bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Maternal and Infant Oral Microbiomes
Authors: Yang Irene , Hu Yi-Juan , Corwin Elizabeth J. , Dunlop Anne L.
Published: July 2020

Setting the stage for good oral health early in life is critical to long-term oral and overall health. This exploratory study aimed to characterize and compare maternal and newborn oral microbiota among mother-infant pairs. Oral samples were collected from 34 pregnant African American women and their infants at 1 to 3 months of age. Extracted 16SrRNA genes were matched to the Human Oral Microbiome Database. Alpha and beta diversity differed significantly between overall maternal and infant microbiomes. Maternal or infant alpha diversity, however, was not differentiated by maternal gingival status. Several demographic and behavioral variables were associated with, but not predictive of, maternal oral microbiome alpha diversity. There was no association, however, among birth mode, feeding mode, and the infant oral microbiome. Megasphaera micronuciformis was the only periodontal pathogen detected among the infants. Notably, maternal gingival status was not associated with the presence/absence of most periodontal pathogens. This study provides an initial description of the maternal and infant oral microbiomes, laying the groundwork for future studies. The perinatal period presents an important opportunity where perinatal nurses and providers can provide oral assessment, education, and referral to quality dental care.
Neonatal Microbiome and Its Relationship to Necrotizing Enterocolitis
Authors: Mattern Jordan , Marin Terri
Published: July 2020

Necrotizing enterocolitis (NEC) occurs in many premature infants hospitalized in the neonatal intensive care unit. About 3% to 15% of very low-weight premature infants develop NEC, with an estimated 30% mortality rate for the cases requiring surgery. Currently, there is no known pathogenesis for NEC in the patient's populations. However, one of the most widely accepted hypotheses is having an abnormal fetal gut microbiome. The purpose of this review is to discuss some current methods of dysbiosis in the neonatal microbiome, such as maternal health, breastfeeding, and delivery method, and then to connect these to the occurrence of NEC in the infant and finally discuss some possibilities for limiting the occurrence of NEC in the future.
Dietary patterns and gestational hypertension in nulliparous pregnant Chinese women
Authors: Chen Xiaoju , Ding Yiling , Shi Lei , Wu Dongcai , Wang Li , Chen Fangrong , Mo Yuqiao
Published: July 2020

It has been well established that dietary patterns play important roles in the pathogenesis and development of hypertension. Our aim was to investigate the association between pregnancy dietary patterns and the risk of hypertension among nulliparous pregnant Chinese women.

A cross-sectional, case-control study.

Three hospitals in Haikou, the capital of Hainan Province, South China.

A total of 2580 participants who reported dietary intake using a validated food frequency questionnaire (FFQ).

Four primary dietary patterns were identified by principal component factor analysis and labeled as traditional Chinese, animal food, Western food, and salty snacks patterns. Women with high scores on pattern characterized by salty snacks were at increased risk.

This study suggests that dietary pattern characterized by salty snack increases the risk of hypertension during pregnancy.
High serum OX40 ligand correlates with severity and mortality in patients with massive cerebral infarction
Authors: Mao Lun-Lin , Chen Wen-Ya , Ma Ai-Jin , Ji Li-Li , Huang Ting-Ting
Published: July 2020

OX40 ligand (OX40L) is a member of tumor necrosis factors (TNF)/TNFR superfamily and is mainly expressed in activated T cells and participates in various inflammatory reactions. However, it remains unclear about the role of serum OX40L as a biomarker of cerebral infarction (CI). This study aimed to explore the possibility of serum OX40L as a meaningful predictor in mortality of CI. Severe CI patients were included to collect clinicopathological and laboratory data and measure serum OX40L level. Patients were followed up after discharge and 60-day survival rate was used as the study endpoint. The results showed that of all 294 patients, 123 (41.8%) died within 60 days after admission. Serum OX40L levels were significantly higher in patients with severe CI compared to healthy controls, and were significantly higher in nonsurvivors compared to survivors (P < .05). The levels of OX40L were correlated with Glasgow Coma Scale score, serum creatinine and high-sensitive C-reactive protein. Multivariate logistic regression analysis showed that serum OX40L level was an independent prognostic factor for 60-day mortality, after control of pulmonary infection, glasgow coma scale score and high-sensitive C-reactive protein (odds ratio = 1.089; 95% confidence interval = 1.053–1.126; P < .001). The receiver operating characteristic (ROC) curve was used to predict the best cut-off of serum OX40L for 60-day survival as 35.5 ng/mL. Patients with high serum OX40L levels (>35.5 ng/mL) had a significantly higher mortality within 60 days (hazard ratio = 2.885; 95% confidence interval = 1.901–4.378). In conclusion, OX40L is a serum biomarker of patients with CI and associated with severity and mortality of this disease.
Treatment outcomes in children with Acute lymphoblastic leukemia with versus without coexisting Down's syndrome
Authors: Liao Wenjun , Liu Ying
Published: July 2020

Background:

Down syndrome (DS) also known as Trisomy 21, is a chromosomal disorder affecting approximately 1 in 732newborns annually in the United States. Children with DS are more likely to develop acute lymphoblastic leukemia (ALL). For the management of pediatric ALL, different treatment protocols have been set up since years. However, ALL children with coexisting DS have shown to have increased therapy-related toxicities compared to those without DS. Therefore, in this study, we aimed to systematically analyze the treatment outcomes in acute ALL children with versus without coexisting DS.

