bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary survival strategies of the female giant panda: optimizing energy resources and expenditure prior to pregnancy by postponing corpus luteum reactivation
Authors: Wauters Jella , Wilson Kirsten S. , Bouts Tim , Vancsok Catherine , Mulot Baptiste , Leclerc Antoine , Haapakoski Marko , Kok José , Kühne Ragnar , Ochs Andreas , McNeilly Alan S. , Rae Mick , Andrew Ruth , Duncan W. Colin , Girling Simon J. , Zhou Quang , Li Rengui , Zhou Yingmin , Cai Kailai , Liu Yuliang , Hou Rong , Valentine Iain , Hildebrandt Thomas B. , Li Desheng , Vanhaecke Lynn
Published: July 2022

The giant panda reproductive physiology shows important similarities with at least six of the eight existing bear species: the occurrence of diapause and/or pseudopregnancy is commonly described in bears. Nevertheless, significant differences including the earlier breeding season with - in general - a single estrus, a shorter delay of implantation and a more variable birth season, indicate an evolutionary adaptation from the seasonal reproductive traits described in hibernating bear species.

In this study we aimed to determine true pregnancy length for giant pandas and to open the discussion on the peculiarities of giant panda reproductive biology, more specifically focusing on the rationale behind their short-seasoned reproductive cycle compared to the other bear species.

For this purpose, metabolic (body weight and fecal output) profiles were matched with endocrine changes, mainly urinary progesterone metabolites, in 5 pregnant, 8 non-birth and 6 pseudopregnant cycles of 6 female giant pandas.

Pregnancy in giant pandas lasts only 42 days from early reactivation of the corpora lutea (CLs) until birth. In addition, our findings urged the need to redefine the generally accepted biphasic progesterone profile into a triphasic primary progesterone rise (corpus luteum dormancy (CLD) I, II and III) prior to entering the active luteal phase (= secondary progesterone rise). Two episodes of progesterone increase (CLDII: 81.20 ± 5.85 days versus CLDIII: 60.80 ± 3.83 days prior to birth for pregnant cycles) were identified, respectively corresponding to CL reactivation (74-88 days prior to birth) and implantation (± 60 days prior to birth) in other bear species. The progesterone concentration during CLDIII was higher in pregnant cycles, indicating a potential communication between maternal tissues and blastocyst(s) enhancing progesterone concentrations and thus allowing optimal priming of uterine tissues to better prepare for blastocyst reactivation/development. Compared with other bear species, giant pandas seem to shorten the active luteal phase, and thus pregnancy, by approximately 30 days by actively postponing CL reactivation.

Potential mechanisms in play overruling and suppressing the evolutionary conserved photoperiodical triggers of CL reactivation are discussed while a parallel study will further elaborate on the CL dynamics during giant panda gestation.
Critical analysis of radical scavenging properties of atorvastatin in methanol recently estimated via density functional theory
Authors: Bâldea Ioan
Published: July 2022

In this communication we draw attention on serious flaws that plague recently reported antioxidant properties of atorvastatin (ATV) in methanol. First and foremost, we emphasize that the O-H bond dissociation energies (BDE) of about 400kcal/mol previously reported are completely wrong. Further, we present results refuting the previous claim that the proton affinity (PA) of ATV is smaller than that of the ascorbic acid. That unfounded claim relies on incorrect data for PA’s ascorbic acid (which we correct here) circulated in the literature. Further, we correct the values of the chemical reactivity indices (e.g., chemical hardness, electrophilicity index, electroaccepting and electrodonating powers), which were inadequately estimated previously via Kohn-Sham HOMO and LUMO energies. Finally, our updated values for O–H bond dissociation enthalpy (BDE = 91.4 kcal/mol) and electron transfer enthalpy (ETE = 105.7kcal/mol) tentatively suggest that direct H-atom transfer (HAT) and sequential proton loss electron transfer (SPLET) may coexist.
VSTM1-v2 does not drive human Th17 cell differentiation
Authors: von Richthofen Helen J. , Hafkamp Florianne M.J. , van Haperen Anouk , de Jong Esther C. , Meyaard Linde
Published: July 2022

Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an immune inhibitory receptor expressed on human myeloid cells. We previously showed that dendritic cell (DC)-driven Th17 cell differentiation of human naive CD4+ T cells requires presence of neutrophils, which is inhibited by SIRL-1 ligation. VSTM1-v2 is a soluble isoform of SIRL-1, which was previously proposed to function as a Th17 polarizing cytokine. Here, we investigated the effect of VSTM1-v2 on DC-driven Th17 cell development. Neutrophils induced DC-driven Th17 cell differentiation, which was not enhanced by VSTM1-v2. Similarly, we found no effect of VSTM1-v2 on cytokine-driven Th17 cell development. Thus, our results do not support a role for VSTM1-v2 in Th17 cell differentiation.
Methyl-SNP-seq reveals dual readouts of methylome and variome at molecule resolution
Authors: Yan Bo , Wang Duan , Vaisvila Romualdas , Sun Zhiyi , Ettwiller Laurence
Published: July 2022

