bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual dimorphism in Belostoma angustum Lauck (Insecta: Heteroptera: Belostomatidae) may be related to paternal care
Authors: Lopes Cassiane Furlan , Stefanello Fabiano , Bugs Christian , Stenert Cristina , Maltchik Leonardo , Ribeiro José Ricardo Inacio
Published: November 2019

The structures involved in parental care are often dimorphic. Female Belostoma angustum water bugs lay eggs on the hemelytra of their mates, where the eggs are brooded until hatching. Males use their hind legs to carry, aerate and protect the eggs. After controlling for covariance between variables, we fitted a series of structural equation models (SEMs) and evaluated the existence of sexual dimorphism in the size of the body and hind legs, in the shape and centroid size of the hemelytrum, and among the static allometry slopes of the size-related differences. Landmarks were used to capture phenotypic variation, by eliminating all non-shape variations with a Procrustes superimposition. Neither the shape of the hemelytrum nor its centroid size was related significantly to the aforementioned linear body measurements. Instead, the differences in the size of the hind legs were mediated by body dimensions only in males. We also found that males were wider and had longer heads than females, according to the SEM intercept values. Our findings suggest that sexual dimorphism in B. angustum may be related to a balance between sexual role reversal and viability costs.
Knowledge Exchange and Social Capital for Freshwater Ecosystem Assessments
Authors: Kuehne Lauren M , Strecker Angela L , Olden Julian D
Published: November 2019

The 1972 Clean Water Act (CWA) provided crucial environmental protections, spurring research and corresponding development of a network of expertise that represents critical human capital in freshwater conservation. We used social network analysis to evaluate collaboration across organizational types and ecosystem focus by examining connections between authors of freshwater assessments published since the CWA. We found that the freshwater assessment network is highly fragmented, with no trend toward centralization. Persistent cohesion around organizational subgroups and minimal bridging ties suggest the network is better positioned for diversification and innovation than for learning and building a strong history of linked expertise. Despite an abundance of research activity from university-affiliated authors, federal agency authors provide a majority of the bonding and bridging capital, and diverse agencies constitute the core network. Together, our results suggest that government agencies currently play a central role in sustaining the network of expertise in freshwater assessment, protection, and conservation.
Towards a natural history of schizophrenia
Authors: Vértes Petra E , Seidlitz Jakob
Published: November 2019

This scientific commentary refers to ‘Evolutionary modifications in human brain connectivity associated with schizophrenia’ by van den Heuvel et al. (doi:10.1093/brain/awz330).
Adult loss of Cacna1a in mice recapitulates childhood absence epilepsy by distinct thalamic bursting mechanisms
Authors: Miao Qing-Long , Herlitze Stefan , Mark Melanie D , Noebels Jeffrey L
Published: November 2019

Inborn errors of CACNA1A-encoded P/Q-type calcium channels impair synaptic transmission, producing early and lifelong neurological deficits, including childhood absence epilepsy, ataxia and dystonia. Whether these impairments owe their pathologies to defective channel function during the critical period for thalamic network stabilization in immature brain remains unclear. Here we show that mice with tamoxifen-induced adult-onset ablation of P/Q channel alpha subunit (iKOp/q) display identical patterns of dysfunction, replicating the inborn loss-of-function phenotypes and, therefore demonstrate that these neurological defects do not rely upon developmental abnormality. Unexpectedly, unlike the inborn model, the adult-onset pattern of excitability changes believed to be pathogenic within the thalamic network is non-canonical. Specifically, adult ablation of P/Q channels does not promote Cacna1g-mediated burst firing or T-type calcium current (IT) in the thalamocortical relay neurons; however, burst firing in thalamocortical relay neurons remains essential as iKOp/q mice generated on a Cacna1g deleted background show substantially diminished seizure generation. Moreover, in thalamic reticular nucleus neurons, burst firing is impaired accompanied by attenuated IT. Interestingly, inborn deletion of thalamic reticular nucleus-enriched, human childhood absence epilepsy-linked gene Cacna1h in iKOp/q mice reduces thalamic reticular nucleus burst firing and promotes rather than reduces seizure, indicating an epileptogenic role for loss-of-function Cacna1h gene variants reported in human childhood absence epilepsy cases. Together, our results demonstrate that P/Q channels remain critical for maintaining normal thalamocortical oscillations and motor control in the adult brain, and suggest that the developmental plasticity of membrane currents regulating pathological rhythmicity is both degenerate and age-dependent.
Re-Enchanting Nature and Medicine
Authors: Ridenour Autumn Alcott
Published: November 2019

Responding to Max Weber’s modern diagnosis of nature, science, and medicine as disenchanted, this article aims to reenvision nature and medicine with a sense of enchantment drawing from the Christian themes of creation, Christology, suffering, and redemption. By reenvisioning nature as enchanted with these theological themes, the vocation of medicine might be revitalized in terms of suffering presence, healing care, and works of mercy toward the neighbor in need.
Seasonal Influenza Vaccine Effectiveness in People With Asthma: A National Test-Negative Design Case-Control Study
Authors: Vasileiou Eleftheria , Sheikh Aziz , Butler Chris C , Robertson Chris , Kavanagh Kimberley , Englishby Tanya , Lone Nazir I , von Wissmann Beatrix , McMenamin Jim , Ritchie Lewis D , Schwarze Jürgen , Gunson Rory , Simpson Colin R
Published: November 2019

Background

Influenza infection is a trigger of asthma attacks. Influenza vaccination can potentially reduce the incidence of influenza in people with asthma, but uptake remains persistently low, partially reflecting concerns about vaccine effectiveness (VE).

