bluuebunny/crossref_metadata_2025 huggingface dataset:
CHOROIDEREMIA
Authors: Pennesi Mark E. , Birch David G. , Duncan Jacque L. , Bennett Jean , Girach Aniz
Published: April 2019

Purpose:

Choroideremia is an incurable, X-linked, recessive retinal dystrophy caused by loss of function mutations in the CHM gene. It is estimated to affect approximately 1 in 50,000 male patients. It is characterized by progressive degeneration of the retinal pigment epithelium, choroid, and photoreceptors, resulting in visual impairment and blindness. There is an unmet need in choroideremia, because currently, there are no approved treatments available for patients with the disease.

Methods:

We review the patient journey, societal impact, and emerging treatments for patients with choroideremia.

Results:

Its relative rarity and similarities with other retinal diseases in early years mean that diagnosis of choroideremia can often be delayed. Furthermore, its impact on affected individuals, and wider society, is also likely underestimated. AAV2-mediated gene therapy is an investigational treatment that aims to replace the faulty CHM gene. Early-phase studies reported potentially important visual acuity gains and maintenance of vision in some patients, and a large Phase 3 program is now underway.

Conclusion:

Choroideremia is a disease with a significant unmet need. Interventions that can treat progression of the disease and improve visual and functional outcomes have the potential to reduce health care costs and enhance patient quality of life.
DNP Program Faculty and Graduates' Knowledge and Use of QI and Safety Processes
Authors: Tovar Elizabeth , Ossege Julianne , Farus-Brown Susan , Zonsius Mary , Morrow Linda
Published: April 2019

Background

Across doctor of nursing practice (DNP) programs, wide variation exists for DNP project expectations and curricular integration of Quality and Safety Education for Nurses competencies.

Purpose

This study examined DNP project characteristics and compared knowledge, skills, and attitudes about quality improvement (QI) processes between DNP program faculty and graduates.

Methods

This descriptive study used a national convenience sample of DNP program faculty and graduates from multiple settings (N = 147) who completed an electronic survey of a modified version of the Quality Improvement Knowledge, Skills, and Attitudes Survey.

Results

Most DNP projects were QI/practice improvement (85.5%) and required interprofessional collaboration (65%) and implementation of a practice change (55.8%) with evaluation (65.5%). DNP program faculty (n = 73) and graduates (n = 30) had no significant differences in QI knowledge or skills; faculty reported less confidence in their knowledge (P = .002) and skills (P = .007) than graduates.

Conclusions

Faculty development efforts to improve QI knowledge and skills for DNP program faculty are needed.
Neuropsychiatric Syndromes in Childhood-Onset Systemic Lupus Erythematosus
Authors: Santos Flávia Patrícia Sena Teixeira , Nascimento Bruno Ramos , Calderaro Débora Cerqueira , Ferreira Gilda Aparecida , Correa Humberto
Published: April 2019

Objective

The aim of this study was to access the prevalence of 19 neuropsychiatric syndromes in childhood-onset systemic lupus erythematosus (cSLE), as defined by the American College of Rheumatology (ACR) in 1999, by performing a systematic review and meta-analysis of relevant publications.

Methods

A literature search from April 1999 to March 2018 identified studies investigating neuropsychiatric syndromes in cSLE patients, applying 1999 ACR Case Definitions, with a sample of at least 20 patients. Case reports, small case series, reviews, articles that did not use 1999 ACR case definitions, and those with adult SLE patients were excluded. The methodological quality of the studies was determined through the Loney quality assessment. Prevalence estimates with a 95% confidence interval were combined using random-effect (DerSimonian-Laird) models.

Results

A total of 143 articles were identified and 9 were included. In a population of 1463 cSLE patients, 351 (29.9%) presented 869 neuropsychiatric cSLE events (2.48 events/patient). The results for each syndrome were headache (52.2%), seizure disorders (48.6%), cognitive dysfunction (32.9%), mood disorder (28.3%), psychosis (22.7%), cerebrovascular disease (19.5%), acute confusional state (15.7%), movement disorder (9.4%), anxiety disorder (7.2%), aseptic meningitis (5.1%), mononeuropathy single/multiplex (4.9%), myelopathy (4.2%), demyelinating syndrome (3.2%), cranial neuropathy (2.7%), polyneuropathy (2.6%), Guillain-Barré syndrome (2.5%), autonomic disorder (1.9%), plexopathy (1.3%), and myasthenia gravis (1.3%).

Conclusions

Neuropsychiatric syndromes are prevalent among cSLE patients. The most prevalent were headaches, seizures, cognitive dysfunction, mood disorders, and psychosis. Determining the prevalence of each neuropsychiatric syndrome in cSLE may improve clinical awareness of these potentially fatal and disabling conditions.
Dermatomyositis Associated With Papillary Thyroid Cancer
Authors: Yilmaz Umut , Ugurlu Serdal
Published: April 2019

Objective

There is a well-known association between malignancy and dermatomyositis but reports of an association between malignancies of the thyroid gland and dermatomyositis are very few. Here we describe a recent case of dermatomyositis found to have thyroid cancer during screening and review the clinical features of the similar cases in literature.

Methods

The case history, treatment responses and follow up data are described. We performed a systematic literature review using the keywords (thyroid cancer OR thyroid carcinoma) AND dermatomyositis.