Covalent modifications of genomic DNA are crucial for most organisms to survive. Amplicon-based high throughput sequencing technologies erase all DNA modifications to retain only sequence information for the four canonical nucleobases, necessitating specialized technologies for ascertaining epigenetic information. To also capture base modification information, we developed Methyl-SNP-seq, a technology that takes advantage of the complementarity of the double helix to extract the methylation and original sequence information from a single DNA molecule. More specifically, Methyl-SNP-seq uses bisulfite conversion of one of the strands to identify cytosine methylation while retaining the sequence of the other strand. As both strands are locked together to link the dual readouts on a single paired-end read, Methyl-SNP-seq allows detecting methylation status of any DNA even without a reference genome. Because one of the strands retains the original 4 nucleotide composition, Methyl-SNP-seq can also be used in conjunction with standard sequence-specific probes for targeted enrichment and amplification. We demonstrate the usefulness of this technology in a broad spectrum of applications ranging from allele-specific methylation analysis in humans to identification of methyltransferase specificity in complex bacterial communities.
The robustness of phylogenetic diversity indices to extinctions
Authors: Manson Kerry
Published: July 2022

Phylogenetic diversity indices provide a formal way to apportion evolutionary history amongst living species. Understanding the properties of these measures is key to determining their applicability in conservation biology settings. In this work, we investigate some questions posed in a recent paper by Fischer, Francis & Wicke appearing inSystematic Biology(Vol. 72(3), 2023). In that paper, it is shown that under certain extinction scenarios, the ranking of the surviving species by their Fair Proportion index scores may be the complete reverse of their ranking beforehand. Our main results here show that this behaviour extends to a large class of phylogenetic diversity indices, including the Equal-Splits index. We also provide a necessary condition for reversals of Fair Proportion rankings to occur on phylogenetic trees whose edge lengths obey the ultrametric constraint. Specific examples of rooted phylogenetic trees displaying these behaviours are given and the impact of our results on the use of phylogenetic diversity indices more generally is discussed.
Host-enemy interactions provide limited biotic resistance for a range-expanding species via reduced apparent competition
Authors: Prior Kirsten M. , Jones Dylan G. , Meadley-Dunphy Shannon A. , Lee Susan , Milks Alyson K. , Daughton Sage , Forbes Andrew A. , Powell Thomas H. Q.
Published: July 2022

As species ranges shift in response to anthropogenic change, they lose coevolved or coadapted interactions and gain novel ones in recipient communities. Range-expanding species may lose or experience weak antagonistic interactions with competitors and enemies, and traits of interacting species will determine the strength of interactions. We leveraged a poleward range expansion of an oak gall wasp that co-occurs on its host plant with other gall wasp species and interacts with shared natural enemies (largely parasitoid wasps). We created quantitative host-parasitoid interaction networks by sampling galls on 400 trees. We compared network structure and function and traits of hosts and parasitoids in the native and expanded range. Interaction networks were less diverse in the expanded range, with low complementarity of parasitoid assemblages among hosts. While whole networks were more generalized in the expanded range, interactions with the range-expanding species were more specialized. This was not due to a loss of specialist enemies but weak apparent competition by shared generalist enemies. Phenological divergence of enemy assemblages attacking the novel and co-occurring hosts was greater in the expanded range that may contribute to weak apparent competition. Given the rate and extent of anthropogenic-driven range expansions, it is pressing to uncover how complex biotic interactions are reassembled.
Nutrition-sensitive Agriculture – Is it possible in Morogoro Rural District? Awareness and practices among farmers
Authors: Sanga Innocent , Msuya John
Published: July 2022

According to FAO (2017), nutrition-sensitive agriculture is an approach that seeks to ensure the production of a variety of affordable, nutritious, culturally appropriate and safe foods in adequate quantity and quality to meet the dietary requirements of populations in a sustainable manner. This study focused on analyzing ways in which the concept is implemented and assessing its awareness among the key nutrition stakeholders. These included government officials from village, ward and district levels, NGOs, agriculture inputs suppliers, food vendors and grain millers. Cross - sectional study design was employed and information from respondents were collected by using semi-structured questionnaires, key informant interviews and transect walk. Data analysis was conducted by using SPSS version 20. It was found that home gardening (85.3%) and livestock keeping (57.4%) were the most practiced ways of nutrition-sensitive agriculture. Other ways, including use of biofortified crops, fish farming, use of watering techniques in production of fruits and vegetables, use of soil fertility conserving techniques and using improved food crop varieties were hardly practiced. Above 90% of household heads knew the importance of agriculture to nutrition being a source of food for household consumption, a source of income and employment, makes easy to access nutrient dense foods in the household and ensuring food security. The study also observed high awareness about the concept even though, the actual implementation was low. It was concluded that, low economic status among the rural poor farmers is the major reasons that have led to the observed low practices of other studied ways of agriculture that are nutrition sensitive. It is recommended that, all key stakeholders should work together to subsidize seeds and other agro-inputs which are needed by the farmers to practice these ways.
Escape From Oncogene-Induced Senescence is Controlled by POU2F2 and Memorized by Chromatin Scars
Authors: Martínez-Zamudio Ricardo Iván , Stefa Alketa , Nabuco José Américo , Vasilopoulos Themistoklis , Simpson Mark , Doré Gregory , Roux Pierre-François , Galan Mark A. , Chokshi Ravi J. , Bischof Oliver , Herbig Utz
Published: July 2022

