bluuebunny/crossref_metadata_2025 huggingface dataset:
Drp-1-Dependent Mitochondrial Fragmentation Contributes to Cobalt Chloride-Induced Toxicity in Caenorhabditis elegans
Authors: Zheng Fuli , Chen Pan , Li Huangyuan , Aschner Michael
Published: June 2020

Excess cobalt may lead to metallosis, characterized by sensorineural hearing loss, visual, and cognitive impairment, and peripheral neuropathy. In the present study, we sought to address the molecular mechanisms of cobalt-induced neurotoxicity, using Caenorhabditis elegans as an experimental model. Exposure to cobalt chloride for 2 h significantly decreased the survival rate and lifespan in nematodes. Cobalt chloride exposure led to increased oxidative stress and upregulation of glutathione S-transferase 4. Consistently, its upstream regulator skn-1, a mammalian homolog of the nuclear factor erythroid 2-related factor 2, was activated. Among the mRNAs examined by quantitative real-time polymerase chain reactions, apoptotic activator egl-1, proapoptotic gene ced-9, autophagic (bec-1 and lgg-1), and mitochondrial fission regulator drp-1 were significantly upregulated upon cobalt exposure, concomitant with mitochondrial fragmentation, as determined by confocal microscopy. Moreover, drp-1 inhibition suppressed the cobalt chloride-induced reactive oxygen species generation, growth defects, and reduced mitochondrial fragmentation. Our novel findings suggest that the acute toxicity of cobalt is mediated by mitochondrial fragmentation and drp-1 upregulation.
V The Early Sixteenth Century
Authors: Smith Edward
Published: June 2020

This chapter has six sections: 1. General: Prose; 2. General: Verse; 3. More; 4. Skelton; 5. Surrey; 6. Wyatt.
Emergence of cascading dynamics in interacting tipping elements of ecology and climate
Authors: Klose Ann Kristin , Karle Volker , Winkelmann Ricarda , Donges Jonathan F.
Published: June 2020

In ecology, climate and other fields, (sub)systems have been identified that can transition into a qualitatively different state when a critical threshold or tipping point in a driving process is crossed. An understanding of those tipping elements is of great interest given the increasing influence of humans on the biophysical Earth system. Complex interactions exist between tipping elements, e.g. physical mechanisms connect subsystems of the climate system. Based on earlier work on such coupled nonlinear systems, we systematically assessed the qualitative long-term behaviour of interacting tipping elements. We developed an understanding of the consequences of interactions on the tipping behaviour allowing for tipping cascades to emerge under certain conditions. The (narrative) application of these qualitative results to real-world examples of interacting tipping elements indicates that tipping cascades with profound consequences may occur: the interacting Greenland ice sheet and thermohaline ocean circulation might tip before the tipping points of the isolated subsystems are crossed. The eutrophication of the first lake in a lake chain might propagate through the following lakes without a crossing of their individual critical nutrient input levels. The possibility of emerging cascading tipping dynamics calls for the development of a unified theory of interacting tipping elements and the quantitative analysis of interacting real-world tipping elements.
On explicit Wiener–Hopf factorization of 2 × 2 matrices in a vicinity of a given matrix
Authors: Ephremidze L. , Spitkovsky I.
Published: June 2020

As it is known, the existence of the Wiener–Hopf factorization for a given matrix is a well-studied problem. Severe difficulties arise, however, when one needs to compute the factors approximately and obtain the partial indices. This problem is very important in various engineering applications and, therefore, remains to be subject of intensive investigations. In the present paper, we approximate a given matrix function and then explicitly factorize the approximation regardless of whether it has stable partial indices. For this reason, a technique developed in the Janashia–Lagvilava matrix spectral factorization method is applied. Numerical simulations illustrate our ideas in simple situations that demonstrate the potential of the method.
Placing limits on long-term variations in quiet-Sun irradiance and their contribution to total solar irradiance and solar radiative forcing of climate
Authors: Lockwood Mike , Ball William T.
Published: June 2020

Recent reconstructions of total solar irradiance (TSI) postulate that quiet-Sun variations could give significant changes to the solar power input to Earth's climate (radiative climate forcings of 0.7–1.1 W m
−2
over 1700–2019) arising from changes in quiet-Sun magnetic fields that have not, as yet, been observed. Reconstructions without such changes yield solar forcings that are smaller by a factor of more than 10. We study the quiet-Sun TSI since 1995 for three reasons: (i) this interval shows rapid decay in average solar activity following the grand solar maximum in 1985 (such that activity in 2019 was broadly equivalent to that in 1900); (ii) there is improved consensus between TSI observations; and (iii) it contains the first modelling of TSI that is independent of the observations. Our analysis shows that the most likely upward drift in quiet-Sun radiative forcing since 1700 is between +0.07 and −0.13 W m
−2
. Hence, we cannot yet discriminate between the quiet-Sun TSI being enhanced or reduced during the Maunder and Dalton sunspot minima, although there is a growing consensus from the combinations of models and observations that it was slightly enhanced. We present reconstructions that add quiet-Sun TSI and its uncertainty to models that reconstruct the effects of sunspots and faculae.
Design and spectral analysis of mixed-carrier communication for sixth-generation networks
Authors: Hussein Ahmed F. , Elgala Hany
Published: June 2020