Methods

We conducted a test-negative designed case-control study to estimate the effectiveness of influenza vaccine in people with asthma in Scotland over 6 seasons (2010/2011 to 2015/2016). We used individual patient–level data from 223 practices, which yielded 1 830 772 patient-years of data that were linked with virological (n = 5910 swabs) data.

Results

Vaccination was associated with an overall 55.0% (95% confidence interval [CI], 45.8–62.7) risk reduction of laboratory-confirmed influenza infections in people with asthma over 6 seasons. There were substantial variations in VE between seasons, influenza strains, and age groups. The highest VE (76.1%; 95% CI, 55.6–87.1) was found in the 2010/2011 season, when the A(H1N1) strain dominated and there was a good antigenic vaccine match. High protection was observed against the A(H1N1) (eg, 2010/2011; 70.7%; 95% CI, 32.5–87.3) and B strains (eg, 2010/2011; 83.2%; 95% CI, 44.3–94.9), but there was lower protection for the A(H3N2) strain (eg, 2014/2015; 26.4%; 95% CI, −12.0 to 51.6). The highest VE against all viral strains was observed in adults aged 18–54 years (57.0%; 95% CI, 42.3–68.0).

Conclusions

Influenza vaccination gave meaningful protection against laboratory-confirmed influenza in people with asthma across all seasons. Strategies to boost influenza vaccine uptake have the potential to substantially reduce influenza-triggered asthma attacks.
Machine Learning to Identify Persons at High-Risk of Human Immunodeficiency Virus Acquisition in Rural Kenya and Uganda
Authors: Balzer Laura B , Havlir Diane V , Kamya Moses R , Chamie Gabriel , Charlebois Edwin D , Clark Tamara D , Koss Catherine A , Kwarisiima Dalsone , Ayieko James , Sang Norton , Kabami Jane , Atukunda Mucunguzi , Jain Vivek , Camlin Carol S , Cohen Craig R , Bukusi Elizabeth A , Van Der Laan Mark , Petersen Maya L
Published: November 2019

Background

In generalized epidemic settings, strategies are needed to prioritize individuals at higher risk of human immunodeficiency virus (HIV) acquisition for prevention services. We used population-level HIV testing data from rural Kenya and Uganda to construct HIV risk scores and assessed their ability to identify seroconversions.

Methods

During 2013–2017, >75% of residents in 16 communities in the SEARCH study were tested annually for HIV. In this population, we evaluated 3 strategies for using demographic factors to predict the 1-year risk of HIV seroconversion: membership in ≥1 known “risk group” (eg, having a spouse living with HIV), a “model-based” risk score constructed with logistic regression, and a “machine learning” risk score constructed with the Super Learner algorithm. We hypothesized machine learning would identify high-risk individuals more efficiently (fewer persons targeted for a fixed sensitivity) and with higher sensitivity (for a fixed number targeted) than either other approach.

Results

A total of 75 558 persons contributed 166 723 person-years of follow-up; 519 seroconverted. Machine learning improved efficiency. To achieve a fixed sensitivity of 50%, the risk-group strategy targeted 42% of the population, the model-based strategy targeted 27%, and machine learning targeted 18%. Machine learning also improved sensitivity. With an upper limit of 45% targeted, the risk-group strategy correctly classified 58% of seroconversions, the model-based strategy 68%, and machine learning 78%.

Conclusions

Machine learning improved classification of individuals at risk of HIV acquisition compared with a model-based approach or reliance on known risk groups and could inform targeting of prevention strategies in generalized epidemic settings.

Clinical Trials Registration

NCT01864603.
Mitochondrial transplantation for myocardial protection in diabetic hearts
Authors: Doulamis Ilias P , Guariento Alvise , Duignan Thomas , Orfany Arzoo , Kido Takashi , Zurakowski David , del Nido Pedro J , McCully James D
Published: November 2019

OBJECTIVES

Type 2 diabetes causes mitochondrial dysfunction, which increases myocardial susceptibility to ischaemia–reperfusion injury. We investigated the efficacy of transplantation of mitochondria isolated from diabetic or non-diabetic donors in providing cardioprotection from warm global ischaemia and reperfusion in the diabetic rat heart.

METHODS

Ex vivo perfused hearts from Zucker diabetic fatty (ZDF fa/fa) rats (n = 6 per group) were subjected to 30 min of warm global ischaemia and 120 min reperfusion. Immediately prior to reperfusion, vehicle alone (VEH) or vehicle containing mitochondria isolated from either ZDF (MTZDF) or non-diabetic Zucker lean (ZL +/?) (MTZL) skeletal muscle were delivered to the coronary arteries via the aortic cannula.

RESULTS

Following 30-min global ischaemia and 120-min reperfusion, left ventricular developed pressure was significantly increased in MTZDF and MTZL groups compared to VEH group (MTZDF: 92.8 ± 5.2 mmHg vs MTZL: 110.7 ± 2.4 mmHg vs VEH: 44.3 ± 5.9 mmHg; P < 0.01 each); and left ventricular end-diastolic pressure was significantly decreased (MTZDF 12.1 ± 1.3 mmHg vs MTZL 8.6 ± 0.8 mmHg vs VEH: 18.6 ± 1.5 mmHg; P = 0.016 for MTZDF vs VEH and P < 0.01 for MTZL vs VEH). Total tissue ATP content was significantly increased in both MT groups compared to VEH group (MTZDF: 18.9 ± 1.5 mmol/mg protein/mg tissue vs MTZL: 28.1 ± 2.3 mmol/mg protein/mg tissue vs VEH: 13.1 ± 0.5 mmol/mg protein/mg tissue; P = 0.018 for MTZDF vs VEH and P < 0.01 for MTZL vs VEH). Infarct size was significantly decreased in the MT groups (MTZDF: 11.8 ± 0.7% vs MTZL: 9.9 ± 0.5% vs VEH: 52.0 ± 1.4%; P < 0.01 each).