Although oncogene-induced senescence (OIS) is a potent tumor-suppressor mechanism, recent studies revealed that cells can escape from OIS with features of transformed cells. However, the mechanisms that promote OIS escape remain unclear, and evidence of post-senescent cells in human cancers is missing. Here, we unravel the regulatory mechanisms underlying OIS escape using dynamic multidimensional profiling. We demonstrate a critical role for AP1 and POU2F2 transcription factors for escape from OIS and identify ‘senescence-associated chromatin scars (SACS)’ as an epigenetic memory of OIS, detectable during colorectal cancer progression. POU2F2 levels are elevated already in precancerous lesions and as cells escape from OIS, and its expression and binding activity to cis-regulatory elements are associated with decreased patient survival. Our results support a model in which POU2F2 exploits a precoded enhancer landscape to promote senescence escape and reveal POU2F2 gene signatures and SACS as valuable biomarkers with diagnostic and prognostic potential.
Biofunctional matrix models reveal mineral-dependent mechanoregulation of bone metastatic breast cancer
Authors: Choi Siyoung , Whitman Matthew A. , Shimpi Adrian A. , Sempertegui Nicole D. , Chiou Aaron , Druso Joseph E. , Verma Akanksha , Lux Stephanie C. , Cheng Zhu , Paszek Matthew , Elemento Olivier , Estroff Lara A. , Fischbach Claudia
Published: July 2022

Bone metastasis is a leading cause of breast cancer-related deaths and often initiated by tumor cell dissemination to osteogenic niches. During new bone formation, osteoblasts first deposit osteoid, the collagen I-rich, unmineralized component of bone ECM, within which carbonated hydroxyapatite nanoparticles subsequently form. However, it remains elusive how bone matrix mineralization dictates tumor cell phenotype due in part to the lack of relevant model systems. Using biofunctional, collagen I-based bone matrix models with physiological, intrafibrillar mineralization, we show that mineralization inhibits proliferation, while inducing a stem-like phenotype in tumor cells. These changes were due to reduced mechanosignaling contradicting the conventional assumption that increased rigidity caused by mineralization stimulates metastatic progression. Our findings are translationally relevant as the presence of mineral reduced tumor growthin vivoand upregulated a gene signature that correlated with decreased patient mortality. Our results could help explain why decreased bone mineral density increases the risk for bone metastasis in patients and highlight that bone metastasis models should integrate organic and inorganic matrix components in a manner that mimics physiological mineralization.
Molecular basis for the pheromone-mediated feeding preference of early-instar Mythimna separata larvae
Authors: Liu Jiyuan , Cheng Shichang , Zhou Tong , Li Ruichi , Tian Zhen
Published: July 2022

Insect sex pheromones are important chemical signals in sexual communication, they are traditionally thought to be inactive to larvae. However, it was found that some lepidopteran larvae can be significantly attracted by sex pheromones of the same species in a food context. Here we reported that the host-feeding choice of early-instar Mythimna separata larvae can be effectively regulated by the sex pheromone component (Z)-11-hexadecenal (Z11-16: Ald). Further exploration revealed that two olfactory proteins, M. separata general odorant binding protein 2 (MsGOBP2) and olfactory receptor 3 (MsOR3), were molecular basis of the host-feeding choice regulation mediated by Z11-16: Ald. Silencing either MsGOBP2 or MsOR3 led to a sharply reduced preference for Z11-16: Ald-spiked hosts. It is possible that the Z11-16: Ald-based preference of the M. separata larvae for host is governed by the interplay between MsGOBP2 and MsOR3. In the present research, the interactions between MsGOBP2 and Z11-16: Ald were also discussed using molecular dynamics-based approaches. Our research explored insight into the Z11-16: Ald-mediated host-feeding choice regulation of M. separata larvae, all the results would aid in developing olfaction-based methods for controlling pests in larval stage.
Diversity and Evolution of Computationally Predicted T Cell Epitopes against Human Respiratory Syncytial Virus
Authors: Chen Jiani , Tan Swan , Avadhanula Vasanthi , Moise Leonard , Piedra Pedro A , De Groot Anne S , Bahl Justin
Published: July 2022

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory infection. Despite more than 60 years of research, there is no licensed vaccine. While B cell response is a major focus for vaccine design, the T cell epitope profile of RSV is also important for vaccine development. Here, we computationally predicted putative T cell epitopes in the Fusion protein (F) and Glycoprotein (G) of RSV wild circulating strains by predicting Major Histocompatibility Complex (MHC) class I and class II binding affinity. We limited our inferences to conserved epitopes in both F and G proteins that have been experimentally validated. We applied multidimensional scaling (MDS) to construct T cell epitope landscapes to investigate the diversity and evolution of T cell profiles across different RSV strains. We find the RSV strains are clustered into three RSV-A groups and two RSV-B groups on this T epitope landscape. These clusters represent divergent RSV strains with potentially different immunogenic profiles. In addition, our results show a greater proportion of F protein T cell epitope content conservation among recent epidemic strains, whereas the G protein T cell epitope content was decreased. Importantly, our results suggest that RSV-A and RSV-B have different patterns of epitope drift and replacement and that RSV-B vaccines may need more frequent updates. Our study provides a novel framework to study RSV T cell epitope evolution. Understanding the patterns of T cell epitope conservation and change may be valuable for vaccine design and assessment.

