bluuebunny/crossref_metadata_2025 huggingface dataset:
Peaceful revolution in genome size: polyploidy in the Nabidae (Heteroptera); autosomes and nuclear DNA content doubling
Authors: Sadílek David , Vilímová Jitka , Urfus Tomáš
Published: October 2020

Genome size and the position of 18S ribosomal DNA (rDNA) were analysed in two Himacerus, eight Nabis and two Prostemma species from the family Nabidae using flow cytometry and fluorescence in situ hybrization techniques. The karyotypes of Nabis biformis and Nabis maoricus, each with 2n = 16 + XY, and Prostemma aeneicolle, with 2n = 26 + XY, were recorded for the first time. All the species displayed one or two 18S rDNA signals on the X chromosome and up to two signals on the Y chromosome. Several females exhibited two different types of X chromosome breakage, namely within or outside of the 18S rDNA region. Measurements of nuclear DNA content revealed significant differences between all three genera under study. Most notably, the nuclear DNA content of Himacerus species, with 2n = 32/36 + XY (2C = 9–10 pg), was double that of Nabis species, with 2n = 16 + XY (2C = 4–6 pg). Therefore, the previously rejected theory of an autosomal polyploidy event in the evolution of the genus Himacerus is strongly supported by the results of the present study and is now being resurrected.
Genetic Variability and Molecular Evolution of Maize Yellow Mosaic Virus Populations from Different Geographic Origins
Authors: Sun Sheng-Ren , Chen Jian-Sheng , He Er-Qi , Huang Mei-Ting , Fu Hua-Ying , Lu Jia-Ju , Gao San-Ji
Published: October 2020

Maize yellow mosaic virus (MaYMV) hosted in various gramineous plants was assigned to the genus Polerovirus (family Luteoviridae) in 2018. However, little is known about its genetic diversity and population structure. In this study, 509 sugarcane leaf samples with mosaic symptoms were collected in 2017 to 2019 from eight sugarcane-growing provinces in China. Reverse-transcription PCR results revealed that four positive-sense RNA viruses were found to infect sugarcane, and the incidence of MaYMV among samples from Fujian, Sichuan, and Guangxi Provinces was 52.1, 9.8, and 2.5%, respectively. Based on 82 partial MaYMV sequences and 46 whole-genome sequences from different host plants, phylogenetic analysis revealed that MaYMV populations are very closely associated with their source geographical regions (China, Africa, and South America). Pairwise identity analysis showed significant variability in genome sequences among MaYMV isolates with genomic nucleotide identities of 91.1 to 99.9%. In addition to codon mutations, insertions or deletions also contributed to genetic variability in individual coding regions, especially in the readthrough protein (P3-P5 fusion protein). Low gene flow and significant genetic differentiation of MaYMV were observed among the three geographical populations, suggesting that environmental adaptation is an important evolutionary force that shapes the genetic structure of MaYMV. Genes in the MaYMV genome were subject to strong negative or purification selection during evolution, except for the movement protein (MP), which was under positive selection pressure. This finding suggests that the MP may play an important role in MaYMV evolution. Taken together, our findings provide basic information for the development of an integrated disease management strategy against MaYMV.
Biological Characteristics and Molecular Mechanism of Procymidone Resistance inStemphylium eturmiunumFrom Garlic
Authors: Chen Wen-chan , Wei Ling-ling , Zheng Huan-huan , Zhang Peng-cheng , Wang Bing-ran , Zhao Wei-cheng , Lou Tian-cheng , Wang Jin , Liu Xia-li , Deng Sheng , Wang Xiao-yu , Chen Chang-jun , Wei Li-hui , Liu Yang
Published: October 2020

Garlic leaf blight caused by Stemphylium eturmiunum was first reported in Jiangsu Province in China. The dicarboximide fungicide (DCF) procymidone is reported to possess broad-spectrum action in inhibiting filamentous fungi and is widely used to control leaf disease of various plants. Of 41 Stemphylium eturmiunum isolates collected in this study from commercial garlic farms in Pizhou and Dafeng counties of Jiangsu Province, eight isolates were resistant to procymidone. The following three phenotypes were categorized according to in vitro responses to DCFs: sensitive, low resistance to iprodione and procymidone, and high resistance to all iprodione and procymidone. The fitness of all resistant isolates was decreased in accordance with data on mycelial growth, conidiation, and virulence. After treatment with 10 µg/ml of procymidone for 4 h, mycelial intracellular glycerol concentrations of resistant isolates were significantly lower than those of sensitive isolates. Positive cross-resistance was observed between dicarboximides and phenylpyrroles, but there was no cross-resistance between dicarboximides and fluazinam or difenoconazole in the two resistant phenotypes. Nucleotide sequence alignment of two-component histidine kinase genes from sensitive and resistant isolates indicated that amino acid mutations were located at the histidine kinase, adenylyl cyclase, methyl-accepting chemotaxis protein and at the phosphatase domain of the N-terminal region and the response regulator domain of the C-terminal region. To our knowledge, this is the first report of DCF resistance in Stemphylium eturmiunum, and these findings will help establish a rational strategy to manage DCF-resistant populations of Stemphylium eturmiunum in the field.
Characterization of High Fludioxonil Resistance in Botrytis cinerea Isolates from Calibrachoa Flowers
Authors: Dowling Madeline , Gelain Jhulia , May De Mio Louise Larissa , Schnabel Guido
Published: October 2020