CONCLUSIONS

Mitochondrial transplantation significantly enhances post-ischaemic myocardial functional recovery and significantly decreases myocellular injury in the diabetic heart.
Exploring health system readiness for adopting interventions to address intimate partner violence: a case study from the occupied Palestinian Territory
Authors: Colombini Manuela , Alkaiyat Abdulsalam , Shaheen Amira , Garcia Moreno Claudia , Feder Gene , Bacchus Loraine
Published: November 2019

Domestic violence (DV) against women is a widespread violation of human rights. Adoption of effective interventions to address DV by health systems may fail if there is no readiness among organizations, institutions, providers and communities. There is, however, a research gap in our understanding of health systems’ readiness to respond to DV. This article describes the use of a health system’s readiness assessment to identify system obstacles to enable successful implementation of a primary health-care (PHC) intervention to address DV in the occupied Palestinian Territory (oPT). This article describes a case study where qualitative methods were used, namely 23 interviews with PHC providers and key informants, one stakeholder meeting with 19 stakeholders, two health facility observations and a document review of legal and policy materials on DV in oPT. We present data on seven dimensions of health systems. Our findings highlight the partial readiness of health systems and services to adopt a new DV intervention. Gaps were identified in: governance (no DV legislation), financial resources (no public funding and limited staff and infrastructure) and information systems (no uniform system), co-ordination (disjointed referral network) and to some extent around the values system (tension between patriarchal views on DV and more gender equal norms). Additional service-level barriers included unclear leadership structure at district level, uncertain roles for front-line staff, limited staff protection and the lack of a private space for identification and counselling. Findings also pointed to concrete actions in each system dimension that were important for effective delivery. This is the first study to use an adapted framework to assess health system readiness (HSR) for implementing an intervention to address DV in low- and middle-income countries. More research is needed on HSR to inform effective implementation and scale up of health-care-based DV interventions.
Fighting the Hype for Predictors of Efficacy in Inflammatory Bowel Disease
Authors: Lopetuso Loris Riccardo , Gasbarrini Antonio
Published: November 2019

Primary or secondary nonresponse to anti-TNF–α due to immunogenicity or treatment-related side effects and the growing presence of innovative biological therapies targeting different cytokines and immune processes raise a clear need for predictors of efficacy for anti-TNF-α treatment.
On the Continuity of the Integrated Density of States in the Disorder
Authors: Shamis Mira
Published: November 2019

Recently, Hislop and Marx studied the dependence of the integrated density of states on the underlying probability distribution for a class of discrete random Schrödinger operators and established a quantitative form of continuity in weak* topology. We develop an alternative approach to the problem, based on Ky Fan inequalities, and establish a sharp version of the estimate of Hislop and Marx. We also consider a corresponding problem for continual random Schrödinger operators on $\mathbb{R}^d$.
Matrix Metalloproteinase-13 in Atherosclerotic Plaque Is Increased by Influenza A Virus Infection
Authors: Lee Han Sol , Noh Ji Yun , Shin Ok Sarah , Song Joon Young , Cheong Hee Jin , Kim Woo Joo
Published: November 2019

Background

Influenza virus infection triggers acute cardiovascular events. Several studies have demonstrated that influenza A virus infection was associated with immune cell influx and increased production of inflammatory cytokines in the atherosclerotic plaque lesion, but the underlying mechanism for these findings is not clear.

Methods

We examined the expression levels of matrix metalloproteinases (MMPs) by influenza A virus infection in human cells using quantitative real-time polymerase chain reaction, Western blot, and human MMP-13 enzyme-linked immunosorbent assay. In an animal study, protein expression in the plaque lesions of apolipoprotein E (ApoE)-deficient mice were analyzed by immunohistochemistry and Western blot.

Results

We confirmed that MMP-13 was increased in influenza A virus-infected cells. In the aorta of infected ApoE-deficient mice, MMP-13 was increased at 3 days after infection. Immunohistochemical staining results suggested that collagen was degraded in the MMP-13 expression area and that macrophages were the main source of MMP-13 expression. Furthermore, the expression of MMP-13 was regulated by influenza A virus through activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway.

Conclusions

In this study, we demonstrated that p38 MAPK-mediated MMP-13 expression by influenza A virus infection led to destabilization of vulnerable atherosclerotic plaques in the artery.
In vitro activity of a novel antibacterial agent, levonadifloxacin, against clinical isolates collected in a prospective, multicentre surveillance study in India during 2016–18
Authors: Appalaraju Boppe , Baveja Sujata , Baliga Shrikala , Shenoy Suchitra , Bhardwaj Renu , Kongre Vaishali , Dattatraya Gogi Suresh , Dhole Tapan , Verma Binita , Mukherjee D N , Gupta Shalini , Shanmugam Priyadarshini , Iravane Jyoti , Mishra Sudhi Ranjan , Barman Purabi , Chopra Shimpi , Hariharan Meenakshi , Surpam Rajendra , Pratap Rana , Joshi Prashant , Khande Hemant , Mane Ashish , Jain Rishi , Bhagwat Sachin
Published: November 2019

Background

Levonadifloxacin is a novel antibiotic belonging to the benzoquinolizine subclass of fluoroquinolones with potent activity against MRSA and quinolone-resistant Staphylococcus aureus. IV levonadifloxacin and its oral prodrug alalevonadifloxacin have recently been approved in India for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) including diabetic foot infections.