The fifth-generation (5G) wireless cellular network is expected to be ready for commercialization within this year. The huge spectrum enabled by the millimetre-wave (mm-Wave) technology is expected to introduce a hype in data usage per user. The 5G is also expected to concurrently support a wide variety of services; however, the practical trade-offs associated with concurrent services require further investigations. In this work, a physical layer (PHY) design to support visible light communications is considered to efficiently support concurrent services that are essential to serve the needs of the sixth-generation (6G) network. A novel communication technique, i.e. mixed-carrier communication (MCC), is proposed. MCC enables simultaneous wireless services such as broadband access, low-rate internet-of-things connectivity, device-free sensing, and device-based localization. This study presents, firstly, a thorough investigation of the design procedure of the novel MCC PHY, secondly, the spectral profile of MCC towards proper spectrum management and interference analysis, and thirdly, performance evaluation based on modelling, simulation and an experimental proof-of-concept. The design steps recommend that the system performance degrades beyond a signal-to-noise ratio (SNR) threshold. For instance, SNR of 25.1 dB and 2.6652 optical power ratio between the communications signal and the driving envelope, for 64-quadrature amplitude modulation (64-QAM), are recommended to avoid performance degradation due to clipping. Simulation results show an interference-immune performance of a properly managed spectrum. For a bit-error-rate (BER) of 10−3, an SNR penalty of 2–5 dB is observed for different interference scenarios. The experimental measurements illustrate a high-quality signal of 21 dB SNR at 50 cm and 10−3BER using 64-QAM.
A generalized fractional-order elastodynamic theory for non-local attenuating media
Authors: Patnaik Sansit , Semperlotti Fabio
Published: June 2020

This study presents a generalized elastodynamic theory, based on fractional-order operators, capable of modelling the propagation of elastic waves in non-local attenuating solids and across complex non-local interfaces. Classical elastodynamics cannot capture hybrid field transport processes that are characterized by simultaneous propagation and diffusion. The proposed continuum mechanics formulation, which combines fractional operators in both time and space, offers unparalleled capabilities to predict the most diverse combinations of multiscale, non-local, dissipative and attenuating elastic energy transport mechanisms. Despite the many features of this theory and the broad range of applications, this work focuses on the behaviour and modelling capabilities of the space-fractional term and on its effect on the elastodynamics of solids. We also derive a generalized fractional-order version of Snell’s Law of refraction and of the corresponding Fresnel’s coefficients. This formulation allows predicting the behaviour of fully coupled elastic waves interacting with non-local interfaces. The theoretical results are validated via direct numerical simulations.
Coral tentacle elasticity promotes anout-of-phasemotion that improves mass transfer
Authors: Malul Dror , Holzman Roi , Shavit Uri
Published: June 2020

Corals rely almost exclusively on the ambient flow of water to support their respiration, photosynthesis, prey capture, heat exchange and reproduction. Coral tentacles extend to the flow, interact with it and oscillate under the influence of waves. Such oscillating motions of flexible appendages are considered adaptive for reducing the drag force on flexible animals in wave-swept environments, but their significance under slower flows is unclear. Usingin situand laboratory measurements of the motion of coral tentacles under wave-induced flow, we investigated the dynamics of the tentacle motion and its impact on mass transfer. We found that tentacle velocity preceded the water velocity by approximately one-quarter of a period. This out-of-phase behaviour enhanced mass transfer at the tentacle tip by up to 25% as compared with an in-phase motion. The enhancement was most pronounced under flows slower than 3.2 cm s−1, which are prevalent in many coral-reef environments. We found that the out-of-phase motion results from the tentacles' elasticity, which can presumably be modified by the animal. Our results suggest that the mechanical properties of coral tentacles may represent an adaptive advantage that improves mass transfer under the limiting conditions of slow ambient flows. Because the mechanism we describe operates by enhancing convective processes, it is expected to enhance other fitness-determining transport phenomena such as heat exchange and particle capture.
Gene expression correlates of social evolution in coral reef butterflyfishes
Authors: Nowicki Jessica P. , Pratchett Morgan S. , Walker Stefan P. W. , Coker Darren J. , O'Connell Lauren A.
Published: June 2020

Animals display remarkable variation in social behaviour. However, outside of rodents, little is known about the neural mechanisms of social variation, and whether they are shared across species and sexes, limiting our understanding of how sociality evolves. Using coral reef butterflyfishes, we examined gene expression correlates of social variation (i.e. pair bonding versus solitary living) within and between species and sexes. In several brain regions, we quantified gene expression of receptors important for social variation in mammals: oxytocin (
OTR
), arginine vasopressin (
V1aR
), dopamine (
D1R, D2R
) and mu-opioid (
MOR
). We found that social variation across individuals of the oval butterflyfish,
Chaetodon lunulatus,
is linked to differences in
OTR
,
V1aR, D1R, D2R
and
MOR
gene expression within several forebrain regions in a sexually dimorphic manner. However, this contrasted with social variation among six species representing a single evolutionary transition from pair-bonded to solitary living. Here,
OTR
expression within the supracommissural part of the ventral telencephalon was higher in pair-bonded than solitary species, specifically in males. These results contribute to the emerging idea that nonapeptide, dopamine and opioid signalling is a central theme to the evolution of sociality across individuals, although the precise mechanism may be flexible across sexes and species.
Climate change and landscape-use patterns influence recent past distribution of giant pandas
Authors: Tang Junfeng , Swaisgood Ronald R. , Owen Megan A. , Zhao Xuzhe , Wei Wei , Pilfold Nicholas W. , Wei Fuwen , Yang Xuyu , Gu Xiaodong , Yang Zhisong , Dai Qiang , Hong Mingsheng , Zhou Hong , Zhang Jindong , Yuan Shibin , Han Han , Zhang Zejun
Published: June 2020

