected human kidney samples and identified cell-type eQTLs by mapping interactions between cell type abundance and genotype. Separately, we generated single cell open chromatin maps (by snATAC-seq) for human kidney samples. We highlight critical enrichment of proximal tubules in kidney function and endothelial cells and distal tubule segments in blood pressure by partitioning heritability using stratified LD-score regression to integrate GWAS with scRNA-seq and snATAC-seq data. Bayesian colocalization analysis nominated more than 200 genes for kidney function and hypertension. Our study clarifies the mechanism of the most commonly used antihypertensive and renal protective drugs and identifies drug repurposing opportunities for kidney disease.

One Sentence Summary

We define causal cell types, genes and mechanism for kidney dysfunction.
DeepDrug: A general graph-based deep learning framework for drug-drug interactions and drug-target interactions prediction
Authors: Yin Qijin , Cao Xusheng , Fan Rui , Liu Qiao , Jiang Rui , Zeng Wanwen
Published: November 2020

Computational approaches for accurate prediction of drug interactions, such as drug-drug interactions (DDIs) and drug-target interactions (DTIs), are highly demanded for biochemical researchers due to the efficiency and cost-effectiveness. Despite the fact that many methods have been proposed and developed to predict DDIs and DTIs respectively, their success is still limited due to a lack of systematic evaluation of the intrinsic properties embedded in the corresponding chemical structure. In this paper, we develop a deep learning framework, named DeepDrug, to overcome the above limitation by using residual graph convolutional networks (RGCNs) and convolutional networks (CNNs) to learn the comprehensive structural and sequential representations of drugs and proteins in order to boost the DDIs and DTIs prediction accuracy. We benchmark our methods in a series of systematic experiments, including binary-class DDIs, multi-class/multi-label DDIs, binary-class DTIs classification and DTIs regression tasks using several datasets. We then demonstrate that DeepDrug outperforms state-of-the-art methods in terms of both accuracy and robustness in predicting DDIs and DTIs with multiple experimental settings. Furthermore, we visualize the structural features learned by DeepDrug RGCN module, which displays compatible and accordant patterns in chemical properties and drug categories, providing additional evidence to support the strong predictive power of DeepDrug. Ultimately, we apply DeepDrug to perform drug repositioning on the whole DrugBank database to discover the potential drug candidates against SARS-CoV-2, where 3 out of 5 top-ranked drugs are reported to be repurposed to potentially treat COVID-19. To sum up, we believe that DeepDrug is an efficient tool in accurate prediction of DDIs and DTIs and provides a promising insight in understanding the underlying mechanism of these biochemical relations. The source code of the DeepDrug can be freely downloaded fromhttps://github.com/wanwenzeng/deepdrug.
The H3.3K27M oncohistone antagonizes reprogramming in Drosophila
Authors: Ahmad Kami , Henikoff Steven
Published: November 2020

Development proceeds by the activation of genes by transcription factors and the inactivation of others by chromatin-mediated gene silencing. In some cases development can be reversed or redirected by mis-expression of master regulator transcription factors. This must involve the activation of previously silenced genes, and such developmental aberrations are thought to underlie a variety of cancers. Here, we express the wing-specific Vestigial master regulator to reprogram the developing eye, and test the role of silencing in reprogramming using an H3.3K27M oncohistone mutation that dominantly inhibits histone H3K27 trimethylation. We find that expression of the oncohistone blocks eye-to-wing reprogramming. CUT&Tag chromatin profiling of mutant tissues shows that H3K27me3 domains are globally reduced with oncohistone expression, suggesting that previous developmental programs must be silenced for effective transformation. Strikingly, mis-expressed Vg and H3.3K27M synergize to stimulate overgrowth of eye tissue, a phenotype that resembles that of mutations in Polycomb Repressive Complex 1 components. Our results imply that growth dysregulation can result from the simple combination of crippled silencing and transcription factor mis-expression, an effect that may explain the origins of oncohistone-bearing cancers.
A new microfluidic concept for successfulin vitroculture of mouse embryos
Authors: Mancini V. , McKeegan P.J , Rutledge A.C. , Codreanu S.G. , Sherrod S.D. , McLean J.A. , Picton H.M , Pensabene V.
Published: November 2020

Innovative techniques for gene editing have enabled accurate animal models of human diseases to be established. In order for these methods to be successfully adopted in the scientific community, the optimization of procedures used for breeding genetically altered mice is required. Among these, thein vitrofertilization (IVF) procedure is still suboptimal and the culture methods do not guarantee the development of competent embryos. Critical aspects in traditionalin vitroembryo culture protocols include the use of mineral oil and the stress induced by repetitive handling of the embryos.

A new microfluidic system was designed to allow for efficientin vitroculture of mouse embryos. Harmful fluidic stress and plastic toxicity were excluded by completing the industry gold standard Mouse Embryo Assay. The potential competence of the embryos developed in the device was quantified in terms of blastocyst rate, outgrowth assay, energy substrate metabolism and expression of genes related to implantation potential.