Objectives

To investigate the in vitro activity of levonadifloxacin against contemporary clinical isolates collected from multiple tertiary care hospitals across India in the Antimicrobial Susceptibility Profiling of Indian Resistotypes (ASPIRE) surveillance study.

Methods

A total of 1376 clinical isolates, consisting of staphylococci (n = 677), streptococci (n = 178), Enterobacterales (n = 320), Pseudomonas aeruginosa (n = 140) and Acinetobacter baumannii (n = 61), collected (2016–18) from 16 tertiary hospitals located across 12 states in India, were included in the study. The MICs of levonadifloxacin and comparator antibiotics were determined using the reference agar dilution method and broth microdilution method.

Results

Levonadifloxacin exhibited potent activity against MSSA (MIC50/90: 0.5/1 mg/L), MRSA (MIC50/90: 0.5/1 mg/L) and levofloxacin-resistant S. aureus (MIC50/90: 1/1 mg/L) isolates. Similarly, potent activity of levonadifloxacin was also observed against CoNS including MDR isolates (MIC50/90: 1/2 mg/L). Against Streptococcus pneumoniae, levonadifloxacin (MIC50/90: 0.5/0.5 mg/L) showed superior activity compared with levofloxacin (MIC50/90: 1/2 mg/L). Among levofloxacin-susceptible Enterobacterales, 80.6% of isolates were inhibited at ≤2 mg/L levonadifloxacin.

Conclusions

Levonadifloxacin displayed potent activity against contemporary MRSA and fluoroquinolone-resistant staphylococcal isolates, thus offering a valuable IV as well as an oral therapeutic option for the treatment of ABSSSIs. Furthermore, levonadifloxacin exhibited a broad-spectrum activity profile as evident from its activity against streptococci and levofloxacin-susceptible Gram-negative isolates.
Synergistic staphylocidal interaction of benzoic acid derivatives (benzoic acid, 4-hydroxybenzoic acid and β-resorcylic acid) and capric acid: mechanism and verification study using artificial skin
Authors: Kim H W , Seok Y S , Rhee M S
Published: November 2019

Objectives

The present study was designed to investigate a synergistic staphylocidal interaction of antimicrobials.

Methods

The widely used preservative benzoic acid (BzA) and its derivatives [4-hydroxybenzoic acid (HA) and β-resorcylic acid (β-RA)] combined with capric acid (CPA) were investigated.

Results

β-RA was identified as the most effective antimicrobial exhibiting synergistic action with CPA against both Staphylococcus aureus and MRSA. For example, a complete reduction of bacteria (>7.3 log reduction) was obtained within 5 min after treatment with 5.0 mM β-RA (0.079%) plus 0.20 mM CPA (0.004%), while treatment with each material individually showed low bactericidal effects (<1.5 log reduction). Flow cytometry analysis identified membrane disruption related to the synergistic mechanisms, including the following: (i) membrane disruption by CPA (69.2% of cells were damaged by 0.20 mM CPA treatment); (ii) antimicrobial entry through the damaged membrane; and (iii) cytoplasmic ion imbalance resulting in cell death. We verified that the synergistic combination was also effective against MRSA on artificial skin (99.989% elimination after 5 min).

Conclusions

We used only consumer-preferred natural-borne antimicrobials and a very small amount of material was needed based on the synergistic effects. Therefore, these antimicrobials can be widely used as alternative anti-MRSA compounds in healthcare products, cosmetics, pharmaceutical products, foods and for environmental hygiene.
Attractiveness of Pheromone Components With and Without the Synergist, Methyl (2E,4E,6Z)-2,4,6-Decatrienoate, to Brown Marmorated Stink Bug (Hemiptera: Pentatomidae)
Authors: Weber Donald C , Morrison William R , Khrimian Ashot , Rice Kevin B , Short Brent D , Herlihy Megan V , Leskey Tracy C
Published: November 2019

The brown marmorated stink bug, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) is attracted to its male-produced aggregation pheromone, a ~3.5:1 mixture of (3S,6S,7R,10S)- and (3R,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol (SSRS and RSRS respectively), and also to the pheromone of its Asian sympatric species Plautia stali Scott (Hemiptera: Pentatomidae), methyl (2E,4E,6Z)-2,4,6-decatrienoate (MDT). A stereoisomeric mixture of (7R) 10,11-epoxy-1-bisabolen-3-ols (= mixed murgantiols) is used together in commercialized products with MDT because the latter is a synergist for H. halys attraction to mixed murgantiols. However, the optimal ratio for MDT combination with mixed murgantiols, and the sensitivity of bug captures to variation in ratio of the two pheromone components, have not been tested to date. Using black pyramid traps at two sites (in Maryland and West Virginia, United States), different ratios of mixed murgantiols to MDT were tested over two entire seasons. Also, captures using various ratios of the two active pheromone stereoisomers were undertaken in month-long trials with and without MDT. Results showed that H. halys adult and nymphal captures were relatively insensitive to the ratio of synthetic pheromone (mixed murgantiols) to MDT, as long as each was present in the trap. Captures of adults and nymphs were responsive to the lure loading of the SSRS isomer, but relatively insensitive to levels of the minor component, RSRS. The relative insensitivity of H. halys to these attractant ratios gives flexibility to development of more cost-efficient synthesis and trapping as well as other semiochemical-based management tactics.
Lethal Images: Analyzing Extremist Visual Propaganda from ISIS and Beyond
Authors: Baele Stephane J , Boyd Katharine A , Coan Travis G
Published: November 2019

