bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of a Hepatitis A Vaccination Campaign During a Hepatitis A Outbreak in Taiwan, 2015–2017: A Modeling Study
Authors: Lin Kuan-Yin , Sun Hsin-Yun , Chen Yi-Hsuan , Lo Yi-Chun , Hsieh Szu-Min , Sheng Wang-Huei , Chuang Yu-Chung , Pan Sung-Ching , Cheng Aristine , Hung Chien-Ching , Fang Chi-Tai , Chang Shan-Chwen
Published: June 2019

Background

Beginning from 2015–2016, unprecedented large outbreaks of acute hepatitis A that predominantly affected men who have sex with men (MSM) reemerged across the continents. We assessed the impact of an early initiated hepatitis A virus (HAV) vaccination campaign that targeted MSM living with human immunodeficiency virus (HIV) during the 2015–2017 hepatitis A outbreak in Taiwan.

Methods

First, we ascertained the effectiveness of HAV vaccination for MSM living with HIV using a nested case-control study of 1470 persons living with HIV who were initially HAV-seronegative. We then fitted a model of HAV transmission among MSM, risk-structured by HIV status, to the actual epidemic curve of reported acute hepatitis A cases in Taiwan during 2015–2017.

Results

Fifty-five cases of acute hepatitis A were matched to 220 controls. Single-dose and 2-dose HAV vaccination provided protection rates of 96.1% and 97.8% among recipient MSM living with HIV, respectively. Model fitting yielded basic reproductive number estimates of 7.26 (MSM living with HIV) and 3.04 (MSM not living with HIV). In a counterfactual scenario without an HAV vaccination campaign, the outbreak would have involved 7153 hepatitis A cases during 2015–2017 in contrast to the 1352 that were observed. We therefore estimated that the HAV vaccination campaign averted 80.7% (sensitivity analysis, 48.8%–92.7%) of acute hepatitis A cases that would otherwise have occurred by the end of 2017.

Conclusions

The early initiated HAV vaccination campaign, which targeted MSM living with HIV, very effectively curtailed the 2015–2017 hepatitis A outbreak in Taiwan.
A Miniature CCA Public Key Encryption Scheme Based on Non-abelian Factorization Problem in Finite Groups of Lie Type
Authors: Hong Haibo , Wang Licheng , Shao Jun , Yan Jianhua , Ahmad Haseeb , Wei Guiyi , Xie Mande , Yang Yixian
Published: June 2019

With the development of Lie theory, Lie groups have attained profound significance in several branches of Mathematics and Physics. In Lie theory, the matrix exponential plays a crucial role between Lie groups and Lie algebras. Meanwhile, as the finite analogue of Lie groups, finite groups of Lie type have potential applications in cryptography due to their unique mathematical structures. In this paper, we first put forward a novel idea of designing cryptosystems based on Lie theory. First of all, combing with discrete logarithm problem and group factorization problem, we proposed several new intractable assumptions based on the matrix exponential in finite groups of Lie type. Subsequently, in analog with Boyen’s scheme (Asiacrypt 2007), we designed a public-key encryption scheme based on the non-abelian factorization problem in finite groups of Lie type. Finally, our proposal was proved to be indistinguishable against adaptively chosen-ciphertext attack in the random oracle model. It is encouraging that our scheme also has the potential to resist against Shor’s quantum algorithm attack.
Barred Owls reduce occupancy and breeding propensity of Northern Spotted Owl in a Washington old-growth forest
Authors: Mangan Anna O , Chestnut Tara , Vogeler Jody C , Breckheimer Ian K , King Wendy M , Bagnall Keith E , Dugger Katie M
Published: June 2019

Protected lands like national parks are important refuges for threatened and endangered species as environmental pressures on wildlife and their habitats increase. The Northern Spotted Owl (Strix occidentalis caurina), a species designated as threatened under the Endangered Species Act, occurs on public lands throughout the western United States including Mount Rainier National Park (MRNP), Washington. With virtually no history of timber harvest or large forest disturbance within MRNP boundaries since the park’s creation in 1899, MRNP provides an ideal place to evaluate potential impacts of climate change and invasive Barred Owls (Strix varia) on the Northern Spotted Owl. We used a multi-state, multi-season occupancy model to investigate how Northern Spotted Owl occupancy dynamics and breeding propensity are related to the presence of Barred Owls, local and regional weather, and habitat characteristics at MRNP from 1997 to 2016. Historical occupancy of Northern Spotted Owl breeding territories in MRNP has declined by 50% in the last 20 yr, and territory occupancy by breeding Northern Spotted Owls also decreased, reaching a low of 25% in 2016. Occupancy rates were higher on territories with steeper terrain and breeding rates were lower when Barred Owls were detected within historical territories. Our results also indicated that breeding propensity was higher when early nesting season temperatures during March and April were higher. In addition, the ability to detect breeding Northern Spotted Owls decreased when Barred Owls were present in the territory. Habitat variables from LiDAR were not correlated with Northern Spotted Owl occupancy dynamics, likely reflecting the dominance of old-growth forest in this protected park. This study illustrates the strong relationship between Barred Owls and Northern Spotted Owl demographics and breeding site selection in a landscape where habitat loss by timber harvest and fire has not occurred.
Hydrogen-dependent autotrophic growth in phototrophic and chemolithotrophic cultures of thermophilic bacteria, Chloroflexus aggregans and Chloroflexus aurantiacus, isolated from Nakabusa hot springs
Authors: Kawai Shigeru , Nishihara Arisa , Matsuura Katsumi , Haruta Shin
Published: June 2019

