Let
f
be a fixed Maass form for SL
3
(ℤ) with Fourier coefficients
A
f
(
m, n
). Let
g
be a Maass cusp form for SL
2
(ℤ) with Laplace eigenvalue
1
4
+
k
2
and Fourier coefficient λ
g
(
n
), or a ...holomorphic cusp form of even weight
k
. Denote by
S
X
(
f
×
g, α, β
) a smoothly weighted sum of
A
f
(1,
n
)λ
g
(
n
)
e
(
αn
β
) for
X
<
n
< 2
X
, where
α
≠ 0 and
β
> 0 are fixed real numbers. The subject matter of the present paper is to prove non-trivial bounds for a sum of
S
X
(
f
×
g, α, β
) over
g
as
k
tends to ∞ with
X
. These bounds for average provide insight for the corresponding resonance barriers toward the Hypothesis S as proposed by Iwaniec, Luo, and Sarnak.
YAP, a key effector of Hippo pathway, is activated by its translocation from cytoplasm to nucleus to regulate gene expression and promote tumorigenesis. Although the mechanism by which YAP is ...suppressed in cytoplasm has been well-studied, how the activated YAP is sequestered in the nucleus remains unknown. Here, we demonstrate that YAP is a nucleocytoplasmic shuttling protein and its nuclear export is controlled by SET1A-mediated mono-methylation of YAP at K342, which disrupts the binding of YAP to CRM1. YAP mimetic methylation knockin mice are more susceptible to colorectal tumorigenesis. Clinically, YAP K342 methylation is reversely correlated with cancer survival. Collectively, our study identifies SET1A-mediated mono-methylation at K342 as an essential regulatory mechanism for regulating YAP activity and tumorigenesis.
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•SET1A methylates YAP at K342•Methylation of YAP by SET1A blocks its nuclear export•SET1A-mediated YAP methylation promotes cell proliferation and tumorigenesis•High levels of YAP K342 methylation and SET1A predict poor prognosis
Fang et al. show that SET1A methylates YAP at K342, resulting in nuclear retention of YAP and increased YAP activity. Yap K342M knockin mice develop more and larger colitis-associated colorectal tumors. YAP K342 methylation in lung and colorectal cancers reversely correlates with patient survival.
Photoacoustic imaging (PAI) and photoacoustic (PA) therapy have promising applications for treating tumors. It is known that the utilization of high‐absorption‐coefficient probes can selectively ...enhance the PAI target contrast and PA tumor therapy efficiency in deep‐seated tissue. Here, the design of a probe with the highest availability of optical‐thermo conversion by using graphene oxide (GO) and dyes via π–π stacking interactions is reported. The GO serves as a base material for loading dyes and quenching dye fluorescence via fluorescence resonance energy transfer (FRET), with the one purpose of maximum of PA efficiency. Experiments verify that the designed fluorescence quenching nanoprobes can produce stronger PA signals than the sum of the separate signals generated in the dye and the GO. Potential applications of the fluorescence quenching nanoprobes are demonstrated, dedicating to enhance PA contrast of targets in deep‐seated tissues and tumors in living mice. PA therapy efficiency both in vitro and in vivo by using the fluorescence quenching nanoprobes is found to be higher than with the commonly used PA therapy agents. Taken together, quenching dye fluorescence via FRET will provide a valid means for developing high‐efficiency PA probes. Fluorescence quenching nanoprobes are likely to become a promising candidate for deep‐seated tumor imaging and therapy.
Fluorescence quenching nanoprobes are composed of fluorescent dyes and graphene oxide via π–π stacking interactions, in which graphene oxide serves as a base material for loading dyes and quenching dye fluorescence via fluorescence resonance energy transfer, with the one purpose of maximum of photoacoustic efficiency. Potential applications of the fluorescence quenching nanoprobes in biomedicine are demonstrated.
