origin and evolution of transporter substrate specificity within the npf family
morten egevang jørgensen, deyang xu, christoph crocoll, david ramírez, mohammed saddik motawia, carl erik olsen, hussam hassan nour-eldin, barbara ann halkier 2017
Despite vast diversity in metabolites and the matching substrate specificity of their transporters, little is known about how evolution of transporter substrate specificities is linked to emergence of substrates via evolution of biosynthetic pathways. Transporter specificity towards the recently evolved glucosinolates characteristic of Brassicales is shown to evolve prior to emergence of glucosinolate biosynthesis. Furthermore, we show that glucosinolate transporters belonging to the ubiquitous NRT1/PTR FAMILY (NPF) likely evolved from transporters of the ancestral cyanogenic glucosides found across more than 2500 species outside of the Brassicales. Biochemical characterization of orthologs along the phylogenetic lineage from cassava to A. thaliana, suggests that alterations in the electrogenicity of the transporters accompanied changes in substrate specificity. Linking the evolutionary path of transporter substrate specificities to that of the biosynthetic pathways, exemplify how transporter substrate specificities originate and evolve as new biosynthesis pathways emerge.
All living cells are surrounded by membranes that protect them from the external environment. The membrane contains proteins called transporters, which move nutrients and other molecules (known as substrates) across the membrane. A variety of transporters have evolved to move the hundreds of thousands of different substrates found in nature.
Plant cells make many different compounds to protect themselves from pests and diseases. A group of transporters known as the NPF family move some of these compounds across the cells outer membrane. The types of substrates they transport vary in different plants. In cassava, for example, NPF transporters move compounds called cyanogenic glucosides, which are poisonous to humans and other animals. On the other hand, NPF transporters in another plant called Arabidopsis thaliana can move bitter-tasting compounds called glucosinolates. The process that makes glucosinolates in plants evolved from the process that makes cyanogenic glucosides.
Can transporters evolve the ability to move a new substrate before or after that substrate first appears? To answer this question, Jørgensen et al. studied the NPF family in A. thaliana, cassava and another plant called papaya that makes both cyanogenic glucosides and glucosinolates. The experiments suggest that NPF transporters able to move both cyanogenic glucosides and glucosinolates evolved before plants evolved the ability to make glucosinolates. Later in evolution, these multi-specific transporters specialized to only move glucosinolates. Jørgensen et al. also show that early glucosinolate transporters could move a broad variety of glucosinolates but later evolved to only transport particular types.
These findings show how transporters and the processes that make compounds in cells may evolve together. A future challenge will be to understand the molecular changes in a transporter that make it specific for a certain substrate. This may help researchers to develop new ways of controlling the amount of toxic compounds in crops we eat by manipulating how the compounds are transported.
environmental change explains cichlid adaptive radiation at lake malawi over the past 1.2 million years
sarah j. ivory, margaret w. blome, john w. king, michael m. mcglue, julia e. cole, andrew s. cohen 2016
Tropical African lakes are well-known to house exceptionally biodiverse assemblages of fish and other aquatic fauna, which are thought to be at risk in the future. Although the modern assemblages are well-studied, direct evidence of the origin of this incredible wealth of species and the mechanisms that drive speciation are virtually unknown. We use a long sedimentary record from Lake Malawi to show that over the last 1.2 My both large-scale climatic and tectonic changes resulted in wet–dry transitions that led to extraordinary habitat variability and rapid diversification events. This work allows us to understand the environmental context of aquatic evolution in the most biodiverse tropical lake.
Long paleoecological records are critical for understanding evolutionary responses to environmental forcing and unparalleled tools for elucidating the mechanisms that lead to the development of regions of high biodiversity. We use a 1.2-My record from Lake Malawi, a textbook example of biological diversification, to document how climate and tectonics have driven ecosystem and evolutionary dynamics. Before ∼800 ka, Lake Malawi was much shallower than today, with higher frequency but much lower amplitude water-level and oxygenation changes. Since ∼800 ka, the lake has experienced much larger environmental fluctuations, best explained by a punctuated, tectonically driven rise in its outlet location and level. Following the reorganization of the basin, a change in the pacing of hydroclimate variability associated with the Mid-Pleistocene Transition resulted in hydrologic change dominated by precession rather than the high-latitude teleconnections recorded elsewhere. During this time, extended, deep lake phases have abruptly alternated with times of extreme aridity and ecosystem variability. Repeated crossings of hydroclimatic thresholds within the lake system were critical for establishing the rhythm of diversification, hybridization, and extinction that dominate the modern system. The chronology of these changes closely matches both the timing and pattern of phylogenetic history inferred independently for the lake’s extraordinary array of cichlid fish species, suggesting a direct link between environmental and evolutionary dynamics.
