bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary Micronodules
Authors: Bueno Juliana
Published: August 2019

A micronodule is a rounded opacity that measures < 3 mm in diameter at CT. Nodules can be located within the lung interstitium, the airspace or both. The differential diagnosis of diseases manifesting with interstitial micronodules varies widely, and affected patients have variable clinical presentations. Familiarity with the anatomy of the pulmonary interstitium is fundamental when assessing micronodules as a concentration of micronodules within a particular compartment may be the imaging clue to the correct diagnosis. Thin-section CT and HRCT are optimal for detection and characterization of pulmonary micronodules; once micronodules are identified, their distribution within the pulmonary interstitium must be determined according to their location with respect to the secondary pulmonary lobule, and characterized as centrilobular, perilymphatic or random.
Idiopathic Interstitial Pneumonias
Authors: Bhalla Sanjeev
Published: August 2019

The idiopathic interstitial pneumonias (IIPs) are a group of diffuse lung diseases that often manifest clinically with increasing dyspnea and hypoxemia. In the most recent revision of the American Thoracic Society/European Respiratory Society statement on IIPs, the major IIPs are divided into 3 groups: chronic fibrosing conditions (usual interstitial pneumonia and nonspecific interstitial pneumonia); smoking-related conditions (respiratory bronchiolitis and desquamative interstitial pneumonia) and acute/subacute IIPs (cryptogenic organizing pneumonia and acute interstitial pneumonia). Although some of these patterns may be seen with other conditions (e.g, NSIP with collagen vascular disease), the term IIP only refers to the idiopathic variants. Interestingly, the smoking-related conditions (RB-ILD and DIP) are included in this idiopathic grouping despite their association with cigarette use.
Congenital Bronchial Atresia
Authors: Benson Ryo E. C.
Published: August 2019

Congenital bronchial atresia (CBA) is a benign congenital abnormality in which there is focal atresia of a segmental bronchus with resultant distal endobronchial mucocele (bronchocele) and surrounding hyperlucent lung. Affected patients are typically young and asymptomatic, and the diagnosis is usually incidental. CBA is an imaging diagnosis that may be suspected on radiography but is usually confirmed on chest CT. The typical imaging appearance is a round, tubular or branching, non-enhancing mucocele with surrounding localized hyperlucent lung. Asymptomatic patients require no further imaging or treatment. However, surgical resection of the affected lung can be considered for symptomatic patients with recurrent pulmonary infections.
Diaphragmatic Abnormalities
Authors: Parkar Nadeem , Bierhals Andrew J.
Published: August 2019

The diaphragm abnormalities chapter discusses a variety of acquired and congenital conditions of the diaphragm, the principal muscle of respiration. Most diaphragmatic abnormalities encountered on imaging relate to abnormal contour or abnormal function. The latter is usually due to phrenic nerve palsy or neoplastic involvement. Abnormal contour often results from congenital thinning (eventration). Herniation and rupture following trauma are associated with a high risk of gastric ischemia and require prompt diagnosis and treatment. Thus, radiologists must be familiar with CT findings of traumatic diaphragmatic injury. Nontraumatic hernias (namely, Bochdalek, foramen of Morgagni and hiatal hernias) have typical imaging appearances as well. Rarely, a subpulmonic pleural effusion may mimic an elevated hemidiaphragm on radiography. A pleural effusion may also invert the diaphragm and impair respiration.
Hemispheric asymmetry in meridional flow and the sunspot cycle
Authors: Lekshmi B , Nandy Dibyendu , Antia H M
Published: August 2019

Magnetohydrodynamic dynamo modelling shows that the large-scale solar meridional plasma flow plays an important role in governing the dynamics of the sunspot cycle. Observations indicate that meridional flow velocities at each solar latitude and depth vary over time and are asymmetric across the equator. Here, using helioseismic observations we explore the temporal variation in the hemispherical asymmetry of near-surface residual (time-varying) component of the Sun’s meridional flow velocity. The meridional flow velocities obtained from Global Oscillation Network Group (GONG) and Helioseismic and Magnetic Imager (HMI) onboard Solar Dynamics Observatory (SDO) ring-diagram pipelines are used in this work. Our data set covers the declining phase of cycle 23 and cycle 24 (from July 2001 till December 2018) and the flow velocities are poleward for the observed depth range. We observe a time delayed anticorrelation between the hemispherical asymmetry in near-surface meridional flow velocities and the sunspot cycle quantified in terms of magnetic flux and sunspot number. Interestingly, asymmetry in meridional flow velocity precedes the asymmetry in sunspot cycle by 3.1–3.5 yr. We propose that meridional flow asymmetry is a precursor of asymmetry in hemispherical cycle strength. The symmetric component of meridional flow is observed to be positively correlated with the corresponding symmetric components of the magnetic cycle, also with a time delay. Our analysis sets important constraints on theories for the origin of meridional plasma flow asymmetries and its temporal variations and is relevant for understanding the role of plasma flux transport processes in determining hemispheric asymmetry in the sunspot cycle.
Components of the diffuse ultraviolet radiation at high latitudes
Authors: Akshaya M S , Murthy Jayant , Ravichandran S , Henry R C , Overduin James
Published: August 2019