The genus Chloroflexus is a deeply branching group of thermophilic filamentous anoxygenic phototrophic bacteria. The bacteria in this genus have been shown to grow well heterotrophically under anaerobic photosynthetic and aerobic respiratory conditions. We examined autotrophic growth in new isolates of Chloroflexus strains from hot springs in Nakabusa, Japan. The isolates belonging to Chloroflexus aggregans (98.7% identity of 16S rRNA gene sequence to the respective type strain) and Chloroflexus aurantiacus (99.9% identity to the respective type strain) grew photoautotrophically under a 24% H2 atmosphere. We also observed chemolithotrophic growth of these isolates under 80% H2 and 5% O2 conditions in the dark. This is the first report showing that Chloroflexus grew under both photoautotrophic and chemolithotrophic conditions in addition to photoheterotrophic and aerobic chemoheterotrophic conditions.
Effect of spacing, parental genotype and harvesting cycle on biomass production in two half-sib progenies of Robinia pseudoacacia L.
Authors: Stankova Tatiana , Gyuleva Veselka , Kalmukov Kancho , Popov Emil , Pérez-Cruzado César , Glushkova Maria , Dimitrov Dimitar N , Dimitrova Proletka , Hristova Hristina , Andonova Ekaterina
Published: June 2019

This study investigated the influence of spacing, parental genotype and harvesting cycle on woody biomass production in open-pollinated families of the locally selected black locust (Robinia pseudoacacia L.) clones ‘Tsarevets’ and ‘Srebarna’ at specific site conditions.

A Nelder experiment with 16, varying along the spokes, nearly-square spacings and two black locust families arranged in alternating sectors, was established in North Central Bulgaria. Alternative harvesting options (‘harvesting cycles’), consisting of one, two or three successive coppicings, were applied and the amounts of dry shoot dendromass collected per plant were accumulated to calculate and analyse the total yield of woody biomass, achievable within 2-, 3- and 4-year periods (‘production period’).

The one-coppicing cycle proved superior for both families, regardless of the length of the production period. Biomass yield in the family of ‘Srebarna’ exceeded that of ‘Tsarevets’ at the wider spacings, when 1 and 2 year-old shoots were harvested, while dendromass production of ‘Tsarevets’ was substantially higher in the 4-year-old shoots. The woody biomass yield per plant increased with spacing, and growth tended to saturation at the lowest densities, enabling derivation of optimal planting densities. The total dendromass yield per hectare was maximized at growing space of around 0.5 m2 per plant for the 2-year production period, while spacing of 1.2–2 m2 was required for production periods of 3 and 4 years. If the results from this experiment can be reliably scaled up in practice then short rotation crops of ‘Srebarna’ and ‘Tsarevets’ families at comparable site conditions should be able to produce annual biomass yields of 9–11 Mg.ha−1.year−1 within a 4-year period, given the optimal planting densities and harvesting regimes prescribed.
Stress Resilience and the Dynamic Regulation of Glucocorticoids
Authors: Vitousek Maren N , Taff Conor C , Ryan Thomas A , Zimmer Cedric
Published: June 2019

Vertebrates respond to a diversity of stressors by rapidly elevating glucocorticoid (GC) levels. The changes in physiology and behavior triggered by this response can be crucial for surviving a variety of challenges. Yet the same process that is invaluable in coping with immediate threats can also impose substantial damage over time. In addition to the pathological effects of long-term exposure to stress hormones, even relatively brief elevations can impair the expression of a variety of behaviors and physiological processes central to fitness, including sexual behavior, parental behavior, and immune function. Therefore, the ability to rapidly and effectively terminate the short-term response to stress may be fundamental to surviving and reproducing in dynamic environments. Here we review the evidence that variation in the ability to terminate the stress response through negative feedback is an important component of stress coping capacity. We suggest that coping capacity may also be influenced by variation in the dynamic regulation of GCs—specifically, the ability to rapidly turn on and off the stress response. Most tests of the fitness effects of these traits to date have focused on organisms experiencing severe or prolonged stressors. Here we use data collected from a long-term study of tree swallows (Tachycineta bicolor) to test whether variation in negative feedback, or other measures of GC regulation, predict components of fitness in non-chronically stressed populations. We find relatively consistent, but generally weak relationships between different fitness components and the strength of negative feedback. Reproductive success was highest in individuals that both mounted a robust stress response and had strong negative feedback. We did not see consistent evidence of a relationship between negative feedback and adult or nestling survival: negative feedback was retained in the best supported models of nestling and adult survival, but in two of three survival-related analyses the intercept-only model received only slightly less support. Both negative feedback and stress-induced GC levels—but not baseline GCs—were individually repeatable. These measures of GC activity did not consistently covary across ages and life history stages, indicating that they are independently regulated. Overall, the patterns seen here are consistent with the predictions that negative feedback—and the dynamic regulation of GCs—are important components of stress coping capacity, but that the fitness benefits of having strong negative feedback during the reproductive period are likely to manifest primarily in individuals exposed to chronic or repeated stressors.
Delays in care seeking, diagnosis and treatment of patients with pulmonary tuberculosis in Hubei, China
Authors: Yang Qin , Tong Yeqing , Yin Xiaoxv , Qiu Lei , Sun Na , Zhao Yuxin , Li Dandan , Li Xiaotong , Gong Yanhong
Published: June 2019

Background

Early diagnosis and treatment are essential for effective tuberculosis (TB) control. However, delays in the diagnosis and treatment of TB in central China have not been sufficiently investigated. This cross-sectional study was conducted between October 2013 and March 2014 in Hubei, China to identify risk factors of delays in care seeking, diagnosis and treatment among patients with TB.

