115 research outputs found
Male-specific Fruitless isoforms have different regulatory roles conferred by distinct zinc finger DNA binding domains
Background: Drosophila melanogaster adult males perform an elaborate courtship ritual to entice females to mate. fruitless (fru), a gene that is one of the key regulators of male courtship behavior, encodes multiple male-specific isoforms (Fru(M)). These isoforms vary in their carboxy-terminal zinc finger domains, which are predicted to facilitate DNA binding. Results: By over-expressing individual Fru(M) isoforms in fru-expressing neurons in either males or females and assaying the global transcriptional response by RNA-sequencing, we show that three Fru(M) isoforms have different regulatory activities that depend on the sex of the fly. We identified several sets of genes regulated downstream of Fru(M) isoforms, including many annotated with neuronal functions. By determining the binding sites of individual Fru(M) isoforms using SELEX we demonstrate that the distinct zinc finger domain of each Fru(M) isoforms confers different DNA binding specificities. A genome-wide search for these binding site sequences finds that the gene sets identified as induced by over-expression of Fru(M) isoforms in males are enriched for genes that contain the binding sites. An analysis of the chromosomal distribution of genes downstream of Fru(M) shows that those that are induced and repressed in males are highly enriched and depleted on the X chromosome, respectively. Conclusions: This study elucidates the different regulatory and DNA binding activities of three Fru(M) isoforms on a genome-wide scale and identifies genes regulated by these isoforms. These results add to our understanding of sex chromosome biology and further support the hypothesis that in some cell-types genes with male-biased expression are enriched on the X chromosome
Symmetric Kondo Lattice States in Doped Strained Twisted Bilayer Graphene
We use the topological heavy fermion (THF) model and its Kondo Lattice (KL)
formulation to study the symmetric Kondo state in twisted bilayer graphene. Via
a large-N approximation, we find a symmetric Kondo (SK) state in KL mode at
fillings . In the SK state, all symmetries are preserved and
the local moments are Kondo screened by the conduction electrons. At the
mean-field level of the THF model at , we also find
a similar symmetric state. We study the stability of the symmetric state by
comparing its energy with the ordered states and find the ordered states to
have lower energy. However, moving away from integer fillings by doping holes
to the light bands, we find the energy difference is reduced, which suggests
the loss of ordering and a tendency towards Kondo screening. In order to
include many-body effects beyond the mean-field approximation, we perform
dynamical mean-field theory (DMFT) calculations on the THF model. We find the
spin susceptibility follows a Curie behavior at down to
where the onset of screening of the local moment becomes
visible. This hints to very low Kondo temperatures at these fillings, in
agreement with the outcome of our mean-field calculations. At non-integer
filling DMFT shows deviations from a
-susceptibility at much higher temperatures, suggesting a more effective
screening of local moments with doping. Finally, we study the effect of a
-rotational-symmetry-breaking strain via mean-field approaches and find
that a symmetric phase (that only breaks symmetry) can be stabilized
at sufficiently large strain at . Our results suggest that
a symmetric Kondo phase is strongly suppressed at integer fillings, but could
be stabilized either at non-integer fillings or by applying strain.Comment: 40 pages, 15 figure
Dynamic, mating-induced gene expression changes in female head and brain tissues of Drosophila melanogaster
BACKGROUND: Drosophila melanogaster females show changes in behavior and physiology after mating that are thought to maximize the number of progeny resulting from the most recent copulation. Sperm and seminal fluid proteins induce post-mating changes in females, however, very little is known about the resulting gene expression changes in female head and central nervous system tissues that contribute to the post-mating response. RESULTS: We determined the temporal gene expression changes in female head tissues 0-2, 24, 48 and 72 hours after mating. Females from each time point had a unique post-mating gene expression response, with 72 hours post-mating having the largest number of genes with significant changes in expression. At most time points, genes expressed in the head fat body that encode products involved in metabolism showed a marked change in expression. Additional analysis of gene expression changes in dissected brain tissues 24 hours post-mating revealed changes in transcript abundance of many genes, notably, the reduced transcript abundance of genes that encode ion channels. CONCLUSIONS: Substantial changes occur in the regulation of many genes in female head tissues after mating, which might underlie aspects of the female post-mating response. These results provide new insights into the physiological and metabolic changes that accompany changes in female behaviors
The NBD-NBD interface is not the sole determinant for transport in ABC transporters
International audienceOne of the most exciting scientific challenges in functional genomics concerns the discovery of biologically relevant patterns from gene expression data. For instance, it is extremely useful to provide putative synexpression groups or transcription modules to molecular biologists. We propose a methodology that has been proved useful in real cases. It is described as a prototypical KDD scenario which starts from raw expression data selection until useful patterns are delivered. Our conceptual contribution is (a) to emphasize how to take the most from recent progress in constraint-based mining of set patterns, and (b) to propose a generic approach for gene expression data enrichment. The methodology has been validated on real data sets
MachiBase: a Drosophila melanogaster 5′-end mRNA transcription database
MachiBase (http://machibase.gi.k.u-tokyo.ac.jp/) provides a comprehensive and freely accessible resource regarding Drosophila melanogaster 5′-end mRNA transcription at different developmental states, supporting studies on the variabilities of promoter transcriptional activities and gene-expression profiles in the fruitfly. The data were generated in conjunction with the recently developed high-throughput genome sequencer Illumina/Solexa using a newly developed 5′-end mRNA collection method
Discerning the ancestry of European Americans in genetic association studies
European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data