Author Summary

Lower respiratory infections caused by human respiratory syncytial virus (RSV) is a global health challenge. B cell epitope immune response has been the major focus of RSV vaccine and therapeutic development. However, T cell epitope induced immunity plays an important role in the resolution of RSV infection. While RSV genetic diversity has been widely reported, few studies focus on RSV T epitope diversity, which can influence vaccine effectiveness. Here, we use computationally predicted T cell epitope profiles of circulating strains to characterize the diversity and evolution of the T cell epitope of RSV A and B. We systematically evaluate the T epitope profile of RSV F and G proteins. We provide a T cell epitope landscape visualization that shows co-circulation of three RSV-A groups and two RSV-B groups, suggesting potentially distinct T cell immunity. Furthermore, our study shows different levels of F and G protein T cell epitope content conservation, which may be important to correlate with duration of vaccine protection. This study provides a novel framework to study RSV T cell epitope evolution, infer RSV T cell immunity at population levels and monitor RSV vaccine effectiveness.
Global environmental drivers of local abundance-mass scaling in soil animal communities
Authors: Antunes Ana Carolina , Gauzens Benoit , Brose Ulrich , Potapov Anton M. , Jochum Malte , Santini Luca , Eisenhauer Nico , Ferlian Olga , Cesarz Simone , Scheu Stefan , Hirt Myriam R.
Published: July 2022

The relationship between species’ body masses and densities is strongly conserved around a three-quarter power law when pooling data across communities. However, studies of local within-community relationships have revealed major deviations from this general pattern, which has profound implications for their stability and functioning. Despite multiple contributions of soil communities to people, there is limited knowledge on the drivers of body mass-abundance relationship in these communities. We compiled a dataset comprising 155 soil-animal communities across four countries (Canada, Germany, Indonesia, USA), all sampled using the same methodology. We tested if variation in local climatic and edaphic conditions drives differences in local body mass-abundance scaling relationships. We found substantial variation in the slopes of this power-law relationship across local communities. Structural equation modeling showed that soil temperature and water content have a positive and negative net effect, respectively, on soil communities. These effects are mediated by changes in local edaphic conditions (soil pH and carbon content) and the body-mass range of the communities. These results highlight ways in which alterations of soil climatic and edaphic conditions interactively impact the distribution of abundance, and thus energy, between populations of small and large animals. These quantitative mechanistic relationships facilitate our understanding of how global changes in environmental conditions, such as temperature and precipitation, will affect community-abundance distributions and thus the stability and functioning of soil-animal communities.
CoxMKF: A Knockoff Filter for High-Dimensional Mediation Analysis with a Survival Outcome in Epigenetic Studies
Authors: Tian Peixin , Yao Minhao , Huang Tao , Liu Zhonghua
Published: July 2022

Motivation

It is of scientific interest to identify DNA methylation CpG sites that might mediate the effect of an environmental exposure on a survival outcome in high-dimensional mediation analysis. However, there is a lack of powerful statistical methods that can provide a guarantee of false discovery rate (FDR) control in finite-sample settings.

Results

In this article, we propose a novel method called CoxMKF, which applies aggregation of multiple knockoffs to a Cox proportional hazards model for a survival outcome with high-dimensional mediators. The proposed CoxMKF can achieve FDR control even in finite-sample settings, which is particularly advantageous when the sample size is not large. Moreover, our proposed CoxMKF can overcome the randomness of the unstable model-X knockoffs. Our simulation results show that CoxMKF controls FDR well in finite samples. We further apply CoxMKF to a lung cancer data set from The Cancer Genome Atlas (TCGA) project with 754 subjects and 365 306 DNA methylation CpG sites, and identify four DNA methylation CpG sites that might mediate the effect of smoking on the overall survival among lung cancer patients.

Availability

The R packageCoxMKFis publicly available athttps://github.com/MinhaoYaooo/CoxMKF.

Contact

zl2509@cumc.columbia.edu.
Negative and positive interspecific interactions involving jellyfish polyps in marine sessile communities
Authors: Boughton Jade , Hirst Andrew G. , Lucas Cathy H. , Spencer Matthew
Published: July 2022

Sessile marine invertebrates on hard substrates are one of the two canonical examples of communities structured by competition, but some aspects of their dynamics remain poorly understood. Jellyfish polyps are an important but under-studied component of these communities.

We determined how jellyfish polyps interact with their potential competitors in sessile marine hard-substrate communities, using a combination of experiments and modelling.

We carried out an experimental study of the interaction between polyps of the moon jellyfish Aurelia aurita and potential competitors on settlement panels, in which we determined the effects of reduction in relative abundance of either A. aurita or potential competitors at two depths. We predicted that removal of potential competitors would result in a relative increase in A. aurita that would not depend on depth, and that removal of A. aurita would result in a relative increase in potential competitors that would be stronger at shallower depths, where oxygen is less likely to be limiting.

