bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic resistomes discovered in the gut microbiomes of Korean swine and cattle
Authors: Lim Suk-Kyung , Kim Dongjun , Moon Dong-Chan , Cho Youna , Rho Mina
Published: May 2020

Background

Antibiotics administered to farm animals have led to increasing prevalence of resistance genes in different microbiomes and environments. While antibiotic treatments help cure infectious diseases in farm animals, the possibility of spreading antibiotic resistance genes into the environment and human microbiomes raises significant concerns. Through long-term evolution, antibiotic resistance genes have mutated, thereby complicating the resistance problems.

Results

In this study, we performed deep sequencing of the gut microbiomes of 36 swine and 41 cattle in Korean farms, and metagenomic analysis to understand the diversity and prevalence of antibiotic resistance genes. We found that aminoglycoside, β-lactam, lincosamide, streptogramin, and tetracycline were the prevalent resistance determinants in both swine and cattle. Tetracycline resistance was abundant and prevalent in cattle and swine. Specifically, tetQ, tetW, tetO, tet32, and tet44 were the 5 most abundant and prevalent tetracycline resistance genes. Their prevalence was almost 100% in swine and cattle. While tetQ was similarly abundant in both swine and cattle, tetW was more abundant in swine than in cattle. Aminoglycoside was the second highest abundant resistance determinant in swine, but not in cattle. In particular, ANT(6) and APH(3′′) were the dominant resistance gene families in swine. β-lactam was also an abundant resistance determinant in both swine and cattle. Cfx was the major contributing gene family conferring resistance against β-lactams.

Conclusions

Antibiotic resistome was more pervasive in swine than in cattle. Specifically, prevalent antibiotic resistance genes (prevalence >50%) were found more in swine than in cattle. Genomic investigation of specific resistance genes from the gut microbiomes of swine and cattle in this study should provide opportunities to better understand the exchange of antibiotic resistance genes in farm animals.
Utilizing pre-polarization to enhance SNMR signals—effect of imperfect switch-off
Authors: Hiller Thomas , Dlugosch Raphael , Müller-Petke Mike
Published: May 2020

Surface nuclear magnetic resonance (SNMR) is a well-established technique for the hydrogeological characterization of the subsurface up to depths of about 150 m. Recently, SNMR has been adapted to investigate also the shallow unsaturated zone with small surface loop setups. Due to the decreased volume, a pre-polarization (PP) field prior to the classical spin excitation is applied to enhance the measured response signal. Depending on the strength and orientation of the applied PP-field, the enhancement can often reach several orders of magnitude in the vicinity of the PP-loop. The theoretically achievable enhancement depends on the assumption of an adiabatic, that is perfect, switch-off of the corresponding PP-field. To study the effect of imperfect switch-off, we incorporate full spin dynamics simulations into the SNMR forward modelling. The affected subsurface volume strongly depends on the chosen PP switch-off ramp and the geometry of the loop setup. Due to the imperfect switch-off, the resulting SNMR sounding curves can have significantly decreased signal amplitudes. For comparison, the signal amplitudes of either a 1 ms exponential or linear switch-off ramp are reduced by 17 and 65 per cent, respectively. Disregarding this effect would therefore yield an underestimation of the corresponding subsurface water content of similar magnitude.
Methods for the robust computation of the long-period seismic spectrum of broad-band arrays
Authors: Caton Ross C , Pavlis Gary L , Thomson David J , Vernon Frank L
Published: May 2020

We describe array methods to search for low signal-to-noise ratio (SNR) signals in long-period seismic data using Fourier analysis. This is motivated by published results that find evidence of solar free oscillations in the Earth's seismic hum. Previous work used data from only one station. In this paper, we describe methods for computing spectra from array data. Arrays reduce noise level through averaging and provide redundancy that we use to distinguish coherent signal from a random background. We describe two algorithms for calculating a robust spectrum from seismic arrays, an algorithm that automatically removes impulsive transient signals from data, a jackknife method for estimating the variance of the spectrum, and a method for assessing the significance of an entire spectral band. We show examples of their application to data recorded by the Homestake Mine 3-D array in Lead, SD and the Piñon Flats PY array. These are two of the quietest small aperture arrays ever deployed in North America. The underground Homestake data has exceptionally low noise, and the borehole sensors of the PY array also have very low noise, making these arrays well suited to finding very weak signals. We find that our methods remove transient signals effectively from the data so that even low-SNR signals in the seismic background can be found and tested. Additionally, we find that the jackknife variance estimate is comparable to the noise floor, and we present initial evidence for solar g-modes in our data through the T2 test, a multivariate generalization of Student's t-test.
Strategies used to establish palliative care in rural low- and middle-income countries: an integrative review
Authors: Aregay Atsede , O’Connor Margaret , Stow Jill , Ayers Nicola , Lee Susan
Published: May 2020