Violent extremist groups regularly use pictures in their propaganda. This practice, however, remains insufficiently understood. Conceptualizing visual images as amplifiers of narratives and emotions, the present article offers an original theoretical framework and measurement method for examining the synchronic and diachronic study of the manipulative use of images by violent extremist groups. We illustrate this framework and method with a systematic analysis of the 2,058 pictures contained in the Islamic State's propaganda magazines targeting Western audiences, exposing the “visual style” of the group, and highlighting the trends and shifts in the evolution of this style following developments on the ground.
DNA barcoding reveals that injected transgenes are predominantly processed by homologous recombination in mouse zygote
Authors: Smirnov Alexander , Fishman Veniamin , Yunusova Anastasia , Korablev Alexey , Serova Irina , Skryabin Boris V , Rozhdestvensky Timofey S , Battulin Nariman
Published: November 2019

Mechanisms that ensure repair of double-strand DNA breaks (DSBs) are instrumental in the integration of foreign DNA into the genome of transgenic organisms. After pronuclear microinjection, exogenous DNA is usually found as a concatemer comprising multiple co-integrated transgene copies. Here, we investigated the contribution of various DSB repair pathways to the concatemer formation. We injected mouse zygotes with a pool of linear DNA molecules carrying unique barcodes at both ends and obtained 10 transgenic embryos with 1–300 transgene copies. Sequencing the barcodes allowed us to assign relative positions to the copies in concatemers and detect recombination events that occurred during integration. Cumulative analysis of approximately 1,000 integrated copies reveals that over 80% of them underwent recombination when their linear ends were processed by synthesis-dependent strand annealing (SDSA) or double-strand break repair (DSBR). We also observed evidence of double Holliday junction (dHJ) formation and crossing over during the concatemer formations. Sequencing indels at the junctions between copies shows that at least 10% of DNA molecules introduced into the zygotes are ligated by non-homologous end joining (NHEJ). Our barcoding approach, verified with Pacific Biosciences Single Molecule Real-Time (SMRT) long-range sequencing, documents high activity of homologous recombination after DNA microinjection.
Atypical organizations and epistatic interactions of CRISPRs and cas clusters in genomes and their mobile genetic elements
Authors: Bernheim Aude , Bikard David , Touchon Marie , Rocha Eduardo P C
Published: November 2019

Prokaryotes use CRISPR–Cas systems for adaptive immunity, but the reasons for the frequent existence of multiple CRISPRs and cas clusters remain poorly understood. Here, we analysed the joint distribution of CRISPR and cas genes in a large set of fully sequenced bacterial genomes and their mobile genetic elements. Our analysis suggests few negative and many positive epistatic interactions between Cas subtypes. The latter often result in complex genetic organizations, where a locus has a single adaptation module and diverse interference mechanisms that might provide more effective immunity. We typed CRISPRs that could not be unambiguously associated with a cas cluster and found that such complex loci tend to have unique type I repeats in multiple CRISPRs. Many chromosomal CRISPRs lack a neighboring Cas system and they often have repeats compatible with the Cas systems encoded in trans. Phages and 25 000 prophages were almost devoid of CRISPR–Cas systems, whereas 3% of plasmids had CRISPR–Cas systems or isolated CRISPRs. The latter were often compatible with the chromosomal cas clusters, suggesting that plasmids can co-opt the latter. These results highlight the importance of interactions between CRISPRs and cas present in multiple copies and in distinct genomic locations in the function and evolution of bacterial immunity.
PELP1 promotes glioblastoma progression by enhancing Wnt/β-catenin signaling
Authors: Sareddy Gangadhara R , Pratap Uday P , Viswanadhapalli Suryavathi , Venkata Prabhakar Pitta , Nair Binoj C , Krishnan Samaya Rajeshwari , Zheng Siyuan , Gilbert Andrea R , Brenner Andrew J , Brann Darrell W , Vadlamudi Ratna K
Published: November 2019

Background

Glioblastoma (GBM) is a deadly neoplasm of the central nervous system. The molecular mechanisms and players that contribute to GBM development is incompletely understood.

Methods

The expression of PELP1 in different grades of glioma and normal brain tissues was analyzed using immunohistochemistry on a tumor tissue array. PELP1 expression in established and primary GBM cell lines was analyzed by Western blotting. The effect of PELP1 knockdown was studied using cell proliferation, colony formation, migration, and invasion assays. Mechanistic studies were conducted using RNA-seq, RT-qPCR, immunoprecipitation, reporter gene assays, and signaling analysis. Mouse orthotopic models were used for preclinical evaluation of PELP1 knock down.

Results

Nuclear receptor coregulator PELP1 is highly expressed in gliomas compared to normal brain tissues, with the highest expression in GBM. PELP1 expression was elevated in established and patient-derived GBM cell lines compared to normal astrocytes. Knockdown of PELP1 resulted in a significant decrease in cell viability, survival, migration, and invasion. Global RNA-sequencing studies demonstrated that PELP1 knockdown significantly reduced the expression of genes involved in the Wnt/β-catenin pathway. Mechanistic studies demonstrated that PELP1 interacts with and functions as a coactivator of β-catenin. Knockdown of PELP1 resulted in a significant increase in survival of mice implanted with U87 and GBM PDX models.