Methods

A total of 1342 patients with TB seen in the designated institutions were included. Multivariate logistic regression was used to analyse factors associated with delays in TB diagnosis and treatment.

Results

Overall, 21.54%, 23.62% and 42.25% of patients with TB experienced delays in care seeking, diagnosis and treatment, respectively. Multivariate logistic regression showed that medical insurance and monthly household income were significantly associated with delays in care seeking. The time to reach a township hospital or the facility of a patient’s first consultation was significantly associated with delays in diagnosis. Sex, education, time to reach a township hospital and the facility where the diagnosis was made were significantly associated with delays in treatment.

Conclusions

Delays in TB diagnosis and treatment in Hubei remain a serious issue. Improvements in the capability and accessibility of health care services are imperative to reduce delays and expedite TB diagnosis and treatment.
Navigation Comparison between a Real and a Virtual Museum: Time-dependent Differences using a Head Mounted Display
Authors: Marín-Morales Javier , Higuera-Trujillo Juan Luis , De-Juan-Ripoll Carla , Llinares Carmen , Guixeres Jaime , Iñarra Susana , Alcañiz Mariano
Published: June 2019

The validity of environmental simulations depends on their capacity to replicate responses produced in physical environments. However, very few studies validate navigation differences in immersive virtual environments, even though these can radically condition space perception and therefore alter the various evoked responses. The objective of this paper is to validate environmental simulations using 3D environments and head-mounted display devices, at behavioural level through navigation. A comparison is undertaken between the free exploration of an art exhibition in a physical museum and a simulation of the same experience. As a first perception validation, the virtual museum shows a high degree of presence. Movement patterns in both ‘museums’ show close similarities, and present significant differences at the beginning of the exploration in terms of the percentage of area explored and the time taken to undertake the tours. Therefore, the results show there are significant time-dependent differences in navigation patterns during the first 2 minutes of the tours. Subsequently, there are no significant differences in navigation in physical and virtual museums. These findings support the use of immersive virtual environments as empirical tools in human behavioural research at navigation level.

Research highlights

The latest generation HMDs show a high degree of presence. There are significant differences in navigation patterns during the first 2 minutes of a tour. Adaptation time need to be considered in future research. Training rooms need to be realistic, to avoid the ‘wow’ effect in the main experiment. Results support the use of Virtual Reality and the latest HMDs as empirical tools in human behavioural research at navigation level.
Omega-3 polyunsaturated fatty acid oral supplements for improving peripheral nerve health: a systematic review and meta-analysis
Authors: Zhang Alexis Ceecee , De Silva Manikkuwadura Eranda Harshan , MacIsaac Richard J , Roberts Leslie , Kamel Jordan , Craig Jennifer P , Busija Ljoudmila , Downie Laura E
Published: June 2019

Context

Peripheral nerve damage can occur in a variety of systemic conditions and can have a profound impact on functional and psychological health. Currently, therapeutic interventions for peripheral nerve damage are limited.

Objective

The aim of this systematic review, conducted in accordance with the Cochrane Collaboration’s handbook and reported according to the PRISMA checklist, was to evaluate the efficacy and safety of omega-3 oral supplements for improving peripheral nerve structure and function.

Data Sources

PubMed, Embase, and Cochrane databases, along with clinical trial registries, were searched from inception to February 2019. Evidence was identified, critically appraised, and synthesized, and the certainty of evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation approach.

Study Selection

Randomized controlled trials assessing the effects of omega-3 oral supplementation on outcomes of peripheral nerve structure, peripheral nerve function, or both were eligible for inclusion. Titles and abstracts of identified articles were independently assessed for potential eligibility by 2 review authors. For studies judged as eligible or potentially eligible, full text articles were retrieved and independently assessed by 2 review authors to determine eligibility; disagreements were resolved by consensus.

Data Extraction

Fifteen trials were included. Two clinically similar studies that investigated the effect of omega-3 supplementation in individuals receiving chemotherapy were meta-analyzed. Pooled data showed a reduced incidence of peripheral neuropathy (RR = 0.58; 95%CI, 0.43–0.77) and a preservation of sensory nerve action potential amplitudes with omega-3 supplementation compared with placebo (MD = 4.19 µV; 95%CI; 2.19–6.19).

Conclusion

This review finds, with low certainty, that omega-3 supplementation attenuates sensory loss and reduces the incidence of neuropathy secondary to oxaliplatin and paclitaxel treatment relative to placebo. There is currently limited evidence to ascertain whether omega-3 supplementation is beneficial in other systemic conditions characterized by peripheral nerve damage.