Globally, 40 million people need palliative care; about 69% are people over 60 years of age. The highest proportion (78%) of adults are from low- and middle-income countries (LMICs), where palliative care still developing and is primarily limited to urban areas. This integrative review describes strategies used by LMICs to establish palliative care in rural areas. A rigorous integrative review methodology was utilized using four electronic databases (Ovid MEDLINE, Ovid Emcare, Embase classic+Embase and CINAHL). The search terms were: ‘palliative care’, ‘hospice care’, ‘end of life care’, ‘home-based care’, ‘volunteer’, ‘rural’, ‘regional’, ‘remote’ and ‘developing countries’ identified by the United Nations (UN) as ‘Africa’, ‘Sub-Saharan Africa’, ‘low-income’ and ‘middle- income countries’. Thirty papers published in English from 1990 to 2019 were included. Papers were appraised for quality and extracted data subjected to analysis using a public health model (policy, drug availability, education and implementation) as a framework to describe strategies for establishing palliative care in rural areas. The methodological quality of the reviewed papers was low, with 7 of the 30 being simple programme descriptions. Despite the inclusion of palliative care in national health policy in some countries, implementation in the community was often reliant on advocacy and financial support from non-government organizations. Networking to coordinate care and medication availability near-patient homes were essential features of implementation. Training, role play, education and mentorship were strategies used to support health providers and volunteers. Home- and community-based palliative care services for rural LMICs communities may best be delivered using a networked service among health professionals, community volunteers, religious leaders and technology.
Circulating Rather Than Alveolar Extracellular Deoxyribonucleic Acid Levels Predict Outcomes in Influenza
Authors: Zhang Nannan , Zhu Liuluan , Zhang Yue , Zhou Chun , Song Rui , Yang Xiaoyu , Huang Linna , Xiong Shuyu , Huang Xu , Xu Fei , Wang Yajie , Wan Gang , Chen Zhihai , Li Ang , Zhan Qingyuan , Zeng Hui
Published: May 2020

Background

High levels of circulating neutrophil extracellular traps (NETs) are associated with a poor prognosis in influenza A infection. It remains unclear whether NETs in the plasma or bronchoalveolar lavage fluid (BALF) can predict clinical outcomes in influenza.

Methods

One hundred eighteen patients who were diagnosed with H1N1 influenza in 2017–2018 were recruited. The NETs were assessed in plasma and BALF samples by quantifying cell-free deoxyribonucleic acid (cfDNA) and protein-DNA complexes. Predictions of severe illness and 60-day mortality were analyzed with receiver operating characteristic curves.

Results

The NET levels were significantly elevated in the BALF and contributed to the pathology of lungs, yet it was not associated with disease severity or mortality in patients severely infected with H1N1. Plasma NET levels were significantly increased in the patients with severe influenza and positively correlated with the oxygen index and sequential organ failure assessment scores. High levels of plasma cfDNA (>286.6 ng/mL) or histone-bound DNA (>9.4 ng/mL) discriminated severe influenza from mild, and even higher levels of cfDNA (>306.3 ng/mL) or histone-bound DNA (>23.1 ng/mL) predicted fatal outcomes in severely ill patients.

Conclusions

The cfDNA and histone-bound DNA in plasma represent early predictive biomarkers for the prognosis of influenza.
Physical Function Impairment and Frailty in Middle-Aged People Living With Human Immunodeficiency Virus in the REPRIEVE Trial Ancillary Study PREPARE
Authors: Umbleja Triin , Brown Todd T , Overton Edgar T , Ribaudo Heather J , Schrack Jennifer A , Fitch Kathleen V , Douglas Pamela S , Grinspoon Steven K , Henn Sarah , Arduino Roberto C , Rodriguez Benigno , Benson Constance A , Erlandson Kristine M
Published: May 2020

Background

People with human immunodeficiency virus (PWH) are at risk for accelerated development of physical function impairment and frailty; both associated with increased risk of falls, hospitalizations, and death. Identifying factors associated with physical function impairment and frailty can help target interventions.

Methods

The REPRIEVE trial enrolled participants 40–75 years of age, receiving stable antiretroviral therapy with CD4+ T-cell count >100 cells/mm3, and with low to moderate cardiovascular disease risk. We conducted a cross-sectional analysis of those concurrently enrolled in the ancillary study PREPARE at enrollment.

Results

Among the 266 participants, the median age was 51 years; 81% were male, and 45% were black, and 28% had hypertension. Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was 25 to <30 in 38% and ≥30 in 30%, 33% had a high waist circumference, 89% were physically inactive, 37% (95% confidence interval, 31%, 43%) had physical function impairment (Short Physical Performance Battery score ≤10), and 6% (4%, 9%) were frail and 42% prefrail. In the adjusted analyses, older age, black race, greater BMI, and physical inactivity were associated with physical function impairment; depression and hypertension were associated with frailty or prefrailty.

Conclusions

Physical function impairment was common among middle-aged PWH; greater BMI and physical inactivity are important modifiable factors that may prevent further decline in physical function with aging.

Clinical Trials Registration

NCT02344290.
Lineage-Specific Expansion of Plasmodium falciparum Parasites With pfhrp2 Deletion in the Greater Mekong Subregion
Authors: Gibbons Justin , Qin Junling , Malla Pallavi , Wang Zenglei , Brashear Awtum , Wang Chengqi , Miao Jun , Adams John H , Kim Kami , Jiang Rays , Cui Liwang
Published: May 2020

Deletion of the pfhrp2 gene in Plasmodium falciparum can lead to false-negative rapid diagnostic test (RDT) results, constituting a major challenge for evidence-based malaria treatment. Here we analyzed the whole genome sequences of 138 P. falciparum clinical samples collected from the China-Myanmar boarder for pfhrp2 and pfhrp3 gene deletions. We found pfhrp2 and pfhrp3 deletions in 9.4% and 3.6% of samples, respectively, with no samples harboring deletions of both genes. The pfhrp2 deletions showed 2 distinct breakpoints, representing 2 different chromosomal deletion events. A phylogenetic analysis performed using genome-wide single-nucleotide polymorphisms revealed that the 2 pfhrp2 breakpoint groups as well as all the pfhrp3-negative parasites formed separate clades, suggesting they might have resulted from clonal expansion of pfhrp2- and pfhrp3-negative parasites. These findings highlight the need for urgent surveys to determine the prevalence of pfhrp2-negative parasites causing false-negative RDT results and a plan for switching of RDTs pending the survey results.
High-Throughput Screening of Kawasaki Disease Sera for Antiviral Antibodies
Authors: Quiat Daniel , Kula Tomasz , Shimizu Chisato , Kanegaye John T , Tremoulet Adriana H , Pitkowsky Zachary , Son MaryBeth , Newburger Jane W , Elledge Stephen J , Burns Jane C
Published: May 2020