Methods:

Electronic databases including the Web of Science, EMBASE, Cochrane Central, MEDLINE, http://www.ClinicalTrials.gov, and Google scholar were searched for publications reporting treatment related outcomes in ALL children with versus without co-existing DS. Several treatment protocols were used accordingly. This study had a long-term follow-up time period ranging from 5 to 10 years. The RevMan 5.3 software was used to carry out this analysis. Odds ratios (OR) with 95% confidence intervals (CI) were used to represent the results post analysis.

Results:

A total number of 31,476 children with ALL enrolled between the years 1981 and 2011 were included. Among the total number of children with ALL, 1303 had coexisting DS. Our results showed that event-free survival was similar in ALL children with versus without DS (odds ratio [OR]: 1.34, 95% confidence interval [CI]: 0.51–3.50; P = .55). Overall mortality (OR: 1.63, 95% CI: 0.86–3.10; P = .13) and participants who achieved clinical remission (OR: 1.04, 95% CI: 0.12–9.29; P = .97) were also similarly manifested. However, treatment-related mortality (OR: 4.29, 95% CI: 2.90–6.36; P = .00001) and induction failure (OR: 2.77, 95% CI: 1.08–7.07; P = .03) were significantly higher in the DS group. Also, total (OR: 1.38, 95% CI: 1.02–1.88; P = .04) and bone marrow relapses (OR: 1.29, 95% CI: 1.00–1.67; P = .05) were significantly higher in ALL children with DS. Nevertheless, central nervous system relapse (OR: 1.15, 95% CI: 0.60–2.20; P = .67), testicular relapse (OR: 0.84, 95% CI: 0.38–1.85; P = .87), and other relapses (OR: 1.12, 95% CI: 0.27–4.62; P = .88) were not significantly different when these outcomes were separately analyzed.

Conclusion:

Based on this analysis of the treatment outcomes in ALL children with versus without DS, event-free survival, overall mortality, and patients who achieved clinical remission were similar during this long-term follow-up time period. However, due to the significantly higher treatment-related mortality, induction failure, and certain relapses in ALL children with DS, new guidelines might have to focus on reconsidering or modifying treatment regimens for ALL children with DS.
A meta-analysis of the safety and effectiveness of pemetrexed compared with gefitinib for pre-treated advanced or metastatic NSCLC
Authors: Lu Xiaoxin , Li Shengshu , Chen Weizong , Zheng Dongyang , Li Yuzhu , Li Fang
Published: July 2020

Background:

The purpose of the current meta-analysis was to compare the oncological outcomes of pemetrexed versus gefitinib in pre-treated advanced or metastatic non-small cell lung cancer (NSCLC) patients.

Methods:

Search the online electronic databases on comparison the effectiveness and adverse effects of pemetrexed versus gefitinib in therapy outcomes of pre-treated NSCLC to September 2019. All studies analyzed the summary odds ratios (ORs) of the main outcomes, including survival efficacy and toxicity complications.

Results:

In all, 5 trials involving 676 subjects were included, with 332 receiving pemetrexed and 344 using gefitinib. The pooled analysis of overall survival (OS) (OR = 0.97, 95%CI = 0.77–1.21, P = .76) and progression-free survival (PFS) (OR = 1.17, 95%CI = 0.60–2.30, P = .65) showed that pemetrexed did not achieve benefit when compared with gefitinib. In the results of subgroup analysis among the EGFR mutation-positive patients, the comparison of gefitinib therapy versus pemetrexed did show PFS benefit 0.35 (95%CI 0.12–1.01; P = .05). In terms of grade 3 or 4 side effects, a similar toxicity profile of both pemetrexed and gefitinib was shown in the incidence rate of rash (P = .045), fatigue (P = .97), thrombocytopenia (P = .68) and anemia (P = .21) between the 2 groups.

Conclusion:

Pemetrexed was not associated with survival benefit than gefitinib therapy among pre-treated NSCLC patients. While, gefitinib showed superior PFS efficacy than pemetrexed for patients with EGFR mutation-type. Future investigations are required to identify relevant biomarkers in selected patients that would most likely benefit from pemetrexed or gefitinib treatment in pre-treated advanced NSCLC patients.
The effect of early dual antiplatelet timing on the microvascular resistance and ventricular function in primary percutaneous coronary intervention
Authors: Firman Doni , Taslim Imammurahman , Wangi Surya Buana , Yonas Emir , Pranata Raymond , Alkatiri Amir Aziz
Published: July 2020

Although dual antiplatelet therapy (DAPT) has been shown to improve index of microcirculatory resistance (IMR), the importance of the early DAPT administration on IMR and left ventricular function has not been clearly defined. In this study, we aimed to assess whether early DAPT administration affect IMR, epicardial flow, and left ventricular function in ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI).

This was a prospective non-randomized study on STEMI receiving primary PCI in a tertiary hospital. All subjects received loading dose DAPT (Aspirin + Clopidogrel) before primary PCI. Patients were then divided into 2 groups, the first group consists of patients receiving DAPT time ≤2 hours and the second group consists of those with DAPT time >2 hours. The primary endpoint of this study was IMR, a microvasculature function index measured quantitatively by pressure-/temperature-tipped guidewire after balloon dilatation. The secondary endpoint was the mean difference of global longitudinal strain (GLS) change at 6 months follow-up, TIMI flow before, and after PCI between the 2 groups.

