bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiome composition shapes rapid genomic adaptation ofDrosophila melanogaster
Authors: Rudman Seth M. , Greenblum Sharon , Hughes Rachel C. , Rajpurohit Subhash , Kiratli Ozan , Lowder Dallin B. , Lemmon Skyler G. , Petrov Dmitri A. , Chaston John M. , Schmidt Paul 
Published: May 2019

AbstractPopulation genomic data has revealed patterns of genetic variation associated with adaptation in many taxa. Yet understanding the adaptive process that drives such patterns is challenging - it requires disentangling the ecological agents of selection, determining the relevant timescales over which evolution occurs, and elucidating the genetic architecture of adaptation. Doing so for the adaptation of hosts to their microbiome is of particular interest with growing recognition of the importance and complexity of host-microbe interactions. Here, we track the pace and genomic architecture of adaptation to an experimental microbiome manipulation in replicate populations ofDrosophila melanogasterin field mesocosms. Manipulation of the microbiome altered population dynamics and increased divergence between treatments in allele frequencies genome-wide, with regions showing strong divergence found on all chromosomes. Moreover, at divergent loci previously associated with adaptation across natural populations, we found that the more common allele in fly populations experimentally enriched for a certain microbial group was also more common in natural populations with high relative abundance of that microbial group. These results suggest that microbiomes may be an agent of selection that shapes the pattern and process of adaptation and, more broadly, that variation in a single ecological factor within a complex environment can drive rapid, polygenic adaptation over short timescales.Significance statementNatural selection can drive evolution over short timescales. However, there is little understanding of which ecological factors are capable of driving rapid evolution and how this rapid evolution alters allele frequencies across the genome. Here we combine a field experiment with population genomic data from natural populations across a latitudinal gradient to assess whether and how microbiome composition drives rapid genomic evolution of host populations. We find that differences in microbiome composition cause divergence in allele frequencies genome-wide, including in genes previously associated with local adaptation. Moreover, we observed concordance between experimental and natural populations in terms of the direction of allele frequency change, suggesting that microbiome composition may be an agent of selection that drives adaptation in the wild.
Nuclear Expression and DNA Binding Capacity of Receptor for Advanced Glycation End Products in Renal Tissue
Authors: Harcourt Brooke E. , McClelland Aaron D. , Yamamoto Hiroshi , Yonekura Hideto , Yamamoto Yasuhiko , Penfold Sally A , Fotheringham Amelia K. , Vesey David A. , Johnson David W. , Coughlan Melinda T. , Cooper Mark E. , Kantharidis Phillip , Forbes Josephine M. 
Published: May 2019

AbstractTheAGERgene encodes for a number of RAGE isoforms, with the membrane bound signal transduction and “decoy” circulating soluble RAGE being the best characterised. Here we demonstrate a novel nuclear isoform of RAGE in mice and human kidney cortex which by cell and size fractionation we determined to be approximately 37kda. This nuclear RAGE isoform is functional and binds to DNA sequences within the upstream 5’ promoter region of its own gene,AGER. This binding was shown to be abrogated by mutating the DNA consensus binding sequences during electromobility shift assay (EMSA) and was independent of NF-□B or AP-1 binding. Cotransfection of expression constructs encoding various RAGE isoforms along withAGERgene promoter reporter-plasmids identified that the most likely source of the nuclear isoform of RAGE was a cleavage product of the nt-RAGE isoform. In obese mice with impaired kidney function, there was increased binding of nuclear RAGE within the A. Region ofagergene promoter with corresponding increases in membrane bound RAGE in renal cells. These findings were reproducedin vitrousing proximal tubule cells. Hence, we postulate that RAGE expression is in part, self-regulated by the binding of a nuclear RAGE isoform to the promoter of theAGERgene (encoding RAGE) in the kidney. We also suggest that this RAGE self-regulation is altered under pathological conditions and this may have implications for chronic kidney disease.
Quantitative analysis and medium components optimizing for culturing a fastidious bacterium Christensenella minuta
Authors: Xiao Hongshi , Liu Binghuan , Yong Jie , Zhou Haiyan 
Published: May 2019