We have used data from the Galaxy Evolution Explorer to study the different components of the diffuse ultraviolet background in the region between the Galactic latitudes 70°–80°. We find an offset at zero dust column density (E(B − V) = 0) of 240 ± 18 photon units in the FUV (1539 Å) and 394 ± 37 photon units in the NUV (2316 Å). This is approximately half of the total observed radiation with the remainder divided between an extragalactic component of 114 ± 18 photon units in the FUV and 194 ± 37 photon units in the NUV and starlight scattered by Galactic dust at high latitudes. The optical constants of the dust grains were found to be a = 0.4 ± 0.1 and g = 0.8 ± 0.1 (FUV) and a = 0.4 ± 0.1 and g = 0.5 ± 0.1 (NUV). We cannot differentiate between a Galactic or extragalactic origin for the zero-offset but can affirm that it is not from any known source.
A parallel and automatically tuned algorithm for multispectral image deconvolution
Authors: Ammanouil R , Ferrari A , Mary D , Ferrari C , Loi F
Published: August 2019

In the era of big data, radio astronomical image reconstruction algorithms are challenged to estimate clean images given limited computing resources and time. This article is driven by the need for large-scale image reconstruction for the future Square Kilometre Array (SKA), which will become in the next decades the largest low and intermediate frequency radio telescope in the world. This work proposes a scalable wide-band deconvolution algorithm called MUFFIN, which stands for ‘MUlti Frequency image reconstruction For radio INterferometry’. MUFFIN estimates the sky images in various frequency bands, given the corresponding dirty images and point spread functions. The reconstruction is achieved by minimizing a data fidelity term and joint spatial and spectral sparse analysis regularization terms. It is consequently non-parametric w.r.t. the spectral behaviour of radio sources. MUFFIN algorithm is endowed with a parallel implementation and an automatic tuning of the regularization parameters, making it scalable and well suited for big data applications such as SKA. Comparisons between MUFFIN and the state-of-the-art wide-band reconstruction algorithm are provided.
Primeval very low-mass stars and brown dwarfs – VII. The discovery of the first wide M + L extreme subdwarf binary
Authors: Zhang (张曾华) ZengHua
Published: August 2019

I present the discovery of the first wide M + L extreme subdwarf binary system Gaia J0452−36AB. The binary is located at a distance of 137.27 $^{+0.68}_{-0.67}$ pc with a projected separation of 15828 ± 78 au. I classified Gaia J0452−36AB as esdM1 and esdL0 subdwarfs, respectively. Gaia J0452−36AB have typical halo kinematics, metallicity of [Fe/H] ≈−1.4, and temperature of ∼ 3550 and 2600 K, respectively. Gaia J0452−36AB is a pair of very low-mass stars with masses of 0.151 $^{+0.029}_{-0.019}$ and 0.0855$^{+0.0014}_{-0.0010}$ M$\odot$, and is a gravitationally bound system. I tested the metallicity consistency of existing M subdwarf classification schemes with Gaia J0452−36AB and a sample of M and L subdwarfs with known metallicity. I found that the metallicity of each M subclass defined by the the metallicity index ζCaH/TiO is not consistent from mid-to-late M subtypes. Because late-type M and L subdwarfs have dusty atmospheres and high surface gravity which have significant impacts on CaH and TiO indices that used in the classification. The metallicity scale of late-type M subdwarfs would be overestimated by the ζCaH/TiO index. I discussed the mass range of M subdwarfs, and explained the lack of late-type M extreme and ultra subdwarfs, and decreasing binary fraction from sdM, to esdM, and usdM subclasses. The four M subclasses have different mass ranges. The comparison between M subclasses is between populations in different mass ranges. I also present the discovery of Ruiz 440-469B, an M8 dwarf wide companion to a cool DA white dwarf, Ruiz 440-469.
Impacts of Interleukin-18 Polymorphisms on the Incidence of Delayed-Onset Cytomegalovirus Infection in a Cohort of Kidney Transplant Recipients
Authors: Pérez-Flores Isabel , Santiago Jose Luis , Fernández-Pérez Cristina , Urcelay Elena , Moreno de la Higuera María Ángeles , Romero Natividad Calvo , Cubillo Beatriz Rodríguez , Sánchez-Fructuoso Ana Isabel
Published: August 2019

Background

The incidence of cytomegalovirus (CMV) infection in solid organ transplant recipients may be reduced by antiviral prophylaxis, but this strategy may lead to delayed-onset CMV infection. The proinflammatory cytokine interleukin (IL)-18 plays a major role in viral host defense responses. This study examines the impacts of 2 single-nucleotide polymorphisms (SNPs) in the promoter region of the IL-18 gene, -607C/A (rs1946518) and -137G/C (rs187238), on the incidence of delayed-onset CMV infection in patients undergoing kidney transplant.

Methods

This retrospective study analyzed 2 IL-18 SNPs in consecutive adult kidney transplant recipients using real-time polymerase chain reaction with TaqMan probes. Participants were enrolled over the period 2005–2013 and stratified according to their IL-18 SNP genotype. The concordance index (Harrell’s c-index) was used as a measure of the discriminatory power of the predictive models constructed with bootstrapping to correct for optimistic bias.

Results

Seven hundred nine patients received transplants in the study period, and 498 met selection criteria. Cytomegalovirus infection and disease incidence were 38% and 7.5%, respectively. In multivariate competing risk regression models, carriers of the -607C/-137G haplotype who received prophylaxis showed a higher incidence of CMV replication after antiviral agent discontinuation (hazard ratio = 2.42 [95% confidence interval, 1.11–5.26]; P = .026), whereas CMV disease was not observed in those given prophylaxis who were noncarriers of this polymorphism (P = .009).