Results

35 year old male presented with an acute onset of symptoms including facial rash, widespread myalgia, muscle weakness and dysphagia. Patient was diagnosed with dermatomyositis based on clinical findings, laboratory, electromyography and imaging results and immunosuppressive treatment initiated. Screening for cancer revealed a papillary thyroid carcinoma. Thyroidectomy was performed and immunosuppressive medication was gradually tapered and stopped. At 24 months following the diagnosis patient remains in remission. This is the 14th reported case of dermatomyositis and thyroid cancer in the English literature. Analysis of data from these 14 cases while revealing conflicting insights about the link between dermatomyositis and thyroid cancer do not rule out this possibility. Treatment of thyroid cancer appeared to have a significant influence on the course of dermatomyositis in at least six of these cases.

Conclusion

Better recognition of the link between dermatomyositis and thyroid cancer may allow physicians to protect some dermatomyositis patients from morbidity and mortality associated with immunosuppression.
FDG PET/CT Demonstrated Precursor B-cell Lymphoblastic Lymphoma in a Pediatric Patient With Hemophilia B
Authors: Liu Zhimou , Yang Xu , Liu Jie , Yang Jigang
Published: April 2019

A 4-year-old boy with history of hemophilia B presented with increasingly enlarged scalp masses. Although they were initially thought as hematomas, unresponsiveness to the therapy lead to suspicion of malignancy, which prompted FDG PET/CT. The FDG PET/CT images demonstrated increased FDG uptake in the scalp masses and cervical lymph nodes. The pathology from the left scalp mass and the left cervical lymph nodes revealed precursor B-cell lymphoblastic lymphoma.
The Value of Plastic Surgery Spinal Closures
Authors: Xu Hope , Rozanski Collin , Taub Peter J.
Published: April 2019

Background

The role of the plastic surgeon in wound management after complications from previous spinal surgeries is well established.

Purpose

The present study evaluates wound complications after plastic surgeon closure of the primary spinal surgery in a large patient population.

Study Design and Setting

This is a retrospective review of spine surgery patients undergoing plastic surgeon closure of spine surgeries at a single tertiary care center.

Patient Sample

Spine surgery patients included those who were referred for plastic surgeon closure due to (a) concerns about patient healing potential, (b) concerns about difficulty of closure, (c) patient request, or (d) difficulties with closure intraoperatively.

Outcome Measures

The outcomes are physiologic measures, including intraoperative and postoperative complications, hospital length of stay, and 30-day readmissions and reoperations.

Methods

Outcomes in this sample were compared with previously published outcomes using 2-sample z tests. The authors have no conflicts of interest.

Results

Nine hundred twenty-eight surgeries were reviewed, of which 782 were included. Fourteen patients (1.8%) required readmission with 30 days. This compares favorably to a pooled analysis of 488,049 patients, in which the 30-day readmission rate was found to be 5.5% (z = 4.5, P < 0.0001). Seven patients (0.89%) had wound infection and 3 (0.38%) wound dehiscence postoperatively, compared with a study of 22,430 patients in the American College of Surgeons National Surgery Quality Improvement Program database, which had an infection incidence of 2.2% (z = 2.5, P = 0.0132) and 0.3% dehiscence rate (z = 0.4, P = 0.6889). The combined incidence of wound complications in the present sample was 1.27%, which is less than the combined incidence of wound complications in the population of 22,430 patients (z = 2.2, P = 0.029).

Conclusions

Thirty-day readmissions and wound complications are intensely scrutinized quality metrics that may lead to reduced reimbursements and other penalties for hospitals. Plastic surgeon closure of index spinal cases decreases these adverse outcomes. Further research must be conducted to determine whether the increased cost of plastic surgeon involvement in these cases is offset by the savings represented by fewer readmissions and complications.
Neuromuscular Electrical Stimulation Improves Energy Substrate Metabolism and Survival in Mice With Acute Endotoxic Shock
Authors: Irahara Takayuki , Sato Norio , Otake Kosuke , Murata Satoru , Inoue Kazuo , Koike Kaoru , Yokota Hiroyuki
Published: April 2019

This study investigated the therapeutic benefits of neuromuscular electrical stimulation (NMES).

C57BL/6 mice were administered lipopolysaccharide (LPS; 20 mg/kg body weight) by intraperitoneal injection and divided into control (C) and NMES groups (n = 10–12 each). The latter received NMES to the bilateral gastrocnemius muscle for 1 h at low or high frequency (LF = 2 Hz and HF = 50 Hz, respectively) and low or high voltage (LV = 10 V and HV = 50 V, respectively). In LF–LV and LF–HV groups, NMES was performed twice and the results were compared with those for mice that received one round of NMES. Changes in energy metabolism were measured by indirect calorimetry up to 24 h; survival was evaluated up to 72 h after LPS administration; peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α expression in the liver and gastrocnemius muscle was evaluated by quantitative PCR; and plasma concentration of interleukin (IL)-6 was determined by enzyme-linked immunosorbent assay.

Survival was improved only in the LF–LV group with one round of NMES (P < 0.01) and the LF–HV group with two rounds of NMES (P < 0.05). Fatty acid oxidation (FAO) was slightly increased in these two groups, whereas carbohydrate oxidation (CHO) was decreased or not changed. Significant upregulation of PGC-1α in muscle as well as a decrease in plasma IL-6 level were also observed in these two groups (P < 0.05).

