bluuebunny/crossref_metadata_2025 huggingface dataset:
Stars made in outflows may populate the stellar halo of the Milky Way
Authors: Yu Sijie , Bullock James S , Wetzel Andrew , Sanderson Robyn E , Graus Andrew S , Boylan-Kolchin Michael , Nierenberg Anna M , Grudić Michael Y , Hopkins Philip F , Kereš Dušan , Faucher-Giguère Claude-André
Published: February 2020

We study stellar-halo formation using six Milky-Way-mass galaxies in FIRE-2 cosmological zoom simulations. We find that $5{-}40{{\ \rm per\ cent}}$ of the outer (50–300 kpc) stellar halo in each system consists of in-situ stars that were born in outflows from the main galaxy. Outflow stars originate from gas accelerated by superbubble winds, which can be compressed, cool, and form co-moving stars. The majority of these stars remain bound to the halo and fall back with orbital properties similar to the rest of the stellar halo at z = 0. In the outer halo, outflow stars are more spatially homogeneous, metal-rich, and alpha-element-enhanced than the accreted stellar halo. At the solar location, up to $\sim \!10 {{\ \rm per\ cent}}$ of our kinematically identified halo stars were born in outflows; the fraction rises to as high as $\sim \!40{{\ \rm per\ cent}}$ for the most metal-rich local halo stars ([Fe/H] >−0.5). Such stars can be retrograde and create features similar to the recently discovered Milky Way ‘Splash’ in phase space. We conclude that the Milky Way stellar halo could contain local counterparts to stars that are observed to form in molecular outflows in distant galaxies. Searches for such a population may provide a new, near-field approach to constraining feedback and outflow physics. A stellar halo contribution from outflows is a phase-reversal of the classic halo formation scenario of Eggen, Lynden-Bell & Sandange, who suggested that halo stars formed in rapidly infalling gas clouds. Stellar outflows may be observable in direct imaging of external galaxies and could provide a source for metal-rich, extreme-velocity stars in the Milky Way.
The spin measurement of the black hole in 4U 1543-47 constrained with the X-ray reflected emission
Authors: Dong Yanting , García Javier A , Steiner James F , Gou Lijun
Published: February 2020

4U 1543-47 is a low-mass X-ray binary that harbours a stellar-mass black hole located in our Milky Way galaxy. In this paper, we revisit seven data sets that were in the Steep Power Law state of the 2002 outburst. The spectra were observed by the Rossi X-ray Timing Explorer. We have carefully modelled the X-ray reflection spectra and made a joint-fit to these spectra with relxill for the reflected emission. We found a moderate black hole spin, which is $0.67_{-0.08}^{+0.15}$ at 90 per cent statistical confidence. Negative and low spins (<0.5) at more than 99 per cent statistical confidence are ruled out. In addition, our results indicate that the model requires a supersolar iron abundance: $5.05_{-0.26}^{+1.21}$, and the inclination angle of the inner disc is $36.3_{-3.4}^{+5.3}$ deg. This inclination angle is appreciably larger than the binary orbital inclination angle (∼21 deg); this difference is possibly a systematic artefact of the artificially low density employed in the reflection model for this X-ray binary system.
When the disc’s away, the stars will play: dynamical masses in the nova-like variable KR Aur with a pinch of accretion
Authors: Rodríguez-Gil P , Shahbaz T , Torres M A P , Gänsicke B T , Izquierdo P , Toloza O , Álvarez-Hernández A , Steeghs D , van Spaandonk L , Koester D , Rodríguez D
Published: February 2020

We obtained time-resolved optical photometry and spectroscopy of the nova-like variable KR  Aurigae in the low state. The spectrum reveals a DAB white dwarf (WD) and a mid-M dwarf companion. Using the companion star’s i-band ellipsoidal modulation we refine the binary orbital period to be P = 3.906519 ± 0.000001 h. The light curve and the spectra show flaring activity due to episodic accretion. One of these events produced brightness oscillations at a period of 27.4 min, that we suggest to be related with the rotation period of a possibly magnetic WD at either 27.4 or 54.8 min. Spectral modelling provided a spectral type of M4–5 for the companion star and $T_{1}=27\, 148$ $\pm \, 496$ K, $\log \, g=8.90 \pm 0.07$, and $\log (\mathrm{He/H})= -0.79^{+0.07}_{-0.08}$ for the WD. By simultaneously fitting absorption- and emission-line radial velocity curves and the ellipsoidal light curve, we determined the stellar masses to be $M_1 = 0.94^{+0.15}_{-0.11}\, {\rm{M}_{\rm \odot}}$ and $M_2 = 0.37^{+0.07}_{-0.07}\,{\rm{M}_{\rm \odot}}$ for the WD and the M-dwarf companion, respectively, and an orbital inclination of $47^{+1^{\rm o}}_{-2^{\rm o}}$. Finally, we analyse time-resolved spectroscopy acquired when the system was at an i-band magnitude of 17.1, about 1.3 mag brighter than it was in the low state. In this intermediate state, the line profiles contain an emission S-wave delayed by ≃0.2 orbital cycle relative to the motion of the WD, similar to what is observed in SW Sextantis stars in the high state.
Genome Architecture Facilitates Phenotypic Plasticity in the Honeybee (Apis mellifera)
Authors: Duncan Elizabeth J , Leask Megan P , Dearden Peter K
Published: February 2020