Conclusions

PELP1 expression is upregulated in GBM and PELP1 signaling via β-catenin axis contributes to GBM progression. Thus, PELP1 could be a potential target for the development of therapeutic intervention in GBM.
Dynamics and manipulation of ferroelectric domain walls in bismuth ferrite thin films
Authors: Xiao Shuyu , Jin Yaming , Lu Xiaomei , Cheong Sang-Wook , Li Jiangyu , Li Yang , Huang Fengzhen , Zhu Jinsong
Published: November 2019

Ferroelectric domain walls differ from domains not only in their crystalline and discrete symmetry, but also in their electronic, magnetic, and mechanical properties. Although domain walls provide a degree of freedom to regulate the physical properties at the nanoscale, the relatively lower controllability prevents their practical applications in nano-devices. In this work, with the advantages of 3D domain configuration detection based on piezoresponse force microscopy, we find that the mobility of three types of domain walls (tail-to-tail, head-to-tail, head-to-head) in (001) BiFeO3 films varies with the applied electrical field. Under low voltages, head-to-tail domain walls are more mobile than other domain walls, while, under high voltages, tail-to-tail domain walls become rather active and possess relatively long average lengths. This is due to the high nucleation energy and relatively low growth energy for charged domain walls. Finally, we demonstrate the manipulation of domain walls through successive electric writings, resulting in well-aligned conduction paths as designed, paving the way for their application in advanced spintronic, memory and communication nano-devices.
Trillions and Trillions: Herpes Simplex Virus–1 Hepatitis in an Immunocompetent Adult
Authors: Ikuta Kevin , Roychoudhury Pavitra , Xie Hong , Mcclurkan Christopher L , Walkiewicz Magdalena , Makhsous Negar , Huang Meei-Li , Beru Yodit , Alam Mariam , Shepherd Amanda , Lamotte Eric D , Patel Kevin , Morris Amy , Ҫoruh Başak , Yu Lei , Bhattacharya Renuka , Cheng Rex , Walter Roland B , Limaye Ajit P , Lockwood Christina M , Holland Steven M , Rakita Robert M , Koelle David M , Greninger Alexander L
Published: November 2019

We describe a case of acute liver failure and myopericarditis due to herpes simplex virus–1 (HSV-1) in an immunocompetent adult. We estimate that, at the height of viremia, the patient contained a quantity of HSV-1 virions approaching that of human cells. The patient recovered with acyclovir that was dose-adjusted for neurotoxicity and developed a vigorous anti-HSV-1 T-cell response.
Property studies of “loner” flares of gamma-ray blazars
Authors: Wang Gege , Wang Zhongxiang , Chen Liang , Zhou Jianeng , Xing Yi
Published: November 2019

We search through $\gamma$-ray data obtained with the Large Area Telescope (LAT) onboard the Fermi Gamma-Ray Space Telescope and find 24 blazars (or candidates) that have a single clear flare event in their 9.5 yr long-term light curves. We define these events as loner flares since each flare stands out significantly above the relatively stable, low-flux light curve. We analyze the LAT data in detail for these 24 sources. The flares in 10 of them are primarily due to a single sharp peak, for which we study by fitting with two different analytic functions. The time durations thus determined for the sharp peaks are in a range of 4–$25\:$d. The $\gamma$-ray spectra of the 24 blazar sources can be described with a power-law or a log-parabola function. We obtain their spectral properties in the flaring and quiescent states, and find that in the flares 16 of the sources have harder emission, three have softer emission, and the other five keep the same emission. We discuss a possible correlation between the differences in photon index in the quiescent and flaring states and photon indices in quiescence. In addition, the sharp peak flares seem to have a tendency of having long time durations and hard emission, possibly related to their physical origin in a blazar jet. Studies of more similar flares will help establish these possible features.
From Bede to Wyclif: The Knowledge of Old English within the Context of Late Middle English Biblical Translation and Beyond
Authors: Solopova Elizabeth
Published: November 2019

The continuity between Old and Middle English periods has been a matter of interest and debate in the field of medieval studies. Though it is widely accepted that Old English texts continued to be copied and used in the twelfth and thirteenth centuries, the possibility that they were collected, read and studied, and influenced scholars and religious thinkers in late medieval England is often rejected as implausible. The reason most commonly given is the difficulty of understanding the Old English language in the late Middle Ages. The present article aims to reassess this view and re-examine evidence for the reading and use of Old English texts in the fourteenth and fifteenth centuries with a primary focus on biblical translation. The article explores the possibility that Middle English glosses that occur in Old English sermon and biblical manuscripts reflect a scholarly interest in these texts, rather than a struggle to understand their language. The article also examines evidence that the translators of the Wycliffite Bible may have had some familiarity with Old English biblical translations, possibly as a result of study of biblical and sermon manuscripts.
Net protein contribution of beef feedlots from 2006 to 2017
Authors: Baber Jessica R , Sawyer Jason E , Holland Ben P , Karr Kendall J , Word Alyssa B , Wickersham Tryon A
Published: November 2019