signal or noise? a null model method for evaluating the significance of turnover pulses
w. andrew barr 2017
diverse non-genetic, allele-specific expression effects shape genetic architecture at the cellular level in the mammalian brain
wei-chao huang et al. 2017
•In vivo genome-wide screen uncovers diverse non-genetic allelic effects
•Non-genetic allelic effects are prevalent in the neonatal mouse brain
•Allelic effects cause mosaics of mutant and wild-type cells for heterozygous mutations
•Allelic effects exist in the primate brain and impact genes linked to mental illness
Interactions between genetic and epigenetic effects shape brain function, behavior, and the risk for mental illness. Random X inactivation and genomic imprinting are epigenetic allelic effects that are well known to influence genetic architecture and disease risk. Less is known about the nature, prevalence, and conservation of other potential epigenetic allelic effects in vivo in the mouse and primate brain. Here we devise genomics, in situ hybridization, and mouse genetics strategies to uncover diverse allelic effects in the brain that are not caused by imprinting or genetic variation. We found allelic effects that are developmental stage and cell type specific, that are prevalent in the neonatal brain, and that cause mosaics of monoallelic brain cells that differentially express wild-type and mutant alleles for heterozygous mutations. Finally, we show that diverse non-genetic allelic effects that impact mental illness risk genes exist in the macaque and human brain. Our findings have potential implications for mammalian brain genetics.
“silencing one gene copy may be a way in which cells fine tune their genetic program at specific times during the lifecycle of the animal, or in discrete places”
impacts of neanderthal-introgressed sequences on the landscape of human gene expression
rajiv c. mccoy, jon wakefield, joshua m. akey 2017
trade-off between transcriptome plasticity and genome evolution in cephalopods
liscovitch-brauer et al. 2017
•Unlike other taxa, cephalopods diversify their proteomes extensively by RNA editing
•Extensive recoding is specific to the behaviorally complex coleiods
•Unlike mammals, cephalopod recoding is evolutionarily conserved and often adaptive
•Transcriptome diversification comes at the expense of slowed-down genome evolution
RNA editing, a post-transcriptional process, allows the diversification of proteomes beyond the genomic blueprint; however it is infrequently used among animals for this purpose. Recent reports suggesting increased levels of RNA editing in squids thus raise the question of the nature and effects of these events. We here show that RNA editing is particularly common in behaviorally sophisticated coleoid cephalopods, with tens of thousands of evolutionarily conserved sites. Editing is enriched in the nervous system, affecting molecules pertinent for excitability and neuronal morphology. The genomic sequence flanking editing sites is highly conserved, suggesting that the process confers a selective advantage. Due to the large number of sites, the surrounding conservation greatly reduces the number of mutations and genomic polymorphisms in protein-coding regions. This trade-off between genome evolution and transcriptome plasticity highlights the importance of RNA recoding as a strategy for diversifying proteins, particularly those associated with neural function.
coupling between distant biofilms and emergence of nutrient time-sharing
liu j et al. 2017
indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the finnish diabetes prevention study
vanessa d. de mello et al. 2017
legacy effects of developmental stages determine the functional role of predators
volker h. w. rudolf & b. g. van allen 2017
self-motion evokes precise spike timing in the primate vestibular system
mohsen jamali, maurice j. chacron, kathleen e. cullen 2016
fishing down nutrients on coral reefs
jacob e. allgeier, abel valdivia, courtney cox, craig a. layman 2016
what does it mean to be human?
gaia vince discovers that analysing the genetics of ancient humans means changing ideas about our evolution 2017
The things that we thought we understood about Europeans are coming unstuck as we examine the genes of more ancient people. For example, it was generally accepted that pale skin evolved so we could get more vitamin D after moving north to where there was little sun and people had to cover up against the cold. But it turns out that it was the Yamnaya people from much further south, tall and brown-eyed, who brought pale skins to Europe. Northern Europeans before then were dark-skinned and got plenty of vitamin D from eating fish.