Clinical features of Kawasaki disease (KD) display overlap with common pediatric viral illnesses, leading some to hypothesize that a viral infection is the inciting event for KD. To investigate viral infection history in KD patients, we performed comprehensive serological profiling using a high-throughput phage immunoprecipitation sequencing assay covering the complete reference protein sequences of known viruses with human tropism. KD and matched febrile control sera did not demonstrate differences in antiviral antibody profiles. We conclude that in the acute and subacute phases of disease, KD patients do not exhibit serologic evidence of exposure to known viruses that differs from controls.
Characterization of AmpC-hyperproducing Escherichia coli from humans and dairy farms collected in parallel in the same geographical region
Authors: Alzayn Maryam , Findlay Jacqueline , Schubert Hannah , Mounsey Oliver , Gould Virginia C , Heesom Kate J , Turner Katy M , Barrett David C , Reyher Kristen K , Avison Matthew B
Published: May 2020

Objectives

To characterize putative AmpC-hyperproducing third-generation cephalosporin-resistant E. coli from dairy farms and their phylogenetic relationships; to identify risk factors for their presence; and to assess evidence for their zoonotic transmission into the local human population.

Methods

Proteomics was used to explain differences in antimicrobial susceptibility. WGS allowed phylogenetic analysis. Multilevel, multivariable logistic regression modelling was used to identify risk factors.

Results

Increased use of amoxicillin/clavulanate was associated with an increased risk of finding AmpC hyperproducers on farms. Expansion of cephalosporin resistance in AmpC hyperproducers was seen in farm isolates with marR mutations (conferring cefoperazone resistance) or when AmpC was mutated (conferring fourth-generation cephalosporin and cefoperazone resistance). Phylogenetic analysis confirmed the dominance of ST88 amongst farm AmpC hyperproducers but there was no evidence for acquisition of farm isolates by members of the local human population.

Conclusions

Clear evidence was found for recent farm-to-farm transmission of AmpC-hyperproducing E. coli and of adaptive mutations to expand resistance. Whilst there was no evidence of isolates entering the local human population, efforts to reduce third-generation cephalosporin resistance on dairy farms must address the high prevalence of AmpC hyperproducers. The finding that amoxicillin/clavulanate use was associated with an increased risk of finding AmpC hyperproducers is important because this is not currently categorized as a highest-priority critically important antimicrobial and so is not currently targeted for specific usage restrictions in the UK.
Identification of Proteus genomic island 2 variants in two clonal Proteus mirabilis isolates with coexistence of a novel genomic resistance island PmGRI1
Authors: Lei Chang-Wei , Yao Tian-Ge , Yan Jia , Li Bo-Yang , Wang Xue-Chun , Zhang Yu , Gao Yu-Feng , Wang Hong-Ning
Published: May 2020

Objectives

To characterize the MDR genomic islands (GIs) in Proteus mirabilis isolates.

Methods

Two P. mirabilis strains (C55 and C74) of chicken origin were subjected to WGS (HiSeq and PacBio) and the MDR GIs were determined.

Results

P. mirabilis strains C55 and C74 are clonal strains and harbour different Proteus genomic island 2 (PGI2) variants (PGI2-C55 and PGI2-C74). The MDR region of PGI2-C55 is composed of two class 1 integrons, separated by a region containing seven copies of IS26 and eight resistance genes, including blaCTX-M-3 and fosA3. The region in PGI2-C74 is a complete In4-type class 1 integron, harbouring five gene cassettes (dfrA16, blaCARB-2, aadA2, cmlA1 and aadA1). In addition, C55 and C74 carry an SXT/R391 integrative and conjugative element (ICEPmiJpn1), harbouring blaCMY-2, and a novel 50.46 kb genomic resistance island named PmGRI1-C55. PmGRI1-C55 harbours a tyrosine-type recombinase/integrase that might be responsible for the integration of PmGRI1-C55 at the 3′ end of tRNA-Sec. It carries an MDR region derived from Tn2670 that harbours a Tn21 region and carries six resistance genes (catA1, blaTEM-1b, aphA1a, sul2, strA and strB). Blast analysis showed diverse PmGRI1 variants in P. mirabilis and Escherichia coli strains.