Feedlot efficiency increases as technologies are adopted and new feed ingredients, especially byproducts, become available and incorporated into diets. Byproduct availability increased in response to the renewable fuels standard of 2005, creating substantial amounts of feedstuffs best used by ruminants. Cereal grains have been partially replaced with human-inedible byproducts, as they provide comparable levels of energy in cattle diets. To evaluate the effects of changes in diet and feedlot production practices on net protein contribution (NPC) and human-edible protein conversion efficiency (HePCE) across time, a deterministic NPC model was used. NPC was assessed for the feedlot industry using lot level production data from 2006 to 2017 for eight commercial feedlots. Ingredient and nutrient composition was collected for a representative starter and finisher diet fed for each year from each feedlot. NPC was calculated by multiplying human-edible protein (HeP) in beef produced per unit of HeP in feed by the protein quality ratio (PQR). Systems with NPC >1 positively contribute to meeting human protein requirements; NPC < 1 indicates competition with humans for HeP. NPC was regressed on year to evaluate temporal change in NPC. Feedlots were categorized as increasing NPC (INC; slope > 0) or constant NPC (CON; slope = 0) according to regression parameter estimates. Four feedlots were categorized as INC and four were CON. The rate of change in PQR was similar for CON and INC (P ≥ 0.79), although rates of change among INC and CON differed for byproduct and cereal grain inclusion (P ≤ 0.01) across years evaluated. Feedlots categorized as INC reduced HeP consumed by 2.39% per year, but CON feedlots did not reduce HeP consumed each year (0.28%). Cattle received and shipped by INC were lighter than those in CON feedlots (P < 0.01). Across years, INC produced more HeP (20.9 vs. 19.2 kg/hd) than CON (P < 0.01), and both feedlot types tended to improve HeP gained over time (0.1 kg per year; P = 0.10). Differences in slope over time for INC and CON were observed for conversion efficiency of HeP (P < 0.01). NPC increased 0.027 units per year for INC (P < 0.01) and was 0.94 in 2017. NPC by the feedlot sector improved from 2006 to 2017, decreasing the amount of human-edible feeds required to produce more high-quality protein from beef.
Temporal dynamics of learning‐promoted synaptic diversity in CA1 pyramidal neurons
Authors: Sakimoto Yuya , Kida Hiroyuki , Mitsushima Dai
Published: November 2019

Although contextual learning requires plasticity at both excitatory and inhibitory (E/I) synapses in cornu ammonis 1 (CA1) neurons, the temporal dynamics across the neuronal population are poorly understood. Using an inhibitory avoidance task, we analyzed the dynamic changes in learning‐induced E/I synaptic plasticity. The training strengthened GABAA receptor‐mediated synapses within 1 min, peaked at 10 min, and lasted for over 60 min. The intracellular loop (Ser408‐409) of GABAA receptor β3 subunit was also phosphorylated within 1 min of training. As the results of strengthening of α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate receptor‐mediated synapses, CA1 pyramidal neurons exhibited broad diversity of E/I synaptic currents within 5 min. Moreover, presynaptic glutamate release probability at basal dendrites also increased within 5 min. To further quantify the diversified E/I synaptic currents, we calculated self‐entropy (bit) for individual neurons. The neurons showed individual levels of the parameter, which rapidly increased within 1 min of training and maintained for over 60 min. These results suggest that learning‐induced synaptic plasticity is critical immediately following encoding rather than during the retrieval phase of the learning. Understanding the temporal dynamics along with the quantification of synaptic diversity would be necessary to identify a failure point for learning‐promoted plasticity in cognitive disorders.—Sakimoto, Y., Kida, H., Mitsushima, D. Temporal dynamics of learning‐promoted synaptic diversity in CA1 pyramidal neurons. FASEB J. 33, 14382‐14393 (2019). www.fasebj.org
What the Radiologist Needs to Know About Breast Trauma
Authors: Goldbach Alyssa R. , Hava Sana , Pascarella Suzanne
Published: November 2019

The breast is injured in a variety of circumstances, including direct trauma, such as from a motor vehicle accident, or iatrogenic, secondary to biopsy or intervention. The severity of reported breast injuries ranges from small hematomas to breast avulsion; the latter injury requires emergent mastectomy to stop active hemorrhage.1 The correlation of multimodality breast imaging with clinical presentation is important for differentiating benign posttraumatic abnormalities from malignant processes, thereby preventing unnecessary workup and intervention.
Systemic biomarkers of eosinophilic chronic rhinosinusitis
Authors: Ho Jacqueline , Earls Peter , Harvey Richard J.
Published: November 2019

Purpose of review

The current understanding of eosinophilic chronic rhinosinusitis (CRS) has developed rapidly over the past decades. Classification of CRS based on the inflammatory endotype more accurately reflects the underlying pathophysiology and better directs treatment. Corticosteroids and more recently biologic agents, target the eosinophil inflammatory that drives this subtype of CRS. Tissue sampling is not always accessible or available and surrogate markers are sought to define this endotype of CRS. The purpose of this review is to assess current systemic predictors of eosinophilic CRS (eCRS) diagnosis.

Recent findings

Blood eosinophils are a moderate surrogate predictor of eCRS. A blood eosinophil count of more than 0.24 × 109/l predicts eCRS with tissue eosinophilia of more than 10 eosinophils per high-power field. It has been further shown that a blood eosinophil count more than 0.45 × 109/l is associated with need for long-term systemic therapy following endoscopic sinus surgery. Other biomarkers reviewed include IgE, eosinophilic cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, IL-5, periostin, eotaxin-3 and IL-16.