There were 40 subjects qualified for the study, 20 subjects in each group. There was no significant difference in IMR (50.90 [34.66] vs 58.06 [45.56], P = .579) between the 2 groups. Early administration of DAPT improved ventricular function at 6 months, reflected by statistically significant greater improvement in terms of ΔGLS (–3.48 [2.61] vs –1.23 [2.87], P = .013) and Δejection fraction (10.65% [8.74] vs –0.75% [12.83], P = .002) in the DAPT time ≤2 hours group compared with DAPT time >2 hours group. TIMI flow before PCI (P = .653) and TIMI flow after PCI (P = .205) were similar in the 2 groups.

Early DAPT administration ≤2 hours may improve left ventricular function, but not IMR and TIMI flow.
Interdialytic blood pressure variability and the risk of stroke in maintenance hemodialysis patients
Authors: Cheng Yue , Li Yunming , Zhang Fan , Zhu Jun , Wang Tao , Wei Meng , Mo Liwen , Li Yi
Published: July 2020

Studies on nondialysis populations have linked visit-to-visit blood pressure (BP) variability (BPV) to cerebrovascular events and mortality. In view of the high prevalence of hypertension in hemodialysis patients, the predictive values of numerous factors for stroke, especially visit-to-visit BPV, were evaluated in this prospective cohort study.

A total of 151 patients were enrolled in this study. The demographic features and various laboratory parameters were analyzed. At each routine hemodialysis visit, the predialysis, intradialysis, and post-dialysis BP measurements were systematically performed. We defined BPV using 4 metrics: standard deviation of the BP, coefficient of variation, average real variability (ARV), and variability independent of mean (VIM). Differences in the predialysis BPs from one treatment to the next (ie, interdialytic variability) and differences in the BPs from predialysis to post-dialysis (ie, intradialytic variability) were both studied in this work.

Twenty-one patients developed stroke and 25 patients died. The multivariate Cox proportional hazards regression model revealed a significant relationship between stroke and the interdialytic BPV (both predialysis systolic BP variability and predialysis diastolic BP variability) and low-density lipoprotein-cholesterol (LDL-C).

Our results indicate that a high interdialytic BPV is associated with an increased risk for stroke that is independent of several factors, including age, sex, antihypertensive medication use, and mean BP over time. There is potential that the optimal treatment goal for hemodialysis patients may be to reduce the interdialytic BPV rather than either the mean BP or the intradialytic BPV.
Description of four Apiotrichum and two Cutaneotrichosporon species isolated from guano samples from bat-inhabited caves in Japan
Authors: Takashima Masako , Kurakado Sanae , Cho Otomi , Kikuchi Ken , Sugiyama Junta , Sugita Takashi
Published: July 2020

Four new yeast species belonging to the genus Apiotrichum and two new yeast species belonging to Cutaneotrichosporon are described for strains isolated from guano samples from bat-inhabited caves in Japan. In 2005, we reported these isolates as Trichosporon species based on sequence analyses of the D1/D2 domain of large subunit (LSU) rRNA genes according to available basidiomycetous yeast classification criteria; however, to date, they have not been officially published as new species with descriptions. Their phylogenetic positions have been reanalysed based on comparison of internal transcribed spacer (ITS) region sequences (including the 5.8S rRNA gene) and the D1/D2 domain of the LSU rRNA gene with those of known species; we confirmed clear separation from previously described species. Physiological and biochemical properties of the isolates also suggest their distinctiveness. Therefore, we describe Apiotrichum akiyoshidainum (holotype JCM 12595T), Apiotrichum chiropterorum (JCM 12594T), Apiotrichum coprophilum (JCM 12596T), Apiotrichum otae (JCM 12593T), Cutaneotrichosporon cavernicola (JCM 12590T) and Cutaneotrichosporon middelhovenii (JCM 12592T) as new species. C. cavernicola showed particularly distinctive morphology including large inflated anomalous cells on the hyphae and germination from the cells, although clear clamp connections on the hyphae were not confirmed. Further study is needed to elucidate the morph of this species.
Vinegar and Its Active Component Acetic Acid Inhibit SARS-CoV-2 InfectionIn VitroandEx Vivo
Authors: Pagani Isabel , Ghezzi Silvia , Clementi Massimo , Poli Guido , Bussi Mario , Pianta Luca , Trimarchi Matteo , Vicenzi Elisa
Published: July 2020

Effective and economical measures are needed to either prevent or inhibit the replication of SARS-CoV-2, the causative agent of COVID-19, in the upper respiratory tract. As fumigation of vinegar at low concentration (0.34%) ameliorated the symptoms of mild SARS-CoV-2 infection, we testedin vitrothe potential antiviral activity of vinegar and of its active component, acetic acid. We here demonstrate that both vinegar and acetic acid indeed strongly inactivate SARS-CoV-2 infectivity in Vero cells. Furthermore, vinegar treatment caused a 90% inhibition of the infectious titer when directly applied to a nasopharyngeal swab transfer medium of a COVID-19 patient. These effects were potentiated if conduced at a temperature of 45 °C vs. 37 °C, a condition that is transiently generated in the upper respiratory tract during fumigation. Our findings are consistent and extend the results of studies performed in the early and mid-20thcentury on the disinfectant capacity of organic acids and can provide an affordable home-made aid to prevent or contain SARS-CoV-2 infection of the upper respiratory tract.
Use of penalized basis splines in estimation of characteristics of seasonal and sporadic infectious disease outbreaks
Authors: Artin Ben , Weinberger Daniel , Pitzer Virginia E. , Warren Joshua L
Published: July 2020