Conclusions

The finding of the two new PGI2 variants highlights that the homologous recombination between shared components of class 1 integrons and transposition by IS26 promote the diversity of MDR regions in PGI2. PmGRI1 is a new GI that carries various resistance genes identified in P. mirabilis and E. coli.
Effects of divergent selection for residual feed intake on nitrogen metabolism and lysine utilization in growing pigs
Authors: Hewitt Deltora J , Dekkers Jack C M , Antonick Treyson , Gheisari Abbasali , Rakhshandeh Amanda R , Rakhshandeh Anoosh
Published: May 2020

A study was conducted to evaluate the effects of divergent genetic selection for residual feed intake (RFI) on nitrogen (N) metabolism and lysine utilization in growing pigs. Twenty-four gilts (body weight [BW] 66 ± 5 kg) were selected from generation nine of the low RFI (LRFI; n = 12) and high RFI (HRFI; n = 12) Iowa State University Yorkshire RFI selection lines. Six pigs from each genetic line were assigned to each of two levels of lysine intake: 70% and 100% of estimated requirements based on the potential of each genetic line for protein deposition (PD) and feed intake. For all diets, lysine was first limiting among amino acids. Using isotope tracer, N-balance, and nutrient digestibility evaluation approaches, whole-body N metabolism and the efficiency of lysine utilization were determined for each treatment group. No significant interaction effects of line and diet on dietary N or gross energy digestibility, PD, and the efficiency of lysine utilization for PD were observed. The line did not have a significant effect on PD and digestibility of dietary N and GE. An increase in lysine intake improved N retention in both lines (from 15.0 to 19.6 g/d, SE 1.44, in LRFI pigs; and from 16.9 to 19.8 g/d, SE 1.67, in HRFI pigs; P < 0.01). At the low lysine intakes and when lysine clearly limited PD, the efficiency of using available lysine intake (above maintenance requirements) for PD was 80% and 91% (SE 4.6) for the LRFI and HRFI pigs, respectively (P = 0.006). There were no significant effects of line or of the line by diet interaction on N flux, protein synthesis, and protein degradation. Lysine intake significantly increased (P < 0.05) N flux (from 119 to 150, SE 8.7 g/d), protein synthesis (from 99 to 117, SE 10.6 g of N/d), and protein degradation (from 85 to 100, SE 6.6 g of N/d). The protein synthesis-to-retention ratio tended to be higher in the LRFI line compared with the HRFI line (6.5 vs. 5.8 SE 0.62; P = 0.06), indicating a tendency for the lower efficiency of PD in this group. Collectively, these results indicate that genetic selection for low RFI is not associated with improvements in lysine utilization efficiency, protein turnover, and nutrient digestibility.
Taxonomic revision of Aegla lata Bond-Buckup & Buckup, 1994 (Decapoda: Anomura: Aeglidae), with the description of a new species of Aegla Leach, 1820 from the Upper Paraná Ecoregion, Brazil
Authors: Marçal Ingrid C , Páez Fernanda P , Souza-Shibatta Lenice , Sofia Silvia H , Teixeira Gustavo M
Published: May 2020

Aegla lata Bond-Buckup & Buckup, 1994 is considered extinct in the type locality. New populations of this species, however, have been found in northern Paraná state, Brazil. We revised the taxonomy of A. lata based on morphological data obtained from the type material and specimens recently obtained from streams of the Tibagi River sub-basin, Paranapanema River basin, Upper Paraná Ecoregion. Moreover, Aegla jacutingan. sp. is described and illustrated. The new species resembles A. lata in the shapes of the body and chelipeds. Both species are nevertheless separated by particular morphological characters of the carapace, chelipeds, and epimeron as well as by molecular (COI mtDNA) differences. Both species can be distinguished from their congeners based on morphological and molecular evidence.
Host Suitability and Fitness-Related Parameters in Coptera haywardi (Hymenoptera: Diapriidae) Reared on Irradiated Ceratitis capitata (Diptera: Tephritidae) Pupae Stemming From the tsl Vienna-8 Genetic Sexing Strain
Authors: Núñez-Campero Segundo R , Suárez Lorena , Buonocore Biancheri María Josefina , Cancino Jorge , Murúa Fernando , Molina Diego , Laría Osvaldo , Aluja Martín , Ovruski Sergio M
Published: May 2020

Coptera haywardi (Ogloblin) is a pupal endoparasitoid of tephritid flies with great potential as a biological control agent worldwide as it does not attack other Diptera. To reach its full potential, its mass rearing needs to be enhanced lowering costs. Here, we focused on the use of irradiated pupae of Ceratitis capitata (Wiedemann) stemming from the temperature-sensitive lethal (tsl) Vienna-8 genetic sexing strain (= CcVienna-8), which is mass-produced in the San Juan Medfly and Parasitoid Mass Rearing Facility in Argentina. Exposure of 1- to 2-d-old CcVienna-8 pupae irradiated at 90 Gy to 6- to 8-d-old C. haywardi females at a 10:1 host/parasitoid ratio for 24 h turned out to be highly successful for the rearing of this parasitoid. High radiation doses (90–100 Gy) did not adversely influence fitness parameters of C. haywardi offspring F1, namely lifetime reproductive rates, adult life expectancy, and survival time. Demographic parameters in C. haywardi F1 from irradiated CcVienna-8 young pupae were improved compared to those values recorded from parasitoid originated from nonirradiated CcVienna-8 pupae. These findings will help to enhance parasitoid mass rearing for augmentative releases against medfly in Argentinean fruit-producing regions.
Growth Performance and Enzymatic Response of the Grasshopper, Calliptamus abbreviatus (Orthoptera: Acrididae), to Six Plant-Derived Compounds
Authors: Wang Yueyue , Huang Xunbing , Chang Babar Hussain , Zhang Zehua
Published: May 2020