Removal of potential competitors resulted in a relative increase in A. aurita at both depths, as predicted. Unexpectedly, removal of A. aurita resulted in a relative decrease in potential competitors at both depths. We investigated a range of models of competition for space, of which the most successful involved enhanced overgrowth of A. aurita by potential competitors, but none of these models was completely able to reproduce the observed pattern.

Our results suggest that interspecific interactions in this canonical example of a competitive system are more complex than is generally believed.
Decisive Roles of Sequence Distributions in the Generalizability ofde novoDeep Learning Models for RNA Secondary Structure Prediction
Authors: Qiu Xiangyun
Published: July 2022

Taking sequences as the only inputs, the class ofde novodeep learning (DL) models for RNA secondary structure prediction has achieved far superior performances than traditional algorithms. However, key questions remain over the statistical underpinning of such models that make no use of physical laws or co-evolutionary information. We present a quantitative study of the capacity and generalizability of a series ofde novoDL models, with a minimal two-module architecture and no post-processing, under varied distributions of the seen and unseen sequences. Our DL models outperform existing methods on commonly used benchmark datasets and demonstrate excellent learning capacities under all sequence distributions. These DL models generalize well over non-identical unseen sequences, but the generalizability degrades rapidly as the sequence distributions of the seen and unseen datasets become dissimilar. Examinations of RNA family-specific behaviors manifest not only disparate familydependent performances but substantial generalization gaps within the same family. We further determine how model generalization decreases with the decrease of sequence similarity via pairwise sequence alignment, providing quantitative insights into the limitations of statistical learning. Model generalizability thus poses a major hurdle for practical uses ofde novoDL models and several tenable avenues for future advances are discussed.
Shared and ethnic background site-specific dietary patterns in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: De Vito Roberta , Stephenson Briana , Sotres-Alvarez Daniela , Siega-Riz Anna-Maria , Mattei Josiemer , Parpinel Maria , Peters Brandilyn A. , Bainter Sierra A. , Daviglus Martha L. , Van Horn Linda , Edefonti Valeria
Published: July 2022

Dietary patterns (DPs) synthesize multiple related dietary components in one or more combined variables. A drawback of DPs is their limited reproducibility across subpopulations, especially adoptinga posterioriDPs, derived using standard multivariate methods [e.g., factor analysis (FA)]. Standard approaches assessing reproducibility of FA-based DPs mostly rely on correlation coefficients/agreement measures between pairs of factors and do not consider any statistical model. Multi-study factor analysis builds upon standard FA model to identify DPs shared across all subpopulations and those specific to some subpopulations. Pattern reproducibility is investigated from a different perspective: a shared DP identified within multi-study factor analysis is “reproducible” since it is common to all subpopulations. Bayesian multi-study factor analysis (BMSFA) has been developed to improve DP retention and identification, two critical issues as the number of subpopulations analyzed increases.

Using baseline (2008-2011) 24-hour dietary recalls from the Hispanic Community Health Study/Study of Latinos (n=16,415), we applied the BMSFA on 42 common nutrients to identify shared and subpopulation-specific DPs where subpopulations were defined as the cross-classification of ethnic background and study site (EBS).

Overall, 4 shared DPs were identified:Plant-based foods, Processed foods, Dairy products, andSeafood. At the subpopulation level, we identified 12 EBS-specific DPs, one for each EBS category, primarily representing variants of foods from animal sources. Different nuances were expressed by subsets of fairly similar EBS-specific DPs, including anAnimal vs. vegetable source, anAnimal source only, and aPoultry vs. dairy productsoverarching DPs. Shared DPs from BMSFA were similar to their counterparts from standard FA and frequentist multi-study factor analysis; EBS-specific DPs from BMSFA were better characterized than those from frequentist multi-study factor analysis.

In conclusion, the BMSFA successfully captured sources of both dietary homogeneity and heterogeneity in a large well-characterized study of US Hispanics/Latino adults by ethnic background and site.
Rucaparib blocks SARS-CoV-2 virus binding to cells and interleukin-6 release in a model of COVID-19
Authors: Papp Henrietta , Bóvári-Biri Judit , Bánfai Krisztina , Juhász Péter , Mahdi Mohamed , Russo Lilian Cristina , Bajusz Dávid , Sipos Adrienn , Petri László , Kemény Ágnes , Madai Mónika , Kuczmog Anett , Batta Gyula , Mózner Orsolya , Vaskó Dorottya , Hirsch Edit , Bohus Péter , Méhes Gábor , Tőzsér József , Curtin Nicola J. , Helyes Zsuzsanna , Tóth Attila , Hoch Nicolas C. , Jakab Ferenc , M. Keserű György , Pongrácz Judit E. , Bai Péter
Published: July 2022