Thus, NMES exerts therapeutic effects under conditions that induce a mild switch in energy metabolism from glucose to lipid predominant metabolism through PGC-1α upregulation and suppression of inflammation, and may be an effective early intervention even in hemodynamically unstable patients.
Tracking DO2 with Compensatory Reserve During Whole Blood Resuscitation in Baboons
Authors: Koons Natalie J. , Nguyen Betty , Suresh Mithun R. , Hinojosa-Laborde Carmen , Convertino Victor A.
Published: April 2019

Hemorrhagic shock can be mitigated by timely and accurate resuscitation designed to restore adequate delivery of oxygen (DO2) by increasing cardiac output (CO). However, standard care of using systolic blood pressure (SBP) as a guide for resuscitation may be ineffective and can potentially be associated with increased morbidity. We have developed a novel vital sign called the compensatory reserve measurement (CRM) generated from analysis of arterial pulse waveform feature changes that has been validated in experimental and clinical models of hemorrhage. We tested the hypothesis that thresholds of DO2 could be accurately defined by CRM, a noninvasive clinical tool, while avoiding over-resuscitation during whole blood resuscitation following a 25% hemorrhage in nonhuman primates. To accomplish this, adult male baboons (n = 12) were exposed to a progressive controlled hemorrhage while sedated that resulted in an average (± SEM) maximal reduction of 508 ± 18 mL of their estimated circulating blood volume of 2,130 ± 60 mL based on body weight. CRM increased from 6 ± 0.01% at the end of hemorrhage to 70 ± 0.02% at the end of resuscitation. By linear regression, CRM values of 6% (end of hemorrhage), 30%, 60%, and 70% (end of resuscitation) corresponded to calculated DO2 values of 5.9 ± 0.34, 7.5 ± 0.87, 9.3 ± 0.76, and 11.6 ± 1.3 mL O2·kg−1·min−1 during resuscitation. As such, return of CRM to ∼65% during resuscitation required only ∼400 mL to restore SBP to 128 ± 6 mmHg, whereas total blood volume replacement resulted in over-resuscitation as indicated by a SBP of 140 ± 7 mmHg compared with an average baseline value of 125 ± 5 mmHg. Consistent with our hypothesis, thresholds of calculated DO2 were associated with specific CRM values. A target resuscitation CRM value of ∼65% minimized the requirement for whole blood while avoiding over-resuscitation. Furthermore, 0% CRM provided a noninvasive metric for determining critical DO2 at approximately 5.3 mL O2·kg−1·min−1.
Exploring the Effects of a Biopoem Writing Intervention on Middle School Students With Autism Spectrum Disorder
Authors: Asaro-Saddler Kristie , Ellis-Robinson Tammy , Eacker Halley
Published: April 2019

The purpose of this study was to explore how poetry writing can promote growth in social cognition, writing, and disciplinary literacy for middle school students diagnosed with autism spectrum disorders. An interpretive qualitative content analysis design was used to explore the instructional discourse and written products of the participants during a writing intervention using biopoems to learn about important people in history. Main findings indicated that participants were able to recognize and use emotion/perspective taking words, that the biopoem structure was effective in organizing their writing and enhancing word choice, and that they demonstrated disciplinary literacy through perspective taking and identification of historical significance. The discourse that accompanied the biopoem lessons included evidence of thinking processes and emerging understandings that resulted from the writing process. The context of conversation also allowed for higher order thinking and intertextuality to occur. Implications for practice and future research are discussed.
Optimizing Mycophenolic Acid Exposure in Kidney Transplant Recipients: Time for Target Concentration Intervention
Authors: Metz David K. , Holford Nick , Kausman Joshua Y. , Walker Amanda , Cranswick Noel , Staatz Christine E. , Barraclough Katherine A. , Ierino Francesco
Published: April 2019

The immunosuppressive agent mycophenolate is used extensively in kidney transplantation, yet dosing strategy applied varies markedly from fixed dosing (“one-dose-fits-all”), to mycophenolic acid (MPA) trough concentration monitoring, to dose optimization to an MPA exposure target (as area under the concentration-time curve [MPA AUC0-12]). This relates in part to inconsistent results in prospective trials of concentration-controlled dosing (CCD). In this review, the totality of evidence supporting mycophenolate CCD is examined: pharmacological characteristics, observational data linking exposure to efficacy and toxicities, and randomized controlled trials of CCD, with attention to dose optimization method and exposure achieved. Fixed dosing of mycophenolate consistently leads to underexposure associated with rejection, as well as overexposure associated with toxicities. When CCD is driven by pharmacokinetic calculation to a target concentration (target concentration intervention), MPA exposure is successfully controlled and clinical benefits are seen. There remains a need for consensus on practical aspects of mycophenolate target concentration intervention in contemporary tacrolimus-containing regimens and future research to define maintenance phase exposure targets. However, given ongoing consequences of both overimmunosuppression and underimmunosuppression in kidney transplantation, impacting short- and long-term outcomes, these should be a priority. The imprecise “one-dose-fits-all” approach should be replaced by the clinically proven MPA target concentration strategy.
Deep Transcranial Magnetic Stimulation for the Treatment of Negative Symptoms in Schizophrenia
Authors: Linsambarth Sergio , Jeria Alvaro , Avirame Keren , Todder Doron , Riquelme Raúl , Stehberg Jimmy
Published: April 2019

Background

Negative symptoms of schizophrenia show limited response to both typical and atypical antipsychotics. Repetitive transcranial magnetic stimulation applied over the prefrontal cortex (PFC) has been proposed as an adjuvant to pharmacological treatment of negative symptoms in schizophrenia, but whether the improvements obtained are specific to negative symptoms or attributable to antidepressant effects is still unclear.