Conclusions

Our findings suggest that the -607C/-137G IL-18 haplotype is associated with a higher incidence of postprophylaxis CMV replication. The prior identification of this polymorphism could help select alternative measures to prevent delayed-onset CMV infection in these patients.
Candidate Predisposition Variants in Kaposi Sarcoma as Detected by Whole-Genome Sequencing
Authors: Rinne Sanni J , Sipilä Lauri J , Sulo Päivi , Jouanguy Emmanuelle , Béziat Vivien , Abel Laurent , Casanova Jean-Laurent , Parvaneh Nima , Balighi Kamran , Guttman-Yassky Emma , Sarid Ronit , Aaltonen Lauri A , Aavikko Mervi
Published: August 2019

Familial clustering of classic Kaposi sarcoma (CKS) is rare with, approximately 100 families reported to date. We studied 2 consanguineous families, 1 Iranian and 1 Israeli, with multiple cases of adult CKS and without overt underlying immunodeficiency. We performed genome-wide linkage analysis and whole-genome sequencing to discover the putative genetic cause for predisposition. A 9-kb homozygous intronic deletion in RP11-259O2.1 in the Iranian family and 2 homozygous variants, 1 in SCUBE2 and the other in CDHR5, in the Israeli family were identified as possible candidates. The presented variants provide a robust starting point for validation in independent samples.
Successful Treatment of Mycobacterium chelonae Keratitis Within a Corneal Transplant Using Intrastromal Amikacin Injections—A Case Report Demonstrating the Fundamental Principles and Challenges of Infective Keratitis Management and Novel Therapeutic Approaches
Authors: Merridew Nancy Louisa , Phagura Ravinder Singh , Anderson Edward , Cooley Louise Anne , Pollock Graeme Alfred , McEwan Belinda , McCartney Paul James , Trad Mohamad-Ali
Published: August 2019

Mycobacterium chelonae keratitis is rare and difficult to treat. This is the first known case worldwide of effective treatment using intrastromal amikacin injections in a corneal transplant recipient who had metastatic breast cancer. The challenges and principles of management, applicable to other causes of infective keratitis, are reviewed.
What Types Should Not Be†
Authors: Bentzen Bruno
Published: August 2019

In a series of papers Ladyman and Presnell raise an interesting challenge of providing a pre-mathematical justification for homotopy type theory. In response, they propose what they claim to be an informal semantics for homotopy type theory where types and terms are regarded as mathematical concepts. The aim of this paper is to raise some issues which need to be resolved for the successful development of their types-as-concepts interpretation.
Self-reported painful joint count and assessor-reported tender joint count as instruments to assess pain in hand osteoarthritis
Authors: Kroon Féline P B , Damman Wendy , van der Plas Johan L , van Beest Sjoerd , Rosendaal Frits R , van der Heijde Désirée , Kloppenburg Margreet
Published: August 2019

Objectives

To evaluate self-reported and assessor-reported joint counts for pain and their value in measuring pain and joint activity in hand OA patients.

Methods

A total of 524 patients marked painful joints on hand diagrams. Nurses assessed tenderness upon palpation. Pain was measured with a visual analogue scale pain and the Australian/Canadian hand OA index subscale pain. Synovitis and bone marrow lesions in right hand distal/proximal interphalangeal joints on MRI served as measure of joint activity. Agreement was assessed on the patient (intraclass correlation coefficient, Bland–Altman plot) and joint level (percentage absolute agreement). Correlations with measures of pain and joint activity were analysed, and joint level associations with synovitis/bone marrow lesions were calculated.

Results

Self-reported painful joint count (median 8, interquartile range 4–13) was consistently higher than assessor-reported tender joint count (3, 1–7). Agreement between patients and nurses on overall scores was low. Percentage absolute agreement on the joint level was 61–89%. Joint counts correlated similarly but weakly with measures of pain and joint activity (r = 0.14–0.38). On the joint level, assessor-reported tenderness was more strongly associated with synovitis/bone marrow lesions than self-reported pain.

Conclusion

In hand OA, self- and assessor-reported joint counts cannot be used interchangeably, and measure other pain aspects than questionnaires. Assessor-reported tenderness was most closely related to MRI-defined joint activity.
How Statelessness, Citizenship, and Out-migration Contribute to Stratification Among Rural Elderly in the Highlands of Thailand
Authors: Flaim Amanda , Williams Lindy B , Ahlquist Daniel B
Published: August 2019

In rural communities across the Global South, families are relying on temporary and permanent out-migration for work to navigate destabilizing agrarian transformations. While research indicates that success of this household livelihood strategy may depend on the legal status of international migrants, precarious legal status is not solely a problem relegated to people who cross national borders. Indeed, millions worldwide are stateless in the countries of their birth. In this mixed-method study, we assess the importance of legal status for elderly well-being among highlanders in Northern Thailand—rural communities that are experiencing both extensive out-migration and protracted statelessness. We find that elderly wealth and work outcomes are shaped by the legal status of both out-migrants and of the rural elderly themselves. Specifically, we show that when rural elderly or their migrant relatives are stateless, the elderly are more likely to engage in wage work and less likely to gain financial benefits of out-migration to the extent that citizens do. Through ethnographic engagement, we locate the contributions of legal status to rural stratification in its complex entanglements with land access and ethno-nationalism in the region, and in the ways that state and market infrastructures deploy citizenship to surveil highlanders and other minorities in Thailand. Amidst growing calls to resolve statelessness in the Global South, our research suggests that the combination of out-migration and uneven extension of citizenship in rural communities is likely to exacerbate stratification, both for migrants and for those who rarely leave home.
Acute Encephalitis Syndrome with an Unusual Diagnosis
Authors: Thomas Mili , Swarnam Kamala , Remadevi Gopika Sekhar , Pillai A Marthanda
Published: August 2019