Climate change is one of the most pervasive threats to biodiversity globally, yet the influence of climate relative to other drivers of species depletion and range contraction remain difficult to disentangle. Here, we examine climatic and non-climatic correlates of giant panda (Ailuropoda melanoleuca) distribution using a large-scale 30 year dataset to evaluate whether a changing climate has already influenced panda distribution. We document several climatic patterns, including increasing temperatures, and alterations to seasonal temperature and precipitation. We found that while climatic factors were the most influential predictors of panda distribution, their importance diminished over time, while landscape variables have become relatively more influential. We conclude that the panda's distribution has been influenced by changing climate, but conservation intervention to manage habitat is working to increasingly offset these negative consequences.
Information transfer efficiency differs in wild chimpanzees and bonobos, but not social cognition
Authors: Girard-Buttoz Cédric , Surbeck Martin , Samuni Liran , Tkaczynski Patrick , Boesch Christophe , Fruth Barbara , Wittig Roman M. , Hohmann Gottfried , Crockford Catherine
Published: June 2020

Several theories have been generated to understand the socio-cognitive mechanisms underlying the unique cooperative abilities of humans. The ‘interdependence hypothesis' posits first, that the cognitive dimension of human cooperation evolved in contexts when several individuals needed to act together to achieve a common goal, like when hunting large prey. Second, the more interdependent individuals are, the more likely they are to provide services to conspecifics in other contexts. Alternatively, the ‘social tolerance hypothesis' proposes that higher social tolerance allows conspecifics to cooperate more efficiently and with a wider range of partners. We conducted the first field experimental evaluation of both hypotheses in our closest living relatives by contrasting chimpanzees to the less interdependent but more tolerant bonobos. We compared each species' performance during a cooperative task: informing conspecifics about a danger. We presented Gaboon viper models to 82 individuals from five wild communities. Chimpanzees arriving late at the snake were significantly more likely to have heard a call and less likely to startle, indicating that chimpanzees were better informed about the presence of the threat than bonobos. This stems from clear species differences in how individuals adjusted their calling decisions to the level of information already available. Chimpanzees were more likely to call and produced more alarm calls when they had not yet heard a call, whereas bonobos did so when they already heard a call. Our results confirm the link between interdependence and cooperation performance. These species differences were most likely driven by differences in motivation rather than in cognitive capacities because both species tended to consider audience knowledge in their decision to call. Our results inform theories on the evolution of human cooperation by linking inter-group competition pressure and in-group cooperative motivation and/or capability.
Cranial endocast of the stem lagomorphMegalagusand brain structure of basal Euarchontoglires
Authors: López-Torres Sergi , Bertrand Ornella C. , Lang Madlen M. , Silcox Mary T. , Fostowicz-Frelik Łucja
Published: June 2020

Early lagomorphs are central to our understanding of how the brain evolved in Glires (rodents, lagomorphs and their kin) from basal members of Euarchontoglires (Glires + Euarchonta, the latter grouping primates, treeshrews, and colugos). Here, we report the first virtual endocast of the fossil lagomorphMegalagus turgidus, from the Orella Member of the Brule Formation, early Oligocene, Nebraska, USA. The specimen represents one of the oldest nearly complete lagomorph skulls known. Primitive aspects of the endocranial morphology inMegalagusinclude large olfactory bulbs, exposure of the midbrain, a small neocortex and a relatively low encephalization quotient. Overall, this suggests a brain morphology closer to that of other basal members of Euarchontoglires (e.g. plesiadapiforms and ischyromyid rodents) than to that of living lagomorphs. However, the well-developed petrosal lobules inMegalagus, comparable to the condition in modern lagomorphs, suggest early specialization in that order for the stabilization of eye movements necessary for accurate visual tracking. Our study sheds new light on the reconstructed morphology of the ancestral brain in Euarchontoglires and fills a critical gap in the understanding of palaeoneuroanatomy of this major group of placental mammals.
Homogenization of carnivorous mammal ensembles caused by global range reductions of large-bodied hypercarnivores during the late Quaternary
Authors: Middleton Owen S. , Scharlemann Jörn P. W. , Sandom Christopher J.
Published: June 2020