The fungicide fludioxonil is one of the most effective single-site fungicides available for managing flower blight caused by Botrytis cinerea on fruit and ornamental crops. Although low and moderate levels of resistance to fludioxonil have been reported in the pathogen across the United States and Europe, high resistance has been reported only from greenhouses in China. In this study, two B. cinerea isolates with high resistance (half maximal effective concentration >100 µg/ml) to fludioxonil were detected on ornamental calibrachoa flowers grown in a greenhouse. These isolates exhibited stable resistance for >20 generations, produced symptoms on calibrachoa flowers sprayed with label rates of fludioxonil, and displayed in vitro fitness penalties with decreased mycelial growth (P < 0.0001) and sporulation (P < 0.0001) compared with sensitive isolates. Highly resistant isolates were identified as MDR1h, containing the ΔL/V497 deletion in mrr1. However, resistance levels and in vitro fitness parameter characteristics were not consistent with this phenotype. One isolate contained the mutation L267V between HAMP domains 1 and 2 of the Bos-1 gene, and both isolates exhibited high osmotic sensitivity and reduced glycerol accumulation in the presence of fludioxonil, indicating that high resistance of these isolates may be associated with the high-osmolarity glycerol mitogen-activated protein kinase pathway.
Total knee replacement explained
Authors: Perkins Amanda
Published: October 2020

In the US, the knee is the second most replaced joint after the hip. Here's what you need to know about management of patients undergoing this procedure.
Success of Surgical Simulation in Orthopedic Training and Applications in Spine Surgery
Authors: Sayari Arash J. , Chen Oscar , Harada Garrett K. , Lopez Gregory D.
Published: October 2020

Study Design:

This was a narrative review.

Objective:

This study aimed to review the current literature on surgical simulation in orthopedics and its application to spine surgery.

Summary of Background Data:

As orthopedic surgery increases in complexity, training becomes more relevant. There have been mandates in the United States for training orthopedic residents the fundamentals of surgical skills; however, few studies have examined the various training options available. Lack of funding, availability, and time are major constraints to surgical simulation options.

Methods:

A PubMed review of the current literature was performed on all relevant articles that examined orthopedic trainees using surgical simulation options. Studies were examined for their thoroughness and application of simulation options to orthopedic surgery.

Results:

Twenty-three studies have explored orthopedic surgical simulation in a setting that objectively assessed trainee performance, most in the field of trauma and arthroscopy. However, there was a lack of consistency in measurements made and skills tested by these simulators. There has only been one study exploring surgical simulation in spine surgery.

Conclusions:

While there has been a growing number of surgical simulators to train orthopedic residents the fundamentals of surgical skills, most of these simulators are not feasible, reproducible, or available to the majority of training centers. Furthermore, the lack of consistency in the objective measurements of these studies makes interpretation of their results difficult. There is a need for more simulation in spine surgery, and future simulators and their respective studies should be reproducible, affordable, applicable to the surgical setting, and easily assembled by various programs across the world.
HCP5 rs2395029 is a rapid and inexpensive alternative to HLA-B*57:01 genotyping to predict abacavir hypersensitivity reaction in Spain
Authors: Zubiaur Pablo , Saiz-Rodríguez Miriam , Villapalos-García Gonzalo , Navares-Gómez Marcos , Koller Dora , Abad-Santos Francisco
Published: October 2020

Abacavir (ABC) is an HIV nucleotide-analogue reverse transcriptase inhibitor that can produce a severe hypersensitivity reaction (ABC-HSR) in about 5% of the patients. The HLA-B*57:01 allele is associated with the development of ABC-HSR. Therefore, HLA-B*57:01 genotyping is required prior to the prescription of ABC. The technique routinely used in our laboratory is the sequence-specific oligonucleotide probes (SSOP) reverse hybridization method followed by Sanger sequencing. This technique is time-consuming and expensive. The single-nucleotide polymorphism (SNP) HCP5 rs2395029 was described to be in complete linkage disequilibrium with HLA-B*57:01. In this study, we aimed to assess the linkage disequilibrium between HCP5 rs2395029 and HLA-B*57:01 in patients receiving medical assistance at our hospital. We selected 226 HIV-infected patients from our hospital who had been routinely genotyped since 2009 with the SSOP and Sanger sequencing method: 49 HLA-B*57:01 positives and 177 negatives. We genotyped them for HCP5 rs2395019 by real time PCR (qPCR). We exploratory performed two copy number variation assays flanking HCP5 rs2395019 to explore possible deletions that could break the linkage disequilibrium with HLA-B*57:01. The concordance between HLA-B*57:01 and the HCP5 rs2395029 G allele was absolute, with a specificity and sensitivity of 100% (95% confidence interval: 93.0–100.0% and 98.0–100.0%, respectively) and estimated positive and negative predictive values of 84.4% (48.1–93.9%) and 99.9% (99.4–100.0%), respectively. No deletions were found at HCP5 flanking regions. The duration and cost of the SSOP-based method was considerably higher than the SNP-based method. Therefore, the HCP5 rs2395029 genotyping method may be alternatively used in the clinical practice.
Telemedicine in cardiac procedures: considerations for a remote future
Authors: Weiss J. Peter
Published: October 2020

Purpose of review

Present a review of relevant literature and suggest a framework for discussion of the considerations affecting the evolution and adoption of Telerobotic Support and Telerobotic Collaboration in the practice of cardiac procedural medicine.