There remains limited data surrounding the prognostic use of biomarkers in eCRS. However, peripheral eosinophilia best predicts the eosinophilic density that best predicts the eCRS phenotype. In addition, it is also prognostic of need for more intensive therapy. Simple haematoxylin and eosin stained sinus mucosa still remains the most reliable tissue for assessment and is more accessible than bronchial biopsies
Fascial plane blocks in thoracic surgery: a new era or plain painful?
Authors: Marciniak Donn , Kelava Marta , Hargrave Jennifer
Published: November 2019

Purpose of review

The demand for well-tolerated, effective, and opioid reducing pain management has become imperative in thoracic surgery. With the recent movement away from neuraxial analgesia for thoracic surgical patients, great interest in alternative analgesic techniques of the chest wall has developed. Multiple fascial plane blocks have been developed for pain management of the lateral chest wall and we present an up-to-date review of these popular new interventions.

Recent findings

The pectoralis and serratus anterior plane blocks may offer effective analgesia of the lateral chest wall for thoracic surgical patients. The erector spinae plane block may offer more extensive analgesic coverage but requires further investigation.

Fascial plane blocks hold the potential for well-tolerated and effective analgesia for thoracic surgical patients as part of a multimodal regimen of pain relief. However, many questions remain regarding block characteristics. As the literature matures, more formal recommendations will be made but quality trials are needed to provide this guidance.
Asymptomatic hyperuricemia: is it really asymptomatic?
Authors: Yip Kevin , Cohen Rebecca E. , Pillinger Michael H.
Published: November 2019

Purpose of review

Hyperuricemia is highly prevalent, affecting approximately 38 million individuals in the United States. However, the significance of asymptomatic hyperuricemia – hyperuricemia in the absence of gout – continues to be debated.

Recent findings

Asymptomatic hyperuricemia results in monosodium urate crystal deposition in tissues, which may promote chronic inflammation. Intracellularly, hyperuricemia inhibits the master regulator adenosine monophosphate (AMP)-associated protein kinase and may condition innate immune responses through durable epigenetic modifications. At the population level, asymptomatic hyperuricemia is associated with multiple comorbidities, including hypertension, chronic kidney disease, coronary artery disease, and diabetes; limitations of these studies include that most are retrospective and some do not rigorously distinguish between asymptomatic hyperuricemia and gout. Treatment studies suggest that urate lowering may reduce the risk of incidence or progression of some of these comorbidities; unfortunately, many of these treatment studies are small or flawed, and not all study results are consistent.

Accumulating evidence suggests that asymptomatic hyperuricemia contributes to the comorbidities with which it associates and that proper asymptomatic hyperuricemia treatment may reduce future risk. Additional prospective trials are needed to definitely establish causality and support decision-making as to whether, and which patients with asymptomatic hyperuricemia would warrant urate-lowering treatment.
Operative Treatment of Pediatric Pelvic and Acetabulum Fractures
Authors: de Ridder Victor A. , Olson Steven A.
Published: November 2019

Pediatric pelvic fractures are rare and differ from adults in etiology, fracture type, and associated injuries. They are observed in multitrauma patients, with severe associated injuries. Treatment of these children in specialized hospitals is likely to provide the best outcome because of the rarity of these fractures. Only a small percentage of the fractures, particularly the displaced ones, need operative treatment with the aim to restore the anatomy of the pelvic ring. In a significant proportion of the operated patients, morbidity and mortality were not linked to the pelvic fractures but to the other associated injuries. Long-term prognosis depends on restoring pelvic symmetry. Nondisplaced fractures of the acetabulum or fractures with minimal displacement with a relatively low roof–arc angle or crush injuries of the triradiate physis are managed nonoperatively. In young patients where continuation of growth is expected, fixation that does not cross the physis anatomically could be used. In some very young children, plate removal may be indicated to allow for continued growth of the acetabulum. One of the major complications in this patient cohort is acetabular dysplasia.
Prevalence and correlates of early-onset menopause among women living with HIV in Canada
Authors: Andany Nisha , Kaida Angela , de Pokomandy Alexandra , Yudin Mark H. , Wang Lu , Kennedy V. Logan , Webster Kath , Loutfy Mona
Published: November 2019

Objective:

Menopause is a pivotal transition for women. Previous studies have suggested increased risk of early menopause (40-45 years) and premature menopause (<40 years) for women with HIV. We aimed to determine age of menopause, prevalence of early menopause and premature menopause, and risk factors for menopause <45 years in Canadian women with HIV.

Methods:

This was a cross-sectional analysis from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study. Analyses were restricted to biologically female participants reporting being postmenopausal (regardless of etiology). Primary outcome was median age at menopause. Predetermined variables, and those with P < 0.10 in univariable analyses were considered for inclusion into multivariable logistic regression model, to determine independent correlates of menopause <45 years.

Results:

229 women were included. Median age of menopause was 48 years (interquartile range 43, 51); 29.7% of women experienced menopause <45 years: 16.6% with early menopause and 13.1% with premature menopause. In univariable analyses, menopause <45 years was more likely (P < 0.05) with birth in Canada, white ethnicity, less than high-school education, smoking, recreational drug use, and hepatitis C co-infection. In multivariable modeling, less than high-school education (adjusted odds ratio [aOR] 2.45, 95% confidence interval [CI] 1.22-4.93) and hepatitis C co-infection (aOR 1.90, 95% CI 1.04-3.50) were independently associated with menopause <45 years.

Conclusions:

In Canadian women with HIV, median age of menopause was 48 years; 3 years younger than the general population. Only lower education and hepatitis C co-infection were independently associated with menopause <45 years, highlighting importance of socioeconomic factors and comorbidities. These findings have implications for counseling and management of women with HIV.