It is the same with lactose tolerance. Around 90 per cent of Europeans have a genetic mutation that allows them to digest milk into adulthood, and scientists had assumed that this gene evolved in farmers in northern Europe, giving them an additional food supply to help survive the long winters. But Eske’s research using the genomes of hundreds of Bronze Age people, who lived after the advent of farming, has cast doubt on this theory too: “We found that the genetic trait was almost non-existent in the European population. This trait only became abundant in the northern European population within the last 2,000 years,” he says.
It turns out that lactose tolerance genes were also introduced by the Yamnaya. “They had a slightly higher tolerance to milk than the European farmers and must have introduced it to the European gene pool. Maybe there was a disaster around 2,000 years ago that caused a population bottleneck and allowed the gene to take off. The Viking sagas talk about the sun becoming black – a major volcanic eruption – that could have caused a massive drop in population size, which could have been where some of that stock takes off with lactose.”
ancient human genomes suggest three ancestral populations for present–day humans
neanderthal behaviour, diet, and disease inferred from ancient dna in dental calculus
laura s. weyrich et al. 2017
variable habitat conditions drive species covariation in the human microbiota
charles k. fisher, thierry mora, aleksandra m. walczak 2017
Two species with similar resource requirements respond in a characteristic way to variations in their habitat—their abundances rise and fall in concert. We use this idea to learn how bacterial populations in the microbiota respond to habitat conditions that vary from person-to-person across the human population. Our mathematical framework shows that habitat fluctuations are sufficient for explaining intra-bodysite correlations in relative species abundances from the Human Microbiome Project. We explicitly show that the relative abundances of closely related species are positively correlated and can be predicted from taxonomic relationships. We identify a small set of functional pathways related to metabolism and maintenance of the cell wall that form the basis of a common resource sharing niche space of the human microbiota.
The human body is inhabited by a vast number of microorganisms comprising the human microbiota. The species composition of the microbiota varies considerably from person-to-person and the relative abundances of some species rise and fall in concert. We introduce a mathematical model where differences in habitat conditions cause most of the variability of the microbiota. A statistical analysis shows that variable habitat conditions are sufficient for explaining the patterns of variation observed across a healthy human population and, as a result, the correlation between the relative abundances of two species reflects how closely related they are rather than how they directly interact with each other.
antibiotic-producing symbionts dynamically transition between plant pathogenicity and insect-defensive mutualism
laura v. flórez et al. 2017
sexual dimorphism and retinal mosaic diversification following the evolution of a violet receptor in butterflies
kyle j. mcculloch et al. 2017
improbable destinies: fate, chance, and the future of evolution
jonathan losos 2017
runes of evolution
simon conway morris 2015
Reference: Biol. Bull. 227: 300–312. (December 2014)
FISH Labeling Reveals a Horizontally Transferred Algal (Vaucheria litorea) Nuclear Gene on a Sea Slug (Elysia chlorotica) Chromosome
JULIE A. SCHWARTZ1, NICHOLAS E. CURTIS2, AND SIDNEY K. PIERCE1,3*
1Department of Integrative Biology, University of South Florida, Tampa, Florida 33620; 2Department of Biology and Chemistry, Ave Maria University, Ave Maria, Florida 34142; and 3Department of Biology, University of Maryland, College Park, Maryland 20742
horizontal gene transfer
not only in simple organisms
horizontal gene transfer is more frequent with increased heterotrophy and contributes to parasite adaptation
zhenzhen yang et al. 2016
Horizontal gene transfer (HGT) is the nonsexual transfer and genomic integration of genetic materials between organisms. In eukaryotes, HGT appears rare, but parasitic plants may be exceptions, as haustorial feeding connections between parasites and their hosts provide intimate cellular contacts that could facilitate DNA transfer between unrelated species. Through analysis of genome-scale data, we identified >50 expressed and likely functional HGT events in one family of parasitic plants. HGT reflected parasite preferences for different host plants and was much more frequent in plants with increasing parasitic dependency. HGT was strongly biased toward expression and protein types likely to contribute to haustorial function, suggesting that functional HGT of host genes may play an important role in adaptive evolution of parasites.