Recent findings

Recent medical practice has undergone remarkable transformation in the adoption of telemedicine. This evolution has been accelerated by the COVID-19 (SARS-CoV-2) pandemic and has largely been focused on outpatient medicine. Clinical studies and opinion articles have highlighted benefits including reduced costs, increased patient engagement, and saved time, while also raising concerns regarding privacy, care quality and data security. Early and current efforts implementing remote procedural medicine have not only demonstrated technical success but also highlighted the many issues that must be resolved before acceptance as a major aspect of everyday patient care.

It is inevitable that remote technologies will play an increasing role in procedural medicine as they have in outpatient clinical medicine. Thoughtful participation by physicians in the evolution of these technologies and their modes of use will be necessary to maximize the benefits to our patients and healthcare systems.
Severity of Respiratory Infections With Seasonal Coronavirus Is Associated With Viral and Bacterial Coinfections
Authors: de Koff Emma M. , van Houten Marlies A. , Sanders Elisabeth A.M. , Bogaert Debby
Published: October 2020

The clinical presentation of human coronavirus (HCoV) infections in children varies strongly. We show that children with an HCoV-associated lower respiratory tract infection more frequently had respiratory syncytial virus codetected and higher abundance of Haemophilus influenzae/haemolyticus than asymptomatic HCoV carriers as well as children with a non-HCoV-associated lower respiratory tract infection. Viral and bacterial cooccurrence may drive symptomatology of HCoV-associated infections including coronavirus disease 2019.
Polaprezinc (Zinc–l-Carnosine Complex) as an Add-on Therapy for Binge Eating Disorder and Bulimia Nervosa, and the Possible Involvement of Zinc Deficiency in These Conditions
Authors: Sakae Kensaku , Suka Machi , Yanagisawa Hiroyuki
Published: October 2020

Background

Zinc plays an important role in appetite regulation.l-Carnosine, an endogenous dipeptide, may also regulate eating behavior via its histaminergic and antiglutamatergic properties. Polaprezinc (zinc–l-carnosine complex) is a medication for gastric ulcers. A small case series reported successful treatment of binge eating with add-on polaprezinc.

Methods

This was an open trial of add-on polaprezinc in patients with binge eating disorder (BED; n = 22) or bulimia nervosa (BN; n = 7) receiving antidepressants. A 4-week baseline period was followed by a 16-week polaprezinc treatment at 150 mg/d (containing 34 mg zinc and 116 mgl-carnosine) in addition to ongoing psychotropic medications. We also assessed their zinc status via a laboratory index and zinc deficiency–related symptoms.

Results

At the study end, both conditions showed a significant reduction in the 4-week frequency of combined objective and subjective binge eating episodes, the 4-week frequency of days when at least 1 such episode occurred (only in BED), several aspects of eating disorder psychopathology (rated by the Eating Disorder Examination–Questionnaire), and comorbid depressive symptoms (rated by the 16-item Quick Inventory of Depressive Symptomatology [Self-Report]). Serum copper/zinc ratio decreased from 1.4 to 1.1 on average in both conditions. All patients had multiple zinc deficiency–related symptoms at baseline that substantially improved after polaprezinc treatment. Overall, the effectiveness of polaprezinc was greater in BED patients than in BN patients, with minor adverse effects.

Conclusions

These findings offer preliminary evidence for the effectiveness of polaprezinc in treating BED and BN and suggest the involvement of zinc deficiency in these conditions.
Advance Care Planning Engagement Among Muslim Community-Dwelling Adults Living in the United States
Authors: Bani Melhem Ghaith A. , Wallace Debra C. , Adams Judith A. , Ross Ratchneewan , Sudha S.
Published: October 2020

Advance care planning (ACP) is a cornerstone of self-determination for the type of care provided at the end of life. Despite many national efforts to improve American adults' engagement in ACP, statistics indicate low engagement. Low engagement, especially among racial and ethnic minority populations, immigrants, people with lower socioeconomic status, young adults, rural residents, or non-English speakers, is common. Advance care planning engagement among Muslims living in the United States has been minimally studied. The purpose of this study was to explore Muslims' engagement in ACP. A cross-sectional descriptive design was used. Participants were recruited from Islamic organizations through convenience and snowball sampling. Engagement in ACP was measured by the Advance Care Planning Engagement Survey. A sample of 148 Muslims (18-79 years of age) participated in the study. The average engagement scores ranged from 1.97 to 2.09, with about two-thirds in the precontemplation stage. Significant differences in engagement scores were found according to health condition and end of life experiences. Results suggest a need for further collaborative efforts by health care providers, policymakers, and researchers to mitigate the disparities in ACP engagement in the American Muslim community.
A High-Reliability Organization Framework for Health Care: A Multiyear Implementation Strategy and Associated Outcomes
Authors: Sculli Gary L. , Pendley-Louis Robin , Neily Julia , Anderson Timothy M. , Isaacks David B. , Knowles Regina , Young-Xu Yinong , Gunnar William
Published: October 2020

Objectives

Applying high-reliability organization (HRO) principles to health care is complex. No consensus exists as to an effective framework for HRO implementation or the direct impact of adoption.

