bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Pelvic Organ Prolapse-related Content on Pinterest
Authors: Pace Lauren A. , Herbert Amber S. , Munir Alia , Malik Rena D.
Published: September 2020

Objectives

Our study is a cross-sectional, qualitative study analyzing pelvic organ prolapse-related content on Pinterest, a social media platform that also functions as a visual search engine. Primary outcomes assessed include quality, understandability, and actionability of content. Secondary outcomes include levels of misinformation and commercial bias. Our study further characterizes sources of prolapse content and treatment modalities discussed.

Methods

A Pinterest search was conducted using the term “pelvic organ prolapse,” analyzing the first 100 relevant results. We examined the publisher of each pin and the writer of linked content. Using validated tools including the Patient Education Materials Assessment Tool and DISCERN criteria, we assessed understandability and actionability of content. We further compared content to professional guidelines for discussing and treating prolapse, evaluating for misinformation. We also evaluated for commercial bias and subjectively rated pin quality.

Results

Of pins evaluated, low understandability was found in 16, low actionability in 30, and low-to-moderate quality in 69. The most common publisher of pins was health and wellness groups, and the most common writer of content was physical therapists. Pelvic floor muscle training (PFMT) is the treatment modality discussed most frequently on Pinterest.

Conclusions

Pinterest content discussing pelvic organ prolapse shows good levels of understandability for patients at all levels of health literacy. However, the number of pins showing poor actionability raises concern that content may not encourage readers to take direct steps toward prolapse assessment and management. In all, a majority of prolapse-related content on Pinterest was of low-to-moderate quality.
Age and Perioperative Outcomes After Implementation of an Enhanced Recovery After Surgery Pathway in Women Undergoing Major Prolapse Repair Surgery
Authors: Carter-Brooks Charelle M. , Romanova Anna L. , DeRenzo Joseph S. , Shepherd Jonathan P. , Zyczynski Halina M.
Published: September 2020

Objective

As perioperative care pathways are developed to improve recovery, there is a need to explore the impact of age. The aim of this study was to compare the impact of a urogynecology-specific enhanced recovery after surgery (ERAS) pathway on perioperative outcomes across 3 age categories: young, middle age, and elderly.

Methods

A retrospective cohort study was conducted assessing same-day discharge, opioid administration, pain scores, and complications differences across and within 3 age categories, young (<61 years), middle age (61–75 years), elderly (>75 years), before and after ERAS implementation.

Results

Among 98 (25.7%) young, 202 (52.9%) middle-aged, and 82 (21.5%) elderly women, distribution before and after ERAS implementation was similar. In each age category, we found a commensurate increase in same-day discharge and decrease in length of stay independent of age. Age was associated with a variable response to opioid administration after ERAS. In women who received opioids, we found there was a greater reduction in opioids in elderly. Young women received 22.5 mg more than middle-aged women, whereas elderly women received 24.3 mg less than middle-aged women (P < 0.0001, P < 0.0001) for a mean difference of 46.8 mg between the youngest and oldest group. We found no significant differences in postanesthesia care unit pain scores with ERAS implementation. Complications did not increase after ERAS implementation in any age group, although younger and elderly women were more likely to experience complications independent of ERAS.

Conclusions

Elderly women had similar outcomes compared with their younger counterparts after implementation of an ERAS pathway. Further research is needed to assess whether our age-related observations are generalizable.
Factors Influencing Selection of Concomitant Total Versus Supracervical Hysterectomy at the Time of Sacrocolpopexy and Associated Perioperative Outcomes
Authors: Slopnick Emily A. , Roberts Kasey , Sheyn David D. , Chapman Graham C. , El-Nashar Sherif , Mahajan Sangeeta T.
Published: September 2020

Objectives

The objective of this study was to describe national practice patterns of hysterectomy type performed with concurrent sacrocolpopexy and determine clinical factors associated with surgical route.

Methods

We used the National Surgical Quality Improvement Program database with hysterectomy data for this retrospective cohort study. We identified sacrocolpopexy cases from 2014 to 2016 with concurrent hysterectomy and stratified patients into supracervical hysterectomy (SCH) or total hysterectomy (TH). As a secondary analysis, we compared the laparoscopic subset of cases. We performed χ2 and backward stepwise logistic regression analyses to identify factors associated with hysterectomy type and compare complication rates.

Results

A total of 4,615 women underwent SCP with hysterectomy: 55.8% TH and 44.2% SCH. Mean ± SD age was 56.5 ± 11.7 years. Gynecologists represent 96.3% of surgeons; 51.2% were urogynecologists. Urogynecologists were more likely than generalists to perform SCH (58.4% vs 41.6%, P < 0.001). Total hysterectomy was associated with younger age (adjusted odds ratio [aOR], 0.98 per year [0.97–0.99]), greater uterine weight (aOR, 1.05 per 10 g [1.03–1.06]), and non-Caucasian race (aOR, 0.73 [0.58–0.92]). Complication rates were equivalent between hysterectomy type (SCH, 6.2% vs TH, 6.2%; P = 0.956). Laparoscopy was used for 84.4% of surgical procedures. In this subgroup, TH was associated with greater uterine weight (aOR, 1.06 per 10 g [1.04–1.08]) and younger age (aOR, 0.97 per year [0.96–0.98]). Complication rates were similar (SCH, 5.1% vs TH, 5.0%; P = 0.824).

