bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermal Responses Differ across Levels of Biological Organization
Authors: Iverson Erik N K , Nix Rachel , Abebe Ash , Havird Justin C 
Published: May 2020

Synopsis
Temperature is one of the most important environmental factors driving the genome-to-phenome relationship. Metabolic rates and related biological processes are predicted to increase with temperature due to the biophysical laws of chemical reactions. However, selection can also act on these processes across scales of biological organization, from individual enzymes to whole organisms. Although some studies have examined thermal responses across multiple scales, there is no general consensus on how these responses vary depending on the level of organization, or whether rates actually follow predicted theoretical patterns such as Arrhenius-like exponential responses or thermal performance curves (TPCs) that show peak responses. Here, we performed a meta-analysis on studies of ectotherms where biological rates were measured across the same set of temperatures, but at multiple levels of biological organization: enzyme activities, mitochondrial respiration, and/or whole-animal metabolic rates. Our final dataset consisted of 235 pairwise comparisons between levels of organization from 13 publications. Thermal responses differed drastically across levels of biological organization, sometimes showing completely opposite patterns. We developed a new effect size metric, “organizational disagreement” (OD) to quantify the difference in responses among levels of biological organization. Overall, rates at higher levels of biological organization (e.g., whole animal metabolic rates) increased more quickly with temperature than rates at lower levels, contrary to our predictions. Responses may differ across levels due to differing consequences of biochemical laws with increasing organization or due to selection for different responses. However, taxa and tissues examined generally did not affect OD. Theoretical TPCs, where rates increase to a peak value and then drop, were only rarely observed (12%), possibly because a broad range of test temperatures was rarely investigated. Exponential increases following Arrhenius predictions were more common (29%). This result suggests a classic assumption about thermal responses in biological rates is rarely observed in empirical datasets, although our results should be interpreted cautiously due to the lack of complete thermal profiles. We advocate for authors to explicitly address OD in their interpretations and to measure thermal responses across a wider, more incremental range of temperatures. These results further emphasize the complexity of connecting the genome to the phenome when environmental plasticity is incorporated: the impact of the environment on the phenotype can depend on the scale of organization considered.
Trade-offs, Pleiotropy, and Shared Molecular Pathways: A Unified View of Constraints on Adaptation
Authors: Mauro Alexander A , Ghalambor Cameron K 
Published: May 2020

Synopsis
The concept of trade-offs permeates our thinking about adaptive evolution because they are exhibited at every level of biological organization, from molecular and cellular processes to organismal and ecological functions. Trade-offs inevitably arise because different traits do not occur in isolation, but instead are imbedded within complex, integrated systems that make up whole organisms. The genetic and mechanistic underpinning of trade-offs can be found in the pleiotropic nodes that occur in the biological pathways shared between traits. Yet, often trade-offs are only understood as statistical correlations, limiting the ability to evaluate the interplay between how selection and constraint interact during adaptive evolution. Here, we first review the classic paradigms in which physiologists and evolutionary biologists have studied trade-offs and highlight the ways in which network and molecular pathway approaches unify these paradigms. We discuss how these approaches allow researchers to evaluate why trade-offs arise and how selection can act to overcome trait correlations and evolutionary constraints. We argue that understanding how the conserved molecular pathways are shared between different traits and functions provides a conceptual framework for evolutionary biologists, physiologists, and molecular biologists to meaningfully work together toward the goal of understanding why correlations and trade-offs occur between traits. We briefly highlight the melanocortin system and the hormonal control of osmoregulation as two case studies where an understanding of shared molecular pathways reveals why trade-offs occur between seemingly unrelated traits. While we recognize that applying such approaches poses challenges and limitations particularly in the context of natural populations, we advocate for the view that focusing on the biological pathways responsible for trade-offs provides a unified conceptual context accessible to a broad range of integrative biologists.
Number of metastatic lymph nodes and zones as prognostic factors in non-small-cell lung cancer
Authors: Maniwa Tomohiro , Ohmura Akiisa , Hiroshima Takashi , Ike Akihiro , Kimura Toru , Nakamura Harumi , Nakatsuka Shin-Ichi , Okami Jiro , Higashiyama Masahiko 
Published: May 2020

Abstract

OBJECTIVES
Characterizing pathological nodes (pNs) by location alone is sometimes inadequate as patients with pN1 or pN2 non-small-cell lung cancer (NSCLC) show prognostic heterogeneity. We aimed to assess the relationship of the number of metastatic lymph nodes (LNs) and zones with prognosis in NSCLC patients.