Objective

The aim of the present study is to determine to which extent the improvements in negative symptoms of schizophrenia obtained after high-frequency stimulation of the bilateral PFC using deep TMS (dTMS) are attributable to antidepressant effects.

Methods

Repetitive dTMS was administered to the PFC in a cohort of 16 patients with schizophrenia under successful pharmacological control of positive symptoms and predominant negative symptoms. Patients were treated using high-frequency (18 Hz) bilateral stimulation applied over the lateral PFC bilaterally using Brainsway H-2 coil. The effects of dTMS on negative symptoms were measured using the Scale for the Assessment of Negative Symptoms and the Positive and Negative Syndrome Scales. We then compared the improvements in negative symptoms obtained in patients showing depressive symptoms (≥7 points) with those found in patients without depression (>7 points), as determined by the Calgary Scale for Depression.

Results

Repetitive dTMS treatment induced significant improvements in negative symptoms as assessed using both Scale for the Assessment of Negative Symptoms and Positive and Negative Syndrome Scales. Comparison of the improvements obtained in patients with or without depression at the beginning of treatment revealed similar improvements in negative symptoms, irrespective of subjacent depression.

Conclusions

Our data suggest that the beneficial effects of high frequency dTMS of the PFC cannot be attributed solely to its antidepressant effects.
Central-Positive Complexes
Authors: Hogan R. Edward , Trammel Emma R. , Farber Nuri B. , Avidan Michael S. , Palanca Ben Julian A.
Published: April 2019

Objectives

Electroencephalography (EEG) allows monitoring of generalized seizures induced during electroconvulsive therapy (ECT). Scalp EEG recordings show different phases of electroencephalographic ictal activity during ECT seizures, documenting a pattern of seizures that may vary within and across individuals. In this case series, we used 64-electrode high-density EEG recording to detect topographic electroencephalographic changes not typically evident with conventional limited montages commonly used during ECT.

Methods

The EEG recordings were acquired from 5 participants (24 ECT sessions) during index courses for treatment-resistant depression. Using previously proposed staging criteria, the ictal EEG and simultaneously acquired video were interpreted by an expert reviewer blinded to study treatment parameters.

Results

The EEG recordings of all seizures showed generalized, high-amplitude, central-positive complexes (CPCs), which emerged at the beginning of phase III (polyspike and slow wave activity), with median duration of 47 seconds (interquartile range, 77 seconds), ranging from 14 to 203 seconds. Although individuals showed variability in frequency and amplitude of CPCs, CPCs typically evolved from 4.0 to 1.5 Hz in frequency and decreased in amplitude as the seizure progressed. Elaborating on previously described phases of ECT-induced electrographic seizures, we describe variability in morphology at seizure termination. Initiation of CPCs typically corresponded with clonic movements, but often terminated after motor signs ceased.

Conclusions

Generalized, high-amplitude, CPCs during ECT are a previously uncharacterized ictal waveform during ECT, which may have important scientific and clinical value. These complexes offer a specific marker for correlating clinical outcomes in ECT and greater understanding of generalized tonic-clonic seizures.
Electroconvulsive Therapy for Neuroleptic Malignant Syndrome
Authors: Morcos Nicholas , Rosinski Amy , Maixner Daniel F.
Published: April 2019

Objectives

Neuroleptic malignant syndrome (NMS) is an uncommon condition associated with significant morbidity and mortality. Data on treatment interventions are limited. In this case series, we sought to describe all NMS cases requiring ECT from a large academic institution over a nearly 2-decade period.

Methods

We retrospectively identified all patients with NMS who were treated with ECT over a 17-year period. Patients were included in the study based on chart review using the International Consensus Diagnostic Criteria for NMS. Data were collected related to clinical findings, treatment course, and response to ECT.

Results

We identified 15 patients meeting the inclusion criteria. Most patients had neurocognitive or schizophrenia spectrum disorders and developed NMS after exposure to multiple antipsychotic drugs. All patients received bitemporal ECT after failed pharmacotherapy for NMS. Electroconvulsive therapy was well tolerated and resulted in a remission rate of 73.3% (n = 11). Patients showed early initial response to ECT (mean of 4.2 treatments), but an average of 17.7 treatments was necessary to minimize recurrence of catatonic signs. One patient died after interruption of the index course of ECT because of severe infection, and another was discharged to hospice care after limited response. These cases highlight the lethality of NMS and its complications despite aggressive treatment measures.