Phenotypic plasticity, the ability of an organism to alter its phenotype in response to an environmental cue, facilitates rapid adaptation to changing environments. Plastic changes in morphology and behavior are underpinned by widespread gene expression changes. However, it is unknown if, or how, genomes are structured to ensure these robust responses. Here, we use repression of honeybee worker ovaries as a model of plasticity. We show that the honeybee genome is structured with respect to plasticity; genes that respond to an environmental trigger are colocated in the honeybee genome in a series of gene clusters, many of which have been assembled in the last 80 My during the evolution of the Apidae. These clusters are marked by histone modifications that prefigure the gene expression changes that occur as the ovary activates, suggesting that these genomic regions are poised to respond plastically. That the linear sequence of the honeybee genome is organized to coordinate widespread gene expression changes in response to environmental influences and that the chromatin organization in these regions is prefigured to respond to these influences is perhaps unexpected and has implications for other examples of plasticity in physiology, evolution, and human disease.
Communication Behaviors During Presidential Elections
Authors: Hmielowski Jay D , Kelvin William F , Hutchens Myiah J , Silva David E , Beam Michael A , Donaway Rebecca R , York Chance
Published: February 2020

In this study, we use an information utility framework to examine people’s communication behaviors during presidential elections. Data from the National Annenberg Election Study (2004, 2008) and Google Trends (2012, 2016) reveal increases in several communication behaviors (e.g., attention to campaign information, discussing politics, internet searches) closer to Election Day. Moreover, these increases were not uniform throughout the election, with increases concentrated around official campaign events (e.g., presidential conventions and debates). In addition, some evidence showed that people are more likely to engage in communication behaviors in battleground compared to nonbattleground states.
Efficacy of plasma exchange in anti-MDA5-positive dermatomyositis with interstitial lung disease under combined immunosuppressive treatment
Authors: Shirakashi Mirei , Nakashima Ran , Tsuji Hideaki , Tanizawa Kiminobu , Handa Tomohiro , Hosono Yuji , Akizuki Shuji , Murakami Kosaku , Hashimoto Motomu , Yoshifuji Hajime , Ohmura Koichiro , Mimori Tsuneyo
Published: February 2020

Objectives

Rapidly progressive interstitial lung disease (RP-ILD) with poor prognosis often accompanies anti-melanoma differentiation-associated gene 5 (MDA5)-positive DM. Combined immunosuppressive therapy, including glucocorticoids, calcineurin inhibitors and intravenous cyclophosphamide (IVCY) is reportedly effective in DM with RP-ILD, but some patients remain resistant to therapy. We examined the utility of plasma exchange (PE) in such intractable cases and investigated the prognostic factors of the disease.

Methods

Thirty-eight anti-MDA5-positive DM-ILD patients who received the combined immunosuppressive therapy were retrospectively reviewed. Their serum cytokines were evaluated by multiplex assay before treatment. The patients were divided into two groups: those who achieved remission without exacerbation of respiratory dysfunction (n = 25, group A) and those who progressed to hypoxemia during the treatment (n = 13, group B).

Results

PE was carried out in eight group B patients, but none of group A. Five of the eight treated with PE survived, while the five untreated patients died (P =0.04). Higher neutrophil lymphocyte ratio, higher serum ferritin, hypoxemia, high-resolution computed tomography (HRCT) score before treatment and increase of Krebs von Lungen-6 (KL-6) in the first 4 weeks of the treatment were the prognostic factors for disease progression. Serum cytokines such as IL-1, IL-6, IL-8, IL-10, IL-12p70, IL-18 and sCD163 levels were higher in group B than group A.

Conclusion

PE should be an effective adjuvant treatment in anti-MDA5-positive DM with RP-ILD. Assessment of basal laboratory tests or monocyte/macrophage-derived cytokines and the increase of KL-6, HRCT score and hypoxemia may help us to predict intractable cases and to make early treatment decisions regarding PE in anti-MDA5-positive DM.
Inter-subject phase synchronization differentiates neural networks underlying physical pain empathy
Authors: Xu Lei , Bolt Taylor , Nomi Jason S , Li Jialin , Zheng Xiaoxiao , Fu Meina , Kendrick Keith M , Becker Benjamin , Uddin Lucina Q
Published: February 2020

Recent approaches for understanding the neural basis of pain empathy emphasize the dynamic construction of networks underlying this multifaceted social cognitive process. Inter-subject phase synchronization (ISPS) is an approach for exploratory analysis of task-fMRI data that reveals brain networks dynamically synchronized to task-features across participants. We applied ISPS to task-fMRI data assessing vicarious pain empathy in healthy participants (n = 238). The task employed physical (limb) and affective (face) painful and corresponding non-painful visual stimuli. ISPS revealed two distinct networks synchronized during physical pain observation, one encompassing anterior insula and midcingulate regions strongly engaged in (vicarious) pain and another encompassing parietal and inferior frontal regions associated with social cognitive processes which may modulate and support the physical pain empathic response. No robust network synchronization was observed for affective pain, possibly reflecting high inter-individual variation in response to socially transmitted pain experiences. ISPS also revealed networks related to task onset or general processing of physical (limb) or affective (face) stimuli which encompassed networks engaged in object manipulation or face processing, respectively. Together, the ISPS approach permits segregation of networks engaged in different psychological processes, providing additional insight into shared neural mechanisms of empathy for physical pain, but not affective pain, across individuals.
Cognitive Enhancing Effect of High-Frequency Neuronavigated rTMS in Chronic Schizophrenia Patients With Predominant Negative Symptoms: A Double-Blind Controlled 32-Week Follow-up Study
Authors: Xiu Mei Hong , Guan Heng Yong , Zhao Jian Min , Wang Ke Qiang , Pan Yan Fen , Su Xiu Ru , Wang Yu Hong , Guo Jin Ming , Jiang Long , Liu Hong Yu , Sun Shi Guang , Wu Hao Ran , Geng Han Song , Liu Xiao Wen , Yu Hui Jing , Wei Bao Chun , Li Xi Po , Trinh Tammy , Tan Shu Ping , Zhang Xiang Yang
Published: February 2020