Plant-derived compounds are sources of biopesticides for the control of insect pests. We compared the growth performance and enzymatic response of the grasshopper Calliptamus abbreviatus Ikonn to six plant-derived compounds (rutin, quercetin, nicotine, matrine, azadirachtin, and rotenone) in laboratory and field trials. When exposed to the six compounds, C. abbreviatus had significantly reduced growth and survival. All the compounds significantly induced an elevated level of reactive oxygen species, indicating oxidative damage. The activity of detoxifying enzymes, including cytochrome P450s, carboxylesterase, glutathione-S-transferase, and UDP-glucuronosyltransferase, and the antioxidant enzymes, including superoxide dismutase, catalase, and peroxidase, all significantly increased after exposure to the six compounds. These data suggest that the six plant-derived compounds had negative effects on C. abbreviatus. Of the six compounds, matrine, azadirachtin, and rotenone were more toxic to C. abbreviatus, followed by nicotine, quercetin, and rutin. These results show the potential of these compounds as botanical pesticides, which can be applied for the biological control of the grasshopper C. abbreviatus.
Prognostic significance of non-urothelial carcinoma of bladder: analysis of nationwide hospital-based cancer registry data in Japan
Authors: Nagumo Yoshiyuki , Kawai Koji , Kojima Takahiro , Shiga Masanobu , Kojo Kosuke , Tanaka Ken , Kandori Shuya , Kimura Tomokazu , Kawahara Takashi , Okuyama Ayako , Higashi Takahiro , Nishiyama Hiroyuki
Published: May 2020

Objectives

To identify the prognosis of pure non-urothelial carcinoma (non-UC) of bladder and to compare them with those of pure urothelial carcinoma (UC).

Methods

We used Japan’s nationwide hospital-based cancer registry data to extract histologically confirmed pure non-UC and UC cases of bladder diagnosed in 2008–2009. We estimated the 5-year overall survival (OS) by a Kaplan–Meier analysis.

Results

A total of 8094 patients with confirmed histological subtypes of bladder cancer were identified. The most common pure non-UC was squamous cell carcinoma (SQ, n = 192, 2.4%) followed by adenocarcinoma (AC, n = 138, 1.7%) and small cell neuroendocrine carcinoma (SmC, n = 54, 0.7%). The proportion of female patients (48%) was significantly higher in the SQ group compared with the pure UC group (P < 0.001). The 5-year OS rate of the non-UC patients was significantly worse than that of the UC patients (40 vs. 61%, P < 0.001). According to stages, the 5-year OS rates of the stage I and III non-UC patients were significantly worse than those of the UC patients (P = 0.001). Considering histologic subtypes and stages, the 5-year OS rates of the stage I SQ patients were worse than those of the AC and SmC patients (46, 68 and 64%, respectively).

Conclusion

The prognosis of pure non-UC was worse than that of pure UC, especially in the stage I and III non-UC patients. To improve these patients’ oncologic outcomes, a more aggressive surgical approach may be necessary in stage I patients with non-UC, especially in pure SQ.
Correlation between optical and UV variability of a large sample of quasars
Authors: Xin Chengcheng , Charisi Maria , Haiman Zoltán , Schiminovich David
Published: May 2020

The variability of quasars across multiple wavelengths is a useful probe of physical conditions in active galactic nuclei. In particular, variable accretion rates, instabilities, and reverberation effects in the accretion disc of a supermassive black hole are expected to produce correlated flux variations in ultraviolet (UV) and optical bands. Recent work has further argued that binary quasars should exhibit strongly correlated UV and optical periodicities. Strong UV–optical correlations have indeed been established in small samples of (N ≲ 30) quasars with well-sampled light curves, and have extended the ‘bluer-when-brighter’ trend previously found within the optical bands. Here, we further test the nature of quasar variability by examining the observed-frame UV–optical correlations among bright quasars extracted from the Half Million Quasars (HMQ) catalogue. We identified a large sample of 1315 quasars in HMQ with overlapping UV and optical light curves from the Galaxy Evolution Explorer and the Catalina Real-time Transient Survey, respectively. We find that strong correlations exist in this much larger sample, but we rule out, at ∼95 per cent confidence, the simple hypothesis that the intrinsic UV and optical variations of all quasars are fully correlated. Our results therefore imply the existence of physical mechanism(s) that can generate uncorrelated optical and UV flux variations.
The SEPT12 complex is required for the establishment of a functional sperm head–tail junction
Authors: Shen Yi-Ru , Wang Han-Yu , Tsai Yung-Chieh , Kuo Yung-Che , Wu Shang-Rung , Wang Chia-Yih , Kuo Pao-Lin
Published: May 2020

The connecting pieces of the sperm neck link the flagellum and the sperm head, and they are important for initiating flagellar beating. The connecting pieces are important building blocks for the sperm neck; however, the mechanism of connecting piece assembly is poorly understood. In the present study, we explored the role of septins in sperm motility and found that Sept12D197N knock-in (KI) mice produce acephalic and immotile spermatozoa. Electron microscopy analysis showed defective connecting pieces in sperm from KI mice, indicating that SEPT12 is required for the establishment of connecting pieces. We also found that SEPT12 formed a complex with SEPT1, SEPT2, SEPT10 and SEPT11 at the sperm neck and that the D197N mutation disrupted the complex, suggesting that the SEPT12 complex is involved in the assembly of connecting pieces. Additionally, we found that SEPT12 interacted and colocalized with γ-tubulin in elongating spermatids, implying that SEPT12 and pericentriolar materials jointly contribute to the formation of connecting pieces. Collectively, our findings suggest that SEPT12 is required for the formation of striated columns, and the capitulum and for maintaining the stability of the sperm head–tail junction.
The human telomeric nucleosome displays distinct structural and dynamic properties
Authors: Soman Aghil , Liew Chong Wai , Teo Hsiang Ling , Berezhnoy Nikolay V , Olieric Vincent , Korolev Nikolay , Rhodes Daniela , Nordenskiöld Lars
Published: May 2020