Conclusions

At the time of sacrocolpopexy, TH is more common than SCH and is associated with younger age and greater uterine weight, although urogynecologists more commonly perform SCH. The overall risk of complications was low and similar between hysterectomy type.
Diagnostic Yield of 18F-FDG PET After Lung Transplantation: A Single-center, Retrospective Cohort Study
Authors: Van Rompaey Winand , Gheysens Olivier , Deroose Christophe M. , Verleden Stijn E. , Vanaudenaerde Bart M. , Ceulemans Laurens J. , Van Raemdonck Dirk E. , Neyrinck Arne P. , Verleden Geert M. , Vos Robin
Published: September 2020

Background.

To investigate the diagnostic yield of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in lung transplant recipients.

Methods.

A single-center, retrospective cohort study including 234 18F-FDG PET examinations in 199 lung transplant recipients. Indication for PET referral, 18F-FDG PET diagnosis/findings and final clinical diagnosis were classified into 3 groups: malignancy, infection/inflammation not otherwise specified, and chronic lung allograft dysfunction with restrictive allograft syndrome phenotype. Sensitivity/specificity analysis was performed to determine accuracy of 18F-FDG PET in each group.

Results.

Sensitivity of 18F-FDG PET for malignancy was 91.4% (95% confidence interval, 82.5%-96.0%) and specificity was 82.3% (95% confidence interval, 74.5%-88.1%). Infection/inflammation not otherwise specified and restrictive allograft syndrome as indication for 18F-FDG PET comprised relatively small groups (14 and 31 cases, respectively). In addition, 18F-FDG PET revealed clinically relevant incidental findings in 15% of cases.

Conclusions.

Referral for 18F-FDG PET after lung transplantation mainly occurred to confirm or rule out malignancy. In this specific setting, 18F-FDG PET has a high diagnostic yield. Accuracy of 18F-FDG PET for other indications is less clear, given small sample sizes. Clinically relevant diagnoses, unrelated to the primary indication for 18F-FDG PET, are found relatively often in this immunocompromised cohort.
Resolution of Citalopram Sexual Adverse Effects With Low Dose of Cariprazine: A Case Report
Authors: Dieci Massimiliano , Trama Annalisa , Mansi Gianluigi
Published: September 2020

Sexual dysfunction is a common adverse effect in selective serotonin reuptake inhibitors users. We report a case of substantial improvement in sexual function with cariprazine at very low dosage.
Nalbuphine Exhibited a Better Adjuvant Than Dexmedetomidine in Supraclavicular Brachial Plexus Block in Youths
Authors: Jiang Changcheng , Xie Wenji , Xie Huijuan , Xie Wenqin , Kang Zhenming , Liu Naizhen
Published: September 2020

Objective

Nalbuphine and dexmedetomidine are both used as anesthesia adjuvants for brachial plexus block, but their efficacy and safety in younger patients are not clear. In this study, we aimed to compare the efficacy and side effects of these 2 drugs in young patients undergoing brachial plexus block.

Methods

We recruited 48 young patients aged 18 to 30 years requiring supraclavicular brachial plexus block. Subjects were randomly divided into 2 groups. Patients in group levobupivacaine+nalbuphine received 28 mL of 0.5% levobupivacaine and 10 mg of nalbuphine diluted in 2 mL 0.9% saline. Patients in group levobupivacaine+dexmedetomidine (LD) received 28 mL of 0.5% levobupivacaine and 0.75 μg/kg dexmedetomidine diluted in 2 mL 0.9% saline. Demographic information, types of fracture, onset time of motor and sensory blocks, duration of block, side effects, and analgesic use were recorded.

Results

We found that the 2 groups did not differ significantly in the demographic profile and fracture type. Compared with group LD, group LD had significantly shorter sensory and motor block onset time, longer block duration, less analgesic need, and less side effects.

Conclusion

In summary, our study suggests that nalbuphine is a better anesthesia adjuvant for supraclavicular brachial plexus block in young patients.
David Ian Olive. 16 April 1937—7 November 2012
Authors: Corrigan Edward , Goddard Peter
Published: September 2020

David Olive, who died in Barton, Cambridgeshire, on 7 November 2012, aged 75, was a theoretical physicist who made seminal contributions to the development of string theory and to our understanding of the structure of quantum field theory. In early work on
S
-matrix theory, he helped to provide the conceptual framework within which string theory was initially formulated. His work, with Gliozzi and Scherk, on supersymmetry in string theory made possible the whole idea of superstrings, now understood as the natural framework for string theory. Olive’s pioneering insights about the duality between electric and magnetic objects in gauge theories were way ahead of their time; it took two decades before his bold and courageous duality conjectures began to be understood. Although somewhat quiet and reserved, he took delight in the company of others, generously sharing his emerging understanding of new ideas with students and colleagues. He was widely influential, not only through the depth and vision of his original work, but also because the clarity, simplicity and elegance of his expositions of new and difficult ideas and theories provided routes into emerging areas of research, both for students and for the theoretical physics community more generally.
Kenneth Henderson Jack. 12 October 1918—28 January 2013
Authors: Jack David , Hampshire Stuart
Published: September 2020