Carnivorous mammals play crucial roles in ecosystems by influencing prey densities and behaviour, and recycling carrion. Yet, the influence of carnivores on global ecosystems has been affected by extinctions and range contractions throughout the Late Pleistocene and Holocene (approx. 130 000 years ago to the current). Large-bodied mammals were particularly affected, but how dietary strategies influenced species' susceptibility to geographical range reductions remains unknown. We investigated (i) the importance of dietary strategies in explaining range reductions of carnivorous mammals (greater than or equal to 5% vertebrate meat consumption) and (ii) differences in functional diversity of continental carnivore ensembles by comparing current, known ranges to current, expected ranges under a present-natural counterfactual scenario. The present-natural counterfactual estimates current mammal ranges had modern humans not expanded out of Africa during the Late Pleistocene and were not a main driver of extinctions and range contractions, alongside changing climates. Ranges of large-bodied hypercarnivorous mammals are currently smaller than expected, compared to smaller-bodied carnivorous mammals that consume less vertebrate meat. This resulted in consistent differences in continental functional diversity, whereby current ensembles of carnivorous mammals have undergone homogenization through structural shifts towards smaller-bodied insectivorous and herbivorous species. The magnitude of ensemble structural shifts varied among continents, with Australia experiencing the greatest difference. Weighting functional diversity by species’ geographical range sizes caused a threefold greater shift in ensemble centroids than when using presence–absence alone. Conservation efforts should acknowledge current reductions in the potential geographical ranges of large-bodied hypercarnivores and aim to restore functional roles in carnivore ensembles, where possible, across continents.
A scientist like me: demographic analysis of biology textbooks reveals both progress and long-term lags
Authors: Wood Sara , Henning Jeremiah A. , Chen Luoying , McKibben Taylor , Smith Michael L. , Weber Marjorie , Zemenick Ash , Ballen Cissy J.
Published: June 2020

Textbooks shape teaching and learning in introductory biology and highlight scientists as potential role models who are responsible for significant discoveries. We explore a potential demographic mismatch between the scientists featured in textbooks and the students who use textbooks to learn core concepts in biology. We conducted a demographic analysis by extracting hundreds of human names from common biology textbooks and assessing the binary gender and race of featured scientists. We found that the most common scientists featured in textbooks are white men. However, women and scientists of colour are increasingly represented in contemporary scientific discoveries. In fact, the proportion of women highlighted in textbooks has increased in lockstep with the proportion of women in the field, indicating that textbooks are matching a changing demographic landscape. Despite these gains, the scientists portrayed in textbooks are not representative of their target audience—the student population. Overall, very few scientists of colour were highlighted, and projections suggest it could take multiple centuries at current rates before we reach inclusive representation. We call upon textbook publishers to expand upon the scientists they highlight to reflect the diverse population of learners in biology.
Comparative micromechanics of bushcricket ears with and without a specialized auditory fovea region in the crista acustica
Authors: Scherberich Jan , Taszus Roxana , Stoessel Alexander , Nowotny Manuela
Published: June 2020

In some insects and vertebrate species, the specific enlargement of sensory cell epithelium facilitates the perception of particular behaviourally relevant signals. The insect auditory fovea in the ear of the bushcricketAncylecha fenestrata(Tettigoniidae: Phaneropterinae) is an example of such an expansion of sensory epithelium. Bushcricket ears developed in convergent evolution anatomical and functional similarities to mammal ears, such as travelling waves and auditory foveae, to process information by sound. As in vertebrate ears, sound induces a motion of this insect hearing organ (crista acustica), which can be characterized by its amplitude and phase response. However, detailed micromechanics in this bushcricket ear with an auditory fovea are yet unknown. Here, we fill this gap in knowledge for bushcricket, by analysing and comparing the ear micromechanics inAncylecha fenestrataand a bushcricket species without auditory fovea (Mecopoda elongata, Tettigoniidae: Mecopodinae) using laser-Doppler vibrometry. We found that the increased size of the crista acustica, expanded by a foveal region inA. fenestrata, leads to higher mechanical amplitudes and longer phase delays inA. fenestratamale ears. Furthermore, area under curve analyses of the organ oscillations reveal that more sensory units are activated by the same stimuli in the males of the auditory fovea-possessing speciesA. fenestrata. The measured increase of phase delay in the region of the auditory fovea supports the conclusion that tilting of the transduction site is important for the effective opening of the involved transduction channels. Our detailed analysis of sound-induced micromechanics in this bushcricket ear demonstrates that an increase of sensory epithelium with foveal characteristics can enhance signal detection and may also improve the neuronal encoding.
Earlier springs enable high-Arctic wolf spiders to produce a second clutch
Authors: Høye Toke T. , Kresse Jean-Claude , Koltz Amanda M. , Bowden Joseph J.
Published: June 2020