Systematic Review Registration

PROSPERO registration number CRD 42018086297
Plasma Proinflammatory Cytokines Are Markers of Disease Severity and Bacterial Burden in Pulmonary Tuberculosis
Authors: Kumar Nathella Pavan , Moideen Kadar , Banurekha Vaithilingam V , Nair Dina , Babu Subash
Published: June 2019

Background

Type 1, type 17, and other proinflammatory cytokines are important in host immunity to tuberculosis (TB) in animal models. However, their role in human immunity to TB is not completely understood.

Methods

To examine the association of proinflammatory cytokines with pulmonary TB (PTB), we examined the plasma levels of type 1 (interferon [IFN]γ and tumor necrosis factor [TNF]α), type 17 (interleukin [IL]-17A and IL-17F), and other proinflammatory (IL-6, IL-12, and IL-1β) cytokines in individuals with PTB, latent TB (LTB), or healthy controls (HC).

Results

Individuals with PTB exhibited significantly higher plasma levels of most of the above cytokines compared with LTB or HC individuals. Principal component analysis based on these cytokines could clearly distinguish PTB from both LTB or HC individuals. Pulmonary TB individuals with bilateral or cavitary disease exhibited significantly higher levels of IFNγ, TNFα, IL-17A, and IL-1β compared with those with unilateral or noncavitary disease. Pulmonary TB individuals also exhibited a significant positive relationship between IFNγ, TNFα, and IL-17A levels and bacterial burdens. In addition, PTB individuals with delayed culture conversion exhibited significantly higher levels of IFNγ, TNFα, IL-17A, and IL-1β at baseline. Finally, the plasma levels of all the cytokines examined were significantly reduced after successful chemotherapy.

Conclusions

Therefore, our data demonstrate that PTB is associated with heightened levels of plasma proinflammatory cytokines, which are reversed after chemotherapy. Our data also reveal that proinflammatory cytokines are markers of disease severity, bacterial burden, and delayed culture conversion in PTB.
Whole-Genome Sequencing to Differentiate Relapse From Reinfection in Community-Onset Bacteremic Acinetobacter baumannii Pneumonia
Authors: Meumann Ella M , Anstey Nicholas M , Currie Bart J , Piera Kim A , Baird Robert , Sarovich Derek S , Davis Joshua S
Published: June 2019

Community-onset bacteremic Acinetobacter baumannii pneumonia recurred in 3 of 30 (10%) patients followed prospectively, all with ongoing hazardous alcohol intake, 3–56 months after initial pneumonia. Paired isolates underwent whole-genome sequencing. Phylogenetic analysis showed that recurrence strains were all distinct from preceding strains, indicating reinfection in susceptible individuals rather than relapse.
Increased Fecal Lactobacillus Is Associated With a Positive Glucose Hydrogen Breath Test in Bangladeshi Children
Authors: Donowitz Jeffrey R , Parikh Hardik I , Taniuchi Mami , Gilchrist Carol A , Haque Rashidul , Kirkpatrick Beth D , Alam Masud , Kakon Shahria Hafiz , Islam Bushra Zarin , Afreen Sajia , Kabir Mamun , Nayak Uma , Colgate E Ross , Carmolli Marya P , Petri William A
Published: June 2019

Background

Glucose hydrogen breath testing is a noninvasive test for small intestine bacterial overgrowth (SIBO). A positive glucose hydrogen breath test is common in children from low-income countries and has been found to be associated with malnutrition as measured by stunted growth. The microbiome associated with positive breath testing is relatively unstudied.

Methods

We performed 16 S V4 rDNA microbiome analysis on the stool of 90 Bangladeshi children aged 2 years from an impoverished neighborhood who were tested at the same time for SIBO by glucose hydrogen breath testing. Data were analyzed by linear discriminant analysis effect size with SIBO as the outcome. Any selected genera were tested individually by Wilcoxon’s rank-sum test to ensure that linear discriminant analysis effect size results were not outlier-skewed.

Results

Linear discriminant analysis effect size analysis identified Lactobacillus (linear discriminate analysis score, 4.59; P = .03) as over-represented in 15 out of the 90 children who were SIBO positive.

Conclusions

These results suggest that glucose hydrogen breath test positivity in children from low-income settings may be due to an upper intestinal Lactobacillus bloom, potentially explaining the association of SIBO with the gut damage and inflammation that leads to malnutrition.
Transcutaneous Electrical Nerve Stimulation Reduces Knee Osteoarthritic Pain by Inhibiting Spinal Glial Cells in Rats
Authors: Hahm Suk-Chan , Song Eseul , Jeon Hochung , Yoon Young Wook , Kim Junesun
Published: June 2019

Background

Transcutaneous electrical nerve stimulation (TENS) is commonly used for pain control. However, the effects of TENS on osteoarthritis (OA) pain and potential underlying mechanisms remain unclear.

Objective

The objective of this study was to investigate the effect of TENS on OA pain treatment and underlying mechanisms related to glial cell inhibition.

Design

This was an experimental study.