Horizontal gene transfer (HGT) is the transfer of genetic material across species boundaries and has been a driving force in prokaryotic evolution. HGT involving eukaryotes appears to be much less frequent, and the functional implications of HGT in eukaryotes are poorly understood. We test the hypothesis that parasitic plants, because of their intimate feeding contacts with host plant tissues, are especially prone to horizontal gene acquisition. We sought evidence of HGTs in transcriptomes of three parasitic members of Orobanchaceae, a plant family containing species spanning the full spectrum of parasitic capabilities, plus the free-living Lindenbergia. Following initial phylogenetic detection and an extensive validation procedure, 52 high-confidence horizontal transfer events were detected, often from lineages of known host plants and with an increasing number of HGT events in species with the greatest parasitic dependence. Analyses of intron sequences in putative donor and recipient lineages provide evidence for integration of genomic fragments far more often than retro-processed RNA sequences. Purifying selection predominates in functionally transferred sequences, with a small fraction of adaptively evolving sites. HGT-acquired genes are preferentially expressed in the haustorium—the organ of parasitic plants—and are strongly biased in predicted gene functions, suggesting that expression products of horizontally acquired genes are contributing to the unique adaptive feeding structure of parasitic plants.
cancer tumors as metazoa 1.0: tapping genes of ancient ancestors
p c w davies and c h lineweaver 2011
canine transmissible venereal tumour
cancer cells enter dormancy after cannibalizing mesenchymal stem/stromal cells (mscs)
thomas j. bartosh, mujib ullah, suzanne zeitouni, joshua beaver, darwin j. prockop 2016
shaping variation in the human immune system
liston, linterman, and carr 2016
Immune responses demonstrate a high level of intra-species variation, compensating for the specialization capacity of pathogens. The recent advent of in-depth immune phenotyping projects in large-scale cohorts has allowed a first look into the factors that shape the inter-individual diversity of the human immune system. Genetic approaches have identified genetic diversity as drivers of 20–40% of the variation between the immune systems of individuals. The remaining 60–80% is shaped by intrinsic factors, with age being the predominant factor, as well as by environmental influences, where cohabitation and chronic viral infections were identified as key mediators. We review and integrate the recent in-depth large-scale studies on human immune diversity and its potential impact on health.
Diversity within the human immune system is stable over the duration of months to years with an elastic response to immunological challenge, allowing the study of immune drivers.
Genetic variation accounts for 20–40% of immune variation, with enrichment of gene variants associated with autoimmunity, inflammatory disease, and susceptibility to infections among the identified genetic drivers.
Among the identified intrinsic drivers of immune variation, age is the most potent, driving a shift from a precursor-biased immune status to an inflammation-biased immune status.
A strong environmental effect on immune variation is observed, as revealed by cohabitation studies, with the strongest individual driver identified to date being chronic viral infection.
bacterial immune system
quorum sensing controls adaptive immunity through the regulation of multiple crispr-cas systems
adrian g. patterson et al. 2016
Quorum sensing regulates the type I-E, I-F, and III-A CRISPR-Cas systems in Serratia
SmaR represses cas gene and CRISPR expression in the absence of AHL signals
Both interference and adaptation are modulated by quorum sensing
Bacteria coordinate their defenses based on cell density and the risk of infection
Bacteria commonly exist in high cell density populations, making them prone to viral predation and horizontal gene transfer (HGT) through transformation and conjugation. To combat these invaders, bacteria possess an arsenal of defenses, such as CRISPR-Cas adaptive immunity. Many bacterial populations coordinate their behavior as cell density increases, using quorum sensing (QS) signaling. In this study, we demonstrate that QS regulation results in increased expression of the type I-E, I-F, and III-A CRISPR-Cas systems in Serratia cells in high-density populations. Strains unable to communicate via QS were less effective at defending against invaders targeted by any of the three CRISPR-Cas systems. Additionally, the acquisition of immunity by the type I-E and I-F systems was impaired in the absence of QS signaling. We propose that bacteria can use chemical communication to modulate the balance between community-level defense requirements in high cell density populations and host fitness costs of basal CRISPR-Cas activity.
immune system where we didn’t expect it
structural and functional features of central nervous system lymphatic vessels
antoine louveau et al. 2015
egress of sperm autoantigen from seminiferous tubules maintains systemic tolerance
kenneth s.k. tung et al. 2017
evolution through loss is different from evolution through gain. currently evolution through gain.