For all but 5 of his 94 years Kenneth Henderson Jack lived, studied, and worked within 10 miles of where he was born, in the North-East of England. Educated in chemistry, he became an X-ray crystallographer. He applied his knowledge of chemistry and his skills in crystallography to the three main areas of materials science: metals, glasses and ceramics. In the 1940s and 1950s he carried out classic studies of the interstitial alloys of the iron–carbon–nitrogen system; between 1957 and 1964, when he worked in industry, he made seminal contributions to glass technology; from 1964 onwards he pioneered a whole new field of oxy-nitride ceramics and glasses, the sialons, and by doing so put his beloved North-East firmly on the international map as a centre of excellence in ceramic science. Ken Jack was fond of saying that, had it not been for World War II, which interrupted his teacher training and took him into university research, he would probably have remained a school teacher and been happy to do so. But, in fact, he did remain a teacher. He was an inspiring lecturer and the researchers who learned their trade by his example went on to lead academic and industrial research groups around the world.
Transient indicators of tipping points in infectious diseases
Authors: O’Regan Suzanne M. , O’Dea Eamon B. , Rohani Pejman , Drake John M.
Published: September 2020

The majority of known early warning indicators of critical transitions rely on asymptotic resilience and critical slowing down. In continuous systems, critical slowing down is mathematically described by a decrease in magnitude of the dominant eigenvalue of the Jacobian matrix on the approach to a critical transition. Here, we show that measures of transient dynamics, specifically, reactivity and the maximum of the amplification envelope, also change systematically as a bifurcation is approached in an important class of models for epidemics of infectious diseases. Furthermore, we introduce indicators designed to detect trends in these measures and find that they reliably classify time series of case notifications simulated from stochastic models according to levels of vaccine uptake. Greater attention should be focused on the potential for systems to exhibit transient amplification of perturbations as a critical threshold is approached, and should be considered when searching for generic leading indicators of tipping points. Awareness of this phenomenon will enrich understanding of the dynamics of complex systems on the verge of a critical transition.
Forecasting resilience profiles of the run-up to regime shifts in nearly-one-dimensional systems
Authors: Adamson Matthew W. , Dawes Jonathan H. P. , Hastings Alan , Hilker Frank M.
Published: September 2020

The forecasting of sudden, irreversible shifts in natural systems is a challenge of great importance, whose realization could allow pre-emptive action to be taken to avoid or mitigate catastrophic transitions, or to help systems adapt to them. In recent years, there have been many advances in the development of such early warning signals. However, much of the current toolbox is based around the tracking of statistical trends and therefore does not aim to estimate the future time scale of transitions or resilience loss. Metric-based indicators are also difficult to implement when systems have inherent oscillations which can dominate the indicator statistics. To resolve these gaps in the toolbox, we use additional system properties to fit parsimonious models to dynamics in order to predict transitions. Here, we consider nearly-one-dimensional systems—higher dimensional systems whose dynamics can be accurately captured by one-dimensional discrete time maps. We show how the nearly one-dimensional dynamics can be used to produce model-based indicators for critical transitions which produce forecasts of the resilience and the time of transitions in the system. A particularly promising feature of this approach is that it allows us to construct early warning signals even for critical transitions of chaotic systems. We demonstrate this approach on two model systems: of phosphorous recycling in a shallow lake, and of an overcompensatory fish population.
Dielectric and energy storage properties of Bi
2
O
3
-B
2
O
3
-SiO
2
doped Ba
0.85
Ca
0.15
Zr
0.1
Ti
0.9
O
3
lead-free glass-ceramics
Authors: Chen Yaohui , Chen Daihua , Meng Liufang , Wan Lingyu , Yao Huilu , Zhai Junyi , Yuan Changlai , Talwar Devki N. , Feng Zhe Chuan
Published: September 2020

A sol–gel method is employed for preparing high quality lead-free glass-ceramic samples (1 −
x
)BCZT-
x
BBS—incorporating Ba
0.85
Ca
0.15
Zr
0.1
Ti
0.9
O
3
(BCZT) powder and Bi
2
O
3
-B
2
O
3
-SiO
2
(BBS) glass-doped additives with different values of
x
(
x
= 0, 0.05, 0.1, 0.15). Systematic investigations are performed to comprehend the structural, dielectric and energy storage characteristics using X-ray diffraction, field-emission scanning electron microscopy, impedance and ferroelectric analyser methods. With appropriate BBS doping (
x
), many fundamental traits including breakdown strength, dielectric loss and energy storage density have shown significant improvements. Low doping-level samples
x
< 0.1 have retained the pure perovskite phase while a second glass phase appeared in samples with
x
≥ 0.1. As the doping level (0.1 ≥
x
> 0) is increased, the average grain size decreased to become better homogeneous materials with improved breakdown energy strengths. Excessive addition of BBS (
x
= 0.15) causes negative effects on microstructures and other traits. The glass-ceramic sample 0.95BCZT-0.05BBS exhibits excellent dielectric permittivity and temperature stability, with the highest energy storage density of 0.3907 J cm
−3
at 130 kV cm
−1
. These results provide good reference to develop lead-free ceramics of high energy storage density.
Ectopic fat accumulation in human astrocytes impairs insulin action
Authors: Heni Martin , Eckstein Sabine S. , Schittenhelm Jens , Böhm Anja , Hogrefe Norbert , Irmler Martin , Beckers Johannes , Hrabě de Angelis Martin , Häring Hans-Ulrich , Fritsche Andreas , Staiger Harald
Published: September 2020