The genus Seseli L., which consists of 125-140 species distributed in the Old World from western Europe and northwestern Africa to China and Japan, is one of the largest and most taxonomically ...difficult genera of Apiaceae Lindl. Although several previous studies have been conducted on Seseli based on limited morphological characteristics and molecular fragments, a robust and comprehensive phylogeny of Seseli remains elusive. Plastomes provide abundant genetic information and have been widely used in studying plant phylogeny and evolution. Consequently, we newly generated the complete plastomes of eleven Seseli taxa. We combined plastome data and morphological characteristics to investigate the phylogeny of Seseli. In our study, we observed that the genome length, gene numbers, IR/SC borders, and repeat composition of the eleven Seseli plastomes were variable. Several appropriate mutation hotspot regions may be developed as candidate DNA barcodes for evolution, phylogeny, and species identification of Seseli. The phylogenetic results identified that Seseli was not a monophyletic group. Moreover, the eleven newly sequenced Seseli taxa did not cluster with S. tortuosum (the type species of Seseli, belonging to the tribe Selineae), where S. delavayi clustered with Eriocycla belonging to the tribe Echinophoreae and the other ten belonged to Selineae. The comparative plastome and morphological characteristics analyses confirmed the reliability of the phylogenetic analyses and implied the complex evolution of Seseli. Combining molecular and morphological data is efficient and useful for studying the phylogeny of Seseli. We suggest that "a narrow sense" of Seseli will be meaningful for further study and the current taxonomic system of Seseli needs to be revised. In summary, our study can provide new insights into the phylogenetic relationships and taxonomic framework of Seseli.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Ferula genus encompasses 180-185 species and is one of the largest genera in Apiaceae, with many of Ferula species possessing important medical value. The previous studies provided more ...information for Ferula, but its infrageneric relationships are still confusing. In addition, its genetic basis of its adaptive evolution remains poorly understood. Plastid genomes with more variable sites have the potential to reconstruct robust phylogeny in plants and investigate the adaptive evolution of plants. Although chloroplast genomes have been reported within the Ferula genus, few studies have been conducted using chloroplast genomes, especially for endemic species in China.
Comprehensively comparative analyses of 22 newly sequenced and assembled plastomes indicated that these plastomes had highly conserved genome structure, gene number, codon usage, and repeats type and distribution, but varied in plastomes size, GC content, and the SC/IR boundaries. Thirteen mutation hotspot regions were detected and they would serve as the promising DNA barcodes candidates for species identification in Ferula and related genera. Phylogenomic analyses with high supports and resolutions showed that Talassia transiliensis and Soranthus meyeri were nested in the Ferula genus, and thus they should be transferred into the Ferula genus. Our phylogenies also indicated the monophyly of subgenera Sinoferula and subgenera Narthex in Ferula genus. Twelve genes with significant posterior probabilities for codon sites were identified in the positively selective analysis, and their function may relate to the photosystem II, ATP subunit, and NADH dehydrogenase. Most of them might play an important role to help Ferula species adapt to high-temperatures, strong-light, and drought habitats.
Plastome data is powerful and efficient to improve the support and resolution of the complicated Ferula phylogeny. Twelve genes with significant posterior probabilities for codon sites were helpful for Ferula to adapt to the harsh environment. Overall, our study supplies a new perspective for comprehending the phylogeny and evolution of Ferula.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tribe Lilieae, encompassing
,
,
, and
, includes economically important crops with a horticultural and medicinal value. It is considered to be a core lineage of Liliaceae, but phylogenetic ...relationships within it, and the timing of the origin of individual clades, remain incompletely resolved. To address these issues, we reconstructed the evolutionary history of the tribe. We sequenced 45 Liliaceae plastomes and combined them with publicly available data (for a total of 139 plastomes) to explore the systematics, origin, divergence, and evolution of Lilieae. Our taxon sampling covers all ten sections of
, all
species, three
species, and major phylogenetic clades of
. Our phylogenetic analysis confirms the monophyly of major sections/subgenera of
and
with strong support. We dated the origin of Lilieae to the Eocene, with genera and species radiations inferred to have occurred in the Miocene. The reconstruction of the ancestral area implies that Lilieae may have originated from the Qinghai-Tibet Plateau (QTP): the Himalayas and Hengduan Mountains and uplifting of the QTP likely promoted divergence within the tribe. Ancestral-state reconstructions of the bulb component number (including bulblets and scales) show a strong correlation with the genus-level phylogenetic diversity in Lilieae. They also predict that the most recent common ancestor of Lilieae had bulbs with numerous bulblets. Based on these observations, we predicted that climatic oscillations associated with the QTP uplift played an important role in the evolution of the Lilieae bulb. Our findings provide a well-supported picture of evolutionary relationships and a useful framework for understanding the pathway of bulb evolution within Lilieae, contributing to a better understanding of the evolutionary history of lilies.
Parkinson’s disease (PD) is a common neurodegenerative disorder primarily caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc). However, the manner of death of ...dopaminergic neurons remains indistinct. Ferroptosis is a form of cell death involving in the iron-dependent accumulation of glutathione depletion and lipid peroxide. Besides, previous studies indicated that ferroptosis might be involved in the death of dopaminergic neurons. In this study, we aim to explore the protective effect of the p62-Keap1-Nrf2 pathway against 6-hydroxydopamine (6-OHDA)-induced ferroptosis in dopaminergic cells. Firstly, our results demonstrated that 6-OHDA-induced ferroptosis could be observed in vivo zebrafish and in vitro human dopaminergic cell line (SH-SY5Y cells) model. Moreover, ferroptosis induced by 6-OHDA mitigates in SH-SY5Y cells upon ferrostatin-1 (Fer, an inhibitor of ferroptosis) treatment via upregulating the protein expression of glutathione peroxidase 4 (GPX4). Then, we found that high p62/SQSTM1 (p62) expression could protect SH-SY5Y cells against ferroptosis through promoting Nrf2 nuclear transfer and upregulating the expression of the antioxidant protein heme oxygenase-1 (HO-1). Ultimately, high p62 expression activates the Nrf2/HO-1 signaling pathway through binding to Kelch-like ECH-associated protein 1 (Keap1). Collectively, the activation of the p62-Keap1-Nrf2 pathway prevents 6-OHDA-induced ferroptosis in SH-SY5Y cells, targeting this pathway in combination with a pharmacological inhibitor of ferroptosis can be a potential approach for PD therapy.