Methods

OA was induced by injection of monosodium iodoacetate into the synovial space of the right knee joint of rats. High-frequency (HF) TENS (100 Hz), low-frequency (LF) TENS (4 Hz), or sham TENS was applied to the ipsilateral knee joint for 20 minutes. Paw withdrawal threshold (PWT), weight bearing, and knee bend score (KBS) were measured. Immunohistochemistry for microglia and astrocytes was performed with L3 to L5 spinal segment samples. To investigate the effects of glial inhibition on OA pain, minocycline, l-α-aminoadipate, or artificial cerebrospinal fluid was injected intrathecally, and PWT and KBS were measured.

Results

Compared with sham TENS, both HF TENS and LF TENS significantly increased PWT, decreased KBS, and inhibited activated microglia in the L3 to L5 segments but did not decrease the total number of microglia, except in the L4 segment (HF TENS). Astrocyte expression was significantly decreased in the L3 to L5 segments following LF TENS and in the L3 segment following HF TENS. Compared with artificial cerebrospinal fluid, both minocycline and l-α-aminoadipate increased PWT and decreased KBS.

Limitations

These results cannot be generalized to humans.

Conclusions

TENS alleviates OA pain in rats by inhibiting activated microglia and reducing astrocyte expression in the spinal cord. Although these results may not be generalizable to chronic pain in patients with OA, within the limitation of the experimental animal model used in the present study, they suggest a possible mechanism and preclinical evidence supporting further experimentation or clinical use of TENS in humans.
Evolution of Plasmodium falciparum drug resistance genes following artemisinin combination therapy in Sudan
Authors: Bakhiet Amani M A , Abdelraheem Mohamed H , Kheir Amani , Omer Samia , Gismelseed Linda , Abdel-Muhsin Abdel-Muhsin A , Naiem Ahmed , Al Hosni Ahmed , Al Dhuhli Amani , Al Rubkhi Maymona , Al-Hamidhi Salama , Gadalla Amal , Mukhtar Moawia , Sultan Ali A , Babiker Hamza A
Published: June 2019

Background

Malaria control efforts in Sudan rely heavily on case management. In 2004, health authorities adopted artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria. However, some recent surveys have reported ACT failure and a prevalent irrational malaria treatment practice. Here we examine whether the widespread use of ACT and failure to adhere to national guidelines have led to the evolution of drug resistance genes.

Methods

We genotyped known drug resistance markers (Pfcrt, Pfmdr-1, Pfdhfr, Pfdhps, Pfk13 propeller) and their flanking microsatellites among Plasmodium falciparum isolates obtained between 2009 and 2016 in different geographical regions in Sudan. Data were then compared with published findings pre-ACT (1992–2003).

Results

A high prevalence of Pfcrt76T, Pfmdr-1-86Y, Pfdhfr51I, Pfdhfr108N, Pfdhps37G was observed in all regions, while no Pfk13 mutations were detected. Compared with pre-ACT data, Pfcrt-76T and Pfmdr-1-86Y have decayed, while Pfdhfr-51I, Pfdhfr-108N and Pfdhps-437G strengthened. Haplotypes Pfcrt-CVIET, Pfmdr-1-NFSND/YFSND, Pfdhfr-ICNI and Pfdhps-SGKAA predominated in all sites. Microsatellites flanking drug resistance genes showed lower diversity than neutral ones, signifying high ACT pressure/selection.

Conclusions

Evaluation of P. falciparum drug resistance genes in Sudan matches the drug deployment pattern. Regular monitoring of these genes, coupled with clinical response, should be considered to combat the spread of ACT resistance.
Phanerozoic Radiation of Ammonia Oxidizing Bacteria
Authors: Ward LM , Johnston DT , Shih PM
Published: June 2019

The modern nitrogen cycle consists of a web of microbially mediated redox transformations. Among the most crucial reactions in this cycle is the oxidation of ammonia to nitrite, an obligately aerobic process performed by a limited number of lineages of bacteria (AOB) and archaea (AOA). As this process has an absolute requirement for O2, the timing of its evolution – especially as it relates to the Great Oxygenation Event ~2.3 billion years ago – remains contested and is pivotal to our understanding of nutrient cycles. To estimate the antiquity of bacterial ammonia oxidation, we performed phylogenetic and molecular clock analyses of AOB. Surprisingly, bacterial ammonia oxidation appears quite young, with crown group clades having originated during Neoproterozoic time (or later) with major radiations occurring during Paleozoic time. These results place the evolution of AOB broadly coincident with the pervasive oxygenation of the deep ocean. The late evolution AOB challenges earlier interpretations of the ancient nitrogen isotope record, predicts a more substantial role for AOA during Precambrian time, and may have implications for understanding of the size and structure of the biogeochemical nitrogen cycle through geologic time.
A novel role for Myosin-Va in mitochondrial fission
Authors: Araujo Jackeline S , Silva-Junior Rui M P , Zhang Tong , Schiavon Cara R , Chu Qian , Wu Melissa , Pontes Carmen L S , Souza Anderson O , Alberici Luciane C , Santos Aline M , Ingle Sadie Bartholomew , Saghatelian Alan , Spudich James , Manor Uri , Espreafico Enilza M
Published: June 2019