aliens in our midst; the ctenophore’s brain suggests that, if evolution began again, intelligence would re-emerge because nature repeats itself
douglas fox 2017
genetic basis for race
nicholas wade 2014 a troublesome inheritance: genes, race, and human history
the 10,000 year explosion; how civilization accelerated human evolution
gregory cochran, henry harpending 2009
cultural basis for healthy habits
dna dispose, but subjects decide. learning and the extended synthesis
markus lindholm 2015
living space, not competition, is evolutionary driver?
this is particularly important because "evolutionary competition" "nature red in tooth and claw" is a prime assumption of our society.
links between global taxonomic diversity, ecological diversity and the expansion of vertebrates on land
sahney et al 2010
evolutionary rescue can prevent extinction following environmental change
graham bell and andrew gonzalez 2009
basically, presence of a few adapted individuals in a large population allows numbers to recover in laboratory i.e. stable conditions. changing conditions not investigated here, only single step change.
The ubiquity of global change and its impacts on biodiversity poses a clear and urgent challenge for evolutionary biologists. In many cases, environmental change is so widespread and rapid that individuals can neither accommodate to them physiologically nor migrate to a more favourable site. Extinction will ensue unless the population adapts fast enough to counter the rate of decline. According to theory, whether populations can be rescued by evolution depends upon several crucial variables: population size, the supply of genetic variation, and the degree of maladaptation to the new environment. Using techniques in experimental evolution we tested the conditions for evolutionary rescue (ER). Hundreds of yeast populations were exposed to normally lethal concentrations of salt in conditions, where the frequency of rescue mutations was estimated and population size was manipulated. In a striking match with theory, we show that ER is possible, and that the recovery of the population may occur within 25 generations. We observed a clear threshold in population size for ER whereby the ancestral population size must be sufficiently large to counter stochastic extinction and contain resistant individuals. These results demonstrate that rapid evolution is an important component of the response of small populations to environmental change.
interface theory of perception http://www.cogsci.uci.edu/~ddhoff/interface.pdf
is our next evolutionary step to learn to control these massive ponderous structures that we have built, of industry, of law, of everything? we are still operating as a society on the individual level and have poor control over the direction of our society.
“junk” dna is not junk
genomic variation within alpha satellite dna influences centromere location on human chromosomes with metastable epialleles
megan e aldrup-macdonald, molly e kuo, lori l sullivan, kimberline chew, beth a sullivan 2016;
l1-associated genomic regions are deleted in somatic cells of the healthy human brain
jennifer erwin et al. 2016
occurrence of harmful gene variants could be the price we pay for the genetic diversity that is otherwise highly beneficial to our survival
excess of deleterious mutations around hla genes reveals evolutionary cost of balancing selection
tobias l. lenz, victor spirin, daniel m. jordan, shamil r. sunyaev 2016
social context, but not individual personality, alters immigrant viability in a spider with mixed social structure
spencer j. ingley, jonathan n. pruitt, inon scharf, jessica purcell 2016
demographic and reproductive plasticity across the depth distribution of a coral reef fish
esther d. goldstein, evan k. d’alessandro, su sponaugle 2016
archean coastal-plain paleosols and life on land
gregory j. retallack, david h. krinsley, robert fischer, joshua j. razink, kurt a. langworthy 2016
There are coastal-plain paleosols in 3.0 Ga Farrel Quartzite, Western Australia.
Paleosols have organic surface (A) and sulfate-rich subsurface (By) horizon.
Comparable profiles are known from deserts of Chile, Antarctica, and Mars.
Microfossils in paleosols include actinobacteria, sulfur bacteria, methanogens.