METHODS
We analysed 1393 patients who underwent lobectomy with mediastinal LN dissection for NSCLC at the Osaka International Cancer Institute between January 2006 and December 2015. Patients were classified into 3 groups according to the number of LNs: n1–3, n4–6 and n7–. We investigated the relationship of prognosis with the number of metastatic LNs and metastatic zones.

RESULTS
In the multivariable analyses, the number of metastatic LNs and zones were not independent factors for overall survival or recurrence-free survival in patients with pN1 disease after adjustment for age, sex, tumour histology and tumour diameter. However, n4–6 (ref. n1–3) was an independent prognostic factor for overall survival [hazard ratio (HR) 4.148, P &lt; 0.001] in those with pN2 disease. There were no significant differences in overall survival and recurrence-free survival between pN1 (HR 0.674, P = 0.175) and pN2n1–3 disease (HR 1.056, P = 0.808). Moreover, patients with pN2 disease with a higher number of metastatic zones had a poor prognosis for recurrence-free survival [3 zones (ref. 1): HR 1.774, P = 0.051, and 4 zones (ref. 1): HR 2.173, P &lt; 0.047].

CONCLUSIONS
The number of metastatic LNs and metastatic zones were useful prognostic factors in NSCLC patients. The findings could help in establishing a new pN classification.
Inhibition of Necroptosis to Prevent Long-term Cardiac Damage During Pneumococcal Pneumonia and Invasive Disease
Authors: Beno Sarah M , Riegler Ashleigh N , Gilley Ryan P , Brissac Terry , Wang Yong , Kruckow Katherine L , Jadapalli Jeevan K , Wright Griffin M , Shenoy Anukul T , Stoner Sara N , Restrepo Marcos I , Deshane Jessy S , Halade Ganesh V , González-Juarbe Norberto , Orihuela Carlos J 
Published: May 2020

Abstract

Background
Streptococcus pneumoniae infection can result in bacteremia with devastating consequences including heart damage. Necroptosis is a proinflammatory form of cell death instigated by pore-forming toxins such as S. pneumoniae pneumolysin. Necroptosis-inhibiting drugs may lessen organ damage during invasive pneumococcal disease (IPD).

Methods
In vitro experiments were carried out with human and mouse cardiomyocytes. Long-term cardiac damage was assessed using high-resolution echocardiography in ampicillin-rescued mice 3 months after challenge with S. pneumoniae. Ponatinib, a necroptosis-inhibiting and Food and Drug Administration–approved drug for lymphocytic leukemia treatment, was administered intraperitoneally alongside ampicillin to test its therapeutic efficacy. Histology of heart sections included hematoxylin-eosin staining for overt damage, immunofluorescence for necroptosis, and Sirius red/fast green staining for collagen deposition.

Results
Cardiomyocyte death and heart damage was due to pneumolysin-mediated necroptosis. IPD leads to long-term cardiac damage, as evidenced by de novo collagen deposition in mouse hearts and a decrease in fractional shortening. Adjunct necroptosis inhibition reduced the number of S. pneumoniae foci observed in hearts of acutely infected mice and serum levels of troponin I. Ponatinib reduced collagen deposition and protected heart function in convalescence.

Conclusions
Acute and long-term cardiac damage incurred during IPD is due in part to cardiomyocyte necroptosis. Necroptosis inhibitors may be a viable adjunct therapy.
The Potential Impact of Long-Acting Cabotegravir for HIV Prevention in South Africa: A Mathematical Modeling Study
Authors: Smith Jennifer A , Garnett Geoffrey P , Hallett Timothy B 
Published: May 2020

Abstract

Background
Although effective, some oral pre-exposure prophylaxis (PrEP) users face barriers to adherence using daily pills, which could be reduced by long-acting formulations. Long-acting cabotegravir (CAB LA) is a potential new injectable formulation for human immunodeficiency virus (HIV) PrEP being tested in phase III trials.