In cancer cells metabolic changes and mitochondrial morphology are coupled. It is known that the cytoskeleton and molecular motors are directly involved in regulating mitochondrial morphology. Here we show that myosin-Va, an actin-based molecular motor, is required for the malignant properties of melanoma cells and localizes to mitochondria in these cells. Knockdown of myosin-Va increases cellular respiration rates and ROS production and decreases glucose uptake and lactate secretion. In addition, knockdown of myosin-Va results in reduced mitochondrial fission and correspondingly elongated mitochondria. We show that myosin-Va interacts with the mitochondrial outer membrane protein Spire1C, an actin-regulatory protein implicated in mitochondrial fission, and that Spire1C recruits myosin-Va to mitochondria. Finally, we show that during mitochondrial fission myosin-Va localization to mitochondria increases, and that myosin-Va localizes to mitochondrial fission sites immediately adjacent to Drp1 punctae. We conclude that myosin-Va facilitates mitochondrial fission. These data implicate myosin-Va as a target for the Warburg effect in melanoma cells.
An immunome perturbation is present in juvenile idiopathic arthritis patients who are in remission and will relapse upon anti-TNFα withdrawal
Authors: Leong Jing Yao , Chen Phyllis , Yeo Joo Guan , Ally Fauziah , Chua Camillus , Hazirah Sharifah Nur , Poh Su Li , Pan Lu , Lai Liyun , Lee Elene Seck Choon , Bathi Loshinidevi D/O Thana ,   PRCSG, Arkachaisri Thaschawee , Lovell Daniel J. , Albani Salvatore
Published: June 2019

Objectives

Biologics treatment with anti-TNFα is efficacious in juvenile idiopathic arthritic (JIA) patients. Despite displaying clinical inactivity during treatment, many patients will flare upon cessation of therapy. The inability to definitively discriminate patients who will relapse or continue to remain in remission after therapy withdrawal is currently a major unmet medical need. CD4 T cells have been implicated in active disease, yet how they contribute to disease persistence despite treatment is unknown.

Methods

We interrogated the circulatory reservoir of CD4+ immune subsets at the single cell resolution with mass cytometry (CyToF) of JIA patients (n=20) who displayed continuous clinical inactivity for at least 6 months with anti-TNFα, and were subsequently withdrawn from therapy for 8 months, and scored as relapse or remission. These patients were examined prior to therapy withdrawal for putative subsets that could discriminate relapse from remission. We verified on a separate JIA cohort (n=16), the continued dysregulation of these circulatory subsets 8 months into therapy withdrawal. The immunological transcriptomic signature of CD4 memory in relapse/remission patients was examined with Nanostring.

Results

An inflammatory memory subset of CD3+CD4+CD45RA−TNFα+ T cells deficient in immune checkpoints (PD1−CD152−) was present in relapse patients prior to therapy withdrawal. Transcriptomic profiling reveals divergence between relapse and remission patients in disease centric pathways involving (a) TCR activation, (b) apoptosis, (c) TNFα, (d) NF-kB and (e) MAPK signalling.

Conclusions

A unique discriminatory immunomic and transcriptomic signature is associated with relapse patients and may explain how relapse occurs.
The absence of F-box motif Encoding Gene SAF1 and Chromatin Associated factor CTF8 together contributes to MMS Resistant and HU Sensitive phenotype in S.cerevisiae
Authors: Sharma Meenu , Verma V. , Bairwa Narendra K
Published: June 2019

The Replication factor-C compex which related to cohesion, constitutes, three subunits called Ctf18, Ctf8 and Dcc1. These three subunit complex assist the loading of PCNA onto the chromosome. None of the replication factor C components are essential for cell viability. The null mutant of the CTF8 inS.cerevisiaeshows the chromosome instability and high frequency of chromosome loss. The SAF1 gene product of S.cerevisiaeinvolved in the degradation of adenine deaminase factor Aah1p by SCF-E3 ligase, which itself is the part of E3 ligase. The ubiquitin marked degradation of Aah1p occurs during nutrient stress which lead to cell enter into the quiescent state. The N-terminus of Saf1p interacts with the Skp1 of SCF-E3 ligase and at C-terminus recruits with Aah1p. Here we have investigated about the binary genetic interaction between the SAF1 and CTF8 genes. The strains containing single and double gene deletions of SAF1 and CTF8 were constructed in the BY4741 genetic background. Further the mutant strains were evaluated for growth fitness, genome stability and response to genotoxic stress caused by hydroxyurea (HU) and methyl methane sulfonate (MMS). Thesaf1Δctf8Δstrain showed the increased growth phenotype in comparison tosaf1Δ, ctf8Δ, andWT strain on YPD medium. Howeversaf1Δctf8Δstrain when grown in the presence MMS showed resistance and HU sensitive phenotype when compared withsaf1Δ, ctf8Δ.The frequency of Ty1 retro-transposition was also elevated insaf1Δctf8Δin comparison to eithersaf1Δorctf8Δ.The number of cells showing the two or multi-nuclei phenotype was also increased insaf1Δctf8Δcells when compared with the eithersaf1Δorctf8Δ.Based on these observations, we report that the absence of both the gene SAF1 and CTF8 together leads to MMS resistance, HU sensitivity, and genome instability. This report warrants the investigation of mechanisms of differential growth phenotype due to loss of SAF1 and CTF8 together in presence of genotoxic stress in future.
Scalable Spike Source Localization in Extracellular Recordings using Amortized Variational Inference
Authors: Hurwitz Cole L. , Xu Kai , Srivastava Akash , Buccino Alessio P. , Hennig Matthias H.
Published: June 2019