Coastal-plain paleosols in the 3.0 Ga Farrel Quartzite of Western Australia have organic surface (A horizon) and sulfate-rich subsurface (By) horizons, like soils of the Atacama Desert of Chile, Dry Valleys of Antarctica, and 3.7 Ga paleosols of Mars. Farrel Quartzite paleosols include previously described microfossils, permineralized by silica in a way comparable with the Devonian Rhynie Chert, a well known permineralized Histosol. Five microfossil morphotypes in the Farrel Quartzite include a variety of spheroidal cells (Archaeosphaeroides) as well as distinctive large spindles (new genus provisionally assigned to cf. Eopoikilofusa). Previously published cell-specific carbon isotopic analyses of the Farrel Quartzite microfossils, and unusually abundant sulfate considering a likely anoxic atmosphere, allow interpretation of these morphotypes as a terrestrial community of actinobacteria, purple sulfur bacteria, and methanogenic Archaea.
the 'out of africa' hypothesis, human genetic diversity, and comparative economic development
quamrul ashraf, oded galor 2013
mutations and sexual recombination transmitted via DNA, distribution changes and also elimination via genetic drift and migration
defined chromosome structure in the genome-reduced bacterium mycoplasma pneumoniae
marie trussart et al. 2017
evolutionary development biology
methylation during lifetime transmitted via germline
maternal h3k27me3 controls dna methylation-independent imprinting
azusa inoue, lan jiang, falong lu, tsukasa suzuki, yi zhang 2017
parent-of-origin dna methylation dynamics during mouse development
yonatan stelzer, hao wu, yuelin song, chikdu s. shivalila, styliani markoulaki, rudolf jaenisch 2016
•In vivo tracing of parent-specific DNA methylation dynamics at single-cell resolution
•Cell-type-specific methylation signatures at the Dlk-Dio3 IG-DMR during development
•Dynamic parent- and cell-type-specific DNA methylation changes in the adult brain
Parent-specific differentially methylated regions (DMRs) are established during gametogenesis and regulate parent-specific expression of imprinted genes. Monoallelic expression of imprinted genes is essential for development, suggesting that imprints are faithfully maintained in embryos and adults. To test this hypothesis, we targeted a reporter for genomic methylation to the imprinted Dlk1-Dio3 intergenic DMR (IG-DMR) to assess the methylation of both parental alleles at single-cell resolution. Biallelic gain or loss of IG-DMR methylation occurred in a small fraction of mouse embryonic stem cells, significantly affecting developmental potency. Mice carrying the reporter in either parental allele showed striking parent-specific changes in IG-DMR methylation, causing substantial and consistent tissue- and cell-type-dependent signatures in embryos and postnatal animals. Furthermore, dynamics in DNA methylation persisted during adult neurogenesis, resulting in inter-individual diversity. This substantial cell-cell DNA methylation heterogeneity implies that dynamic DNA methylation variations in the adult may be of functional importance.
krab zinc-finger proteins contribute to the evolution of gene regulatory networks
michaël imbeault, pierre-yves helleboid, didier trono 2017
germ line-inherited h3k27me3 restricts enhancer function during maternal-to-zygotic transition
zenk f et al. 2017
a heterochromatin-dependent transcription machinery drives piRNA expression
peter refsing andersen et al. 2017
the epitranscriptome of noncoding rnas in cancer
manel esteller, pier paolo pandolfi 2017
reconsidering plant memory: intersections between stress recovery, rna turnover, and epigenetics
crisp et al. 2016
intrinsically disordered proteins drive emergence and inheritance of biological traits
sohini chakrabortee et al. 2016
genetic evidence for elevated pathogenicity of mitochondrial dna heteroplasmy in autism spectrum disorder
wang y, picard m, gu z 2016
classification and adaptive behavior prediction of children with autism spectrum disorder based upon multivariate data analysis of markers of oxidative stress and dna methylation
daniel p. howsmon, uwe kruger, stepan melnyk, s. jill james, juergen hahn 2017
mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis
d a rossignol, r e frye 2011
mitochondrial function controls intestinal epithelial stemness and proliferation
emanuel berger et al. 2016
perhaps conscious change in particular direction can lead to epigenetic change
they continue to look for pathways in which, for example, serotonin directly influences behavior via chemical changes in the brain. but what if the real mechanism is actually indirect, that epigenetic changes are constantly happening and what serotonin does is tip the balance towards a certain population of epigenetic variance, which in turn causes the behavior we observe
when I get enough sleep, ideas and connections and creativity just seem to flow. could this be through epigenetic change too?
adolescent binge-pattern alcohol exposure alters genome-wide dna methylation patterns in the hypothalamus of alcohol-naïve male offspring
annadorothea animes 2016
cell autonomous regulation of herpes and influenza virus infection by the circadian clock
rachel s. edgara et al. 2016
local modulation of human brain responses by circadian rhythmicity and sleep debt
vincenzo muto et al 2016