Methods
We use a mathematical model of the HIV epidemic in South Africa to simulate CAB LA uptake by population groups with different levels of HIV risk. We compare the trajectory of the HIV epidemic until 2050 with and without CAB LA to estimate the impact of the intervention.

Results
Delivering CAB LA to 10% of the adult population could avert more than 15% of new infections from 2023 to 2050. The impact would be lower but more efficient if delivered to populations at higher HIV risk: 127 person-years of CAB LA use would be required to avert one HIV infection within 5 years if used by all adults and 47 person-years if used only by the highest risk women.

Conclusions
If efficacious, a CAB LA intervention could have a substantial impact on the course of the HIV epidemic in South Africa. Uptake by those at the highest risk of infection, particularly young women, could improve the efficiency of any intervention.
Perspective from the African Court on Human and Peoples’ Rights
Authors: Kioko Ben 
Published: May 2020

Abstract
This practice note seeks to highlight the experience of the African Court on Human and Peoples’ Rights in monitoring and ensuring the implementation of its decisions. It outlines the implementation mechanisms in place, some specific areas and judgments and their status of implementation. An attempt is also made to outline the tools that have worked, challenges, and key lessons to be learned.
Leaking of secret military reports qualifies as reporting of current events
Authors: Jütte Bernd Justin , Priora Giulia 
Published: May 2020

Abstract
German Federal Supreme Court, Judgment of 30 April 2020, I ZR 139/15—‘Afghanistan Papiere II’
The German Federal Supreme Court (BGH) followed the Court of Justice of the European Union (CJEU) in its interpretation of the exception for the reporting of current events.
Epistemic responsibility in the face of a pandemic
Authors: Levy Neil , Savulescu Julian 
Published: May 2020

Abstract
Should non-experts defer to epidemiologists with regard to the response to the coronavirus pandemic? We argue that deference is required with regard to settled science: non-experts (that is, people who may possess expertise of their own but whose expertise is not relevant to a particular question) ought to defer with regard to climate science and the efficacy of vaccines. However, we suggest that this deference is warranted because these questions have been appropriately probed many times by many different kinds of people. While non-experts should defer to epidemiologists with regard to matters within the sphere of epidemiology specifically, responding to the pandemic requires expertise from many fields. We best build a consensus worth deferring to by contributing our expertise now. Ethicists and philosophers are not epistemically arrogant if they question policy responses. Rather, they play a responsible role in building a reliable consensus.
COVID-19 contact tracing apps: a stress test for privacy, the GDPR, and data protection regimes
Authors: Bradford Laura , Aboy Mateo , Liddell Kathleen 
Published: May 2020

Abstract
Digital surveillance has played a key role in containing the COVID-19 outbreak in China, Singapore, Israel, and South Korea. Google and Apple recently announced the intention to build interfaces to allow Bluetooth contact tracking using Android and iPhone devices. In this article, we look at the compatibility of the proposed Apple/Google Bluetooth exposure notification system with Western privacy and data protection regimes and principles, including the General Data Protection Regulation (GDPR). Somewhat counter-intuitively, the GDPR’s expansive scope is not a hindrance, but rather an advantage in conditions of uncertainty such as a pandemic. Its principle-based approach offers a functional blueprint for system design that is compatible with fundamental rights. By contrast, narrower, sector-specific rules such as the US Health Insurance Portability and Accountability Act (HIPAA), and even the new California Consumer Privacy Act (CCPA), leave gaps that may prove difficult to bridge in the middle of an emergency.
Ambiguities in using telomere length for age determination in two North American bat species
Authors: Ineson Katherine M , O’Shea Thomas J , Kilpatrick C William , Parise Katy L , Foster Jeffrey T 
Published: May 2020