AbstractChristensenella minuta is a heritable bacterium with controversial physiologies associating with both obesity and potential pathogenicity. Since this bacterium is fastidious to culture, it is hardly to well understand its biological feature. We develop a strategy for statistical analysis of this low abundant strain and optimize culture condition to make a significant improvement on its biomass and facilitate the researches about the metabolism and function of this bacterium. Basing on the fluorogenic quantitative technology, a quantitative approach was successfully constructed for Christensenella minuta by plotting Ct value from fluorescence quantitative PCR against the logarithm of concentration gradient of plasmids containing 16S rDNA of the strain. This method exhibited to have specificity on analyzing the strain biomass statistically. For improving the strain biomass, “komodo” predicted to optimize medium components and metabonomics analysis explored the catabolites addition effects on culture improvement. With the aid of Plackett-Burman and Box-Behnken in Design-Expert 8.0.6, the PB and response surface experiment were designed and analyzed from the single factor results. On the modified GAM medium, the strain concentration was found increasing markedly by 10 times. The addition of some amino acids, vitamins and inorganic salts has contributions for the strain multiplication, especially L-cysteine, VB6 and NaCl. The addition of 55 mg/L of L-cysteine, 20.5 mg/L VB6 and 55 g/L NaCl into the modified GAM medium increased the biomass by 3.59 times compared to the biomass on only modified GAM medium according to the response surface experiment. Through the newly constructed method, we successfully analyzed the amount of Christensenella minuta and obtained a novel medium to increase biomass significantly.ImportanceChristensenella minuta is a heritable bacterium with controversial physiologies associating with both obesity and potential pathogenicity. Since this bacterium is fastidious to culture, it is hard to well understand its biological feature. We develop a strategy for statistical analysis of this low abundant strain and optimize culture condition to make a significant improvement on its biomass and facilitate the researches about the metabolism and function of this bacterium. This work combined the prediction tools and experiments to improve the medium components of C. munita and successfully enhance the culturing and increase biomass by more than 10-fold. From this perspective, the project throws some new ideas and also enables access to new knowledge and information in uncultured microbial resources.
Boosting with ALVAC-HIV and AIDSVAX B/E enhances Env constant region 1 and 2 antibody-dependent cellular cytotoxicity
Authors: Easterhoff David , Pollara Justin , Luo Kan , Tolbert William D. , Young Brianna , Mielke Dieter , Jha Shalini , O’Connell Robert J. , Vasan Sandhya , Kim Jerome , Michael Nelson L. , Excler Jean-Louis , Robb Merlin L. , Rerks-Ngarm Supachai , Kaewkungwal Jaranit , Pitisuttithum Punnee , Nitayaphan Sorachai , Sinangil Faruk , Tartaglia James , Phogat Sanjay , Kepler Thomas B. , Alam S. Munir , Wiehe Kevin , Saunders Kevin O. , Montefiori David C. , Tomaras Georgia D. , Moody M. Anthony , Pazgier Marzena , Haynes Barton F. , Ferrari Guido 
Published: May 2019

AbstractInduction of protective antibodies is a critical goal of HIV-1 vaccine development. One strategy is to induce non-neutralizing antibodies that kill virus-infected cells as these antibody specificities have been implicated in slowing HIV-1 disease progression and in protection. HIV-1 Env constant region 1 and 2 (C1C2) antibodies frequently contain potent antibody dependent cellular cytotoxicity (ADCC) making them a vaccine target. Here we explore the effect of delayed and repetitive boosting of RV144 vaccinee recipients with ALVAC/AIDSVAX B/E on the C1C2-specific antibody repertoire. It was found that boosting increased clonal lineage specific ADCC breadth and potency. A ligand crystal structure of a vaccine-induced broad and potent ADCC-mediating C1C2-specific antibody showed that it bound a highly conserved Env gp120 epitope. Thus, rationally designed boosting strategies to affinity mature these type of IgG C1C2-specific antibody responses may be one method by which to make an improved HIV vaccine with higher efficacy than seen in the RV144 trial.SignificanceOver one million people become infected with HIV-1 each year making the development of an efficacious HIV-1 vaccine an important unmet medical need. The RV144 human HIV-1 vaccine-regimen is the only HIV-1 clinical trial to date to demonstrate vaccine-efficacy. An area of focus has been on identifying ways by which to improve upon RV144 vaccine-efficacy. The RV305 HIV-1 vaccine-regimen was a follow-up boost of RV144 vaccine-recipients that occurred 6-8 years after the conclusion of RV144. Our studies focused on the effect of delayed boosting in humans on the vaccine-induced antibody repertoire. It was found that boosting with a HIV-1 Env vaccine increased antibody-mediated effector function potency and breadth.
Invasion and extinction dynamics of mating types under facultative sexual reproduction
Authors: Czuppon Peter , Constable George W. A. 
Published: May 2019