Astrocytes provide neurons with structural support and energy in form of lactate, modulate synaptic transmission, are insulin sensitive and act as gatekeeper for water, ions, glutamate and second messengers. Furthermore, astrocytes are important for glucose sensing, possess neuroendocrine functions and also play an important role in cerebral lipid metabolism. To answer the question, if there is a connection between lipid metabolism and insulin action in human astrocytes, we investigated if storage of ectopic lipids in human astrocytes has an impact on insulin signalling in those cells. Human astrocytes were cultured in the presence of a lipid emulsion, consisting of fatty acids and triglycerides, to induce ectopic lipid storage. After several days, cells were stimulated with insulin and gene expression profiling was performed. In addition, phosphorylation of Akt as well as glycogen synthesis and cell proliferation was assessed. Ectopic lipid storage was detected in human astrocytes after lipid exposure and lipid storage was persistent even when the fat emulsion was removed from the cell culture medium. Chronic exposure to lipids induced profound changes in the gene expression profile, whereby some genes showed a reversible gene expression profile upon removal of fat, and some did not. This included FOXO-dependent expression patterns. Furthermore, insulin-induced phosphorylation of Akt was diminished and also insulin-induced glycogen synthesis and proliferation was impaired in lipid-laden astrocytes. Chronic lipid exposure induces lipid storage in human astrocytes accompanied by insulin resistance. Analyses of the gene expression pattern indicated the potential of a partially reversible gene expression profile. Targeting astrocytic insulin resistance by reducing ectopic lipid load might represent a promising treatment target for insulin resistance of the brain in obesity, diabetes and neurodegeneration.
Biomechanical properties of a buzz-pollinated flower
Authors: Brito Vinicius Lourenço Garcia , Nunes Carlos Eduardo Pereira , Resende Caique Rocha , Montealegre-Zapata Fernando , Vallejo-Marín Mario
Published: September 2020

Approximately half of all bee species use vibrations to remove pollen from plants with diverse floral morphologies. In many buzz-pollinated flowers, these mechanical vibrations generated by bees are transmitted through floral tissues, principally pollen-containing anthers, causing pollen to be ejected from small openings (pores or slits) at the tip of the stamen. Despite the importance of substrate-borne vibrations for both bees and plants, few studies to date have characterized the transmission properties of floral vibrations. In this study, we use contactless laser vibrometry to evaluate the transmission of vibrations in the corolla and anthers of buzz-pollinated flowers of
Solanum rostratum
, and measure vibrations in three spatial axes. We found that floral vibrations conserve their dominant frequency (300 Hz) as they are transmitted throughout the flower. We also found that vibration amplitude at anthers and petals can be up to greater than 400% higher than input amplitude applied at the receptacle at the base of the flower, and that anthers vibrate with a higher amplitude velocity than petals. Together, these results suggest that vibrations travel differently through floral structures and across different spatial axes. As pollen release is a function of vibration amplitude, we conjecture that bees might benefit from applying vibrations in the axes associated with higher vibration amplification.
Natronomonas halophila sp. nov. and Natronomonas salina sp. nov., two novel halophilic archaea
Authors: Yin Xue-Meng , Yang Xiao-Yan , Hou Jing , Zhu Lin , Cui Heng-Lin
Published: September 2020

Two halophilic archaeal strains, C90T and YPL13T, were isolated from a salt lake and a salt mine in PR China. The two strains were found to form two clusters (97.5 and 89.5 % similarity between them, respectively) separating them from the three current members of the genus

Natronomonas

(95.4–97.0 % and 86.6–89.3 % similarity, respectively) on the basis of the 16S rRNA and rpoB′ gene sequence similarities and phylogenetic analysis. Diverse phenotypic characteristics differentiate strains C90T and YPL13T from current

Natronomonas

members. The polar lipids of strain C90T were phosphatidic acid, phosphatidylglycerol (PG), phosphatidylglycerol phosphate methyl ester (PGP-Me), phosphatidylglycerol sulphate, two unidentified glycolipids, a major glycolipid and a minor glycolipid, while those of strain YPL13T were PG, PGP-Me, two unidentified phospholipids and a glycolipid. The average nucleotide identity (ANI) and in silico DNA–DNA hybridization (isDDH) values between the two strains were 79.8 and 27.1 %, respectively, which were much lower than the threshold values proposed as a species boundaries (ANI 95–96 % and isDDH 70 %), which revealed that the two strains represent two novel species; these values (ANI 76.6–80.0 % and isDDH 21.6–27.0 %) of the strains examined in this study and the current members of

Natronomonas

are much lower than the recommended threshold values, suggesting that strains C90T and YPL13T represent two genomically different species of

Natronomonas

. These results showed that strains C90T (=CGMCC 1.13738T=JCM 32961T) and YPL13T (=CGMCC 1.13884T=JCM 31111T) represent two novel species of

Natronomonas

, for which the names Natronomonas halophila sp. nov. and Natronomonas salina sp. nov. are proposed.
Leveraging pathogen sequence and contact tracing data to enhance vaccine trials in emerging epidemics
Authors: Kahn Rebecca , Wang Rui , Leavitt Sarah V. , Hanage William P. , Lipsitch Marc
Published: September 2020

Introduction:

Advance planning of the design and analysis of vaccine trials conducted during infectious disease outbreaks increases our ability to rapidly define the efficacy and potential impact of a vaccine and inform public health response. Vaccine efficacy against infectiousness (VEI) is an important measure for understanding the full impact of a vaccine, yet it is currently not identifiable in many vaccine trial designs because it requires knowledge of the vaccination status of infectors. Recent advances in pathogen genomics have improved our ability to accurately reconstruct transmission networks. We aim to assess if augmenting classical randomized controlled trial designs with pathogen sequence and contact tracing data can permit these trials to estimate VEI.