Methods

The Veterans Health Administration (VHA) National Center for Patient Safety established the high-reliability hospital (HRH) model for HRO adoption and piloted HRH in collaboration with the Truman VA Medical Center (Truman) during a 3-year intervention period (January 1, 2016–December 31, 2018). High-reliability hospital components are as follows: annual patient safety (PS) assessment, annual PS culture survey, annual root cause analysis training, daily leadership walk-arounds, monthly PS forum, annual processes standardization review, Just Culture training, unit-based Clinical Team Training, unit-based continuous improvement projects, and annual Clinical Team Training simulation education. The impact of HRH was examined using a PS Culture Survey, PS event reporting, and quality outcomes of standardized mortality rate and complication rate.

Results

Truman internally improved PS culture and PS event reporting rates resulting in outcomes better than all VHA facilities (All VHA; P < 0.001 and P < 0.001, respectively). Low-harm PS event reporting increased (P < 0.001); however, serious safety event rate remained unchanged versus All VHA. Significant improvement in Truman standardized mortality rate and complication rate versus All VHA occurred immediately and were sustained through intervention (slopes, P < 0.001 and P < 0.020; respectively).

Conclusions

High-reliability hospital is an effective framework for HRO implementation and will be applied to 18 additional VHA sites. Based on these results, the expected outcome will be improved PS culture and overall PS event reporting. The impact of HRH on serious safety event rate and quality measures requires further study.
COVID-19 Susceptibility and Outcomes Among People Living With HIV in San Francisco
Authors: Sachdev Darpun , Mara Elise , Hsu Ling , Scheer Susan , Rutherford George , Enanoria Wayne , Gandhi Monica
Published: October 2020

Introduction:

Studies to examine whether HIV predisposes to a higher incidence of COVID-19 or more severe disease are accumulating. Initial studies from New York City suggested more severe disease among people living with HIV (PLWH), but this was during a time when hospitals were over-capacity and health systems stretched. This report presents the incidence and outcomes among PLWH with COVID-19 in San Francisco over the first 6 months of the pandemic.

Methods:

Community transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first reported in San Francisco on March 5, 2020. This report examines the match of the San Francisco Department of Public Health COVID-19 testing database and the San Francisco Department of Public Health HIV Surveillance case registry from March 24, 2020, to September 3, 2020.

Results:

Among 4252 COVID-19 tests performed among PLWH, 4.5% (N = 193) were positive for COVID-19, compared with a 3.5% (N = 9626) positivity rate among the 272,555 people without HIV tested for COVID-19 (P < 0.001). The mean age of those infected with HIV/COVID-19 was 48 years (20–76), 38.9% White, 38.3% Latinx, 11.9% Black, and 91.2% were men. Only 54.6% of coinfected PLWH were housed, with the remainder marginally housed. The rate of severe illness with COVID-19 was not increased among PLWH.

Discussion:

In San Francisco, susceptibility to COVID-19 was increased among PLWH over the first 6 months of the pandemic, although clinical outcomes were similar to those without HIV. Homelessness and higher rates of congregate living situations among PLWH likely accounted for this disparity. Special efforts to house patients with marginal housing during the COVID-19 pandemic are needed.
Clinical application of non-coding RNAs in sepsis
Authors: Iro Mildred A. , Soundara Pandi Sudha Priya
Published: October 2020

Purpose of review

Studies indicating that non-coding RNAs (ncRNAs) play a regulatory role in sepsis are increasing rapidly. This present review summarizes recent publications on the role of microRNAs and long non-coding RNAs (lncRNAs) in sepsis.

Recent findings

MicroRNAs (miRNAs) and lncRNAs are being identified as potential sepsis biomarkers and therapeutic targets. Experimental studies have examined the biological mechanisms that might underpin the regulatory role of these ncRNAs in sepsis.

Clinical applications of miRNAs and lncRNAs in sepsis are on the horizon. These data could lead to the identification of novel treatments or indeed support the repurposing of existing drugs for sepsis. Validation of the findings from these preliminary studies and crucially integration of multiomics datasets will undoubtedly revolutionize the clinical management of sepsis.
Do the Benefits of Educational Attainment for Late-life Cognition Differ by Racial/Ethnic Group?
Authors: Eng Chloe W. , Glymour Medellena Maria , Gilsanz Paola , Mungas Dan M. , Mayeda Elizabeth R. , Meyer Oanh L. , Whitmer Rachel A.
Published: October 2020

Introduction:

Educational attainment is associated with late-life cognitive performance and dementia; few studies have examined diverse racial/ethnic groups to assess whether the association differs by race/ethnicity.

Methods:

We investigated whether the association between educational attainment and cognition differed between White, Black, Asian, and Latino participants in the Kaiser Healthy Aging and Diverse Life Experiences study (n=1348). Covariate-adjusted multivariable linear regression models examined domains of verbal episodic memory, semantic memory, and executive functioning.

Results:

We observed significant effect heterogeneity by race/ethnicity only for verbal episodic memory (P=0.0198), for which any schooling between high school and college was beneficial for White, Asian, and Black participants, but not Latino participants. We found no evidence of heterogeneity for semantic memory or executive function.