Conclusions

Bitemporal ECT was well tolerated and effective in treating NMS refractory to pharmacotherapy. We suggest that ECT be considered early in cases of NMS that are refractory to pharmacological interventions, especially if the underlying condition is also responsive to ECT.
The distribution of epistasis on simple fitness landscapes
Authors: Fraïsse Christelle , Welch John J.
Published: April 2019

Fitness interactions between mutations can influence a population’s evolution in many different ways. While epistatic effects are difficult to measure precisely, important information is captured by the mean and variance of log fitnesses for individuals carrying different numbers of mutations. We derive predictions for these quantities from a class of simple fitness landscapes, based on models of optimizing selection on quantitative traits. We also explore extensions to the models, including modular pleiotropy, variable effect sizes, mutational bias and maladaptation of the wild type. We illustrate our approach by reanalysing a large dataset of mutant effects in a yeast snoRNA (small nucleolar RNA). Though characterized by some large epistatic effects, these data give a good overall fit to the non-epistatic null model, suggesting that epistasis might have limited influence on the evolutionary dynamics in this system. We also show how the amount of epistasis depends on both the underlying fitness landscape and the distribution of mutations, and so is expected to vary in consistent ways between new mutations, standing variation and fixed mutations.
Coupling of palaeontological and neontological reef coral data improves forecasts of biodiversity responses under global climatic change
Authors: Jones Lewis A. , Mannion Philip D. , Farnsworth Alexander , Valdes Paul J. , Kelland Sarah-Jane , Allison Peter A.
Published: April 2019

Reef corals are currently undergoing climatically driven poleward range expansions, with some evidence for equatorial range retractions. Predicting their response to future climate scenarios is critical to their conservation, but ecological models are based only on short-term observations. The fossil record provides the only empirical evidence for the long-term response of organisms under perturbed climate states. The palaeontological record from the Last Interglacial (LIG; 125 000 years ago), a time of global warming, suggests that reef corals experienced poleward range shifts and an equatorial decline relative to their modern distribution. However, this record is spatio-temporally biased, and existing methods cannot account for data absence. Here, we use ecological niche modelling to estimate reef corals' realized niche and LIG distribution, based on modern and fossil occurrences. We then make inferences about modelled habitability under two future climate change scenarios (RCP4.5 and RCP8.5). Reef coral ranges during the LIG were comparable to the present, with no prominent equatorial decrease in habitability. Reef corals are likely to experience poleward range expansion and large equatorial declines under RCP4.5 and RCP8.5. However, this range expansion is probably optimistic in the face of anthropogenic climate change. Incorporation of fossil data in niche models improves forecasts of biodiversity responses under global climatic change.
Thermal switch of oscillation frequency in Belousov–Zhabotinsky liquid marbles
Authors: Adamatzky Andrew , Fullarton Claire , Phillips Neil , De Lacy Costello Ben , Draper Thomas C.
Published: April 2019

External control of oscillation dynamics in the Belousov–Zhabotinsky (BZ) reaction is important for many applications including encoding computing schemes. When considering the BZ reaction, there are limited studies dealing with thermal cycling, particularly cooling, for external control. Recently, liquid marbles (LMs) have been demonstrated as a means of confining the BZ reaction in a system containing a solid–liquid interface. BZ LMs were prepared by rolling 50 μl droplets in polyethylene (PE) powder. Oscillations of electrical potential differences within the marble were recorded by inserting a pair of electrodes through the LM powder coating into the BZ solution core. Electrical potential differences of up to 100 mV were observed with an average period of oscillation
ca
44 s. BZ LMs were subsequently frozen to −1°C to observe changes in the frequency of electrical potential oscillations. The frequency of oscillations reduced upon freezing to 11 mHz cf. 23 mHz at ambient temperature. The oscillation frequency of the frozen BZ LM returned to 23 mHz upon warming to ambient temperature. Several cycles of frequency fluctuations were able to be achieved.
Text-mined fossil biodiversity dynamics using machine learning
Authors: Kopperud Bjørn Tore , Lidgard Scott , Liow Lee Hsiang
Published: April 2019

Documented occurrences of fossil taxa are the empirical foundation for understanding large-scale biodiversity changes and evolutionary dynamics in deep time. The fossil record contains vast amounts of understudied taxa. Yet the compilation of huge volumes of data remains a labour-intensive impediment to a more complete understanding of Earth's biodiversity history. Even so, many occurrence records of species and genera in these taxa can be uncovered in the palaeontological literature. Here, we extract observations of fossils and their inferred ages from unstructured text in books and scientific articles using machine-learning approaches. We use Bryozoa, a group of marine invertebrates with a rich fossil record, as a case study. Building on recent advances in computational linguistics, we develop a pipeline to recognize taxonomic names and geologic time intervals in published literature and use supervised learning to machine-read whether the species in question occurred in a given age interval. Intermediate machine error rates appear comparable to human error rates in a simple trial, and resulting genus richness curves capture the main features of published fossil diversity studies of bryozoans. We believe our automated pipeline, that greatly reduced the time required to compile our dataset, can help others compile similar data for other taxa.
Marine reserves shape seascapes on scales visible from space
Authors: Madin Elizabeth M. P. , Harborne Alastair R. , Harmer Aaron M. T. , Luiz Osmar J. , Atwood Trisha B. , Sullivan Brian J. , Madin Joshua S.
Published: April 2019