There is often a need to estimate the characteristics of epidemics or seasonality from infectious disease data. For instance, accurately estimating the start and end date of respiratory syncytial virus (RSV) epidemics can be used to optimize the initiation of prophylactic medication. Many widely-used methods for describing these characteristics begin with a regression model fit to a time series of disease incidence. The fitted model is then often used to calculate the quantities of interest. Calculation of these quantities from the fitted regression model typically involves combining together different components of the fitted model, and consequently only point estimates (rather than measures of uncertainty) of those quantities can be made in a straightforward way. Motivated by attempts to estimate the optimal timing of prophylaxis for RSV, we developed a general method for obtaining confidence intervals for characteristics of seasonal and sporadic infectious disease outbreaks. To do this, we use multivariate sampling of a generalized additive model with penalized basis splines. Our approach provides robust confidence intervals regardless of the complexity of the calculations of the outcome measures, and it generalizes to other systems (including outbreaks of other infectious diseases). Here we present our general approach, its application to RSV, and an R package that provides a convenient interface for conducting and validating this type of analysis in other areas.
Persistent lymphocytopenia does not increase nosocomial infection risk in the ICU
Authors: Varkila Meri R.J. , Marrec Louise , Daix Thomas , Hoefer Imo E , Haitjema Saskia , Bonten Marc J.M. , Cremer Olaf L.
Published: July 2020

Background

Lymphocytopenia is frequent in critically ill patients and has been associated with an increased risk of nosocomial infections and death in the ICU. Immunotherapies to promote recovery of lymphocyte counts have therefore been proposed. However, it is unknown if lymphocytopenia is a direct cause of ICU-acquired infections and death, or merely a marker of disease severity. We set out to study the prevalence, temporal evolution, and clinical correlates of lymphocytopenia in ICU patients, and estimate the attributable risk of lymphocytopenia in ICU-acquired infections.

Methods

We assessed the association between persistent lymphocytopenia (absolute lymphocyte counts <1×10^9/L on day 4) and ICU-acquired infections using multivariable competing risk Cox-regression analyses.

Results

Among 2302 patients admitted to a Dutch tertiary ICU having sepsis, trauma, or major surgery between 2011 and 2018, persistent lymphocytopenia was observed in 980 (42.6%) subjects. Lymphocyte counts remained relatively stable during early ICU admission, and the median duration of lymphocytopenia was 3 (IQR 1-6) days among exposed patients. ICU-acquired infections occurred in 239 (18.1%) patients without and 214 (21.8%) patients with persistent lymphocytopenia (p=0.03). However, in multivariable survival analysis persistent lymphocytopenia was not associated with infection occurrence, either directly (adjusted cause-specific HR 1.08, 95% CI, 0.90–1.31) or indirectly (subdistribution HR 1.09, 95% CI, 0.91–1.32). Sensitivity analyses did not alter these findings.

Conclusion

Persistent lymphocytopenia was not associated with a higher incidence rate of nosocomial infections in critically ill patients. This challenges the rationale for using absolute lymphocyte counts as a therapeutic target to prevent ICU-acquired infections.
Reconstitution of the host holobiont in germ-free rats acutely increases bone growth and affects marrow cellular content
Authors: Czernik PJ , Golonka RM , Chakraborty S , Yeoh BS , Abokor A , Saha P , Yeo JY , Mell B , Cheng X , Baroi S , Joe B , Vijay-Kumar M , Lecka-Czernik B
Published: July 2020

In recent years there has been growing evidence regarding the effect of microbiota on the skeletal growth and homeostasis. Here we present, for the first time, accelerated longitudinal and radial bone growth in young (7-week-old) germ-free male rats after short-term exposure to a newly established gut microbiota. Changes in bone mass and structure were analyzed after 10 days following the onset of colonization through cohousing with conventional rats and revealed unprecedented acceleration of bone accrual in cortical and trabecular compartments, increased bone tissue mineral density, improved proliferation and hypertrophy of growth plate chondrocytes, bone lengthening, and preferential deposition of periosteal bone in tibia diaphysis. In addition, the number of small-in-size adipocytes increased, while the number of megakaryocytes decreased, in the bone marrow of conventionalized germ-free rats. The observed changes in bone status were paralleled with a positive shift in microbiota composition towards short chain fatty acids (SCFA)-producing microbes, which reflected a dramatic increase in cecal concentration of SCFA, specifically butyrate. Further, reconstitution of the host holobiont increased hepatic expression of IGF-1 and its circulating levels, implicating an involvement of the somatotropic axis. Increased serum levels of 25-hydroxy vitamin D and alkaline phosphatase pointed toward an active process of bone formation. The acute stimulatory effect on bone growth occurred independently of body mass increase and resembled reversal of dysbiosis in adolescence, which is marked by rapid skeletal expansion. These findings may help in developing microbiota-based therapeutics to combat bone related disorders resulting from hormonal defects and/or malnutrition in children and adolescence.
Open Source ImmGen: network perspective on metabolic diversity among mononuclear phagocytes
Authors: Gainullina Anastasiia , Huang Li-Hao , Todorov Helena , Kim Kiwook , Yng Lim Sheau , Kent Andrew , Jia Baosen , Seddu Kumba , Krchma Karen , Wu Jun , Crozat Karine , Tomasello Elena , Narang Vipin , Dress Regine , See Peter , Scott Charlotte , Gibbings Sophie , Bajpai Geetika , Desai Jigar V. , Maier Barbara , This Sébastien , Wang Peter , Aguilar Stephanie Vargas , Poupel Lucie , Dussaud Sébastien , Zhou Tyng-An , Angeli Veronique , Blander J. Magarian , Choi Kyunghee , Dalod Marc , Dzhagalov Ivan , Gautier Emmanuel L. , Jakubzick Claudia , Lavine Kory , Lionakis Michail S. , Paidassi Helena , Sieweke Michael H. , Ginhoux Florent , Guilliams Martin , Benoist Christophe , Merad Miriam , Randolph Gwendalyn J. , Sergushichev Alexey , Artyomov Maxim N. ,   ImmGen Consortium
Published: July 2020