The Möbius function
μ
(
n
)
is known for containing limited information on the prime factorization of
n
. Its known algorithms, however, are all based on factorization and hence are exponentially ...slow on
log
n
. Consequently, a faster algorithm of
μ
(
n
)
could potentially lead to a fast algorithm of prime factorization which in turn would throw doubt upon the security of most public-key cryptosystems. This research introduces novel approaches to compute
μ
(
n
)
using random forests and neural networks, harnessing the additive properties of
μ
(
n
)
. The machine learning models are trained on a substantial dataset with 317,284 observations (80%), comprising five feature variables, including values of
n
within the range of
4
×
10
9
. We implement the Random Forest with Random Inputs (RFRI) and Feedforward Neural Network (FNN) architectures. The RFRI model achieves a predictive accuracy of 0.9493, a recall of 0.5865, and a precision of 0.6626. On the other hand, the FNN model attains a predictive accuracy of 0.7871, a recall of 0.9477, and a precision of 0.2784. These results strongly support the effectiveness and validity of the proposed algorithms.
Waterborne pathogens and their associated diseases are major threats to public health, and surveillance of pathogens and identification of the sources of pollution are imperative for preventing ...infections. However, simultaneously quantitative detection of multiple pathogens and pollution sources in water environments is the major challenge. In this study, we developed and validated a highly sensitive (mostly >80%) and highly specific (>99%) high-throughput quantitative PCR (HT-qPCR) approach, which could simultaneously quantify 68 marker genes of 33 human pathogens and 23 fecal markers of 10 hosts. The HT-qPCR approach was then successfully used to investigate pathogens and fecal pollution in marine recreational water samples of Xiamen, China. Totally, seven pathogenic marker genes were found in 13 beach bathing waters, which targeted Acanthamoeba spp., Clostridium perfringens, enteropathogenic Escherichia coli, Klebsiella pneumoniae, Vibrio cholera/V. parahaemolyticus and Legionella spp.. Fecal markers from human and dog were the most frequently detected, indicating human and dog feces were the main contamination in the recreational waters. Nanopore sequencing of full-length 16S rRNA gene revealed that 28 potential human pathogens were detected and electrical conductivity, salinity, oxidation-reduction potential and dissolved oxygen were significantly correlated with the variation in bacterial community. Our results demonstrated that HT-qPCR approach had the potential rapid quantification of microbial contamination, providing useful data for assessment of microbial pathogen associated health risk and development of management practices to protect human health.
•High-throughput qPCR was developed for diagnosing pathogens and fecal pollution.•68 marker genes of 33 pathogens and 23 fecal markers of 10 hosts were targeted.•Seven pathogen markers were detected in 13 marine recreational waters.•Human and dog feces were the major fecal contamination sources.•Nanopore sequencing was applied for analyzing full-length 16S rRNA genes.
Abstract
We have collected 10,025 foreground–background quasar pairs with projected distances
d
p
< 500 kpc from the large quasar catalog of the Sloan Digital Sky Survey DR16Q. We investigate the ...properties of the Mg
ii
absorption lines with
W
r
> 0.15 Å around foreground quasars, including both the line of sight (LOS; of foreground quasars) and transverse (TRA; perpendicular to the LOS) absorptions. Both the equivalent width (the correlation coefficient
ρ
= −0.915 and the probability
P
< 10
−4
of no correlation) and incident rate (
ρ
= −0.964 and
P
< 10
−6
) of TRA Mg
ii
absorption lines are obviously anticorrelated with projected distance. The incident rate of TRA Mg
ii
absorption lines is obviously (>4
σ
) greater than that of LOS Mg
ii
absorption lines at projected distances
d
p
< 200 kpc, while the TRA and LOS Mg
ii
both have similar (<3
σ
) incident rates at scales
d
p
> 200 kpc. The anisotropic radiation from quasars would be the most possible interpretation for the anisotropic absorption around quasars. This could also indicate that the quasar radiation is not obviously impacting the gas halos of quasars at scales
d
p
> 200 kpc.
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