Four-year old boy was admitted with acute onset of fever with seizures and altered sensorium. His mother had history of contact with influenza A H1N1 virus (H1N1) infection. Blood counts, electrolytes, blood sugar and ammonia were normal. Liver enzymes were mildly elevated. CSF study showed elevated protein, normal sugar and no pleocytosis. Cerebrospinal fluid (CSF) viral panel was negative. Magnetic resonance imaging brain was suggestive of acute necrotizing encephalopathy. His throat swab and sputum polymerase chain reaction was positive for H1N1. He was managed with ventilation, intravenous steroids and other supportive measures. At discharge his sensorium improved but had neurological sequelae. We are presenting this case as this is a very rare complication of H1N1 infection with high rate of mortality. Early supportive measures and steroids/intravenous immunoglobulin may save the patient.
Childhood Scurvy: A Nearly Extinct Disease Posing a New Diagnostic Challenge, a Case Report
Authors: Gupta Neeraj , Toteja Nisha , Sasidharan Rohit , Singh Kuldeep
Published: August 2019

Scurvy is seldom encountered in modern day clinical practice. Children can present with nonspecific features which can mimic several other common conditions. We describe here a four-year-old child who presented with severe pain and weakness of bilateral lower limbs and found to be severely malnourished. The diagnosis of scurvy was suspected in the context of underlying malnutrition after excluding other ominous pathologies. Pathognomic radiological changes clinched the diagnosis, and the best supportive evidence was the dramatic response to vitamin C supplementation.
Evaluation of the Active Melioidosis Detect™ test as a point-of-care tool for the early diagnosis of melioidosis: a comparison with culture in Laos
Authors: Rizzi Maria Chiara , Rattanavong Sayaphet , Bouthasavong Latsaniphone , Seubsanith Amphayvanh , Vongsouvath Manivanh , Davong Viengmon , De Silvestri Annalisa , Manciulli Tommaso , Newton Paul N , Dance David A B
Published: August 2019

Background

Melioidosis is difficult to diagnose clinically and culture of Burkholderia pseudomallei is the current, imperfect gold standard. However, a reliable point-of-care test (POCT) could enable earlier treatment and improve outcomes.

Methods

We evaluated the sensitivity and specificity of the Active Melioidosis Detect™ (AMD) rapid test as a POCT and determined how much it reduced the time to diagnosis compared with culture.

Results

We tested 106 whole blood, plasma and buffy coat samples, 96 urine, 28 sputum and 20 pus samples from 112 patients, of whom 26 (23.2%) were culture-positive for B. pseudomallei. AMD sensitivity and specificity were 65.4 and 87.2%, respectively, the latter related to 10 weak positive reactions on urine samples, considered likely false positives. The positive predictive value was 60.7%, negative predictive value was 89.3% and concordance rate between operators reading the test was 95.7%; time to diagnosis decreased by a median of 23 h.

Conclusions

Our findings confirm that a strongly positive AMD result can reduce the time to diagnosis of melioidosis. However, the AMD currently has a disappointing overall sensitivity, especially with blood fractions, and specificity problems when testing urine samples.
Evidence for a giant parrot from the Early Miocene of New Zealand
Authors: Worthy Trevor H. , Hand Suzanne J. , Archer Michael , Scofield R. Paul , De Pietri Vanesa L.
Published: August 2019

Insular avifaunas have repeatedly spawned evolutionary novelties in the form of unusually large, often flightless species. We report fossils from the Early Miocene St Bathans Fauna of New Zealand that attests to the former existence of a giant psittaciform, which is described as a new genus and species. The fossils are two incomplete tibiotarsi from a bird with an estimated mass of 7 kg, double that of the heaviest known parrot, the kakapoStrigops habroptila. These psittaciform fossils show that parrots join the growing group of avian taxa prone to giantism in insular species, currently restricted to palaeognaths, anatids, sylviornithids, columbids, aptornithids, ciconiids, tytonids, falconids and accipitrids.
A seed flying like a bullet: ballistic seed dispersal in Chinese witch-hazel (Hamamelis mollisOLIV., Hamamelidaceae)
Authors: Poppinga Simon , Böse Anne-Sophie , Seidel Robin , Hesse Linnea , Leupold Jochen , Caliaro Sandra , Speck Thomas
Published: August 2019

The fruits of Chinese witch-hazel (Hamamelis mollis, Hamamelidaceae) act as ‘drying squeeze catapults', shooting their seeds several metres away. During desiccation, the exocarp shrinks and splits open, and subsequent endocarp deformation is a complex three-dimensional shape change, including formation of dehiscence lines, opening of the apical part and formation of a constriction at the middle part. Owing to the constriction forming, mechanical pressure is increasingly applied on the seed until ejection. We describe a structural latch system consisting of connective cellular structures between endocarp and seed, which break with a distinct cracking sound upon ejection. A maximum seed velocity of 12.3 m s−1, maximum launch acceleration of 19 853 m s−2(approx. 2000g) and maximum seed rotational velocity of 25 714 min−1were measured. We argue that miniscule morphological differences between the inner endocarp surface and seed, which features a notable ridge, are responsible for putting spin on the seed. This hypothesis is further corroborated by the observation that there is no preferential seed rotation direction among fruits. Our findings show thatH. mollishas evolved similar mechanisms for stabilizing a ‘shot out’ seed as humans use for stabilizing rifle bullets and are discussed in an ecological (dispersal biology), biomechanical (seed ballistics) and functional–morphological (fine-tuning and morphospace of functional endocarps) contexts, and promising additional aspects for future studies are proposed.
Ruminococcus gnavus bacteraemia in a patient with multiple haematological malignancies
Authors: Gren Caroline , Spiegelhauer Malene Roed , Rotbain Emelie Curovic , Ehmsen Boje Kvorning , Kampmann Peter , Andersen Leif Percival
Published: August 2019