Spiders at southern latitudes commonly produce multiple clutches, but this has not been observed at high latitudes where activity seasons are much shorter. Yet the timing of snowmelt is advancing in the Arctic, which may allow some species to produce an additional clutch. To determine if this is already happening, we used specimens of the wolf spiderPardosa glacialiscaught by pitfall traps from the long-term (1996–2014) monitoring programme at Zackenberg, NE Greenland. We dissected individual egg sacs and counted the number of eggs and partially developed juveniles, and measured carapace width of the mothers. Upon the discovery of a bimodal frequency distribution of clutch sizes, as is typical for wolf spiders at lower latitudes producing a second clutch, we assigned egg sacs to being a first or second clutch depending on clutch size. We tested whether the median capture date differed among first and second clutches, whether clutch size was correlated to female size, and whether the proportion of second clutches produced within a season was related to climate. We found that assigned second clutches appeared significantly later in the season than first clutches. In years with earlier snowmelt, first clutches occurred earlier and the proportion of second clutches produced was larger. Likely, females produce their first clutch earlier in those years which allow them time to produce another clutch. Clutch size for first clutches was correlated to female size, while this was not the case for second clutches. Our results provide the first evidence for Arctic invertebrates producing additional clutches in response to warming. This could be a common but overlooked phenomenon due to the challenges associated with long-term collection of life-history data in the Arctic. Moreover, given that wolf spiders are a widely distributed, important tundra predator, we may expect to see population and food web consequences of their increased reproductive rates.
No link between nymph and adult coloration in shield bugs: weak selection by predators
Authors: Medina Iliana , Vega-Trejo Regina , Wallenius Thomas , Esquerré Damien , León Constanza , Perez Daniela M. , Head Megan L.
Published: June 2020

Many organisms use different antipredator strategies throughout their life, but little is known about the reasons or implications of such changes. For years, it has been suggested that selection by predators should favour uniformity in local warning signals. If this is the case, we would expect high resemblance in colour across life stages in aposematic animals where young and adults share similar morphology and habitat. In this study, we used shield bugs (Hemiptera: Pentatomoidea) to test whether colour and colour diversity evolve similarly at different life stages. Since many of these bugs are considered to be aposematic, we also combined multi-species analyses with predation experiments on the cotton harlequin bug to test whether there is evidence of selection for uniformity in colour across life stages. Overall, we show that the diversity of colours used by both life stages is comparable, but adults are more cryptic than nymphs. We also demonstrate that nymphs and adults of the same species do not tend to look alike. Experiments on our model system suggest that predators can generalise among life stages that look different, and exhibit strong neophobia. Altogether, our results show no evidence of selection favouring colour similarity between adults and nymphs in this speciose clade.
Pseudooceanicola pacificus sp. nov., isolated from deep-sea sediment of the Pacific Ocean
Authors: Lyu Lina , Lai Qiliang , Li Jianyang , Shao Zongze , Yu Zhiqiang
Published: June 2020

A Gram-strain-negative, rod-shaped, aerobic bacterium, designated 216_PA32_1T, was isolated from deep-sea sediment of the Pacific Ocean. Cells of strain 216_PA32_1T were non-motile, oxidase-positive and catalase-negative. The strain could grow at temperatures of 10–45 °C (optimum, 32–35 °C), at pH 5.0–10.0 (optimum, 6.0–7.0) and at salinities of 0–10% (optimum, 2–8%). The principal fatty acid (>10 %) was summed feature 8 (C18:1
ω6c/ω7c). The sole respiratory quinone was Q10 (100 %). The polar lipids included phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, phosphatidylmonomethylethanolamine, two unidentified phospholipids and five unidentified aminolipids. The G+C content of the chromosomal DNA was 66.3 mol%. According to the 16S rRNA gene similarity, strain 216_PA32_1T showed the highest sequence similarity to

Pseudooceanicola nitratireducens

JLT 1210T (97.3 %), followed by

Pseudooceanicola nanhaiensis

SS011B1-20T (97.1 %). Phylogenetic trees indicated that strain 216_PA32_1T clustered with strain

P. nanhaiensis

SS011B1-20T. The average nucleotide identity and the DNA–DNA hybridization values between strain 216_PA32_1T and all species of the genus

Pseudooceanicola

were below 79.5 and 20.6%, respectively. A combination of the phylogenetic, phenotypic, chemotaxonomic and genomic evidence demonstrated that strain 216_PA32_1T represents a novel species of the genus

Pseudooceanicola

, for which the name Pseudooceanicola pacificus sp. nov. is proposed. The type strain is 216_PA32_1T (=MCCC 1A14128T=KCTC 72688T).
Practical considerations for measuring the effective reproductive number,Rt
Authors: Gostic Katelyn M. , McGough Lauren , Baskerville Edward B. , Abbott Sam , Joshi Keya , Tedijanto Christine , Kahn Rebecca , Niehus Rene , Hay James , De Salazar Pablo M. , Hellewell Joel , Meakin Sophie , Munday James , Bosse Nikos I. , Sherrat Katharine , Thompson Robin N. , White Laura F. , Huisman Jana S. , Scire Jérémie , Bonhoeffer Sebastian , Stadler Tanja , Wallinga Jacco , Funk Sebastian , Lipsitch Marc , Cobey Sarah
Published: June 2020

Estimation of the effective reproductive number,Rt, is important for detecting changes in disease transmission over time. During the COVID-19 pandemic, policymakers and public health officials are usingRtto assess the effectiveness of interventions and to inform policy. However, estimation ofRtfrom available data presents several challenges, with critical implications for the interpretation of the course of the pandemic. The purpose of this document is to summarize these challenges, illustrate them with examples from synthetic data, and, where possible, make recommendations. For near real-time estimation ofRt, we recommend the approach of Cori et al. (2013), which uses data from before time t and empirical estimates of the distribution of time between infections. Methods that require data from after timet, such as Wallinga and Teunis (2004), are conceptually and methodologically less suited for near real-time estimation, but may be appropriate for retrospective analyses of how individuals infected at different time points contributed to spread. We advise against using methods derived from Bettencourt and Ribeiro (2008), as the resultingRtestimates may be biased if the underlying structural assumptions are not met. Two key challenges common to all approaches are accurate specification of the generation interval and reconstruction of the time series of new infections from observations occurring long after the moment of transmission. Naive approaches for dealing with observation delays, such as subtracting delays sampled from a distribution, can introduce bias. We provide suggestions for how to mitigate this and other technical challenges and highlight open problems inRtestimation.