Discussion:

With the exception of Latino performance on verbal episodic memory, more education consistently predicted better cognitive scores to a similar extent across racial/ethnic groups, despite likely heterogenous educational and social experiences.
Using Test Positivity and Reported Case Rates to Estimate State-Level COVID-19 Prevalence and Seroprevalence in the United States
Authors: Chiu Weihsueh A. , Ndeffo-Mbah Martial L.
Published: October 2020

Accurate estimates of infection prevalence and seroprevalence are essential for evaluating and informing public health responses needed to address the ongoing spread of COVID-19 in the United States. A data-driven Bayesian single parameter semi-empirical model was developed and used to evaluate state-level prevalence and seroprevalence of COVID-19 using daily reported cases and test positivity ratios. COVID-19 prevalence is well-approximated by the geometric mean of the positivity rate and the reported case rate. As of December 8, 2020, we estimate nation-wide a prevalence of 1.4% [Credible Interval (CrI): 0.8%-1.9%] and a seroprevalence of 11.1% [CrI: 10.1%-12.2%], with state-level prevalence ranging from 0.3% [CrI: 0.2%-0.4%] in Maine to 3.0% [CrI: 1.1%-5.7%] in Pennsylvania, and seroprevalence from 1.4% [CrI: 1.0%-2.0%] in Maine to 22% [CrI: 18%-27%] in New York. The use of this simple and easy-to-communicate model will improve the ability to make public health decisions that effectively respond to the ongoing pandemic.

Biographical Sketch of Authors

Dr. Weihsueh A. Chiu, is a professor of environmental health sciences at Texas A&M University. He is an expert in data-driven Bayesian modeling of public health related dynamical systems. Dr. Martial L. Ndeffo-Mbah, is an Assistant Professor of Epidemiology at Texas A&M University. He is an expert in mathematical and computational modeling of infectious diseases.

Summary Line

Relying on reported cases and test positivity rates individually can result in incorrect inferences as to the spread of COVID-19, and public health decision-making can be improved by instead using their geometric mean as a measure of COVID-19 prevalence and transmission.
Safely Reopening K-12 Schools During the COVID-19 Pandemic
Authors: Shelley Courtney D. , Chadwick Philippa S. , Manore Carrie , Del Valle Sara Y.
Published: October 2020

Early school closures were a consistent, nationwide response to the COVID-19 pandemic in mid-March due to the role that children play in spreading influenza. This left us with limited understanding of COVID-19 transmission in children until several states reopened schools for the 2020-2021 school year. While early school closures were likely beneficial in protecting children in the initial stages of the pandemic in the U.S., long-term closures pose significant cumulative effects in children who rely on schools for instruction and additional social services, and for parents who need to balance work and childcare obligations. Reopening schools safely is a high priority for many interested stakeholders.

Proposed in-person school reopening plans include traditional, 100% school capacity, five days per week instruction, hybrid scenarios with reduced in-person instruction and virtual learning, and various reduced school capacity schedules with non-pharmaceutical interventions in place. To assess the potential impacts of different reopening plans, we created a modified SIR-type transmission model that captures multiple known pathways of COVID-19 transmission in a 100,000-person community.

Our results show that plans that utilize consecutive days in school and divide students into separated smaller cohorts who attend school together, as well as plans that emphasize distance learning, are better able to suppress disease spread and reduce risk from an introduced infective into the community. Plans with more consecutive school days are protective for both the schoolchildren and surrounding community by acting to separate the larger intermixing population into smaller intermixing subpopulations. The “Five-Day Switch” plan, which separates students into two cohorts, each of whom attend in-person learning for five consecutive days followed by five days of distance learning, best captures these protective attributes. All modeled plans assumed initially disease-free communities and that children’s interactions with the community are greatly reduced during instructional days, both for in-person and distance learning.
A virulence associated siderophore importer causes antimicrobial efflux inKlebsiella pneumoniae
Authors: Farzand Robeena , Rajakumar Kumar , Barer Michael R , Freestone Primrose P E , Mukamolova Galina V , Oggioni Marco R , O’Hare Helen M
Published: October 2020

The accessory genome of many pathogenic bacteria includes ABC transporters that scavenge metal by siderophore uptake and ABC transporters that contribute to antimicrobial resistance by multidrug efflux. There are mechanistic and recently recognised structural similarities between siderophore importer proteins and efflux pumps. Here we investigated the influence of siderophore importer YbtPQ on antimicrobial resistance ofKlebsiella pneumoniae. YbtPQ is encoded in the yersiniabactin cluster in a prevalent mobile genetic element ICEKp, and is also common in pathogenicity islands ofEscherichia coliandYersiniaspecies, where yersiniabactin enhances virulence. Deletion of ICEKp increased the sensitivity ofK. pneumoniaeto all antimicrobials tested. The mechanism was dependent on the yersiniabactin importer YbtPQ and involved antimicrobial efflux, since it was affected by the inhibitor reserpine. The element ICEKp is naturally highly mobile, indeed the accessory genome ofK. pneumoniaeis recognised as a reservoir of genes for the emergence of hospital outbreak strains and for transfer to other Gram-negative pathogens. Introduction of ICEKp, or a plasmid encoding YbtPQ, toE. colidecreased its sensitivity to a broad range of antimicrobials. Thus, a confirmed siderophore importer, on a rapidly evolving and highly mobile element capable of interspecies transfer, may have a secondary function exporting antimicrobials.
Plasmodesmata-localized proteins and reactive oxygen species orchestrate light-induced rapid systemic signaling in Arabidopsis
Authors: Fichman Yosef , Myers Ronald J. , Grant DeAna G. , Mittler Ron
Published: October 2020