Quantum textures of the many-body wavefunctions in magic-angle graphene
Interactions among electrons create novel many-body quantum phases of matter
with wavefunctions that often reflect electronic correlation effects, broken
symmetries, and novel collective excitations. A wide range of quantum phases
has been discovered in MATBG, including correlated insulating, unconventional
superconducting, and magnetic topological phases. The lack of microscopic
information, including precise knowledge of possible broken symmetries, has
thus far hampered our understanding of MATBG's correlated phases. Here we use
high-resolution scanning tunneling microscopy to directly probe the
wavefunctions of the correlated phases in MATBG. The squares of the
wavefunctions of gapped phases, including those of the correlated insulators,
pseudogap, and superconducting phases, show distinct patterns of broken
symmetry with a x super-periodicity on the graphene
atomic lattice that has a complex spatial dependence on the moir\'e
superlattice scale. We introduce a symmetry-based analysis to describe our
measurements of the wavefunctions of MATBG's correlated phases with a set of
complex-valued local order parameters. For the correlated insulators in MATBG,
at fillings of = 2 electrons per moir\'e unit cell relative to
charge neutrality, we compare the observed quantum textures to those expected
for proposed theoretical ground states. In typical MATBG devices, the textures
of correlated insulators' wavefunctions closely match those of the
theoretically proposed IKS order, while in ultra-low-strain samples our data
has local symmetries like those of a T-IVC phase. We also study the
wavefunction of MATBG's superconducting state, revealing strong signatures of
intervalley coherence that can only be distinguished from those of the
insulator with our phase-sensitive measurements.Comment: 5 figure
PbCu(PO4)(OH): Phonon bands, Localized Flat Band Magnetism, Models, and Chemical Analysis
In a series of recent reports, doped lead apatite (LK-99) has been proposed
as a candidate ambient temperature and pressure superconductor. However, from
both an experimental and theoretical perspective, these claims are largely
unsubstantiated. To this end, our synthesis and subsequent analysis of an LK-99
sample reveals a multiphase material that does not exhibit high-temperature
superconductivity. We study the structure of this phase with single-crystal
X-ray diffraction (SXRD) and find a structure consistent with doped
. However, the material is
transparent which rules out a superconducting nature. From ab initio defect
formation energy calculations, we find that the material likely hosts
anions, rather than divalent anions, within the
hexagonal channels and that Cu substitution is highly thermodynamically
disfavored. Phonon spectra on the equilibrium structures reveal numerous
unstable phonon modes. Together, these calculations suggest it is doubtful that
Cu enters the structure in meaningful concentrations, despite initial attempts
to model LK-99 in this way. However for the sake of completeness, we perform ab
initio calculations of the topology, quantum geometry, and Wannier function
localization in the Cu-dominated flat bands of four separate doped structures.
In all cases, we find they are atomically localized by irreps, Wilson loops,
and the Fubini-Study metric. It is unlikely that such bands can support strong
superfluidity, and instead are susceptible to ferromagnetism (or out-of-plane
antiferromagnetism) at low temperatures, which we find in ab initio studies. In
sum, could more likely be
a magnet, rather than an ambient temperature and pressure superconductor.Comment: 39 pages including appendices. Updated defect calculations and
energy-dispersive X-ray spectroscopy dat
Somatic sex-specific transcriptome differences in Drosophila revealed by whole transcriptome sequencing
<p>Abstract</p> <p>Background</p> <p>Understanding animal development and physiology at a molecular-biological level has been advanced by the ability to determine at high resolution the repertoire of mRNA molecules by whole transcriptome resequencing. This includes the ability to detect and quantify rare abundance transcripts and isoform-specific mRNA variants produced from a gene.</p> <p>The sex hierarchy consists of a pre-mRNA splicing cascade that directs the production of sex-specific transcription factors that specify nearly all sexual dimorphism. We have used deep RNA sequencing to gain insight into how the Drosophila sex hierarchy generates somatic sex differences, by examining gene and transcript isoform expression differences between the sexes in adult head tissues.</p> <p>Results</p> <p>Here we find 1,381 genes that differ in overall expression levels and 1,370 isoform-specific transcripts that differ between males and females. Additionally, we find 512 genes not regulated downstream of <it>transformer </it>that are significantly more highly expressed in males than females. These 512 genes are enriched on the × chromosome and reside adjacent to dosage compensation complex entry sites, which taken together suggests that their residence on the × chromosome might be sufficient to confer male-biased expression. There are no transcription unit structural features, from a set of features, that are robustly significantly different in the genes with significant sex differences in the ratio of isoform-specific transcripts, as compared to random isoform-specific transcripts, suggesting that there is no single molecular mechanism that generates isoform-specific transcript differences between the sexes, even though the sex hierarchy is known to include three pre-mRNA splicing factors.</p> <p>Conclusions</p> <p>We identify thousands of genes that show sex-specific differences in overall gene expression levels, and identify hundreds of additional genes that have differences in the abundance of isoform-specific transcripts. No transcription unit structural feature was robustly enriched in the sex-differentially expressed transcript isoforms. Additionally, we found that many genes with male-biased expression were enriched on the × chromosome and reside adjacent to dosage compensation entry sites, suggesting that differences in sex chromosome composition contributes to dimorphism in gene expression. Taken together, this study provides new insight into the molecular underpinnings of sexual differentiation.</p
Sperm-Storage Defects and Live Birth in Drosophila Females Lacking Spermathecal Secretory Cells
Transgenic Drosophila are used to identify the functions of a small set of secretory cells that are typically associated with the sperm-storage organs of female insects
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