Accumulating studies have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve cognitive dysfunction of the patients with schizophrenia (SCZ), but with inconsistent results. The present study aims to assess the efficacy of different frequencies of neuronavigated rTMS in ameliorating cognitive impairments and alleviating the psychotic symptoms. A total of 120 patients were randomly assigned to 3 groups: 20 Hz rTMS (n = 40), 10 Hz rTMS (n = 40), or sham stimulation (n = 40) for 8 weeks, and then followed up at week 32. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess the cognitive functions of the patients at baseline, at the end of week 8, and week 32 follow-up. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 2, week 4, week 6, week 8, and week 32 follow-up. Our results demonstrated that 20 Hz rTMS treatment produced an effective therapeutic benefit on immediate memory of patients with chronic SCZ at week 8, but not in the 10 Hz group. Interestingly, both 10 Hz and 20 Hz rTMS treatments produced delayed effects on cognitive functions at the 6-month follow-up. Moreover, in both 10 Hz rTMS and 20 Hz rTMS, the improvements in RBANS total score were positively correlated with the reduction of PANSS positive subscore at the 6-month follow-up. Stepwise regression analysis identified that the visuospatial/constructional index, immediate memory index, and prolactin at baseline were predictors for the improvement of cognitive impairments in the patients. Our results suggest that add-on HF rTMS could be an effective treatment for cognitive impairments in patients with chronic SCZ, with a delayed effect. Trial registration: clinicaltrials.gov identifier—NCT03774927.
Clinical Features of Rickettsial Infection in Children in Tropical Australia—A Report of 15 Cases
Authors: Stewart Alexandra G A , Smith Simon , Binotto Enzo , Hanson Josh
Published: February 2020

Rickettsial infections are an under-recognized cause of acute, undifferentiated fever in the tropics. In Asia, intensive care unit (ICU) admission rates as high as 21% and case-fatality rates of up to 5% have been reported. This 20-year retrospective audit of children and adults with serologically confirmed scrub typhus or spotted fever group (SFG) infection was performed at a tertiary-referral hospital in tropical Australia. There were 15 paediatric cases during the study period (11 scrub typhus, 3 SFG and 1 undifferentiated). Hypotension [5/15 (33%)], tachycardia [6/15 (40%)] and tachypnoea [6/15 (40%)] were common at presentation. Children were more likely to be hypotensive at admission than adults [5/15 (33%) vs. 5/118 (4%), p = 0.002]. However, no child died or was admitted to ICU, compared with 18/120 (15%) adults who required ICU support during the study period, one of whom died. Paediatric rickettsial infections have a relatively benign clinical course in tropical Australia with serious complications appearing far less frequently than have been reported in the Asian literature.
Hydrogeniiclostidium mannosilyticum gen. nov., sp. nov. isolated from human faeces
Authors: Chaplin Andrei V. , Sokolova Sofia R. , Shcherbakova Victoria A. , Suzina Natalia E. , Kochetkova Taisiya O. , Goltsov Andrey Y. , Trofimov Dmitriy Y. , Efimov Boris A.
Published: February 2020

A strain of obligately anaerobic, spore-forming, Gram-positive rods was isolated from child faeces and characterized both phenotypically and genotypically. Phylogenetic analysis based on 16S rRNA gene and whole genome sequencing revealed the strain to represent a member of the family

Ruminococcaceae

distant from described species and genera. The strain was moderately saccharolytic with mannose as the preferred substrate and produced lactic acid, acetic acid and H2 as the end products. The major cellular long-chain fatty acids were C16 : 0 and C16 : 0 aldehyde. The genomic DNA G+C content was 52.3 mol%. On the basis of chemotaxonomic and genomic properties it was concluded that the strain represents a novel species in a new genus within the family

Ruminococcaceae

, for which the name Hydrogeniiclostidium mannosilyticum gen. nov., sp. nov. is proposed. The type strain of Hydrogeniiclostidium mannosilyticum is ASD2818T (=VKM B-3268T=JCM 33295T).
Bradyrhizobium ivorense sp. nov. as a potential local bioinoculant for Cajanus cajan cultures in Côte d’Ivoire
Authors: Fossou Romain K. , Pothier Joël F. , Zézé Adolphe , Perret Xavier
Published: February 2020

For many smallholder farmers of Sub-Saharan Africa, pigeonpea (Cajanus cajan) is an important crop to make ends meet. To ascertain the taxonomic status of pigeonpea isolates of Côte d’Ivoire previously identified as bradyrhizobia, a polyphasic approach was applied to strains CI-1BT, CI-14A, CI-19D and CI-41S. Phylogeny of 16S ribosomal RNA (rRNA) genes placed these nodule isolates in a separate lineage from current species of the

B. elkanii

super clade. In phylogenetic analyses of single and concatenated partial dnaK, glnII, gyrB, recA and rpoB sequences, the C. cajan isolates again formed a separate lineage, with strain CI-1BT sharing the highest sequence similarity (95.2 %) with

B. tropiciagri

SEMIA 6148T. Comparative genomic analyses corroborated the novel species status, with 86 % ANIb and 89 % ANIm as the highest average nucleotide identity (ANI) values with