Determining the positions of neurons in an extracellular recording is useful for investigating functional properties of the underlying neural circuitry. In this work, we present a Bayesian modelling approach for localizing the source of individual spikes on high-density, microelectrode arrays. To allow for scalable inference, we implement our model as a variational autoencoder and perform amortized variational inference. We evaluate our method on both biophysically realistic simulated and real extracellular datasets, demonstrating that it is more accurate than and can improve spike sorting performance over heuristic localization methods such as center of mass.
SPECS: A non-parameteric method to identify tissue-specific molecular features for unbalanced sample groups
Authors: Everaert Celine , Volders Pieter-Jan , Morlion Annelien , Thas Olivier , Mestdagh Pieter
Published: June 2019

To understand biology and differences among various tissues or cell types, one typically searches for molecular features that display characteristic abundance patterns. Several specificity metrics have been introduced to identify tissue-specific molecular features, but these either require an equal number of replicates per tissue or they can’t handle replicates at all. We describe a non-parametric specificity score that is compatible with unequal sample group sizes. To demonstrate its usefulness, the specificity score was calculated on all GTEx samples, detecting known and novel tissue-specific genes. A webtool was developed to browse these results for genes or tissues of interest. An example python implementation of SPECS is available at https://github.ugent.be/ceeverae/SPECs. The precalculated SPECS results on the GTEx data are available through a user-friendly browser at specs.cmgg.be.
Mind the gap: micro-expansion joints drastically decrease the bending of FIB-milled cryo-lamellae
Authors: Wolff Georg , Limpens Ronald W. A. L. , Zheng Shawn , Snijder Eric J. , Agard David A. , Koster Abraham J. , Bárcena Montserrat
Published: June 2019

Cryo-focussed ion beam (FIB)-milling of biological samples can be used to generate thin electron-transparent slices from cells grown or deposited on EM grids. These so called cryo-lamellae allow high-resolution structural studies of the natural cellular environment by in situ cryo-electron tomography. However, the cryo-lamella workflow is a low-throughput technique and can easily be obstructed by technical issues like the bending of the lamellae during the final cryo-FIB-milling steps. The severity of lamella bending seems to correlate with shrinkage of the EM grid support film at cryogenic temperatures, which could generate tensions that may be transferred onto the thin lamella, leading to its bending and breakage. To protect the lamellae from these forces, we milled “micro-expansion joints” alongside the lamellae, creating gaps in the support that can act as physical buffers to safely absorb material motion. We demonstrate that the presence of such micro-expansion joints drastically decreases lamella bending. Furthermore, we show that this adaptation does not create instabilities that could constrain subsequent parts of the cryo-lamella workflow, as we obtained high-quality Volta phase plate tomograms revealing macromolecules in their natural structural context. The minimal additional effort required to implement micro-expansion joints in the cryo-FIB-milling workflow makes them an easy solution against cryo-lamella bending in any biological sample milled on EM grids.
Comparative analyses of saprotrophy in Salisapilia sapeloensis and diverse plant pathogenic oomycetes reveal lifestyle-specific gene expression
Authors: de Vries Sophie , de Vries Jan , Archibald John M , Slamovits Claudio H
Published: June 2019

Oomycetes include many well-studied, devastating plant pathogens. Across oomycete diversity, plant-infecting lineages are interspersed by non-pathogenic ones. Unfortunately, our understanding of the evolution of lifestyle switches is hampered by a scarcity of data on the molecular biology of saprotrophic oomycetes, ecologically important primary colonizers of dead tissue that can serve as informative reference points for understanding the evolution of pathogens. Here, we established Salisapilia sapeloensis growing on axenic litter as a tractable system for the study of saprotrophic oomycetes. We generated multiple transcriptomes from S. sapeloensis and compared them to (a) 22 oomycete genomes and (b) the transcriptomes of eight pathogenic oomycetes grown under 13 conditions (three pathogenic lifestyles, six hosts/substrates, and four tissues). From these analyses we obtained a global perspective on the gene expression signatures of oomycete lifestyles. Our data reveal that oomycete saprotrophs and pathogens use generally similar molecular mechanisms for colonization, but exhibit distinct expression patterns. We identify S. sapeloensis' specific array and expression of carbohydrate-active enzymes and regulatory differences in pathogenicity-associated factors, including the virulence factor EpiC2B. Further, S. sapeloensis was found to express only a small repertoire of effector genes. In conclusion, our analyses reveal lifestyle-specific gene regulatory signatures and suggest that, in addition to variation in gene content, shifts in gene regulatory networks might underpin the evolution of oomycete lifestyles.
functionInk: An efficient method to detect functional groups in multidimensional networks reveals the hidden structure of ecological communities
Authors: Pascual-García Alberto , Bell Thomas
Published: June 2019

Complex networks have been useful to link experimental data with mechanistic models, and have become widely used across many scientific disciplines. Recently, the increasing amount and complexity of data, particularly in biology, has prompted the development of multidimensional networks, where dimensions reflect the multiple qualitative properties of nodes, links, or both. As a consequence, traditional quantities computed in single dimensional networks should be adapted to incorporate this new information. A particularly important problem is the detection of communities, namely sets of nodes sharing certain properties, which reduces the complexity of the networks, hence facilitating its interpretation.