Marine reserves can effectively restore harvested populations, and ‘mega-reserves’ increasingly protect large tracts of ocean. However, no method exists of monitoring ecological responses at this large scale. Herbivory is a key mechanism structuring ecosystems, and this consumer–resource interaction's strength on coral reefs can indicate ecosystem health. We screened 1372, and measured features of 214, reefs throughout Australia's Great Barrier Reef using high-resolution satellite imagery, combined with remote underwater videography and assays on a subset, to quantify the prevalence, size and potential causes of ‘grazing halos’. Halos are known to be seascape-scale footprints of herbivory and other ecological interactions. Here we show that these halo-like footprints are more prevalent in reserves, particularly older ones (approx. 40 years old), resulting in predictable changes to reef habitat at scales visible from space. While the direct mechanisms for this pattern are relatively clear, the indirect mechanisms remain untested. By combining remote sensing and behavioural ecology, our findings demonstrate that reserves can shape large-scale habitat structure by altering herbivores' functional importance, suggesting that reserves may have greater value in restoring ecosystems than previously appreciated. Additionally, our results show that we can now detect macro-patterns in reef species interactions using freely available satellite imagery. Low-cost, ecosystem-level observation tools will be critical as reserves increase in number and scope; further investigation into whether halos may help seems warranted.
Significance statement
: Marine reserves are a widely used tool to mitigate fishing impacts on marine ecosystems. Predicting reserves' large-scale effects on habitat structure and ecosystem functioning is a major challenge, however, because these effects unfold over longer and larger scales than most ecological studies. We use a unique approach merging remote sensing and behavioural ecology to detect ecosystem change within reserves in Australia's vast Great Barrier Reef. We find evidence of changes in reefs' algal habitat structure occurring over large spatial (thousands of kilometres) and temporal (40+ years) scales, demonstrating that reserves can alter herbivory and habitat structure in predictable ways. This approach demonstrates that we can now detect aspects of reefs' ecological responses to protection even in remote and inaccessible reefs globally.
In-ovo antiviral assay of methanolic leaf extract of Cymbopogon citratus (Lemon grass) on Newcastle disease virus
Authors: Abraham-Oyiguh Joseph , Zakka Abigail W. , Onwuatuegwu Joseph Taiwo C. , Sulaiman Lanre K. , Muhammad Salamatu Y.
Published: April 2019

This study determined the in-ovo antiviral effect of crude Methanolic leaf extract of Cymbopogon citratus on Newcastle disease virus. Cold extraction was carried out using analytical grade methanol. Phytochemical screening of the crude extract was carried out using standard procedures. Antiviral assay was carried out in nine-day old specific pathogen free embryonated hens’ eggs in three designs made of five eggs per group (Virus with extract, virus only and un-inoculated groups) with concentrations ranging from 12.5 to 100 mg ml−1. Egg toxicity of the extract was determined for concentrations of 12.5, 25, 50, 100, 200, 300 and 400 mg ml−1. Inoculated eggs were incubated at 37 °C and observed daily for 96 h for embryo survival and mortality. Spot haemagglutination was carried out on bacteria-free allantoic fluid from the embryonated eggs to detect the presence of the virus. Phytochemical assay revealed the presence of saponins, flavonoids, steroids, terpenes, phlebotannins and terpenoids. Mild toxicity was observed at concentrations of 100 mg ml−1 and above. There was no haemagglutination of fluid from the eggs inoculated with a combination of Virus and extract at concentrations of 50 and 100 mg ml−1. The current findings demonstrated that leaf extract of Cymbopogon citratus has potential medicinal value as well as antiviral activity against Newcastle disease virus in-vivo. The specific mechanism of action remains to be studied to further elucidate on its potential as a therapeutic product for the treatment of Newcastle Disease.
In-depth profiling of calcite precipitation by environmental bacteria reveals fundamental mechanistic differences with relevance to application
Authors: Reeksting Bianca , Paine Kevin , Gebhard Susanne
Published: April 2019

Microbially-induced calcite precipitation (MICP) is ubiquitous in nature and has become an area of interest for environmental, geotechnical, and civil engineering applications. These include bioremediation, soil engineering, and self-healing of cementitious materials. To date, ureolytic bacteria have been favoured due to their ability to rapidly increase the pH of the environment through the hydrolysis of urea and thereby induce precipitation of calcite. However, the requirement for urea can contribute to nitrogen-loading in the environment and prove to be incompatible in certain applications, such as in self-healing concrete where it delays setting. Non-ureolytic bacteria are thought to be less efficient at MICP as they lack the ability to hydrolyze urea and thus to induce rapid increases in pH. Profiling of environmental bacteria has revealed the fundamentally different mechanisms that ureolytic and non-ureolytic bacteria utilize to precipitate calcite. These affect the timing of MICP and morphology of the crystals, but not necessarily the overall quantity of calcite precipitated. Furthermore, we show that MICP facilitated by non-ureolytic bacteria results in precipitates that contain significant organic components. These precipitates appear to have increased volume and cohesiveness, which may prove advantageous in application. Our findings offer important new insights into the use of MICP for geotechnical and environmental engineering and will enable us to create a toolbox of microbial precipitators tailored for specific applications.
Molecular epidemiology and antimicrobial resistance of Corynebacterium diphtheriae and Corynebacterium ulcerans strains isolated in the UK between 2004-2017
Authors: Fraz Zahra , Litt David , Duncan John , Mann Ginder , Pike Rachel , Chand Meera , Gower Charlotte , Amirthalingam Gayatri , Fry Norman
Published: April 2019