Telomeres protect the ends of our chromosomes and are key to maintaining genomic integrity during cell division and differentiation. However, our knowledge of telomeric chromatin and nucleosome structure at the molecular level is limited. Here, we aimed to define the structure, dynamics as well as properties in solution of the human telomeric nucleosome. We first determined the 2.2 Å crystal structure of a human telomeric nucleosome core particle (NCP) containing 145 bp DNA, which revealed the same helical path for the DNA as well as symmetric stretching in both halves of the NCP as that of the 145 bp ‘601’ NCP. In solution, the telomeric nucleosome exhibited a less stable and a markedly more dynamic structure compared to NCPs containing DNA positioning sequences. These observations provide molecular insights into how telomeric DNA forms nucleosomes and chromatin and advance our understanding of the unique biological role of telomeres.
InteractomeSeq: a web server for the identification and profiling of domains and epitopes from phage display and next generation sequencing data
Authors: Puccio Simone , Grillo Giorgio , Consiglio Arianna , Soluri Maria Felicia , Sblattero Daniele , Cotella Diego , Santoro Claudio , Liuni Sabino , Bellis Gianluca De , Lugli Enrico , Peano Clelia , Licciulli Flavio
Published: May 2020

High-Throughput Sequencing technologies are transforming many research fields, including the analysis of phage display libraries. The phage display technology coupled with deep sequencing was introduced more than a decade ago and holds the potential to circumvent the traditional laborious picking and testing of individual phage rescued clones. However, from a bioinformatics point of view, the analysis of this kind of data was always performed by adapting tools designed for other purposes, thus not considering the noise background typical of the ‘interactome sequencing’ approach and the heterogeneity of the data. InteractomeSeq is a web server allowing data analysis of protein domains (‘domainome’) or epitopes (‘epitome’) from either Eukaryotic or Prokaryotic genomic phage libraries generated and selected by following an Interactome sequencing approach. InteractomeSeq allows users to upload raw sequencing data and to obtain an accurate characterization of domainome/epitome profiles after setting the parameters required to tune the analysis. The release of this tool is relevant for the scientific and clinical community, because InteractomeSeq will fill an existing gap in the field of large-scale biomarkers profiling, reverse vaccinology, and structural/functional studies, thus contributing essential information for gene annotation or antigen identification. InteractomeSeq is freely available at https://InteractomeSeq.ba.itb.cnr.it/
3D-GNOME 2.0: a three-dimensional genome modeling engine for predicting structural variation-driven alterations of chromatin spatial structure in the human genome
Authors: Wlasnowolski Michal , Sadowski Michal , Czarnota Tymon , Jodkowska Karolina , Szalaj Przemyslaw , Tang Zhonghui , Ruan Yijun , Plewczynski Dariusz
Published: May 2020

Structural variants (SVs) that alter DNA sequence emerge as a driving force involved in the reorganisation of DNA spatial folding, thus affecting gene transcription. In this work, we describe an improved version of our integrated web service for structural modeling of three-dimensional genome (3D-GNOME), which now incorporates all types of SVs to model changes to the reference 3D conformation of chromatin. In 3D-GNOME 2.0, the default reference 3D genome structure is generated using ChIA-PET data from the GM12878 cell line and SVs data are sourced from the population-scale catalogue of SVs identified by the 1000 Genomes Consortium. However, users may also submit their own structural data to set a customized reference genome structure, and/or a custom input list of SVs. 3D-GNOME 2.0 provides novel tools to inspect, visualize and compare 3D models for regions that differ in terms of their linear genomic sequence. Contact diagrams are displayed to compare the reference 3D structure with the one altered by SVs. In our opinion, 3D-GNOME 2.0 is a unique online tool for modeling and analyzing conformational changes to the human genome induced by SVs across populations. It can be freely accessed at https://3dgnome.cent.uw.edu.pl/.
DNA damage invokes mitophagy through a pathway involving Spata18
Authors: Dan Xiuli , Babbar Mansi , Moore Anthony , Wechter Noah , Tian Jingyan , Mohanty Joy G , Croteau Deborah L , Bohr Vilhelm A
Published: May 2020

Mitochondria are vital for cellular energy supply and intracellular signaling after stress. Here, we aimed to investigate how mitochondria respond to acute DNA damage with respect to mitophagy, which is an important mitochondrial quality control process. Our results show that mitophagy increases after DNA damage in primary fibroblasts, murine neurons and Caenorhabditis elegans neurons. Our results indicate that modulation of mitophagy after DNA damage is independent of the type of DNA damage stimuli used and that the protein Spata18 is an important player in this process. Knockdown of Spata18 suppresses mitophagy, disturbs mitochondrial Ca2+ homeostasis, affects ATP production, and attenuates DNA repair. Importantly, mitophagy after DNA damage is a vital cellular response to maintain mitochondrial functions and DNA repair.
Deep sequencing of non-enzymatic RNA primer extension
Authors: Duzdevich Daniel , Carr Christopher E , Szostak Jack W
Published: May 2020