We present a case of

Ruminococcus gnavus

sepsis in a woman suffering from multiple myeloma and myelodysplastic syndrome.

R. gnavus

, a Gram-positive coccus and a gut commensal, has been described in nine cases of infection in the literature, with most infections having occurred in patients with either gastrointestinal symptoms or prosthesis infections. In this case,

R gnavus

was identified by mass spectrometry, and showed susceptibility to penicillin, meropenem, tetracycline, metronidazole and clindamycin. The patient was successfully treated initially with intravenous piperacillin/tazobactam and metronidazole, and then switched to oral penicillin and metronidazole. The cause of infection is hypothesized to have been a shift in the gut microbiota towards an excess growth of

R. gnavus

caused by immunosuppression, and bacterial translocation across a vulnerable mucosal barrier due to prednisolone treatment and severe thrombocytopenia.
Melanoblast transcriptome analysis reveals novel pathways promoting melanoma metastasis
Authors: Marie Kerrie L. , Sassano Antonella , Yang Howard H. , Michalowski Aleksandra M. , Michael Helen T. , Guo Theresa , Tsai Yien Che , Weissman Allan M. , Lee Maxwell P. , Jenkins Lisa M. , Zaidi M. Raza , Pérez-Guijarro Eva , Day Chi-Ping , Arnheiter Heinz , Davis Sean , Meltzer Paul S. , Merlino Glenn , Mishra Pravin J.
Published: August 2019

Cutaneous malignant melanoma is an aggressive cancer of melanocytes with a strong propensity to metastasize. We posited that melanoma cells acquire metastatic capability by adopting an embryonic-like phenotype, and that a lineage approach would uncover novel metastatic melanoma biology. We used a genetically engineered mouse model to generate a rich melanoblast transcriptome dataset, identified melanoblast-specific genes whose expression contributed to metastatic competence, and derived a 43-gene signature that predicted patient survival. We identified a melanoblast gene,KDELR3, whose loss impaired experimental metastasis. In contrast,KDELR1deficiency enhanced metastasis, providing the first example of different disease etiologies within the KDELR-family of retrograde transporters. We show that KDELR3 regulates the metastasis suppressor, KAI1, and report an interaction with the E3 ubiquitin-protein ligase gp78, a regulator of KAI1 degradation. Our work demonstrates that the melanoblast transcriptome can be mined to uncover novel targetable pathways for melanoma therapy.
Lipid droplet accumulating microglia represent a dysfunctional and pro-inflammatory state in the aging brain
Authors: Marschallinger Julia , Iram Tal , Zardeneta Macy , Lee Song E. , Lehallier Benoit , Haney Michael S. , Pluvinage John V. , Mathur Vidhu , Hahn Oliver , Morgens David W. , Kim Justin , Tevini Julia , Felder Thomas K. , Wolinski Heimo , Bertozzi Carolyn R. , Bassik Michael C. , Aigner Ludwig , Wyss-Coray Tony
Published: August 2019

Microglia become progressively activated and seemingly dysfunctional with age, and genetic studies have linked these cells to the pathogenesis of a growing number of neurodegenerative diseases. Here we report a striking buildup of lipid droplets in microglia with aging in mouse and human brains. These cells, which we call lipid droplet-accumulating microglia (LAM), are defective in phagocytosis, produce high levels of reactive oxygen species, and secrete pro-inflammatory cytokines. RNA sequencing analysis of LAM revealed a transcriptional profile driven by innate inflammation distinct from previously reported microglial states. An unbiased CRISPR-Cas9 screen identified genetic modifiers of lipid droplet formation; surprisingly, variants of several of these genes, including progranulin, are causes of autosomal dominant forms of human neurodegenerative diseases. We thus propose that LAM contribute to age-related and genetic forms of neurodegeneration.
SIZ1 is a nuclear host target of the nematode effector GpRbp1 from Globodera pallida that acts as a negative regulator of basal plant defense to cyst nematodes
Authors: Diaz-Granados Amalia , Sterken Mark G. , Persoon Jarno , Overmars Hein , Pokhare Somnath S. , Mazur Magdalena J , Martin-Ramirez Sergio , Holterman Martijn , Martin Eliza C. , Pomp Rikus , Finkers-Tomczak Anna , Roosien Jan , Elashry Abdenaser , Grundler Florian , Petrescu Andrei J , Smant Geert , Goverse Aska
Published: August 2019