The genus Corynebacterium includes three potentially toxigenic species, C. diphtheriae, C. ulcerans and C. pseudotuberculosis, capable of causing diphtheria, a severe disease in humans. The aims of this study were to undertake Multi-Locus Sequence Typing (MLST) on a panel of both toxigenic and non-toxigenic C. diphtheriae and C. ulcerans strains (20 toxigenic and29 non-toxigenic C. diphtheriae, 17 toxigenic and 14 non-toxigenic C. ulcerans) isolated in the UK between 2004 and 2017, and use these results to determine the molecular epidemiology within the UK. Antibiotic sensitivity testing was also undertaken (20 toxigenic and 88 non-toxigenic C. diphtheriae, 17 toxigenic and 14 non-toxigenic C. ulcerans) and their profiles compared. The MLST results showed that C. diphtheriae and C. ulcerans isolates formed two distinct genetic populations and that C. diphtheriae isolates with intermediate penicillin resistance demonstrated sequence types which were genetically related. The results also showed that ST32 was most prevalent (31%, 9/29 isolates) amongst non-toxigenic C. diphtheriae. Non-toxigenic C. ulcerans isolates demonstrating intermediate penicillin resistance formed distinct genetic populations and appeared distantly related or unrelated. There were 75 % (15 isolates) of toxigenic C. diphtheriae isolates, 35 % (6 isolates) of toxigenic C. ulcerans isolates, 30 % (26 isolates) non-toxigenic C. diphtheriae and 43 % (6 isolates) of non-toxigenic C. ulcerans which demonstrated intermediate penicillin resistance. Linezolid and vancomycin were the only antibiotics which demonstrated 100 % sensitive profiles for all isolate groups. These data will help inform public health guidance and management of corynebacteria infections caused by these species.
Mechanistic analysis of the minimalistic twin-arginine translocation system found in Bacillus subtilis
Authors: Cherry Jon , Palmer Tracy
Published: April 2019

The twin-arginine translocation (Tat) machinery mediates the transport of folded proteins across the cytoplasmic membranes of prokaryotes and thylakoid membranes of chloroplasts. In Gram-negative bacteria three integral membrane components, TatA, TatB and TatC, are essential for generating an active complex. Most Gram-positive bacteria however, have a minimalist Tat complex formed solely from TatA and TatC subunits. Bacillus subtilis encodes two TatAC systems; TatAdCd and TatAyCy. These complexes operate in parallel but have differing substrate specificities. To date, little is known about how the B. subtilis TatAC-complexes assemble, however, the Escherichia coli TatABC complex is well studied and a substrate-triggered positional exchange of TatA and TatB has been identified as the first step in the assembly of an active complex. In this study, we aim to identify site specific interactions taking place between the B. subtilis Tat components and how these interactions differ whilst the complex is engaged in transport of a substrate. Molecular modelling was used to identify likely interaction interfaces between TatA and TatC, and site-directed mutagenesis was used to generate single cysteine variants of both proteins. Subsequently in vivo disulfide crosslinking was undertaken in both E. coli and B.subtilis, in the presence and absence of overproduced Tat substrates, to determine changes that occur between resting state and activated complexes. Overall, this work will enable us to outline a possible mechanism of assembly in TatAC-complexes of Gram-positive bacteria and identify whether the two distinct translocases assemble in a similar fashion.
Assessing and optimising culturing methods for the associated-bacteria of two species of deep-sea sponges (class Hexactinellida) for antimicrobial bioprospecting
Authors: Hesketh Best Poppy , Howell Kerry , Upton Mathew , Bishop Alistair , Warburton Philip , Foster Nicola , Koch Matthew
Published: April 2019

There is a need for novel classes of antimicrobials to be discovered in order to tackle the growing challenges of antimicrobial resistance. Deep-sea sponges are drawing much attention due to the phylogenetically diverse and dense communities of microbes that live within their tissues. Bioprospecting these sponges offers the possibility of exploring a niche environment that could contain novel classes of antimicrobials. To assess the suitability of Pheronema carpenteri (class Hexactinellida, order Amphidiscosida) and Rhabdodictyum sp. (class Hexactinellida, order Lyssacinosida) as a source of antimicrobials, cultivation-dependent strategies were employed. We assess the culturability of sponge-associated bacterial from P. carpenteri (n=3) and Rhabdodictyum sp. (n=2) using8 treatments; 4 temperature incubation treatments (4, 15, 22–25 and 28 °C), nutritional additives (Sponge spicule extract and a low nutrient heterotrophic media additive), and finally a 24 h enrichment stage. Recovered isolates were screen recovered sponge associated-bacteria isolates for bioactivity against Escherichia coli and Micrococcus luteus. Isolates demonstrating high activity were then tested against 7 clinically relevant pathogens; Staphylococcus aurerus 6571, Streptococcus pyogenes, E. coli 1077, Salmonella enterica Serovar Typhimurium LT2, Klebsiella pneumonia 681, Mycoccoccus phlei and Candida albicans. More isolates were recovered from Rhabdodictyum sp. than P. carpenteri (P<0.005). Isolates recovered from P. carpenteri demonstrate high antibacterial activity against both Gram-positive and Gram-negative strains. 112 isolates in total were found to be bioactive against M. luteus, 55 of which were active against both M. luteus and E. coli. The highest potion of bioactive compounds derived from a 15°C treatment and from the inclusion of Sponge Spicule Extract as a nutritional additive. This research presents the first attempts of bioprospecting these two species of deep-sea sponges and thus far has shown promise in their suitability.
The Type III CRISPR-Cas system of Mycobacterium tuberculosis
Authors: Grüschow Sabine , Athukoralage Januka , Hoogeboom Tess , White Malcolm F.
Published: April 2019