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus, is a major global health challenge, as there is no efficient treatment for the moderate to severe disease. ADP-ribosylation events are involved in regulating the life cycle of coronaviruses and the inflammatory reactions of the host, hence we assessed the repurposing of registered PARP inhibitors for the treatment of COVID-19. We detected high levels of oxidative stress and strong PARylation in all cell types in the lungs of COVID-19 patients. Interestingly, rucaparib, unlike other PARP inhibitors, reduced SARS-CoV-2 infection rate through binding to the conserved 493-498 amino acid region located in the spike-ACE2 interface in the spike protein and prevented viruses from binding to ACE2. In addition, the spike protein-induced overexpression of IL-6, a key cytokine in COVID-19, was inhibited by rucaparib at pharmacologically relevant concentrations. These findings build a case for repurposing rucaparib for treating COVID-19 disease.
Risk Factors of Developing Contralateral Breast Cancer After Treatment of a First Primary Breast Cancer
Authors: Avatefi Maryam , Hadavand-Siri Fatemeh , Hashemi-Nazari Seyed-Saeed , Akbari Mohammad Esmaeil
Published: July 2022

Introduction

Breast cancer (BC) is the most common cancer among women worldwide. This study aimed to determine the disease-free interval (DFI) and the effect of risk factors and characteristics of first primary breast cancer survivors on the progression of contralateral breast cancer (CBC).

Method

In this retrospective cohort study, we identified 5003 women (containing 145 CBC and 4858 BC survivors) diagnosed with BC between 2000 and 2020 in the cancer research center. CBC was diagnosed at least 6 months after detection of primary BC. Kaplan–Meier method was used to indicate DFI and survival curves. To determine the risk factors of CBC, the Cox proportional hazard regression model was employed.

Results

The median time interval among primary BC and CBC was 7.10 years (average: 7.57, range: 0.49-19.95). The 5-year DFI was 97%. The median age of CBC and primary BC patients was 47 (range 17-78) and 48 (range 17-90), respectively. ER+, PR+, and HER2+ were reported in 72.13%, 66.67%, and 30% of CBC patients. Also, 69.57% of patients had IDC pathology type and 81.90% and 83.64% of the patients were treated with adjuvant chemotherapy and external radiotherapy. More than half of the participants had no family history of BC (69.57%). The hazard ratio indicates that women 60-70 years old, a higher number of involved lymph nodes, and recurrence had significant relationships with CBC.

Conclusion

This is the first study to investigate the risk factors of CBC and disease-free interval among BC survivors. Women with higher lymph node metastasis have a lower chance to develop CBC and patients with recurrence are at higher risk for CBC.
Evaluating the impact of e-registration and mHealth on institutional delivery in hazard-prone areas of Bangladesh: A protocol for a non-randomized controlled cluster trial
Authors: Chowdhury Anika Tasneem , Jabeen Sabrina , Sultana Zeeba Zahra , Rahman Ahmed Ehsanur , Arifeen Shams El , Hossain Ahmed
Published: July 2022

Background

Despite substantial progress, Bangladesh still has a high rate of maternal deaths owing to difficulties during pregnancy, delivery, and the postpartum period. Increasing facility delivery is mandatory to reach the goal of bringing down the MMR to <70 deaths/100,000 live births by 2030. In the era of digitalization, the introduction of e-registration and mHealth may aid the government in reaching this target. The southern part of Bangladesh is a hazard-prone area, where service uptake from institutions is low. This study aimed to determine the effect of an e-registration tracking system and mHealth counseling on institutional deliveries to pregnant mothers in hazard-prone areas of southern Bangladesh.

Methods

We will conduct an open-label, two-arm, non-randomized controlled cluster trial for six months and use three hazard-prone areas for intervention and another three hazard-prone areas for control. We will collect data at baseline and end-line of the study period using a structured questionnaire. We will enroll at least 268 pregnant mothers from the intervention and 268 pregnant mothers from the control areas after screening based on the inclusion and exclusion criteria. Pregnancy information will be obtained from the Family Welfare Assistant register. We will follow the participants until their delivery and exclude those respondents from the study who will have post-dated delivery, migrate out, lost to follow-up, or die during the study period. Random-intercept mixed-effect logistic regression will be performed to explain the relationship of e-registration and mHealth package with institutional delivery.

Discussion

Institutional delivery is still uncommon in Southern Bangladesh despite several interventions. Innovative approaches like e-registration and mHealth counseling may be helpful to bring women to health facilities.

Trial registration

This experiment is registered in the open science framework (registration number: DOI 10.17605/OSF.IO/YZE5C) and https://www.clinicaltrials.gov/ (registration number: NCT05398978).
Mitigation of gastrointestinal graft versus host disease with tocilizumab prophylaxis is accompanied by preservation of microbial diversity and attenuation of enterococcal domination
Authors: Chhabra Saurabh , Szabo Aniko , Clurman Annelie , McShane Katelynn , Waters Nicholas , Eastwood Daniel , Samanas Lisa , Fei Teng , Armijo Gabriel , Abedin Sameen , Longo Walter , Hari Parameswaran , Hamadani Mehdi , Shah Nirav N. , Runaas Lyndsey , Jerkins James H. , van den Brink Marcel , Peled Jonathan U. , Drobyski William R.
Published: July 2022