Life emerging in an RNA world is expected to propagate RNA as hereditary information, requiring some form of primitive replication without enzymes. Non-enzymatic template-directed RNA primer extension is a model of the copying step in this posited form of replication. The sequence space accessed by primer extension dictates potential pathways to self-replication and, eventually, ribozymes. Which sequences can be accessed? What is the fidelity of the reaction? Does the recently illuminated mechanism of primer extension affect the distribution of sequences that can be copied? How do sequence features respond to experimental conditions and prebiotically relevant contexts? To help answer these and related questions, we here introduce a deep-sequencing methodology for studying RNA primer extension. We have designed and vetted special RNA constructs for this purpose, honed a protocol for sample preparation and developed custom software that analyzes sequencing data. We apply this new methodology to proof-of-concept controls, and demonstrate that it works as expected and reports on key features of the sequences accessed by primer extension.
Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs
Authors: Sharma Sunny , Grudzien-Nogalska Ewa , Hamilton Keith , Jiao Xinfu , Yang Jun , Tong Liang , Kiledjian Megerditch
Published: May 2020

We recently reported the presence of nicotinamide adenine dinucleotide (NAD)-capped RNAs in mammalian cells and a role for DXO and the Nudix hydrolase Nudt12 in decapping NAD-capped RNAs (deNADding) in cells. Analysis of 5′caps has revealed that in addition to NAD, mammalian RNAs also contain other metabolite caps including flavin adenine dinucleotide (FAD) and dephosphoCoA (dpCoA). In the present study we systematically screened all mammalian Nudix proteins for their potential deNADing, FAD cap decapping (deFADding) and dpCoA cap decapping (deCoAping) activity. We demonstrate that Nudt16 is a novel deNADding enzyme in mammalian cells. Additionally, we identified seven Nudix proteins—Nudt2, Nudt7, Nudt8, Nudt12, Nudt15, Nudt16 and Nudt19, to possess deCoAping activity in vitro. Moreover, our screening revealed that both mammalian Nudt2 and Nudt16 hydrolyze FAD-capped RNAs in vitro with Nudt16 regulating levels of FAD-capped RNAs in cells. All decapping activities identified hydrolyze the metabolite cap substrate within the diphosphate linkage. Crystal structure of human Nudt16 in complex with FAD at 2.7 Å resolution provide molecular insights into the binding and metal-coordinated hydrolysis of FAD by Nudt16. In summary, our study identifies novel cellular deNADding and deFADding enzymes and establishes a foundation for the selective functionality of the Nudix decapping enzymes on non-canonical metabolite caps.
Noncoding Y RNAs regulate the levels, subcellular distribution and protein interactions of their Ro60 autoantigen partner
Authors: Leng Yuanyuan , Sim Soyeong , Magidson Valentin , Wolin Sandra L
Published: May 2020

Noncoding Y RNAs are abundant in animal cells and present in many bacteria. These RNAs are bound and stabilized by Ro60, a ring-shaped protein that is a target of autoantibodies in patients with systemic lupus erythematosus. Studies in bacteria revealed that Y RNA tethers Ro60 to a ring-shaped exoribonuclease, forming a double-ringed RNP machine specialized for structured RNA degradation. In addition to functioning as a tether, the bacterial RNA gates access of substrates to the Ro60 cavity. To identify roles for Y RNAs in mammals, we used CRISPR to generate mouse embryonic stem cells lacking one or both of the two murine Y RNAs. Despite reports that animal cell Y RNAs are essential for DNA replication, cells lacking these RNAs divide normally. However, Ro60 levels are reduced, revealing that Y RNA binding is required for Ro60 to accumulate to wild-type levels. Y RNAs regulate the subcellular location of Ro60, since Ro60 is reduced in the cytoplasm and increased in nucleoli when Y RNAs are absent. Last, we show that Y RNAs tether Ro60 to diverse effector proteins to generate specialized RNPs. Together, our data demonstrate that the roles of Y RNAs are intimately connected to that of their Ro60 partner.
Identifying key predictors of mortality in young patients on chronic haemodialysis—a machine learning approach
Authors: Gotta Verena , Tancev Georgi , Marsenic Olivera , Vogt Julia E , Pfister Marc
Published: May 2020

Background

The mortality risk remains significant in paediatric and adult patients on chronic haemodialysis (HD) treatment. We aimed to identify factors associated with mortality in patients who started HD as children and continued HD as adults.

Methods

The data originated from a cohort of patients <30 years of age who started HD in childhood (≤19 years) on thrice-weekly HD in outpatient DaVita dialysis centres between 2004 and 2016. Patients with at least 5 years of follow-up since the initiation of HD or death within 5 years were included; 105 variables relating to demographics, HD treatment and laboratory measurements were evaluated as predictors of 5-year mortality utilizing a machine learning approach (random forest).

Results

A total of 363 patients were included in the analysis, with 84 patients having started HD at <12 years of age. Low albumin and elevated lactate dehydrogenase (LDH) were the two most important predictors of 5-year mortality. Other predictors included elevated red blood cell distribution width or blood pressure and decreased red blood cell count, haemoglobin, albumin:globulin ratio, ultrafiltration rate, z-score weight for age or single-pool Kt/V (below target). Mortality was predicted with an accuracy of 81%.