Soil-borne cyst nematodes are obligatory sedentary parasites that cause severe losses to cultivation of major crops such as potato and soybean. Cyst nematodes establish specialised permanent feeding sites within the roots of their host by manipulating plant morphology and physiology through secreted effectors. Here we identified host targets of effector GpRbp-1 and studied their roles in plant-nematode interactions. GpRbp-1 was found to interact in yeast and in planta with the potato and Arabidopsis homologues of Siz/PIAS-type E3 SUMO ligase SIZ1. Our results show that a pathogen effector targets the master regulator SIZ1 in plant cells, which has not been demonstrated earlier to our knowledge. The interaction of GpRbp-1 and SIZ1 localizes to the plant nucleus, suggesting that the nuclear functions of SIZ1 as regulator of plant immunity and physiology may be modulated by GpRbp-1. Furthermore, nematode infection assays and transcriptomic profiling indicate that SIZ1 is required for susceptibility to cyst nematodes. So, these data indicate that E3 SUMO ligases may play an important role in plant-nematode interactions. Based on the prediction of SUMO acceptor and interaction sites in GpRbp-1, a model is proposed in which the effector may recruit SIZ1 to be SUMOylated for full functionality in host cells.

Significance statement

Here we show that a pathogen effector can target SIZ1, a key protein involved in regulating several aspects of plant biology, most likely to manipulate the SUMOylation of host proteins for successful infection of plants.
Maternal malnutrition impacts placental morphology and transport. An origin for poor offspring growth and vulnerability to disease
Authors: Connor Kristin L , Kibschull Mark , Matysiak-Zablocki Elzbieta , Nguyen Tina Tu-Thu Ngoc , Matthews Stephen G , Lye Stephen J , Bloise Enrrico
Published: August 2019

The placenta promotes fetal growth through nutrient transfer and selective barrier systems. An optimally developed placenta can adapt to changes in the pregnancy environment, buffering the fetus from adverse exposures. We hypothesised that the placenta adapts differently to suboptimal maternal diets, evidenced by changes in placental morphology, developmental markers, and key transport systems. Mice were fed a control diet (CON) during pregnancy, or undernourished (UN) by 30% of control intake from gestational day (GD)5.5-18.5, or fed 60% high fat diet (HF) eight weeks before and during pregnancy. At GD18.5, placental morphometry, development, and transport were assessed. Junctional and labyrinthine areas of UN and HF placentae were smaller than CON by >10%. Fetal blood space area and fetal blood space:fetal weight ratios were reduced in HF vs. CON and UN. Trophoblast giant cell marker Ctsq mRNA expression was lower in UN vs. HF, and expression of glycogen cell markers Cx31.1 and Pcdh12 was lower in HF vs. UN. Efflux transporter Abcb1a mRNA expression was lower in HF vs. UN, and Abcg2 expression was lower in UN vs. HF. mRNA expression of fatty acid binding protein Fabppm was higher in UN vs. CON and HF. mRNA and protein levels of the lipid transporter FAT/CD36 were lower in UN, and FATP4 protein levels were lower in HF vs. UN. UN placentae appear less mature with aberrant transport. HF placentae adapt to excessive nutrient supply. Understanding placental adaptations to common nutritional adversities may reveal mechanisms underlying the developmental origins of later disease.
Inferring neuronal ionic conductances from membrane potentials using CNNs
Authors: Ben-Shalom Roy , Balewski Jan , Siththaranjan Anand , Baratham Vyassa , Kyoung Henry , Kim Kyung Geun , Bender Kevin J. , Bouchard Kristofer E.
Published: August 2019

The neuron is the fundamental unit of computation in the nervous system, and different neuron types produce different temporal patterns of voltage fluctuations in response to input currents. Understanding the mechanism of single neuron firing patterns requires accurate knowledge of the spatial densities of diverse ion channels along the membrane. However, direct measurements of these microscopic variables are difficult to obtain experimentally. Alternatively, one can attempt to infer those microscopic variables from the membrane potential (a mesoscopic variable), or features thereof, which are more experimentally tractable. One approach in this direction is to infer the ionic densities as parameters of a neuronal model. Traditionally this is done using a Multi-Objective Optimization (MOO) method to minimize the differences between features extracted from a simulated neuron’s membrane potential and the same features extracted from target data. Here, we use Convolutional Neural Networks (CNNs) to directly regress generative parameters (e.g., ionic conductances, membrane resistance, etc.,) from simulated time-varying membrane potentials in response to an input stimulus. We simulated diverse neuron models of increasing complexity (Izikivich: 4 parameters; Hodgkin-Huxley: 7 parameters; Mainen-Sejnowski: 10 parameters) with a large range of variation in the underlying parameter values. We show that hyperparameter optimized CNNs can accurately infer the values of generative variables for these neuron models, and that these results far surpass the previous state-of-the-art method (MOO). We discuss the benefits of optimizing the CNN architecture, improvements in accuracy with additional training data, and some observed limitations. Based on these results, we propose that CNNs may be able to infer the spatial distribution of diverse ionic densities from spatially resolved measurements of neuronal membrane potentials (e.g. voltage imaging).
Kaposi’s sarcoma-associated herpesvirus ORF66 is essential for late gene expression and virus production via interaction with ORF34
Authors: Watanabe Tadashi , Nishimura Mayu , Izumi Taisuke , Kuriyama Kazushi , Iwaisako Yuki , Hosokawa Kouhei , Takaori-Kondo Akifumi , Fujimuro Masahiro
Published: August 2019