B. elkanii

USDA 76T. Although CI-1BT, CI-14A, CI-19D and CI-41S shared similar phenotypic and metabolic properties, growth of CI-41S was slower in/on various media. Symbiotic efficacy varied significantly between isolates, with CI-1BT and CI-41S scoring on the C. cajan ‘Light-Brown’ landrace as the most and least proficient bacteria, respectively. Also proficient on Vigna radiata (mung bean), Vigna unguiculata (cowpea, niébé) and additional C. cajan cultivars, CI-1BT represents a potential bioinoculant adapted to local soil conditions and capable of fostering the growth of diverse legume crops in Côte d'Ivoire. Given the data presented here, we propose the 19 C. cajan isolates to belong to a novel species called Bradyrhizobium ivorense sp. nov., with CI-1BT (=CCOS 1862T=CCMM B1296T) as a type strain.
Infection Dynamics of Coronavirus Disease 2019 (Covid-19) Modeled with the Integration of the Eyring’s Rate Process Theory and Free Volume Concept
Authors: Hao Tian
Published: February 2020

The Eyring’s rate process theory and free volume concept, two very popular theories in chemistry and physics fields, are employed to treat infectious disease transmissions. The susceptible individuals are assumed to move stochastically from one place to another. The virus particle transmission rate is assumed to obey the Eyring’s rate process theory and also controlled by how much free volume available in a system. The transmission process is considered to be a sequential chemical reaction, and the concentrations or fractions of four epidemiological compartments, the susceptible, the exposed, the infected, and the removed, can be derived and calculated. The obtained equations show that the basic reproduction number,R0, is not a constant, dependent on the volume fraction of virus particles, virus particle size, and virus particle packing structure, the energy barrier associated with susceptible individuals, and environment temperature. The developed models are applied to treat coronavirus disease 2019 (Covid-19) transmission and make predictions on peak time, peak infected, andR0. Our work provides a simple and straightforward approach to estimate how infection diseases evolve and how many people may be infected.
ACCLIMATION OF PHOTOSYNTHESIS TO THE ENVIRONMENT 1 regulates Photosystem II Supercomplex dynamics in response to light inChlamydomonas reinhardtii
Authors: Chazaux Marie , Caffarri Stefano , Da Graça Juliane , Cuiné Stephan , Floriani Magali , Brzezowski Pawel , Peltier Gilles , Genty Bernard , Alric Jean , Johnson Xenie
Published: March 2020

Photosynthetic organisms require acclimation mechanisms to regulate photosynthesis in response to light conditions. Here, two mutant alleles ofACCLIMATION OF PHOTOSYNTHESIS TO THE ENVIRONMENT 1(ape1) have been characterized inChlamydomonas reinhardtii.Theape1mutants are photosensitive and show PSII photoinhibition during high light acclimation or under high light stress. Theape1mutants retain more PSII super-complexes and have changes to thylakoid stacking relative to control strains during photosynthetic growth at different light intensities. The APE1 protein is found in all oxygenic phototrophs and encodes a 25 kDa thylakoid protein that interacts with the Photosystem II core complex as monomers, dimers and supercomplexes. We propose a model where APE1 bound to PSII supercomplexes releases core complexes and promotes PSII heterogeneity influencing the stacking of Chlamydomonas thylakoids. APE1 is a regulator in light acclimation and its function is to reduce over-excitation of PSII centres and avoid PSII photoinhibition to increase the resilience of photosynthesis to high light.
Prediction of the Epidemic of COVID-19 Based on Quarantined Surveillance in China
Authors: Li Rui , Lu Wenliang , Yang Xifei , Feng Peihua , Muqimova Ozarina , Chen Xiaoping , Wei Gang
Published: February 2020

Backgroud and Objective

To predict the epidemic of COVID-19 based on quarantined surveillance from real world in China by modified SEIR model different from the previous simply mathematical model.

Design and Methods

We forecasted the epidemic of COVID-19 based on current clinical and epidemiological data and built a modified SEIR model to consider both the infectivity during incubation period and the influence on the epidemic from strict quarantined measures.

Results

The peak time of the curve for the infected newly diagnosed as COVID-19 should substantially present on Feb. 5, 2020 (in non-Hubei areas) and Feb. 19, 2020 (in Hubei). It is estimated that the peak of the curve of the cumulative confirmed cases will appear in non-Hubei areas on Mar. 3, 2020 and in Hubei province on Mar. 10, 2020, and the total number of the patients diagnosed as COVID-19 is 18,000 in non-Hubei areas and 78,000-96,000 in Hubei. The Chinese COVID-19 epidemic can be completetly controlled in May, 2020.

Conclusions

COVID-19 is only a local outbreak in Hubei Province, China. It can be probably avoided the pandemic of global SARS-CoV-2 cases rise with the great efforts by Chinese government and its people.
ABC of Endometriosis Surgery: Aqua Blue Contrast Technique
Authors: Seckin Tamer , Yuksel Bahar , Seckin Serin , Ayhan Ayse
Published: February 2020

Objective

Peritoneal endometriosis is the most prevalent yet least diagnosed type due to its unrecognizable nature on imaging modalities especially non- pigmented lesions would escape the surgeons’ eye and experience during diagnostic laparoscopy. We used color adjuvant by the technique called Aqua Blue Contrast Technique (ABCT) to optimize the view and to improve results.

Material methods

Patient charts who undergone surgery from 2014 to 2015 and their 5 year follow up data, along with two different control groups, have been analyzed retrospectively. As the first group the patients who had conventional surgery without the use of ABCT) were included, the second group were patients who had ABCT applied on both pelvic side walls but not in cul-de-sac and as the third group the patients who had the surgery with the use of ABCT in all peritoneal cavity have been analyzed. Cases involving ovarian endometriomas and DIE were excluded.