Author summary

The effective reproductive number,Rt, is a key epidemic parameter used to assess whether an epidemic is growing, shrinking or holding steady.Rtestimates can be used as a near real-time indicator of epidemic growth or to assess the effectiveness of interventions. But due to delays between infection and case observation, estimatingRtin near real-time, and correctly inferring the timing of changes inRtis challenging. Here, we provide an overview of challenges and best practices for accurate, timelyRtestimation.
EXERCISE-INDUCED BENEFITS ON GLUCOSE HANDLING IN A MODEL OF DIET-INDUCED OBESITY ARE REDUCED BY CONCURRENT NICOTINAMIDE MONONUCLEOTIDE
Authors: Yu Josephine , Laybutt D. Ross , Kim Lynn-Jee , Quek Lake-Ee , Wu Lindsay E. , Morris Margaret J. , Youngson Neil A.
Published: June 2020

Objective

Almost 40% of adults worldwide are classified as overweight or obese. Exercise is a beneficial intervention in obesity, partly due to increases in mitochondrial activity, with a potential role for the concomitant increase in nicotinamide adenine dinucleotide (NAD+). Recent studies have shown that increasing NAD+levels through pharmacological supplementation with precursors such as nicotinamide mononucleotide (NMN) improved metabolic health in high fat diet (HFD) fed mice. We examined the combined effects of NMN and treadmill exercise on the metabolic dysregulation in HFD-induced obesity.

Methods

Five-week old female C57BL/6J mice were exposed to control diet or HFD. Mice fed HFD were treated with NMN in drinking water (400mg/kg; HNMN), treadmill exercise (HEx) or combined NMN and exercise (HNEx).

Results

Unexpectedly, NMN administration impaired several aspects of exercise-induced benefits in HFD mice, including glucose tolerance, glucose stimulated insulin secretion from islets and reduced hepatic triglyceride accumulation. Mechanistically, HNEx mice displayed increased antioxidant and reduced prooxidant gene expression in both islets and muscle, suggesting that altered redox status is associated with the loss of exercise-induced health benefits with NMN co-treatment.

Conclusion

Our data show that NMN treatment blocks the beneficial metabolic effects of exercise in a mouse model of diet-induced obesity in association with disturbances in redox metabolism.

Highlights

NMN dampened exercise-induced benefits on glucose handling in diet-induced obesity.

NMN administration in exercise enhanced ratio of antioxidants to prooxidants.

We suggest NMN administration may not be beneficial when NAD+levels are replete.
PCAT: An integrated portal for genomic and preclinical testing data of pediatric cancer patient-derived xenograft models
Authors: Yang Juechen , Li Qilin , Noureen Nighat , Fang Yanbing , Kurmasheva Raushan , Houghton Peter , Wang Xiaojing , Zheng Siyuan
Published: June 2020

Although cancer is the leading cause of disease-related mortality in children, the relative rarity of pediatric cancers poses a significant challenge for developing novel therapeutics to further improve prognosis. Patient-derived xenograft (PDX) models, which are usually developed from high-risk tumors, are a useful platform to study molecular driver events, identify biomarkers, and prioritize therapeutic agents. Here we developPDX forChildhoodCancerTherapeutics (PCAT), a new integrated portal for pediatric cancer PDX models. Distinct from previously reported PDX portals, PCAT is focused on pediatric cancer models and provides intuitive interfaces for querying and data mining. The current release comprises 324 models and their associated clinical and genomic data, including gene expression, mutation, and copy number alteration. Importantly, PCAT curates preclinical testing results for 68 models and 79 therapeutic agents manually collected from individual agent testing studies published since 2008. To facilitate comparisons of patterns between patient tumors and PDX models, PCAT curates clinical and molecular data of patient tumors from the TARGET project. In addition, PCAT provides access to gene fusions identified in nearly 1,000 TARGET samples. PCAT was built using R-shiny and MySQL. The portal can be accessed athttp://pcat.zhenglab.infoorhttp://www.pedtranscriptome.org.
Detailed phylogenetic analysis of SARS-CoV-2 reveals latent capacity to bind human ACE2 receptor
Authors: Brintnell Erin , Gupta Mehul , Anderson Dave W
Published: June 2020