Mass spectrometry analyses identified plastic-related compounds released in medium, and confirmed leaching of low molecular weight species into the culture medium that might be associated to un-crosslinked PDMS.

Finally, these data show the potential for the system to study preimplantation embryo development and to improve human IVF techniques.
Temporal patterning of the central nervous system by a shared transcription factor code
Authors: Sagner Andreas , Zhang Isabel , Watson Thomas , Lazaro Jorge , Melchionda Manuela , Briscoe James
Published: November 2020

The molecular mechanisms that ensure the reproducible generation of neuronal diversity in the vertebrate nervous system are incompletely understood. Here we provide evidence of a temporal patterning program consisting of cohorts of transcription factors expressed in neurons generated at successive developmental timepoints. This program acts in parallel to spatial patterning, diversifying neurons throughout the nervous system and in neurons differentiated in-vitro from stem cells. We demonstrate the TGFβ signalling pathway controls the pace of the temporal program. Furthermore, targeted perturbation of components of the temporal program, Nfia and Nfib, reveals their requirement for the generation of late-born neuronal subtypes. Together, our results provide evidence for the existence of a previously unappreciated global temporal program of neuronal subtype identity and suggest that the integration of spatial and temporal patterning programs diversifies and organises neuronal subtypes in the vertebrate nervous system.
Tonic dopamine, uncertainty and basal ganglia action selection
Authors: Gilbertson Tom , Steele Douglas
Published: November 2020

To make optimal decisions in uncertain circumstances flexible adaption of behaviour is required; exploring alternatives when the best choice is unknown, exploiting what is known when that is best. Using a detailed computational model of the basal ganglia, we propose that switches between exploratory and exploitative decisions can be mediated by the interaction between tonic dopamine and cortical input to the basal ganglia. We show that a biologically detailed action selection circuit model of the basal ganglia, endowed with dopamine dependant striatal plasticity, can optimally solve the explore-exploit problem, estimating the true underlying state of a noisy Gaussian diffusion process. Critical to the model’s performance was a fluctuating level of tonic dopamine which increased under conditions of uncertainty. With an optimal range of tonic dopamine, explore-exploit decision making was mediated by the effects of tonic dopamine on the precision of the model action selection mechanism. Under conditions of uncertain reward pay-out, the model’s reduced selectivity allowed disinhibition of multiple alternative actions to be explored at random. Conversely, when uncertainly about reward pay-out was low, enhanced selectivity of the action selection circuit was enhanced, facilitating exploitation of the high value choice. When integrated with phasic dopamine dependant influences on cortico-striatal plasticity, the model’s performance was at the level of the Kalman filter which provides an optimal solution for the task. Our model provides an integrative account of the relationship between phasic and tonic dopamine and the action selection function of the basal ganglia and supports the idea that this subcortical neural circuit may have evolved to facilitate decision making in non-stationary reward environments, allowing a number of experimental predictions with relevance to abnormal decision making in neuropsychiatric and neurological disease.
High-throughput imaging of mRNA at the single-cell level in human primary immune cells
Authors: Gadkari Manasi , Sun Jing , Carcamo Adrian , Alessi Hugh , Hu Zonghui , Fraser Iain D.C. , Pegoraro Gianluca , Franco Luis M.
Published: November 2020

Measurement of gene expression at the single-cell level has led to important advances in the study of transcriptional regulation programs in healthy and disease states. In particular, single-cell gene expression approaches have shed light on the high level of transcriptional heterogeneity of individual cells, both at baseline and in response to experimental or environmental perturbations. We have developed a method for High-Content Imaging (HCI)-based quantification of transcript abundance at the single-cell level in primary human immune cells and have validated its performance under multiple experimental conditions to demonstrate its general applicability. This method, which we abbreviate as hcHCR, combines the high sensitivity of the hybridization chain reaction (HCR) for the visualization of mRNA molecules in single cells, with the speed, scalability, and technical reproducibility of HCI. We first tested eight microscopy-compatible attachment substrates for short-term culture of primary human B cells, T cells, monocytes, or neutrophils. We then miniaturized HCR in a 384-well format and documented the ability of the method to detect increased or decreased transcript abundance at the single-cell level in thousands of cells for each experimental condition by HCI. Furthermore, we demonstrated the feasibility of multiplexing gene expression measurements by simultaneously assaying the abundance of two transcripts per cell, both at baseline and in response to an experimental stimulus. Finally, we tested the robustness of the assay to technical and biological variation. We anticipate that hcHCR will be a suitable and cost-effective assay for low- to medium-throughput chemical, genetic or functional genomic screens in primary human cells, with the possibility of performing personalized screens or screens on cells obtained from patients with a specific disease.