Methods:

We develop a transmission model with a vaccine trial in an outbreak setting, incorporate pathogen sequence evolution data and sampling as well as contact tracing data, and assign probabilities to likely infectors. We then propose and evaluate the performance of an estimator of VEI.

Results:

We find that under perfect knowledge of infector-infectee pairs, we are able to accurately estimate VEI. Use of sequence data results in imperfect reconstruction of the transmission networks, biasing estimates of VEI towards the null, with approaches using deep sequence data performing better than approaches using consensus sequence data. Inclusion of contact tracing data reduces the bias.

Conclusion:

Pathogen genomics enhance identifiability of VEI from individually randomized controlled trials, but imperfect transmission network reconstruction biases the estimates towards the null and limits our ability to detect VEI. Given the consistent direction of the bias, estimates obtained from trials using these methods will provide lower bounds on the true VEI. A combination of sequence and epidemiologic data results in the most accurate estimates, underscoring the importance of contact tracing in reconstructing transmission networks.
Assessing and Predicting Efficacy of Dance Intervention for Parkinson’s Disease
Authors: Krotinger Anna , Loui Psyche
Published: September 2020

Parkinson’s disease (PD) is associated with a loss of internal cueing systems, affecting rhythmic motor tasks such as walking and speech production. Music and dance encourage spontaneous rhythmic coupling between sensory and motor systems; this has inspired the development of dance programs for PD. Here we assessed the therapeutic outcome and some underlying cognitive mechanisms of dance classes for PD, as measured by neuropsychological assessments of disease severity as well as quantitative assessments of rhythmic ability and sensorimotor experience. We assessed prior music and dance experience, beat perception (Beat Alignment Test), sensorimotor coupling (tapping to high- and low-groove songs), and disease severity (Unified Parkinson’s Disease Rating Scale in PD individuals) before and after four months of weekly dance classes. PD individuals performed better on UPDRS after four months of weekly dance classes, suggesting efficacy of dance intervention. Greater post-intervention improvements in UPDRS were associated with the presence of prior dance experience and with more accurate sensorimotor coupling. Prior dance experience was additionally associated with enhanced sensorimotor coupling during tapping to both high-groove and low-groove songs. These results show that dance classes for PD improve both qualitative and quantitative assessments of disease symptoms. The association between these improvements and dance experience suggests that rhythmic motor training, a mechanism underlying dance training, impacts improvements in parkinsonian symptoms following a dance intervention.
Predictive regulatory and metabolic network models for systems analysis ofClostridioides difficile
Authors: Arrieta-Ortiz Mario L. , Immanuel Selva Rupa Christinal , Turkarslan Serdar , Wu Wei Ju , Girinathan Brintha P. , Worley Jay N. , DiBenedetto Nicholas , Soutourina Olga , Peltier Johann , Dupuy Bruno , Bry Lynn , Baliga Nitin S.
Published: September 2020

ThoughClostridioides difficileis among the most studied anaerobes, the interplay of metabolism and regulation that underlies its ability to colonize the human gut is unknown. We have compiled public resources into three models and a portal to support comprehensive systems analysis ofC. difficile. First, by leveraging 151 transcriptomes from 11 studies we generated a regulatory model (EGRIN) that organizes 90% ofC. difficilegenes into 297 high quality conditional co-regulation modules. EGRIN predictions, validated with independent datasets, recapitulated and extended regulons of key transcription factors, implicating new genes for sporulation, carbohydrate transport and metabolism. Second, by advancing a metabolic model, we discovered that 15 amino acids, diverse carbohydrates, and 10 metabolic genes are essential forC. difficilegrowth within an intestinal environment. Finally, by integrating EGRIN with the metabolic model, we developed a PRIME model that revealed unprecedented insights into combinatorial control of essential processes forin vivocolonization ofC. difficileand its interactions with commensals. We have developed an interactive web portal (http://networks.systemsbiology.net/cdiff-portal/) to disseminate all data, algorithms, and models to support collaborative systems analyses ofC. difficile.
First genome ofLabyrinthula, an opportunistic seagrass pathogen, reveals novel insight into marine protist phylogeny, ecology and CAZyme cell-wall degradation
Authors: Tan Mun Hua , Loke Stella , Croft Laurence J. , Gleason Frank H. , Lange Lene , Pilgaard Bo , Trevathan-Tackett Stacey M.
Published: September 2020