A common feature in the gastrointestinal (GI) tract during allogeneic hematopoietic stem cell transplantation is the loss of microbial diversity and emergence of opportunistic pathogens that can adversely impact survival. Consequently, preventing transplant-associated dysbiosis is an emerging strategy for optimizing treatment outcomes. In this study, we examined the effect of an extended tocilizumab administration schedule in addition to tacrolimus/methotrexate (Tac/MTX) as graft versus host disease (GVHD) prophylaxis on microbial composition in the GI tract along with overall transplant outcomes. Twenty-nine patients received busulfan-based myeloablative conditioning and were transplanted with HLA-matched related or unrelated peripheral blood stem cell grafts. The primary end point of the trial was GVHD-free relapse-free survival (GRFS) at 12 months. The cumulative incidences of grades 2-4 and 3-4 acute GVHD were 10.5% and 7% at day 180, respectively. There was one case of GVHD of the lower GI tract within the first 12 months. Non-relapse mortality and relapse-free survival were 3.4% and 86.2% at one year, respectively. GRFS was 38% at one year which was significantly higher than the pre-specified historical control rate of 20% (p=0.02) and therefore met the primary end point of the trial. Fecal samples from this patient population were sequenced and computationally analyzed centrally along with a demographically matched control cohort that received only Tac/MTX for GVHD prophylaxis. This comparative analysis revealed significantly less loss of α-diversity and reduced emergence of pathogenic organisms such as enterococcus in tocilizumab-treated recipients, demonstrating that loss of microbial diversity and enterococcal domination is attenuated in these patients. (Clinicaltrial.gov Identifier: NCT03699631).
Real World Evidence of Effectiveness of COVID-19 Vaccines and Anti SARS-CoV-2 Monoclonal Antibodies Against Post-Acute Sequelae of SARS-CoV-2 Infection
Authors: Tannous Jonika , Pan Alan P. , Potter Thomas , Bako Abdulaziz , Dlouhy Katharine , Drews Ashley , Sostman H. Dirk , Vahidy Farhaan S.
Published: July 2022

Background

We evaluated the effectiveness of COVID-19 vaccines and monoclonal antibodies (mAb) against Post-Acute Sequelae of SARS-CoV-2 infection (PASC), an emerging public health problem.

Methods and Findings

In a retrospective cohort study, we identified patients with clinically significant PASC using a COVID-19 specific, electronic medical record-based surveillance and outcomes registry from an 8-hospital tertiary healthcare system in the greater Houston metropolitan (primary analyses). Analyses were then replicated across a global research network database. We included all adults (>= 18) who survived beyond 28-days of their index infection. PASC was defined as experiencing constitutional (palpitations, malaise / fatigue, headache) or systemic (sleep disorder, shortness of breath, mood / anxiety disorders, cough, and cognitive impairment) symptoms beyond 28-day post-infection period. Instances of PASC were excluded if the symptoms were present pre-COVID or if they resolved within four weeks of initial infection. We fit multivariable logistic regression models and report estimated likelihood of PASC associated with vaccination or mAb treatment as adjusted odds ratios (aOR) with 95% confidence intervals (CI).

Primary analyses included 53,239 subjects (54.9% female), of whom 5,929, 11.1% (CI: 10.9 - 11.4), experienced PASC. Both, vaccinated breakthrough cases (vs. unvaccinated) and mAb treated patients (vs. untreated) had lower likelihoods for developing PASC, aOR (CI): 0.58 (0.52, 0.66), and 0.77 (0.69, 0.86), respectively. Vaccination was associated with decreased odds of developing all constitutional and systemic symptoms except for taste and smell changes. For all symptoms, vaccination was associated with lower likelihood of experiencing PASC compared to mAb treatment. Replication analysis found almost identical frequency of PASC (11.2%) and similar protective effects against PASC for the COVID-19 vaccine: aOR (CI) 0.25 (0.21 - 0.30) and mAb treatment: 0.62 (0.59 - 0.66).

Discussion

Although both COVID-19 vaccines and mAbs decreased the likelihood of PASC, at present, vaccination is the most effective tool to potentially prevent long-term clinical and socio-economic consequences of COVID-19.
GeoWaVe: Geometric median clustering with weighted voting for ensemble clustering of cytometry data
Authors: Burton Ross J. , Cuff Simone M. , Morgan Matt P. , Artemiou Andreas , Eberl Matthias
Published: July 2022

Motivation

Clustering is an unsupervised method for identifying structure in unlabelled data. In the context of cytometry, is typically used to categorise cells into subpopulations of similar phenotype. However, clustering is greatly dependent on hyperparameters and the data to which it is applied as each algorithm makes different assumptions and generates a different ‘view’ of the dataset. As such, the choice of clustering algorithm can significantly influence results, and there is often not one preferred method but different insights to be obtained from different methods. To overcome these limitations, consensus approaches are needed that directly address the effect of competing algorithms, which to our knowledge has not been applied to cytometry.

Results

We present a novel ensemble clustering methodology based on geometric median clustering with weighted voting (GeoWaVe). Compared to graph ensemble clustering methods that have gained popularity in scRNA-seq analysis, GeoWaVe performed favourably on different sets of high-dimensional mass and flow cytometry data. Our findings provide proof of concept for the power of consensus methods to make the analysis, visualisation and interpretation of cytometry data more robust and reproducible. The wide availability of ensemble clustering methods is likely to have a profound impact on our understanding of cellular responses, clinical conditions, and therapeutic and diagnostic options.