Systemic signaling and systemic acquired acclimation (SAA) are key to the survival of plants during episodes of abiotic stress. These processes depend on a continuous chain of cell-to-cell signaling events that extends from the initial tissue that senses the stress (local tissue) to the entire plant (systemic tissues). Among the different systemic signaling molecules and processes thought to be involved in this cell-to-cell signaling mechanism are reactive oxygen species (ROS), calcium, electric and hydraulic signals. How these different signals and processes are interlinked, and how they transmit the systemic signal all the way from the local tissue to the entire plant, remain however largely unknown. Here, studying the systemic response ofArabidopsis thalianato a local treatment of excess light stress, we report that respiratory burst oxidase homolog D (RBOHD)-generated ROS enhance cell-to-cell transport and plasmodesmata (PD) pore size in a process that depends on the function of PD-localized proteins (PDLPs) 1 and 5, promoting the cell-to-cell transport of systemic signals during responses to light stress. We further identify aquaporins, and several different calcium-permeable channels, belonging to the glutamate receptor-like, mechanosensitive small conductance-like, and cyclic nucleotide-gated families, as involved in this process, but determine that their function is primarily required for the maintenance of the signal in each cell along the path of the systemic signal, as well as for the establishment of acclimation at the local and systemic tissues. PD and RBOHD-generated ROS orchestrate therefore light stress-induced rapid cell-to-cell spread of systemic signals in Arabidopsis.

One-sentence summary

Respiratory burst oxidase homolog D-generated reactive oxygen species enhance cell-to-cell transport and plasmodesmata (PD) pore size in a process that depends on the function of the PD-localized proteins (PDLPs) 1 and 5, promoting the cell-to-cell transport of rapid systemic signals during the response of Arabidopsis to excess light stress.
Circadian fluctuations in glucocorticoid level predict perceptual discrimination sensitivity
Authors: Obleser Jonas , Kreitewolf Jens , Vielhauer Ricarda , Lindner Fanny , David Carolin , Oster Henrik , Tune Sarah
Published: October 2020

Slow neurobiological rhythms, such as the circadian secretion of glucocorticoid (GC) hormones, modulate a wide variety of body functions. Whether and how such endocrine fluctuations also exert an influence on perceptual abilities is largely uncharted. Here, we show that phasic, moderate increases in GC availability prove beneficial to auditory discrimination. In an age-varying sample of N = 68 healthy human participants, we characterise the covariation of saliva cortisol with perceptual sensitivity in an auditory pitch-discrimination task at five time points across the sleep--wake cycle. First, momentary saliva cortisol levels were captured well by the time relative to wake-up and overall sleep duration. Second, within individuals, higher cortisol level just prior to behavioural testing predicted better pitch discrimination ability, expressed as a steepened psychometric curve. This effect of glucocorticoids held under a set of statistical control models. Our results pave the way for more in-depth studies on neuroendocrinological determinants of sensory encoding and perception.
Breeding Program Optimization for Genomic Selection in Winter Wheat
Authors: Calvert Megan , Evers Byron , Wang Xu , Fritz Allan , Poland Jesse
Published: October 2020

Developing methodologies in the fields of phenomics and genomic prediction have the potential to increase the production of crop species by accelerating germplasm improvement. The integration of these technologies into germplasm improvement and breeding programs requires evidence that there will be a direct economic benefit to the program. We determined a basic set of parameters, such as prediction accuracy greater than 0.3, the ability to genotype over 7 lines for the cost of one phenotypic evaluation, and heritability levels below 0.4, at which the use of genomic selection would be of economic benefit in terms of genetic gain and operational costs to the Kansas State University (KSU) winter wheat breeding program. The breeding program was then examined to determine whether the parameters benefitting genomic selection were observed or achievable in a practical sense. Our results show that the KSU winter wheat breeding program is at a decision point with regards to their primary means of selection. A few operational changes to increase prediction accuracy would place the program in the parameter space where genomic selection is expected to outpace the current phenotypic selection methodology at a parity of the operation cost and would be of greatest benefit to the program.
Prevalence of Mild Cognitive Impairment in the Lothian Birth Cohort 1936
Authors: Welstead Miles , Luciano Michelle , Muniz-Terrera Graciela , Taylor Adele M. , Russ Tom C.
Published: October 2020

Background

The Lothian Birth Cohort 1936 (LBC1936) is a highly-phenotyped longitudinal study of cognitive and brain ageing. Given its substantial clinical importance, we derived an indicator of mild cognitive impairment (MCI) as well as amnestic and non-amnestic subtypes at three time points.

Methods

MCI status was derived at three waves of the LBC1936 at ages 76 (n=567), 79 (n=441), and 82 years (n=341). A general MCI category was derived as well as amnestic MCI (aMCI) and non-amnestic MCI (naMCI). A comparison was made between MCI derivations using normative data from the LBC1936 cohort versus the general UK population.