Labyrinthulaspp. are saprobic, marine protists that also act as opportunistic pathogens and are the causative agents of seagrass wasting disease (SWD). Despite the threat of local- and large-scale SWD outbreaks, there are currently gaps in our understanding of the drivers of SWD, particularly surroundingLabyrinthulavirulence and ecology. Given these uncertainties, we investigatedLabyrinthulafrom a novel genomic perspective by presenting the first draft genome and predicted proteome of a pathogenic isolate ofLabyrinthulaSR_Ha_C, generated from a hybrid assembly of Nanopore and Illumina sequences. Phylogenetic and cross-phyla comparisons revealed insights into the evolutionary history of Stramenopiles. Genome annotation showed evidence of glideosome-type machinery and an apicoplast protein typically found in protist pathogens and parasites. Proteins involved inLabyrinthula’s actin-myosin mode of transport, as well as carbohydrate degradation were also prevalent. Further, CAZyme functional predictions revealed a repertoire of enzymes involved in breakdown of cell-wall and carbohydrate storage compounds common to seagrasses. The relatively low number of CAZymes annotated from the genome ofLabyrinthulaSR_Ha_C compared to other Labyrinthulea species may reflect the conservative annotation parameters, a specialised substrate affinity and the scarcity of characterised protist enzymes. Inherently, there is high probability for finding both unique and novel enzymes fromLabyrinthulaspp. This study provides resources for further exploration ofLabyrinthulaecology and evolution, and will hopefully be the catalyst for new hypothesis-driven SWD research revealing more details of molecular interactions betweenLabyrinthulaspecies and its host substrate.
Inducible expression of humanC9ORF7236x G4C2hexanucleotide repeats is sufficient to cause RAN translation and rapid muscular atrophy in mice
Authors: Riemslagh F.W. , van der Toorn E.C. , Verhagen R.F.M , Maas A. , Bosman L.W.J. , Hukema R.K. , Willemsen R.
Published: September 2020

The hexanucleotide G4C2repeat expansion in the first intron of theC9ORF72gene explains the majority of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) cases. Numerous studies have indicated the toxicity of dipeptide repeats (DPRs) which are produced via repeat-associated non-AUG (RAN) translation from the repeat expansion and accumulate in the brain of C9FTD/ALS patients. Mouse models expressing the humanC9ORF72repeat and/or DPRs show variable pathological, functional and behavioral characteristics of FTD and ALS. Here, we report a new Tet-on inducible mouse model that expresses 36x pure G4C2repeats with 100bp upstream and downstream human flanking regions. Brain specific expression causes the formation of sporadic sense DPRs aggregates upon 6 months dox induction but no apparent neurodegeneration. Expression in the rest of the body evokes abundant sense DPRs in multiple organs, leading to weight loss, neuromuscular junction disruption, myopathy and a locomotor phenotype within the time frame of four weeks. We did not observe any RNA foci or pTDP-43 pathology. Accumulation of DPRs and the myopathy phenotype could be prevented when 36x G4C2repeat expression was stopped after 1 week. After 2 weeks of expression, the phenotype could not be reversed, even though DPR levels were reduced. In conclusion, expression of 36x pure G4C2repeats including 100bp human flanking regions is sufficient for RAN translation of sense DPRs and evokes a functional locomotor phenotype. Our inducible mouse model highlights the importance of early diagnosis and treatment for C9FTD/ALS patients.

Summary statement

Only 36 C9ORF72 repeats are sufficient for RAN translation in a new mouse model for ALS and FTD. Reducing toxic dipeptides can prevent but not reverse the phenotype.
MetaNetX/MNXref - unified namespace for metabolites and biochemical reactions in the context of metabolic models
Authors: Moretti Sébastien , Tran Van Du T. , Mehl Florence , Ibberson Mark , Pagni Marco
Published: September 2020

MetaNetX/MNXref is a reconciliation of metabolites and biochemical reactions providing cross-links between major public biochemistry and Genome-Scale Metabolic Network (GSMN) databases. The new release brings several improvements with respect to the quality of the reconciliation, with particular attention dedicated to preserving the intrinsic properties of GSMN models. The MetaNetX website (https://www.metanetx.org/) provides access to the full database and online services. A major improvement is for mapping of user-provided GSMNs to MXNref, which now provides diagnostic messages about model content. In addition to the website and flat files, the resource can now be accessed through a SPARQL endpoint (https://rdf.metanetx.org).
An Engineered Genetic Circuit for Lactose Intolerance Alleviation Coupled with Gut Microbiota Recovery
Authors: Cheng Mingyue , Cheng Zhangyu , Yu Yiyan , Liu Wangjie , Li Ruihao , Guo Zhenyi , Qin Jiyue , Zeng Zhi , Di Lin , Mo Yufeng , Pan Chunxiu , Liang Yuanhao , Li Jinman , Tong Yigang , Yan Yunjun , Zhan Yi , Ning Kang
Published: September 2020

Background

Lactose malabsorption occurs in around 68% of the world populations, causing lactose intolerance (LI) symptoms such as abdominal pain, bloating and diarrhoea. To alleviate LI, previous studies mainly focused on strengthening intestinal β-galactosidase activity but neglected the inconspicuous colon pH drop caused by gut microbes’ fermentation on non-hydrolysed lactose. The colon pH drop will reduce intestinal β-galactosidase activity and influence the intestinal homeostasis.

Results

Here, we synthesized a tri-stable-switch circuit equipped with high β-galactosidase activity and pH rescue ability. This circuit can switch in functionality between expression of β-galactosidase and expression of l-lactate dehydrogenase in respond to intestinal lactose signal and intestinal pH signal. We confirmed the circuit functionality was efficient using 12-hrsin vitroculture at a range of pH levels, as well as 6-hrsin vivosimulations in mice colon. Moreover, another 21-days mice trial indicated that this circuit can recover lactose-effected gut microbiota of mice to the status (enterotypes) similar to that of mice without lactose intake.