Availability and implementation

GeoWaVe is available as part of the CytoCluster packagehttps://github.com/burtonrj/CytoCluster.

Contact

Ross.Burton@wales.nhs.uk
Temnothorax rugatulus ants do not change their nest walls in response to environmental humidity
Authors: Chism Greg T. , Faron Wiley , Dornhaus Anna
Published: July 2022

Animal architectures are interesting biological phenomena that can greatly increase the fitness of the builder and exist in a variety of forms and functions across taxa. Among the most intricate architectures are social insect nests, which may have several functions, one of which is the control of internal microclimate. In social insects, the regulation particularly of humidity in the nest can be crucial for the survival and growth of the brood. Though much is known on how nest excavating social insects respond to environmental humidity, little is known about how ants that build on to pre-existing cavities respond. Here we use the rock ant Temnothorax rugatulus to determine whether and how colonies respond to environmental humidity by building and changing their nest architectures in pre-existing nest spaces. We specifically test the hypothesis that T. rugatulus colonies build different nest walls, e.g. wider or denser ones, in response to lower environmental humidity. We allowed T. rugatulus colonies to build nest walls with two substrates across a 0-100% relative humidity gradient. We further compare the porosity - empty volume in built nest walls - of natural T. rugatulus nest walls with these artificial building substrates and the substrate compositions of built walls from our experiment. We found that humidity did not influence the nest walls T. rugatulus colonies built in our experiment, concluding that regulating humidity is likely not a key function of T. rugatulus nest wall architecture. We also found that the porosities of the artificial substrate that was predominantly used by the ants in our experiment were like the porosity of natural T. rugatulus nest walls, indicating that ants had constant preferences for particular substrates. Physical nest wall features, including porosity, are therefore unlikely to be flexibly regulated in response to external humidity, but may be adaptations in other ways.
Visualization of a Limonene Synthesis Metabolon inside Living Bacteria by Hyperspectral SRS Microscopy
Authors: Zhang Jing , Shin Jonghyeon , Tague Nathan , Lin Haonan , Zhang Meng , Ge Xiaowei , Wong Wilson , Dunlop Mary J. , Cheng Ji-Xin
Published: July 2022

Metabolons consisting of cellular structure elements and sequential metabolic enzymes are expected to be involved in diverse biological processes. However, direct visualization of metabolons in prokaryotic cells is still challenging. In this study, we report direct visualization of concentrated subcellular regions of limonene synthesis inside single engineeredEscherichia coliby using hyperspectral stimulated Raman scattering (hSRS) microscopy. Equipped with spectral unmixing, hSRS imaging provides a reliable method to quantify intracellular limonene content. InE. colistrains with a complete limonene synthesis pathway, intracellular limonene is found locally concentrated and colocalized with proteins. Furthermore, dual-modality SRS and two-photon fluorescence imaging showed colocalization of limonene and GFP-fused limonene synthase.

Significance Statement

Monitoring biosynthesis activity at the single-cell level is key to metabolic engineering but is still difficult to achieve in a label-free manner. Using hyperspectral stimulated Raman scattering imaging in the 670-900 cm−1region, we visualized localized limonene synthesis inside engineeredE. coli. The colocalization of limonene and GFP-fused limonene synthase was confirmed by co-registered stimulated Raman scattering and two-photon fluorescence images. Our finding suggests a limonene synthesis metabolon with a polar distribution inside the cells. This finding expands our knowledge ofde novolimonene biosynthesis in engineered bacteria and highlights the potential of SRS chemical imaging in metabolic engineering research.
Genome-wide identification and characterization of the HSP gene superfamily in apple snails (Gastropoda: Ampullariidae) and expression analysis under temperature stress
Authors: Gao Yue , Li Jia-Nan , Pu Jia-Jia , Tao Ke-Xin , Zhao Xing-Xing , Yang Qian-Qian
Published: July 2022

Heat shock proteins (HSPs) play important roles in the response to various stresses as molecular chaperones. Apple snails from the family Ampullariidae have become economically important due to several species mainly from the genusPomaceawere invasive. The recent release of the genomes of ampullariids (P. canaliculata, P. maculata, Lanistes nyassanus, andMarisa cornuarietis) has opened the opportunity for a comprehensive analysis of the HSP superfamily. We identified that the number of HSP fromP. canaliculata(PcaHSPs) was greater than that from the other three species. A total of 42 PcaHSPs were distributed on 12 chromosomes and were classified into the families of HSP90, HSP70, HSP60, HSP40, HSP20, and HSP10. Each family formed a monophyletic clade on the phylogenetic trees, except for the HSP40 family. We identified tandem duplication of paralogous genes in PcaHSP70 and PcaHSP20. The RNA-seq data show that the expression profiles of PcaHSPs in different tissues have similar patterns, except that several PcaHSP20 genes revealed tissue-specific expression levels. Moreover, we identified that there were more HSP genes with stronger induction levels in response to hot than cold stress. Our findings will be helpful for future studies on stress response and adaptation focusing on HSPs in apple snails.