Results

MCI rates showed a proportional increase at each wave between 76 and 82 years from 15% to 18%. Rates of MCI subtypes also showed a proportional increase over time: aMCI 4% to 6%; naMCI 12% to 16%. Higher rates of MCI were found when using the LBC1936 normative data to derive MCI classification rather than UK-wide norms.

Conclusions

We found that MCI and aMCI rates in the LBC1936 were consistent with previous research. However, naMCI rates were higher than expected. Future LBC1936 research should assess the predictive factors associated with MCI prevalence to validate previous findings and identify novel risk factors.
BugSeq: a highly accurate cloud platform for long-read metagenomic analyses
Authors: Fan Jeremy , Huang Steven , Chorlton Samuel D
Published: October 2020

Background

As the use of nanopore sequencing for metagenomic analysis increases, tools capable of performing long-read taxonomic classification in a fast and accurate manner are needed. Existing tools were either designed for short-read data (eg. Centrifuge) or take days to analyse modern sequencer outputs (eg. MetaMaps).

Results

We present BugSeq, a novel, highly accurate metagenomic classifier for nanopore reads. BugSeq (F1=0.91-0.95) offers better read classification than MetaMaps (F1=0.89-0.94) in a fraction of the time. BugSeq significantly improves on the accuracy of Centrifuge (F1=0.79-0.93) while offering competitive run times. We apply BugSeq to metagenomic sequencing of 41 samples from patients with lower respiratory tract infections and show that it produces greater concordance with microbiological culture and qPCR compared with “What’s In My Pot” analysis.

Conclusion

BugSeq is deployed to the cloud for easy and scalable long-read metagenomic analyses. BugSeq is freely available for non-commercial use athttps://bugseq.com/free.

Contact

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In VivoValidation of Bimolecular Fluorescence Complementation (BiFC) to Investigate Aggregate Formation in Amyotrophic Lateral Sclerosis (ALS)
Authors: Don Emily K , Maschirow Alina , Radford Rowan A W , Scherer Natalie M , Vidal-Itriago Andres , Hogan Alison , Maurel Cindy , Formella Isabel , Stoddart Jack J , Hall Thomas E , Lee Albert , Shi Bingyang , Cole Nicholas J , Laird Angela S , Badrock Andrew P , Chung Roger S , Morsch Marco
Published: October 2020

Amyotrophic lateral sclerosis (ALS) is a form of motor neuron disease (MND) that is characterized by the progressive loss of motor neurons within the spinal cord, brainstem and motor cortex. Although ALS clinically manifests as a heterogeneous disease, with varying disease onset and survival, a unifying feature is the presence of ubiquitinated cytoplasmic protein inclusion aggregates containing TDP-43. However, the precise mechanisms linking protein inclusions and aggregation to neuronal loss are currently poorly understood.

Bimolecular Fluorescence Complementation (BiFC) takes advantage the association of fluorophore fragments (non-fluorescent on their own) that are attached to an aggregation prone protein of interest. Interaction of the proteins of interest allows for the fluorescent reporter protein to fold into its native state and emit a fluorescent signal. Here, we combined the power of BiFC with the advantages of the zebrafish system to validate, optimize and visualize of the formation of ALS-linked aggregates in real time in a vertebrate model. We further providein vivovalidation of the selectivity of this technique and demonstrate reduced spontaneous self-assembly of the non-fluorescent fragmentsin vivoby introducing a fluorophore mutation. Additionally, we report preliminary findings on the dynamic aggregation of the ALS-linked hallmark proteins Fus and TDP-43 in their corresponding nuclear and cytoplasmic compartments using BiFC.

Overall, our data demonstrates the suitability of this BiFC approach to study and characterize ALS-linked aggregate formationin vivo. Importantly, the same principle can be applied in the context of other neurodegenerative diseases and has therefore critical implications to advance our understanding of pathologies that underlie aberrant protein aggregation.
Dementia risk factors modify hubs but leave other connectivity measures unchanged in asymptomatic individuals: a graph theoretical analysis
Authors: Clarke Hannah , Messaritaki Eirini , Dimitriadis Stavros I , Metzler-Baddeley Claudia
Published: October 2020

Background

Alzheimer’s Disease (AD) is the most common form of dementia with genetic and environmental risk contributing to its development. Graph theoretical analyses of brain networks constructed from structural and functional MRI measurements have identified connectivity changes in AD and individuals with mild cognitive impairment (MCI). However, brain connectivity in asymptomatic individuals at risk of AD remains poorly understood.

Methods

We analysed diffusion-weighted magnetic resonance imaging (dMRI) data from 160 asymptomatic individuals (38-71 years) from the Cardiff Ageing and Risk of Dementia Study (CARDS). We calculated white matter tracts and constructed whole-brain, default-mode-network and visual structural brain networks that incorporate multiple structural metrics as edge weights. We then calculated the relationship of three AD risk factors, namely Apolipoprotein-E ε4 genotype (APOE4), family history (FH) of dementia, and central obesity, on graph theoretical measures and hubs.

Results

We observed no risk-related differences in clustering coefficients, characteristic path lengths, eccentricity, diameter and radius across the whole-brain, default-mode-network or visual system. However, a hub in the right paracentral lobule was present in all high-risk groups (FH, APOE4, obese) but absent in low-risk groups (no FH, APOE4-ve, healthy weight).