Conclusions

Mortality in paediatric and young adult patients on chronic HD is associated with multifactorial markers of nutrition, inflammation, anaemia and dialysis dose. This highlights the importance of multimodal intervention strategies besides adequate HD treatment as determined by Kt/V alone. The association with elevated LDH was not previously reported and may indicate the relevance of blood–membrane interactions, organ malperfusion or haematologic and metabolic changes during maintenance HD in this population.
A Narrative Review of Early Oral Stepdown Therapy for the Treatment of Uncomplicated Staphylococcus aureus Bacteremia: Yay or Nay?
Authors: Dagher Michael , Fowler Vance G , Wright Patty W , Staub Milner B
Published: May 2020

Historically, intravenous (IV) antibiotics have been the cornerstone of treatment for uncomplicated Staphylococcus aureus bacteremia (SAB). However, IV antibiotics are expensive, increase the rates of hospital readmission, and can be associated with catheter-related complications. As a result, the potential role of oral antibiotics in the treatment of uncomplicated SAB has become a subject of interest. This narrative review article aims to summarize key arguments for and against the use of oral antibiotics to complete treatment of uncomplicated SAB and evaluates the available evidence for specific oral regimens. We conclude that evidence suggests that oral step-down therapy can be an alternative for select patients who meet the criteria for uncomplicated SAB and will comply with medical treatment and outpatient follow-up. Of the currently studied regimens discussed in this article, linezolid has the most support, followed by fluoroquinolone plus rifampin.
FLASHING: New high-velocity H2O masers in IRAS 18286−0959
Authors: Imai Hiroshi , Uno Yuri , Maeyama Daichi , Yamaguchi Ryosuke , Amada Kei , Hamae Yuhki , Orosz Gabor , Gómez José F , Tafoya Daniel , Uscanga Lucero , Burns Ross A
Published: May 2020

We discovered new high-velocity components of H2O maser emission in one of the “water fountain” sources, IRAS 18286−0959, which has been monitored using the Nobeyama 45 m telescope in the FLASHING (Finest Legacy Acquisitions of SiO- and H2O-maser Ignitions by Nobeyama Generation) project since 2018 December. The maser spectra show new components with extremely high expansion velocities (>200 km s−1 projected in the line of sight), some of which are located symmetrically in the spectrum with respect to the systemic velocity. They were also mapped with KaVA (KVN and VERA Combined Array) in 2019 March. We located some of these maser components closer to the central stellar system than other high-velocity components (50–200 km s−1) that have been confirmed to be associated with the known bipolar outflow. The new components would have flashed in the fast collimated jet at a speed of over 300 km s−1 (soon) after 2011 when they had not been detected. The fastest of the new components seem to indicate rapid deceleration in these spectra; however, our present monitoring is still too sparse to unambiguously confirm it (up to 50 km s−1 yr−1) and too short to reveal their terminal expansion velocity, which will be equal to the expansion velocity that has been observed ($v$exp ∼ 120 km s−1). Future occurrences of such extreme-velocity components may provide a good opportunity to investigate possible recurrent outflow ignitions. Thus, the sculpture of the parental envelope will be traced by the dense gas that is entrained by the fast jet and exhibits spectacular distributions of the relatively stable maser features.
Tissue Dielectric Constant Measures in Women With and Without Clinical Trunk Lymphedema Following Breast Cancer Surgery: A 78-Week Longitudinal Study
Authors: Koehler Linda A , Mayrovitz Harvey N
Published: May 2020

Objective

Following breast cancer surgery with lymph node removal, women are at risk of developing lymphedema in the upper extremity or trunk. Currently, trunk lymphedema diagnosis relies on a clinical assessment because no quantifiable standard method exists. Tissue dielectric constant (TDC) values are quantifiable measures of localized skin tissue water and may be able to detect trunk lymphedema. The goal of this study was to (1) compare parameters derived from TDC measurements with those derived from clinically accepted criteria for trunk lymphedema in women following breast cancer surgery and (2) explore the potential utility of TDC to detect trunk lymphedema early in its progression.

Methods

This prospective longitudinal study, a secondary analysis from a larger study, observed women with and without clinically determined truncal lymphedema following breast cancer surgery. TDC was measured on the lateral trunk wall at post-surgery weeks 2, 4, 12, and 78 in women who had surgical breast cancer treatment with lymph node removal. Clinical assessment for trunk lymphedema was determined at 78 weeks by a lymphedema expert. Comparison of TDC measurements in women with and without clinical trunk lymphedema was analyzed.

Results

Clinical assessment identified trunk lymphedema in 15 out of 32 women at 78 weeks. These women had TDC ratios statistically higher than women without truncal lymphedema.

Conclusion

The overall findings indicate that TDC has the ability to quantify trunk lymphedema and might be valuable in early detection.

Impact

TDC may be a beneficial tool in the early detection of breast cancer–related trunk lymphedema, which could trigger intervention.

Lay Summary

A new device may help recognize trunk lymphedema in patients with breast cancer so they could receive appropriate treatment.
COVID-19 response in northwest Syria: innovation and community engagement in a complex conflict
Authors: Ekzayez Abdulkarim , al-Khalil Munzer , Jasiem Mohamad , Al Saleh Raed , Alzoubi Zedoun , Meagher Kristen , Patel Preeti
Published: May 2020

Despite lacking capacity and resources, the health system in the northwest Syria is using innovative approaches for the containment of COVID-19. Lessons drawn from previous outbreaks in the region, such as the polio outbreak in 2013 and the annual seasonal influenza, have enabled the Early Warning and Response Network, a surveillance system to develop mechanisms of predicting risk and strengthening surveillance for the new pandemic. Social media tools such as WhatsApp are effectively collecting health information and communicating health messaging about COVID-19. Community engagement has also been scaled up, mobilizing local resources and encouraging thousands of volunteers to join the ‘Volunteers against Corona’ campaign. Bottom-up local governance technical entities, such as Idleb Health Directorate and the White Helmets, have played key leadership role in the response. These efforts need to be scaled up to prevent the transmission of COVID-19 in a region chronically affected by a complex armed conflict.