AbstractThe age of an animal, determined by time (chronological age) as well as genetic and environmental factors (biological age), influences the likelihood of mortality and reproduction and thus the animal’s contribution to population growth. For many long-lived species, such as bats, a lack of external and morphological indicators has made determining age a challenge, leading researchers to examine genetic markers of age for application to demographic studies. One widely studied biomarker of age is telomere length, which has been related both to chronological and biological age across taxa, but only recently has begun to be studied in bats. We assessed telomere length from the DNA of known-age and minimum known-age individuals of two bat species using a quantitative PCR assay. We determined that telomere length was quadratically related to chronological age in big brown bats (Eptesicus fuscus), although it had little predictive power for accurate age determination of unknown-age individuals. The relationship was different in little brown bats (Myotis lucifugus), where telomere length instead was correlated with biological age, apparently due to infection and wing damage associated with white-nose syndrome. Furthermore, we showed that wing biopsies currently are a better tissue source for studying telomere length in bats than guano and buccal swabs; the results from the latter group were more variable and potentially influenced by storage time. Refinement of collection and assessment methods for different non-lethally collected tissues will be important for longitudinal sampling to better understand telomere dynamics in these long-lived species. Although further work is needed to develop a biomarker capable of determining chronological age in bats, our results suggest that biological age, as reflected in telomere length, may be influenced by extrinsic stressors such as disease.
Make it bloom! CONSTANS contributes to day neutrality in rose
Authors: Denoyes Béatrice , Gaston Amèlia , Rothan Christophe 
Published: May 2020

This article comments on:
Lu J, Sun J, Jiang A, Bai M, Fan C, Liu J, Ning G, Wang C. 2020. Alternate expression of CONSTANS-LIKE 4 in short days and CONSTANS in long days facilitates day-neutral response in Rosa chinensis. Journal of Experimental Botany 71, 4057–4068
Eclipsing binaries in the OGLE variable star catalogue: long-period evolved systems
Authors: Hoyman Barış , Bulut Sara , Özdarcan Orkun , Çakırlı Ömür 
Published: May 2020

ABSTRACT
Red giant stars are proving to be an exceptional source of information for testing models of stellar evolution, as photometric and spectroscopic analysis has opened up a window into their interiors, providing an exciting chance to develop highly constrained stellar models. In this study, we present a determination of precise fundamental physical parameters belonging to five detached, double-lined, eclipsing binary stars in the Large and Small Magellanic Clouds containing G- or early K-type giant stars with extended envelopes. We also derived the distances to the systems by using a temperature–colour relation and compared these distances with the measurements provided in the literature. The measured stellar masses are in the range 1.8–3.0 M⊙ and comparison with the PAdova and TRieste Stellar Evolution Code (PARSEC) isochrones gives ages between 0.4 and 1.1 Gyr. The derived uncertainties for individual masses and radii of components are better than 3 and 7 per cent, respectively, for these systems. Additionally, we performed atmospheric parameter determination and [M/H] analysis for each, where we disentangled the spectra.
Pig-a gene mutation assay study design: critical assessment of 3- versus 28-day repeat-dose treatment schedules
Authors: Elhajouji Azeddine , Hove Tamsanqa Tafara , O’Connell Oliver , Martus Hansjoerg , Dertinger Stephen D 
Published: May 2020