AbstractIn sexually reproducing isogamous species, syngamy between gametes is generally not indiscriminate, but rather restricted to occurring between complementary self-incompatible mating types. A longstanding question regards the evolutionary pressures that control the number of mating types observed in natural populations, which ranges from two to many thousands. Here, we describe a population genetic null model of this reproductive system and derive expressions for the stationary probability distribution of the number of mating types, the establishment probability of a newly arising mating type and the mean time to extinction of a resident type. Our results yield that the average rate of sexual reproduction in a population correlates positively with the expected number of mating types observed. We further show that the low number of mating types predicted in the rare-sex regime is primarily driven by low invasion probabilities of new mating type alleles, with established resident alleles being very stable over long evolutionary periods. Moreover, our model naturally exhibits varying selection strength dependent on the number of present mating types. This results in higher extinction and lower invasion rates for an increasing number of residents.
The dynamics of stem and crown groups
Authors: Budd Graham E. , Mann Richard P. 
Published: May 2019

ABSTRACTThe fossil record of the origins of major groups is of great interests to many biologists, especially when the fossil record apparently conflicts with timings based on molecular clock estimates. Here we model the diversity of “stem” (basal) and “crown” (modern) members of groups as seen in the fossil record, using a “birth-death model”. Under background conditions, the stem group members must diversify rapidly until the modern crown group emerges, at which point their diversity rapidly collapses, followed shortly by their extinction. Mass extinctions can disturb this pattern to create very diverse stem groups such as the dinosaurs and trilobites. Understanding these null-hypothesis patterns is essential for framing ecological and evolutionary explanations for how major groups originate and subsequently evolve.
Genomic basis of circannual rhythm in the european corn borer moth
Authors: Kozak Genevieve M. , Wadsworth Crista B. , Kahne Shoshanna C. , Bogdanowicz Steven M. , Harrison Richard G. , Coates Brad S. , Dopman Erik B. 
Published: May 2019

ABSTRACTGenetic variation in life-history timing allows populations to synchronize with seasonal cycles but little is known about the molecular mechanisms that produce differences in circannual rhythm in nature. Changes in diapause timing in the European corn borer moth (Ostrinia nubilalis) have facilitated rapid response to shifts in winter length encountered during range expansion and from climate change, with some populations emerging from diapause earlier to produce an additional generation per year. We identify genomic variation associated with changes in the time spent in winter diapause and show evidence that the circadian clock genes period (per) and pigment dispersing factor receptor (Pdfr) interact to underlie this adaptive polymorphism in circannual rhythm. Per and Pdfr are located within two epistatic QTL, strongly differ in allele frequency among individuals that pupate earlier or later, have the highest linkage disequilibrium among gene pairs in the QTL regions despite separation by > 4 megabases, and possess amino-acid changes likely to affect function. One per mutation in linkage disequilibrium with Pdfr creates a novel putative clock-cycle binding site found exclusively in populations that pupate later. We find associated changes in free-running daily circadian rhythm, with longer daily rhythms in individuals that end diapause early. These results support a modular connection between circadian and circannual timers and provide testable hypotheses about the physiological role of the circadian clock in seasonal synchrony. Winter length is expected to continually shorten from climate warming and we predict these gene candidates will be targets of selection for future adaptation and population persistence.
Histone Tail Dynamics in Partially Disassembled Nucleosomes During Chromatin Remodeling
Authors: Kameda T. , Awazu A. , Togashi Y. 
Published: May 2019