Conclusions

Taken together, the tri-stable-switch circuit can serve as a promising prototype for LI symptoms relief, especially by flexibly adapting to environmental variation, stabilizing colon pH and restoring gut microbiota.
Sequence memory in recurrent neuronal network can develop without structured input
Authors: Loidolt Matthias , Rudelt Lucas , Priesemann Viola
Published: September 2020

How does spontaneous activity during development prepare cortico-cortical connections for sensory input? We here analyse the development of sequence memory, an intrinsic feature of recurrent networks that supports temporal perception. We use a recurrent neural network model with homeostatic and spike-timing-dependent plasticity (STDP). This model has been shown to learn specific sequences from structured input. We show that development even under unstructured input increases unspecific sequence memory. Moreover, networks “pre-shaped” by such unstructured input subsequently learn specific sequences faster. The key structural substrate is the emergence of strong and directed synapses due to STDP and synaptic competition. These construct self-amplifying preferential paths of activity, which can quickly encode new input sequences. Our results suggest that memory traces are not printed on atabula rasa, but instead harness building blocks already present in the brain.
High-quality carnivore genomes from roadkill samples enable species delimitation in aardwolf and bat-eared fox
Authors: Allio Rémi , Tilak Marie-Ka , Scornavacca Céline , Avenant Nico L. , Corre Erwan , Nabholz Benoit , Delsuc Frédéric
Published: September 2020

In a context of ongoing biodiversity erosion, obtaining genomic resources from wildlife is becoming essential for conservation. The thousands of yearly mammalian roadkill could potentially provide a useful source material for genomic surveys. To illustrate the potential of this underexploited resource, we used roadkill samples to sequence reference genomes and study the genomic diversity of the bat-eared fox (Otocyon megalotis) and the aardwolf (Proteles cristata) for which subspecies have been defined based on similar disjunct distributions in Eastern and Southern Africa. By developing an optimized DNA extraction protocol, we successfully obtained long reads using the Oxford Nanopore Technologies (ONT) MinION device. For the first time in mammals, we obtained two reference genomes with high contiguity and gene completeness by combining ONT long reads with Illumina short reads using hybrid assembly. Based on re-sequencing data from few other roakill samples, the comparison of the genetic differentiation between our two pairs of subspecies to that of pairs of well-defined species across Carnivora showed that the two subspecies of aardwolf might warrant species status (P. cristataandP. septentrionalis), whereas the two subspecies of bat-eared fox might not. Moreover, using these data, we conducted demographic analyses that revealed similar trajectories between Eastern and Southern populations of both species, suggesting that their population sizes have been shaped by similar environmental fluctuations. Finally, we obtained a well resolved genome-scale phylogeny for Carnivora with evidence for incomplete lineage sorting among the three main arctoid lineages. Overall, our cost-effective strategy opens the way for large-scale population genomic studies and phylogenomics of mammalian wildlife using roadkill.
Converting Microwave Ovens into Plasma-Generating Decontamination Units for N-95 Respirators
Authors: Ruzic David N. , Oh Chamteut , Puthussery Joseph V. , Patel Dhruval , Jeckell Zach , Verma Vishal , Nguyen Thanh H.
Published: September 2020

We show how a common microwave oven, a coat-hanger and a coffee cup can be used to decontaminate N-95 respirators in 30 seconds. Tulane virus in the artificial saliva was reduced by >3 log andGeobacillus stearothermophilusspores were reduced by >6 log. Respirators maintained filtration and fit even after 10 cycles. Filtration and fit tests performed by the CDC confirmed there was no damage to the respirators. Spectroscopy of the plasma reveals that OH and C-containing radicals as the most prevalent active species.
Emergence and expansion of highly infectious spike:D614G mutant SARS-CoV-2 in central India
Authors: Sharma Shashi , Dash Paban Kumar , Sharma Sushil K , Srivastava Ambuj , Kumar Jyoti S , Karothia B.S. , Chelvam K T , Singh Sandip , Gupta Abhay , Yadav Ram Govind , Yadav Ruchi , Greshma TS , Kushwah Pramod , Bhushan Ravi , Nagar D.P. , Nandan Manvendra , Kumar Subodh , Thavaselvam Duraipandian , Dubey Devendra Kumar
Published: September 2020

COVID 19 has emerged as global pandemic with largest damage to the economy and human psyche. The genomic signature deciphered during the ongoing pandemic period is valuable to understand the virus evolutionary patterns and spread across the globe. Increased availability of genome information of circulating strain in our country will enable to generate selective details in virulent and non virulent markers to prophylaxis and therapeutic interventions. The first case of SARS CoV-2 was detected in Chambal region of Madhya Pradesh state in mid of March 2020 followed by multiple introduction events and expansion of COVID-19 cases within 3 months in this region. We analyzed around 5000 COVID -19 suspected samples referred to Defence Research and Development Establishment, Gwalior, Madhya Pradesh. A total of 136 cases were found positive over a span of three months period this includes virus introduction to region and further spread. Whole genome sequences employing Oxford nanopore technology were deciphered for 26 SARS-CoV-2 circulating in 10 different districts in Madhya Pradesh State of India. The region witnessed index cases with multiple travel history responsible for introduction of COVID-19 followed by remarkable expansion of virus. The genome wide substitutions including in important viral proteins were observed. The detailed phylogenetic analysis revealed the circulating SARS-CoV-2 clustered in multiple clades A2a, A4 and B. The cluster wise segregation was observed suggesting multiple introduction links and evolution of virus in the region. This is the first comprehensive details of whole genome sequence analysis from central India region, which will add genome wide knowledge towards diagnostic and therapeutic interventions.
Adaptive evolution in DNMT2 supports its role in the dipteran immune response
Authors: Bhattacharya Tamanash , Rice Danny W. , Hardy Richard W. , Newton Irene L.G.
Published: September 2020