Results

All patients have been followed up for up to 5 years. In group 1, the recurrence within the postoperative 3 years was 11.9%, and 16.1% after 5 years of surgery. The recurrence of 3 years period and 5 years period for the patients in group 2 were 8.7& and 12.1% respectively. The patients in group 3 recurred 3.2% in the 3 years period and the 4.3% recurrence rate calculated as 4.5% for the following 5 years after surgery.

Conclusion

Results indicate elimination of high-end spectrum of light using aqua blue contrast technique with hydrodistension of the retroperitoneum enhances the surgeon’s vision, allows lesions otherwise not detected with white light.
Hypokalemia and Clinical Implications in Patients with Coronavirus Disease 2019 (COVID-19)
Authors: Chen Dong , Li Xiaokun , Song Qifa , Hu Chenchan , Su Feifei , Dai Jianyi , Ye Yinghai , Huang Jianping , Zhang Xiaoming
Published: February 2020

BACKGROUND

SARS-CoV-2 has caused a series of COVID-19 globally. SARS-CoV-2 binds angiotensin I converting enzyme 2 (ACE2) of renin–angiotensin system (RAS) and causes prevalent hypokalemia

METHODS

The patients with COVID-19 were classified into severe hypokalemia, hypokalemia, and normokalemia group. The study aimed to determine the relationship between hypokalemia and clinical features, the underlying causes and clinical implications of hypokalemia.

RESULTS

By Feb 15, 2020, 175 patients with COVID-19 (92 women and 83 men; median age, 46 [IQR, 34–54] years) were admitted to hospital in Wenzhou, China, consisting 39 severe hypokalemia-, 69 hypokalemia-, and 67 normokalemia patients. Gastrointestinal symptoms were not associated with hypokalemia among 108 hypokalemia patients (P> 0.05). Body temperature, CK, CK-MB, LDH, and CRP were significantly associated with the severity of hypokalemia (P<0.01). 93% of severe and critically ill patients had hypokalemia which was most common among elevated CK, CK-MB, LDH, and CRP. Urine K+loss was the primary cause of hypokalemia. 1 severe hypokalemia patients was given 3 g/day, adding up to an average of 34 (SD=4) g potassium during hospital stay. The exciting finding was that patients responded well to K+supplements when they were inclined to recovery.

CONCLUSIONS

Hypokalemia is prevailing in patients with COVID-19. The correction of hypokalemia is challenging because of continuous renal K+loss resulting from the degradation of ACE2. The end of urine K+loss indicates a good prognosis and may be a reliable, in-time, and sensitive biomarker directly reflecting the end of adverse effect on RAS system.
Changes of the Commensal Microbiome during Treatment are Associated with Clinical Response in Nasopharyngeal Carcinoma Patients
Authors: Huang Tingting , Debelius Justine , Ploner Alexander , Xiao Xiling , Zhang Tingting , Hu Kai , Zhang Zhe , Wang Rensheng , Ye Weimin
Published: February 2020

Abstracts

The human microbiome has been suggested to be involved in the regulation of response to anticancer therapies. However, little is known regarding changes of commensal microbes in cancer patients during radiotherapy and whether these changes are associated with response to treatment. We conducted a prospective, longitudinal cohort with sixty-two newly diagnosed nasopharyngeal carcinoma (NPC) patients who were scheduled for radiotherapy-based treatment. Nasopharyngeal swabs were collected longitudinally before radiotherapy, during radiotherapy, and after radiotherapy. The nasopharyngeal microbiome was assessed using 16S rRNA amplicon sequencing. All patients were followed up to 24 months to define an early or late clinical response. We demonstrated the beta-diversity of the nasopharyngeal microbiome showed temporal changes throughout treatment. The magnitude of changes was stably and significantly different between the early and late responders. The temporal microbial networks among NPC patients with early response differed significantly from those with late response. Seven amplicon sequence variants (ASVs) mapped to Corynebacterium were lost during treatment. Twenty-eight abundant ASVs differed by patients’ responses throughout treatment. Among them, 10 ASVs differed between the early responders and late responders before getting any treatment and the difference was consistent along the radiotherapy course. This study addressed the temporal changes of the nasopharyngeal microbiome in NPC patients during radiotherapy and suggested a significant association with clinical response. The subject-specific changes of the nasopharyngeal microbiome might serve as a potential predictor for clinical response to radiotherapy.

Importance

The human microbiome has been suggested to be involved in the regulation of response to anticancer therapies. However, little is known regarding changes of commensal microbes in cancer patients during radiotherapy and whether these changes have an impact on response to treatment. In this longitudinal study of nasopharyngeal carcinoma patients, we demonstrate that the temporal changes of the nasopharyngeal microbiome in NPC patients during radiotherapy-based treatment and suggest a significant association with patients’ clinical response. We identify 28 abundant amplicon sequence variants differed significantly between the early and late responders throughout treatment. Among them, 10 are consistently differed by patients’ responses. These subject-specific changes might serve as a potential predictor for clinical response to radiotherapy. To the best of our knowledge, this is the first example that the commensal microbiome may influence the response to radiotherapy-based treatment in cancer patients.
A Generic Neural Network Approach to Infer Segmenting Classifiers for Disease-Associated Regions in Medical Images
Authors: Schuhmacher David , Gerwert Klaus , Mosig Axel
Published: February 2020

Abstract

In many settings in digital pathology or radiology, it is of predominant importance to train classifiers that can segment disease-associated regions in medical images. While numerous deep learning approaches, most notably U-Nets, exist to learn segmentations, these approaches typically require reference segmentations as training data. As a consequence, obtaining pixel level annotations of histopathological samples has become a major bottleneck to establish segmentation learning approaches. Our contribution introduces a neural network approach to avoid the annotation bottleneck in the first place: our approach requires two-class labels such as cancer vs. healthy at the sample level only. Using these sample-labels, a meta-network is trained that infers a segmenting neural network which will segment the disease-associated region (e.g. tumor) that is present in the cancer samples, but not in the healthy samples. This process results in a network, e.g. a U-Net, that can segment tumor regions in arbitrary further samples of the same type.