SARS-CoV-2 is a unique event, having emerged suddenly as a highly infectious viral pathogen for human populations. Previous phylogenetic analyses show its closest known evolutionary relative to be a virus detected in bats (RaTG13), with a common assumption that SARS-CoV-2 evolved from a zoonotic ancestor via recent genetic changes (likely in the Spike protein receptor binding domain – or RBD) that enabled it to infect humans. We used detailed phylogenetic analysis, ancestral sequence reconstruction, and in situ molecular dynamics simulations to examine the Spike-RBD’s functional evolution, finding that the common ancestral virus with RaTG13, dating to at least 2013, possessed high binding affinity to the human ACE2 receptor. This suggests that SARS-CoV-2 likely possessed a latent capacity to bind to human cellular targets (though this may not have been sufficient for successful infection) and emphasizes the importance to expand the cataloging and monitoring of viruses circulating in both human and non-human populations.
Evolution of nuptial gifts and its coevolutionary dynamics with “masculine” female traits for multiple mating
Authors: Kamimura Yoshitaka , Yoshizawa Kazunori , Lienhard Charles , Ferreira Rodrigo L. , Abe Jun
Published: June 2020

Many male animals donate nutritive materials during courtship or mating to their female mates. Donation of large-sized gifts, though costly to prepare, can result in increased sperm transfer during mating and delayed remating of the females, resulting in a higher paternity Nuptial gifting sometimes causes severe female-female competition for obtaining gifts (i.e., sex-role reversal in mate competition) and female polyandry, changing the intensity of sperm competition and the resultant paternity gains. We built a theoretical model to analyze such coevolutionary feedbacks between nuptial gift size (male trait) and propensity for multiple mating (female trait). Our genetically explicit, individual-based computer simulations demonstrate that a positive correlation between donated gift size and the resultant paternity gain is a requisite for the co-occurrence of large-sized gifts and females’ competitive multiple mating for the gifts. When donation of gifts imposes monandry, exaggeration in nuptial gift size also occurs under the assumption that the last male monopolizes paternity. We also analyzed the causes and consequences of the evolution of a female persistence trait in trading of nuptial gifts, that is, double receptacles for nuptial gifts known to occur in an insect group with a “female penis” (Neotroglaspp.).
Rapid and Efficient BAC Recombineering: Gain & Loss Screening System
Authors: Kuk Myeong Uk , Oh Sekyung , Park Joon Tae
Published: June 2020

Recombineering has been developed to modify bacterial artificial chromosome (BAC) via homologous recombination. Nevertheless, as a screening strategy to identify the correct clone was not properly developed, it was difficult to obtain a correct clone within a limited time period. To address these issues, we developed a new screening method (a gain & loss screening system) that enables the efficient identification of the recombineered clone. Simple inoculation of cells into LB medium with appropriate antibiotics visually revealed the positive clones within 24 h. DNA sequencing confirmed 100% accuracy of this screening method by showing that all positive clones exhibited recombinant sequences. Furthermore, our new method allowed us to complete the entire procedure consisting of 1strecombineering, flip-out and 2ndrecombineering in just 13 days. Overall, our new strategy may provide a new avenue for BAC recombeerining, as evidenced by markedly increased accuracy and subsequently shortened recombineering duration.
Logistic Approach to COVID - 19 Epidemic Evolution in Brazil
Authors: de Assis Altair Souza , de Carvalho Vinicius Werneck
Published: June 2020

We study in this work the temporal evolution of local and global contaminated population by coronavirus. We access those information analytically and numerically using a logistic model. It is shown, using diferent data from The Brazilian Ministry of Health (MS), The World Health Organization - WHO, and The Niteroi Health Foundation (FMS), the contaminated population ramping-up curves, the population inflection, the population saturation - plateau regime, and also the time related to these population evolution regimes. Based on the simulations, approaches are proposed at this more advanced phase of the pandemic, which might generate effectiveness at the actions of society in general, in a way that those actions could generate effective and efficient results, and this means a more organized war against this pandemic, a better way to induce the economy resumption, and also to create a more intense public awareness on the contamination hubs and surges that may emerge due to the reduction of social isolation.
Comorbidities might be a risk factor for the incidence of COVID-19: Evidence from a web-based survey of 780,961 participants
Authors: Alam Mohammad Rahanur , Kabir Md. Ruhul , Reza Sompa
Published: June 2020

Background

The global pandemic of COVID-19 is posing the biggest threat to humanity through its ubiquitous effect of unfathomable magnitude. It has been responsible for over four hundred thousand death worldwide to date. There has been evidence that various comorbidities have a higher risk associated with case fatality. Although COVID-19 is a viral disease, there might be an association between different comorbidities and the occurrence of the disease.

Method

Sociodemographic and medical history data on different comorbidities such as asthma, diabetes, liver disease, lung disease, heart disease, kidney disease, hypertension, and obesity were collected by a web-based self-reported survey between 25th March 2020 to 4th June 2020 by the Nexoid United Kingdom. Univariate and multivariate logistic regression analyses were done using these risk factors as independent variables.

Result

A total of 780,961 participants from 183 different countries and territories participated in this study. Among them, 1516 participants were diagnosed with COVID-19 prior to this study. A significant risk association was observed for age above 60 years, female gender as well as different pre-existing disease conditions such as diabetes, kidney disease, liver disease, and heart diseases. Asthma and diabetes were the major dominant comorbidities among patients, and patients with existing diabetes were 1.464 (AOR: 1.464; 95% CI: 1.228-1.744), more likely to develop the disease than others who did not diagnose as diseased.