We dissect metabolic variability of mononuclear phagocyte (MNP) subpopulations across different tissues through integrative analysis of three large scale datasets. Specifically, we introduce ImmGen MNP Open Source dataset that profiled 337 samples and extended previous ImmGen effort which included 202 samples of mononuclear phagocytes and their progenitors. Next, we analysed Tabula Muris Senis dataset to extract data for 51,364 myeloid cells from 18 tissues. Taken together, a compendium of data assembled in this work covers phagocytic populations found across 38 different tissues. To analyse common metabolic features, we developed novel network-based computational approach for unbiased identification of key metabolic subnetworks based on cellular transcriptional profiles in large-scale datasets. Using ImmGen MNP Open Source dataset as baseline, we define 9 metabolic subnetworks that encapsulate the metabolic differences within mononuclear phagocytes, and demonstrate that these features are robustly found across all three datasets, including lipid metabolism, cholesterol biosynthesis, glycolysis, and a set of fatty acid related metabolic pathways, as well as nucleotide and folate metabolism. We systematically define major features specific to macrophage and dendritic cell subpopulations. Among other things, we find that cholesterol synthesis appears particularly active within the migratory dendritic cells. We demonstrate that interference with this pathway through statins administration diminishes migratory capacity of the dendritic cellsin vivo. This result demonstrates the power of our approach and highlights importance of metabolic diversity among mononuclear phagocytes.
Production of moth sex pheromones for pest control by yeast fermentation
Authors: Holkenbrink Carina , Ding Bao-Jian , Wang Hong-Lei , Dam Marie Inger , Petkevicius Karolis , Kildegaard Kanchana Rueksomtawin , Wenning Leonie , Sinkwitz Christina , Lorántfy Bettina , Koutsoumpeli Eleni , França Lucas , Pires Marina , Bernardi Carmem , Urrutia William , Mafra-Neto Agenor , Ferreira Bruno Sommer , Raptopoulos Dimitris , Konstantopoulou Maria , Löfstedt Christer , Borodina Irina
Published: July 2020

The use of insect sex pheromones is an alternative technology for pest control in agriculture and forestry, which, in contrast to insecticides, does not have adverse effects on human health or environment and is efficient also against insecticide-resistant insect populations.1,2Due to the high cost of chemically synthesized pheromones, mating disruption applications are currently primarily targeting higher value crops, such as fruits.3Here we demonstrate a biotechnological method for the production of pheromones of economically important moth pests using engineered yeast cell factories. Biosynthetic pathways towards several pheromones or their precursors were reconstructed in the oleaginous yeastYarrowia lipolytica, which was further metabolically engineered for improved pheromone biosynthesis by decreasing fatty alcohol degradation and downregulating storage lipid accumulation. The sex pheromone of the cotton bollwormHelicoverpa armigerawas produced by oxidation of fermented fatty alcohols into corresponding aldehydes. The resulting pheromone was just as efficient and specific for trapping ofH. armigeramale moths in cotton fields in Greece as a synthetic pheromone mixture. We further demonstrated the production of the main pheromone component of the fall armywormSpodoptera frugiperda. Our work describes a biotech platform for the production of commercially relevant titres of moth pheromones for pest control by yeast fermentation.

Significance statement

Agriculture largely relies on insecticides and genetically modified crops for pest control, however alternative solutions are required due to emerging resistance, toxicity and regulatory issues, and consumer preferences. Mating disruption with sex pheromones that act by preventing insect reproduction is considered the most promising and scalable alternative to insecticides. This method is highly efficient and safe for human health and environment. The likelihood of insect resistance development is very low and can be handled by adjusting the pheromone composition. The high cost of chemically synthesized pheromones is the major barrier for the wider adoption of pheromones. A novel method based on yeast fermentation enables the production of insect sex pheromones as a lower cost from renewable feedstocks.
Highly Accurate Cancer Phenotype Prediction with AKLIMATE, a Stacked Kernel Learner Integrating Multimodal Genomic Data and Pathway Knowledge
Authors: Uzunangelov Vladislav , Wong Christopher K. , Stuart Joshua M.
Published: July 2020