In this work, we propose an operative definition of “function” for the nodes in multidimensional networks, and we exploit this definition to show that it is possible to detect two types of communities: i) modules, which are communities more densely connected within their members than with nodes belonging to other communities, and ii) guilds, which are sets of nodes connected with the same neighbours, even if they are not connected themselves. We provide two quantities to optimally detect both types of communities, whose relative values reflect their importance in the network.

The flexibility of the method allowed us to analyze different ecological examples encompassing mutualistic, trophic and microbial networks. We showed that by considering both metrics we were able to obtain deeper ecological insights about how these different ecological communities were structured. The method mapped pools of species with properties that were known in advance, such as plants and pollinators. Other types of communities found, when contrasted with external data, turned out to be ecologically meaningful, allowing us to identify species with important functional roles or the influence of environmental variables. Furthermore, we found the method was sensitive to community-level topological properties like the nestedness.

In ecology there is often a need to identify groupings including trophic levels, guilds, functional groups, or ecotypes.The method is therefore important in providing an objective means of distinguishing modules and guilds. The method we developed, functionInk (functional linkage), is computationally efficient at handling large multidimensional networks since it does not require optimization procedures or tests of robustness. The method is available at: HTTPS://GITHUB.COM/APASCUALGARCIA/FUNCTIONINK.
The Impact of Antimalarial Resistance on the Genetic Structure ofPlasmodium falciparumin the DRC
Authors: Verity Robert , Aydemir Ozkan , Brazeau Nicholas F. , Watson Oliver J. , Hathaway Nicholas J. , Kashamuka Mwandagalirwa Melchior , Marsh Patrick W. , Thwai Kyaw , Fulton Travis , Denton Madeline , Morgan Andrew P. , Parr Jonathan B. , Tumwebaze Patrick K. , Conrad Melissa , Rosenthal Philip J. , Ishengoma Deus S. , Ngondi Jeremiah , Gutman Julie , Mulenga Modest , Norris Douglas E. , Moss William J. , Mensah Benedicta A , Myers-Hansen James L , Ghansah Anita , Tshefu Antoinette K , Ghani Azra C. , Meshnick Steven R. , Bailey Jeffrey A. , Juliano Jonathan J.
Published: June 2019

The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequenced 2537Plasmodium falciparuminfections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a novel high-throughput genotyping tool. We identified an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identified highly related parasites over large geographic distances, indicative of gene flow and migration. Our results were consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.
Nubp2is required for cranial neural crest survival in the mouse
Authors: DiStasio Andrew , Paulding David , Chatuverdi Praneet , Stottmann Rolf W.
Published: June 2019

The N-ethyl-N-nitrosourea (ENU) forward genetic screen is a useful tool for the unbiased discovery of novel mechanisms regulating developmental processes. We recovered thedorothymutation in such a screen designed to recover recessive mutations affecting craniofacial development in the mouse.Dorothyembryos die prenatally and exhibit many striking phenotypes commonly associated with ciliopathies, including a severe midfacial clefting phenotype. We used exome sequencing to discover a missense mutation in Nucleotide Binding Protein 2 (Nubp2) to be causative. This finding was confirmed with a complementation analysis between thedorothyallele and aNubp2null allele (Nubp2Null). We demonstrate thatNubp2is indispensable for embryogenesis. NUBP2 is implicated in both the Cytosolic Iron/Sulfur cluster Assembly (CIA) pathway and in the negative regulation of ciliogenesis. Conditional ablation ofNubp2in the neural crest lineage withWnt1-crerecapitulates thedorothycraniofacial phenotype. Using this model, we found that the proportion of ciliated cells in the craniofacial mesenchyme was unchanged, and that markers of the Shh, Fgf, and Bmp signaling pathways are unaltered. Finally, we show that the phenotype results from a marked increase in apoptosis within the craniofacial mesenchyme.

Summary Statement

An ENU screen identifies a novel allele ofNubp2which is then demonstrated to be required for cranial neural crest survival and proper midfacial development.
Ecological scaffolding and the evolution of individuality: the transition from cells to multicellular life
Authors: Black Andrew J , Bourrat Pierrick , Rainey Paul B
Published: June 2019

Evolutionary transitions in individuality are central to the emergence of biological complexity. Recent experiments provide glimpses of processes underpinning the transition from single cells to multicellular life and draw attention to the critical role of ecology. Here we emphasise this ecological dimension and argue that its current absence from theoretical frameworks hampers development of general explanatory solutions. Using mechanistic mathematical models, we show how a minimal ecological structure comprised of patchily distributed resources and between patch dispersal can scaffold Darwinian-like properties on collectives of cells. This scaffolding causes cells to participate directly in the process of evolution by natural selection as if they were members of multicellular collectives, with collectives participating in a death-birth process arising from the interplay between the timing of dispersal events and the rate of resource utilisation by cells. When this timescale is sufficiently long and new collectives are founded by single cells, collectives experience conditions that favour evolution of a reproductive division of labour. Together our simple model makes explicit key events in the major evolutionary transition to multicellularity. It also makes predictions concerning the life history of certain pathogens and serves as an ecological recipe for experimental realisation of evolutionary transitions.