We establish and validate our approach in the context of digital label-free pathology, where hyperspectral infrared microscopy is used to segment and characterize the disease status of histopathological samples. Trained on a data set comprising infrared microscopic images of 100 tissue microarray spots labelled as either cancerous or cancer-free, the approach yields a U-Net that reliably identifies tumor regions or the absence of tumor in an independent test set involving 40 samples.

While our present work is focused on training a U-Net for infrared microscopic images, the approach is generic in the sense that it can be adapted to other image modalities and essentially arbitrary segmenting network topologies.
The abundant-centre is not all that abundant: a comment to Osorio-Olvera et al. 2020
Authors: Dallas Tad , Pironon Samuel , Santini Luca
Published: February 2020

Species abundance is expected to decrease from the centre towards the edge of their ecological niches (abundant niche-centre hypothesis). Recently, Osorio-Olveraet al. (2020) reported strong support for the abundant niche-centre relationship in North American birds. We demonstrate here that methodological decisions strongly affected perceived support. Avoiding these issues casts doubt on conclusions by Osorio-Olvera et al. and the putative support for the abundant nichecentre hypothesis in North American birds.
Predicting the effect of statins on cancer risk using genetic variants: a Mendelian randomization study in UK Biobank
Authors: Carter Paul , Vithayathil Mathew , Kar Siddhartha , Potluri Rahul , Mason Amy M. , Larsson Susanna C. , Burgess Stephen
Published: February 2020

Laboratory studies have suggested oncogenic roles of lipids, as well as anticarcinogenic effects of statins. We here assess the potential effect of statin therapy on cancer risk in Mendelian randomization analyses. We obtained genetic associations with the risk of overall and 22 site-specific cancers for 367,703 individuals in UK Biobank. In total, 75,037 individuals had a cancer event. Variants in the HMGCR gene region, which represent proxies for statin treatment, were associated with overall cancer risk (OR per 1 standard deviation increase in LDL-cholesterol 1.32, 95% CI 1.13-1.53, p=0.0003), but variants in gene regions representing alternative lipid-lowering treatment targets (PCSK9, LDLR, NPC1L1, APOC3, LPL) were not. Genetically-predicted LDL-cholesterol was not associated with overall cancer risk (OR 1.01, 95% CI 0.98-1.05, p=0.50). Our results predict that statins reduce cancer risk, but other lipid-lowering treatments do not. This suggests that statins reduce cancer risk through a cholesterol independent pathway.
High-content screening for rare respiratory diseases: readthrough therapy in primary ciliary dyskinesia
Authors: Lee Dani Do Hyang , Cardinale Daniela , Nigro Ersilia , Butler Colin R. , Rutman Andrew , Fassad Mahmoud R. , Hirst Robert A. , Moulding Dale , Agrotis Alexander , Forsythe Elisabeth , Peckham Daniel , Robson Evie , Smith Claire M. , Somavarapu Satyanarayana , Beales Philip L. , Hart Stephen L. , Janes Sam M. , Mitchison Hannah M. , Ketteler Robin , Hynds Robert E. , O’Callaghan Christopher
Published: February 2020

Development of therapeutic approaches for rare respiratory diseases is hampered by the lack of systems that allow medium-to-high-throughput screening of fully differentiated respiratory epithelium from affected patients. This is a particular problem for primary ciliary dyskinesia (PCD), a rare genetic disease caused by mutations in genes that adversely affect ciliary movement and consequently mucociliary transport. Primary cell culture of basal epithelial cells from nasal brush biopsies, followed by ciliated differentiation at air-liquid interface (ALI) has proven to be a useful tool in PCD diagnostics but the technique’s broader utility, including in pre-clinical PCD research, has been limited by the number of basal cells that it is possible to expand from such biopsies. Here, we describe a high-content, imaging-based screening method, enabled by extensive expansion of PCD patient basal cells and their culture into differentiated human respiratory epithelium in miniaturised 96-well transwell format ALI cultures. Analyses of ciliary beat pattern, beat frequency and ultrastructure indicate that a range of different PCD defects are retained in these cultures. We perform a proof-of-principle personalized investigation in reduced generation of motile cilia (RGMC), a rare and very severe form of PCD, in this case caused by a homozygous nonsense mutation (c.441C>A; p.Cys147*) in theMCIDASgene. The screening system allowed multiple drugs inducing translational readthrough to be evaluated alone or in combination with inhibitors of nonsense-mediated decay. Restoration of basal body formation in the patient’s nasal epithelial cells was seenin vitro, suggesting a novel avenue for drug evaluation and development in PCD.