AbstractNucleosomes are structural units of the chromosome consisting of DNA wrapped around histone proteins, and play important roles in compaction and regulation of the chromatin structure. While the structure and dynamics of canonical nucleosomes have been studied extensively, those of nucleosomes in intermediate states, that occur when their structure or positioning is modulated, have been less understood. In particular, the dynamic features of partially disassembled nucleosomes have not been discussed in previous studies. Using all-atom molecular dynamics simulations, in this study, we investigated the dynamics and stability of nucleosome structures lacking a histone-dimer. DNA in nucleosomes lacking a histone H2A/H2B dimer was drastically deformed due to loss of local interactions between DNA and histones. In contrast, conformation of DNA in nucleosomes lacking H3/H4 was similar to the canonical nucleosome, as the H2A C-terminal domain infiltrated the space originally occupied by the dissociated H3/H4 histones and stabilized DNA in close proximity. Our results suggest that, besides histone chaperones, the intrinsic dynamics of nucleosomes support the exchange of H2A/H2B, which is significantly more frequent than that of H3/H4.Statement of SignificanceEukaryotic chromosomes are composed of nucleosomes, in which the DNA wraps around the core histone proteins. To enable transcription and replication of DNA, or to modulate these functions by exchange of histones, nucleosomes should be at least partially disassembled, as evidenced by the observation of nucleosome structures lacking an H2A/H2B histone dimer by crystallography. The dynamic behavior of nucleosomes in such intermediate states may affect gene expression and repair, however it has not been completely elucidated so far. In this study, we adopted molecular dynamics simulations to analyze the conformational changes in partially disassembled nucleosomes. Enhanced structural fluctuations of DNA were observed in these nucleosomes, which may, as well as specific histone chaperones, support the exchange of H2A/H2B.
Early origin and deep conservation of enhancers in animals
Authors: Wong Emily S , Tan Siew Zhuan , Garside Victoria , Vanwalleghem Gilles , Gaiti Federico , Scott Ethan , McGlinn Edwina , Francois Mathias , Degnan Bernard M 
Published: May 2019

AbstractTranscription factors (TFs) bind DNA enhancer sequences to regulate gene transcription in animals. Unlike TFs, the evolution of enhancers has been difficult to trace because of their rapid evolution. Here, we show enhancers from the sponge Amphimedon queenslandica can drive cell type-specific reporter gene expression in zebrafish and mouse, despite sponge and vertebrate lineages diverging over 700 million years ago. Although sponge enhancers, which are present in both highly conserved syntenic gene regions (Islet–Scaper, Ccne1–Uri and Tdrd3–Diaph3) and sponge-specific intergenic regions, have no significant sequence identity with vertebrate genomic sequences, the type and frequency of TF binding motifs in the sponge enhancer allow for the identification of homologous enhancers in bilaterians. Islet enhancers identified in human and mouse Scaper genes drive zebrafish reporter expression patterns that are almost identical to the sponge Islet enhancer. The existence of homologous enhancers in these disparate metazoans suggests animal development is controlled by TF-enhancer DNA interactions that were present in the first multicellular animals.One-sentence summaryEnhancer activity is conserved across 700 million years of trans-phyletic divergence.
Rapid identification of homozygosity and site of wild relative introgressions in wheat through chromosome-specific KASP genotyping assays
Authors: Grewal Surbhi , Hubbart-Edwards Stella , Yang Caiyun , Devi Urmila , Baker Lauren , Heath Jack , Ashling Stephen , Scholefield Duncan , Howells Caroline , Yarde Jermaine , Isaac Peter , King Ian P. , King Julie 
Published: May 2019