Kaposi’s sarcoma-associated herpesvirus (KSHV) is closely associated with B-cell and endothelial cell malignancies. After the initial infection, KSHV retains its viral genome in the nucleus of the host cell and establishes a lifelong latency. During lytic infection, KSHV encoded lytic-related proteins are expressed in a sequential manner and are classified as immediate early, early, and late gene transcripts. The transcriptional initiation of KSHV late genes is thought to require the complex formation of the virus specific pre-initiation complex (vPIC), which may consist of at least 6 transcription factors (ORF18, 24, 30, 31, 34, and 66). However, the functional role of ORF66 in vPIC during KSHV replication remains largely unclear. Here, we generated ORF66-deficient KSHV using a BAC system to evaluate its role during viral replication. While ORF66-deficient KSHV demonstrated mainly attenuated late gene expression and decreased viral production, viral DNA replication was unaffected. CHIP analysis showed that ORF66 bound to the promoters of late gene (K8.1), but did not to those of latent gene (ORF72), immediate early gene (ORF16) and early gene (ORF46/47). Furthermore, we found that three highly conserved C-X-X-C sequences and a conserved leucine-repeat in the C-terminal region of ORF66 were essential for interaction with ORF34 and viral production. The interaction between ORF66 and ORF34 occurred in a zinc-dependent manner. Our data support a model, in which ORF66 serves as a critical vPIC component to promote late viral gene expression and viral production.

IMPORTANCE

KSHV ORF66, a late gene product, and vPIC are thought to contribute significantly to late gene expression during the lytic replication. However, the physiological importance of ORF66 in terms of viral replication and vPIC formation remains poorly understood. Therfore, we generated a ORF66-deficient BAC clone and evaluated its viral replication. Results showed that ORF66 played a critical role in virus production and the transcription of L genes. To our knowledge, this is the first report showing ORF66 function in virus replication using ORF66-deficient KSHV. We also clarified that ORF66 interacted with the transcription start site ofK8.1gene, a late gene. Furthermore, we identified the ORF34-binding motifs in the ORF66 C-terminus: three C-X-X-C sequences and a leucine-repeat sequence, which are highly conserved among β- and γ-herpesviruses. Our study provides insights into the regulatory mechanisms of not only the late gene expression of KSHV but also those of other herpesviruses.
The PRMT7-dependent methylation of shank2 modulates invasion-proliferation switching during breast cancer metastasis
Authors: Liu Yingqi , Liu Xiaoqing , Liu Lingxia , Wang Yibo , Peng Lu , Liu Jiayuan , Li Lingling , Zhang Lian , Wang Guannan , Li Honghuan , Liu Dongxu , Huang Baiqu , Lu Jun , Zhang Yu
Published: August 2019

Invasiveness of cancer cells is associated with proliferation inhibition in multiple types of cancers. Here, we identified the pivotal roles of Arginine methyltransferase PRMT7 in promoting invasion and attenuating proliferation of breast cancer cells. PRMT7 exerted its functions through binding to the scaffold protein shank2 to induce the di-methylation of shank2 at R240. Shank2 R240 methylation exposed ANK domain by disrupting its SPN-ANK domain blockade. Moreover, shank2 R240 methylation rendered recruitment of FAK that elicited the FAK auto-phosphorylation, which consequently augmented the shank2-dependent migration and invasion of breast cancer cells. On the other hand, the shank2 R240 methylation impeded proliferation of breast cancer cells by antagonizing the Ras-Raf binding via tethering the mono-ubiquitinated H-Ras. These findings characterize the PRMT7-dependent shank2 methylation as a key player in mediating reciprocal switching between invasion and proliferation, also point to the value of shank2 R240 methylation as a target for tumour metastasis treatment strategies.
The Gene Expression Deconvolution Interactive Tool (GEDIT): Accurate Cell Type Quantification from Gene Expression Data
Authors: Nadel Brian B. , Lopez David , Montoya Dennis J. , Ma Feiyang , Waddel Hannah , Khan Misha M. , Mangul Serghei , Pellegrini Matteo
Published: August 2019

The cell type composition of heterogeneous tissue samples can be a critical variable in both clinical and laboratory settings. However, current experimental methods of cell type quantification (e.g. cell flow cytometry) are costly, time consuming, and can introduce bias. Computational approaches that infer cell type abundance from expression data offer an alternate solution. While these methods have gained popularity, most are limited to predicting hematopoietic cell types and do not produce accurate predictions for stromal cell types. Many of these methods are also limited to particular platforms, whether RNA-seq or specific microarrays. We present the Gene Expression Deconvolution Interactive Tool (GEDIT), a tool that overcomes these limitations, compares favorably with existing methods, and provides superior versatility. Using both simulated and experimental data, we extensively evaluate the performance of GEDIT and demonstrate that it returns robust results under a wide variety of conditions. These conditions include a variety of platforms (microarray and RNA-seq), tissue types (blood and stromal), and species (human and mouse). Finally, we provide reference data from eight sources spanning a wide variety of stromal and hematopoietic types in both human and mouse. This reference database allows the user to obtain estimates for a wide variety of tissue samples without having to provide their own data. GEDIT also accepts user submitted reference data, thus allowing the estimation of any cell type or subtype, provided that reference data is available.