Advancements in sequencing have led to the proliferation of multi-omic profiles of human cells under different conditions and perturbations. In addition, several databases have amassed information about pathways and gene “signatures” – patterns of gene expression associated with specific cellular and phenotypic contexts. An important current challenge in systems biology is to leverage such knowledge about gene coordination to maximize the predictive power and generalization of models applied to high-throughput datasets. However, few such integrative approaches exist that also provide interpretable results quantifying the importance of individual genes and pathways to model accuracy. We introduce AKLI-MATE, a first kernel-based stacked learner that seamlessly incorporates multi-omics feature data with prior information in the form of pathways for either regression or classification tasks. AKLIMATE uses a novel multiple-kernel learning framework where individual kernels capture the prediction propensities recorded in random forests, each built from a specific pathway gene set that integrates all omics data for its member genes. AKLIMATE outperforms state-of-the-art methods on diverse phenotype learning tasks, including predicting microsatellite instability in endometrial and colorectal cancer, survival in breast cancer, and cell line response to gene knockdowns. We show how AKLIMATE is able to connect feature data across data platforms through their common pathways to identify examples of several known and novel contributors of cancer and synthetic lethality.
Concurrent visual working memory bias in sequential integration of approximate number
Authors: Kang Zhiqi , Spitzer Bernhard
Published: July 2020

Previous work has shown bidirectional crosstalk between Working Memory (WM) and perception such that the contents of WM can alter concurrent percepts and vice versa. Here, we examine WM-perception interactions in a new task setting. Participants judged the proportion of colored dots in a stream of visual displays while concurrently holding location- and color information in memory. Spatiotemporally resolved psychometrics disclosed a modulation of perceptual sensitivity consistent with a bias of visual spatial attention towards the memorized location. However, this effect was short-lived, suggesting that the visuospatial WM information was rapidly deprioritized during processing of new perceptual information. Independently, we observed robust bidirectional biases of categorical color judgments, in that perceptual decisions and mnemonic reports were attracted to each other. These biases occurred without reductions in overall perceptual sensitivity compared to control conditions without a concurrent WM load. The results conceptually replicate and extend previous findings in visual search and suggest that crosstalk between WM and perception can arise at multiple levels, from sensory-perceptual to decisional processing.
Methylation-Based Age Estimation in a Wild Mouse
Authors: Little Tom J. , O’Toole Aine N. , Rambaut Andrew , Chandra Tamir , Marioni Riccardo , Pedersen Amy B.
Published: July 2020

The age structure of populations, or the ageing rate of individuals, impacts aspects of ecology, epidemiology and conservation. Yet for many wild organisms, age is an inaccessible trait. In many cases measuring age or ageing rates in the wild requires molecular biomarkers of age. Epigenetic clocks based on DNA methylation have been shown to accurately estimate the age of humans and laboratory mice, but they also show variable ticking rates that are associated with mortality risk above and beyond that predicted by chronological age. Thus, epigenetic clocks are proving to be useful markers of both chronological and biological age, and they are beginning to be applied to wild mammals and birds. We have acquired strong evidence that an accurate clock is possible for the wood mouseApodemus sylvaticusby adapting epigenetic information from the laboratory mouse (Mus musculus).Apodemus sylvaticus isa well-studied, common small mammal in the UK and Europe, which is amenable to large-scale experimental perturbations and longitudinal sampling of individuals across their lives. These features of the wood mouse system offer opportunities to disentangle causal relationships between ageing rates and environmental stress. Our wood mouse epigenetic clock is PCR-based, and so requires only tiny amounts of tissue accessible through non-destructive sampling. We quantified methylation using Oxford Nanopore sequencing technology and present a new bioinformatics pipeline for data analysis. We thus describe a new and generalizable system that should enable ecologists and other field biologists to go from small tissue samples to an epigenetic clock for their study animal, which will enable investigations of ageing in the wild which where previously inaccessible.
High-speed compressed-sensing fluorescence lifetime imaging microscopy of live cells
Authors: Ma Yayao , Lee Youngjae , Best-Popescu Catherine , Gao Liang
Published: July 2020

We present high-resolution, high-speed fluorescence lifetime imaging microscopy (FLIM) of live cells based on a compressed sensing scheme. By leveraging the compressibility of biological scenes in a specific domain, we simultaneously record the time-lapse fluorescence decay upon pulsed laser excitation within a large field of view. The resultant system, referred to as compressed FLIM, can acquire a widefield fluorescence lifetime image within a single camera exposure, eliminating the motion artifact and minimizing the photobleaching and phototoxicity. The imaging speed, limited only by the readout speed of the camera, is up to 100 Hz. We demonstrated the utility of compressed FLIM in imaging various transient dynamics at the microscopic scale.
An ancient deletion in the ABO gene affects the composition of the porcine microbiome by altering intestinal N-acetyl-galactosamine concentrations
Authors: Yang Hui , Wu Jinyuan , Huang Xiaochang , Zhou Yunyan , Zhang Yifeng , Liu Min , Liu Qin , Ke Shanlin , He Maozhang , Fu Hao , Fang Shaoming , Xiong Xinwei , Jiang Hui , Chen Zhe , Wu Zhongzi , Gong Huanfa , Tong Xinkai , Huang Yizhong , Ma Junwu , Gao Jun , Charlier Carole , Coppieters Wouter , Shagam Lev , Zhang Zhiyan , Ai Huashui , Yang Bin , Georges Michel , Chen Congying , Huang Lusheng
Published: July 2020