Discussion

We identified no risk-related effects on graph theoretical metrics in the structural brain networks of cognitively healthy individuals. However, high-risk was associated with a hub in the right paracentral lobule, an area with motor and sensory functions related to the lower limb. If this phenotype is shown to predict symptom development in longitudinal studies, it could be used as an early biomarker of AD.

Impact Statement

Alzheimer’s Disease is a common form of dementia which to date has no cure. Identifying early biomarkers will aid the discovery and development of treatments that may slow AD progression in the future. In this paper we report that asymptomatic individuals at heightened risk of dementia due to their family history, Apolipoprotein-E ε4 genotype and body adiposity have a hub in the right paracentral lobule which is absent in low-risk groups. If this phenotype were to predict the development of symptoms in a longitudinal study of the same cohort, it could provide an early biomarker of disease progression.
Antifragile therapy
Authors: West Jeffrey , Desai Bina , Strobl Maximilian , Pierik Luke , Velde Robert Vander , Armagost Cole , Miles Richard , Robertson-Tessi Mark , Marusyk Andriy , Anderson Alexander R. A.
Published: October 2020

Antifragility is a recently coined word used to describe the opposite of fragility. Systems or organisms can be described as antifragile if they derive a benefit from systemic variability, volatility, randomness, or disorder. Herein, we introduce a mathematical framework to quantify the fragility or antifragility of cancer cell lines in response to treatment variability. This framework enables straightforward prediction of the optimal dose treatment schedule for a range of treatment schedules with identical cumulative dose. We apply this framework to non-small-cell lung cancer cell lines with evolved resistance to ten anti-cancer drugs. We show the utility of this antifragile framework when applied to 1) treatment resistance, and 2) collateral sensitivity of sequential monotherapies.
The Polyadenosine RNA Binding Protein ZC3H14 is Required in Mice for Proper Dendritic Spine Density
Authors: Jones Stephanie K. , Rha Jennifer , Kim Sarah , Morris Kevin J. , Omotade Omotola F. , Moberg Kenneth H. , Myers Kenneth R. , Corbett Anita H.
Published: October 2020

ZC3H14 (Zinc fingerCysCysCysHis domain-containing protein14), an evolutionarily conserved member of a class of tandem zinc finger (CCCH) polyadenosine (polyA) RNA binding proteins, is associated with a form of heritable, nonsyndromic autosomal recessive intellectual disability. Previous studies of a loss of function mouse model,Zc3h14Δex13/Δex13, provide evidence that ZC3H14 is essential for proper brain function, specifically for working memory. To expand on these findings, we analyzed the dendrites and dendritic spines of hippocampal neurons fromZc3h14Δex13/Δex13mice, bothin situandin vitro.These studies reveal that loss of ZC3H14 is associated with a decrease in total spine density in hippocampal neuronsin vitroas well as in the dentate gyrus of 5-month old mice analyzedin situ. This reduction in spine densityin vitroresults from a decrease in the number of mushroom-shaped spines, which is rescued by exogenous expression of ZC3H14. We next performed biochemical analyses of synaptosomes prepared from whole wild-type andZc3h14Δex13/Δex13mouse brains to determine if there are changes in steady state levels of postsynaptic proteins upon loss of ZC3H14. We found that ZC3H14 is present within synaptosomes and that a crucial postsynaptic protein, CaMKIIα, is significantly increased in these synaptosomal fractions upon loss of ZC3H14. Together, these results demonstrate that ZC3H14 is necessary for proper dendritic spine density in cultured hippocampal neurons and in some regions of the mouse brain. These findings provide insight into how a ubiquitously expressed RNA binding protein leads to neuronal-specific defects that result in brain dysfunction.
Phylogenetic evidence of headful packaging strategy in gene transfer agents
Authors: Esterman Emma , Wolf Yuri I. , Kogay Roman , Koonin Eugene V. , Zhaxybayeva Olga
Published: October 2020

Gene transfer agents (GTAs) are virus-like particles encoded and produced by many bacteria and archaea. Unlike viruses, GTAs package fragments of the host genome instead of the genes that encode the components of the GTA itself. As a result of this non-specific DNA packaging, GTAs can transfer genes within bacterial and archaeal communities. GTAs clearly evolved from viruses and are thought to have been maintained in prokaryotic genomes due to the advantages associated with their DNA transfer capacity. The most-studied GTA is produced by the alphaproteobacteriumRhodobacter capsulatus(RcGTA), which packages random portions of the host genome at a lower DNA density than usually observed in tailed bacterial viruses. How the DNA packaging properties of RcGTA evolved from those of the ancestral virus remains unknown. To address this question, we reconstructed the evolutionary history of the large subunit of the terminase (TerL), a highly conserved enzyme used by viruses and GTAs to package DNA. We found that RcGTA-like TerLs grouped within viruses that employ the headful packaging strategy. Because distinct mechanisms of viral DNA packaging correspond to differences in the TerL amino acid sequence, our finding suggests that RcGTA evolved from a headful packaging virus. Headful packaging is the least sequence-specific mode of DNA packaging, which would facilitate the switch from packaging of the viral genome to packaging random pieces of the host genome during GTA evolution.