Conclusion

Older adults, female as well as people with comorbidities such as diabetes mellitus, heart disease, kidney disease, and liver disease, are the most vulnerable population for COVID-19. However, further studies should be carried out to explain the pathway of these risk associations.
4S-DT: Self Supervised Super Sample Decomposition for Transfer learning with application to COVID-19 detection
Authors: Abbas Asmaa , Abdelsamea Mohammed M. , Gaber Mohamed Medhat
Published: June 2020

Due to the high availability of large-scale annotated image datasets, knowledge transfer from pre-trained models showed outstanding performance in medical image classification. However, building a robust image classification model for datasets with data irregularity or imbalanced classes can be a very challenging task, especially in the medical imaging domain. In this paper, we propose a novel deep convolutional neural network, we called Self Supervised Super Sample Decomposition for Transfer learning (4S-DT) model.4S-DTencourages a coarse-to-fine transfer learning from large-scale image recognition tasks to a specific chest X-ray image classification task using a generic self-supervised sample decomposition approach. Our main contribution is a novel self-supervised learning mechanism guided by a super sample decomposition of unlabelled chest X-ray images.4S-DThelps in improving the robustness of knowledge transformation via a downstream learning strategy with a class-decomposition layer to simplify the local structure of the data.4S-DTcan deal with any irregularities in the image dataset by investigating its class boundaries using a downstream class-decomposition mechanism. We used 50,000 unlabelled chest X-ray images to achieve our coarse-to-fine transfer learning with an application to COVID-19 detection, as an exemplar.4S-DThas achieved a high accuracy of 99.8% (95% CI: 99.44 %, 99.98%) in the detection of COVID-19 cases on a large dataset and an accuracy of 97.54% (95% CI: 96.22%, 98.91%) on an extended test set enriched by augmented images of a small dataset, out of which all real COVID-19 cases were detected, which was the highest accuracy obtained when compared to other methods.
TzanckNet: A convolutional neural network to identify cells in the cytology of erosive-vesiculobullous diseases
Authors: Noyan Mehmet Alican , Durdu Murat , Eskiocak Ali Haydar
Published: June 2020

Tzanck smear test is a low-cost, rapid and reliable tool which can be used for the diagnosis of many erosive-vesiculobullous, tumoral and granulomatous diseases. Currently its use is limited mainly due to lack of experience in interpretation of the smears. We developed a deep learning model, TzanckNet, that can identify cells in Tzanck smear test findings. TzanckNet was trained on a retrospective development dataset of 2260 Tzanck smear images collected between December 2006 – December 2019. The finalized model was evaluated using a prospective validation dataset of 359 Tzanck smear images collected from 15 patients during January 2020. It is designed to recognize six cell types (acantholytic cells, eosinophils, hypha, multinucleated giant cells, normal keratinocytes and tadpole cells). For 359 images and 6 cell types, TzanckNet made 2154 predictions. The accuracy was 94.3 % (95% CI 93.4 to 95.3), the sensitivity was 83.7 % (95% CI 80.3 to 87.0) and the specificity was 97.3 % (95% CI 96.5 to 98.1). The area under the receiver operating characteristic curve was 0.974. Our results show that TzanckNet has the potential to lower the experience barrier needed to use this test, broadening its user base, and hence improving patient well-being.
Assessment of scoring functions to rank the quality of 3D subtomogram clusters from cryo-electron tomography
Authors: Singla Jitin , White Kate L. , Stevens Raymond C. , Alber Frank
Published: June 2020

Cryo-electron tomography provides the opportunity for unsupervised discovery of endogenous complexes in situ. This process usually requires particle picking, clustering and alignment of subtomograms to produce an average structure of the complex. When applied to heterogeneous samples, template-free clustering and alignment of subtomograms can potentially lead to the discovery of structures for unknown endogenous complexes. However, such methods require useful scoring functions to measure the quality of aligned subtomogram clusters, which can be compromised by contaminations from misclassified complexes and alignment errors. To our knowledge, a comprehensive survey to assess the effectiveness of scoring functions for ranking the quality of subtomogram clusters does not exist yet. Here, we provide such a study and assess a total of 15 scoring functions for evaluating the quality of the subtomogram clusters, which differ in the amount of structural misalignments and contaminations due to misclassified complexes. We assessed both experimental and simulated subtomograms as ground truth data sets. Our analysis shows that the robustness of scoring functions varies largely. Most scores are sensitive to the signal-to-noise ratio of subtomograms and often require Gaussian filtering as preprocessing for improved performance. Two scoring functions, Spectral SNR-based Fourier Shell Correlation and Pearson Correlation in the Fourier domain with missing wedge correction, show a robust ranking of subtomogram clusters even without any preprocessing and irrespective of SNR levels of subtomograms. Of these two scoring functions, Spectral SNR-based Fourier Shell Correlation was fastest to compute and is a better choice for handling large numbers of subtomograms. Our results provide a guidance for choosing a scoring function for template-free approaches to detect complexes from heterogeneous samples.