We describe primary cell culture of nasal epithelial cells from patients with primary ciliary dyskinesia including differentiatiation of these to a ciliary phenotype and high-content screening in miniaturised air-liquid interface cultures.
Massive windborne migration of Sahelian insects: Diversity, seasonality, altitude, and direction
Authors: Florio J , Verú L , Dao A , Yaro AS , Diallo M , Sanogo ZL , Samaké D , Huestis DL , Yossi O , Talamas E , Chomorro L , Frank JH , Biondi M , Morkel C , Bartlett C , Linton Y-M , Strobach E , Chapman JW , Reynolds DR , Faiman R , Krajacich BJ , Smith CS , Lehmann T
Published: February 2020

Knowledge on long-distance migration of insects is especially important for food security, public health, and conservation–issues that are especially significant in Africa. During the wet season, the Sahel nourishes diverse life forms which are soon purged by the long dry season. Windborne migration is a key strategy enabling exploitation of such ephemeral havens. However, our knowledge of these large-scale movements remains sparse due to the virtual invisibility of insects flying at altitude. In this first cross-season investigation (3 years) of the aerial insect fauna over Africa, we sampled crepuscular and nocturnal insects flying 40–290 m above ground in four Sahelian villages in Mali, using sticky nets mounted on tethered helium-filled balloons. Nearly half a million insects were caught, representing at least thirteen insect orders following preliminary sorting of the collections. At least 100 insect families were determined to have been captured at altitude in samples collected on 222 nets, obtained in 125 collections over 96 nights. Control nets (raised momentarily to >40 m during system launch and retrieval) confirmed that the insects were captured at altitude, not near the ground. Thirteen ecologically and phylogenetically diverse species were studied in detail. The flight activity of all species peaked during the wet season every year across localities up to ~100 km apart, and occurred over multiple nights, suggesting regular migrations. Species differed in flight altitude, seasonality, and correlations with aerial temperatures, humidity, and wind speed. All taxa exhibited frequent migrations on southerly winds, accounting for the recolonization of the Sahel from southern source populations. “Return” southward movement at the end of the wet season occurred in most taxa but no selectivity for such winds was detected. Extrapolation of aerial density to estimate the seasonal number of migrants crossing Mali at latitude 14°N suggested numbers in the trillions, even for the modestly abundant taxa. Assuming 2–10 hours of flight, the nightly distances traversed exceed tens and even hundreds of kilometers. Two migration strategies were proposed: “residential Sahelian migration” and “round trip migration”. The unprecedented magnitude and diversity of long-range windborne insect migrations highlight the importance of this life strategy in their impact on Sahelian and neighboring ecosystems.
Redefining CD4 T cell residency: Helper T cells orchestrate protective humoral immunity in the lung
Authors: Swarnalekha Nivedya , Schreiner David , Litzler Ludivine C , Iftikhar Saadia , Kirchmeier Daniel , Künzli Marco , King Carolyn G
Published: February 2020

Influenza is a severe and acute respiratory pathogen, and a significant cause for morbidity, particularly in young children and the elderly. Following influenza infection, clonally expanded T cells take up permanent residence in the lung where they are poised to rapidly respond to challenge infection. The non-circulating status of these tissue resident memory (TRM) cells makes them an attractive target for vaccination. While many studies have characterized CD8 TRM cells, less is known about the heterogeneity and protective capacity of CD4 TRM cells. Here we characterized the dynamics and transcriptional regulation of lung resident CD4 T cells to define a non-lymphoid signature that removes the bias created by the prevalence of Th1 helper cells during viral infection. We identified a novel population of long-lived T resident helper (TRH) cells that requires intrinsic Bcl6 expression for their differentiation. Although TRH cells also depend on B cells, they are generated independently of T follicular helper effector cells in the lymph node. In contrast to lung resident Th1 cells, TRH cells are tightly co-localized with B cells in inducible Bronchus Associated Lymphoid Tissue (iBALT). Deletion of Bcl6 in CD4 T cells prior to heterotypic challenge infection results in redistribution of CD4 T cells outside of iBALT areas and impaired local antibody production. These data highlight lung iBALT as a niche for the homeostasis and survival of TRH cells, and further suggest that vaccination strategies to selectively induce TRH cells can improve protective immunity in the tissue.
In search of the RNA world on Mars
Authors: Mojarro Angel , Jin Lin , Szostak Jack W. , Head James W. , Zuber Maria T.
Published: February 2020

Advances in origins of life research and prebiotic chemistry suggest that life as we know it may have emerged from an earlier RNA World. However, it has been difficult to reconcile the conditions used in laboratory experiments with real-world geochemical environments that may have existed on the early Earth and hosted the origin(s) of life. This challenge is in part due to geologic resurfacing and recycling that have erased the overwhelming majority of the Earth’s prebiotic history. We therefore propose that Mars, a planet frozen in time, comprised of many surfaces that have remained relatively unchanged since their formation >4 Gya, is the best alternative to search for environments consistent with geochemical requirements imposed by the RNA world. In this study we synthesizein situand orbital observations of Mars and modeling of its early atmosphere into solutions containing a range of pHs and concentrations of prebiotically relevant metals (Fe2+, Mg2+, and Mn2+), spanning various candidate aqueous environments. We then experimentally determine RNA degradation kinetics due to metal-catalyzed hydrolysis and evaluate whether early Mars could have been permissive towards the accumulation of long-lived RNA polymers. Our results indicate that a Mg2+-rich basalt sourcing metals to a slightly acidic (pH 5.4) aqueous environment mediates the slowest rates of metal-catalyzed RNA hydrolysis, though geologic evidence and modeling of basalt weathering suggest that aquifers on Mars would be near neutral (pH ∼7). Moreover, oxidizing conditions on Mars have major consequences regarding the availability oxygen-sensitive prebiotic metals (i.e., Fe2+and Mn2+) very early in its history due to increased RNA degradation rates and precipitation. Overall, 1) low pH better preserves RNA than basic conditions at high concentrations; 2) acidic to neutral pH environments with Fe2+or Mn2+will hydrolyze more RNA; and 3) alkaline environments with Mg2+dramatically hydrolyze more RNA.
Conserved regulation of omptin proteases by the PhoPQ two-component regulatory system in Enterobacteriaceae
Authors: Cho Youn Hee , Aziz Monir Riasad Fadle , Sutradhar Tanuja , Bashal Jasika , Cojocari Veronica , McPhee Joseph B.
Published: February 2020