Author Summary

The Gene Expression Deconvolution Interactive Tool (GEDIT) is a robust and accurate tool that uses gene expression data to estimate cell type abundances. Extensive testing on a variety of tissue types and technological platforms demonstrates that GEDIT provides greater versatility than other cell type deconvolution tools. GEDIT utilizes reference data describing the expression profile of purified cell types, and we provide in the software package a library of reference matrices from various sources. GEDIT is also flexible and allows the user to supply custom reference matrices. A GUI interface for GEDIT is available at http://webtools.mcdb.ucla.edu/, and source code and reference matrices are available at https://github.com/BNadel/GEDIT.
When two mindfulnesses meet
Authors: Lakatos Louis , Turcotte Josée , Oddson Bruce
Published: August 2019

The study of mindfulness proceeds from a number of perspectives. Two of the best-known academic conceptualizations of mindfulness are those identified with Kabat-Zinn and Langer. These conceptions, meditative and socio-cognitive, have been built from different foundations and have been argued to be quite distinct. However, Hart, Ivtzan and Hart1suggested that self-regulation of attention is a mediator between the two. To put this hypothesis to a test, a convenience sample of participants (n = 208) were asked to complete the Five Facet Mindfulness Questionnaire (FFMQ), Langer Mindfulness Scale (LMS), and the Self-Regulation Scale (SRS), a measure of the self-regulation of attention. These three dispositional measures were shown to be correlated. Self-regulation passes a statistical test for partial mediation of the relationship between the two measures of mindfulness. This suggests that reliance on the capacity to regulate attention in pursuit of a goal is shared by these two approaches to mindfulness. However, there is no clear conceptual basis for mediation in either particular direction. Further, the correlation between the LMS and FFMQ is highest for those with the highest SRS scores; we discuss the implications for conceptual distinctions within mindfulness.
Rapid computation of rotary derivatives for subsonic and low transonic flows
Authors: Fu Jian-Ming , Tang Hai-Min , Chen Hong-Quan
Published: August 2019

Purpose

The purpose of this paper is to develop a new approach for rapid computation of subsonic and low-transonic rotary derivatives with the available steady solutions obtained by Euler computational fluid dynamics (CFD) codes.

Design/methodology/approach

The approach is achieved by the perturbation on the steady-state pressure of Euler CFD codes. The resulting perturbation relation is established at a reference Mach number between rotary derivatives and normal velocity on surface due to angular velocity. The solution of the reference Mach number is generated technically by Prandtl–Glauert compressibility correction based on any Mach number of interest under the assumption of simple strip theory. Rotary derivatives of any Mach number of interest are then inversely predicted by the Prandtl–Glauert rule based on the reference Mach number aforementioned.

Findings

The resulting method has been verified for three typical different cases of the Basic Finner Reference Projectile, the Standard Dynamics Model Aircraft and the Orion Crew Module. In comparison with the original perturbation method, the performance at subsonic and low-transonic Mach numbers has significantly improved with satisfactory accuracy for most design efforts.

Originality/value

The approach presented is verified to be an efficient way for computation of subsonic and low-transonic rotary derivatives, which are performed almost at the same time as an accounting solution of steady Euler equations.
A formulation of membrane finite elements with true drilling rotation
Authors: Boutagouga Djamel
Published: August 2019

Purpose

This paper aims to describe the formulation of a displacement-based triangular membrane finite element with true drilling rotational degree of freedom (DOF).

Design/methodology/approach

The presented formulation incorporates the true drilling rotation provided by continuum mechanics into the displacement field by way of using the polynomial interpolation. Unlike the linked interpolation, that uses a geometric transformation between displacement and vertex rotations, in this work, the interpolation of the displacement field in terms of nodal drilling rotations is obtained following an unusual approach that does not imply any presumed geometric transformation.

Findings

New relationship linking the mid-side normal displacement to corner node drilling rotations is derived. The resulting new element with true drilling rotation is compatible and does not include any problem-dependent parameter that may influence the results. The spurious zero-energy mode is stabilized in a careful way that preserves the true drilling rotational degrees of freedom (DOFs).

Originality/value

Several works dealing with membrane elements with vertex rotational DOFs have been published with improved convergence rate, however, owing to the need for incorporating rotations in the finite element meshes involving solids, shells and beam elements, having finite elements with true drilling rotational DOFs is more appreciated.
A global sensitivity analysis-assisted sequential optimization tool for plant-fin heat sink design
Authors: Li Enying , Zhou Zheng , Wang Hu , Cai Kang
Published: August 2019

Purpose

This study aims to suggest and develops a global sensitivity analysis-assisted multi-level sequential optimization method for the heat transfer problem.

Design/methodology/approach

Compared with other surrogate-assisted optimization methods, the distinctive characteristic of the suggested method is to decompose the original problem into several layers according to the global sensitivity index. The optimization starts with the several most important design variables by the support vector regression-based efficient global optimization method. Then, when the optimization process progresses, the filtered design variables should be involved in optimization one by one or the setting value. Therefore, in each layer, the design space should be reduced according to the previous optimization result. To improve the accuracy of the global sensitivity index, a novel global sensitivity analysis method based on the variance-based method incorporating a random sampling high-dimensional model representation is introduced.

Findings

The advantage of this method lies in its capability to solve complicated problems with a limited number of sample points. Moreover, to enhance the reliability of optimum, the support vector regression-based global efficient optimization is used to optimize in each layer.

Practical implications

The developed optimization tool is built by MATLAB and can be integrated by commercial software, such as ABAQUS and COMSOL. Lastly, this tool is integrated with COMSOL and applied to the plant-fin heat sink design. Compared with the initial temperature, the temperature after design is over 49°. Moreover, the relationships among all design variables are also disclosed clearly.

Originality/value

The D-MORPH-HDMR is integrated to obtain the coupling relativities among the design variables efficiently. The suggested method can be decomposed into multiplier layers according to the GSI. The SVR-EGO is used to optimize the sub-problem because of its robustness of modeling.