SummaryFor future food security it is important that wheat, one of the most widely consumed crops in the world, can survive the threat of abiotic and biotic stresses. New genetic variation is currently being introduced into wheat through introgressions from its wild relatives. For trait discovery, it is necessary that each introgression is homozygous and hence stable. Breeding programs rely on efficient genotyping platforms for marker-assisted selection (MAS). Recently, single nucleotide polymorphism (SNP) based markers have been made available on high-throughput Axiom® SNP genotyping arrays. However, these arrays are inflexible in their design and sample numbers, making their use unsuitable for long-term MAS. SNPs can potentially be converted into Kompetitive allele-specific PCR (KASP™) assays which are comparatively cost-effective and efficient for low-density genotyping of introgression lines. However, due to the polyploid nature of wheat, KASP assays for homoeologous SNPs can have difficulty in distinguishing between heterozygous and homozygous hybrid lines in a backcross population. To identify co-dominant SNPs, that can differentiate between heterozygotes and homozygotes, we PCR-amplified and sequenced genomic DNA from potential single-copy regions of the wheat genome and compared them to orthologous copies from different wild relatives. A panel of 620 chromosome-specific KASP assays have been developed that allow rapid detection of wild relative segments and provide information on their homozygosity and site of introgression in the wheat genome. A set of 90 chromosome-nonspecific assays was also produced that can be used for genotyping introgression lines. These multipurpose KASP assays represent a powerful tool for wheat breeders worldwide.
A First-Order Design Requirement to Prevent Edema in Mechanical Counter-Pressure Space Suit Garments
Authors: Carr Christopher E. , Treviño Loretta 
Published: May 2019

ABSTRACTIntroductionMechanical counter-pressure (MCP) space suits may provide enhanced mobility relative to gas-pressure space suits. One challenge to realizing operational MCP suits is the potential for edema caused by spatial variations in the applied body-surface pressure (dP). We determined a first-order requirement for these variations.MethodsDarcy’s law relates volume flux, of fluid from capillaries to the interstitial space, to transmural hydraulic and osmotic pressure differences. Albumin and fibrinogen levels determine, to first order, the capillary oncotic pressure (COP). We estimated dP, neglecting hydrostatic pressure differences, by equating the volume flux under MCP and under normal with the volume flux under abnormal variations in COP; then we compared these estimates to results from MCP garment studies.ResultsNormal COP varies from 20-32 mm Hg; with constant hydraulic conductivity, dP≈12 mm Hg. In nephrotic syndrome, COP may drop to 11 mm Hg, yielding dP≈15 mm Hg relative to mid-normal COP. Previous studies found dPmax =151 mm Hg (MCP glove; finger and hand dorsum relative to palm), dPmax=51 mm Hg (MCP arm; finger, hand dorsum, and wrist relative to arm), and dP=52, 90 and 239 mm Hg (three MCP lower leg garments).ConclusionsMCP garments with dPmax≤12 mm Hg are unlikely to produce edema or restrict capillary blood flow; however, garments with dPmax>12 mm Hg will not necessarily produce edema. For example, the hydrostatic pressure gradient at the feet in 1g can range from 70-90 mm Hg. Current garment prototypes do not meet our conservative design requirement.
An asexual flower ofSilene latifoliaandMicrobotryum lychnidis-dioicaepromoting its sexual-organ development
Authors: Kawamoto Hiroki , Yamanaka Kaori , koizumi Ayako , Ishii Kotaro , Kazama Yusuke , Abe Tomoko , Kawano Shigeyuki 
Published: May 2019

AbstractSilene latifoliais a dioecious flowering plant with sex chromosomes in the family Caryophyllaceae. Development of a gynoecium and stamens are suppressed in the male and female flowers ofS. latifolia, respectively.Microbtryum lychnidis-dioicaepromotes stamen development when it infects the female flower. If suppression of the stamen and gynoecium development is regulated by the same mechanism, suppression of gynoecium and stamen development is released simultaneously with the infection byM. lychnidis-dioicae. To assess this hypothesis, an asexual mutant, without gynoecium or stamen, was infected withM. lychnidis-dioicae. A filament of the stamen in the infected asexual mutant was elongated at stages 11 and 12 of the flower bud development as well as the male, but the gynoecium did not form. Instead of the gynoecium, a filamentous structure was suppressed as in the male flower. Developmental suppression of the stamen was released byM. lychnidis-dioicae, but that of gynoecium development was not released. It is thought, therefore, that the suppression of gynoecium development was not released by the infection ofM. lychnidis-dioicae. M. lychnidis-dioicaewould have a function similar to SPF since the elongation of the stamen that is not observed in the healthy asexual mutant was observed after stage 8 of flower bud development. Such an infection experiment also that the Y chromosome of the asexual mutant has genes related to the differentiation of archesporial cells, but none related to maturation of the tapetal cells.