Eukaryotic nucleic acid methyltransferase (MTase) proteins are essential mediators of epigenetic and epitranscriptomic regulation. DNMT2 belongs to a large, conserved family of DNA MTases found in many organisms, including holometabolous insects like fruit flies and mosquitoes, where it is the lone MTase. Interestingly, despite its nomenclature, DNMT2 is not a DNA MTase, but instead targets and methylates RNA species. A growing body of literature suggest DNMT2 mediates the host immune response against a wide range of pathogens, including RNA viruses. Evidence of adaptive evolution, in the form of positive selection, can often be found in genes that are engaged in conflict with pathogens like viruses. Here we identify and describe evidence of positive selection that has occurred at different times over the course of DNMT2 evolution within dipteran insects. We identify specific codons within each ortholog that are under positive selection, and find they are restricted to four distinct domains of the protein and likely influence substrate binding, target recognition, and adaptation of unique intermolecular interactions. Additionally, we describe the role of the Drosophila-specific host protein IPOD, in regulating the expression and/or function of fruit fly DNMT2. Finally, heterologous expression of these orthologs suggest that DNMT2’s role as an antiviral is host dependent, indicating a requirement for additional host-specific factors. Collectively, our findings highlight the adaptive evolution of DNMT2 in Dipteran insects, underscoring its role as an important, albeit non-canonical, regulator of host-pathogen interactions in mosquitoes and fruit flies.
Hymenoptera associated eukaryotic virome lacks host specificity
Authors: Deboutte Ward , Beller Leen , Yinda Claude Kwe , Shi Chenyan , Smets Lena , Vanmechelen Bert , Conceição-Neto Nadia , Dallmeier Kai , Maes Piet , de Graaf Dirk C , Matthijnssens Jelle
Published: September 2020

Recent advancements in sequencing technologies and metagenomic studies have increased the knowledge of the virosphere associated with honey bees tremendously. In this study, viral-like particle enrichment and deep sequencing was deployed to detect viral communities in managed Belgian honey bees. A substantial number of previously undescribed divergent virus genomes was detected, including a rhabdovirus and a recombinant virus possessing a divergentLake Sinai Viruscapsid and a Hepe-like polymerase. Furthermore, screening > 5,000 public sequencing datasets for the retrieved set of viral genomes revealed an additional plethora of undetected, divergent viruses present in a wide range of Hymenoptera species. The unexpected high number of shared viral genomes within the Apidae family and across different families within the order Hymenoptera suggests that many of these viruses are highly promiscuous, that virus sharing within and between Hymenoptera families occurs frequently, and that the concept of species-specific viral taxa inside the Hymenoptera should be revisited. In particular, this estimation implies that sharing of several viral species, thought to be specific for bees, across other eukaryotic taxa is rampant. This study provides important insights on the host taxonomical breadth of some of the known “bee viruses” and might have important implications on strategies to combat viruses that are relevant to pollinators.
Rubisco adaptation is more limited by phylogenetic constraint than by catalytic trade-off
Authors: Bouvier Jacques W. , Emms David M. , Rhodes Timothy , Bolton Jai S. , Brasnett Amelia , Eddershaw Alice , Nielsen Jochem R. , Unitt Anastasia , Whitney Spencer M. , Kelly Steven
Published: September 2020

Rubisco assimilates CO2to form the sugars that fuel life on earth. Correlations between rubisco kinetic traits across species have led to the proposition that rubisco adaptation is highly constrained by catalytic trade-offs. However, these analyses did not consider the phylogenetic context of the enzymes that were analysed. Thus, it is possible that the correlations observed were an artefact of the presence of phylogenetic signal in rubisco kinetics and the phylogenetic relationship between the species that were sampled. Here, we conducted a phylogenetically-resolved analysis of rubisco kinetics and show that there is a significant phylogenetic signal in rubisco kinetic traits. We re-evaluated the extent of catalytic trade-offs accounting for this phylogenetic signal and found that all were attenuated. Following phylogenetic correction, the largest catalytic trade-offs were observed between the Michaelis constant for CO2and carboxylase turnover (∼21-37 %), and between the Michaelis constants for CO2and O2(∼9-19 %), respectively. All other catalytic trade-offs were substantially attenuated such that they were marginal (<9 %) or non-significant. This phylogenetically resolved analysis of rubisco kinetic evolution also identified kinetic changes that occur concomitant with the evolution of C4photosynthesis. Finally, we show that phylogenetic constraints (most likely caused by a slow rate of molecular evolution) have played a larger role than catalytic trade-offs in limiting the evolution of rubisco kinetics. Thus, although there is strong evidence for some catalytic trade-offs, rubisco adaptation has been more limited by phylogenetic constraint than by the combined action of all such trade-offs.