We have generated a large heterogenous stock population by intercrossing eight divergent pig breeds for multiple generations. We have analyzed the composition of the intestinal microbiota at different ages and anatomical locations in > 1,000 6th- and 7th- generation animals. We show that, under conditions of exacerbated genetic yet controlled environmental variability, microbiota composition and abundance of specific taxa (includingChristensenellaceae) are heritable in this monogastric omnivore. We fine-map a QTL with major effect on the abundance ofErysipelotrichaceaeto chromosome 1q and show that it is caused by a common 2.3-Kb deletion inactivating the ABO acetyl-galactosaminyl-transferase gene. We show that this deletion is a trans-species polymorphism that is ≥3.5 million years old and under balancing selection. We demonstrate that it acts by decreasing the concentrations of N-acetyl-galactosamine in the cecum thereby reducing the abundance ofErysipelotrichaceaestrains that have the capacity to import and catabolize N-acetyl-galactosamine.
Using SNAP-tag for facile construction of dye-based biosensors in living cells
Authors: Pinkin Nicholas K. , Liu Bei , Pimenta Frederico M. , Hahn Klaus M.
Published: July 2020

Fluorescent biosensors based on environment-sensitive dyes have important advantages over alternative methodologies such as FRET, including the potential for enhanced brightness, elimination of bleaching artifacts, and more possibilities for multiplexing. However, such biosensors have been difficult to use because they required proteins to be covalently labeled and reintroduced into cells. Recent development of self-labeling enzymes that covalently react with membrane-permeable dyes (e.g. SNAP-tag) provide an opportunity to easily generate dye-based biosensors within cells. Here, we generate a new biosensor for Cdc42 activation by positioning SNAP-tag between Cdc42 and a peptide that binds selectively to active Cdc42. We generate a membrane-permeable Nile Red derivative that exhibits 50-fold fluorescence enhancement upon covalent labeling of the biosensor, then optimize the biosensor so the dye undergoes a 20 nm emission shift upon Cdc42 activation, enabling ratiometric imaging with a single dye. The biosensor, named SNAPsense Cdc42, is validated by examining its response to known regulatory proteins and studying Cdc42 activation during protrusion in living cells. Variants using other dyes are also presented.
Early life nociception is influenced by peripheral growth hormone signaling
Authors: Dourson Adam J. , Ford Zachary K. , Green Kathryn J. , McCrossan Carolyn E. , Hofmann Megan C. , Hudgins Renita C. , Jankowski Michael P.
Published: July 2020

A number of cellular systems work in concert to modulate nociceptive processing in the periphery, but the mechanisms that regulate neonatal nociception may be distinct compared to adults. Our previous work indicated a relationship between neonatal hypersensitivity and growth hormone (GH) signaling. Here, we explored the peripheral mechanisms by which GH modulated neonatal nociception under normal and injury conditions (incision). We found that GH receptor signaling in primary afferents maintains a tonic inhibition of peripheral hypersensitivity. After injury, a macrophage dependent displacement of injury-site GH was found to modulate neuronal transcription at least in part via serum response factor regulation. A single GH injection into the injured hindpaw muscle effectively restored available GH signaling to neurons and prevented acute pain-like behaviors, primary afferent sensitization, and neuronal gene expression changes. GH treatment also inhibited long-term somatosensory changes observed after repeated peripheral insult. Results may indicate a novel mechanism of neonatal nociception.

Significance statement

Although it is noted that mechanisms of pain development in early life are unique compared to adults, little research focuses on neonatal-specific peripheral mechanisms of nociception. This gap is evident in the lack of specialized care for infants following an injury including surgeries. This report evaluates how distinct cellular systems in the periphery including the endocrine, immune and nervous systems work together to modulate neonatal-specific nociception. We uncovered a novel mechanism by which muscle injury induces a macrophage-dependent sequestration of peripheral growth hormone that effectively removes its normal tonic inhibition of neonatal nociceptors to promote acute pain-like behaviors. Results indicate a possible new strategy for treatment of neonatal post-surgical pain.
Application of deep neural network reveals novel effects of maternal pre-conception exposure to nicotine on rat pup behavior
Authors: Torabi Reza , Jenkins Serena , Harker Allonna , Whishaw Ian Q. , Gibb Robbin , Luczak Artur
Published: July 2020

We present a deep neural network for data-driven analyses of infant rat behavior in an open field task. The network was applied to study the effect of maternal nicotine exposure prior to conception on offspring motor development. The neural network outperformed human expert designed animal locomotion measures in distinguishing rat pups born to nicotine exposed dams versus control dams. Notably, the network discovered novel movement alterations in posture, movement initiation and a stereotypy in “warm-up” behavior (the initiation of movement along specific dimensions) that were predictive of nicotine exposure. The results suggest that maternal preconception nicotine exposure delays and alters offspring motor development. In summary, we demonstrated that a deep neural network can automatically assess animal behavior with high accuracy, and that it offers a data-driven approach to investigating pharmacological effects on brain development.