Bacteria that colonize eukaryotic surfaces interact with numerous host-produced molecules that have antimicrobial activity. Bacteria have evolved numerous strategies to both detect and resist these molecules, and in gram-negative bacteria these include alterations of the cell surface lipopolysaccharide structure and/or charge and the production of proteases that can degrade these antimicrobial molecules. Many of the lipopolysaccharide alterations found in enteric bacteria are controlled by the PhoPQ and PmrAB two-component regulatory systems. Here, we show that omptin family proteases fromEscherichia coliandCitrobacter rodentiumare induced by growth in low Mg2+. We further show that deletion of PhoP eliminates omptin protease activity, transcriptional regulation and protein levels. We identify conserved PhoP-binding sites in the promoters of theE. coliomptin genes,ompT,ompPandarlCas well as incroPofCitrobacter rodentiumand show that mutation of the putative PhoP-binding site in theompTpromoter abrogates PhoP-dependent expression. Finally, we show that despite the conserved PhoP-dependent regulation, each of theE. coliomptin proteins has differential activity toward a particular substrate, suggesting that each omptin may contribute to resistance to a particular repertoire of host-defense peptides, depending on the particular environment in which each evolved.
POU6F2 Positive Retinal Ganglion Cells a Novel Group of ON-OFF Directionally Selective Subtypes in the Mouse Retina
Authors: Li Ying , Wang Jiaxing , King Rebecca , Geisert Eldon E.
Published: February 2020

Purpose

Previously we identified POU6F2 as a genetic link between central corneal thickness (CCT) and risk of open-angle glaucoma. The present study is designed to characterize the POU6F2-positive retinal ganglion cells (RGCs).

Methods

The Thy1-YFP-H mouse was used to identify the structure of POU6F2-positive RGCs in the retina. In the retina of the Thy1-YFP-H mouse approximately 3% of the RGCs were labeled with yellow fluorescent protein. These retinas were stained for POU6F2 to identify the morphology of the POU6F2 subtypes in 3D reconstructions of the labeled RGCs. Multiple retinal cell markers were also co-stained with POU6F2 to characterize the molecular signature of the POU6F2-positive RGCs. DBA/2J glaucoma models were used to test the role of POU6F2 in injury.

Results

In the retina POU6F2 labels 32.9% of the RGCs in the DBA/2J retina (16.1% heavily and 16.8% lightly labeled). In 3D constructions of Thy1-YFP-H positive RGCs, the heavily labeled POU6F2-positive cells had dendrites in the inner plexiform layer that were bistratified and appeared to be ON-OFF directionally selective cells. The lightly labeled POU6F2 RGCs displayed 3 different dendritic distributions, with dendrites in the ON sublaminae only, OFF sublaminae only, or bistratified. The POU6F2-positive cells partially co-stained withCdh6. The POU6F2-positive cells do not co-stain with CART and SATB2 (markers for ON-OFF directionally selective RGC), SMI32 (a marker for alpha RGCs), or ChAT and GAD67(markers for amacrine cells). The POU6F2-positive cells were sensitive to injury. In DBA/2J glaucoma model, at 8 months of age there was a 22% loss of RGCs (labeled with RBPMS) while there was 73% loss of the heavily labeled POU6F2 RGCs.

Conclusions

POU6F2 is a marker for a novel group of RGC subtypes that are ON-OFF directionally selective RGCs that are sensitive to glaucomatous injury.
Metabolic multi-stability and hysteresis in a model aerobe-anaerobe microbiome community
Authors: Khazaei Tahmineh , Williams Rory L. , Bogatyrev Said R. , Doyle John C. , Henry Christopher S. , Ismagilov Rustem F.
Published: February 2020

Changes in the composition of the human microbiome are associated with health and disease. Some microbiome states persist in seemingly unfavorable conditions, e.g., the proliferation of aerobe-anaerobe communities in oxygen-exposed environments in wounds or small intestinal bacterial overgrowth. However, it remains unclear how different stable microbiome states can exist under the same conditions, or why some states persist under seemingly unfavorable conditions. Here, using two microbes relevant to the human microbiome, we combine genome-scale mathematical modeling, bioreactor experiments, transcriptomics, and dynamical systems theory, to show that multi-stability and hysteresis (MSH) is a mechanism that can describe the shift from an aerobe-dominated state to a resilient, paradoxically persistent aerobe-anaerobe state. We examine the impact of changing oxygen and nutrient regimes and identify factors, including changes in metabolism and gene expression, that lead to MSH. When analyzing the transitions between the two states in this system, the familiar conceptual connection between causation and correlation is broken and MSH must be used to interpret the dynamics. Using MSH to analyze microbiome dynamics will improve our conceptual understanding of the stability of microbiome states and the transitions among microbiome states.

One sentence summary

Multi-stability and hysteresis (MSH) is a potential mechanism to describe shifts to and persistence of aerobe-anaerobe communities in the microbiome.