Background

Bacteria and archaea have developed a number of strategies to keep the influx of mobile genetic elements (MGEs) such as viruses and plasmids in check. CRISPR-Cas systems provide adaptive immunity; all types of CRISPR-Cas systems have in common the genes for uptake of genetic information from the invading MGE but differ in the composition of the effector complex that directs and enforces the immune response. The genome of Mycobacterium tuberculosis encodes a Class 1, type III-A CRISPR-Cas system that has not been studied in detail.

Methodology

We used heterologous production of the mycobacterial CRISPR-Cas genes. Purification of the enzymes enabled in vitro biochemical characterisation of the adaptation, maturation and interference proteins. Reconstitution of the system in E. coli was used to demonstrate functionality in vivo.

Results

Maturation of crRNA through the action of Cas6 proceeded as expected, generating canonical CRISPR RNAs (crRNAs). The type III effector complex, consisting of Csm1-5, was shown to bind crRNA and cleave target RNA with the typical 6 nt spacing, display ssDNase activity and produce the cyclic oligoadenylate signalling molecule. The latter clearly activated the ribonuclease Csm6, an essential element in type III immunity. The M. tuberculosis type III CRISPR-Cas system was also reconstituted in E. coli where it provided plasmid immunity, demonstrating the functionality in vivo.

Conclusions

All elements of the M. tuberculosis type III CRISPR-Cas system are functional in vitro and in vivo. These studies lay the foundation for further investigations into the mechanism of adaptive immunity and possible applications in biotechnology.
Uncovering the dark matter of the metagenome one read at a time
Authors: Dimonaco Nicholas , Creevey Chris , Hoehndorf Robert , Kulmanov Maxat , Liuwei Wang , Clare Amanda , Aubrey Wayne , Kenobi Kim
Published: April 2019

Contemporary metagenomic annotation methods have proven insufficient in our attempts to better understand the complex environments around us. We call the yet to be annotated part of a metagenome it’s ‘dark matter’. The Gene Ontology (GO) is a hierarchical vocabulary used to describe gene product function and a large collection of curated genes with GO annotations already exists. DeepGO utilises deep learning to build models from these curated genes and gene products to predict GO categories for novel proteins. One of the major problems with metagenomic studies today is the process of assembling the environmental DNA sequences into their original genomes. This is difficult, with chimeric metagenomically assembled genomes being common. To avoid this and the computational and time expense, we have modified DeepGO to perform protein function prediction directly from sequence reads with limited protein coding sequence prediction. Three independent models were trained as the following; The first 50 amino acids of a protein were used for training, The last 50 amino acids were used for training, A phasing window of 50 amino acids was used to train across the entirety of a protein sequence. These models were chosen to learn from the different parts of a protein sequence we are likely to capture from only the short unassembled sequence reads. We compared the three models by producing a mock metagenomic community consisting of 6 model bacterial genomes. We evaluated the functions predicted from the unassembled sequence reads and the protein coding sequences predicted from the assembled metagenome.
Genome annotation of Poly(lactic acid) degradingPseudomonas aeruginosaandSphingobacterium sp.
Authors: Satti Sadia Mehmood , Shah Aamer Ali , Auras Rafael , Marsh Terence L.
Published: April 2019

Pseudomonas aeruginosaandSphinogobacterium sp. are well known for their ability to decontaminate many environmental pollutants like PAHs, dyes, pesticides and plastics. The present study reports the annotation of genomes fromP. aeruginosaandSphinogobacterium sp. that were isolated from compost, based on their ability to degrade poly(lactic acid), PLA, at mesophillic temperatures (~30°C). Draft genomes of both the strains were assembled from Illumina reads, annotated and viewed with an aim of gaining insight into the genetic elements involved in degradation of PLA. The draft-assembled genome of strainSphinogobacteriumstrain S2 was 5,604,691 bp in length with 435 contigs (maximum length of 434,971 bp) and an average G+C content of 43.5%. The assembled genome ofP. aeruginosastrain S3 was 6,631,638 bp long with 303 contigs (maximum contig length of 659,181 bp) and an average G+C content 66.17 %. A total of 5,385 (60% with annotation) and 6,437 (80% with annotation) protein-coding genes were predicted for strains S2 and S3 respectively. Catabolic genes for biodegradation of xenobiotic and aromatic compounds were identified on both draft genomes. Both strains were found to have the genes attributable to the establishment and regulation of biofilm, with more extensive annotation for this in S3. The genome ofP. aeruginosaS3 had the complete cascade of genes involved in the transport and utilization of lactate whileSphinogobacterium strainS2 lacked lactate permease, consistent with its inability to grow on lactate. As a whole, our results reveal and predict the genetic elements providing both strains with the ability to degrade PLA at mesophilic temperature.