Abstract
The in vivo Pig-a assay is being used in safety studies to evaluate the potential of chemicals to induce somatic cell gene mutations. Ongoing work is aimed at developing an Organisation for Economic Cooperation and Development (OECD) test guideline to support routine use for regulatory purposes (OECD project number 4.93). Among the details that will need to be articulated in an eventual guideline are recommended treatment and harvest schedules. With this in mind, experiments reported herein were performed with Wistar Han rats exposed to aristolochic acid I (AA), 1,3-propane sultone, chlorambucil, thiotepa or melphalan using each of two commonly used treatment schedules: 3 or 28 consecutive days. In the case of the 3-day studies, blood was collected for Pig-a analysis on days 15 or 16 and 29 or 30. For the 28-day studies blood was collected on day 29 or 30. The effect of treatment on mutant reticulocytes and mutant erythrocytes was evaluated with parametric pair-wise tests. While each of the five mutagens increased mutant phenotype cell frequencies irrespective of study design, statistical significance was consistently achieved at lower dose levels when the 28-day format was used (e.g. 2.75 vs 20 mg/kg/bw for AA). To more thoroughly investigate the dose–response relationships, benchmark dose (BMD) analyses were performed with PROAST software. These results corroborate the pair-wise testing results in that lower BMD values were obtained with the 28-day design. Finally, mutagenic potency, as measured by BMD analyses, most consistently correlated with the mutagens’ tumorigenic dose 50 values when the lengthier treatment schedule was used. Collectively, these results suggest that both 3- and 28-day treatment schedules have merit in hazard identification-type studies. That being said, for the purpose of regulatory safety assessments, there are clear advantages to study designs that utilise protracted exposures.
Cdk9 and H2Bub1 signal to Clr6-CII/Rpd3S to suppress aberrant antisense transcription
Authors: Sansó Miriam , Parua Pabitra K , Pinto Daniel , Svensson J Peter , Pagé Viviane , Bitton Danny A , MacKinnon Sarah , Garcia Patricia , Hidalgo Elena , Bähler Jürg , Tanny Jason C , Fisher Robert P 
Published: May 2020

AbstractMono-ubiquitylation of histone H2B (H2Bub1) and phosphorylation of elongation factor Spt5 by cyclin-dependent kinase 9 (Cdk9) occur during transcription by RNA polymerase II (RNAPII), and are mutually dependent in fission yeast. It remained unclear whether Cdk9 and H2Bub1 cooperate to regulate the expression of individual genes. Here, we show that Cdk9 inhibition or H2Bub1 loss induces intragenic antisense transcription of ∼10% of fission yeast genes, with each perturbation affecting largely distinct subsets; ablation of both pathways de-represses antisense transcription of over half the genome. H2Bub1 and phospho-Spt5 have similar genome-wide distributions; both modifications are enriched, and directly proportional to each other, in coding regions, and decrease abruptly around the cleavage and polyadenylation signal (CPS). Cdk9-dependence of antisense suppression at specific genes correlates with high H2Bub1 occupancy, and with promoter-proximal RNAPII pausing. Genetic interactions link Cdk9, H2Bub1 and the histone deacetylase Clr6-CII, while combined Cdk9 inhibition and H2Bub1 loss impair Clr6-CII recruitment to chromatin and lead to decreased occupancy and increased acetylation of histones within gene coding regions. These results uncover novel interactions between co-transcriptional histone modification pathways, which link regulation of RNAPII transcription elongation to suppression of aberrant initiation.
RaptRanker: in silico RNA aptamer selection from HT-SELEX experiment based on local sequence and structure information
Authors: Ishida Ryoga , Adachi Tatsuo , Yokota Aya , Yoshihara Hidehito , Aoki Kazuteru , Nakamura Yoshikazu , Hamada Michiaki 
Published: May 2020

Abstract
Aptamers are short single-stranded RNA/DNA molecules that bind to specific target molecules. Aptamers with high binding-affinity and target specificity are identified using an in vitro procedure called high throughput systematic evolution of ligands by exponential enrichment (HT-SELEX). However, the development of aptamer affinity reagents takes a considerable amount of time and is costly because HT-SELEX produces a large dataset of candidate sequences, some of which have insufficient binding-affinity. Here, we present RNA aptamer Ranker (RaptRanker), a novel in silico method for identifying high binding-affinity aptamers from HT-SELEX data by scoring and ranking. RaptRanker analyzes HT-SELEX data by evaluating the nucleotide sequence and secondary structure simultaneously, and by ranking according to scores reflecting local structure and sequence frequencies. To evaluate the performance of RaptRanker, we performed two new HT-SELEX experiments, and evaluated binding affinities of a part of sequences that include aptamers with low binding-affinity. In both datasets, the performance of RaptRanker was superior to Frequency, Enrichment and MPBind. We also confirmed that the consideration of secondary structures is effective in HT-SELEX data analysis, and that RaptRanker successfully predicted the essential subsequence motifs in each identified sequence.