Significance

Relating neuronal activity to behavior is crucial to understand brain function. Despite the staggering progress in monitoring brain activity, behavioral analyses still do not differ much from methods developed 30-50 years ago. The reason for that is the difficulty for automated video analyses to detect small differences in complex movements. Here we show that applying deep neuronal networks for automated video analyses can help to solve this problem. More importantly, knowledge extracted from the network allowed to identify subtle changes in multiple behavioral components, which were caused by maternal preconception nicotine exposure in rat pups. Thus, the examples presented here show how neuronal networks can guide the development of more accurate behavioral tests to assess symptoms of neurological disorders.
Strain-level analysis ofBifidobacterium spp. from gut microbiomes of adults of differing lactase persistence genotypes
Authors: Schmidt Victor , Enav Hagay , Spector Timothy , Youngblut Nicholas D. , Ley Ruth
Published: July 2020

One of the strongest associations between human genetics and the gut microbiome is a greater relative abundance ofBifidobacteriumin adults with lactase gene(LCT)SNPs associated with lactase-non persistence (GG genotypes), versus lactase persistence (AA/AG genotypes). To gain a finer grained phylogenetic resolution of this association, we interrogated 1,680 16S rRNA libraries and 245 metagenomes from gut microbiomes of adults with varying lactase persistence genotypes. We further employed a novel genome-capture based enrichment ofBifidobacteriumDNA from a subset of these metagenomes, including monozygotic (MZ) twin pairs, each sampled 2 or 3 times.B. adolescentisandB. longumwere the most abundantBifidobacteriumspecies regardless of hostLCT-genotype.LCT-genotypes could not be discriminated based on relative abundances ofBifidobacteriumspecies orBifidobacteriumcommunity structure. Metagenomic analysis ofBifidobacterium-enrichedDNA revealed intra-individual temporal stability ofB. longum, B. adolescentis,andB. bifidumstrains against the background of a changeable microbiome. We also observed greater strain sharing within MZ twin pairs compared to unrelated individuals, and within GG compared to AA/AG individuals, but no effect of hostLCTgenotype onBifidobacteriumstrain composition. Our results support a “rising tide lift all boats” model for the dominant Bifidobacteria in the adult gut: their higher abundance in lactase-non persistent compared to lactase-persistent individuals results from an expansion at the genus level.Bifidobacteriumspecies are known to be transmitted from mother to child and stable within individuals in infancy and childhood: our results extend this stability into adulthood.

IMPORTANCE

When human populations domesticated animals to drink their milk they adapted genetically with the ability to digest milk into adulthood (lactase persistence). The gut microbiomes of lactase non-persistent people (LNP) differ from those of lactase-persistent people (LP) by containing more bacteria belonging to the Bifidobacteria. These beneficial gut bacteria, which fall into many species, are known to degrade milk in the baby gut. Here, we asked if adult LP and LNP microbiomes differ in the species of Bifidobacteria present. We studied the gut microbiomes of LP and LNP adults, including twins, sampled at several times. In particular, we used a technique to selectively pull out the DNA belonging to the Bifidobacteria: analysis of these DNA segments allowed us to compare Bifidobacteria at the strain level. Our results show that the LNP enhance the abundance of Bifidobacteria regardless of species. We also noted that a person’s specific strains are recoverable several years later, and twins tend to share the same ones. Given that Bifidobacteria are inherited from mother to child, strain stability over time in adulthood suggests long term, multi-generational inheritance.
Intracellular Group AStreptococcusinduces Golgi fragmentation to impair host defenses through Streptolysin O and NAD-glycohydrolase
Authors: Nozawa Takashi , Iibushi Junpei , Toh Hirotaka , Minowa-Nozawa Atsuko , Murase Kazunori , Aikawa Chihiro , Nakagawa Ichiro
Published: July 2020

Group AStreptococcus(GAS;Streptococcus pyogenes) is a major human pathogen that causes streptococcal pharyngitis, skin and soft-tissue infections, and life-threatening conditions such as streptococcal toxic-shock syndrome. During infection, GAS not only invades diverse host cells, but also injects effector proteins such as NAD-glycohydrolase (Nga) into the host cells through a streptolysin O (SLO)-dependent mechanism without invading the cells; Nga and SLO are two major virulence factors that are associated with increased bacterial virulence. Here, we have shown that the invading GAS induces fragmentation of the Golgi complex and inhibits anterograde transport in the infected host cells through the secreted toxins SLO and Nga. GAS infection-induced Golgi fragmentation required both bacterial invasion and SLO-mediated Nga translocation into the host cytosol. The cellular Golgi network is critical for the sorting of surface molecules and thus is essential for epithelial barrier integrity and the immune response of macrophages to pathogens. In epithelial cells, inhibition of anterograde trafficking by invading GAS and Nga resulted in the redistribution of E-cadherin to the cytosol and an increase in bacterial translocation across the epithelial barrier. Moreover, in macrophages, interleukin-8 secretion in response to GAS infection was found to be suppressed by intracellular GAS and Nga. Our findings reveal a previously undescribed bacterial invasion-dependent function of Nga as well as a previously unrecognized GAS-host interaction that is associated GAS pathogenesis.

Importance

Two prominent virulence factors of GAS, SLO and Nga, have been established to be linked to enhanced pathogenicity of prevalent GAS strains. Recent advances show that SLO and Nga are important for intracellular survival of GAS in epithelial cells and macrophages. Here, we found that invading GAS disrupt the Golgi complex in host cells by SLO and Nga. We showed that GAS-induced Golgi fragmentation requires bacterial invasion into host cells, SLO pore-formation activity, and Nga NADase activity. GAS-induced Golgi fragmentation resulted in the impairment of epithelial barrier and chemokine secretion in macrophages. This immune inhibition property of SLO and Nga by intracellular GAS indicates that the invasion of GAS is associated with virulence exerted by SLO and Nga.